Search

Tumour hypoxia renders cancer cells resistant to cancer therapy, resulting in markedly worse clinical outcomes. To find clinical candidate compounds that reduce hypoxia in tumours, we conducted a high throughput screen for oxygen consumption rate (OCR) reduction and identified a number of drugs with this property. For this study we focused on the antimalarial, atovaquone. Atovaquone rapidly decreases the OCR by more than 80% in a wide range of cancer cell lines at pharmacological concentrations. In addition, atovaquone eradicates hypoxia in FaDu, HCT116 and H1299 spheroids. Similarly, it virtually eliminates hypoxia in FaDu and HCT116 xenografts in nude mice, and causes a significant tumour growth delay when combined with radiation. Atovaquone is a ubiquinone analogue, and decreases the OCR by inhibiting mitochondrial complex III. We are now undertaking clinical studies to assess whether atovaquone reduces tumour hypoxia in patients, thereby increasing the efficacy of radiotherapy.

The Appalachian Regional Commission’s definition of the Appalachian region is the one used most often by researchers, politicians, and the popular press. The uncritical use of this definition of Appalachia raises issues of both selection bias and excess heterogeneity in regression analysis of Appalachian income and growth. The ARC was created as part of President Johnson’s war on poverty, and the geographical extent of its purview has been driven by politics and by the geography of poverty, neither of which is exogenous. It is well known that the use of endogenous variables to choose a sample creates bias and inconsistency in estimation of regression coefficients. To identify the counties that belong to the Appalachian region exogenously we use an algorithm based on three criteria: topography, contiguity, and prevalence of slavery in the 1860 census. We apply our sample to growth regressions using data from 1970 to 2008, addressing the question of the existence of a resource curse from coal extraction. For this model we find strong evidence of excess heterogeneity, but not bias.

The objective of the study was to estimate the effect of depression on health care utilization and costs in patients newly diagnosed with type 2 diabetes. Patients were identified during a four-year enrollment period (1998-2001) from a Medicaid claims database. The final cohort consisted of 4,294 patients with type 2 diabetes (1,525 patients with depression; 2,769 patients without depression). Multivariate results indicated that significant utilization differences existed between the two groups: Patients who were depressed incurred a higher number of physician office visits, emergency room/inpatient admissions, and more prescriptions compared with patients who had diabetes but were not depressed. Patients with depression had nearly 65% higher overall health care costs than those without depression. Recognizing that depression is as a risk factor for increasing health care expenditures has the potential to improve diabetes management and related outcomes.