Background: Gastric cancer (GC) ranks as one of the major causes of mortality due to cancer worldwide. Materials and Methods: Using whole-genome a group of 14 GC cases. Results
Paraoxonase 1 (PON1) is a glycosylated enzyme that is found associated with high-density lipoproteins in blood. In addition to its endogenous antioxidant role, this enzyme is also involved in hydrolysis of organophosphate (OP) pesticides in plasma. PON1 activity shows great variability in the population as a result of a polymorphism in the coding sequence that is expressed as a Glu(Q)/Arg(R) substitution at position 192 of the amino acid sequence. The aim of this study was to determine the activity levels (phenotype) and genotype of PON1 in a group of 85 agricultural workers occupationally exposed to OP pesticides and compared to 97 control subjects without occupational exposure. Allelic and genotypic frequencies of PON1Q192R polymorphism, as well as their catalytic activities, were established for the first time in a group of agricultural Chilean workers. The Q allele was more frequently represented in our studied population (approximately 60%). The Q allele is less efficient than the R allele at metabolizing chlorpyrifos (CPF), the most widely used OP pesticide in the geographical areas where samples were obtained. Further, a large interindividual variability in PON1 activity was observed, suggesting wide variation of individual susceptibility to CPF, an issue that needs to be considered in human monitoring studies.
The cytotoxic mechanism of the saponin QS-21 and its aglycone quillaic acid (QA) was studied on human gastric cancer cells (SNU1 and KATO III). Both compounds showed in vitro cytotoxic activity with IC50 values: 7.1 μM (QS-21) and 13.6 μM (QA) on SNU1 cells; 7.4 μM (QS-21) and 67 μM (QA) on KATO III cells. QS-21 and QA induce apoptosis on SNU1 and KATO III, as demonstrated by TUNEL, Annexin-V and Caspase Assays. Additionally, we performed in silico docking studies simulating the binding of both triterpenic compounds to key proteins involved in apoptotic pathways. The binding energies (∆Gbin) thus calculated, suggest that the pro-apoptotic protein Bid might be a plausible target involved in the apoptotic effect of both triterpenic compounds. Although QA shows some antiproliferative effects on SNU1 cells cultured in vitro, our results suggest that QS-21 is a more powerful antitumor agent, which merits further investigation regarding their properties as potential therapeutic agents for gastric cancer.
The aim of this study was to develop a non-invasive diagnostic test for the detection of Helicobacter pylori in stool samples from digestive symptomatic patients, using a new protocol of nested-qPCR. A total of 143 patients were invited to participate in the study. A gastric biopsy of each patient was collected for Rapid Urease Testing (RUT) and histology by Giemsa stain. A fecal sample for nested-qPCR analysis was also obtained. DNA was extracted from the fecal samples, and conventional PCR followed by qPCR of the ureC gene of H. pylori was carried out. We evaluated the presence of H. pylori, in 103 females and 40 males, mean (± SD) age of 56.5 ± 14.18. The sensitivity of RUT to detect the infection was 67.0% (95% C.I.: 57.2 - 75.8) and specificity was 92.3% (95% C.I.: 76.5 - 99.1). Histology by Giemsa stain, commonly used as a reference for H. pylori detection, showed a sensitivity of 98.6% (95% C.I.: 92.5 - 100.0) and a specificity of 89.7% (95% C.I.: 72.7 - 97.8). In contrast, detection of H. pylori infection in stools by nested-qPCR showed a sensitivity of 100% (95% C.I.: 94.9 - 100.0) and a specificity of 83.9% (95% C.I.: 66.3 - 94.6). Our test, based in nested-qPCR is a better diagnostic alternative than conventional RUT, and is similar to histology by Giemsa stain in the detection of H. pylori, by which the test could be used for non-invasive diagnosis in clinical practice.
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