The Experts below are selected from a list of 56595 Experts worldwide ranked by ideXlab platform
Leanne M Wiedemann - One of the best experts on this subject based on the ideXlab platform.
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bmp signaling inhibits intestinal stem cell self renewal through suppression of wnt β catenin signaling
Nature Genetics, 2004Co-Authors: Jiwang Zhang, Weigang Tong, Ossama Tawfik, Jason T Ross, David H Scoville, Qiang Tian, Xin Zeng, Leanne M WiedemannAbstract:In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile Polyposis syndrome, juvenile intestinal Polyposis and Cowden disease, respectively. The development of Polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile Polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal Polyposis resembling human juvenile Polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.
David H Scoville - One of the best experts on this subject based on the ideXlab platform.
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bmp signaling inhibits intestinal stem cell self renewal through suppression of wnt β catenin signaling
Nature Genetics, 2004Co-Authors: Xi C He, Jiwang Zhang, Weigang Tong, Ossama Tawfik, Jason T Ross, David H Scoville, Qiang Tian, Xin Zeng, Xi HeAbstract:In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile Polyposis syndrome1, juvenile intestinal Polyposis2 and Cowden disease3, respectively. The development of Polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways4,5. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile Polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal Polyposis resembling human juvenile Polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase–Akt, mediates the convergence of the BMP and Wnt pathways on control of β-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.
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bmp signaling inhibits intestinal stem cell self renewal through suppression of wnt β catenin signaling
Nature Genetics, 2004Co-Authors: Jiwang Zhang, Weigang Tong, Ossama Tawfik, Jason T Ross, David H Scoville, Qiang Tian, Xin Zeng, Leanne M WiedemannAbstract:In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile Polyposis syndrome, juvenile intestinal Polyposis and Cowden disease, respectively. The development of Polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile Polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal Polyposis resembling human juvenile Polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.
Menachem Moshkowitz - One of the best experts on this subject based on the ideXlab platform.
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Small Bowel Polyposis Syndromes
Current Gastroenterology Reports, 2011Co-Authors: Nadir Arber, Menachem MoshkowitzAbstract:Intestinal Polyposis syndromes are relatively rare. However, it is important for clinicians to recognize the potential risks of these syndromes. Based on histology, these syndromes can be classified mainly into hamartomatous Polyposis syndromes and familial adenomatous Polyposis (FAP), which affects mainly the large intestine. This review discusses the clinical manifestations and underlying genetics of the most common small intestinal Polyposis syndromes: Peutz-Jeghers syndrome (PJS), juvenile Polyposis (JP), PTEN hamartoma tumor syndrome (PHTS), and the small intestinal implications of familial adenomatous Polyposis (FAP).
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Small Bowel Polyposis Syndromes
Current Gastroenterology Reports, 2011Co-Authors: Nadir Arber, Menachem MoshkowitzAbstract:Intestinal Polyposis syndromes are relatively rare. However, it is important for clinicians to recognize the potential risks of these syndromes. Based on histology, these syndromes can be classified mainly into hamartomatous Polyposis syndromes and familial adenomatous Polyposis (FAP), which affects mainly the large intestine. This review discusses the clinical manifestations and underlying genetics of the most common small intestinal Polyposis syndromes: Peutz-Jeghers syndrome (PJS), juvenile Polyposis (JP), PTEN hamartoma tumor syndrome (PHTS), and the small intestinal implications of familial adenomatous Polyposis (FAP).
Tuncay Yilmazlar - One of the best experts on this subject based on the ideXlab platform.
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The Mutation Spectrum of the APC Gene in Turkish Patients with Familial Adenomatous Polyposis
Diseases of the colon and rectum, 2007Co-Authors: Berrin Tunca, Gulsah Cecener, Unal Egeli, Abdullah Zorluoglu, Tuncay YilmazlarAbstract:Purpose Familial adenomatous Polyposis, an autosomal-dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps, results from mutations in the adenomatous Polyposis coli tumor suppressor gene. This study was designed to investigate adenomatous Polyposis coli gene mutations in members of Turkish families with familial adenomatous Polyposis to constitute an adenomatous Polyposis coli mutation spectrum for the Turkish population and to determine specific biomarkers for use in the early diagnosis of familial adenomatous Polyposis.
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Investigation of APC mutations in a Turkish familial adenomatous Polyposis family by heterodublex analysis.
Diseases of the colon and rectum, 2005Co-Authors: Berrin Tunca, Gulsah Cecener, Unal Egeli, Mirco Menigatti, Piero Benatti, Monica Pedroni, A Scarselli, F Borghi, Elisa Sala, Tuncay YilmazlarAbstract:PURPOSE: Familial adenomatous Polyposis is an autosomal dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps. Mutations in the adenomatous Polyposis coli gene are primarily responsible for the development of this disease. This study was designed to investigation of adenomatous Polyposis coli (APC) gene mutations in members of familial adenomatous Polyposis family to identify individuals at risk of the disease. METHODS: We examined one patient with familial adenomatous Polyposis and 21 family members including one affected person from familial adenomatous Polyposis and 20 nonsymptomatic persons. We studied E, D, F, and G segments of exon 15 of the adenomatous Polyposis coli gene by heteroduplex analysis. RESULTS: We used silver staining method for staining. We found a mutation for five persons at segment F of exon 15 of the adenomatous Polyposis coli gene. Two of them were affected by colorectal cancer, one of whom was the proband, and the other three were non-symptomatic family members. The pathogenetic mutation was a T deletion at codon 1172, causing a frameshift in the adenomatous Polyposis coli gene, as a result of the sequencing analysis of these cases. CONCLUSIONS: Investigation of adenomatous Polyposis coli gene mutations is very important for the identification of genetic susceptibility to colorectal cancer and for the definition of tumor developing at an early stage. Furthermore, the identification of this mutation for the first time in a Turkish family will be useful to foster further studies on familial adenomatous Polyposis in Turkey.
Allan D Spigelman - One of the best experts on this subject based on the ideXlab platform.
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NTHL1-associate Polyposis: first Australian case report
Familial Cancer, 2019Co-Authors: Alexandra Groves, Margaret Gleeson, Allan D SpigelmanAbstract:While familial adenomatous Polyposis accounts for approximately 1% of all colorectal cancer, the genetic cause underlying the development of multiple colonic adenomas remains unsolved in many patients. Adenomatous Polyposis syndromes can be divided into: familial adenomatous Polyposis, MUTYH -associated Polyposis, polymerase proofreading associated Polyposis and the recently described NTHL1 -associated Polyposis (NAP). NAP is characterised by recessive inheritance, attenuated adenomatous Polyposis, colonic cancer(s) and possible extracolonic malignancies. To date, 11 cases have been reported as having germline homozygous or compound heterozygous mutations in the base excision repair gene NTHL1 . Here we present a further case of a 65-year-old male with a history of adenomatous Polyposis and bladder cancer, who has a previously described homozygous nonsense variant in the NTHL1 gene. This case is consistent with the emerging phenotype previously described of multiple colorectal adenomas and at least one primary tumour, adding to the small but growing body of literature about NAP.
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Extracolonic Polyposis in familial adenomatous Polyposis: so near and yet so far
Gut, 2004Co-Authors: Allan D SpigelmanAbstract:There is a need to develop effective preventative and/or curative strategies for duodenal Polyposis in patients with familial adenomatous Polyposis Extracolonic polyps in familial adenomatous Polyposis (FAP) were described in the stomach by Hauser in 1895 and in the duodenum by Funkenstein in 1904.1 These findings postdate the first description of colonic lesions consistent with Polyposis, described by Menzel in 1721, although this case is probably a description of inflammatory polyps.1 The first case of adenomatous Polyposis may have been recorded by Corvisart in 1847.1 However, the first definite accounts of the disease were given by Chargelaigue in 1859 in a 16 year old girl and a 21 year old man.1 While Polyposis has thus been reasonably well described for hundreds of years and the coexistence of extracolonic polyps in this syndrome has been known for over 100 years, it was not until …
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Familial adenomatous Polyposis and duodenal lymphoma: report of a case.
Diseases of the colon and rectum, 2003Co-Authors: Frank A. Frizelle, C. T. Hemmings, M. R. Whitehead, Allan D SpigelmanAbstract:The occurrence of duodenal Polyposis is well recognized in familial adenomatous Polyposis. Lymphoid hyperplasia in association with familial adenomatous Polyposis usually occurs in the terminal ileum, but it can occur in the duodenum and may be endoscopically difficult to distinguish from an adenoma. A case report is presented in which a 54-yearold male with familial adenomatous Polyposis, who 20 years earlier had a subtotal colectomy and ileorectal anastomosis, presented with a large rectal villous tumor and was found to have a duodenal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The role of lymphoid hyperplasia in the development of mucosa-associated lymphoid tissue lymphoma is discussed, as well as the issue of mucosa-associated lymphoid tissue lymphoma in familial adenomatous Polyposis. In cases in which biopsies of polypoid lesions in patients with familial adenomatous Polyposis show dense lymphoid aggregates, flow cytometry may assist in the diagnosis.
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Biliary bile acid profiles in familial adenomatous Polyposis.
The British journal of surgery, 1991Co-Authors: Allan D Spigelman, R. W. Owen, M. J. Hill, R. K. S. PhillipsAbstract:Patients with familial adenomatous Polyposis have an excess risk for adenomas and cancers of the upper and lower gastrointestinal tract. In the upper intestine these lesions occur mainly around the ampulla of Vater and they parallel mucosal exposure to bile. In view of this finding and of evidence that bile acids play a role in colorectal carcinogenesis, biliary bile acid profiles were determined in 29 patients with familial adenomatous Polyposis (12 before colectomy, 17 after colectomy) and in 28 patients without familial adenomatous Polyposis (all with colons in situ). Patients with familial adenomatous Polyposis had a higher total biliary bile acid concentration than the others. The bile of patients with Polyposis had a greater proportion of chenodeoxycholic acid and a lower proportion of deoxycholic acid than did the bile of patients without Polyposis. The ratio of chenodeoxycholic acid and its metabolite lithocholic acid to cholic acid and its metabolite deoxycholic acid, which is related to subsequent bile acid profiles in the colon, was higher in patients with Polyposis. Because bile acids influence cellular proliferation, these findings may be of importance with respect to intestinal adenoma and cancer growth.
