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Abstract: The metastasis-associated gene 1 (mta1) was identified initially in rat highly metastatic cancer cell lines and found to be a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. The gene for mouse mta1 was screened and its genomic structure was determined. It consists of 21 exons spanning 40 kb of genomic DNA. The full-length mouse Mta1 cDNA contained a 2145 nucleotide open reading frame encoding 715 amino acids. In addition to the full-length cDNA, several alternative splicing variants were found. Some differences in the splicing variants found were observed among various mouse organs and cells examined by the semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The cDNAs of the splicing variants were inserted into green fluorescent protein (GFP) expression vector and the subcellular localization of the GFP-Mta1 fusion proteins were analyzed. Knowledge of the Mta1 gene expression pattern will be useful in better understanding its functional diversity. [Copyright &y& Elsevier]

Discusses a mechanism that mediated the repression of 92-kDa type IV collagenase (MMP-9) expression by metastases-associated gene MTA1. Finding that MTA1 binds to the MMP-9 promoter; Repression of expression of such type of IV collagenase via histone-dependent and independent mechanism.

Summary: Background: Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone. Methods: In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled betweeen March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40–60 mg depending on patient''s body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m2 cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670. Findings: 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13·0 months [IQR 7·6–21·9]) than in those assigned to S-1 alone (11·0 months [5·6–19·8]; hazard ratio for death, 0·77; 95% CI 0·61–0·98; p=0·04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6·0 months [3·3–12·9] vs 4·0 months [2·1–6·8]; p<0·0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43–65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23–41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group. Interpretation: S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer. [Copyright &y& Elsevier]

Endoscopic mucosal resection (EMR) has been widely accepted as a minimally invasive and standard treatment for early gastric cancers without ulceration or signs of submucosal invasion and meeting the criteria for diameter, macroscopic appearance, and well- or moderately differentiated histology. However, EMR cannot be applied to some cases owing to technical difficulties relating to the intragastric location of the cancers even when the above criteria are satisfied. We report here a new approach to EMR for early cancers of the cardia located close to the esophagocardia junction that are outside the indications for ordinary EMR. [Copyright &y& Elsevier]