Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with the human immunodeficiency virus (HIV) invariably leads to the development of acquired immunodeficiency syndrome (AIDS) in most infected humans, yet does so rarely, if at all, in HIV-infected chimpanzees. The differences between the two species are not due to differences in cellular receptors or an inability of the chimpanzee to be infected, but rather to the lack of pan-immune activation in the infected primate. This results in reduced apoptotic death in CD4+ T-helper lymphocytes and a lower viral load. In humans the degree of chronic immune activation correlates with virus load and clinical outcome with high immune activation leading to high viral loads and the more rapid progression to AIDS and death. The type of immune perturbation seen in HIV-associated AIDS is similar to that of chronic graft-versus-host disease (GVHD) where reduced cell-mediated immune (CMI) responses occur early in the course of the disease and where humoral responses (HI) predominate. A reduced CMI response occurs in a number of chronic infectious diseases, including tuberculosis and leishmaniasis. More recently, it has become increasingly apparent that the CMI response is suppressed in virtually all malignant diseases, including melanoma and colorectal and prostate cancer. This raises the possibility that, as the malignant process develops, the cancer cells evolve to subvert the CMI response. Moreover, the reduced CMI response seen in colorectal cancer (CRC) patients is completely reversed following curative surgery strongly supporting the hypothesis that CRC can suppress the systemic immune response. Wound healing, ovulation, embryo implantation, and fetal growth are all associated with suppressed CMI and neovascularization (the formation of new blood vessels) or angiogenesis (the formation of new blood vessels from an existing vasculature). If unresolved, wound healing results in chronic inflammation, which can give rise to the phenomenon of "scar cancers." Indeed all the chronic inflammatory conditions known to be associated with the subsequent development of malignant disease, including chronic obstructive airway disease (COPD), ulcerative colitis (UC), and asbestosis, give rise to similar proangiogenic, suppressed CMI, and HI-predominant environments. In keeping with this CMI-associated cytokines such as interleukin (IL)-2 and interferon (IFN)-gamma tend to be antiangiogenic, whereas HI cytokines such as IL-6 tend to be proangiogenic. Furthermore, chronic immune activation leads to the synthesis and release of factors such as macrophage inflammatory protein (MIP)-1 that inhibit apoptosis through suppression of p53 activity. The "Golden Triangle" of suppressed CMI, angiogenesis, and reduced apoptosis would provide the ideal environment for the serial mutations to occur that are required for the development of malignant disease. If the observed association is relevant to carcinogenesis, then treatments aimed at reducing the components of these inflammatory conditions may be useful both in the setting of chemoprevention and the therapeutic management of established disease.
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PMID:Chronic immune activation and inflammation in the pathogenesis of AIDS and cancer. 1188 29

Selenium is an essential trace element involved in several key metabolic activities via selenoproteins, enzymes that are essential to protect against oxidative damage and to regulate immune function. Selenium also may have other health benefits unrelated to its enzymatic functions. It may provide important health benefits to people whose oxidative stress loads are high, such as those with inflammatory or infectious diseases like rheumatoid arthritis or human immunodeficiency virus/acquired immunodeficiency syndrome, or who are at high risk for cancers, particularly prostate cancer. Some studies have generated compelling evidence that selenium is beneficial, either alone or in conjunction with other micronutrients. Additional data from large clinical trials that provide the highest level of evidence will be key to determining the benefits accrued at various selenium intake levels. When the strength of the evidence becomes sufficient, clinical health professionals will need to use dietary and clinical assessment methods to ensure that people at increased risk for cancer or inflammatory and infectious diseases can be appropriately advised about selenium intake.
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PMID:The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. 1597 98

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.
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PMID:A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer. 1635 94

Composite promoters combining the prostate-specific antigen (PSA) enhancer core element with promoter elements derived from gene coding for human prostate-specific transglutaminase gene, prostate-specific membrane antigen gene, prostate-specific antigen, rat probasin or phosphoglycerate kinase were characterized for their ability to specifically express the enhanced green fluorescent protein (EGFP) gene in prostate versus non-prostate cancer cell lines when transferred with a human immunodeficiency virus-1-based lentiviral vector. By themselves minimal proximal promoter elements were found to inefficiently promote relevant tissue-specific expression; in all the vectors tested, addition of the PSA enhancer core element markedly improved EGFP expression in LnCaP, a cancer prostate cell line used as a model for prostate cancer. The composite promoter was inactive in HuH7, a hepatocarcinoma cell line used as a model of neighboring non-prostate cancer cells. Among the promoters tested, the combination of the PSA enhancer and the rat probasin promoter showed both high specificity and a strong EGFP expression. Neither a high viral input nor the presence of the cPPT/CTS sequence affected composite promoter behavior. Our data suggest that composite prostate-specific promoters constructed by combining key elements from various promoters can improve and/or confer tissue specific expression in a lentiviral vector context.
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PMID:Use of the PSA enhancer core element to modulate the expression of prostate- and non-prostate-specific basal promoters in a lentiviral vector context. 1674 21

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer.
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PMID:Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis. 1698 36

The marine organisms produce many metabolic substances with numerous pharmacological activities. It has been suggested that ilimaquinone, a metabolite of sea sponge, can induce vesiculation of the Golgi apparatus and display several biological activities, such as anti-human immunodeficiency virus, anti-inflammation as well as anti-microbial activities. In this study, the sulforhodamine B assays showed that ilimaquinone induced a concentration-dependent anti-proliferative effect in several types of cancer cell lines, including prostate cancer PC-3 and LNCaP, non-small cell lung cancer A549 and hepatocellular carcinoma Hep3B cells. The anticancer mechanism of ilimaquinone in the representative PC-3 cells was identified. Ilimaquinone induced a time-dependent increase of G(1) phase arrest and a subsequent increase of hypodiploid sub-G(1) phase (apoptosis) of the cell cycle. The arrest of the cell cycle was associated with a sustained high level of nuclear cyclin E but the absence of DNA synthesis by flow cytometric analysis, indicating an incomplete S phase. Although ilimaquinone-induced Golgi vesiculation, the data showed that the inhibition of cancer cell growth was not through the Golgi fragmentation. Several biological kinases and transcription factors were examined in this study. The data demonstrated that ilimaquinone did not activate extracellular signal-regulated kinase and phosphatidylinositol 3-kinase but induce the up-regulation and nuclear translocation of growth arrest and DNA damage inducible gene 153 (CHOP/GADD153). Furthermore, ilimaquinone-mediated anti-proliferative effect is significantly reduced in the antisense CHOP/GADD153-overexpressing cells. Ilimaquinone also inhibited DNA binding of NF-kappaB; however, this inhibitory effect could not explain ilimaquinone-induced anticancer effect. In summary, it is suggested that ilimaquinone induces the anti-proliferative effect through the G(1) arrest of the cell cycle and the up-regulation and nuclear translocation of CHOP/GADD153.
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PMID:Ilimaquinone, a marine sponge metabolite, displays anticancer activity via GADD153-mediated pathway. 1714 May 62

The objective of this study was to evaluate the scientific evidence on flaxseed, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. Electronic searches were conducted in 9 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion/exclusion criteria are used for selection. Grades were assigned using an evidence-based grading rationale. A review of the literature on flaxseed yielded 13 categories for which flaxseed had been studied in humans, including constipation/laxative, attention-deficit hyperactivity disorder, hyperlipidemia, atherosclerosis/coronary artery disease, breast cancer, cyclic mastalgia (breast pain), menopausal symptoms, hyperglycemia/diabetes, hypertension, lupus nephritis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and prostate cancer. Most of the available evidence investigates the efficacy of alpha-linoleic acid found in flaxseed compared with fish oil, and almost all of the available studies are poor quality. Although flaxseed and flaxseed oil have several promising future uses, the available literature does not support recommendation for any condition at this time.
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PMID:Flax and flaxseed oil (Linum usitatissimum): a review by the Natural Standard Research Collaboration. 1776 Nov 28

A substantial health burden results from medical problems affecting the male genital tract, including chronic morbidity conditions affecting a large proportion of men, such as benign prostatic hypertrophy and prostatitis, and potentially lethal conditions, such as prostate cancer and human immunodeficiency virus transmission. Rational approaches to therapeutics in these conditions should benefit from understanding local pharmacokinetics and pharmacodynamics of active drugs within the male genital tract. However, the description of drug distribution into the male genital tract has been largely limited to total, rather than protein-free drug concentrations in the whole ejaculate at one or two time points within a dosing interval, which may be misleading in understanding local drug action. Recent innovations enable a quantitative understanding of protein-free drug kinetics into semen and drug distribution into individual male genital tract glands. These methods may benefit therapeutics through optimization of targeted drug delivery and facilitate drug development for diseases related to these glands.
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PMID:Male genital tract pharmacology: developments in quantitative methods to better understand a complex peripheral compartment. 1778 63

Study of male genital tract (MGT) pharmacology is relevant to the treatment of prostatitis, prostate cancer, infertility, and seminal human immunodeficiency virus transmission. However, the time course of drug concentrations in the MGT is largely unknown. To determine the feasibility of frequent semen sampling in assessing the pharmacokinetics of the MGT, we administered efavirenz, indinavir, and zidovudine to subjects to achieve steady-state levels and then collected semen samples at sequentially decreasing ejaculation intervals. The volume of seminal plasma decreased from 4.0 (1.2-5.1) ml (median with range) at 48 h after the baseline ejaculation to 0.72 (0.45-1.6) ml 1 h after a previous ejaculation, which was still adequate for drug concentration assessment. The seminal fructose concentration also decreased. However, the concentration of prostate-specific antigen and all three drugs did not decrease, even if the ejaculation intervals decreased to 1 h. Thus, semi-intensive semen sampling can be used to assess MGT pharmacokinetics.
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PMID:Effect of semen sampling frequency on seminal antiretroviral drug concentration. 1791 41

The accessory glands of the male genital tract are the sites of several major health problems, including benign prostatic hyperplasia, prostate cancer, and human immunodeficiency virus (HIV) transmission. We aimed to validate and improve our noninvasive method for the quantitation of drug concentrations in these physiological subcompartments. Twenty-seven men were dosed with 100 mg desipramine (a weak base) and 975 mg aspirin (a weak acid) and ejaculated their semen in 1 pass across 5 compartments of a collection device 2.5 hours later. A Bayesian latent-variable model previously developed by our group was further advanced for the estimation of drug concentrations in prostate and seminal vesicles based on drug and biomarker concentrations in the split ejaculate. Under normality assumptions, desipramine concentration (with 95% credible intervals) in prostate and seminal vesicles were 27 (8.3-52) ng/mL and 7.6 (4.0-11) ng/mL, respectively; salicylate concentration in prostate and seminal vesicles were 2.0 (0.093-6.5) microg/mL, and 9.9 (8.2-12) microg/mL, respectively. The prostate-to-seminal vesicles concentration ratio was 0.20 (0.0087-0.75) for salicylate and 3.6 (0.91-9.9) for desipramine. We conclude that our quantitative analysis along with the split ejaculate method is sensitive, reproducible, and applicable for the assessment of pharmacokinetics of the accessory glands of the male genital tract.
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PMID:Noninvasive quantitation of drug concentration in prostate and seminal vesicles: improvement and validation with desipramine and aspirin. 1809 13


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