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
More filters
Journal ArticleDOI
The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth
Valérian Dormoy,Sabrina Danilin,Véronique Lindner,Lionel Thomas,Sylvie Rothhut,Catherine Coquard,Jean-Jacques Helwig,Didier Jacqmin,Hervé Lang,Thierry Massfelder +9 more
TL;DR: These findings support targeting SHH for the treatment of CRCC and pave the way for innovative and additional investigations in a broad range of cancers.
Journal ArticleDOI
Hedgehog signaling in human hepatocellular carcinoma.
TL;DR: Evidence that hedgehog signaling may be activated in some HCC tumors is provided for the first time and the results indicate that the hedgehog pathway may be a new candidate for therapeutic targeting in HCC.
Journal ArticleDOI
Intestinal mucosal atrophy and adaptation.
TL;DR: Current understanding of the basic science surrounding adaptation is summarized, the wide range of potential targets for therapeutic intervention are delineated, and how these might be incorporated into an overall treatment plan are discussed.
Journal ArticleDOI
Gastric cancer stem cells: evidence, potential markers, and clinical implications
Daniel Brungs,Morteza Aghmesheh,Kara L. Vine,Kara L. Vine,Therese M. Becker,Martin G Carolan,Marie Ranson,Marie Ranson +7 more
TL;DR: A review of the current evidence for CSC in gastric cancer, with an emphasis on candidate CSC markers, clinical implications, and potential therapeutic approaches, concludes that targeting the CSC population may be essential in preventing the recurrence and spread of a tumour.
Journal ArticleDOI
Inflammatory pathways in the early steps of colorectal cancer development.
TL;DR: In this article, the inflammatory pathways involved in the early stages of colorectal cancer were examined, with a particular emphasis on colon cancer, and proteins, such as cyclooxygenases and resolvins, are crucial in these inflammatory pathways.
References
More filters
Journal ArticleDOI
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
TL;DR: Osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation.
Journal ArticleDOI
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
TL;DR: It is concluded that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of H SCs by regulating niche size.
Journal ArticleDOI
Hedgehog signaling in animal development: paradigms and principles.
TL;DR: In their screen for mutations that disrupt the Drosophila larval body plan, these authors identified several that cause the duplication of denticles and an accompanying loss of naked cuticle, characteristic of the posterior half of each segment.
Journal ArticleDOI
Purification and Characterization of Mouse Hematopoietic Stem Cells
TL;DR: Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers and thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors.
Journal ArticleDOI
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
TL;DR: The prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloids lineages is reported.
Related Papers (5)
Hedgehog signaling in animal development: paradigms and principles.
Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome
Heidi Hahn,Carol Wicking,Peter G. Zaphiropoulos,Mae R. Gailani,Susan Shanley,Abirami Chidambaram,Igor Vorechovsky,Erika Holmberg,Anne Birgitte Undén,Susan Gillies,Kylie Negus,Ian M. Smyth,Carolyn Pressman,David J. Leffell,Bernard Gerrard,Alisa M. Goldstein,Michael Dean,Rune Toftgård,Georgia Chenevix-Trench,Brandon J. Wainwright,Allen E. Bale +20 more