Molecular Targets And Candidate Prostate Cancer Prevention Agents

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Discoveries and technologies associated with the National Institute of Health Human Genome Project32 and the National Cancer Institute (NCI) Cancer Genome Anatomy Project (C-GAP)33 promise innovative molecular targets for prostate cancer prevention. When evaluating the role of potential new agents, several critical questions must be considered.34 For example, does the agent inhibit growth or cause regression in existing models of prostate cancer? What is the agent's toxicity profile? Can it be given effectively in an oral dose? Is cost a factor? Have phase I trials in humans been conducted? Is the mechanism of action known and can its effects be ? Is there a suitable target population for testing? The answer to these and other pressing questions regarding chemoprevention agents are critically important and can only be answered through systematic study.

Existing putative prostate cancer prevention agents can be classified into those intended to inhibit ongoing cellular mechanisms, such as sex steroid signaling, differentiation or proliferation, pro-apoptosis and angiogenesis, and those intended to reverse or prevent progressive DNA damage, such as gene therapy, growth factor therapy or antioxidant therapy35 (Table 10.1). Observational data suggest that the hormonal milieu during early prostate development is an important determinant of subsequent cancer formation. Castration early in life nearly eliminates the risk of BPH and prostatic cancer in subsequent years. Additionally, because of the known hormone dependency that normal prostate epithelia and prostate cancer cells exhibit, sex steroid hormone signaling has been aggressively targeted for chemotherapeutic and chemopreventative strategies. Recent studies evaluating the role of 5a-reductase inhibition and androgen deprivation for patients with premalignant changes (PIN) are yet to be completed.36 Many 'natural' remedies for prostate cancer are believed to contain phytoestrogens that target sex steroid pathways.37 Several promising agents thought to affect cell differentiation and proliferation are also being explored including retinoids and vitamin D analogs.38 The goal of other novel strategies including inhibition of growth signaling and antiapoptotic pathways is to target transformed cells without adversely affecting normal cellular turnover. It remains to be seen if this is clinically feasible.

Perhaps a more attainable strategy is to prevent initial or progressive DNA damage. Epidemiologic studies provide encouraging preliminary data suggesting antioxidant nutrients, such as selenium, vitamin E and lycopene, are associated with decreased prostate cancer risk.39-42 Oxidative stress has been implicated in the early events initiating prostate cancer and there is strong evidence that endogenous or exogenous reactive oxygen species (ROS) damage lipids, proteins and nucleic acids. Oxidative modifications are thought to be directly mutagenic and may alter gene function including p53, c-fos and c-jun.43'44 The effects of two antioxidants are actively being studied as part of the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which aims to enrol over 32000 men throughout the USA and Canada over 7-12 years.9 Further prostate cancer prevention approaches, including the use of gene therapy and/or growth factors, await more convincing proof of the principle in the adjuvant setting.

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Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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