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)

l-Carrageenan is a polysulphated carbohydrate that antagonises some heparin-binding growth factors. We assessed the effect of l-carrageenan on the proliferation of a panel of cell lines, some of which require heparin-binding growth factors for mitogenesis. The importance of growth factor antagonism for the anti-proliferative activity was also determined. Cell proliferation was determined by cell counts and a tetrazolium dye (MTT) assay, and DNA synthesis was determined by thymidine incorporation. The proliferation of the basic fibroblast growth factor (bFGF)-dependent endothelial cell line FBHE was inhibited by daily administration of l-carrageenan in a dose-dependent manner [concentration inhibiting cell growth by 50% (IC50 value), approx. 0.5 microgram/ml]. However, excess bFGF did not reverse the inhibitory effect. DNA synthesis was completely inhibited by concentrations of l-carrageenan that nonetheless allowed significant protein synthesis to occur. The proliferation of the androgen-dependent prostate-carcinoma cell line LNCaP was also inhibited by l-carrageenan (IC50 value, 5.5 micrograms/ml) and the cells were arrested at the G1/S boundary. l-Carrageenan inhibited DNA synthesis in MCF-7 cells stimulated by bFGF and transforming growth factor alpha (TGF alpha) but not in those stimulated by insulin-like growth factor 1 (IGF-1). Blocking IGF-1-mediated DNA synthesis with anti-IGF-1 receptor antibody alpha IR3 enhanced the inhibitory activity of l-carrageenan against MCF-7 cells grown in serum. A number of other transformed and non-transformed cell lines were either partially inhibited or not inhibited by l-carrageenan. l-Carrageenan had low anti-coagulant activity. l-Carrageenan is a selective anti-proliferative agent and warrants further investigation for anti-angiogenic therapy (in view of its activity against endothelial cells) and for the treatment of androgen-dependent prostate cancer.
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PMID:Selective inhibition of cell proliferation and DNA synthesis by the polysulphated carbohydrate l-carrageenan. 762 52

We have investigated three prostatic cancer cell lines, PC-3, DU-145, and LNCa.FGC, and found that all three cell lines can grow in serum-free medium without the addition of exogenous growth factors. All three cell lines produce substantial amounts of insulin-like growth factor 1 (IGF-1) that is secreted in the medium and they all display constitutively autophosphorylated IGF-1 receptors; two of the cell lines overexpress IGF-1 receptor RNA. The growth of all three cell lines is inhibited by an antisense oligodeoxynucleotide to IGF-1 receptor RNA or by peptide analogues of IGF-1 that compete with IGF-1 binding to its receptor. Our results indicate that these three cell lines grow by an autocrine loop in which the overproduced IGF-1 activates its receptor. Interference with the activation of the receptor leads to cessation of growth.
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PMID:Inhibition of growth of prostatic cancer cell lines by peptide analogues of insulin-like growth factor 1. 843 54

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.
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PMID:Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. 982 88

Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small cell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice >/=6 months of age (38 mice total) was 50%. The development of neoplasia in these transgenic mice appeared to follow a stepwise progression through early preneoplastic changes that ultimately culminated in frank neoplasia. These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.
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PMID:Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. 1073 98

Further well designed studies are urgently needed to clarify if use of prostate-specific antigen (PSA) as a diagnostic test for prostate cancer can be improved by incorporating measurements of serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding-protein 3 (IGFBP-3), and if these measurements might also identify men at higher risk.
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PMID:Can measurements of IGF-1 and IGFBP-3 improve the sensitivity of prostate-cancer screening? 1137 64

The importance of insulin-like growth factor 1 (IGF-1) in human serum for the early diagnosis of prostate cancer is controversial. The IGF-1/PSA ratio may improve the performance of prostate specific antigen (PSA) as a prostate cancer marker. IGF-1, along with PSA and free PSA concentration, was measured in the serum of 34 patients with prostate cancer and in 131 patients with benign prostatic hyperplasia (BPH). Although IGF-1 concentration did not significantly differ between the groups, PSA/IGF-1 ratio could clearly distinguish the two groups. In patients with cancer but not in patients with BPH, IGF-1 concentration correlated with PSA and free PSA. The values of PSA and free PSA correlated with each other for both groups. Receivers Operating Curve (ROC) analysis indicated a better sensitivity to specificity ratio for PSA/IGF-1 than for PSA or Free/Total (F/T) PSA.
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PMID:The significance of PSA/IGF-1 ratio in differentiating benign prostate hyperplasia from prostate cancer. 1138 Nov 96

The local microenvironment at the sites of cancer metastases protects tumour cells from anticancer drug-induced apoptosis via mechanisms, such as soluble growth factors and cytokines. The concept of antisurvival factor (ASF) therapy as a component of anticancer treatments aims at neutralising the protective effect conferred upon cancer cells by the survival factor(s) derived by the local microenvironment, in order to enhance the sensitivity and/or reverse the resistance of tumour cells to other anticancer therapeutic strategies. Herein, we review the translation of this concept from ex vivo studies to clinical applications in the setting of prostate cancer refractory to androgen ablation (stage D3). At this stage, which predominantly involves bone metastases, insulin-like growth factor 1 (IGF-1) production (either growth hormone (GH)-dependent or GH-independent) can protect tumour cells from apoptosis, despite the significant suppression of androgens. The application of the ASF therapeutic concept involves the combination of dexamethasone (which suppresses GH-independent IGF-1) and somatostatin analogue (which suppresses endocrine, GH-dependent IGF-1) with the pro-apoptotic effect of the testicular androgen suppression by sustained use of LHRH analogues. In stage D3, patients who had failed anti-androgen withdrawal, chemotherapy and also had several other adverse prognostic features, the ASF-based combination achieved durable objective responses and major symptomatic improvement, paving the way for future applications of this approach. The ASF-based combination therapy illustrates a novel paradigm in cancer treatment: anti-tumour treatment strategies may not only aim at directly inducing cancer cell apoptosis, but can also target the tumour microenvironment and neutralise the protection it confers on metastatic cancer cells. The favourable toxicity profile of this therapeutic approach calls for its testing in a randomised controlled setting in metastatic prostate cancer and, conceivably, in other IGF-1-responsive malignancies.
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PMID:Combination of dexamethasone and a somatostatin analogue in the treatment of advanced prostate cancer. 1182 17

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

There are no established risk factors for prostate cancer other than age, ethnic group, and family history. For dietary factors, the WCRF/AICR reported that diets high in vegetables were possibly protective, and that regular consumption of red meat, fat, saturated/animal fat, and milk and any products possibly increased risk. Among nutritional factors, a protective effect of lycopene, vitamin E, selenium, and perhaps fish oil and phytoestrogens appear particularly promising, although no definite answers have yet emerged. Although hormonal influences are biologically plausible, observational studies of androgen have not produced consistent results. While, insulin-like growth factor 1 could be a risk factor. Based on these evidences, several chemoprevention trials were launched using 5-alpha reductase inhibitor, selenium, vitamin E and so on.
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PMID:[Risk factors and current chemoprevention studies in prostate cancer]. 1571 86

Prostate cancer has become a major public health problem worldwide. Yet, the etiology of prostate cancer remains largely unknown. Dietary factors, dietary supplements, and physical activity might be important in the prevention of the disease. In the majority of studies, it was observed that high consumption of meat and dairy products has been linked to a greater risk. In contrast, frequent consumption of fatty fish and tomato products has been associated with a reduced risk. It has been shown consistently that high levels of circulating insulin-like growth factor 1 (IGF-1) are associated with an increased risk of prostate cancer. Dietary factors are also recognized as determinants of circulating IGF-1, thus changes in diet may influence IGF-1 concentrations in serum. Furthermore, increased intake of vitamin E and selenium (from supplements) has been shown in intervention studies to decrease the risk. Possibly, high level of physical activity is also associated with decreased risk of prostate cancer. The accumulated scientific evidence concerning the associations between diet, lifestyle, and risk of prostate cancer development suggests that there are some identified modifiable risk factors that it might be recommended to change in order to decrease the risk for this common cancer site.
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PMID:Diet, lifestyle and risk of prostate cancer. 1616 10


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