Etoposide (VP16) is a topoisomerase II inhibitor and has been used for the treatment of non-small cell lung cancer (NSCLC). Xeroderma pigmentosum complementation group C (XPC) protein is a DNA damage recognition factor in nucleotide excision repair and involved in regulating NSCLC cell proliferation and viability. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) enhanced etoposide-induced cytotoxicity in NSCLC cells through modulating the XPC expression. We found that etoposide increased XPC expression in an AKT activation manner in 2 squamous cell carcinoma H1703 and H520 cells. Knockdown of XPC using siRNA or inactivation of AKT by pharmacological inhibitor PI3K inhibitor (LY294002) enhanced the cytotoxic effects of etoposide. In contrast, enforced expression of XPC cDNA or AKT-CA (a constitutively active form of AKT) reduced the cytotoxicity and cell growth inhibition of etoposide. Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell growth inhibition of etoposide in NSCLC cells, which were associated with the downregulation of XPC expression and inactivation of AKT. Our findings suggested that the Hsp90 inhibition induced XPC downregulation involved in enhancing the etoposide-induced cytotoxicity in H1703 and H520 cells.
This study used Medicare Part B claims and enrollment data to estimate the prevalence of macular disease in Kansas at county and area levels. Spatial analysis by aggregated county clusters was assessed with standardized prevalence ratios and 95% confidence intervals, and a thematic map was produced to illustrate geographic distribution. A total of 17888 unduplicated claims were identified among 335132 beneficiaries older than age 64 years. Compared with the state prevalence of 5.34%, the central agricultural area showed a disproportionately high macular disease prevalence.
Although encouraging, a more robust study is needed to reasonably attribute the persistence of this significantly lower TB rate to this brief intensive intervention.
Older adults are not sufficiently physically active and do not consume sufficient fruits and vegetables to achieve health benefits, such as an improved health-related quality of life (HRQL). As a result, an innovative gardening intervention, comprised of stretching exercises, the teaching of home garden knowledge and skills, and the preparation and taste testing of fruits and vegetables, was developed to target increased: (a) confidence to garden and to consume fruits and vegetables, (b) physical activity, (c) fruit and vegetable consumption, and (d) HRQL. Seven older adults, aged 60 years or older, participated in the gardening intervention and 10 older adults participated in the control group during the fall. Measures of confidence, physical activity (i.e., gardening), fruit and vegetable consumption, and HRQL were obtained at baseline and at the end of the 10-week program. Findings revealed that, at baseline, intervention participants had significantly higher confidence to garden compared to control participants but at end-program intervention and control participants did not significantly differ in any of the outcome variables. Bivariate findings also revealed that intervention participants who had higher confidence to garden or to consume fruits and vegetables at baseline also gardened more at end-program. Thus, interventions targeting confidence to garden and to consume fruits and vegetables may be effective in improving gardening (i.e., physical activity) behavior. Findings also suggest that seasonal change may be one influential moderator of the gardening program on confidence and gardening and fruit and vegetable consumption behavior change. Future research should examine the impact of the program in different seasons to clarify the effects.
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