Mitochondrial permeability transition pore as a selective target for anti-cancer therapy.

Mitochondrial outer membrane permeabilization (MOMP) is the ultimate step in dozens of lethal apoptotic signal transduction pathways which converge on mitochondria. One of the representative systems proposed to be responsible for the MOMP is the mitochondrial permeability transition pore (MPTP). Although the molecular composition of the MPTP is not clearly understood, the MPTP attracts much interest as a promising target for resolving two conundrums regarding cancer treatment: tumor selectivity and resistance to treatment. The regulation of the MPTP is closely related to metabolic reprogramming in cancer cells including mitochondrial alterations. Restoration of deregulated apoptotic machinery in cancer cells by tumor-specific modulation of the MPTP could therefore be a promising anti-cancer strategy. Currently, a number of MPTP-targeting agents are under pre-clinical and clinical studies. Here, we reviewed the structure and regulation of the MPTP as well as the current status of the development of promising MPTP-targeting drugs.

Reducing sex under the influence of drugs or alcohol for patients in substance abuse treatment.

AIMS: In a previous report, the effectiveness of the Real Men Are Safe (REMAS) intervention in reducing the number of unprotected sexual occasions among male drug abuse treatment patients was demonstrated. A secondary aim of REMAS was to reduce the frequency with which men engage in sex under the influence (SUI) of drugs or alcohol. DESIGN: Men in methadone maintenance (n = 173) or out-patient psychosocial treatment (n = 104) completed assessments at baseline, 3 and 6 months post-intervention. PARTICIPANTS: The participants were assigned randomly to attend either REMAS (five sessions containing information, motivational exercises and skills training, including one session specifically targeting reducing SUI) or human immunodeficiency virus (HIV) education (HIV-Ed; one session containing HIV prevention information). SUI during the most recent sexual event served as the primary outcome in a repeated measures logistic regression model. FINDINGS: Men assigned to the REMAS condition reporting SUI at the most recent sexual event decreased from 36.8% at baseline to 25.7% at 3 months compared to a increase from 36.9% to 38.3% in the HIV-Ed condition (t(intervention) = -2.16, P = 0.032). No difference between the treatment groups was evident at 6-month follow-up. At each assessment time-point, sex with a casual partner versus a regular partner, and being in methadone maintenance versus psychosocial out-patient treatment, were associated with engaging in SUI. CONCLUSIONS: Overall, a motivational and skills training HIV prevention intervention designed for men was associated with greater reduction in SUI than standard HIV education at the 3-month follow-up.

Predictors of condom use among men enrolled in drug treatment programs.

This study identified predictors of condom use and developed a model of condom use in a sample of men (n = 324) enrolled in drug treatment. Utilizing a series of logistic regression analyses reported condom use was predicted by possession of condoms, future intention to use condoms, future intention to increase condom use, having a high-risk partner, low Condom Barriers Scale scores, being unmarried and ethnic minority status. A probit path analysis revealed the following model of condom use among men in drug treatment: Taking condoms from clinic stocks was the best predictor of condom possession, which in turn was the best predictor of condom use. These study findings identify condom availability in treatment programs as an important risk reduction intervention. Treatment programs can apply these predictors of condom use to better identify individuals at risk for HIV and sexually transmitted infections to better target prevention interventions.

Motivational and skills training HIV/sexually transmitted infection sexual risk reduction groups for men.

The effectiveness of a motivational and skills training HIV/AIDS group intervention designed for men in substance abuse treatment was evaluated. Men in methadone maintenance (n = 288) or outpatient psychosocial treatment (n = 302) completed assessments at baseline, 2 weeks, 3 months, and 6 months postintervention. Participants were randomly assigned to attend either Real Men Are Safe (REMAS; five sessions containing information, motivational exercises, and skills training) or HIV education (HIV-Ed; one session containing HIV prevention information). REMAS participants engaged in significantly fewer unprotected vaginal and anal sexual intercourse occasions (USO) during the 90 days prior to the 3- and 6-month follow-ups than HIV-Ed participants. Completing REMAS resulted in an even stronger effect: Completers reduced their number of USO by 21% from baseline to 6-month follow-up. In contrast, HIV-Ed completers increased the number of USO by 2%. A motivational and skills training HIV prevention intervention designed for men was associated with greater sexual risk reduction over standard HIV-Ed. Substance abuse treatment programs can therefore help reduce sexual risk among their clientele by providing a more intensive intervention than what is traditionally provided.

Hypermethylation of the COX-2 gene is a potential prognostic marker for cervical cancer.

AIM: The aim of the present study was to evaluate the DNA hypermethylation profiles of 14 genes known to be associated with tumor behavior and their clinical significance in cervical cancer. METHOD: The clinical features of 82 patients with stage IB cervical cancer were analyzed in terms of DNA hypermethylation of 14 genes (hMLH1, p16, COX-2, CDH1, APC, DAPK, MGMT, p14, RASSF1A, RUNX3, TIMP3, FHIT, THBS1, and HLTF). RESULTS: Of 14 genes investigated, only hypermethylation of COX-2 showed significant association with poor disease-free survival (P = 0.001). To further investigate an alteration in COX-2 expression by DNA hypermethylation, immunohistochemistry for COX-2 protein was performed in the cervical cancer tissues. We found no significant association between hypermethylation and expression patterns of the COX-2 gene. CONCLUSIONS: The present results suggest that DNA hypermethylation of the COX-2 gene may be a potential prognostic marker in early stage cervical cancer, the underlying mechanism of which is independent of gene silencing.

Knowledge of and interest in hepatitis C treatment at a methadone clinic.

This study describes knowledge about hepatitis C virus (HCV) infection and interest in treatment among 110 opiate dependent patients from an opiate dependence treatment program in San Francisco. None had been treated for HCV and only 30% had been evaluated for HCV treatment. While only 34% knew about HCV treatment, 54% of the sample became "definitely interested" in HCV treatment after hearing the risks and benefits. Men were approximately five times more likely than women to know of some HCV treatment. Whites were seven times and Latinos were about six times more likely than African-Americans to know about HCV treatment. Our findings suggest that methadone programs can play an important role in increasing access to HCV treatment through educating patients about treatment options.