MOHELNIKOVA-DUCHONOVA, B., M. KOCIK, B. DUCHONOVA, V. BRYNYCHOVA, M. OLIVERIUS, Jan HLAVSA, E. HONSOVA, Jan MAZANEC, Zdeněk KALA, I. OJIMA, D.J. HUGHES, J.E. DOHERTY, H.A. MURRAY, M.A. CROCKARD, R. LEMSTROVA and P. SOUCEK. Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216. PHARMACOGENOMICS JOURNAL. LONDON: NATURE PUBLISHING GROUP, 2017, vol. 17, No 5, p. 452-460. ISSN 1470-269X. Available from: https://dx.doi.org/10.1038/tpj.2016.55.
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Basic information
Original name Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216
Authors MOHELNIKOVA-DUCHONOVA, B. (203 Czech Republic), M. KOCIK (203 Czech Republic), B. DUCHONOVA (203 Czech Republic), V. BRYNYCHOVA (203 Czech Republic), M. OLIVERIUS (203 Czech Republic), Jan HLAVSA (203 Czech Republic, guarantor, belonging to the institution), E. HONSOVA (203 Czech Republic), Jan MAZANEC (203 Czech Republic, belonging to the institution), Zdeněk KALA (203 Czech Republic, belonging to the institution), I. OJIMA (840 United States of America), D.J. HUGHES (372 Ireland), J.E. DOHERTY (826 United Kingdom of Great Britain and Northern Ireland), H.A. MURRAY (826 United Kingdom of Great Britain and Northern Ireland), M.A. CROCKARD (826 United Kingdom of Great Britain and Northern Ireland), R. LEMSTROVA (203 Czech Republic) and P. SOUCEK (203 Czech Republic).
Edition PHARMACOGENOMICS JOURNAL, LONDON, NATURE PUBLISHING GROUP, 2017, 1470-269X.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10603 Genetics and heredity
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 3.812
RIV identification code RIV/00216224:14110/17:00098092
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1038/tpj.2016.55
UT WoS 000411849200008
Keywords in English pancreatic cancer
Tags EL OK
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 21/3/2018 16:09.
Abstract
The Hedgehog pathway is one of the major driver pathways in pancreatic ductal adenocarcinoma. This study investigated prognostic importance of Hedgehog signaling pathway in pancreatic cancer patients who underwent a radical resection. Tumors and adjacent non-neoplastic pancreatic tissues were obtained from 45 patients with histologically verified pancreatic cancer. The effect of experimental taxane chemotherapy on the expression of Hedgehog pathway was evaluated in vivo using a mouse xenograft model prepared using pancreatic cancer cell line Paca-44. Mice were treated by experimental Stony Brook Taxane SB-T-1216. The transcript profile of 34 Hedgehog pathway genes in patients and xenografts was assessed using quantitative PCR. The Hedgehog pathway was strongly overexpressed in pancreatic tumors and upregulation of SHH, IHH, HHAT and PTCH1 was associated with a trend toward decreased patient survival. No association of Hedgehog pathway expression with KRAS mutation status was found in tumors. Sonic hedgehog ligand was overexpressed, but all other downstream genes were downregulated by SB-T-1216 treatment in vivo. Suppression of HH pathway expression in vivo by taxane-based chemotherapy suggests a new mechanism of action for treatment of this aggressive
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