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Noriyasu Chika, Minoru Fukuchi, Okihide Suzuki, Tetsuya Ito, Azusa Yamamoto, Toru Ishiguro, Youichi Kumagai, Keiichiro Ishibashi, Erito Mochiki, Hideyuki Ishida
The loss of mismatch repair(MMR)function as a result of MLH1 promoter methylation is closely correlated with high frequency microsatellite instability, and tumors with such characteristics are resistant to anticancer drugs such as 5-FU. We examined the incidence and characteristics of deficient MMR(dMMR)in elderly gastric cancer patients by performing a comprehensive immunohistochemical screening. The study was conducted in 199 patients diagnosed with gastric cancer, aged 75 years or older, who underwent a gastrectomy between April 2005 and January 2014...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Michael T Schweizer, Heather H Cheng, Maria S Tretiakova, Funda Vakar-Lopez, Nola Klemfuss, Eric Q Konnick, Elahe A Mostaghel, Peter S Nelson, Evan Y Yu, R Bruce Montgomery, Lawrence D True, Colin C Pritchard
Precision oncology entails making treatment decisions based on a tumor's molecular characteristics. For prostate cancer, identifying clinically relevant molecular subgroups is challenging, as molecular profiling is not routine outside of academic centers. Since histologic variants of other cancers correlates with specific genomic alterations, we sought to determine if ductal adenocarcinoma of the prostate (dPC) - a rare and aggressive histopathologic variant - was associated with any recurrent actionable mutations...
October 15, 2016: Oncotarget
Takashi Takeda, Kouji Banno, Megumi Yanokura, Masataka Adachi, Moito Iijima, Haruko Kunitomi, Kanako Nakamura, Miho Iida, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki
Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP)...
October 14, 2016: Genes
Siavash Rahimi, Iolia Akaev, Costa Repanos, Peter A Brennan, Jean Daniel Dubois
Primary lingual intestinal-type adenocarcinomas are extremely rare with only a few cases described. A case with immunohistochemical expression of Androgen Receptor (AR) which was treated solely by chemo-radiotherapy is reported herein. A 54-year-old male was referred with symptoms of fullness in his tongue. Clinical examination showed an asymmetry of the tongue with a hard mass palpable within the middle of the tongue. Biopsy showed intestinal-type adenocarcinoma. The tumour showed positive staining with cytokeratin 7, cytokeratin 20, CDX2, AR, β-catenin and was mismatch repair proteins (MMR) proficient...
October 17, 2016: Head and Neck Pathology
Zhaohui Jin, Harry H Yoon
Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade...
October 2016: Journal of Gastrointestinal Oncology
Manojkumar Bupathi, Christina Wu
Colorectal cancer (CRC) is a heterogeneous disease for which the treatment backbone has primarily been cytotoxic chemotherapy. With better understanding of the involved molecular mechanisms, it is now known that there are a number of epigenetic and genetic events, which are involved in CRC pathogenesis. Specific biomarkers have been identified which can be used to determine the clinical outcome of patients beyond tumor staging and predict for treatment efficacy. Molecular testing is now routinely performed to select for patients that will benefit the most from targeted agents and immunotherapy...
October 2016: Journal of Gastrointestinal Oncology
Kelsey M Boyle, Jacqueline K Barton
DNA has been exploited as a biological target of chemotherapeutics since the 1940s. Traditional chemotherapeutics, such as cisplatin and DNA-alkylating agents, rely primarily on increased uptake by rapidly proliferating cancer cells for therapeutic effects, but this strategy can result in off-target toxicity in healthy tissue. Recently, research interests have shifted towards targeted chemotherapeutics, in which a drug targets a specific biological signature of cancer, resulting in selective toxicity towards cancerous cells...
October 1, 2016: Inorganica Chimica Acta
Marcus M Dillon, Way Sung, Robert Sebra, Michael Lynch, Vaughn S Cooper
The vast diversity in nucleotide composition and architecture among bacterial genomes may be partly explained by inherent biases in the rates and spectra of spontaneous mutations. Bacterial genomes with multiple chromosomes are relatively unusual but some are relevant to human health, none more so than the causative agent of cholera, Vibrio cholerae Here, we present the genome-wide mutation spectra in wild-type and mismatch repair (MMR) defective backgrounds of two Vibrio species, the low-%GC squid symbiont V...
October 15, 2016: Molecular Biology and Evolution
E Stelloo, A M L Jansen, E M Osse, R A Nout, C L Creutzberg, D Ruano, D N Church, H Morreau, V T H B M Smit, T van Wezel, T Bosse
BACKGROUND: Mismatch repair (MMR)-deficiency analysis is increasingly recommended for all endometrial cancers, as it identifies Lynch syndrome-patients, and is emerging as a prognostic classifier to guide adjuvant treatment. The aim of this study was to define the optimal approach for MMR-deficiency testing and to clarify discrepancies between microsatellite instability (MSI) analysis and immunohistochemical (IHC) analysis of MMR protein expression. PATIENTS AND METHODS: 696 endometrial cancers were analyzed for MSI (pentaplex panel) and MMR protein expression (IHC)...
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Wynand Paul Roos, Andrea Krumm
Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD(+) dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair...
October 13, 2016: Nucleic Acids Research
Rama Kandasamy, Merryn Voysey, Fiona McQuaid, Karlijn de Nie, Rebecca Ryan, Olivia Orr, Ulrike Uhlig, Charles Sande, Daniel O'Connor, Andrew J Pollard
OBJECTIVE:  To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus. DESIGN:  Systematic review of randomised controlled trials, cohort studies, and case-control studies. DATA SOURCES:  Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included...
October 13, 2016: BMJ: British Medical Journal
Ha Young Woo, Yoon Sung Bae, Jie-Hyun Kim, Sang Kil Lee, Yong Chan Lee, Jae-Ho Cheong, Sung Hoon Noh, Hyunki Kim
BACKGROUND: Gastric "crawling-type" adenocarcinoma (CRA) is a tumor histologically characterized by irregularly fused glands with low-grade cellular atypia that tends to spread laterally in the mucosa. To date, the expression characteristics of the key molecules involved in CRA, including receptor tyrosine kinases (RTKs), mismatch repair (MMR) proteins, phosphatase and tensin homolog (PTEN), as well as the Epstein-Barr virus (EBV) status, have yet to be uncovered. METHODS: We constructed tissue microarrays of 94 CRAs, 72 conventional-type differentiated adenocarcinomas (CDAs), and 71 intramucosal poorly cohesive adenocarcinomas (PCAs) from early gastric cancers to evaluate and compare the pathological and expression profiles of potential key molecules for molecular classification (EBV; four MMR proteins-MLH1, MSH2, PMS2, and MSH6; three RTKs-HER2, MET, and EGFR; PTEN; and p53)...
October 12, 2016: Gastric Cancer
Laetitia Duval, François-Charles Wolff, Martin McKee, Bayard Roberts
AIM: To investigate differences in vaccination coverage between Roma and otherwise comparable non-Roma children, including factors associated with the vaccination gap, health care access and discrimination faced by Roma. METHODS: We analyse data from the Roma Regional Survey 2011 implemented in twelve countries of Central and South-East Europe. Our sample comprises 8233 children aged up to 6 with 7072 Roma children and 1161 non-Roma children. Estimates of the Roma vaccination gap are estimated using Logit regressions...
October 7, 2016: Vaccine
Ranee Seither, Kayla Calhoun, Jenelle Mellerson, Cynthia L Knighton, Erica Street, Vance Dietz, J Michael Underwood
State-mandated vaccination requirements for school entry protect children and communities against vaccine-preventable diseases (1). Each school year, federally funded immunization programs (e.g., states, territories, jurisdictions) collect and report kindergarten vaccination data to CDC. This report describes vaccination coverage estimates in all 50 states and the District of Columbia (DC), and the estimated number of kindergartners with at least one vaccine exemption in 47 states and DC, during the 2015-16 school year...
October 7, 2016: MMWR. Morbidity and Mortality Weekly Report
Holly A Hill, Laurie D Elam-Evans, David Yankey, James A Singleton, Vance Dietz
Sustained high coverage with recommended vaccinations among children has kept many vaccine-preventable diseases at low levels in the United States (1). To assess coverage with vaccinations recommended for children by age 2 years in the United States (2), CDC analyzed data collected by the 2015 National Immunization Survey (NIS) for children aged 19-35 months (born January 2012-May 2014). Overall, coverage did not change during 2014-2015. Coverage in 2015 was highest for ≥3 doses of poliovirus vaccine (93...
October 7, 2016: MMWR. Morbidity and Mortality Weekly Report
Catharina A Nordin, Peter Michaelson, Gunvor Gard, Margareta K Eriksson
BACKGROUND: Web-based interventions with a focus on behavior change have been used for pain management, but studies of Web-based interventions integrated in clinical practice are lacking. To emphasize the development of cognitive skills and behavior, and to increase activity and self-care in rehabilitation, the Web Behavior Change Program for Activity (Web-BCPA) was developed and added to multimodal pain rehabilitation (MMR). OBJECTIVE: The objective of our study was to evaluate the effects of MMR in combination with the Web-BCPA compared with MMR among persons with persistent musculoskeletal pain in primary health care on pain intensity, self-efficacy, and copying, as part of a larger collection of data...
October 5, 2016: Journal of Medical Internet Research
J B Wang, D L Ma, J Y Li, Q D Sun, Y E Liu
The aim of this study was to investigate the clinical significance of the expression of DNA mismatch repair (MMR) genes in patients subjected to radical surgical removal of colon cancer, as well as their correlation with disease prognosis. Ninety stage II and III colon cancer patients who received laparoscopic radical resection of colon cancer at our hospital were recruited in this study. The expression of hMLH1, hMSH2, hMSH6, and hPMS2 in the resected tumor tissues was examined by SP immunohistochemistry, in order to analyze the relationship between defective DNA MMR (dMMR) and the clinico-pathological features and prognosis of colon cancer...
August 19, 2016: Genetics and Molecular Research: GMR
Paul A Gastañaduy, Jeremy Budd, Nicholas Fisher, Susan B Redd, Jackie Fletcher, Julie Miller, Dwight J McFadden, Jennifer Rota, Paul A Rota, Carole Hickman, Brian Fowler, Lilith Tatham, Gregory S Wallace, Sietske de Fijter, Amy Parker Fiebelkorn, Mary DiOrio
Background Although measles was eliminated in the United States in 2000, importations of the virus continue to cause outbreaks. We describe the epidemiologic features of an outbreak of measles that originated from two unvaccinated Amish men in whom measles was incubating at the time of their return to the United States from the Philippines and explore the effect of public health responses on limiting the spread of measles. Methods We performed descriptive analyses of data on demographic characteristics, clinical and laboratory evaluations, and vaccination coverage...
October 6, 2016: New England Journal of Medicine
P S Parfrey, E Dicks, O Parfrey, P J McNicholas, H Noseworthy, M O Woods, C Negriin, J Green
As Newfoundland has the highest rate of familial CRC in the world, we started a population-based clinic to provide colonoscopic and Lynch syndrome (LS) screening recommendations to families of CRC patients based on family risk. Of 1091 incident patients 52% provided a family history. Seventy-two percent of families were at low or intermediate-low risk of CRC and colonoscopic screening recommendations were provided by letter. Twenty eight per cent were at high and intermediate-high risk and were referred to the genetic counsellor, but only 30% (N = 48) were interviewed by study end...
October 3, 2016: Clinical Genetics
Florence Mgawadere, Regine Unkels, Adetoro Adegoke, Nynke van den Broek
BACKGROUND: Assessing the feasibility of conducting a prospective Reproductive Age Mortality Survey (RAMOS) study in the low-income setting of Mangochi District, Malawi to obtain cotemporaneous estimates of the number, cause of and conditions associated with maternal deaths (MD) in all women of reproductive age (WRA) (n = 207 688). METHODS: MD among all deaths of WRA were identified using the ICD-10 definition. Cause of death and contributing conditions identified by a panel of experts using the classification system for deaths during pregnancy, childbirth and puerperium (ICD-MM)...
September 29, 2016: BMC Pregnancy and Childbirth
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