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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
Matthias Holzlechner, Katharina Strasser, Elitsa Zareva, Luise Steinhaeuser, Hanna Birnleitner, Andrea Beer, Michael Bergmann, Rudolf Oehler, Martina Marchetti-Deschmann
Tissue-resident immune cells differ from the corresponding blood cells in many functional aspects. Although the proteome of blood immune cells is well investigated there are almost no data on tissue-resident immune cells. Here we explored the potential of MALDI-TOF-MS imaging (MSI) to investigate these cells in colon tissue, which exhibits a strong immune infiltration. MSI identified several proteinaceous markers that colocalized with specific structures of the colon such as mucosa or muscularis mucosae in six patients...
October 18, 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
#12
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...
September 30, 2016: 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
#13
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
https://www.readbyqxmd.com/read/27622020/extracellular-hsp110-skews-macrophage-polarization-in-colorectal-cancer
#14
Kevin Berthenet, Christophe Boudesco, Ada Collura, Magali Svrcek, Sarah Richaud, Arlette Hammann, Sebastien Causse, Nadhir Yousfi, Kristell Wanherdrick, Laurence Duplomb, Alex Duval, Carmen Garrido, Gaetan Jego
HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110 inactivating mutation (HSP110DE9). In this work, we have used patients' biopsies and human CRC cells grown in vitro and in vivo (xenografts) to demonstrate that (1) HSP110 is secreted by CRC cells and that the amount of this extracellular HSP110 is strongly decreased by the expression of the mutant HSP110DE9, (2) Supernatants from CRC cells overexpressing HSP110 or purified recombinant human HSP110 (LPS-free) affect macrophage differentiation/polarization by favoring a pro-tumor, anti-inflammatory profile, (3) Conversely, inhibition of HSP110 (expression of siRNA, HSP110DE9 or immunodepletion) induced the formation of macrophages with a cytotoxic, pro-inflammatory profile...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27600984/toward-a-molecular-classification-of-synchronous-colorectal-cancer-clinical-and-molecular-characterization
#15
María Arriba, Ricardo Sánchez, Daniel Rueda, Laura Gómez, Juan L García, Yolanda Rodríguez, José Antonio Pajares, Jessica Pérez, Miguel Urioste, Rogelio González Sarmiento, José Perea
BACKGROUND: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood. PATIENTS AND METHODS: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor...
August 9, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/27494849/twist1-induced-epithelial-mesenchymal-transition-according-to-microsatellite-instability-status-in-colon-cancer-cells
#16
Bo Young Oh, So-Young Kim, Yeo Song Lee, Hye Kyung Hong, Tae Won Kim, Seok Hyung Kim, Woo Yong Lee, Yong Beom Cho
Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit impaired epithelial-mesenchymal transition (EMT), but little is known about the underlying mechanisms of this phenomenon. In this study, we investigated the role of Twist1 and its downstream signaling cascades in EMT induction according to MSI status. To investigate the effects of Twist1 on EMT induction according to MSI status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways were evaluated via in vitro and in vivo experiments...
August 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27430658/serrated-polyposis-associated-with-a-family-history-of-colorectal-cancer-and-or-polyps-the-preferential-location-of-polyps-in-the-colon-and-rectum-defines-two-molecular-entities
#17
Patrícia Silva, Cristina Albuquerque, Pedro Lage, Vanessa Fontes, Ricardo Fonseca, Inês Vitoriano, Bruno Filipe, Paula Rodrigues, Susana Moita, Sara Ferreira, Rita Sousa, Isabel Claro, Carlos Nobre Leitão, Paula Chaves, António Dias Pereira
Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0...
September 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27429617/low-level-of-microsatellite-instability-correlates-with-poor-clinical-prognosis-in-stage-ii-colorectal-cancer-patients
#18
Ehsan Nazemalhosseini Mojarad, Seyed Mohammad Hossein Kashfi, Hanieh Mirtalebi, Mohammad Yaghoob Taleghani, Pedram Azimzadeh, Sanaz Savabkar, Mohammad Amin Pourhoseingholi, Hasan Jalaeikhoo, Hamid Asadzadeh Aghdaei, Peter J K Kuppen, Mohammad Reza Zali
The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance...
2016: Journal of Oncology
https://www.readbyqxmd.com/read/27422471/primary-colon-adenosquamous-carcinoma-in-a-patient-with-lynch-syndrome-a-new-histologic-subtype-associated-with-microsatellite-instability
#19
Virginia E Duncan, Shuko Harada, Todd M Stevens
We report a case of a 53-year-old woman who presented with rectal bleeding and a 9.5 cm hemicircumferential ascending colon mass. Histology revealed adenosquamous carcinoma (ASC), a rare subtype comprised of malignant squamous and glandular elements. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression in squamous and glandular components, indicative of microsatellite instability (MSI). MSI is caused by loss-of-function defects in DNA mismatch repair genes, leading to increased susceptibility to a variety of neoplasms; the role of MSI in colorectal ASC is unknown...
October 2016: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27376251/clinicopathological-characteristics-of-serrated-polyps-as-precursors-to-colorectal-cancer-current-status-and-management
#20
Koichi Okamoto, Shinji Kitamura, Tetsuo Kimura, Tadahiko Nakagawa, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Tetsuji Takayama
Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers (CRCs). Accordingly, serrated polyps such as traditional serrated adenoma (TSA) and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into 3 subtypes, consisting of hyperplastic polyp (HP), SSA/P, and TSA, according to the World Health Organization (WHO) classification...
July 4, 2016: Journal of Gastroenterology and Hepatology
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