Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation.</p> <p>Methods</p> <p>To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs).</p> <p>Results</p> <p>Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 <it>vs. </it>11.02 ± 8.03, <it>p </it>= 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 <it>vs</it>. 1.22 ± 0.66, <it>p </it>< 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls.</p> <p>Conclusion</p> <p>Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted.</p

Preparation of starch carbamates in homogeneous phase using different mixing conditions

The preparation of starch carbamates of wrinkled pea starch in homogeneous phase catalysed by dibutyltin dilaurate in DMSO as solvent is described. The empfloyed isocyanates have linear alkyl chains with 7, 9, 11, 15 or 18 carbon atoms. Starch carbamates with equal degrees of substitution and different alkyl chains lengths were synthesised in a reaction flask. The preparation of carbamates with equal alkyl chain length and different degrees of substitution was also possible. The structures of the polymers were characterised by elemental analysis, IR- and H-1-NMR-spectroscopy. The behaviour of the prepared starch carbamates under thermal loading was investigated by using Differential Scanning Calorimetry (DSC) and a hot press. In addition, for 1-undecyl isocyanate the starch carbamate was prepared both in a kneader and an extruder. The differences in reaction conditions and the results were discussed

Expression and functionality of TRPV1 in breast cancer cells

Lea V Weber,1 Klaudia Al-Refae,1 Gerhard W&ouml;lk,2 Gabriele Bonatz,3 Janine Altm&uuml;ller,4 Christian Becker,4 G&uuml;nter Gisselmann,1 Hanns Hatt1 1Department of Cell Physiology, Ruhr‑University Bochum, Bochum, 2Herz-Jesu-Krankenhaus, Dernbach, 3Augusta Kliniken Bochum, Bochum, 4Cologne Center for Genomics, University of Cologne, Cologne, Germany Abstract: Transient receptor potential (TRP) channels contribute to the regulation of intracellular calcium, which can promote cancer hallmarks in cases of dysregulation of gene transcription and calcium-dependent pro-proliferative or anti-apoptotic mechanisms. Several studies have begun to elucidate the roles of TRPV1, TRPV6, TRPM8, and TRPC1 in cancer progression; however, no study has examined the expression profiles of human TRP channels in breast cancer on a large scale. This study focused on the expression and functionality of TRPV1, a nonselective cation channel that was found to be expressed in different carcinoma tissues. Next-generation sequencing analyses revealed the expression of TRPV1 in several native breast cancer tissues, which was subsequently validated via reverse transcriptase-polymerase chain reaction. Activation of TRPV1 by its ligand capsaicin was associated with the growth inhibition of some cancer cell types; however, the signaling components involved are complex. In this study, stimulation by the TRPV1 agonist, capsaicin, of SUM149PT cells, a model system for the most aggressive breast cancer subtype, triple-negative breast cancer, led to intracellular calcium signals that were diminished by the specific TRPV1 antagonist, capsazepin. Activation of TRPV1 by capsaicin caused significant inhibition of cancer cell growth and induced apoptosis and necrosis. In conclusion, the current study revealed the expression profiles of human TRP channels in 60 different breast cancer tissues and cell lines and furthermore validated the antitumor activity of TRPV1 against SUM149PT breast cancer cells, indicating that activation of TRPV1 could be used as a therapeutic target, even in the most aggressive breast cancer types. Keywords: TRP channels, TRPV1, next-generation sequencing, breast cancer, apoptosis, necrosis, anti-proliferativ

Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications

Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size, DNA aneuploidy, lack of steroid hormone receptors, young age, and increased topoisomerase II alpha and Ki-67 expression levels. The correlation of p53 and c-erbB-2 was not significant. Topoisomerase II alpha and Ki-67 scores closely paralleled each other, indicating that both reflect the proliferative activity of tumour cells. A univariate analysis of overall (OS), specific (SS), and disease-free survival (DFS) revealed all the above-mentioned parameters to be statistically significant except patient age, which was relevant only to overall survival. Multivariate analysis with inclusion of all covariates selected tumour size and proliferation (topoisomerase II alpha and Ki-67) indices as independent predictors of survival in all three models. No additional information was gained by p53 or c-erbB-2. It is concluded that the proliferative activity, as assessed by topoisomerase II alpha or Ki-67 immunostaining, is the most useful indicator of breast cancer prognosis, except for tumour size

PTEN mutations do not cause nuclear beta-catenin accumulation in endometrial carcinomas

PTEN and β-catenin mutations constitute the predominant genetic alterations in endometrioid carcinomas of the endometrium. PTEN encodes a dual-specificity phosphatase with lipid phosphatase and protein tyrosine phosphatase activities that regulate both apoptosis and interactions with the extracellular matrix. Recent studies have associated PTEN mutations with tumorigenesis of prostate carcinoma via the Wnt signaling pathway, leading to nuclear β-catenin accumulation. To elucidate the potential interaction of PTEN and β-catenin in endometrial cancer, we performed mutation analyses of the entire PTEN gene and of exon 3 of the β-catenin gene that is most frequently targeted by mutations. A total of 82 endometrial carcinomas comprising 62 type I endometrioid carcinomas and 20 type II high-grade carcinomas were investigated. In addition in a subset of 22 carcinomas, the intracellular β-catenin distribution was analyzed by immunohistochemistry. Overall, 20 (24.4%) of 82 tumors revealed mutations in the PTEN gene, and 16 (19.5%) of 82, in the β-catenin gene. Six tumors (7.3%) showed mutations in both the PTEN and β-catenin gene. Mutations were mainly detected in endometrioid carcinomas of the endometrium. As expected, a striking nuclear accumulation of β-catenin could be shown in tumors with β-catenin mutations. In the vast majority of tumors with PTEN mutations, a regular staining pattern of the cytoplasmic and membranous compartments was found. We therefore conclude that, in contrast to prostate cancer, mutations in the PTEN gene seem not to affect cellular distribution of the β-catenin protein in endometrial carcinomas