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https://www.readbyqxmd.com/read/28093453/interactions-between-microsatellite-instability-and-human-gut-colonization-by-escherichia-coli-in-colorectal-cancer
#1
Johan Gagnière, Virginie Bonnin, Anne-Sophie Jarrousse, Emilie Cardamone, Allison Agus, Nancy Uhrhammer, Pierre Sauvanet, Pierre Déchelotte, Nicolas Barnich, Richard Bonnet, Denis Pezet, Mathilde Bonnet
Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli (E. coli) could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway which leads to microsatellite instability (MSI). This work, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells...
16, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28087988/cpg-island-methylator-phenotype-is-an-independent-predictor-of-survival-after-curative-resection-for-colorectal-cancer-a-prospective-cohort-study
#2
Chang Hyun Kim, Jung Wook Huh, Hyeong Rok Kim, Young Jin Kim
BACKGROUND AND AIMS: The CpG island methylator phenotype (CIMP) is found in approximately 30% of colorectal cancer (CRC) cases. However, the role of CIMP status in predicting oncologic outcomes in curatively resected CRC is still unclear. STUDY: Between January 2006 and December 2006, we retrospectively reviewed 157 consecutive patients who underwent curative surgery for CRC. Prognostic significance of CIMP status was evaluated using reverse transcriptase-polymerase chain reaction...
January 14, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28040692/prognostic-value-of-braf%C3%A2-and%C3%A2-kras%C3%A2-mutations-in-msi-and-mss-stage-iii-colon-cancer
#3
Julien Taieb, Karine Le Malicot, Qian Shi, Frédérique Penault Lorca, Olivier Bouché, Josep Tabernero, Enrico Mini, Richard M Goldberg, Gunnar Folprecht, Jean Luc Van Laethem, Daniel J Sargent, Steven R Alberts, Jean Francois Emile, Pierre Laurent Puig, Frank A Sinicrope
BACKGROUND: The prognostic value of BRAF and KRAS mutations within microsatellite-unstable (MSI) and microsatellite-stable (MSS) subgroups of resected colon carcinoma patients remains controversial. We examined this question in prospectively collected biospecimens from stage III colon cancer with separate analysis of MSI and MSS tumors from patients receiving adjuvant FOLFOX +/- cetuximab in two adjuvant therapy trials. METHODS: Three groups were defined: BRAF Mutant, KRAS Mutant, and double wild-type...
May 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28000726/heterogeneity-of-paclitaxel-distribution-in-different-tumor-models-assessed-by-maldi-mass-spectrometry-imaging
#4
Silvia Giordano, Massimo Zucchetti, Alessandra Decio, Marta Cesca, Ilaria Fuso Nerini, Marika Maiezza, Mariella Ferrari, Simonetta Andrea Licandro, Roberta Frapolli, Raffaella Giavazzi, D'Incalci Maurizio, Enrico Davoli, Lavinia Morosi
The penetration of anticancer drugs in solid tumors is important to ensure the therapeutic effect, so methods are needed to understand drug distribution in different parts of the tumor. Mass spectrometry imaging (MSI) has great potential in this field to visualize drug distribution in organs and tumor tissues with good spatial resolution and superior specificity. We present an accurate and reproducible imaging method to investigate the variation of drug distribution in different parts of solid tumors. The method was applied to study the distribution of paclitaxel in three ovarian cancer models with different histopathological characteristics and in colon cancer (HCT116), breast cancer (MDA-MB-231) and malignant pleural mesothelioma (MPM487)...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27979806/cytotoxic-t-cells-and-granzyme-b-associated-with-improved-colorectal-cancer-survival-in-a-prospective-cohort-of-older-women
#5
Anna E Prizment, Robert A Vierkant, Thomas C Smyrk, Lori S Tillmans, Heather H Nelson, Charles F Lynch, Thomas Pengo, Stephen N Thibodeau, Timothy R Church, James R Cerhan, Kristin E Anderson, Paul J Limburg
BACKGROUND: Host immune response may predict the course of colorectal cancer (CRC). We examined the survival of 468 CRC patients associated with two tumor-infiltrating immune biomarkers - the number of cytotoxic T lymphocytes (CTL) and the activated CTLs, as reflected by the number of cells expressing granzyme B (GZMB) in the prospective Iowa Women's Health Study. METHODS: Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (for CTL) and GZMB antibodies...
December 15, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27938333/pseudomyxoma-peritonei-of-a-mature-ovarian-teratoma-caused-by-mismatch-repair-deficiency-in-a-patient-with-lynch-syndrome-a-case-report
#6
Yoshimasa Gohda, Rei Noguchi, Tomoko Horie, Toru Igari, Harumi Nakamura, Yasunori Ohta, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Seira Hatakeyama, Nozomi Yusa, Yoichi Furukawa, Hideaki Yano
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1-2 cases per million individuals per year. PMP is characterized by the accumulation of abundant mucinous or gelatinous fluid derived from disseminated tumorous cells. Most of the tumorous cells are originated from rupture of appendiceal neoplasms, but some are from the metastasis of cancer of the colon, ovary, fallopian tube, urachus, colorectum, gallbladder, stomach, pancreas, lung and breast. Although frequent mutations in KRAS and/or GNAS genes have been reported, precise molecular mechanism underlying PMP remains to be elucidated...
December 9, 2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27925331/the-mirna-landscape-of-colorectal-polyps
#7
Martha L Slattery, Jennifer S Herrick, Roger K Wolff, Lila E Mullany, John R Stevens, Wade Samowitz
The genomic landscape of adenomas and polyps may help define disease pathways. Expression of miRNAs in adenomas and polyps may importantly contribute to these pathways. We evaluated miRNA expression in 293 polyp-normal colorectal mucosa pairs. Polyps were classified as either adenomatous polyp (AD), hyperplastic polyp (HP), or sessile serrated polyp (SSP). We compared these miRNA expression profiles in polyps to miRNA expression in microsatellite unstable (MSI) and stable (MSS) tumors. A False Discovery Rate (FDR) of 0...
December 7, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27889996/elevated-microsatellite-alterations-at-selected-tetranucleotide-repeats-emast-and-microsatellite-instability-in-patients-with-colorectal-cancer-and-its-clinical-features
#8
H S Lee, K U Park, D-W Kim, M H Ihn, W H Kim, A N Seo, H E Chang, S K Nam, S Y Lee, H-K Oh, S-B Kang
PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status...
November 23, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27859935/single-nucleotide-polymorphisms-within-micrornas-microrna-targets-and-microrna-biogenesis-genes-and-their-impact-on-colorectal-cancer-survival
#9
Lila E Mullany, Jennifer S Herrick, Roger K Wolff, Martha L Slattery
We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1115 cases and 1173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status...
November 18, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27853901/microsatellite-instability-was-not-associated-with-survival-in-stage-iii-colon-cancer-treated-with-adjuvant-chemotherapy-of-oxaliplatin-and-infusional-5-fluorouracil-and-leucovorin-folfox
#10
Jeong Eun Kim, Yong Sang Hong, Hwa Jung Kim, Kyu-Pyo Kim, Sun Young Kim, Seok-Byung Lim, In Ja Park, Chan Wook Kim, Yong Sik Yoon, Chang Sik Yu, Jin Cheon Kim, Ji Hun Kim, Tae Won Kim
BACKGROUND: The impact of microsatellite instability (MSI) on survival in stage III colon cancer treated with adjuvant 5-fluorouracil-oxaliplatin combination (FOLFOX) chemotherapy is not clear. We evaluated the association between MSI and survival in this population. METHODS: We analyzed 598 patients with curatively resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy. We determined MSI status using polymerase chain reaction amplification; tumors were classified as high MSI (MSI-H, ≥2 unstable markers), low MSI (MSI-L, 1 unstable marker), or microsatellite stable (MSS, no unstable marker)...
November 16, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27836416/associations-of-defect-mismatch-repair-genes-with-prognosis-and-heredity-in-sporadic-colorectal-cancer
#11
L Ghanipour, K Jirström, M Sundström, B Glimelius, H Birgisson
BACKGROUND: Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. MATERIAL AND METHODS: Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases...
October 31, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27835699/gasdermin-c-is-upregulated-by-inactivation-of-transforming-growth-factor-%C3%AE-receptor-type-ii-in-the-presence-of-mutated-apc-promoting-colorectal-cancer-proliferation
#12
Masashi Miguchi, Takao Hinoi, Manabu Shimomura, Tomohiro Adachi, Yasufumi Saito, Hiroaki Niitsu, Masatoshi Kochi, Haruki Sada, Yusuke Sotomaru, Tsuneo Ikenoue, Kunitoshi Shigeyasu, Kohji Tanakaya, Yasuhiko Kitadai, Kazuhiro Sentani, Naohide Oue, Wataru Yasui, Hideki Ohdan
Mutations in TGFBR2, a component of the transforming growth factor (TGF)-β signaling pathway, occur in high-frequency microsatellite instability (MSI-H) colorectal cancer (CRC). In mouse models, Tgfbr2 inactivation in the intestinal epithelium accelerates the development of malignant intestinal tumors in combination with disruption of the Wnt-β-catenin pathway. However, no studies have further identified the genes influenced by TGFBR2 inactivation following disruption of the Wnt-β-catenin pathway. We previously described CDX2P-G19Cre;Apcflox/flox mice, which is stochastically null for Apc in the colon epithelium...
2016: PloS One
https://www.readbyqxmd.com/read/27819670/hsp110-promotes-colorectal-cancer-growth-through-stat3-activation
#13
K Berthenet, A'dem Bokhari, A Lagrange, G Marcion, C Boudesco, S Causse, A De Thonel, M Svrcek, A R Goloudina, S Dumont, A Hammann, D S Biard, O N Demidov, R Seigneuric, A Duval, A Collura, G Jego, C Garrido
Heat shock protein 110 (HSP110) is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps cells survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently shown that colorectal cancer patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110-inactivating mutation (HSP110DE9). In this work, we used patient biopsies, human colorectal cancer cells grown in vitro and in vivo (xenografts), and intestinal crypts to demonstrate that HSP110 is also involved in colon cancer growth...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27811854/no-association-of-cpg-island-methylator-phenotype-and-colorectal-cancer-survival-population-based-study
#14
Min Jia, Lina Jansen, Viola Walter, Katrin Tagscherer, Wilfried Roth, Esther Herpel, Matthias Kloor, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister
BACKGROUND: Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. METHODS: The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27781259/-research-progress-of-serrated-polyposis-syndrome
#15
Shihao Dong, Jingsong Chen
Serrated polyposis syndrome (SPS) is closely associated with the initiation and development of colorectal cancer (CRC), however, there is few research on SPS in China. Serrated polyps can be divided into hyperplastic polyps, sessile serrated polyps and traditional serrated polyps. The diagnosis standard of SPS is as following: (1) There are at least 5 serrated lesions in proximal colon, and diameter of more than 2 lesions is >10 mm; (2) The patient has one serrated polyp with family history of SPS; (3) More than 20 serrated polyps can be found in the entire large bowel...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27780077/association-of-cigarette-smoking-and-microrna-expression-in-rectal-cancer-insight-into-tumor-phenotype
#16
Lila E Mullany, Jennifer S Herrick, Roger K Wolff, John R Stevens, Martha L Slattery
Smoking is known to influence messenger RNA (mRNA) expression in colorectal cancer (CRC) cases. As microRNAs (miRNAs) are known repressors of mRNAs, we hypothesize that smoking may influence miRNA expression, thus altering mRNA expression. Our sample consisted of 1447 CRC cases that had normal colorectal mucosa and carcinoma miRNA data and lifestyle data. We examined current smoking, current versus never and former versus never (C/F/N) smoking(1), and pack-years smoked with miRNA expression in normal mucosa as well as differential miRNA expression between paired normal and carcinoma tissue for colon and rectal tissue to determine associations between smoking and miRNA expression...
December 2016: Cancer Epidemiology
https://www.readbyqxmd.com/read/27777940/epigenetic-regulation-of-human-dclk-1-gene-during-colon-carcinogenesis-clinical-and-mechanistic-implications
#17
COMMENT
Pomila Singh, Malaney O'Connell, Sarkar Shubhashish
Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27755872/in-situ-characterization-of-tissue-resident-immune-cells-by-maldi-mass-spectrometry-imaging
#18
Matthias Holzlechner, Katharina Strasser, Elitsa Zareva, Luise Steinhäuser, Hanna Birnleitner, Andrea Beer, Michael Bergmann, Rudolf Oehler, Martina Marchetti-Deschmann
Tissue-resident immune cells differ from their corresponding blood cells in many functional aspects. Although the proteome of blood immune cells has been well-investigated, there are almost no data on tissue-resident immune cells. Here, we explored the potential of using MALDI-TOF-MS imaging (MSI) to investigate these cells in colon tissue, which exhibits a strong infiltration of immune cells. MSI identified several proteinaceous markers that colocalized with specific structures of the colon, such as mucosa or muscularis mucosae, in six patients...
November 3, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27687006/fatty-acid-binding-protein-1-is-preferentially-lost-in-microsatellite-instable-colorectal-carcinomas-and-is-immune-modulated-via-the-interferon-%C3%AE-pathway
#19
Stephanie M Wood, Anthony J Gill, Alexander S Brodsky, Shaolei Lu, Kenneth Friedman, Galina Karashchuk, Kara Lombardo, Dongfang Yang, Murray B Resnick
Fatty acid-binding protein 1 (FABP1) is an intracellular protein responsible for the transportation of long chain fatty acids. Aside from its functions in lipid metabolism and cellular differentiation, FABP1 also plays a role in inflammation through its interaction with peroxisome proliferator-activated receptors (PPARs). Previously, we compared expression of colonic epithelium genes in a subset of microsatellite instable (MSI) colorectal carcinomas (medullary carcinomas) to normal colonic mucosa and found that FABP1 expression was markedly decreased in the tumors...
January 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27623135/microsatellite-instability-in-melanoma-a-comprehensive-review
#20
Ondřej Kubeček, Jindřich Kopecký
Microsatellite instability (MSI) and mismatch repair deficiency are an emerging issue in oncology and molecular pathology. Besides being associated with better clinical outcome in colon cancer, MSI also harbors the potential to predict response to chemotherapy and immunotherapy. MSI was also observed in other solid tumors, including endometrial cancer, ovarian cancer, and melanoma, besides colon cancer. Strong evidence shows that MSI is a frequent event in melanoma. However, the data on MSI prevalence, pathogenesis, and clinical consequences in melanoma are limited...
September 12, 2016: Melanoma Research
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