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https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#1
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29767751/clinicopathological-and-molecular-differences-between-right-sided-and-left-sided-colorectal-cancer-in-japanese-patients
#2
Soichiro Natsume, Tatsuro Yamaguchi, Misato Takao, Takeru Iijima, Rika Wakaume, Keiichi Takahashi, Hiroshi Matsumoto, Daisuke Nakano, Shin-Ichiro Horiguchi, Koichi Koizumi, Michiko Miyaki
Background: The aim of this study was to clarify clinicopathological features, frequencies of molecular biomarkers, and prognoses in Japanese colorectal cancer patients and compare them with right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC). Methods: We consecutively selected 575 colorectal cancer patients who underwent surgical resection from 2008 to 2011. RCC was located from the cecum to the transverse colon, and LCRC was located from the splenic flexure to the rectum...
May 15, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#3
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29743854/microsatellite-instability-in-colorectal-cancer
#4
REVIEW
Jafar Nouri Nojadeh, Shahin Behrouz Sharif, Ebrahim Sakhinia
Colorectal cancer (CRC) is a heterogeneous disease that is caused by the interaction of genetic and environmental factors. Although it is one of the most common cancers worldwide, CRC would be one of the most curable cancers if it is detected in the early stages. Molecular changes that occur in colorectal cancer may be categorized into three main groups: 1) Chromosomal Instability (CIN), 2) Microsatellite Instability (MSI), and 3) CpG Island Methylator phenotype (CIMP). Microsatellites, also known as Short Tandem Repeats (STRs) are small (1-6 base pairs) repeating stretches of DNA scattered throughout the entire genome and account for approximately 3 % of the human genome...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/29725538/appendiceal-carcinoma-associated-with-microsatellite-instability
#5
Angélica Morales-Miranda, Ismael Domínguez Rosado, Carlos Chan Núñez, Fredy Chable Montero
Approximately 15% of colorectal cancer (CRC) cases exhibit microsatellite instability (MSI), which appears to be associated with unique biological behavior. The present study presents a case of appendiceal carcinoma associated with MSI that responded well to adjuvant chemotherapy. Clinical, pathological and immunohistochemical (IHC) characteristics have been described. The 60-year-old male patient had suffered from recurrent lower abdominal pain associated with abdominal distention for 6 months; then, following an acute attack, he was subjected to laparoscopic appendectomy...
May 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29705788/immunotherapy-of-colon-cancer
#6
Alexander Stein, Gunnar Folprecht
In contrast to other tumour types inhibitors of PD-1/-L1 or CTLA 4 have not yet shown relevant efficacy in unselected colorectal cancer. Based on the high mutational burden, deficient mismatch repair (dMMR) or microsatellite instable (MSI-H) tumours are yet the only subgroup, which is amenable to checkpoint inhibition. These tumours show relevant and durable responses in the refractory setting by PD-1/-L1 +/- CTLA 4 inhibition. Thus, ongoing phase 3 trials in this subgroup evaluate immunotherapy in the adjuvant setting as well as in the first line metastatic setting with or without chemotherapy...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29701748/mlh1-deficiency-in-normal-mouse-colon-mucosa-associates-with-chromosomally-unstable-colon-cancer
#7
Marjaana Pussila, Petri Törönen, Elisabet Einarsdottir, Shintaro Katayama, Kaarel Krjutškov, Liisa Holm, Juha Kere, Päivi Peltomäki, Markus J Mäkinen, Jere Linden, Minna Nyström
Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis...
April 26, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29686976/microsatellite-instability-in-mouse-models-of-colorectal-cancer
#8
Nicola Currey, Joseph J Daniel, Dessislava N Mladenova, Jane E Dahlstrom, Maija R J Kohonen-Corish
Microsatellite instability (MSI) is caused by DNA mismatch repair deficiency and is an important prognostic and predictive biomarker in colorectal cancer but relatively few studies have exploited mouse models in the study of its clinical utility. Furthermore, most previous studies have looked at MSI in the small intestine rather than the colon of mismatch repair deficient Msh2 -knockout (KO) mice. Here we compared Msh2 -KO, p53 -KO, and wild type (WT) mice that were treated with the carcinogen azoxymethane (AOM) and the nonsteroidal anti-inflammatory drug sulindac or received no treatment...
2018: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29661177/loss-of-zg16-is-associated-with-molecular-and-clinicopathological-phenotypes-of-colorectal-cancer
#9
Hui Meng, Wencai Li, Lisa A Boardman, Liang Wang
BACKGROUND: Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC. METHODS: We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29660527/the-association-between-mutations-in-braf-and-colorectal-cancer-specific-survival-depends-on-microsatellite-status-and-tumor-stage
#10
Hendrik Bläker, Elizabeth Alwers, Alexander Arnold, Esther Herpel, Katrin E Tagscherer, Wilfried Roth, Lina Jansen, Viola Walter, Matthias Kloor, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister
BACKGROUND & AIMS: Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability (MSI-H) and BRAF mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage-specific prognostic value of combined testing for MSI-H and BRAF for patients with colorectal cancer (CRC). METHODS: We performed a retrospective analysis of colorectal tumor samples collected from 1995 patients at 22 hospitals in Germany, between 2003 and 2010...
April 13, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29643917/predictive-and-prognostic-implications-of-mutation-profiling-and-microsatellite-instability-status-in-patients-with-metastatic-colorectal-carcinoma
#11
Jianhua Liu, Weiqiang Zeng, Chengzhi Huang, Junjiang Wang, Dongyang Yang, Dong Ma
To investigate whether mutation profiling and microsatellite instability (MSI) status were associated with clinicopathological features and the prognosis in metastatic colorectal cancer (mCRC), mutations in RAS (including KRAS , NRAS , and HRAS ) and BRAF were determined by Sanger sequencing. Tumor mismatch repair proteins and MSI status were examined using immunohistochemistry and polymerase chain reaction, respectively. The clinical value of these abnormalities was statistically analyzed, and prognostic value of different treatment regimens was also evaluated...
2018: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29594445/the-prognostic-implications-of-primary-tumor-location-on-recurrence-in-early-stage-colorectal-cancer-with-no-associated-risk-factors
#12
Sung Il Kang, Duck-Woo Kim, Yoonjin Kwak, Hye-Seung Lee, Min Hyun Kim, Myung Jo Kim, Heung-Kwon Oh, Sung-Bum Kang
PURPOSE: Recently, several reports have suggested that tumor location serves as a prognostic biomarker in advanced colorectal cancer. However, the prognostic implication of tumor location in patients with early-stage colorectal cancer remains unclear. This study was aimed to examine the prognostic implication of tumor location in patients with early-stage colorectal cancer. METHODS: Patients with stage I and low-risk stage II colorectal cancer, treated with radical surgery in a hospital setting between May 2003 and September 2014, were retrospectively reviewed...
March 28, 2018: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/29523759/landscape-of-tumor-mutation-load-mismatch-repair-deficiency-and-pd-l1-expression-in-a-large-patient-cohort-of-gastrointestinal-cancers
#13
Mohamed E Salem, Alberto Puccini, Axel Grothey, Derek Raghavan, Richard M Goldberg, Joanne Xiu, W Michael Korn, Benjamin A Weinberg, Jimmy J Hwang, Anthony F Shields, John L Marshall, Philip A Philip, Heinz-Josef Lenz
The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Here, a total of 4,125 tumors from 14 different gastrointestinal cancer sites were studied using validated assays. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor specimens using the NextSeq platform...
May 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29520442/cd274-lag3-and-ido1-expressions-in-tumor-infiltrating-immune-cells-as-prognostic-biomarker-for-patients-with-msi-high-colon-cancer
#14
Soo Jung Lee, Sun-Young Jun, In Hee Lee, Byung Woog Kang, Su Yeon Park, Hye Jin Kim, Jun Seok Park, Gyu-Seog Choi, Ghilsuk Yoon, Jong Gwang Kim
PURPOSE: This study attempted to reveal the prognostic impact of microsatellite instability-high (MSI-H) colon cancer with tumor-infiltrating immune cells (TIICs) and immune checkpoint protein expression, which are good candidates for immunotherapy. MATERIALS AND METHODS: The study included 89 patients with MSI-H colon cancer who underwent curative surgery at Kyungpook National University Chilgok Hospital. The expression status of specific inhibitory receptors, such as CD274 (programmed death-ligand 1, PD-L1), PDCD1 (programmed cell death 1, PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and indolamine 2'3'-dioxygenase 1 (IDO1), was retrospectively analyzed using immunohistochemistry (IHC)...
June 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29507659/lrp1-expression-in-colon-cancer-predicts-clinical-outcome
#15
Camille Boulagnon-Rombi, Christophe Schneider, Chloé Leandri, Albin Jeanne, Virginie Grybek, Aude Marchal Bressenot, Coralie Barbe, Benjamin Marquet, Saviz Nasri, Christelle Coquelet, Caroline Fichel, Nicole Bouland, Arnaud Bonnomet, Reza Kianmanesh, Anne-Sophie Lebre, Olivier Bouché, Marie-Danièle Diebold, Georges Bellon, Stéphane Dedieu
LRP1 (low-density lipoprotein receptor-related protein 1), a multifunctional endocytic receptor, has recently been identified as a hub within a biomarker network for multi-cancer clinical outcome prediction. As its role in colon cancer has not yet been characterized, we here investigate the relationship between LRP1 and outcome. Materials and Methods: LRP1 mRNA expression was determined in colon adenocarcinoma and paired colon mucosa samples, as well as in stromal and tumor cells obtained after laser capture microdissection...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29490919/mlh1-rhemac-hereditary-nonpolyposis-colorectal-cancer-syndrome-in-rhesus-macaques
#16
David W Brammer, Patrick J Gillespie, Mei Tian, Daniel Young, Muthuswamy Raveendran, Lawrence E Williams, Mihai Gagea, Fernando J Benavides, Carlos J Perez, Russell R Broaddus, Bruce J Bernacky, Kirstin F Barnhart, Mian M Alauddin, Manoop S Bhutani, Richard A Gibbs, Richard L Sidman, Renata Pasqualini, Wadih Arap, Jeffrey Rogers, Christian R Abee, Juri G Gelovani
Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon...
March 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29378905/overt-increase-of-oxidative-stress-and-dna-damage-in-murine-and-human-colitis-and-colitis-associated-neoplasia
#17
Adrian Frick, Vineeta Khare, Gregor Paul, Michaela Lang, Franziska Ferk, Siegfried Knasmüller, Andrea Beer, Georg Oberhuber, Christoph Gasche
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated-cancer (CAC); however, the underlying processes of disease progression are not completely understood. Here, the molecular processes of inflammation-driven colon carcinogenesis were investigated using IL10-deficient mice (IL10 KO). IL10 KO mice were euthanized after development of colitis and dysplasia. IHC was performed for markers of colitis-induced DNA damage (CIDD): oxidative DNA lesions (8-oxoG), double-strand breaks (DSB; γH2AX)...
April 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29344557/in-colonic-%C3%AF-0-rho0-cells-reduced-mitochondrial-function-mediates-transcriptomic-alterations-associated-with-cancer
#18
Harrison M Penrose, Sandra Heller, Chloe Cable, Hani Nakhoul, Nate Ungerleider, Melody Baddoo, Zachary F Pursell, Erik K Flemington, Susan E Crawford, Suzana D Savkovic
Background: Mitochondrial reprogramming has emerged as a hallmark of cancer pathobiology. Although it is believed this reprogramming is essential for cancer cells to thrive, how it supports cancer pathobiology is unclear. We previously generated colonic ρ0 (rho0) cells with reduced mitochondrial energy function and acquired their transcriptional signature. Here, we utilized a bioinformatics approach to identify their changes linked to cancer pathobiology. Methods: Human colon cancer HCT116 cells, control and ρ0, were used for qPCR...
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29284010/safety-and-antitumor-activity-of-the-anti-pd-1-antibody-pembrolizumab-in-patients-with-advanced-colorectal-carcinoma
#19
MULTICENTER STUDY
Bert H O'Neil, John M Wallmark, David Lorente, Elena Elez, Judith Raimbourg, Carlos Gomez-Roca, Samuel Ejadi, Sarina A Piha-Paul, Mark N Stein, Albiruni R Abdul Razak, Katia Dotti, Armando Santoro, Roger B Cohen, Marlena Gould, Sanatan Saraf, Karen Stein, Sae-Won Han
BACKGROUND: Colorectal cancers (CRCs) expressing programmed death ligand 1 (PD-L1) have poor prognosis. In the multicohort KEYNOTE-028 trial, the anti-PD-1 antibody pembrolizumab was evaluated in 20 PD-L1-positive advanced solid tumors. Herein, we report results for the advanced CRC cohort. METHODS: Patients with advanced, treatment-resistant PD-L1-positive carcinoma of the colon or rectum were enrolled, regardless of microsatellite instability (MSI) status. Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until disease progression/unacceptable toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/29230882/molecular-profiling-and-genome-wide-analysis-based-on-somatic-copy-number-alterations-in-advanced-colorectal-cancers
#20
Tamotsu Sugai, Yayoi Takahashi, Makoto Eizuka, Ryo Sugimoto, Yasuko Fujita, Wataru Habano, Kouki Otsuka, Akira Sasaki, Eiichiro Yamamoto, Takayuki Matsumoto, Hiromu Suzuki
To characterize somatic alterations in colorectal cancer (CRC), we conducted a genome-scale analysis of 106 CRC specimens. We assessed comprehensive somatic copy number alterations (SCNAs) in these CRC specimens. In addition, we examined microsatellite instability (MSI; low and high), genetic mutations (KRAS, BRAF, TP53, and PIK3CA), and DNA methylation status (classified into low, intermediate, and high type). We stratified molecular alterations in the CRCs using a hierarchical cluster analysis. The examined CRCs could be categorized into three subgroups using hierarchical cluster analysis...
March 2018: Molecular Carcinogenesis
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