Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression

Recent development of genetically engineered mouse models (GEMs) for pancreatic cancer (PC) that recapitulates human disease progression has helped to identify new strategies to delay/inhibit PC development. We first found that expression of the pancreatic tumor-initiating/cancer stem cells (CSC) marker DclK1 occurs in early stage PC and in both early and late pancreatic intraepithelial neoplasia (PanIN) and that it increases as disease progresses in GEM and also in human PC. Genome-wide next generation sequencing of pancreatic ductal adenocarcinoma (PDAC) from GEM mice revealed significantly increased DclK1 along with inflammatory genes. Genetic ablation of cyclo-oxygenase-2 (COX-2) decreased DclK1 in GEM. Induction of inflammation/pancreatitis with cerulein in GEM mice increased DclK1, and the novel dual COX/5-lipoxygenase (5-LOX) inhibitor licofelone reduced it. Dietary licofelone significantly inhibited the incidence of PDAC and carcinoma in situ with significant inhibition of pancreatic CSCs. Licofelone suppressed pancreatic tumor COX-2 and 5-LOX activities and modulated miRNAs characteristic of CSC and inflammation in correlation with PDAC inhibition. These results offer a preclinical proof of concept to target the inflammation initiation to inhibit cancer stem cells early for improving the treatment of pancreatic cancers, with immediate clinical implications for repositioning dual COX/5-LOX inhibitors in human trials for high risk patients.     

Prevalence of dental fluorosis in rural areas of Davangere, India

OBJECTIVES: To assess the prevalence and severity of dental fluorosis and its relationship with fluoride levels in drinking water. DESIGN: Twelve villages with similar climate, diet, socioeconomic conditions and altitudes were selected from rural areas of Davangere district, Karnataka, India. The fluoride concentration in drinking water was estimated by the Ion Selective Electrode Method. Dean's Index was used to assess the dental fluorosis. Karl-Pearson coefficient for correlation and simple regression analysis were used to evaluate the association between the water fluoride levels and the community fluorosis index (CFI). RESULTS: The study group consisted of 1,131, 12-15-year-old school children. The fluoride levels in drinking water of selected villages were in the range of 0.22-3.41ppm. A stepwise increase in the prevalence of dental fluorosis with corresponding increase in water fluoride content, 13.2% at 0.22ppm F to 100% at 3.41 ppm F, was found. There was a significant positive linear correlation (r=0.99) between CFI and water fluoride level. CONCLUSION: Dental fluorosis is a major dental public health problem among children in Davangere district and is related to drinking water with 0.74ppm fluoride or above.     

Molecular markers and targets for colorectal cancer prevention

Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from promoting/ developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the biological and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarker in biomolecular pathway are elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.     

Briarane diterpenes diminish COX-2 expression in human colon adenocarcinoma cells

Exploration of a soft coral (Briareum sp.) from Vanuatu led to the isolation of three new briaranes, designated brialalepolides A (1), B (2), and C (3). Compounds 2 and 3 reduced the expression of COX-2 in human colon adenocarcinoma cells, as well as in murine macrophage cells. This is significant because the metabolic products of COX-2 have been implicated in the pathogenesis of colon cancer and other diseases.     

Male circumcision for HIV prevention - a cross-sectional study on awareness among young people and adults in rural Uganda

Background  

Medical male circumcision is now part of a comprehensive approach to HIV prevention. It has been shown that awareness of the protective effect of male circumcision leads to high acceptability towards the introduction of medical male circumcision services within countries. The objective of this survey was to identify factors determining awareness of male circumcision for HIV prevention.