Effect of feijoa sellowiana acetonic extract on proliferation inhibition and apoptosis induction in human gastric cancer cells

Gastric cancer (GC) still represents a relevant health problem in the world for both incidence and mortality rates. Many studies underlined that natural products consumption could reduce GC risk, indicating flavonoids as responsible for the beneficial effects through the modulation of several biological processes, such as the inhibition of cancer antioxidant defense and induction of apoptosis. Since Feijoa sellowiana fruit is known to contain high amounts of flavonoids, among which is flavone, we evaluated the antiproliferative and proapoptotic effects of F. sellowiana acetonic extract on GC cell lines through MTS and Annexin-V FITC assays. Among three GC cell lines tested, SNU-1 results being sensitive to both the F. sellowiana acetonic extract and synthetic flavone, which was used as the reference treatment. Moreover, we evaluated their antioxidant effects, assessing the activity of the antioxidant enzymes supeoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in polymorphonuclear cells. We found a significant increase of their activity after exposure to both F. sellowiana acetonic extract and flavone, supporting the idea that a diet that includes flavone-rich fruits could be of benefit for health. In addition to this antioxidant effect on normal cells, this study indicates, for the first time, an anticancer effect of F. sellowiana acetonic extract in GC cells

Cationic Channel TRPV2 Overexpression Promotes Resistance to Cisplatin-Induced Apoptosis in Gastric Cancer Cells

Gastric cancer (GC) is characterized by poor efficacy and modest clinical impact of current therapies, in which apoptosis evasion is relevant. Intracellular calcium homeostasis dysregulation is associated with apoptosis escaping, and aberrant expression of calcium regulator genes could promote GC drug resistance. Since we previously found a prognostic value for TRPV2 calcium channel expression in GC, we aimed to characterize the role of TRPV2 in cisplatin resistance. Using the TCGA-STAD dataset, we performed a differential gene expression analysis between GC samples in upper and lower tertiles of TRPV2 expression, and then through a gene set analysis, we highlighted the enriched ontology and canonical pathways. We used qRT-PCR to assess TRPV2 expression in three GC cell lines and flow cytometry to evaluate cisplatin-induced cell death rates. Calcium green-1-AM assay was used to estimate differences in intracellular Ca2+ concentrations after inhibition of TRPV2. We engineered AGS cell line to overexpress TRPV2 and used confocal microscopy to quantify its overexpression and localization and flow cytometry to evaluate their sensitivity to cisplatin. Consistent with our hypothesis, among enriched gene sets, we found a significant number of those involved in the regulation of apoptosis. Subsequently, we found an inverse correlation between TRPV2 expression and sensitivity to cisplatin in GC cell lines. Moreover, we demonstrated that inhibition of TRPV2 activity by tranilast blocks the efflux of Ca2+ ions and, in combination with cisplatin, induced a significant increase of apoptotic cells (p = 0.004). We also demonstrated that TRPV2 exogenous expression confers a drug-resistant phenotype, and that tranilast is able to revert this phenotype, restoring cisplatin sensitivity. Our findings consistently suggested that TRPV2 could be a potential target for overcoming cisplatin resistance by promoting apoptosis. Notably, our data are a prerequisite for the potential reposition of tranilast to the treatment of GC patients and anticipate the in vivo evaluation

History of cancer in first degree relatives of Barrett's esophagus patients : a case-control study

Background and objective: Familial clusters of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have been reported. This study evaluates the history of cancer in BE patients families. Methods: In two years, patients with BE (272), esophagitis (456) and controls (517) were recruited in 12 Italian Endoscopy Units. Cancer family history in first-degree (FD) relatives was determined by a questionnaire. Results: Approximately 53% of BE, 51% of esophagitis, and 48% of controls had at least one relative affected by any type of malignancy. Probands with at least one esophageal or gastric (E/G) cancer-affected relative showed a BE risk which was at least eighty-five percent higher than that of probands without affected relatives. The relative risk of BE was 4.18, 95% CL = 0.76-23.04 if a FD relative had early (mean age <= 50 years) onset E/G cancer compared to late onset E/G cancer. Conclusion: In this sample there was no evidence that a family history of cancer was associated with the diagnosis of BE. An intriguing result was the association between the occurrence of E/G cancers at earlier ages (< 50 years) among BE relatives with respect the control group. This could suggest a genetic contribution in onset of these tumors, but the sample was too small to demonstrate a significant association. Further exploration of family history of E/G cancer and a diagnosis of BE in larger samples is warranted

Real-time determination of gastric juice pH with EndoFaster® for atrophic gastritis assessment

Background: In patients with atrophic gastritis involving gastric body mucosa the pH value of gastric juice is distinctly increased, so that pH assessment would allow predict this precancerous lesion. We tested whether EndoFaster® − a device allowing real-time pH measure and H. pylori diagnosis – may optimize the need of taking gastric biopsies. Methods: In this prospective, multicentre study, the accuracy of EndoFaster® for ruling out gastric atrophy involving corporal mucosa was assessed. Real-time pH and ammonium determination was performed by aspirating 3–6 ml gastric juice during endoscopy. Histology performed on 5 standard gastric biopsies was used as gold standard. Results: A total of 1008 consecutive patients were observed in 12 centres. At histology, gastric body mucosa atrophy/metaplasia was detected in 65 (6.4%) cases, and a pH value &gt;4.5 in the gastric juice was observed in 150 patients. The values of EndoFaster® performance in predicting the presence of atrophic gastritis were as follow: 51% sensitivity, 84% specificity, 18% PPV, 96% NPV, and 82% accuracy. The NPV value was not distinctly affected by neither ongoing proton pump inhibitor therapy nor H. pylori infection. By considering also data of ammonium concentrations, the values of EndoFaster® in detecting extensive atrophy on gastric mucosa were 74% sensitivity, 84% specificity, 24% PPV, 98% NPV, and 83% accuracy. Conclusion: The very high NPV of EndoFaster® might allow to safely rule out presence of atrophic gastritis, reducing the need of taking gastric biopsies in unselected patients managed in clinical practic

Endoscopic resection for superficial colorectal neoplasia in Italy: A prospective multicentre study

background: since there are few prospective studies on colorectal endoscopic resection to date, we aimed to prospectively assess safety and efficacy of endoscopic resection in a cohort of Italian patients.Methods: Prospective multicentre assessment of resection of sessile polyps or non-polypoid lesions &gt;= 10 mm in size or smaller (if depressed). outcome measures included complete excision, morbidity, mortality, and residual/recurrence at 12 months.results: overall, 1012 resections in 928 patients were analysed (62.4% sessile polyps, 28.8% laterally spreading tumours, 8.7% depressed non-polypoid lesions). Lesions were prevalent in the proximal colon. Enbloc resection was possible in 715/1012 cases (70.7%), whereas piecemeal resection was required in 297 (29.3%). Endoscopically complete excision was achieved in 866 cases (85.6%). Adverse events occurred in 83 (8.2%), and no deaths occurred. Independent predictors of 12-month residual/recurrence were the location of the lesion in the proximal colon (OR 2.22 [95% CI 1.16-4.26]; p = 0.015) and piecemeal endoscopic resection (OR 2.76 [95% CI 1.56-4.87]; p = 0.0005). Limitations of the study were: potential expertise bias, no data on eligible and potentially resectable excluded lesions, high percentage of lesions &lt; 20 mm, follow-up limited to 1 year.conclusion: In this registry study the endoscopic resection of colorectal lesions was safe and achieved high rates of long-term endoscopic clearance. (C) 2013 editrice gastroenterologica Italiana S.r.l. published by elsevier Ltd. all rights reserved

Endoscopic resection for superficial colorectal neoplasia in Italy: A prospective multicentre study

Background: Since there are few prospective studies on colorectal endoscopic resection to date, we aimed to prospectively assess safety and efficacy of endoscopic resection in a cohort of Italian patients.Methods: Prospective multicentre assessment of resection of sessile polyps or non-polypoid lesions &gt;= 10 mm in size or smaller (if depressed). Outcome measures included complete excision, morbidity, mortality, and residual/recurrence at 12 months.Results: Overall, 1012 resections in 928 patients were analysed (62.4% sessile polyps, 28.8% laterally spreading tumours, 8.7% depressed non-polypoid lesions). Lesions were prevalent in the proximal colon. Enbloc resection was possible in 715/1012 cases (70.7%), whereas piecemeal resection was required in 297 (29.3%). Endoscopically complete excision was achieved in 866 cases (85.6%). Adverse events occurred in 83 (8.2%), and no deaths occurred. Independent predictors of 12-month residual/recurrence were the location of the lesion in the proximal colon (OR 2.22 [95% CI 1.16-4.26]; p = 0.015) and piecemeal endoscopic resection (OR 2.76 [95% CI 1.56-4.87]; p = 0.0005). Limitations of the study were: potential expertise bias, no data on eligible and potentially resectable excluded lesions, high percentage of lesions &lt; 20 mm, follow-up limited to 1 year.Conclusion: In this registry study the endoscopic resection of colorectal lesions was safe and achieved high rates of long-term endoscopic clearance. (C) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Prevalence of nonpolypoid colorectal neoplasia: an italian multicenter observational study

BACKGROUND AND STUDY AIM: The aim of this study was to assess the prevalence of nonpolypoid lesions (NPLs) in Italy and their risk of containing neoplasia or advanced histology.PATIENTS AND METHODS: This was a multicenter cross-sectional observational study on consecutive patients undergoing total colonoscopy over a 3-month period in 80 Italian centers.RESULTS: In all, 27,400 total colonoscopies were analyzed. Cancer was diagnosed in 801 patients (2.9 %). A total of 6553 precancerous lesions were detected in 5609 patients. Of these, 4154 patients (74.1 %) had polypoid lesions and 1455 patients (25.9 %) had NPLs. Therefore, the prevalence of NPLs was 5.3 % (95 %CI 5.0 - 5.6). NPLs larger than 10 mm were detected in 254 patients (17.5 %). NPLs were more predominant in the proximal colon (OR 2.92, 95 %CI 2.56 - 3.43; P &lt; 0.0001 vs. polypoid lesions). Neoplastic tissue was diagnosed in 79.0 % and advanced histology (high-grade intraepithelial neoplasia or more) in 20.9 % of resected lesions. The risk of advanced histology was similar for polypoid and nonpolypoid lesions when adjusted for size. Depressed lesions had the highest risk of advanced histology (OR 10.56, 95 %CI 6.02 - 18.55; P &lt; 0.0000 vs. flat-elevated). Age was an independent predictor of both neoplasia and advanced histology ( P = 0.0001).CONCLUSIONS: NPLs are relatively common in the Italian population, with a prevalence similar to that in other Western series. NPLs are not more aggressive than polypoid lesions, except for those with depressed morphology