Hedgehog pathway overexpression in pancreatic cancer is
abrogated by new-generation taxoid SB-T-1216

J 2017

Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216

MOHELNIKOVA-DUCHONOVA, B., M. KOCIK, B. DUCHONOVA, V. BRYNYCHOVA, M. OLIVERIUS et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10603 Genetics and heredity

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Abstract

V originále

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

Citovat

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.

@article{1394046,
   author = {MohelnikovaandDuchonova, B. and Kocik, M. and Duchonova, B. and Brynychova, V. and Oliverius, M. and Hlavsa, Jan and Honsova, E. and Mazanec, Jan and Kala, Zdeněk and Ojima, I. and Hughes, D.J. and Doherty, J.E. and Murray, H.A. and Crockard, M.A. and Lemstrova, R. and Soucek, P.},
   article_location = {LONDON},
   article_number = {5},
   doi = {http://dx.doi.org/10.1038/tpj.2016.55},
   keywords = {pancreatic cancer},
   language = {eng},
   issn = {1470-269X},
   journal = {PHARMACOGENOMICS JOURNAL},
   title = {Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216},
   volume = {17},
   year = {2017}
}

TY  - JOUR
ID  - 1394046
AU  - Mohelnikova-Duchonova, B. - Kocik, M. - Duchonova, B. - Brynychova, V. - Oliverius, M. - Hlavsa, Jan - Honsova, E. - Mazanec, Jan - Kala, Zdeněk - Ojima, I. - Hughes, D.J. - Doherty, J.E. - Murray, H.A. - Crockard, M.A. - Lemstrova, R. - Soucek, P.
PY  - 2017
TI  - Hedgehog pathway overexpression in pancreatic cancer is abrogated by new-generation taxoid SB-T-1216
JF  - PHARMACOGENOMICS JOURNAL
VL  - 17
IS  - 5
SP  - 452-460
EP  - 452-460
PB  - NATURE PUBLISHING GROUP
SN  - 1470269X
KW  - pancreatic cancer
N2  - 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
ER  -

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. \textit{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.

Detailed Information on Publication Record