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
Functional compensation in Hedgehog signaling during mouse prostate development.
TL;DR: A surprising degree of functional redundancy operating both at the level of the ligand and at thelevel of transcriptional regulation that effectively mitigates phenotypes associated with Hh-signaling perturbations is revealed.
Journal ArticleDOI
Apoptosis, proliferation and differentiation patterns are influenced by Zebularine and SAHA in pancreatic cancer models
Daniel Neureiter,Steffen Zopf,Thorsten Leu,Otto Dietze,Cornelia Hauser-Kronberger,Eckhart G. Hahn,Christoph Herold,Matthias Ocker +7 more
TL;DR: Epigenetic modulation via inhibition of DNA methyltransferase and histone deacetylase induces apoptosis in human pancreatic cancer cells in vitro and delays xenograft growth in vivo, which is associated with a morphological/molecular phenotypic stabilization.
Journal ArticleDOI
Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling
Rajashree Rana,Candace E. Carroll,Ho-Jin Lee,Ju Bao,Suresh Marada,Christy R. Grace,Cristina D. Guibao,Stacey K. Ogden,Jie Zheng +8 more
TL;DR: The NMR solution structure of the Drosophila SmoCRD is presented, and interactions between the glucocorticoid budesonide (Bud) and the Smo CRDs from both Drosophile and human are described.
Journal ArticleDOI
Biomedical applications of poisonous plant research.
TL;DR: Advances in biomedical applications of the toxins of Veratrum californicum (western false hellebore), Lupinus species (lupines), and Astragalus and Oxytropis species (locoweeds) are illustrated.
Journal ArticleDOI
Genome-wide analysis of CDX2 binding in intestinal epithelial cells (Caco-2).
Mette Boyd,Morten Hartvig Hansen,Tine G.K. Jensen,Anna Perearnau,Anders Krüger Olsen,Lotte L. Bram,Mads Bak,Niels Tommerup,Jørgen Olsen,Jesper T. Troelsen +9 more
TL;DR: The ChIP-seq technique combines chromatin immunoprecipitation with next generation sequencing resulting in a high throughput experimental method of identifying direct targets of specific transcription factors, leading to the identification of the direct binding of CDX2 to several known and novel target genes in the intestinal cell.
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
TL;DR: Osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation.
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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
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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