RESUMO
PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients. However, the appropriated treatment orders remained controvertible. We investigated the efficacy of treatment orders between bevacizumab plus chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary adenocarcinoma. PATIENTS AND METHODS: This study involved 40 EGFR-mutant patients with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the response rate (ORR) and overall survival (OS) were evaluated. RESULTS: Median PFS of Bev + CP treatment was significantly longer in first-line than non-first-line settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR-mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and 31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP, respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6-12.8) months for Bev + CP group and 4.7 (95% CI 4.4-5.0) months for GP group with the hazard ratio of 0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P = 0.415). However, there was no significant difference in median OS (33.7 vs 27.8 months, P = 0.293). CONCLUSIONS: First-line Bev + CP followed by EGFR-TKIs might possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen significantly prolonged PFS in first-line than non-first-line settings. These findings warrant further investigations.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Talipes equinovarus is a common congenital deformity. COL9A1 polymorphisms are associated with the development of articular cartilage-related diseases. In the current study, we evaluated the relationship between COL9A1 rs1135056, rs35470562, and rs592121 genetic polymorphisms and risk of congenital talipes equinovarus. Between January 2013 and July 2015, 87 children with congenital talipes equinovarus and 174 control subjects were recruited from the Fourth People's Hospital of Shaanxi and the First Hospital of Yulin. Genotyping of COL9A1 rs1135056, rs35470562, and rs592121 was performed using polymerase chain reaction-restriction fragment length polymorphism. Using conditional regression analysis, the AA genotype of COL9A1 rs35470562 was found to be significantly associated with increased risk of congenital talipes equinovarus compared to the GG genotype [odds ratio (OR) = 2.60, 95% confidence interval (CI) = 1.06-6.32]. In addition, under a recessive model, rs35470562 AA carriers were observed to be at higher risk for this condition in comparison to individuals with GG or GA genotypes (OR = 2.23, 95%CI = 1.03-5.04). However, no significant relationship was established between the COL9A1 rs1135056 and rs592121 polymorphisms and congenital talipes equinovarus in any of the genetic models tested. In conclusion, our results indicate that the COL9A1 rs35470562 variant may contribute to congenital talipes equinovarus susceptibility in the Chinese population examined.
Assuntos
Povo Asiático/genética , Pé Torto Equinovaro/genética , Colágeno Tipo IX/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Pré-Escolar , Demografia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Biofilm-forming bacteria are highly resistant to antibiotics, host immune defenses, and other external conditions. The formation of biofilms plays a key role in colonization and infection. To explore the mechanism of biofilm formation, mutant strains of Proteus vulgaris XC 2 were generated by Tn5 random transposon insertion. Only one biofilm defective bacterial species was identified from among 500 mutants. Inactivation of the glpC gene coding an anaerobic glycerol-3-phosphate dehydrogenase subunit C was identified by sequence analysis of the biofilm defective strain. Differences were detected in the growth phenotypes of the wild-type and mutant strains under pH, antibiotic, and organic solvent stress conditions. Furthermore, we observed an increase in the phagocytosis of the biofilm defective strain by the mouse macrophage RAW264.7 cell line compared to the wild-type strain. This study shows that the glpC gene plays an important role in biofilm formation, in addition to imparting pH, organic solvent, and antibiotic tolerance, and defense against phagocytosis to Proteus sp. The results further clarified the mechanism of biofilm formation at the genomic level, and indicated the importance of the glpC gene in this process. This data may provide innovative therapeutic measures against P. vulgaris infections; furthermore, as an important crocodile pathogen, this study also has important significance in the protection of Chinese alligators.
Assuntos
Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Glicerolfosfato Desidrogenase/genética , Infecções por Proteus/veterinária , Proteus vulgaris/genética , Proteus vulgaris/imunologia , Adaptação Fisiológica/imunologia , Jacarés e Crocodilos/microbiologia , Animais , Proteínas de Bactérias/imunologia , Biofilmes/efeitos dos fármacos , Linhagem Celular , Cicloexanos/farmacologia , Elementos de DNA Transponíveis , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Glicerolfosfato Desidrogenase/imunologia , Hexanos/farmacologia , Concentração de Íons de Hidrogênio , Evasão da Resposta Imune , Macrófagos/microbiologia , Camundongos , Mutação , Infecções por Proteus/microbiologia , Infecções por Proteus/patologia , Proteus vulgaris/efeitos dos fármacos , Proteus vulgaris/isolamento & purificação , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologiaRESUMO
Hepatocellular carcinoma (HCC) is one of the most life-threatening malignancies worldwide. Defects in DNA repair genes may increase the risk of HCC. X-ray cross-complementing group 1 gene (XRCC1) is a major DNA repair gene involved in base excision re-pair. Recently, several studies have indicated that an association exists between XRCC1 polymorphism and HCC, particularly the Arg280His polymorphism. However, the data is inconsistent and incomplete. In this study, we conducted a meta-analysis to investigate the association between the XRCC1 Arg280His polymorphism and HCC risk. A total of 10 case-control studies included 1848 HCC cases and 1969 controls were examined in this analysis. Our results suggest that variant geno-types of the XRCC1 Arg280His gene are associated with a significantly increased risk of HCC in homozygote comparison (HisHis vs ArgArg, odds ratio, 1.55, 95% confidence interval, 1.10-2.18, P = 0.013); no het-erogeneity was observed (I2 = 0%). Our analysis suggests that the XRCC1 Arg280His polymorphism is associated with a higher risk of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Expressão Gênica , Homozigoto , Humanos , Neoplasias Hepáticas/patologia , Modelos Genéticos , Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
BACKGROUND: Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. METHODS: Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. RESULTS: The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (<9 %). No new safety signals were reported. Objective response rate in 195 evaluable Chinese patients was 68.8 %, including four complete responses (2.1 %). Time to disease progression (TTP) and overall survival were 8.8 and 18.5 months, respectively. CONCLUSIONS: The safety and efficacy of first-line bevacizumab-based treatment in Chinese population with advanced NS-NSCLC are consistent with those in previous studies as well as in Asian subgroup population from SAiL study. No new safety signals were reported.