CDK5 in oncology: recent advances and future prospects.

Selective abrogation of cyclin-dependent kinases (CDK) activity is a highly promising strategy in cancer treatment. The atypical CDK, CDK5 has long been known for its role in neurodegenerative diseases, and is becoming an attractive drug target for cancer therapy. Myriads of recent studies have uncovered that aberrant expression of CDK5 contributes to the oncogenic initiation and progression of multiple solid and hematological malignancies. CDK5 is also implicated in the regulation of cancer stem cell biology. In this review, we present the current state of knowledge of CDK5 as a druggable target for cancer treatment. We also provide a detailed outlook of designing selective and potent inhibitors of this enzyme.

Outcomes of highly active antiretroviral therapy and its predictors: a cohort study focusing on tuberculosis co-infection in South West Ethiopia.

BACKGROUND: In this study, we hypothesized that TB co-infection independently increases the risk of poor treatment outcomes in such patients even if they are on antiretroviral therapy (ART). Therefore, this study was aimed at investigating this hypothesis among cohort of adult PLWHs in South West Ethiopia. METHODOLOGY: Cohort study comparing the immunologic and clinical outcomes of 130 HIV/TB co-infected and 520 only HIV patients starting ART was enrolled. Chi square and student t test were used to compare outcome variables and logistic regression was used to assess the effect of TB on treatment failure. RESULTS: In this study, TB co-infection didn't increase immunologic failure even in univariate analysis at both 6 [OR, 1.10 (0.59-1.69), P = 0.85] and 12 months [OR, 1.06 (0.58-1.93), P = 0.89] of ART initiation. However, it increased the risk of clinical failure at both 6 [Adjusted Odd Ratio (AOR), 2.90 (1.41-6.09), P = 0.028] and 12 months [AOR, 2.93 (1.41-6.09), P = 0.004] of ART initiation. CONCLUSION: This study showed that TB co-infection didn't adversely affect the immunologic outcomes, weight and hemoglobin responses even though it increased the risk of clinical failure nearly three times. Therefore, beside the concern given for TB prevention and treatment, several patient and policy related factors need to be addressed to maximally benefit from highly active antiretroviral therapy rollout in resource limited settings.

New hope for eradication of HIV from the body: the role of polymeric nanomedicines in HIV/AIDS pharmacotherapy.

Human immunodeficiency virus continued to be the greatest challenge and killer disease of the 21st century despite the advent of potent highly active antiretroviral therapy which are limited by their severe adverse effects, significant drug interactions, frequent dosing, limited bioavailability, and less access to viral reservoir sites like macrophages. Nano-medicines are becoming new hopes in avoiding these shortcomings of conventional antiretroviral drugs. The emphasis of this review is mainly the application of polymers based nanomedicines in pharmacotherapy of HIV/AIDS. Most of the studies to date on this area are in vitro and human clinical trials are totally missed. However, many interesting points are uncovered through this review like the possibility of achieving high intracellular concentration of drugs, very good antiretroviral activity, improved bioavailability, reduced toxicity and release of the drugs from nanocarriers for long time reducing the need for frequent dosing. Indeed, a lot of assignments left behind for researchers to overcome the challenges hindering the wider application of nanomedicines in treatment of HIV/AIDS.