Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Racial/Ethnic and Poverty Disparities in Human Papillomavirus Vaccination Completion

Background: Two vaccines against human papillomavirus (HPV), a necessary cause of cervical cancer, are currently licensed and recommended for routine administration in the U.S. to girls in a three-dose series. Purpose: This study examined effects of race/ethnicity, poverty, and year on completion of the three-dose HPV vaccine series among those who initiated vaccination. Methods: Data from the 2008–2009 National Immunization Survey-Teen for girls aged 13–17 years who received at least one dose of HPV vaccine (n_7606) were analyzed in 2010–2011 using logistic regression to adjust for covariates including measures of access to care. Results: During this 2-year period, 55% of adolescent girls who initiated vaccination completed the three-dose series. Completion was signifıcantly higher in 2009 (60%) compared to 2008 (48%; p_0.001). After controlling for covariates, adolescents who were black (AOR_0.48, 95% CI_0.40, 0.57) or Hispanic (AOR_0.75, 95% CI_0.64, 0.88) were signifıcantly less likely to complete vaccination than whites. Adolescents living below the federal poverty level were signifıcantly less likely to complete vaccination than adolescents with household incomes _$75,000 (AOR_0.76, 95% CI_0.63, 0.92). There was no signifıcant interaction between race/ethnicity and year (p_0.92). Although poverty was associated with lower completion rates in 2008, this association was not observed in 2009 (p_0.05 for poverty–year interaction). Conclusions: HPV vaccination completion rates increased between 2008 and 2009. However, signifıcant differences by race/ethnicity and poverty were observed, and the racial/ethnic differences persisted

Socioeconomic Status and Foodborne Pathogens in Connecticut, USA, 2000–2011

Foodborne pathogens cause >9 million illnesses annually. Food safety efforts address the entire food chain, but an essential strategy for preventing foodborne disease is educating consumers and food preparers. To better understand the epidemiology of foodborne disease and to direct prevention efforts, we examined incidence of Salmonella infection, Shiga toxin–producing Escherichia coli infection, and hemolytic uremic syndrome by census tract–level socioeconomic status (SES) in the Connecticut Foodborne Diseases Active Surveillance Network site for 2000–2011. Addresses of case-patients were geocoded to census tracts and linked to census tract–level SES data. Higher census tract–level SES was associated with Shiga toxin–producing Escherichia coli, regardless of serotype; hemolytic uremic syndrome; salmonellosis in persons ≥5 years of age; and some Salmonella serotypes. A reverse association was found for salmonellosis in children <5 years of age and for 1 Salmonella serotype. These findings will inform education and prevention efforts as well as further research