RNA interference against human papillomavirus oncogenes in cervical cancer cells results in increased sensitivity to cisplatin

Targeted inhibition of oncogenes in tumor cells is a rational approach toward the development of cancer therapies based on RNA interference (RNAi). Tumors caused by human papillomavirus (HPV) infection are an ideal model system for RNAi-based cancer therapies because the oncogenes that cause cervical cancer, E6 and E7, are expressed only in cancerous cells. We investigated whether targeting HPV E6 and E7 oncogenes yields cancer cells more sensitive to chemotherapy by cisplatin, the chemotherapeutic agent currently used for the treatment of advanced cervical cancer. We have designed siRNAs directed against the HPV E6 oncogene that simultaneously targets both E6 and E7, which results in an 80% reduction in E7 protein and reactivation of the p53 pathway. The loss of E6 and E7 resulted in a reduction in cellular viability concurrent with the induction of cellular senescence. Interference was specific in that no effect on HPV-negative cells was observed. We demonstrate that RNAi against E6 and E7 oncogenes enhances the chemotherapeutic effect of cisplatin in HeLa cells. The IC50 for HeLa cells treated with cisplatin was 9.4 mu M, but after the addition of a lentivirus-delivered shRNA against E6, the IC50 was reduced almost 4-fold to 2.4 mu M. We also observed a decrease in E7 expression with a concurrent increase in p53 protein levels upon cotreatment with shRNA and cisplatin over that seen with individual treatment alone. Our results provide strong evidence that loss of E6 and E7 results in increased sensitivity to cisplatin, probably because of increased p53 levels.

Increase in skin cancer screening during a community-based randomized intervention trial

Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community-based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3-year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross-sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole-body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole-body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women ≥50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self-examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole-body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered. © 2005 Wiley-Liss, Inc.

Using fear appeals to promote cancer screening - are we scaring the wrong people?

There is debate regarding the use of fear appeals (emphasizing severe threats to health) in social marketing, to encourage preventive behaviours, such as screening for breast cancer. While it has been found that fear appeals may result in attitude and behaviour change there is also the risk of inciting inappropriate levels of fear, motivating the wrong audience or instigating maladaptive behaviour in the target group such as denial or defensive avoidance. This study examined the impact of an experimental threat manipulation for mammography screening on a group of women in regional Australia. The study found that varying the level of threat had no impact on stated intentions of the women to undergo mammographic screening. However, it also found that high-threat messages resulted in stronger negative emotional reactions and greater perceived susceptibility among younger women who are not the target group for screening in Australia. The results of this study emphasize the importance of limiting the use of high levels of threat in social marketing campaigns, and ensuring that campaigns are appropriately designed to specifically impact upon and motivate the target group. Copyright © 2006 John Wiley & Sons, Ltd.

Predictors of emotional well-being following a 'false positive' breast cancer screening result

Using a short-term longitudinal design, and consistent with a stress and coping perspective, this study examined the main and stress-buffering effects of social support and coping on emotional well-being following a 'false positive' breast cancer screening result. Immediately prior to obtaining results of follow-up assessment, 178 women completed measures of emotional well-being, stress appraisal, coping strategies and social support. Six weeks later, 85 women found to be cancer free completed a measure of well-being. Hierarchical regression analyses were used to examine the effects of social support and coping on well-being after controlling for initial well-being and stress appraisal. Consistent with predictions, avoidant coping was associated with higher levels of emotional well-being and social support was found to have a stress buffering effect on well-being. Active-cognitive coping strategies had a stress-buffering effect on well-being. Findings suggest that social support and coping do influence emotional well-being following recall for follow-up assessment of a 'false positive' breast cancer screening result.

Anticancer effects of Curcuma C20-dialdehyde against colon and cervical cancer cell lines

Background: Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials and Methods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of 65.4±1.74 μg/ml, 58.4±5.20 μg/ml and 72.0±0.03 μg/ml, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.

Prostate cancer screening

Universal screening for prostate cancer (Pca) using prostate-specific antigen-based testing is not recommended, as the potential harms of screening (overdiagnosis and overtreatment) outweigh potential benefits. The case for Pca screening requires a paradigm shift, which emphasizes the risks of screening over the risks of undetected cancer. Physicians are encouraged to use shared decision making with patients who express an interest in Pca screening, taking into account both the patient's screening preferences and individual risk profile. New models of care informed by the Patient Protection and Affordable Care Act are intended to assist clinicians in providing recommended preventive services. © 2014 Elsevier Inc.