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Hereditary non-polyposis colorectal cancer (HNPCC; OMIM 120435-6) is a cancer-susceptibility syndrome linked to inherited defects in human mismatch repair (MMR) genes. Germline missense human MLH1 (hMLH1) mutations are frequently detected in HNPCC (ref. 3), making functional characterization of mutations in hMLH1 critical to the development of genetic(More)
PURPOSE This phase III study compared treatment with weekly paclitaxel and biweekly irinotecan in patients with advanced gastric cancer refractory to treatment with fluoropyrimidine plus platinum. PATIENTS AND METHODS Patients were randomly assigned to receive either paclitaxel (80 mg/m(2) on days 1, 8, and 15, every 4 weeks) or irinotecan (150 mg/m(2) on(More)
The functional characterization of nonsynonymous single nucleotide polymorphisms in human mismatch repair (MMR) genes has been critical to evaluate their pathogenicity for hereditary nonpolyposis colorectal cancer. We previously established an assay for detecting loss-of-function mutations in the MLH1 gene using a dominant mutator effect of human MLH1(More)
496 Background: Sequential combination with irinotecan (CPT-11) and S-1 (IRIS) is active and safe regimen against mCRC (ASCO2008, abstract #4107, T. Yoshioka et al. Br J Cancer 101: 1972-77, 2009). The aim of this prospective randomized pilot study was to compare safety (CTCAE v3.0, primary endpoint) and efficacy (RR and PFS, secondary endpoint) of IRIS(More)
We have screened the p53 status of 156 human cell lines, including 142 tumor cell lines from 27 different tumor types and 14 cell lines from normal tissues by using functional analysis of separated alleles in yeast. This assay enables us to score wild-type p53 expression on the basis of the ability of expressed p53 to transactivate the reporter gene HIS3(More)
The detection of inactivating mutations in tumor suppressor genes is critical to their characterization, as well as to the development of diagnostic testing. Most approaches for mutational screening of germ-line specimens are complicated by the fact that mutations are heterozygous and that missense mutations are difficult to interpret in the absence of(More)
BACKGROUND Anti-epidermal growth factor receptor (EGFR) antibodies, cetuximab, and panitumumab are established as a new treatment option for metastatic colorectal cancer (mCRC). Among activating mutations downstream of EGFR, the KRAS mutation, which is present in 30-45 % of CRC patients, has shown to be a predictive biomarker of resistance to anti-EGFR(More)
Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (CRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti-EGFR treatment. We investigated the genome-wide DNA methylation status in metastatic colorectal cancer to identify associations between the(More)
BACKGROUND Both irinotecan (CPT-11) and S-1 are active against colorectal cancer; however, as S-1 is a prodrug of 5-fluorouracil (5-FU), 5-FU and its metabolites might inhibit the antitumour effect of CPT-11. Therefore, we designed a sequential combination, in which CPT-11 infusion was given on day 1 and S-1 was given orally at 80 mg m(-2) per day on days(More)
BACKGROUND The requirement of central venous (CV) port implantation is increasing with the increase in the number of cancer patients and advancement in chemotherapy. In our division, medical oncologists have implanted all CV ports to save time and consultation costs to other departments. Recently, upper arm implantation has become the first choice as a safe(More)