Journal ArticleDOI
Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours
David M. Berman,Sunil S. Karhadkar,Anirban Maitra,Rocío Montes de Oca,Meg R. Gerstenblith,Kimberly J. Briggs,Antony R. Parker,Yutaka Shimada,James R. Eshleman,D. Neil Watkins,Philip A. Beachy +10 more
TLDR
A wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathways antagonist.Abstract:
Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.read more
Citations
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Deciphering the role of hedgehog signaling in pancreatic cancer.
TL;DR: This review will summarize what the authors know about hedgehog signaling in pancreatic cancer, and try to explain the contradicting roles of Hedgehog signaling as well as the reason(s) behind the failed clinical trials.
Book
New advances on disease biomarkers and molecular targets in biomedicine
Npy Lee,CY Cheung,Jmc Luk +2 more
Journal ArticleDOI
Cancer Stem Cell and Gastrointestinal Cancer: Current Status, Targeted Therapy and Future Implications
TL;DR: Findings related to the role and identification of CSCs in GI-cancers are reviewed and the crucial pathways involved in regulatingCSCs populations’ development and drug resistance are discussed, and use of the tumoroid culture to test novel C SCs-targeted cancer therapies are discussed.
Journal ArticleDOI
Novel molecular targets for the treatment of gastroenteropancreatic endocrine tumors: answers and unsolved problems.
Gabriele Capurso,Volker Fendrich,Maria Rinzivillo,Francesco Panzuto,Detlef K. Bartsch,Gianfranco Delle Fave +5 more
TL;DR: The goals of the present review are to elucidate the possible advantage of combined treatments in overcoming induced resistances, and to identify biomarkers able to predict clinical efficacy.
Journal ArticleDOI
Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.
TL;DR: Experimental studies in the zebrafish are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.
References
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Osteoblastic cells regulate the haematopoietic stem cell niche
Laura M. Calvi,Gregor B. Adams,Kathryn W. Weibrecht,Jonathan M. Weber,David P. Olson,M. C. Knight,Roderick P. Martin,Ernestina Schipani,P. Divieti,F. R. Bringhurst,Laurie A. Milner,Henry M. Kronenberg,David T. Scadden +12 more
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Identification of the haematopoietic stem cell niche and control of the niche size
Jiwang Zhang,Chao Niu,Ling Ye,Haiyang Huang,Xi C. He,Wei Gang Tong,Jason Ross,Jeffrey S. Haug,Teri Johnson,Jian Q. Feng,Stephen E. Harris,Leanne M. Wiedemann,Leanne M. Wiedemann,Yuji Mishina,Linheng Li,Linheng Li +15 more
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Hedgehog signaling in animal development: paradigms and principles.
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Journal ArticleDOI
Purification and Characterization of Mouse Hematopoietic Stem Cells
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A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
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