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Microsatellite instability

Kaname Miyashita, Kei Fujii, Kenichi Taguchi, Mototsugu Shimokawa, Mitsuaki A Yoshida, Yasunobu Abe, Jun Okamura, Shinya Oda, Naokuni Uike
PURPOSE: Microsatellite instability (MSI) has been a long-standing biomarker candidate for drug resistance in tumour cells. Despite numerous clinical studies, the data in the literature are not conclusive. The complexity of the MSI phenomenon in some malignancies may, at least partly, account for the discrepancy. In addition, methodological problems are also pointed out in the assay techniques. We previously established a unique fluorescent technique in which the major methodological problems in conventional assays are overcome...
October 25, 2016: Journal of Cancer Research and Clinical Oncology
Mengying Wu, Zhuojia Lin, Xiaonan Li, Xiaoru Xin, Jiahui An, Qidi Zheng, Yuxin Yang, Dongdong Lu
The dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Our results demonstrate HULC, MALAT1 and TRF2 are highly expressed in human hepatocellular carcinoma tissues, and HULC plus MALAT1 overexpression drastically promotes the growth of liver cancer stem cells. Mechanistically, both HULC and MALAT1 overexpression enhanced RNA polII, P300, CREPT to load on the promoter region of telomere repeat-binding factor 2(TRF2), triggering the overexpression, phosphorylation and SUMOylation of TRF2...
October 26, 2016: Scientific Reports
Shihao Dong, Jingsong Chen
Serrated polyposis syndrome (SPS) is closely associated with the initiation and development of colorectal cancer (CRC), however, there is few research on SPS in China. Serrated polyps can be divided into hyperplastic polyps, sessile serrated polyps and traditional serrated polyps. The diagnosis standard of SPS is as following: (1) There are at least 5 serrated lesions in proximal colon, and diameter of more than 2 lesions is >10 mm; (2) The patient has one serrated polyp with family history of SPS; (3) More than 20 serrated polyps can be found in the entire large bowel...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Takayuki Nagasawa, Tamotsu Sugai, Tadahiro Shoji, Wataru Habano, Toru Sugiyama
OBJECTIVE: Endometrial adenocarcinomas are characterized by the presence of many single tumor glands in which multiple genetic changes have accumulated. To elucidate the differences in molecular abnormalities among single tumor glands, individual tumor glands were analyzed and microsatellite alterations (loss of heterozygosity (LOH) and microsatellite instability [MSI]) were examined using the crypt isolation method in glands from each tumor from patients with endometrial carcinoma. METHODS: Twenty-five patients with endometrial adenocarcinoma who underwent surgery were included in this study...
November 2016: International Journal of Gynecological Cancer
Wayne Ng, Joo-Shik Shin, Tao Yang, Tara Roberts, Bin Wang, Jarrad Begg, Cheok Soon Lee
No abstract text is available yet for this article.
February 2016: Pathology
Harini Edirisinghe, Anita Mani
No abstract text is available yet for this article.
February 2016: Pathology
Tomio Arai, Yoko Matsuda, Junko Aida, Kaiyo Takubo
No abstract text is available yet for this article.
February 2016: Pathology
Gabriele Picco, Consalvo Petti, Francesco Sassi, Katia Grillone, Giorgia Migliardi, Teresa Rossi, Claudio Isella, Federica Di Nicolantonio, Ivana Sarotto, Anna Sapino, Alberto Bardelli, Livio Trusolino, Andrea Bertotti, Enzo Medico
BACKGROUND: The NEDD8 conjugation pathway modulates the ubiquitination and activity of a wide range of intracellular proteins, and its blockade by pevonedistat is emerging as a promising therapeutic approach in various cancer settings. However, systematic characterization of pevonedistat efficacy in specific tumor types and definition of response predictors are still missing. METHODS: We investigated in vitro sensitivity to pevonedistat in 122 colorectal cancer (CRC) cell lines by an ATP-based proliferation assay and evaluated apoptosis and DNA content by flow cytometry...
February 2017: Journal of the National Cancer Institute
C Velter, F Bourlond, C Wettle, B Lioure, D Lipsker, C Maugard, B Cribier
BACKGROUND: Muir-Torre syndrome (MTS), a cutaneous variant of Lynch syndrome, consists of hereditary predisposition to cutaneous tumours and gastrointestinal and gynaecological neoplasms, with autosomal dominant transmission. It is associated with mutations in genes coding for proteins in the DNA mismatch repair system. PATIENTS AND METHODS: Herein, we report a case of a male patient presenting Waldenstrom's macroglobulinemia since the age of 50 and which, after the age of 65 years, developed into sebaceous tumours (5 sebaceous adenomas, 1 sebaceoma, 1 sebaceous carcinoma) and colonic lesions (4 adenomas)...
October 19, 2016: Annales de Dermatologie et de Vénéréologie
Violeta N Kovacheva, Nasir M Rajpoot
BACKGROUND: New bioimaging techniques capable of visualising the co-location of numerous proteins within individual cells have been proposed to study tumour heterogeneity of neighbouring cells within the same tissue specimen. These techniques have highlighted the need to better understand the interplay between proteins in terms of their colocalisation. RESULTS: We recently proposed a cellular-level model of the healthy and cancerous colonic crypt microenvironments...
October 22, 2016: BMC Bioinformatics
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
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
Maria G Kuba, Allison Wasserman, Cindy L Vnencak-Jones, Julia A Bridge, Lan Gellert, Omar Hameed, Giovanna A Giannico
OBJECTIVES: Primary carcinoid tumor of the renal pelvis is a rare neoplasm with few cases reported in the literature. Here we present the clinical and histopathologic findings of a primary carcinoid tumor arising in the left renal pelvis of a horseshoe kidney in a 61-year-old female patient. MATERIALS AND METHODS: Pathologic features were evaluated with standard hematoxylin and eosin sections and immunohistochemical studies. A literature review was performed to place our case in context to previous reports...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Markovic Srdjan, Antic Jadranka, Dimitrijevic Ivan, Zogovic Branimir, Bojic Daniela, Svorcan Petar, Markovic Velimir, Krivokapic Zoran
BACKGROUND & OBJECTIVES: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data. METHODS: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009)...
May 2016: Indian Journal of Medical Research
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
Yoshiki Nando, Jiro Watari, Chiyomi Ito, Ken Hara, Takahisa Yamasaki, Takuya Okugawa, Takashi Kondo, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Yoshio Ohda, Tadayuki Oshima, Hirokazu Fukui, Nagahide Matsubara, Naohiro Tomita, Seiichi Hirota, Hiroto Miwa
It is recommended that small (6-10 mm) lesions be treated with endoscopic resection (ER), while diminutive (≤ 5 mm) lesions are not currently an indication for ER according to the Japanese guidelines. The aim of this study was to evaluate the molecular alterations, and therefore treatment indications, in diminutive vs. small tubular adenoma (TA). We prospectively analyzed genetic instability, including microsatellite instability (MSI) and loss of heterozygosity, methylation status, KRAS/BRAF mutations, and Ki-67 staining in 96 TAs without a villous component...
October 13, 2016: Human Pathology
Joo Hwa Lee, Nam Jin Yoo, Min Sung Kim, Sug Hyung Lee
Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H)...
October 15, 2016: Pathology Oncology Research: POR
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
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
Łukasz J Sznajder, Michał Michalak, Katarzyna Taylor, Piotr Cywoniuk, Michał Kabza, Agnieszka Wojtkowiak-Szlachcic, Magdalena Matłoka, Patryk Konieczny, Krzysztof Sobczak
Muscleblind-like (MBNL) proteins are critical RNA processing factors in development. MBNL activity is disrupted in the neuromuscular disease myotonic dystrophy type 1 (DM1), due to the instability of a non-coding microsatellite in the DMPK gene and the expression of CUG expansion (CUG(exp)) RNAs. Pathogenic interactions between MBNL and CUG(exp) RNA lead to the formation of nuclear complexes termed foci and prevent MBNL function in pre-mRNA processing. The existence of multiple MBNL genes, as well as multiple protein isoforms, raises the question of whether different MBNL proteins possess unique or redundant functions...
October 12, 2016: Nucleic Acids Research
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