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https://www.readbyqxmd.com/read/29155997/immune-activation-and-benefit-from-avelumab-in-ebv-positive-gastric-cancer
#1
Anshuman Panda, Janice M Mehnert, Kim M Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Michael Kane, Levi Sokol, Mark N Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann W Silk, Joseph Aisner, Nancy Chan, Jyoti Malhotra, Melissa Frankel, Howard L Kaufman, Siraj Ali, Jeffrey S Ross, Eileen P White, Gyan Bhanot, Shridar Ganesan
Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA. Analysis of The Cancer Genome Atlas gastric cancer data (25 EBV+, 80 microsatellite-instable [MSI], 310 microsatellite-stable [MSS]) showed that EBV-positive tumors were MSS...
November 15, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29155564/mass-spectrometry-imaging-a-review-of-emerging-advancements-and-future-insights
#2
Amanda R Buchberger, Kellen DeLaney, Jillian Johnson, Lingjun Li
Mass spectrometry imaging (MSI) is a powerful tool that enables untargeted investigations into the spatial distribution of molecular species in a variety of samples. It has the capability to image thousands of molecules, such as metabolites, lipids, peptides, proteins, and glycans, in a single experiment without labeling. The combination of information gained from mass spectrometry (MS) and visualization of spatial distributions in thin sample sections makes this a valuable chemical analysis tool useful for biological specimen characterization...
November 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29153449/the-changing-epidemiology-of-open-fractures-in-vehicle-occupants-pedestrians-motorcyclists-and-cyclists
#3
Dennis Winkler, Stuart T Goudie, Charles M Court-Brown
AIMS: To investigate the changing epidemiology of open fractures in vehicle occupants, pedestrians, motorcyclists and cyclists. MATERIALS AND METHODS: Data on all non-spinal open fractures admitted to the Royal Infirmary of Edinburgh after a road traffic accident between 1988 and 2010 were collected and analysed to provide information about the changing epidemiology in different patient groups. Demographic information was collected on all patients with the severity of injury being analysed with the Injury Severity Score (ISS), Musculoskeletal Index (MSI) and the number of open fractures...
November 14, 2017: Injury
https://www.readbyqxmd.com/read/29153096/correlations-between-microsatellite-instability-ercc1-xrcc1-polymorphism-and-clinical-characteristics-and-folfox-adjuvant-chemotherapy-effect-of-colorectal-cancer-patients
#4
Liping Zhang, Jiangman Zhao, Bin Yu, Xinjiang Song, Guogang Sun, Lijiang Han, Lu Wang, Shu Dong
Patients with MSI colorectal tumor have good prognosis and cannot benefit from 5-fluorouracil (5-Fu)-based chemotherapy reported by previous studies. While, single nucleotide polymorphisms (SNP) of ERCC1 and XRCC1 have be proved to influence clinical outcome of colorectal cancer patients treated with oxaliplatin-based chemotherapy. We aim to study the correlation between molecular status and clinical- pathological features, and their effect on CRC patients' clinical outcome treated with mFOLFOX6 adjuvant chemotherapy...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29147610/host-immune-response-index-in-gastric-cancer-identified-by-comprehensive-analyses-of-tumor-immunity
#5
Charny Park, Junhun Cho, Jeeyun Lee, So Young Kang, Ji Yeong An, Min Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Won Ki Kang, Insuk Sohn, Sin Ho Jung, Myung-Soo Kang, Kyoung-Mee Kim
Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147604/tap1-down-regulation-elicits-immune-escape-and-poor-prognosis-in-colorectal-cancer
#6
Agnes Ling, Anna Löfgren-Burström, Pär Larsson, Xingru Li, Maria L Wikberg, Åke Öberg, Roger Stenling, Sofia Edin, Richard Palmqvist
The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29144791/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-i-colorectal-cancer-microsatellite-instability-testing-and-clinical-implications
#7
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker...
November 16, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29137623/analysis-of-factors-influencing-molecular-testing-at-diagnostic-of-colorectal-cancer
#8
Quentin Thiebault, Gautier Defossez, Lucie Karayan-Tapon, Pierre Ingrand, Christine Silvain, David Tougeron
BACKGROUND: The aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing. METHODS: All incident CRC cases in 2010 were identified in the Poitou-Charentes General Cancer Registry. The exhaustive molecular testing performed was accessed in the French molecular genetics platform...
November 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29137387/infrequently-expressed-mirnas-influence-survival-after-diagnosis-with-colorectal-cancer
#9
Martha L Slattery, Andrew J Pellatt, Frances Y Lee, Jennifer S Herrick, Wade S Samowitz, John R Stevens, Roger K Wolff, Lila E Mullany
Half of miRNAs expressed in colorectal tissue are expressed < 50% of the population. Many infrequently expressed miRNAs have low levels of expression. We hypothesize that less frequently expressed miRNAs, when expressed at higher levels, influence both disease stage and survival after diagnosis with colorectal cancer (CRC); low levels of expression may be background noise. We examine 304 infrequently expressed miRNAs in 1893 population-based cases of CRC with paired carcinoma and normal mucosa miRNA profiles...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137273/programmed-death-ligand-1-and-met-co-expression-is-a-poor-prognostic-factor-in-gastric-cancers-after-resection
#10
Mi Jung Kwon, Kab-Choong Kim, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hye Kyung Lee, Ho Suk Kang, Kyueng-Whan Min
Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial. We performed in situ hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132872/an-nrg-oncology-gog-study-of-molecular-classification-for-risk-prediction-in-endometrioid-endometrial-cancer
#11
Casey M Cosgrove, David L Tritchler, David E Cohn, David G Mutch, Craig M Rush, Heather A Lankes, William T Creasman, David S Miller, Nilsa C Ramirez, Melissa A Geller, Matthew A Powell, Floor J Backes, Lisa M Landrum, Cynthia Timmers, Adrian A Suarez, Richard J Zaino, Michael L Pearl, Paul A DiSilvestro, Shashikant B Lele, Paul J Goodfellow
OBJECTIVES: The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. METHODS: Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes...
November 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29128931/universal-determination-of-microsatellite-instability-using-bat26-as-a-single-marker-in-an-argentine-colorectal-cancer-cohort
#12
María Laura González, Natalia Causada-Calo, Juan Pablo Santino, Mev Dominguez-Valentin, Fabiana Alejandra Ferro, Inés Sammartino, Pablo Germán Kalfayan, Maria Alicia Verzura, Tamara Alejandra Piñero, Andrea Romina Cajal, Walter Pavicic, Carlos Vaccaro
Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included...
November 11, 2017: Familial Cancer
https://www.readbyqxmd.com/read/29126141/gastric-carcinomas-with-lymphoid-stroma-categorization-and-comparison-with-solid-type-colonic-carcinomas
#13
Raul S Gonzalez, Justin M M Cates, Frank Revetta, Loralee A McMahon, Kay Washington
Objectives: To determine whether histologic features could help identify gastric carcinomas with lymphoid stroma associated with microsatellite instability (MSI) (ie, "medullary carcinomas"), Epstein-Barr virus (EBV) infection (termed lymphoepithelioma-like carcinomas in other organ systems), or neither. Methods: We identified 17 solid-type gastric carcinomas with lymphoid stroma, assessed EBV and MSI status, and compared features across groups. We also compared them with 51 solid-type colorectal adenocarcinomas...
November 8, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29124284/ca-2-nuclear-factor-of-activated-t-cells-signaling-is-enriched-in-early-onset-rectal-tumors-devoid-of-canonical-wnt-activation
#14
Raju Kumar, Ratheesh Raman, Viswakalyan Kotapalli, Swarnalata Gowrishankar, Saumyadipta Pyne, Jonathan R Pollack, Murali D Bashyam
Our previous extensive analysis revealed a significant proportion of early-onset colorectal tumors from India to be localized to the rectum in younger individuals and devoid of deregulated Wnt/β-catenin signaling. In the current study, we performed a comprehensive genome-wide analysis of clinically well-annotated microsatellite stable early-onset sporadic rectal cancer (EOSRC) samples. Results revealed extensive DNA copy number alterations in rectal tumors in the absence of deregulated Wnt/β-catenin signaling...
November 9, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29123583/medullary-colonic-carcinoma-with-microsatellite-instability-has-lower-survival-compared-with-conventional-colonic-adenocarcinoma-with-microsatellite-instability
#15
Miguel A Gómez-Álvarez, Leonardo S Lino-Silva, Rosa A Salcedo-Hernández, Alejandro Padilla-Rosciano, Erika B Ruiz-García, Horacio N López-Basave, German Calderillo-Ruiz, José M Aguilar-Romero, Jorge A Domínguez-Rodríguez, Ángel Herrera-Gómez, Abelardo Meneses-García
Introduction: Colorectal medullary carcinoma (MC) is a rare subtype of poorly differentiated adenocarcinoma (PDA) with unclear prognostic significance. Microsatellite instable (MSI) colorectal carcinomas have demonstrated better prognosis in clinical stage II. Aim: To analyze the survival and clinicopathological characteristics of MCs versus PDAs with MSI in clinical stage III. Material and methods: We studied 22 cases of PDAs with MSI versus 10 MCs...
2017: Przegla̜d Gastroenterologiczny
https://www.readbyqxmd.com/read/29122777/genetic-predictors-of-response-to-systemic-therapy-in-esophagogastric-cancer
#16
Yelena Y Janjigian, Francisco Sanchez-Vega, Philip Jonsson, Walid K Chatila, Jaclyn F Hechtman, Geoffrey Y Ku, Jamie C Riches, Yaelle Tuvy, Ritika Kundra, Nancy Bouvier, Efsevia Vakiani, Jianjiong Gao, Zachary J Heins, Benjamin E Gross, David P Kelsen, Liying Zhang, Vivian E Strong, Mark Schattner, Hans Gerdes, Daniel G Coit, Manjit Bains, Zsofia K Stadler, Valerie W Rusch, David R Jones, Daniela Molena, Jinru Shia, Mark E Robson, Marinela Capanu, Sumit Middha, Ahmet Zehir, David M Hyman, Maurizio Scaltriti, Marc Ladanyi, Neal Rosen, David H Ilson, Michael F Berger, Laura Tang, Barry S Taylor, David B Solit, Nikolaus Schultz
The incidence of esophagogastric cancer is rapidly rising but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of metastatic esophagogastric cancer patients. There was no association between HRD defects and response to platinum-based chemotherapy. Patients with MSI-H tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy...
November 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29122612/maldi-imaging-of-enzymatic-degradation-of-glycerides-by-lipase-on-textile-surface
#17
Jonatan Hall-Andersen, Svend G Kaasgaard, Christian Janfelt
Most modern laundry detergents contain enzymes such as proteases, amylases, and lipases for more efficient removal of stains containing proteins, carbohydrates, and lipids during wash at low temperature. The function of the lipases is to hydrolyse the hydrophobic triglycerides from fats and oils to the more hydrophilic lipids diglycerides, monoglycerides and free fatty acids. Here, we use MALDI imaging to study the effect of enzymatic degradation of triglycerides by lipases directly on the textile surface. Textile samples were created by using swatches of different textile blends, adding a lipid stain and simulating washing cycles using well-defined detergents with lipase concentrations ranging between 0 and 0...
November 6, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29116623/kras-mutation-in-gastric-cancer-and-prognostication-associated-with-microsatellite-instability-status
#18
Karol Polom, Kakoli Das, Daniele Marrelli, Giandomenico Roviello, Valeria Pascale, Costantino Voglino, Henry Rho, Patrick Tan, Franco Roviello
Microsatellite instability (MSI) is one of the subgroups based on the new molecular classification of gastric cancer (GC). In this study, we analyzed the role of KRAS status in MSI GC and the impact of MSI status on KRAS mutation. We performed analysis on 595 GC patients. Polymerase chain reaction (PCR) was used for the screening of KRAS mutation (exon 2) and 5 quasi-monomorphic mononucleotide repeats, namely, BAT-26, BAT-25, NR -24, NR-21, and NR-27 were used to determine the MSI status. The KRAS and MSI status were then compared with clinicopathologic data of the GC patients...
November 8, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29113157/lack-of-microsatellite-instability-in-gastrointestinal-stromal-tumors
#19
Nathália C Campanella, Cristovam Scapulatempo-Neto, Lucas Faria Abrahão-Machado, Antônio Talvane Torres De Oliveira, Gustavo N Berardinelli, Denise Peixoto Guimarães, Rui M Reis
The microsatellite instability (MSI) phenotype may constitute an important biomarker for patient response to immunotherapy, particularly to anti-programmed death-1 inhibitors. MSI is a type of genomic instability caused by a defect in DNA mismatch repair (MMR) proteins, which is present mainly in colorectal cancer and its hereditary form, hereditary nonpolyposis colorectal cancer. Gastrointestinal stromal tumor (GIST) development is associated with activating mutations of KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor α (PDGFRA), which are oncogenes that predict the response to imatinib mesylate...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29109289/host-based-lipid-inflammation-drives-pathogenesis-in-francisella-infection
#20
Alison J Scott, Julia Maria Post, Raissa Lerner, Shane R Ellis, Joshua Lieberman, Kari Ann Shirey, Ron M A Heeren, Laura Bindila, Robert K Ernst
Mass spectrometry imaging (MSI) was used to elucidate host lipids involved in the inflammatory signaling pathway generated at the host-pathogen interface during a septic bacterial infection. Using Francisella novicida as a model organism, a bacterial lipid virulence factor (endotoxin) was imaged and identified along with host phospholipids involved in the splenic response in murine tissues. Here, we demonstrate detection and distribution of endotoxin in a lethal murine F. novicida infection model, in addition to determining the temporally and spatially resolved innate lipid inflammatory response in both 2D and 3D renderings using MSI...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
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