[The influence of CYP2A6 polymorphism on adjuvant S-1 chemotherapy outcomes in patients with curatively resected gastric cancer].

Objective: Oral fiuoropyrimidine S-1 contains tegafur, gimeracil, oteracil. Tegafur is the major active prodrug, which is metabolized to 5-Fu by cytochrome P4502A6 (CYP2A6). This research investigated the association between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients. Methods: A total of 200 patients diagnosed pathological stage Ⅱ-Ⅲ gastric cancer were included in this study, who were received adjuvant S-1 chemotherapy regimens after curative surgery (40 mg/m(2,) bid, d1-28, rest 2 weeks, every 6 weeks one cycle). Additionally, the wild-type allele (CYP2A6*1) and four variant alleles (CYP2A6*4, *7, *9, *10) were genotyped. Results: A total of 200 patients were enrolled in this study with a median follow-up of 46.5 months. The 3-year recurrence free survival rates were 95.9% for W/W (n=49), 83.1% for W/V (n=94), and 72.5% for V/V (n=57), with significant difference (P=0.032). Grade ≥3 hematologic toxicities of three genotype groups were without difference (10.2% vs 14.9% vs 10.5%, P=0.628). Conclusions: CYP2A6 genotypes correlate with the survival of S-1 chemotherapy. And its polymorphism detection can provide individualized guidance for adjuvant chemotherapy options in patients with gastric cancer.

Integrative microRNA-mRNA and protein-protein interaction analysis in pancreatic neuroendocrine tumors.

OBJECTIVE: Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations of the molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of microRNA and messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors. MATERIALS AND METHODS: The messenger RNA and microRNA expression profile of GSE43796 were downloaded, including 6 samples with pancreatic neuroendocrine tumors and 5 healthy samples. First, the Limma package was utilized to distinguish the differentially expressed messenger RNA and microRNA separately. Then we used microRNA Walk databases to predict the target genes of the differentially expressed microRNAs (DE-microRNAs), and selected differentially expressed target genes whose expression was reversely correlated with microRNAs. Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the functions and pathways of target genes. In addition, we constructed a regulatory miRNAs-target genes network and a protein-protein interaction network. RESULTS: There were 28 differentially expressed microRNAs and 859 differentially expressed messenger RNAs, including 253 potential target genes. These target genes mainly enriched in ABC transporters pathway. In this network, hsa-miR-7-2-3p demonstrated the highest connectivities whereas KLF12 was the mRNAs with the highest connectivities. CXCL12 was identified as the hub of the protein-protein interaction sub-network. CONCLUSIONS: The genes involved in ABC transporters and Type II diabetes mellitus pathway, KLF12 and CXCL12 may play an important role in the progression of pancreatic neuroendocrine tumors. However, more experimental studies are required.

The energetics and structure of rutile TiO(2)(110).

Density functional theory and a pseudopotential plane wave method are applied to study electronic and structural properties of the defect-free TiO(2)(110) surface. The variations of the surface energy, work function, and atomic displacements are examined for partially and fully relaxed slabs modelling the rutile (110) surface, and consisting of up to 33 atomic layers. Relatively small relaxations of atomic positions in the outermost layers have a strong influence on the calculated surface energies and work functions. The effect of nonequivalence of the odd-even layer terminations is explored. A simple method is proposed which allows one to estimate accurate surface energies for relaxed systems from calculations for partially relaxed slabs.

Cupric ion/ascorbate/hydrogen peroxide-induced DNA damage: DNA-bound copper ion primarily induces base modifications.

The kinetics of frank DNA strand breaks and DNA base modifications produced by Cu(II)/ascorbate/H2O2 were simultaneously determined in purified human genomic DNA in vitro. Modified bases were determined by cleavage with Escherichia coli enzymes Nth protein (modified pyrimidines) and Fpg protein (modified purines). Single-stranded lesion frequency before (frank strand breaks) and after (modified bases) Nth or Fpg protein digestion was quantified by neutral glyoxal gel electrophoresis. Dialysis of EDTA-treated genomic DNA purified by standard proteinase K digestion/phenol extraction was necessary to remove low molecular weight species, probably transition metal ions and metal ion chelators, which supported frank strand breaks in the presence of ascorbate + H2O2 without supplemental copper ions. We then established a kinetic model of the DNA-damaging reactions caused by Cu(II) + ascorbate + H2O2. The principal new assumption in our model was that DNA base modifications were caused exclusively by DNA-bound Cu(I) and frank strand breaks by non-DNA-bound Cu(I). The model was simulated by computer using published rate constants. The computer simulation quantitatively predicted: (1) the rate of H2O2 degradation, which was measured using an H2O2-sensitive electrode, (2) the linearity of accumulation of DNA strand breaks and modified bases over the reaction period, (3) the rate of modified base accumulation, and (4) the dependence of modified base and frank strand production on initial Cu(II) concentration. The simulation significantly overestimated the rate of frank strand break accumulation, suggesting either that the ultimate oxidizing species that attacks the sugar-phosphate backbone is a less-reactive species than the hydroxyl radical used in the model and/or an unidentified hydroxyl radical-scavenging species was present in the reactions. Our experimental data are consistent with a model of copper ion-DNA interaction in which DNA-bound Cu(I) primarily mediates DNA base modifications and nonbound Cu(I) primarily mediates frank strand break production.

[Quality of clinical trials of Chinese herbal drugs, a review of 314 published papers].

The study was based on a review of clinical trials for herbal drugs published in various journals. Three journals selected were Chinese Journal of Integrated Traditional and Western Medicine (JITWM), Journal of Traditional Chinese Medicine (JTCM), and a provincial Journal of Traditional Medicine (JTM). In order to reflect different levels of the journal, each paper of the clinical trials of herbal drugs in the above-mentioned journals during the survey years, 1991, 1987 and 1980 (or 1981) was reviewed using a standard checklist and quantified through a score system. A total of 314 paper were reviewed, in which 179 in 1991, 82 in 1987, and 53 in 1980 and 1981. Controlled trials were found in 86% of JITWM, 40.8% of JTCM, and 26.8% of JTM in 1991. Although there was an increased trend in the use or randomized trials, it still showed a lower proportion, respectively 52.9% in JITWM, 36.0% in JTCM, and 11.1% in JTM. We found that the quality of clinical trials in JITWM was the first, JTCM the second, JTM the third and showed a gradually improved trend with time.

Differential effect of platelets on plasminogen activation by tissue plasminogen activator, urokinase, and streptokinase.

In this report, we have examined the effects of platelets on plasminogen activation by different activators. Platelets enhance activation of plasminogen by both 1- and 2-chain tissue plasminogen activator (t-PA). The primary effect of platelets is to lower the Km with a corresponding 5-8-fold increase in the kcat/Km. The effect is saturable with respect to the platelet concentration. Platelets enhance activation of both glu- and lys-plasminogen by t-PA. Platelets have no effect on plasminogen activation by streptokinase, and high and low molecular weight urokinase. Thus, there are marked differences in the effects of platelets on plasminogen activation depending on the plasminogen activator. These differences are likely to reflect differences in the interaction between platelets and the plasminogen activators.