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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Journal ArticleDOI
The Prognostic Significance of the Hedgehog Signaling Pathway in Colorectal Cancer
Vassilis Papadopoulos,Konstantinos Tsapakidis,Natalia A. Riobo Del Galdo,Christos Papandreou,Francesco Del Galdo,Alan Anthoney,Nikos Sakellaridis,Konstantinos Dimas,Konstantinos Kamposioras +8 more
TL;DR: According to the studies reviewed herein the activation of the Hh pathway seems to be correlated with adverse clinicopathological features and worse survival, however, to date study results show significant variability with regard to the effect on outcomes.
Journal ArticleDOI
Hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation
Beate Alinger,Tobias Kiesslich,Christian Datz,Fritz Aberger,F. Strasser,Frieder Berr,Otto Dietze,Klaus Kaserer,Cornelia Hauser-Kronberger +8 more
TL;DR: It is concluded that Hedgehog signaling is involved rather in constant differentiation and renewing of the colonic lining epithelium than in cancer formation, growth, or proliferation.
Patent
Cyclopamine lactam analogs and methods of use thereof
TL;DR: In this paper, the present invention relates to steroidal alkaloids useful in the treatment of hedgehog pathway related disorders, particularly cancer, and is related to the present paper.
Journal ArticleDOI
Pancreatic cancer stem cells and relevance to cancer treatments.
Filip Bednar,Diane M. Simeone +1 more
TL;DR: Recent evidence supports the existence of human pancreatic cancer stem cells, which appear to drive tumor initiation and progression and are particularly resistant to cell death induced by radiation or chemotherapy.
Journal ArticleDOI
Relationships between the autonomic nervous system, humoral factors and immune functions in the intestine.
TL;DR: The present review focuses on the relationships between the gene expression and the intestine, and furthermore, presents the evidence and gastrointestinal diseases of the autonomic nervous system, the humoral factors, and the immune functions related intestinal proliferation and apoptosis.
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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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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Purification and Characterization of Mouse Hematopoietic Stem Cells
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Journal ArticleDOI
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
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