The Experts below are selected from a list of 4698 Experts worldwide ranked by ideXlab platform
Takeo Iwama - One of the best experts on this subject based on the ideXlab platform.
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a proposed staging system and stage specific interventions for familial adenomatous Polyposis
Gastrointestinal Endoscopy, 2016Co-Authors: Patrick M Lynch, Jeffrey S Morris, Sijin Wen, Shailesh M Advani, William A Ross, George J Chang, Miguel A Rodriguezbigas, Gottumukkala S Raju, Luigi Ricciardiello, Takeo IwamaAbstract:Background and Aims It is not possible to accurately count adenomas in many patients with familial adenomatous Polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract Polyposis. Methods Twenty-four Colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. Results The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. Conclusions The proposed FAP Colon Polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of Polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.
Eric R Fearon - One of the best experts on this subject based on the ideXlab platform.
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tissue specific effects of reduced β catenin expression on adenomatous Polyposis coli mutation instigated tumorigenesis in mouse Colon and ovarian epithelium
PLOS Genetics, 2015Co-Authors: Naoya Sakamoto, Maranne Green, Alexandra B Wiese, Megan Green, Aytekin Akyol, Yali Zhai, Rong Wu, Eric R FearonAbstract:Adenomatous Polyposis coli (APC) inactivating mutations are present in most human colorectal cancers and some other cancers. The APC protein regulates the β-catenin protein pool that functions as a co-activator of T cell factor (TCF)-regulated transcription in Wnt pathway signaling. We studied effects of reduced dosage of the Ctnnb1 gene encoding β-catenin in Apc-mutation-induced Colon and ovarian mouse tumorigenesis and cell culture models. Concurrent somatic inactivation of one Ctnnb1 allele, dramatically inhibited Apc mutation-induced Colon Polyposis and greatly extended Apc-mutant mouse survival. Ctnnb1 hemizygous dose markedly inhibited increases in β-catenin levels in the cytoplasm and nucleus following Apc inactivation in Colon epithelium, with attenuated expression of key β-catenin/TCF-regulated target genes, including those encoding the EphB2/B3 receptors, the stem cell marker Lgr5, and Myc, leading to maintenance of crypt compartmentalization and restriction of stem and proliferating cells to the crypt base. A critical threshold for β-catenin levels in TCF-regulated transcription was uncovered for Apc mutation-induced effects in Colon epithelium, along with evidence of a feed-forward role for β-catenin in Ctnnb1 gene expression and CTNNB1 transcription. The active β-catenin protein pool was highly sensitive to CTNNB1 transcript levels in Colon cancer cells. In mouse ovarian endometrioid adenocarcinomas (OEAs) arising from Apc- and Pten-inactivation, while Ctnnb1 hemizygous dose affected β-catenin levels and some β-catenin/TCF target genes, Myc induction was retained and OEAs arose in a fashion akin to that seen with intact Ctnnb1 gene dose. Our findings indicate Ctnnb1 gene dose exerts tissue-specific differences in Apc mutation-instigated tumorigenesis. Differential expression of selected β-catenin/TCF-regulated genes, such as Myc, likely underlies context-dependent effects of Ctnnb1 gene dosage in tumorigenesis.
Fotini Gounari - One of the best experts on this subject based on the ideXlab platform.
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cell intrinsic deregulated s catenin signaling promotes expansion of bone marrow derived connective tissue type mast cells systemic inflammation and Colon cancer
Frontiers in Immunology, 2019Co-Authors: Abdulrahman Saadalla, Mariana Machado Lima, Fu Nien Tsai, Abu Osman, Mahendra Pal Singh, David R Linden, Kristen L Dennis, S Mansour M Haeryfar, Michael F Gurish, Fotini GounariAbstract:Mast cells constitutively express s-catenin and expand in solid tumors such as Colon and skin cancer. However, the role of s-catenin signaling in mast cells and the cause or effect of mast cell expansion and tumor growth has yet to be established. In earlier studies we used mast cell depletion and protease staining approaches, to provide evidence for a causative role of mast cells in small bowel Polyposis, and related specific phenotypes and distributions of tumor infiltrating mast cells to stages of tumor growth. Here we report that, stabilization of s-catenin expands mast cells to promote high incidence of Colon Polyposis and infrequent small bowel polyps and skin cancer. Expression of a dominant acting s-catenin in mast cells (5CreCAT) stimulated maturation and expression of granule stored proteases. Both mucosal and connective tissue type mast cells accumulated in Colonic small bowel polyps independent of gender, and mice developed chronic systemic inflammation with splenomegaly. Reconstitution of Polyposis-prone mice with bone marrow from 5CreCAT mice resulted in focal expansion of connective tissue like mast cells, which are normally rare in benign polyps and characteristically expand during adenoma-to-carcinoma transition. Our findings highlight a hitherto unknown contribution of s-catenin signaling in mast cells to their maturation and to increased risk of Colon cancer.
Kanji Kuma - One of the best experts on this subject based on the ideXlab platform.
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cribriform morular variant of papillary thyroid carcinoma clue to early detection of familial adenomatous Polyposis associated Colon cancer
World Journal of Surgery, 2004Co-Authors: Chisato Tomoda, Akira Miyauchi, Takashi Uruno, Yuuki Takamura, Yasuhiro Ito, Akihiro Miya, Kaoru Kobayashi, Fumio Matsuzuka, Seiji Kuma, Kanji KumaAbstract:The cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) is a rare histologic subtype of PTC that shows a combination of growth patterns including cribriform and spindle cell areas. The thyroid cancer with this unique histology was originally reported in patients with familial adenomatous Polyposis (FAP), although it was later found in patients without Polyposis as well. Because of its rarity, its clinical features are not clear. We reviewed seven patients with CMV-PTC who were found among 4194 patients with PTC in our pathology files between June 1991 and March 2003. The prevalence of CMV was 0.16% among all PTCs. We invited these patients to our hospital so we could obtain a detailed family history and recommend Colonoscopic examination and germline APC gene analysis. Two patients without subjective symptoms had Polyposis of the Colon and Colon cancers. Germline APC gene mutations were found in both patients. The father of a patient who refused the invitation was revealed to have undergone surgery for Colon Polyposis. In the remaining four patients, neither Polyposis nor APC gene mutation was found. Common clinical features included a young age (mean 25 years), predominance of females, circumscribed tumors, negative node metastasis, and no recurrence of the thyroid cancer after surgery. Two of the three patients with Colon Polyposis had bilateral multiple thyroid tumors, whereas the remaining four (without Polyposis) had a solitary tumor. The histopathology of CMV in patients with PTC should arouse a suspicion of FAP, especially if there are multiple tumors. This finding can lead to early detection of Colon cancer.
Patrick M Lynch - One of the best experts on this subject based on the ideXlab platform.
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a proposed staging system and stage specific interventions for familial adenomatous Polyposis
Gastrointestinal Endoscopy, 2016Co-Authors: Patrick M Lynch, Jeffrey S Morris, Sijin Wen, Shailesh M Advani, William A Ross, George J Chang, Miguel A Rodriguezbigas, Gottumukkala S Raju, Luigi Ricciardiello, Takeo IwamaAbstract:Background and Aims It is not possible to accurately count adenomas in many patients with familial adenomatous Polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract Polyposis. Methods Twenty-four Colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. Results The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. Conclusions The proposed FAP Colon Polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of Polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.