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https://www.readbyqxmd.com/read/28819720/immunohistochemical-null-phenotype-for-mismatch-repair-proteins-in-colonic-carcinoma-associated-with-concurrent-mlh1-hypermethylation-and-msh2-somatic-mutations
#1
Tao Wang, Zsofia K Stadler, Liying Zhang, Martin R Weiser, Olca Basturk, Jaclyn F Hechtman, Efsevia Vakiani, Lenard B Saltz, David S Klimstra, Jinru Shia
Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2)...
August 17, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28819700/sporadic-endometrial-adenocarcinoma-with-mmr-deficiency-due-to-biallelic-msh2-somatic-mutations
#2
Bruno Buecher, Antoine De Pauw, Louis Bazire, Claude Houdayer, Alice Fievet, Virginie Moncoutier, Fereshteh Farkhondeh, Samia Melaabi, Dominique Stoppa Lyonnet, Lisa Golmard
The invalidation of the Mismatch Repair (MMR) system is responsible for a so-called "deficient MMR" phenotype (dMMR) characterized by microsatellite instability and abnormal pattern of expression of MMR proteins in tumor tissue. This phenotype occurs in at least 20% of sporadic endometrial adenocarcinomas by epigenetic silencing of MLH1 gene. It is also observed in virtually all tumors occurring in patients with Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs...
August 17, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28816556/maternal-mortality-in-the-last-triennium-of-the-millennium-development-goal-era-at-the-obafemi-awolowo-university-teaching-hospitals-complex-ile-ife-nigeria
#3
Ibraheem Olayemi Awowole, Olusegun Olalekan Badejoko, Oluwafemi Kuti, Omotade Adebimpe Ijarotimi, Oluwaseun Oludotun Sowemimo, Ifeoluwa Emmanuel Ogunduyile
The maternal mortality ratio (MMR) of Nigeria remains high. This retrospective study aims to suggest evidence-based strategies towards achieving the sustainable development goal target 3.1 at the Obafemi Awolowo University Teaching Hospital (OAUTHC), Nigeria by providing contemporary data on MMR between October 2012 and September 2015. There were 86 maternal deaths and 5243 live births over the triennium, with annual MMRs of 1744, 1622 and 1512/100,000 live births, respectively. Fifty-six (65.2%) were postpartum deaths, while 44 (51...
August 17, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#4
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28807928/role-of-translesion-synthesis-dna-polymerases-in-dna-replication-in-the-presence-of-a-weak-dna-polymerase-%C3%AE-in-saccharomyces-cerevisiae
#5
Likui Zhang, Yanchao Huang, Xinyuan Zhu, Yuxiao Wang, Haoqiang Shi, Min Chen, Kunming Dong, Xiaojian Zhou
Translesion synthesis (TLS) DNA polymerases (pols) are often mutagenic for lesion bypass due to their low fidelity. Here, we isolated a weak yeast DNA pol δ mutant that possessed amino acid substitution V592G by genetic selection. The pol3-V592G cells were sensitive to hydroxyurea (HU), which increases the requirement for dNTPs, and their HU sensitivity was suppressed by L612M substitution. We also demonstrated that V592G substitution suppressed the phosphonoacetic acid (PAA) sensitivity of pol3-L612M cells, suggesting a cycle of mutual suppression in the HU- and PAA-sensitive yeast DNA pol δ mutants as similarly observed in the optA1- and PAA-sensitive T4 DNA pol mutants...
August 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28806450/evaluation-of-combination-measles-mumps-rubella-varicella-vaccine-introduction-in-australia
#6
Kristine Macartney, Heather F Gidding, Lieu Trinh, Han Wang, Aditi Dey, Brynley Hull, Karen Orr, Jocelynne McRae, Peter Richmond, Michael Gold, Nigel Crawford, Jennifer A Kynaston, Peter McIntyre, Nicholas Wood
Importance: Incorporating combination vaccines, such as the measles-mumps-rubella-varicella (MMRV) vaccine, into immunization schedules should be evaluated from a benefit-risk perspective. Use of MMRV vaccine poses challenges due to a recognized increased risk of febrile seizures (FSs) when used as the first dose in the second year of life. Conversely, completion by age 2 years of measles, mumps, rubella, and varicella immunization may offer improved disease control. Objective: To evaluate the effect on safety and coverage of earlier (age 18 months) scheduling of MMRV vaccine as the second dose of measles-containing vaccine (MCV) in Australia...
August 14, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28798865/measles-misinformation-and-risk-personal-belief-exemptions-and-the-mmr-vaccine
#7
Johnathan Bowes
No abstract text is available yet for this article.
December 2016: Journal of Law and the Biosciences
https://www.readbyqxmd.com/read/28797728/utilization-and-impact-of-european-immunization-week-to-increase-measles-mumps-rubella-vaccine-uptake-in-austria-in-2016
#8
P Kreidl, Catharina de Kat
This paper describes engagement in European Immunization Week (EIW) in Tyrol, Austria in April 2016 and an assessment of its possible impact on demand for measles, mumps, rubella vaccination (MMR). It further describes the output of a knowledge, attitudes and practice (KAP) survey conducted during EIW, showing that 93% (188/202) of respondents were in favor of vaccination in general and 90% (192/214) perceived MMR vaccination to be important. MMR vaccination was perceived as important by more participants than other vaccinations...
August 7, 2017: Vaccine
https://www.readbyqxmd.com/read/28794186/hfq-links-translation-repression-to-stress-induced-mutagenesis-in-e-coli
#9
Jiandong Chen, Susan Gottesman
Mismatch repair (MMR) is a conserved mechanism exploited by cells to correct DNA replication errors both in growing cells and under nongrowing conditions. Hfq (host factor for RNA bacteriophage Qβ replication), a bacterial Lsm family RNA-binding protein, chaperones RNA-RNA interactions between regulatory small RNAs (sRNAs) and target messenger RNAs (mRNAs), leading to alterations of mRNA translation and/or stability. Hfq has been reported to post-transcriptionally repress the DNA MMR gene mutS in stationary phase, possibly limiting MMR to allow increased mutagenesis...
August 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28791408/-retracted-effects-of-the-eukaryotic-initiation-factor-6-gene-on-expression-levels-of-inflammatory-mediators-in-m2-macrophages-during-scar-repair
#10
Yong-Qiang Bai, Jian-Ke Feng, Qing-Fu Zhang, Hong-Zhi Wu, Ya-Ru Du, Wei Wei
Following the publication of this article, we regret to report that we have been unable to reproduce the results presented in the paper in our subsequent studies. At the present time, we have not been able to ascertain the reason behind this. Therefore, we would like to retract this article from publication. All the named authors agree to this retraction. We regret any inconvenience to the readers that this retraction will cause. [The original article was published in Molecular Medicine Reports 14: 819-824, 2016; DOI: 10...
August 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28790115/msh2-loss-in-primary-prostate-cancer
#11
Liana Guedes, Emmanuel S Antonarakis, Michael T Schweizer, Nooshin Mirkheshti, Fawaz Almutairi, Jong Chul Park, Stephanie A Glavaris, Jessica L Hicks, Mario A Eisenberger, Angelo M De Marzo, Jonathan I Epstein, William B Isaacs, James R Eshleman, Colin C Pritchard, Tamara L Lotan
PURPOSE: Inactivation of mismatch repair (MMR) genes may predict sensitivity to immunotherapy in metastatic prostate cancers. We studied primary prostate tumors with MMR defects. EXPERIMENTAL DESIGN: 1133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas (NEPC) were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing (NGS). Microsatellite instability (MSI) was assessed by PCR and NGS (mSINGS). RESULTS: Of primary adenocarcinomas and NEPC, 1...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28783711/mmr-deficiency-and-brca2-egfr-ntrk-mutations
#12
Prashanth Gokare, Amriti R Lulla, Wafik S El-Deiry
No abstract text is available yet for this article.
August 3, 2017: Aging
https://www.readbyqxmd.com/read/28776572/molecular-based-classification-algorithm-for-endometrial-carcinoma-categorizes-ovarian-endometrioid-carcinoma-into-prognostically-significant-groups
#13
Carlos Parra-Herran, Jordan Lerner-Ellis, Bin Xu, Sam Khalouei, Dina Bassiouny, Matthew Cesari, Nadia Ismiil, Sharon Nofech-Mozes
The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR), and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma, their role in predicting its molecular profile and prognosis is still not fully explored. Patients with ovarian endometrioid carcinomas treated surgically in a 14-year period were selected...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28770104/immunoscore-in-mismatch-repair-proficient-and-deficient-colon-cancer
#14
Erkki-Ville Wirta, Toni Seppälä, Marjukka Friman, Juha Väyrynen, Maarit Ahtiainen, Hannu Kautiainen, Teijo Kuopio, Ilmo Kellokumpu, Jukka-Pekka Mecklin, Jan Böhm
The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8...
July 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28769742/reproducibility-of-quantitative-brain-imaging-using-a-pet-only-and-a-combined-pet-mr-system
#15
Martin L Lassen, Otto Muzik, Thomas Beyer, Marcus Hacker, Claes Nøhr Ladefoged, Jacobo Cal-González, Wolfgang Wadsak, Ivo Rausch, Oliver Langer, Martin Bauer
The purpose of this study was to test the feasibility of migrating a quantitative brain imaging protocol from a positron emission tomography (PET)-only system to an integrated PET/MR system. Potential differences in both absolute radiotracer concentration as well as in the derived kinetic parameters as a function of PET system choice have been investigated. Five healthy volunteers underwent dynamic (R)-[(11)C]verapamil imaging on the same day using a GE-Advance (PET-only) and a Siemens Biograph mMR system (PET/MR)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28767665/systematic-immunohistochemical-screening-for-mismatch-repair-and-ercc1-gene-expression-from-colorectal-cancers-in-china-clinicopathological-characteristics-and-effects-on-survival
#16
Pan Li, Zhitao Xiao, Todd A Braciak, Qingjian Ou, Gong Chen, Fuat S Oduncu
BACKGROUND: We performed a systematic screening of colorectal cancer (CRC) tissues to investigate whether mismatch repair (MMR) status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP). METHODS: The expression of four MMR genes and ERCC1 were assessed by immunohistochemistry (IHC) from cancer tissue samples of 2233 consecutive CRC patients...
2017: PloS One
https://www.readbyqxmd.com/read/28765196/in-silico-systems-biology-analysis-of-variants-of-uncertain-significance-in-lynch-syndrome-supports-the-prioritization-of-functional-molecular-validation
#17
Ester Borras, Kyle Chang, Mala Pande, Amanda Cuddy, Jennifer L Bosch, Sarah Bannon, Maureen E Mork, Miguel Rodriguez-Bigas, Melissa Taggart, Patrick M Lynch, Y Nancy You, Eduardo Vilar
Lynch syndrome (LS) is a genetic condition secondary to germline alterations in the DNA mismatch repair (MMR) genes with 30% of changes being variants of uncertain significance (VUS). Our aim was to perform an in silico re-classification of VUS from a large single institutional cohort that will help prioritizing functional validation. A total of 54 VUS were detected with 33 (61%) novel variants. We integrated family history, pathology, and genetic information along with supporting evidence from 8 different in silico tools at the RNA and protein level...
August 1, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28761604/-colon-adenocarcinoma-and-synchronous-type-1-papillary-renal-cell-carcinoma-a-unique-association
#18
Asma Sassi, Dhouha Bacha, Ghofrane Talbi, Sana Ben Slama, Rahma Boughriba, Zeineb Mzoughi, Saadia Bouraoui, Ahlem Lahmar
The detection of primary tumors synchronous with colorectal cancer has been the subject of multiple publications. This association can occur sporadically or fall under the framework of well defined clinical syndromes such as Lynch syndrome. Synchronous association of colorectal cancer (CRC) and renal cell carcinoma is rare. It is even more rare when renal cell carcinoma is of papillary origin, with only 2 cases reported in the literature. The association between CRC and renal cell carcinoma does not seem to be related to mismatch repair proteins (MMR) abnormality and does not include, up to now, any clinical syndrome...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28761360/analysis-of-clinical-characteristics-and-efficacy-of-chronic-myeloid-leukemia-onset-with-extreme-thrombocytosis-in-the-era-of-tyrosine-kinase-inhibitors
#19
Zhihe Liu, Hongqiong Fan, Yuying Li, Chunshui Liu
The aim of this study was to investigate the clinical characteristics and efficacy of chronic myeloid leukemia (CML) onset with extreme thrombocytosis. A total of 121 newly diagnosed and untreated CML patients in chronic phase with complete clinical information from the First Hospital of Jilin University, from January 2010 to December 2014 were retrospectively recruited. Based on the platelet (PLT) count, 22 patients were assigned into CML with thrombocytosis (CML-T) group (PLT >1,000×10(9)/L) and 65 patients were classified into CML without extreme thrombocytosis (CML-N) group (PLT ≤1,000×10(9)/L)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28761354/pd-1-blockade-restores-impaired-function-of-ex-vivo-expanded-cd8-t-cells-and-enhances-apoptosis-in-mismatch-repair-deficient-epcam-pd-l1-cancer-cells
#20
Rajeev Kumar, Fang Yu, Yuan-Huan Zhen, Bo Li, Jun Wang, Yuan Yang, Hui-Xin Ge, Ping-Sheng Hu, Jin Xiu
BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic function of expanded CD8(+) CTLs and interactions with tumor cells investigated after blocking of PD-1...
2017: OncoTargets and Therapy
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