Background: The aim of this study was to assess the predictive value of tumor expression of nine genes on clinical outcome in patients with advanced NSCLC receiving platinum-gemcitabine chemotherapy.Methods: Quantitative PCR or immunohistochemistry were used to analyze the expression of beta-tubuline IIA (TUBB2A),beta-tubuline III (TUBB3), BRCA1, ERCC1, Abraxas (ABRX) and RAP80 in mRNA isolated from paraffin-embedded tumor biopsies of 45 NSCLC patients treated as part of a larger observational trial. All patients received first-line platinum-gemcitabine chemotherapy for stage IIIB or IV NSCLC.Results: Median progression-free survival (PFS) was 7 months, overall survival (OS) 12 months. A partial treatment response was found in 14 patients (33%). Patients with low ERCC1 or ABRX expression had a significantly better response to chemotherapy (R = -0.45, p < 0.01 for ERCC1; R = -0.40, p = 0.016 for ABRX). A significant correlation was found between the individual time for PFS and the expression of both ERCC1 (R = -0.36, p = 0.015) and ABRX (R = -0.46, p = 0.001). Patients with low ERCC1 expression had a longer OS as compared to patients with high ERCC1 expression (HR = 0.26, log-rank p = 0.02).Conclusions: The study confirms tumor expression of ERCC1 as a predictor for clinical outcome in patients with advanced NSCLC receiving platinum-based chemotherapy, and found ABRX expression to be similarly predictive of clinical outcome. Prospective validation is warranted and - if confirmed - non platinum-containing chemotherapy should be explored as the preferred treatment in patients with high ERCC1 or ABRX expression and no activating mutations of EGFR. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
In Vietnam, the high prevalence of Helicobacter pylori infection represents a serious health problem. Virulence genes of H. pylori have been associated to increased risk of severe gastrointestinal diseases and the genetic background differs in geographical areas. We investigated cagA and vacA genotypes of H. pylori from dyspeptic patients from central Vietnam and the correlation with clinical outcomes; we also performed sequencing analysis of partial cagA gene.Overall, 84% of strains were cagA-positive, 75% were East-Asian type with a prevalence of vacAs1i1m1 and vacAs1i1m2 genotypes (66.7% and 33.3%, respectively) and 9% were Western type vacAs1i1m1 (n = 4) and vacAs1i1m2 (n = 4); vacAs1i2m2 (n = 4) and vacAs2i2m2 (n = 2) genotypes were associated to cagA-negative. Strains from gastric ulcer and cancer were of East-Asian type, while cagA-negative or Western strains were from gastritis and duodenal ulcer. H. pylori strains from gastric ulcer patients were predominantly vacAs1i1m1 compared to other vacA genotypes (p < 0.05). East-Asian type strains vacAs1i1m1 or vacAs1i1m2 were found in gastric cancer patients and also in less severe disease. Phylogenetic tree analysis of CagA sequences showed the co-circulation of H. pylori of different geographical origins with Western sequences closer related to Cambodia, one of the entry of Western strains in Southeast-Asia through human migrations. Sequence analysis revealed in two Western type strains a chimeric CagA-3′ region with identity with East-Asian CagA suggesting recombination event in the process of evolution among East-Asian and Western H. pylori strains. Moreover, polymorphism in CagA multimerization (CM) motif was observed including new East-Asian CM motifs. In conclusion, we have found in central Vietnam a geographically dependent diversity of cagA genotype, with higher rates of cagA-negative and Western-type strains compared with other nation's parts that can partly explain the lower risk of gastric cancer. The polymorphism of CM motifs may explain the variability of disease manifestations of vacAs1i1m1 and s1i1m2 East-Asian isolates.
The effects of variations in the placement of inoculum in soil on the infectivity and disease protection ability of a sterile red fungus (SRF) was investigated. The ability of the SRF to spread in soil and to infect wheat plants either from pre-infected wheat plants or from an introduced source of inoculum was also examined. Experiments were carried out by placing the SRF inoculum at different distances (0, 1, 3, 5, 7 or 9 cm) from the plant and at different depths (0, 2, 4, 6, 8 or 10cm) in soil. Nylon mesh bags used in this study allowed the passage of fungal hyphae but prevented the free movement of wheat roots in soil. The furthest distance for the placement of the SRF inoculum for successful root colonization was found to e 3 cm. This distance was used to detect the differences in the period required to infect and colonize the wheat roots by the SRF in comparison with the take-all fungus. It was observed that the SRF maintains the initial advantage of early arrival on the wheat roots for protecting the plant from the take-all fungus. The SRF was also found to colonize and protect plant roots more effectively when it was placed below the seed at sowing than at a 3 cm distance from the plant. Although the potential for the SRF to spread from plant to plant exists, it may still be necessary to introduce the SRF inoculum close to each wheat seed at sowing.
The reactions of recoil 76,77,82Br atoms—produced by the Se(p,n)Br reactions from gaseous H2Se, (CH3)2Se and (CF3)2Se—with CH4, CH3F, CH3Cl, CH3Br, CF4, CF3H and CF3Br have been studied. As a consequence of the high initial energy, it is supposed that the Br isotopes react as neutral atoms. The results are in general very difficult to interpret, because of radiolysis, especially of perfluorocompounds. Furthermore, high yields of labeled CH3Br∗ are found in all monohalomethanes, probably as a consequence of an increase in the temperature during the irradiation. The hydrogen substitution yield decreases from CH4 via CH3F and CH3Cl to CH3Br, which may be explained by the better moderating ability of the heavier halomethanes.
Direct exposure of solid tyrosine, iodotyrosine, chloroquine-phosphate and bovine serum albumine to 76Kr and 77Kr resulted in low (<1%) 76.77Br labeling yields, but higher yields (⪖30%) for liquid acetic acid and molten haloacetic acids were obtained in this way. The 76Kr − 76Br/KBrO3 indirect exposure technique gave yields between 22 and 95% for tyrosine, iodotyrosine, chloroquinephosphate, uracil and iodouracil. The exposure of KBrO3 is not necessary; the same labeling results were obtained for tyrosine when 82Br− and KBrO3 were used instead of 76Kr → 76Br exposed KBrO3; the mechanism probably proceeds via labeled Br2.