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https://www.readbyqxmd.com/read/28512763/impact-of-mlh1-expression-on-tumour-evolution-after-curative-surgical-tumour-resection-in-a-murine-orthotopic-xenograft-model-for-human-msi-colon-cancer
#1
Katy Meunier, Marianne Ferron, Claire Calmel, Jean-François Fléjou, Marc Pocard, Françoise Praz
Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumour evolution after curative surgical resection using a xenograft tumour model. Transplantable tumours established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals...
May 16, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#2
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507641/a-case-report-of-muir-torre-syndrome-in-a-woman-with-breast-cancer-and-msi-low-skin-squamous-cell-carcinoma
#3
Caroline Kientz, Marie-Odile Joly, Laurence Faivre, Alix Clemenson, Sophie Dalac, Côme Lepage, Caroline Chapusot, Caroline Jacquot, Renaud Schiappa, Marine Lebrun
BACKGROUND: The tumor spectrum in the Lynch syndrome is well defined, comprising an increased risk of developing colonic and extracolonic malignancies. Muir-Torre syndrome is a variant with a higher risk of skin disease. Patients have been described carrying mutations in the mismatch repair genes and presenting tumors with unusual histology or affected organ not part of the Lynch syndrome spectrum. Hence, the real link between Lynch syndrome, or Muir-Torre syndrome, and these tumors remains difficult to assess...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/28481899/lumican-and-versican-protein-expression-are-associated-with-colorectal-adenoma-to-carcinoma-progression
#4
Meike de Wit, Beatriz Carvalho, Pien M Delis-van Diemen, Carolien van Alphen, Jeroen A M Beliën, Gerrit A Meijer, Remond J A Fijneman
BACKGROUND: One prominent event associated with colorectal adenoma-to-carcinoma progression is genomic instability. Approximately 85% of colorectal cancer cases exhibit chromosomal instability characterized by accumulation of chromosome copy number aberrations (CNAs). Adenomas with gain of chromosome 8q, 13q, and/or 20q are at high risk of progression to cancer. Tumor progression is also associated with expansion of the extracellular matrix (ECM) and the activation of non-malignant cells within the tumor stroma...
2017: PloS One
https://www.readbyqxmd.com/read/28471193/-molecular-pathology-of-colorectal-cancer-microsatellite-instability-the-detection-the-relationship-to-the-pathophysiology-and-prognosis
#5
V Brychtová, R Šefr, R Hrstka, P Vídeňská, B Bencsiková, B Hanáková, L Zdražilová Dubská, R Nenutil, E Budinská
BACKGROUND: Colorectal carcinoma (CRC) is third most common cancer worldwide with very heterogenous character. In most cases, it is caused by sporadic events leading to disruption of epithelial cells of the colon. The minority evolves from germline mutations associated with hereditary cancer syndromes. Mechanisms leading to mutations of oncogenes, tumour suppressors and genes of DNA repair mechanisms include: 1. chromosomal instability, 2. microsatellite instability and 3. CpG island methylator phenotype...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28458789/microsatellite-instability-in-medullary-carcinoma-of-the-colon
#6
Mario Martinotti, Fernando Cirillo, Marco Ungari, Giulia Tanzi, Giovanni Rolando, Antonio Tarasconi, Valerio Ranieri, Paolo Aulisa, Marco Vismarra, Massimo Rovatti, Monica Trombatore
Medullary carcinoma (MC) of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI). We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis...
March 24, 2017: Rare Tumors
https://www.readbyqxmd.com/read/28453697/prediction-of-overall-survival-in-stage-ii-and-iii-colon-cancer-beyond-tnm-system-a-retrospective-pooled-biomarker-study
#7
R Dienstmann, M J Mason, F A Sinicrope, A I Phipps, S Tejpar, A Nesbakken, S A Danielsen, A Sveen, D D Buchanan, M Clendenning, C Rosty, B Bot, S R Alberts, J Milburn Jessup, R A Lothe, M Delorenzi, P A Newcomb, D Sargent, J Guinney
Background: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods: After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28416736/nomo-1-gene-is-deleted-in-early-onset-colorectal-cancer
#8
José Perea, Juan Luis García, Jessica Pérez, Daniel Rueda, María Arriba, Yolanda Rodríguez, Miguel Urioste, Rogelio González-Sarmiento
To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess the status of NOMO1, a gene located in that region, we analyzed differential clinicopathological, familial and molecular features of CRC subsets with and without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We confirmed the region by fluorescence in-situ hybridization, and Quantitative Real-Time PCR analyzed the status of NOMO1 in different age-of-onset and Microsatellite Instability (MSI)-status CRC subsets...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28367107/microsatellite-instability-pathway-and-emast-in-colorectal-cancer
#9
John M Carethers
Microsatellite instability (MSI) refers to the biochemical detection of frameshifted microsatellite sequences from genomic DNA. Genesis of MSI is due to defective DNA mismatch repair (MMR) that fails to correct post DNA replicative slippage mistakes at microsatellites. Most of the estimated 100,000 genomic microsatellites are non-coding; however, ~150-300 microsatellites are coding such that, when frameshifted during the pathogenesis of an MSI tumor, can generate immunogenic neopeptide antigens that limit the growth of tumor and prolong patient survival...
February 2017: Current Colorectal Cancer Reports
https://www.readbyqxmd.com/read/28328000/cdx2-prognostic-value-in-stage-ii-iii-resected-colon-cancer-is-related-to-cms-classification
#10
C Pilati, J Taieb, R Balogoun, L Marisa, A de Reyniès, P Laurent-Puig
Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer...
February 27, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325827/sessile-serrated-polyps-and-colon-cancer-prevention
#11
REVIEW
Shahrooz Rashtak, Rafaela Rego, Seth R Sweetser, Frank A Sinicrope
Evidence suggests that up to one fifth of colorectal carcinomas develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic colorectal carcinomas with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps...
May 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28300842/cd95-ligand-induces-senescence-in-mismatch-repair-deficient-human-colon-cancer-via-chronic-caspase-mediated-induction-of-dna-damage
#12
Danielle A Raats, Nicola Frenkel, Susanne J van Schelven, Inne HMBorel Rinkes, Jamila Laoukili, Onno Kranenburg
CD95 is best known for its ability to induce apoptosis via a well-characterized pathway involving caspase-mediated proteolytic events. However, in apoptosis-resistant cell lines of diverse cancer types stimulation of CD95 primarily has pro-tumorigenic effects that affect many of the hallmarks of cancer. For instance, in colon cancer cells with a mutant KRAS gene CD95 primarily promotes invasion and metastasis. In the current study, we further investigated the context dependency of the consequences of CD95 activation in colon cancer...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28293327/the-dynamic-dna-methylation-landscape-of-the-mutl-homolog-1-shore-is-altered-by-mlh1-93g-a-polymorphism-in-normal-tissues-and-colorectal-cancer
#13
Andrea J Savio, Miralem Mrkonjic, Mathieu Lemire, Steven Gallinger, Julia A Knight, Bharat Bapat
BACKGROUND: Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 (MLH1), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 (MLH1-93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28241187/mismatch-repair-deficiency-microsatellite-instability-and-survival-an-exploratory-analysis-of-the-medical-research-council-adjuvant-gastric-infusional-chemotherapy-magic-trial
#14
Elizabeth C Smyth, Andrew Wotherspoon, Clare Peckitt, David Gonzalez, Sanna Hulkki-Wilson, Zakaria Eltahir, Matteo Fassan, Massimo Rugge, Nicola Valeri, Alicia Okines, Madeleine Hewish, William Allum, Sally Stenning, Matthew Nankivell, Ruth Langley, David Cunningham
Importance: Mismatch repair (MMR) deficiency (MMRD) and microsatellite instability (MSI) are prognostic for survival in many cancers and for resistance to fluoropyrimidines in early colon cancer. However, the effect of MMRD and MSI in curatively resected gastric cancer treated with perioperative chemotherapy is unknown. Objective: To examine the association among MMRD, MSI, and survival in patients with resectable gastroesophageal cancer randomized to surgery alone or perioperative epirubicin, cisplatin, and fluorouracil chemotherapy in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial...
February 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28210747/extent-of-field-change-in-colorectal-cancers-with-braf-mutation
#15
Aaron Poh, Heidi Sian Ying Chang, Kok Yang Tan, Xin Xiu Sam, Avery Khoo, Shoa Nian Choo, Min En Nga, Wei Keat Wan
INTRODUCTION: Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS: Eight microsatellite instability-high (MSI-H) tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis...
February 17, 2017: Singapore Medical Journal
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#16
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28165633/back-to-the-future-routine-morphological-assessment-of-the-tumour-microenvironment-is-prognostic-in-stage-ii-iii-colon-cancer-in-a-large-population-based-study
#17
Seán O Hynes, Helen G Coleman, Paul J Kelly, Steven Irwin, Roisin F O'Neill, Ronan T Gray, Claire McGready, Philip D Dunne, Stephen McQuaid, Jacqueline A James, Manuel Salto-Tellez, Maurice B Loughrey
AIMS: Both morphological and molecular approaches have highlighted the biological and prognostic importance of the tumour microenvironment in colorectal cancer (CRC). Despite this, microscopic assessment of the tumour microenvironment has not been adopted into routine practice. The study aim was to identify those tumour microenvironmental features that are most likely to provide prognostic information and be feasible to use in routine pathology reporting practice. METHODS AND RESULTS: On the basis of existing evidence, we selected specific morphological features relating to peritumoral inflammatory and stromal responses, agreed criteria for scoring, and assessed these in representative haematoxylin and eosin (H&E)-stained whole tumour sections from a population-based cohort of 445 stage II/III colon cancer cases...
February 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28160106/variable-levels-of-long-noncoding-rna-expression-in-dna-mismatch-repair-proficient-early-stage-colon-cancer
#18
Qian Li, Nanshan Li, Yueqiong Lao, Wu Lin, Guojun Jiang, Nan Wei, Canghai Wang, Kuiliang Liu, Jing Wu
BACKGROUND: Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer. AIMS: This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC). METHODS: The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR)...
May 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28133101/-evaluation-of-braf-v600e-mutations-in-high-level-microsatellite-instability-msi-h-colon-cancer-comparison-between-genetic-testing-and-immunohistochemical-staining
#19
Takehiko Sakimoto, Noriyasu Chika, Okihide Suzuki, Keiichiro Ishibashi, Tetsuhiko Tachikawa, Kiwamu Akagi, Hidetaka Eguchi, Yasushi Okazaki, Hideyuki Ishida
BRAF V600E mutation plays an important role in the serrated neoplasia pathway of colorectal tumorigenesis and is a negative predictive factor for chemotherapy response as well as a prognostic factor in patients with colorectal cancer. To evaluate BRAF V600E mutations, a conventional polymerase chain reaction(PCR)is performed but recently immunohistochemistry (IHC)with a BRAF antibody has been used. Although similarities between the PCR and IHC methods have been reported, some investigators have doubts about the usefulness of IHC for BRAF mutation analysis...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28106826/colorectal-carcinoma-a-general-overview-and-future-perspectives-in-colorectal-cancer
#20
REVIEW
Inés Mármol, Cristina Sánchez-de-Diego, Alberto Pradilla Dieste, Elena Cerrada, María Jesús Rodriguez Yoldi
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism...
January 19, 2017: International Journal of Molecular Sciences
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