Активность

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that remains incurable because of late diagnosis, which renders any therapeutic intervention challenging. Most PDAC patients develop de novo diabetes, which exacerbates their morbidity and mortality. How PDAC triggers diabetes is still unfolding. Using a mouse model of KrasG12D-driven PDAC, which faithfully recapitulates the progression of the human disease, we observed a massive and selective depletion of β-cells, occurring very early at the stages of preneoplastic lesions. Mechanistically, we found that increased TGF beta (TGF-β) signaling during PDAC progression caused erosion of β-cell mass through apoptosis. Suppressing TGF-β signaling, either pharmacologically through TGF-β immunoneutralization or genetically through deletion of Smad4 or TGF-β type II receptor (TβRII), afforded substantial protection against PDAC-driven β-cell depletion. From a translational perspective, both activation of TGF-β signaling and depletion of β-cells frequently occur in human PDAC, providing a mechanistic explanation for the pathogenesis of diabetes in PDAC patients, and further implicating new-onset diabetes as a potential early prognostic marker for PDAC. © 2020 Parajuli et al.Social, economic, and cultural factors have been associated with the level of participation in cervical cancer screening programs. This study identified factors associated with nonparticipation in cervical cancer screening, as well as reasons for not attending, in the context of a population-based, cluster-randomized trial in Ethiopia. A total of 2,356 women aged 30 to 49 years in 22 clusters were invited to receive one of two screening approaches, namely human papillomavirus (HPV) self-sampling or visual inspection with acetic acid (VIA). Participants and nonparticipants were analyzed according to their sociodemographic and economic characteristics. Reasons were determined for the refusal of women to participate in either screening method. Autophagy activator More women in the VIA arm compared to the HPV arm declined participation in the screening [adjusted OR (AOR) 3.5; 95% confidence interval (CI), 2.6-4.8]. Women who declined attending screening were more often living in rural areas (AOR = 2.0; 95% CI, 1.1-3.5) and were engaged in informal occupations (AOR = 1.6; 95% CI, 1.1-2.4). The majority of nonattendants perceived themselves to be at no risk of cervical cancer (83.1%). The main reasons given for not attending screening for both screening approaches were lack of time to attend screening, self-assertion of being healthy, and fear of screening. We found that perceived time constraints and the perception of being at no risk of getting the disease were the most important barriers to screening. Living in rural settings and informal occupation were also associated with lower participation. Offering a swift and convenient screening service could increase the participation of women in cervical cancer screening at the community level. ©2020 American Association for Cancer Research.BACKGROUND Colorectal cancer incidence and mortality have declined with increased screening and scientific advances in treatment. However, improvement in colorectal cancer outcomes has not been equal for all groups and disparities have persisted over time. METHODS Data from the California Cancer Registry were used to estimate changes in 5-year colorectal cancer-specific survival over three diagnostic time periods 1997-2002, 2003-2008, and 2009-2014. Analyses included all patients in California with colorectal cancer as a first primary malignancy. Multivariable Cox proportional hazard regression models were used to evaluate the effect of race/ethnicity, insurance status, and neighborhood socioeconomic status (nSES) on 5-year colorectal cancer-specific survival. RESULTS On the basis of a population-based sample of 197,060 colorectal cancer cases, racial/ethnic survival disparities decreased over time among non-Hispanic Blacks (NHB) compared with non-Hispanic Whites (NHW), after adjusting for demographic, clinical, and treatment characteristics. For cases diagnosed 1997-2002, colorectal cancer-specific hazard rates were higher for NHB [HR, 1.12; 95% confidence interval (CI), 1.06-1.19] and lower for Asians/Pacific Islanders (HR, 0.92; 95% CI, 0.87-0.96) and Hispanics (HR, 0.94; 95% CI, 0.90-0.99) compared with NHW. In 2009-2014, colorectal cancer-specific HR for NHB was not significantly different to the rate observed for NHW (HR, 1.03; 95% CI, 0.97-1.10). There were no changes in disparities in nSES, but increasing disparities by health insurance status. CONCLUSIONS We found a decrease in survival disparities over time by race/ethnicity, but a persistence of disparities by neighborhood socioeconomic status and health insurance status. IMPACT Further investigation into the drivers for these disparities can help direct policy and practice toward health equity for all groups. ©2020 American Association for Cancer Research.The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID-19 Symptom Tracker mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hotspots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health. Copyright ©2020, American Association for Cancer Research.