Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells

Many mitotic kinases have been targeted for the development of anti-cancer drugs, and inhibitors of these kinases have been expected to perform well for cancer therapy. Efforts focused on selecting good targets and finding specific drugs to target are especially needed, largely due to the increased frequency of anti-cancer drugs used in the treatment of lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell survival. We found that ursolic acid (UA) inhibits the catalytic activity of VRK1 via direct binding to the catalytic domain of VRK1. UA weakens surveillance mechanisms by blocking 53BP1 foci formation induced by VRK1 in lung cancer cells, and possesses synergistic anti-cancer effects with DNA damaging drugs. Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients

Update and Overview of Practical Epidemiologic Aspects of HIV/AIDS among Injection Drug Users in the United States

In a changing public health landscape in which local, state, and federal agencies must confront threats of bioterrorism, emerging infections, and numerous chronic diseases, transmission of HIV among injection drug users (IDUs) continues to be an important public health issue and one of the driving forces behind the HIV epidemic. Using a computerized MEDLINE search of published articles from January 1981 through October 2005, we conducted a literature review of practical epidemiologic aspects of HIV/AIDS among IDUs in the United States. Although recent trends indicate a decline in the proportion of newly diagnosed HIV infections associated with injection drug use, drug-use behaviors overall still account for 32% of new HIV diagnoses. Factors in addition to syringe sharing contribute to HIV transmission among IDUs: risky sexual behaviors, sharing of drug preparation equipment and drug solutions, and contextual and social factors. Promising approaches for HIV prevention include rapid HIV testing, office-based substance abuse treatment, behavioral interventions, improved communication about syringe exchange programs, and case management. HIV among IDUs continues to be an important public health problem in the 21st century. It is imperative that public health agencies continue to monitor and combat the HIV epidemic among IDUs to ensure that hard-won gains will not be eroded

Role of Autophagy in HIV Pathogenesis and Drug Abuse

Autophagy is a highly regulated process in which excessive cytoplasmic materials are captured and degraded during deprivation conditions. The unique nature of autophagy that clears invasive microorganisms has made it an important cellular defense mechanism in a variety of clinical situations. In recent years, it has become increasingly clear that autophagy is extensively involved in the pathology of HIV-1. To ensure survival of the virus, HIV-1 viral proteins modulate and utilize autophagy pathway so that biosynthesis of the virus is maximized. At the same time, the abuse of illicit drugs such as methamphetamine, cocaine, morphine, and alcohol is thought to be a significant risk factor for the acquirement and progression of HIV-1. During drug-induced toxicity, autophagic activity has been proved to be altered in various cell types. Here we review the current literature on the interaction between autophagy, HIV-1, and drug abuse, and discuss the complex role of autophagy during HIV-1 pathogenesis in co-exposure to illicit drugs