Course Information

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)
RNDr. Vendula Hlaváčková Pospíchalová, Ph.D. (lecturer)

Guaranteed by

prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Mon 19. 2. to Sun 26. 5. Tue 10:00–11:50 B11/305

Prerequisites

Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 9 fields of study the course is directly associated with, display

Course objectives

The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.

Learning outcomes

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

The course is finished by written exam.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)
RNDr. Vendula Hlaváčková Pospíchalová, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)

Guaranteed by

prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Prerequisites

Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 9 fields of study the course is directly associated with, display

Course objectives

The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.

Learning outcomes

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

The course is finished by written exam.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

The course is taught annually.
The course is taught: every week.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)

Guaranteed by

prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 10:00–11:50 B11/333

Prerequisites

Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 9 fields of study the course is directly associated with, display

Course objectives

The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.

Learning outcomes

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished first by short written exam. Students must answer about 10 questions which go through all topics discoursed. This is followed by detail oral examination which is evaluated together with written exam by the teacher.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)

Guaranteed by

prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 10:00–11:50 B11/333

Prerequisites

Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 9 fields of study the course is directly associated with, display

Course objectives

The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.

Learning outcomes

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished first by short written exam. Students must answer about 10 questions which go through all topics discoursed. This is followed by detail oral examination which is evaluated together with written exam by the teacher.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)

Guaranteed by

prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Mon 1. 3. to Fri 14. 5. Tue 11:00–12:50 online_B3

Prerequisites

Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 9 fields of study the course is directly associated with, display

Course objectives

The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.

Learning outcomes

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished first by short written exam. Students must answer about 10 questions which go through all topics discoursed. This is followed by detail oral examination which is evaluated together with written exam by the teacher.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)

Guaranteed by

prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 10:00–11:50 BFU

Prerequisites

Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 9 fields of study the course is directly associated with, display

Course objectives

The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.

Learning outcomes

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished first by short written exam. Students must answer about 10 questions which go through all topics discoursed. This is followed by detail oral examination which is evaluated together with written exam by the teacher.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Mon 18. 2. to Fri 17. 5. Tue 11:00–12:50 BFU

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue classification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); proto-oncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomeres, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer; Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. nongenotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assessment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished by written exam evaluated by the teacher. Students must answer about 20 questions which go through all topics discoursed. 60% of correct answers is needed to pass.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 11:00–12:50 B11/333

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue classification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); proto-oncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomeres, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer; Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. nongenotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assessment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished by written exam evaluated by the teacher. Students must answer about 20 questions which go through all topics discoursed. 60% of correct answers is needed to pass.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Mechanisms of carcinogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Mon 20. 2. to Mon 22. 5. Tue 13:00–15:50 BFU

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue classification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); proto-oncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomeres, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer; Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. nongenotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assessment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished by written exam evaluated by the teacher. Students must answer about 20 questions which go through all topics discoursed. 60% of correct answers is needed to pass.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Thu 10:00–11:50 D36/215

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue classification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); proto-oncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomeres, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer; Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. nongenotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assessment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished by written exam evaluated by the teacher. Students must answer about 20 questions which go through all topics discoursed. 60% of correct answers is needed to pass.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Thu 9:00–10:50 D36/215

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue classification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); proto-oncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomeres, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer; Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. nongenotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assessment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished by written exam followed by oral examination evaluated by the teacher. In written exam students must answer about 10 questions which go through all topics discoursed. 60% of correct answers is needed to pass.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 13:00–14:50 D36/212

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue classification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); proto-oncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomeres, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer; Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. nongenotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assessment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

required literature
• Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info

recommended literature
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info

Teaching methods

Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.

Assessment methods

Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished by written exam evaluated by the teacher. Students must answer about 20 questions which go through all topics discoursed. 60% of correct answers is needed to pass.

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Bi7070 Physiology of Cell Systems
Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

• Molecular Biology and Genetics (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB)
• Special Biology (programme PřF, N-EXB, specialization Ekotoxikologie)
• Special Biology (programme PřF, N-EXB, specialization Experimentální biologie živočichů a imunologie)

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Teaching methods

Lectures and class discussion

Assessment methods

final written exam

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further comments (probably available only in Czech)

Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 11 fields of study the course is directly associated with, display

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Teaching methods

Lectures and class discussion

Assessment methods

final written exam

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Teaching methods

Lectures and class discussion

Assessment methods

final written exam

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 8:00–9:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Teaching methods

Lectures and class discussion

Assessment methods

final written exam

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias). It is focused on principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy.
Main objectives are summarized as follows:
- to understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level;
- to understand molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes;
- to understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis;
- to learn principles of use of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Assessment methods

lectures final written exam

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Assessment methods (in Czech)

písemná zkouška

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Assessment methods (in Czech)

písemná zkouška

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer), doc. RNDr. Martin Vácha, Ph.D. (deputy)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 6 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Assessment methods (in Czech)

písemná zkouška

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

Study Materials
The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer), doc. RNDr. Martin Vácha, Ph.D. (deputy)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
RECETOX – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 6 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer), doc. RNDr. Martin Vácha, Ph.D. (deputy)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
RECETOX – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Timetable

Tue 13:00–14:50 BFU

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 6 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

The course is taught annually.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer), doc. RNDr. Martin Vácha, Ph.D. (deputy)
prof. RNDr. Jakub Hofman, Ph.D. (assistant)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
RECETOX – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 6 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

The course is taught annually.
The course is taught: every week.

Bi8110 Genotoxicity and cancerogenesis

The information about the term spring 2012 - acreditation is not made public

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Teaching methods

Lectures and class discussion

Assessment methods

final written exam

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further Comments

The course is taught annually.
The course is taught: every week.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias); describe principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis; formulate an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components); discuss problems of cancer prevention, diagnosis and therapy; understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level; interpret the molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes; explain mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.

Syllabus

• Cancer origin and development;
• Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
• Molecular basis of carcinogenesis;
• Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
• Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
• Immortalization; importance of telomers, telomerase and other factors.
• Non-genotoxic (epigenetic) mechanisms;
• DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
• Cytokine pathological effects;
• Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
• Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
• Cell communication;
• Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
• Metastases;
• Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
• Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
• Development of specific cancer types (genetic and epigenetic causes);
• Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
• The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
• Endogenous carcinogenesis; hormone-dependent cancers.
• Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
• Environmental factors in carcinogenesis;
• Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
• The effects of harmful environmental factors;
• Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
• Nutritional aspects of carcinogenesis;
• Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
• Contemporary system of detection of carcinogenic effects of compounds;
• Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
• Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
• Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
• Cancer prevention, diagnostics and treatment;
• Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
• Predictive oncology;
• Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.

Literature

• ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
• Nutritional oncology. Edited by David Heber. 2nd ed. Boston: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. URL info
• Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
• Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
• Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
• Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
• ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
• KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
• KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
• HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. New York: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. URL info
• + doporučené speciální separáty a schemata z přednášek

Teaching methods

Lectures and class discussion

Assessment methods

final written exam

Language of instruction

Czech

Follow-Up Courses

• Bi6871 Health Risks
• Bi7070 Physiology of Cell Systems

Further Comments

The course is taught annually.
The course is taught: every week.

Bi8110 Genotoxicity and cancerogenesis

Extent and Intensity

2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).

Teacher(s)

prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)

Guaranteed by

prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.

Prerequisites

Passing through lecture of Physiology of cell systems is neccessary

Course Enrolment Limitations

The course is also offered to the students of the fields other than those the course is directly associated with.

fields of study / plans the course is directly associated with

there are 7 fields of study the course is directly associated with, display

Course objectives

Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer. It is focused on principles leading to disruptions in signal transduction inside a cell and cell cycle deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy, to present methods of detection of carcinogenic potential of environmental polutants and their profit in experimental ecotoxicology.

Syllabus

• 1. Genetic and epigenetic aspects of carcinogenesis. Process of carcinogenesis Tumor classification The stages of carcinogenesis Mutagenesis Initiation Promotion Progression 2. Modulations of signal transduction. Oncogenes and tumor supressor genes Changes in regulation of cytokinetics e. g. cell cycle, proliferation, differentiation and apoptosis Perturbation of homeostasis Inter- and intracellular communication Adhesion Immortalization Metastases Angiogenesis 3. Disorders in differentiation Pathological effects of cytokines 4. Origin of specific types of tumors (leukemias, breast, colon, liver, skin cancer) 5. Prevention, diagnosis and tumor therapy 6. Predictive oncology Prognostic vs. predictive factors Data management 7. The role of environmental factors in carcinogenesis Genotoxic vs. epigenetic effects 8. Nutrition aspects of carcinogenesis 9. Current system of detection of carcinogenic properties of risk substances Prospectives of experimental ecotoxicology

Literature

• What you need to know about cancer, Scientific American - Special Issue, September 1996
• FREMUTH, František. Regulace a inhibice růstu normálních a nádorových buněk. 1. vyd. Praha: Státní pedagogické nakladatelství, 1986, 223 s. info
• J. Neuwirt, E. Nečas: Kmenové buňky a krevní choroby, Avicenum Praha 1981
• V. Wagner, M. Wagnerová: Ekoimunologie, Avicenum, Praha 1988
• ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
• P. Klener: Chemoterapie v komplexní léčbě zhoubných nádorů a hemoblastóz, Avicenum, Praha 1987
• Hemopoietic growth factors, oncogenes and cytokines in clinical hematology (Eds. E. Cacciola, A. B. Deisseroth, R. Giustolisi), Karger1994
• The cytokine handbook, ed. A. W. Thompson, Academic Press New York, 199
• J. Hofmanová, A. Kozubík: Apoptóza a nádorová onemocnění - Přehled, Klinická onkologie 8, 5, 1995.
• A. Kozubík, J. Hofmanová: Hodnocení účinků negenotoxicky působících polutantů. Sborník konference ERA 97, Hodnocení rizik pro životní prostředí, Brno 1997, str. 220-225.
• A. Kozubík, J. Hofmanová: Význam nenasycených mastných kyselin v rozvoji a chemoprofylaxi nádorů kolorekta - Přehled, Klinická onkologie 1999
• + doporučené speciální separáty a schemata z přednášek

Assessment methods (in Czech)

písemná zkouška

Language of instruction

Czech

Follow-Up Courses

• C6870 Health Risks
• C6880 Biochemistry of Xenobiotics
• C7530 Physiology of Cell Systems

Further Comments

The course is taught annually.
The course is taught: every week.

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