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)

Vasomotor hot flashes are a common problem in women who are postmenopausal or receiving antiestrogen treatment for breast cancer. Hot flashes are also a common problem after orchiectomy/luteinizing hormone-releasing hormone therapy, occurring generally in 50% to 66% of these men. Prescribed treatments for hot flashes for men on hormonal ablation treatment for prostate cancer are well documented. These conventional agents have shown good results, but their long-term efficacy, safety, and cost are still questioned. Therefore, the search for other viable agents, including nontraditional treatments, continues. Complementary/alternative treatments to alleviate hot flashes in women have generated an enormous amount of interest. However, these options have received little attention in men with hot flashes. Research with vitamin E, soy, black cohosh, red clover, and numerous other alternative treatments in women may provide some indirect but valuable insight on their potential effectiveness in men. Many of these alternatives have been a disappointment in recent randomized trials of women, and it is likely that there will be similar results with men. However, numerous supplements have yet to be tested in a clinical trial against a placebo, and clinicians should become aware of this ever-increasing list. Patients should be made aware of the primary importance of lifestyle interventions that could partially affect hot flashes and immediately affect overall health, especially during the period of androgen suppression, when it is not uncommon to observe accelerated weight changes and insulin insensitivity. Otherwise, recent research with older and newer conventional agents, such as antidepressants or estrogen/progesterone, should be emphasized at this time for moderate-to-severe hot flashes that profoundly affect daily activities and/or sleep. Antidepressant supplements (St. John's wort) or acupuncture could also be an attractive option in future investigations. Low-dose estrogen seems particularly attractive, because it is inexpensive and may simultaneously reduce hot flashes and the risk of osteoporosis in men receiving long-term androgen suppression therapy; however, the potential for cardiovascular complications must be further investigated. Ultimately, adequate research (vs placebo) should determine the fate of the alternative supplements proposed for hot flash reduction.
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PMID:Complementary/alternative therapies for reducing hot flashes in prostate cancer patients: reevaluating the existing indirect data from studies of breast cancer and postmenopausal women. 1193 33

Measurement of obesity is not as simple as its definition. Currently, several methods of measuring obesity are used in clinical studies. Skinfold thickness, crude weight, lean body mass (LBM), body mass index (BMI), and waist-to-hip ratio (WHR) are some of the more popular methods, but each contains its inherent strengths and flaws. In general, the results of the largest studies on prostate cancer and obesity have not been conclusive. One of the largest studies found an inverse relation to prostate cancer in the youngest age groups. The age and duration of obesity or any rapid changes in weight gain, along with other unhealthy exposures, may have some relation to prostate cancer incidence and mortality. Early intrinsic or extrinsic exposure to estrogen or estrogenlike compounds may provide a protective effect. The timing and duration of a higher estrogen and/or lower testosterone exposure may have a beneficial or detrimental impact on the prognosis of an established prostate tumor. Negative exposures over time such as low levels of sex hormone-binding globulin (SHBG), a greater exposure to growth factors, elevated insulin levels, greater sympathetic activity, higher cholesterol levels, immune system dysfunction, inadequate diets, smoking status, and other factors may be associated with an increased risk of prostate cancer and other diseases. Obesity may also be associated with other cancers for similar and different reasons. For example, morbidity and mortality from postmenopausal breast cancer, colon, kidney, and other cancers are potentially associated with obesity. Other comorbidities such as cataracts, coronary heart disease, diabetes, erectile dysfunction, hypertension, and others are also associated with obesity. The 2 largest prospective studies on BMI and overall mortality have also demonstrated the substantial negative impact of excess weight on society. Prostate cancer risk and obesity need further research to establish if a true association exists, but at this time, does it really matter? Overall, the profound adverse effect of being obese on general health is dramatic, and this is what clinicians and patients need to remember.
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PMID:Is obesity a risk factor for prostate cancer, and does it even matter? A hypothesis and different perspective. 1193 35

The pineal hormone melatonin is the mediator of external light to physiologic adaptation to day and night rhythms, it regulates reproduction in animals but attempts to utilize melatonin in women for contraception have failed. Melatonin seems to be the natural hormone to facilitate sleep in insomniac patients and causes no hang over. When applied together with benzodiazepine it allows reduction of benzodiazepine without withdrawal effects. It should be applied 2 h before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma-aminobutyric acid- and benzodiazepine receptor explaining its success in treatment of seizures in children and in adults. Constant application of benzodiazepine reduced the production of natural melatonin in rats, supporting the evidence that long-term application of benzodiazepine in humans does not restore sleeping habits but reduces natural sleeping habits even more. Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. Some oncostatic properties are supported by cell culture work and studies in animals. In Nordic countries indigenous people suffer less from breast and prostate cancer, winter darkness seems to protect. The supposedly increased melatonin levels created the 'melatonin hypothesis'. Epidemiological studies did show that blind people indeed have half the rate of breast cancers, supporting the hypothesis. Controversial results concerning melatonin and insulin resistance and glucose tolerance have been published. In postmenopausal women application of melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women should avoid melatonin, since its teratogenic effect is not known. Patients suffering from non-hormone dependent tumors, like leukemia, should avoid melanin, since tumor growth was promoted in animal experiments. It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe.
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PMID:Melatonin deficiencies in women. 1195 97

Inhibiting androgen receptor (AR) activation through medical or surgical castration and blockade of AR-androgen binding is the cornerstone of treatment for advanced prostate cancer. However, in most cases tumor growth eventually becomes androgen independent. Alternative mechanisms of AR activation, some of which involve growth factor receptor signaling, have been demonstrated in prostate cancer models, and it is likely that a number of autocrine and paracrine growth factor ligand-receptor interactions such as those of epidermal growth factors, fibroblast growth factors, and insulin-like growth factors contribute to the androgen independent phenotype by promoting cell proliferation and survival. Blocking activation and signaling through growth factor receptors and upstream signaling proteins has emerged as a credible approach to cancer treatment. Successful application of this approach in prostate cancer using a growing array of small molecule kinase inhibitors, antibodies, and antisense oligonucleotides will be greatly accelerated by elucidation of the key signaling pathways that maintain the androgen independent phenotype.
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PMID:Signaling inhibitors in the treatment of prostate cancer. 1209 76

The endothelins, a family of potent vasoconstricting peptides, have been implicated in the pathophysiology of advanced prostate cancer. Two endothelin receptors, ET-A and ET-B are found in normal prostate tissue. Malignant prostate cells are notable for the loss of ET-B receptors and increased levels of endothelin-1 [ET-1]; this distortion of the endothelin system may be a significant factor in the progression of prostate cancer. Proposed roles for endothelin in prostate cancer include growth promotion, apoptosis inhibition, bone formation, and stimulation of nociceptive receptors. ET-1 can act alone as a mitogen, but its effects are greatest as a comitogen with a variety of growth factors, including basic fibroblast growth factor, insulin-like growth factors, and platelet derived growth factor. Although their exact functions are unclear, ET-1, in conjunction with vascular endothelial growth factor, appears to play a major role in tumor angiogenesis. By a variety of methods, ET-1 alters the balance of osteoblast and osteoclasts to the favor new bone formation that is characteristic of metastatic disease. Several studies indicate that the refractory pain of metastatic cancer is related to the direct nociceptive effects ET-1. These findings suggest that ET receptors are promising therapeutic targets for pharmacologic intervention. Early clinical trials indicate that the ET-A receptor antagonist used in prostate cancer is reasonably well tolerated with mild but pervasive symptoms related to ET-1's vasoconstrictive effects. Results of ongoing clinical trials are eagerly awaited in order to see if the hypothetical promise of ET antagonism will result in clinical success.
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PMID:Endothelin-1 as a target for therapeutic intervention in prostate cancer. 1209 77

Insulin-like growth factor binding protein (IGFBP)-3, a p53-response gene, can induce apoptosis in an IGF-independent manner. Here we demonstrate that IGFBP-3 mediates p53-induced apoptosis during serum starvation using two foil neoplastic cell models: one which introduces p53 activity and one which eliminates it. We created a doxycycline-inducible p53 model from the p53-negative PC-3 prostate cancer cell line. Doxycycline treatment increased both p53 and IGFBP-3 levels. It also augmented apoptosis, but not during insulin-like growth factor-I co-treatment. In a second model, lung carcinoma H460 cells expressing fully functional p53 were stably transfected with E6, which targets p53 for degradation. H460-E6 cells contained less p53 and IGFBP-3 than control neo-transfected cells, and proteasome blockade restored both. In serum deprivation, H460-E6 cells had enhanced growth and less apoptosis than did H460-neo cells. Reductions in H460-neo apoptosis, comparable in magnitude to H460-E6, were achieved by adding anti-IGFBP-3-antibody or IGFBP-3 antisense oligomers, but not non-specific immunoglobulin or IGFBP-3 sense oligomers. In summary, turning p53 in two foil neoplastic cell models induced IGFBP-3 expression and increased apoptosis during serum starvation, an effect inhibited by insulin-like growth factor-I treatment and specific IGFBP-3 blockade. This is the first demonstration of inhibition of p53 action by antagonizing IGFBP-3.
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PMID:IGFBP-3 mediates p53-induced apoptosis during serum starvation. 1211 29

Prostate cancer risk is associated with a high-fat diet and a sedentary lifestyle. Placing men on a low-fat diet-and-exercise intervention reduces serum hormones, including estradiol, insulin, and free testosterone, that may play a role in prostate cancer growth. Eight men participated in a low-fat diet-and-exercise program for a mean of 14.2 yr, and LNCaP cell growth in culture was measured in medium supplemented with 10% of each subject's serum as well as with testosterone, estradiol, and insulin added singly or in combination. These results were compared in the fetal bovine serum (FBS)-stimulated growth and cell growth in serum obtained from a control group of 14 overweight men. In separate tissue culture experiments, LNCaP and PC-3 cell growth was also measured in response to the addition of testosterone, estradiol, or insulin to steroid-stripped FBS. LNCaP cell growth in medium with subject serum was 40% less than in FBS-stimulated medium and 49% less than in medium with serum from control, overweight men. Addition of testosterone, estradiol, and insulin to serum from diet-and-exercise subjects significantly stimulated LNCaP cell growth in vitro but accounted for only about half of the difference between the control and diet-and-exercise subjects. Thus other serum changes must also account for the significant reduction in LNCaP cell growth observed using medium with serum from the diet-and-exercise subjects in the cell culture assay.
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PMID:Role of testosterone, estradiol, and insulin in diet- and exercise-induced reductions in serum-stimulated prostate cancer cell growth in vitro. 1223 42

DU145 prostate carcinoma cells cultured on type III collagen possessed a highly migratory potential which was twice as much as HT-29 colon carcinoma cells. Prior to attachment to collagen, DU145 cells were highly reactive for fibronectin and after attachment clear zones between cells and collagen suggested protease activity. HT-29 cells attached to type III collagen forming dome-like polyps, however, tight and/or gap junctions were not observed. hFob osteoblasts were co-cultured with DU145 to establish a prostate cancer-collagen matrix barrier-bone cell metastasis model. Osteoblasts maintained their differentiated osteoblastic characteristics on one side of the collagen barrier, demonstrating high alkaline phosphatase, osteocalcin and insulin growth factor (IGF) activities. hFob cell growth was prominent adjacent to demineralized bone matrix particles (BMPs) embedded in type III collagen. The collagen matrix was deteriorated on the DU145 side of the collagen barrier. The DU145-collagen III-hFob model will allow an evaluation of the influence of the matrix on prostate cancer-bone cell interaction and regulation by growth factors.
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PMID:Culture and co-culture of DU145 prostate carcinoma, osteoblasts and HT-29 colon carcinoma cells on a fabricated type III collagen matrix. 1240 57

Insulin resistance and compensatory hyperinsulinaemia are thought to be the underlying factors in the metabolic or insulin-resistance syndrome and can be controlled by diet and exercise. Hyperinsulinaemia has been shown to have a direct effect on the live, suppressing the production of sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding proteins 1 and 2 (IGFBP-1, -2) while stimulating the production of insulin-like growth factor 1 (IGF-1). These factors have been proposed to be important modulators of hormone-related cancers, such as prostate cancer. Men adopting a low-fat diet and daily exercise reduced their levels of serum insulin and IGF-1, while increasing their levels of IGFBP-1 and sex hormone-binding globulin (SHBG). Cell-culture studies with LNCaP prostate cancer cells showed apoptosis of tumour cells and a reduction in serum-stimulated cell growth in the post diet and exercise serum. These results suggest that prostate cancer may be another aspect of the insulin-resistance syndrome and that adopting a low-fat diet combined with regular exercise may reduce the risk for prostate and other hormone-related cancers. This needs to be tested with prospective studies.
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PMID:Prostate cancer: another aspect of the insulin-resistance syndrome? 1245 75

The Insulin-like Growth Factor (IGF) network in prostate tissue represents a key element in normal and tumour growth. It can provide us with new markers for prognosis or diagnosis and targets for treatment of prostate diseases. This short review introduces the IGF network in general and in the prostate gland, summarises the modifications observed in tumours and discusses the importance of a new family of low affinity IGF-binding proteins. Further studies on the IGF network will enrich our understanding of prostate tumourigenesis and its control and therefore provide new therapeutics to master the IGF network
Prostate Cancer Prostatic Dis 1999 Mar
PMID:Insulin-like Growth Factor (IGF) Network and Prostate Pathologies. 1249 40


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