31 research outputs found

    New insights into the synergism of nucleoside analogs with radiotherapy

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    Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells

    Consensus guidelines for the use and interpretation of angiogenesis assays

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    The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

    The human adrenal cortex: growth control and disorders

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    Barriers to condom use among women at risk of HIV/AIDS: a qualitative study from Iran

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    <p>Abstract</p> <p>Background</p> <p>The growing trend of women infected with HIV through sexual transmission is alarming. Factors influencing condom use have not yet been fully identified, especially in countries with conservative cultures and backgrounds. The present study aimed to explore the barriers of condom use in Iranian women at risk of HIV.</p> <p>Methods</p> <p>Using the grounded theory methodology, participants’ experiences and their perceptions regarding condom were collected during semi structured in depth interviews. Participants were 22 women, aged 21–49 years, considered to be at risk for HIV, due to their own or their partner’s sexual behaviors. Qualitative analysis of the data was conducted manually and was guided by constant comparative analysis.</p> <p>Results</p> <p>Two main barriers, personal and socio-environmental emerged from data analysis. Lack of perceived threat, absence of protective motivation, inadequate knowledge, perceived lack of control, negative attitudes towards condom and misperception were the major personal barriers, while unsupportive environments and cultural norms were the common socio-environmental barriers to condom use among these at risk women.</p> <p>Conclusions</p> <p>These critical barriers have to be addressed for implementing effective prevention programs against HIV among populations at risk for HIV.</p
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