Association analysis of colorectal cancer susceptibility variants with gastric cancer in a Chinese Han population.

Evidence suggests that some genetic variants are risk factors for both colorectal cancer (CRC) and gastric cancer (GC). Thus, we selected 12 reported single nucleotide polymorphisms (SNPs) from genome-wide association studies of CRC and conducted this case-control study to assess the associations between these SNPs and the risk for GC in a southern Chinese population. All SNPs were genotyped in 249 individuals with GC and 292 healthy population-matched subjects using the Sequenom MassArray iPLEX System. Association analyses based on the c2 test and binary logistic regression were performed to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. A stratified analysis by gender was also performed. Borderline significant associations were observed for rs4444235 (P = 0.070) and rs10411210 (P = 0.084), both fitting the overdominant model. The rs4444235 CT genotype showed a protective effect (OR = 0.72, 95%CI = 0.50-1.03), while the rs10411210 CT genotype was a risk factor (OR = 1.40, 95%CI = 0.96-2.05) as compared with the CC+TT genotype. In the female subgroup, the rs6983267 GT genotype (compared with TT, OR = 2.31, 95%CI = 1.07-4.99) and the rs10505477 CT genotype (compared with TT, OR = 2.36, 95%CI = 1.09-5.11) significantly increased the risk for GC. No significant association was detected for the other SNPs. These results provide evidence that known genetic variants associated with CRC risk may also confer risk for GC.

Significance of relaxin-2 expression in hepatocellular carcinoma: relation with clinicopathological parameters.

BACKGROUND: A number of putative roles, including the modulation of tumor growth, neovascularization, metastasis and oncogenic progression, have been correlated to relaxin-2 overexpression. However, the clinical significance of relaxin-2 expression in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of relaxin-2 in HCC and determine its correlation with tumor progression and prognosis. PATIENTS AND METHODS: 180 HCC patients who had undergone curative liver resection were selected and immunohistochemistry was performed to analyze relaxin-2 expression in the respective tumors. RESULTS: Immunohistochemistry confirmed relaxin-2 overexpression in HCC tissues compared with their adjacent nonneoplastic tissues (p < 0.01). Additionally, immunostaining showed more relaxin-2 positive cells in the higher tumor grade (III) than in the lower tumor stage (I, II; p = 0.026). Moreover, HCC patients with high relaxin-2 expression were significantly associated with lower 5-year overall survival (p < 0.01) and lower 5-year disease-free survival (p < 0.01), respectively. Furthermore, immunostaining showed more relaxin-2 positive cells in the tumor recurrence (ETR) patients than non-ETR patients (p = 0.001). The Cox proportional hazards model further showed that relaxin-2 was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 1.872, 95% confidence interval [CI] = 1.18-5.146, p = 0.023) and 5-year overall survival (HR = 3.637, CI = 1.443-7.15, p = 0.001) in HCC. CONCLUSIONS: Our data suggest for the first time that the overexpression of relaxin-2 protein in HCC tissues is of predictive value on tumor progression and poor prognosis.

Association of DNMT1 and DNMT3B polymorphisms with breast cancer risk in Han Chinese women from South China.

Patterns of DNA methylation are established and maintained by a family of DNA methyltransferases (DNMTs). Aberrant promoter DNA methylation of tumor suppressor genes is found in breast cancer. Association studies between DNMT gene polymorphisms and breast cancer in various populations have reported inconsistent results. This study assessed the associations of single nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A, DNMT3B, DNMT3L, and DNMT2 with breast cancer among Han Chinese women from South China. Sixteen SNPs (rs2114724, rs2228611, rs2228612, rs8101866, and rs16999593 in DNMT1; rs13420827, rs11887120, rs13428812, rs1550117, rs11695471, and rs6733301 in DNMT3A; rs2424908, rs2424913, and rs6087990 in DNMT3B; rs113593938 in DNMT3L, and rs11254413 in DNMT2) in 408 women with breast cancer and 469 controls were genotyped using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Two SNPs, rs16999593 in DNMT1 and rs2424908 in DNMT3B, were significantly associated with breast cancer risk. The heterozygous genotype CT of rs16999593 was associated with increased breast cancer risk [odds ratio (OR) = 1.60; 95% confidence interval (95%CI) = 1.20-2.14; P = 0.0052], whereas rs2424908 was associated with decreased risk (OR = 0.62; 95%CI = 0.46-0.84; P = 0.0061). Other DNMT polymorphisms showed no significant associations with breast cancer risk in the study population. Haplotype CGTC of rs2114724, rs2228611, rs8101866, and rs16999593 in DNMT1 differed significantly as a risk factor between the case and control groups (OR = 1.51; 95%CI = 1.18-1.93; P = 0.0012). The heterozygous genotypes of rs16999593 in DNMT1 and rs2424908 in DNMT3B were strongly associated with breast cancer risk.

[The cause of brackets lost in fixed appliance].

OBJECTIVE: To discusses the causes of brackets lost in fixed appliance. METHODS: Thirty-eight patients received three kinds of adhesives, with a total of adhesive brackets 1,303, including 325 edgewise brackets and 978 Begg brackets. The three adhesives were JJ enamel adhesive, TF non mixed orthodontic adhesive and 3M light-cured composite. RESULTS: The overall rate of bracket lost was 54.3% (707/1,303), including 63.8% in mandibular teeth brackets, 36.2% of maxillary teeth brackets. On statistical analysis, there were significant differences between 3M light cured composite and other two adhesives (chi(2)=24.39, 8.63, P<0.01), but no significant difference between the JJ enamel adhesive and TF no-mixed orthodontic adhesive (chi(2)=1.48, P>0.05). CONCLUSION: There were many factors related to bracket lost. The lowest rate of bracket lost was noted in 3M light cured composite among three adhesives.

Deficiency of phosphatidylinositol-linked membrane proteins on erythrocytes of different subpopulations in paroxysmal nocturnal hemoglobinuria.

The surface phosphatidylinositol (PI)-linked proteins on membrane of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes (PNHE) was analysed by a flowcytometer (FACS 420). It was found that the loss of acetylcholinesterase (AchE) and decay accelerating factor (DAF), two PI-linked proteins, from cell membrane of PNHE was not synchronous. The hemolysis rates of DAF (-) and AchE (-) PNHE were much higher than that of mixed population in cobra-venom factor (CoF) lysis test. Intact PNHE remaining after CoF lysis had relatively lower immunofluorescent labeling rate of AchE on membrane in comparison with normal erythrocytes. It implied that this subpopulation, in spite of being insensitive to complement lysis, was still abnormal in terms of the amount of PI-linked protein on cell membrane. When these intact PNHE remaining after CoF lysis were incubated with activated polymorphonuclear leukocytes (PMN) for three hours, immunofluorescent labeling of AchE on PNHE was prominently decreased. This indicated that reactive oxidants released from activated PMN might injure PI-linked proteins.

Daphnetin: a novel antimalarial agent with in vitro and in vivo activity.

Daphnetin is a dihydroxycoumarin that is being used in China for the treatment of coagulation disorders. It is also a chelator and an antioxidant. In vitro, daphnetin causes a 50% inhibition (IC50) of 3H-hypoxanthine incorporation by Plasmodium falciparum at concentrations between 25 and 40 microM. Several related compounds, such as scopoletin, 2, 3-dihydroxybenzoic acid and 3, 4-dihydroxybenzoic acid show no inhibitory activity. The antimalarial activity of daphnetin is inhibited by the addition of iron. Daphnetin does not appear to be an oxidant drug, since it does not spontaneously generate superoxide in vitro. However, it does alkylate bovine serum albumin when incubated in the presence of iron. In vivo, daphnetin significantly prolongs survival of P. yoelli-infected mice.

Activated oxygen generation by a primaquine metabolite: inhibition by antioxidants derived from Chinese herbal remedies.

Primaquine is an important antimalarial drug which causes hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PDH) deficiency, probably due to oxidant generation by its metabolites. One of primaquine's metabolites, 5,6-dihydroxy-8-aminoquinoline (AQD), was found to cause chemiluminescence (CL) in vitro when incubated in the presence of luminol. This CL is inhibited by catalase and deferoxamine, unaffected by mannitol, and stimulated by superoxide dismutase (SOD), suggesting that it is mediated by H2O2. Three antioxidants (daphnetin, ferulate, and maltol), derived from Chinese herbal remedies, inhibited AQD- and H2O2-mediated CL, whereas a fourth, anisodamine, had no effect. Daphnetin also potently inhibited H2O2-mediated lipid peroxidation as measured by the production of thibarbituric acid reacting substances (TBARS). Thus, the possibility is raised that an antioxidant might be able to mitigate the oxidant hemolytic effects of primaquine.

Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action.

Artemisinin (qinghaosu), is a promising new antimalarial drug derived from an ancient Chinese herbal remedy. When [13-14C]artemisinin is added to cultures of Plasmodium falciparum, it is converted into a product with different solubility and chromatographic properties than the parent drug. Artemisinin reacts with hemin in aqueous solution to form an adduct with an apparent molecular weight of 914 which has identical chromatographic, solubility, and electrophoretic behavior to the parasite-derived product. The reaction between artemisinin and hemin, when carried out in the presence of red cell membranes, leads to the oxidation of protein thiols. Malarial parasites are rich in hemin; artemisinin's reactivity toward hemin may explain its selective toxicity to malarial parasites.

Targeted anti-tumor agents and their cytotoxicity on gastric cancer cells in vitro.

Several chemotherapeutic drugs including methotrexate, daunomycin, mitomycin C and toxin such as ricin, A chain of ricin were chosen to conjugate with murine monoclonal antibodies MGb2 and MG11. The drugs were linked to antibody directly or through human serum albumin as intermediary. The ELISA results showed that the antibody retained well the antigen-binding capacity during conjugation. These conjugates showed highly selective cytotoxic effect on target cells. In chronic cytotoxicity tests, the cytotoxic effect of these conjugates on human gastric cancer cells KATOIII was quite similar to that of free drugs or ricin, but greater than that of irrelevant conjugates, while they had a little effect on non-target cells, suggesting that the selective cytotoxicity on target cells of the conjugates be mediated by antibodies.

[Peroxidative antimalaria mechanism of sodium artesunate].

Peroxidative antimalaria action of sodium artesunate was studied in vitro. Under alkaline conditions, sodium artesunate could produce active oxygen species, including the superoxide anion (O2-) and hydrogen peroxide (H2O2), but no O2- or H2O2 was produced by the drug at pH 7.4. However, sodium artesunate could increase the concentration of O2- and H2O2 in erythrocytes by increasing membrane lipid peroxidation, with this action being more marked in infected than in normal erythrocytes.

[Inhibitory effect of chemically and enzymatically treated erythrocytic membrane on the invasion of Plasmodium falciparum merozoites].

By treating chemically and enzymatically erythrocytic membrane to change its structure and properties, the recognition of merozoite to erythrocyte and the effect of erythrocyte skeleton protein on the invasion of P. falciparum (Fc c-1/HN) were studied. It was found that the invasion of merozoite into erythrocyte digested with trypsin was greatly decreased; merozoite invasion into the erythrocyte treated with neuraminidase or wheat germ agglutinin (WGA) was partially inhibited; erythrocytes treated with cross-linker diamide and depolymerizer colchicine, N-ethyl maleinimide (NEM) of skeleton protein had evident resistance to invasion; the invasion of merozoite into erythrocyte treated with 2.0 mM of NEM was completely blocked.

[Changes in antioxidative system in erythrocytes infected with Plasmodium falciparum].

In order to probe into the redox state in erythrocytes infected with P. falciparum, parasites of Hainan strain (FCC-1/HN) were cultured in vitro and trophozoites and schizonts were obtained by Percoll gradient separation. The effects of P. falciparum infection on antioxidative system and active oxygen level in erythrocytes were studied. It was found that the activities of superoxide dismutase, catalase and the content of reduced glutathione in infected erythrocytes were markedly decreased, while the activities of glutathione peroxidase and glutathione reductase in infected erythrocytes remained unchanged. There was no evident increase in superoxide in infected erythrocytes. However, the level of hydrogen peroxide in infected erythrocytes was markedly increased.

Effect of sodium artesunate on malaria infected human erythrocytes.

Oxidative stress in malaria infected human erythrocytes is augmented and the anti-oxidant system is attenuated as compared with normal RBC's. Exacerbation of intra-erythrocytic oxidative stress might provide a means to kill the parasites. Sodium artesunate (SA), an effective Chinese anti-malaria drug, markedly increased the levels of active oxygen species and production of malonyldialdehyde in normal red blood cells and, to a greater extent, in malaria infected red blood cells. SA caused a remarkable decrease of unsaturated fatty acids content in normal red blood cell membrane. These suggest that the anti-oxidative system in red blood cells infected with malaria is jeopardized. Certain active oxygen species generated and accumulated in such red blood cells might in turn kill the parasites. SA augmented intracellular O2-. and H2O2 production, and this may partly account for its antimalaria action.