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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Hedgehog inhibition mediates radiation sensitivity in mouse xenograft models of human esophageal adenocarcinoma.
Jennifer Teichman,Lorin Dodbiba,Henry Thai,Andrew Fleet,Trevor Morey,Lucy Liu,Lucy Liu,Madison McGregor,Dangxiao Cheng,Zhuo Chen,Gail Darling,Yonathan Brhane,Yuyao Song,Osvaldo Espin-Garcia,Wei Xu,Wei Xu,Hala Girgis,Joerg Schwock,Helen Mackay,Robert G. Bristow,Robert G. Bristow,Laurie Ailles,Laurie Ailles,Geoffrey Liu,Geoffrey Liu +24 more
TL;DR: Hh signaling mediates the radiation response in some EAC PDX models, and inhibition of this pathway may augment the efficacy of radiation in tumours that are Hh dependent.
Journal ArticleDOI
Lentivirus-mediated silencing of the PTC1 and PTC2 genes promotes recovery from spinal cord injury by activating the Hedgehog signaling pathway in a rat model
TL;DR: Activation of the Hh signaling pathway by silencing PTC1 and PTC2 may reduce inflammation and may ultimately promote SCI recovery, and may provide new insights into therapeutic indications and regenerative recovery tools for the treatment of SCI.
Journal ArticleDOI
Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer:
Abu Shadat Mohammod Noman,Rashed R Parag,Muhammad I. Rashid,Mohammad Z. Rahman,Ali Asgar Chowdhury,Afrin Sultana,Chandsultana Jerin,Ayesha Siddiqua,Lutfur Rahman,Afsana Shirin,Junayed Nayeem,Reaz Mahmud,Sonam Akther,Rajib Shil,Ikram Hossain,S. S. Alam,Arfina Chowdhury,Shabnam B. Basher,Abul Hasan,Shammy Bithy,Jannatul Aklima,Mizanur Rahman,Nabila Chowdhury,Tahmina Banu,Bedri Karakas,Herman Yeger,Walid A. Farhat,Syed S. Islam +27 more
TL;DR: It is suggested that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.
Journal ArticleDOI
Development of Novel Targeted Agents in the Treatment of Metastatic Colorectal Cancer
TL;DR: Although the field of drug development in CRC was stagnant during a period of numerous large trials with approved agents, multiple new agents are currently in development and this review discusses molecular pathways and novel targeted agents in the treatment of CRC.
Journal ArticleDOI
Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer.
Grigorios Rallis,Triantafyllia Koletsa,Zenia Saridaki,Kyriaki Manousou,Georgia-Angeliki Koliou,Ioannis Kostopoulos,Vassiliki Kotoula,Thomas Makatsoris,Helen P. Kourea,Georgia Raptou,Sofia Chrisafi,Epaminontas Samantas,Kleo Papaparaskeva,Elissavet Pazarli,Pavlos Papakostas,Georgia Kafiri,Davide Mauri,Alexandra Papoudou-Bai,Christos Christodoulou,Kalliopi Petraki,Nikolaos Dombros,Dimitrios Pectasides,George Fountzilas +22 more
TL;DR: Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.
References
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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.
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Hedgehog signaling in animal development: paradigms and principles.
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