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)

The incidence and progression of urologic diseases, as well as several urologic cancers.depend on many interrelated factors, such as obesity, diet, genetics, environment, age, and the immune system. Obesity is a risk factor for stress urinary incontinence, ED, infertility, and renal calculi. Numerous publications have demonstrated that a high dietary intake of fat increases prostate cancer risk, although the mechanisms are not clear. Although some reports may demonstrate an association between obesity and prostate cancer, it may be hard to establish because, in general, men with obesity have a high-fat diet. Obesity, recurrent urinary tract infections, increased intake of protein and fried foods, and female sex seem to increase the risk of renal cancer. Environmental toxins seem to be the major factors affecting the incidence of bladder cancers. Thus, dietary modification and other public health measures directed at reducing weight may reduce the incidence of urologic illnesses. More studies are necessary to determine the therapeutic effects of weight loss and dietary modification on the incidence and progression of urologic tumors.
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PMID:The impact of obesity in urology. 1512 7

Diethylstilbestrol is a synthetic nonsteroidal estrogen that was used to prevent miscarriage and other pregnancy complications between 1938 and 1971 in the United States. In 1971, the U.S. Food and Drug Administration issued a warning about the use of diethylstilbestrol during pregnancy after a relationship between exposure to this synthetic estrogen and the development of clear cell adenocarcinoma of the vagina and cervix was found in young women whose mothers had taken diethylstilbestrol while they were pregnant. Although diethylstilbestrol has not been given to pregnant women in the United States for more than 30 years, its effects continue to be seen. Women who took diethylstilbestrol during pregnancy have a slightly higher risk of breast cancer than the general population and therefore should be encouraged to have regular mammography. Women who were exposed to diethylstilbestrol in utero may have structural reproductive tract anomalies, an increased infertility rate, and poor pregnancy outcomes. However, the majority of these women have been able to deliver successfully. Recommendations for gynecologic examinations include vaginal and cervical digital palpation, which may provide the only evidence of clear cell adenocarcinoma. Initial colposcopic examination should be considered; if the findings are abnormal, colposcopy should be repeated annually. If the initial colposcopic examination is normal, annual cervical and vaginal cytology is recommended. Because of the higher risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, obstetric consultation may be required for pregnant women who had in utero diethylstilbestrol exposure. The male offspring of women who took diethylstilbestrol during pregnancy have an increased incidence of genital abnormalities and a possibly increased risk of prostate and testicular cancer. Routine prostate cancer screening and testicular self-examination should be encouraged.
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PMID:Diethylstilbestrol exposure. 1516 59

The androgen receptor (AR) mediates androgen action determining male sexual phenotypes and promotion of spermatogenesis. Mutations in the AR cause various degrees of androgen resistance resulting in a range of androgen insensitivity syndromes. A single copy gene in the X chromosome encodes the AR. The gene contains a polymorphic triple repeat sequence [(CAG)n] with 9-36 repeats in the normal population, and displays ethnic dependence. In vitro, there is an inverse correlation between CAG repeat length and AR function. Associations exist between short alleles and prostate cancer in men or clinical hyperandrogenism in women. Expansion of the CAG tract > 40 repeats leads to spinal bulbar muscular atrophy (SBMA, Kennedy disease), an adult onset neurodegenerative disease that also presents with low virilization and spermatogenetic defects. The disease may show evidence of anticipation (increasing severity with succeeding generations accompanying further expansion of repeat length). Twelve studies involving Singaporean, Australian, North American and Japanese men reported a relationship between AR CAG repeat length and male infertility, whereas 10 studies, most of them European, found no association. Differences in hereditary or acquired factors in these populations may explain the equivocality. However, statistical methods, sample sizes, study definition and control populations, in addition to laboratory methods vary widely within the published papers, and could affect the results and conclusions. Current data is insufficient to conclude whether IVF patients who display AR CAG expansion may transfer infertility or premutation of neurodegenerative disease to their descendants. We recommend screening of AR CAG repeat length, at least in those populations where an association between repeat length and infertility could be found.
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PMID:[Androgen receptor and male infertility]. 1552 1

Suppression of sex steroid production based on desensitisation and down-regulation of pituitary gonadotropin-releasing hormone (GnRH)-receptors by agonistic GnRH-analogues resulting in the blockage of gonadotropin release from the anterior pituitary gland is a well-established approach in a variety of clinical conditions. Antagonistic analogues of GnRH exert their effect by competing with endogenous GnRH for pituitary binding sites. Because of the lack of any intrinsic activity of these compounds, the characteristic initial 'flare-up' effect of GnRH-agonist administration is absent. A more rapid suppression of gonadotropin release from the pituitary gland can be achieved, enabling shorter treatment regimes in ovarian hyperstimulation for assisted reproduction. As yet, GnRH-antagonists have attained market approval only for the indication of premature luteinizing hormone (LH) surge prevention in controlled ovarian hyperstimulation and palliative treatment of advanced prostatic cancer. However, GnRH-antagonists may be useful in a variety of other malignant and non-malignant indications where rapid sex steroid suppression is desired, such as uterine leiomyomas, endometriosis, gynaecological cancers or benign prostatic hyperplasia. In the context of infertility treatment, available data on the application of GnRH-antagonists in the treatment of endometriosis and uterine leiomyomas are reviewed.
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PMID:GnRH-antagonists in reproductive medicine. 1599 Oct 15

The prostate is a glandular male accessory sex organ vital for normal fertility. It provides the prostatic component of seminal plasma which nourishes and protects sperm following ejaculation. Prostasomes are small (40-500 nm) membrane-bound vesicles produced by epithelial cells lining the prostate acini and are a component of prostatic secretions. Although the existence of these particles has been known for many years, their full function and relevance to reproductive health are largely unknown. Proteomic studies have shown a wide range of proteins (enzymes, structural proteins and novel, unannotated proteins) present in or on the surface of prostasomes providing them with a diverse nature. Interestingly prostasomes are able to fuse with sperm, this event and the associated transfer of proteins lies at the heart of many of their proposed functions. Sperm motility is increased by the presence of prostasomes and their fusion prevents premature acrosome reactions. Prostasomes have been shown to aid protection of sperm within the female reproductive tract because of immunosuppressive, antioxidant and antibacterial properties. Clinically these functions imply a role for prostasomes in male factor infertility. However, the very functions that promote fertility may have negative connotations in later life; recent work has suggested that prostasomes are involved in prostate cancer. Clearly more work is needed to clarify the role of these novel particles and their impact on men's health.
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PMID:Prostasomes--their effects on human male reproduction and fertility. 1637 3

Two polymorphic trinucleotide repeats of human androgen receptor gene (hAR), CAG and GGN which encode glutamine and glycine, have been shown to be associated with human diseases. The number of repeats ranges from 8 to 35 for the CAG and from 10 to 30 for the GGN in human populations. Longer CAG repeats are associated with reduced hAR transcriptional activity, spinal bulbar muscular atrophy and lower cognitive function in older men, whereas shorter CAG repeats are associated with increased risk of prostate cancer and infertility in men. The functional roles of the CAG and GGN repeats have not been clarified. In order to compare the sequence of the CAG and GGN regions in apes, we analyzed 57 chimpanzees, 18 gorillas, 20 orangutans, 16 agile gibbons, and 17 siamangs by PCR and electrophoresis. Two bonobos and one long-tailed macaque were also sequenced and the sequences of all species were aligned, respectively, with one human registered sequence. Seventeen different alleles (4, 7, 8, 9, 12, 14, 15, and 17-26 repeats) and 11 alleles (11-14 and 16-22 repeats) were detected at the CAG and the GGN loci, respectively. Although the repeat tract was conserved among apes, chimpanzees had alleles with a wide range of repeat lengths: (CAG)(14-26) and (GGN)(14-22). Gorillas were less polymorphic with the (CAG)(8) and (GGN)(19) alleles being most common, and orangutans exhibited monomorphic (CAG)(11) and (GGN)(22) alleles. On the other hand, agile gibbons and siamangs had the shortest (CAG)(4) allele, but showed variable length of GGN repeats (11-13 in agile gibbons and 16-21 in siamangs). In chimpanzees, frequent haplotypes consisting of short CAG repeats and long GGN repeats or vice versa was observed as in humans.
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PMID:Comparison of androgen receptor CAG and GGN repeat length polymorphism in humans and apes. 1646 55

Lonidamine (LND) is a compound originally developed as an infertility drug. By capitalizing on the unique energy requirements of many solid tumors including benign prostatic hyperplasia (BPH), LND has shown efficacy as an adjunct to either radiation or chemotherapy in the treatment of several advanced solid organ malignancies such as lung, breast, head and neck, and liver metastases. It has an excellent safety profile in over 20 years of use in Italy in thousands of cancer patients. Preliminary data suggest that it is safe and effective in the treatment of lower urinary tract symptoms associated with BPH by metabolically targeting the unique dependency of the prostate on energy production by glycolysis instead of the aerobe Krebs cycle. The observed effects include a fast reduction in serum prostate-specific antigen and prostate volume, and simultaneous improvements in symptoms and urinary flow rate. The fact that prostate cancer and high-grade prostatic intraepithelial neoplasia have similar metabolic circumstances suggests that LND might also be effective in various stages of the prostate cancer carcinogenesis.
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PMID:The development of lonidamine for benign prostatic hyperplasia and other indications. 1698 56

The asynchronous secretion of gonadotrope LH and FSH under the control of GnRH is crucial for ovarian cyclicity but the underlying mechanism is not fully resolved. Because prostaglandins (PG) are autocrine regulators in many tissues, we determined whether they have this role in gonadotropes. We first demonstrated that GnRH stimulates PG synthesis by induction of cyclooxygenase-2, via the protein kinase C/c-Src/phosphatidylinositol 3'-kinase/MAPK pathway in the LbetaT2 gonadotrope cell line. We then demonstrated that PGF(2alpha) and PGI2, but not PGE2 inhibited GnRH receptor expression by inhibition of phosphoinositide turnover. PGF(2alpha), but not PGI2 or PGE2, reduced GnRH-induction of LHbeta gene expression, but not the alpha-gonadotropin subunit or the FSHbeta subunit genes. The prostanoid receptors EP1, EP2, FP, and IP were expressed in rat gonadotropes. Incubations of rat pituitaries with PGF(2alpha), but not PGI2 or PGE2, inhibited GnRH-induced LH secretion, whereas the cyclooxygenase inhibitor, indomethacin, stimulated GnRH-induced LH secretion. None of these treatments had any effect on GnRH-induced FSH secretion. The findings have thus elaborated a novel GnRH signaling pathway mediated by PGF(2alpha)-FP and PGI2-IP, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and differentially inhibit LH and FSH release. These findings provide a mechanism for asynchronous LH and FSH secretions and suggest the use of combination therapies of GnRH and prostanoid analogs to treat infertility, diseases with unbalanced LH and FSH secretion and in hormone-dependent diseases such as prostatic cancer.
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PMID:Reciprocal cross talk between gonadotropin-releasing hormone (GnRH) and prostaglandin receptors regulates GnRH receptor expression and differential gonadotropin secretion. 1713 45

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

Geoffrey Wingfield Harris' demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the G(q) signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention.
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PMID:Diversity of actions of GnRHs mediated by ligand-induced selective signaling. 1797 9


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