The DNA mismatch repair gene hMLH1 is reported to function in mutation avoidance, cell cycle checkpoint control, the cytotoxicity of various DNA-damaging agents, and transcription-coupled nucleotide excision repair. Formal proof of the involvement of hMLH1 in these processes requires single gene complementation. We have stably expressed hMLH1 from a transfected cDNA in Mlh1-deficient mouse embr...

Somatic mutations in DNA mismatch repair genes have been observed in sporadic tumors as well as cell lines and xenografts derived from such tumors implicating genetic defects of mismatch repair genes in the development of such tumors. However, the proportion of sporadic tumors in which mismatch repair genes have been inactivated has not been determined accurately. We have analyzed 66 sporadic c...

Purpose: The aim of the study was to investigate the effect of deficiency of hMLH1 and hMSH2 expression on the prognosis of early gastric cancer (EGC) in Chinese populations. Methods: A total of 160 EGC patients who underwent curative gastrectomy with lymphadenectomy from January 2011 to July 2014 at Xinhua Hospital were evaluated. The expression rates of hMLH1 and hMSH2 were examined using tis...

Biliary tract cancer is of highly malignancy with a poor 5-year survival. However, established chemotherapeutic regimens have not yet been established. Previously, we have reported that hMLH1, a mismatch repair (MMR) gene was frequently (57%) found to be lacking in surgically resected biliary tract carcinomas and the patients lacking the expression of hMLH1 revealed a poorer prognosis than thos...

The frequency of synchronous or metachronous multiple primary carcinomas in patients with gastrointestinal carcinoma or colorectal carcinoma (CRC) has been reported to be approximately 10%. We determined the role of hMSH2 and hMLH1 in double carcinomas with both GC and CRC. Fifty-six patients with synchronous or metachronous colorectal carcinoma with gastric carcinoma (CRC with GC), and 69 pati...

PURPOSE Sporadic colorectal cancers with high-frequency microsatellite instability (MSI-H) are related to hypermethylation of mismatch repair (MMR) genes and a higher frequency of BRAF mutations than Lynch syndrome. We estimated the feasibility of hereditary colorectal cancer based on hMLH1 methylation and BRAF mutations. METHODS Between May 2005 and June 2011, we enrolled all 33 analyzed pat...

PURPOSE The aim of this study was to evaluate the responsiveness to CPT-11 with respect to hMLH1 and hMSH2 protein expressions in primary colorectal tumors. MATERIALS AND METHODS 91 patients with colorectal cancer treated having undergone surgery and postoperative CPT-11-based adjuvant chemotherapy, between 1997 and 2002, were prospectively recruited. Tumor samples were immunohistochemically ...

Mismatch repair is a highly conserved system that ensures replication ®delity by repairing mispairs after DNA synthesis. In humans, the two protein heterodimers hMutSa (hMSH2-hMSH6) and hMutLa (hMLH1-hPMS2) constitute the centre of the repair reaction. After recognising a DNA replication error, hMutSa recruits hMutLa, which then is thought to transduce the repair signal to the excision machiner...

We analyzed the hMLH1 and hMSH2 genes in 30 unrelated hereditary nonpolyposis colorectal cancer (HNPCC) patients using mutational and immunohistochemical analyses combined whenever possible with primer extension assays, designed to estimate hMLH1 and hMSH2 transcript expression in peripheral blood lymphocytes. Single-strand conformational polymorphism screening and PCR-direct sequencing reveale...

Estrogen is reported to have a protective effect on colon cancer; however, the underlying mechanism is unclear. Impaired mismatch repair plays an important role in colonic carcinogenesis. The purpose of this study was to investigate the association of estrogen on regulating mismatch repair expression in colonic epithelial cells. In cultured COLO205 cells, the effect of estradiol (E2) and antago...