UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PA-III is one of the four transplantable cell lines propagated in vitro in cell monolayer cultures from four spontaneously developed prostate cancer tumors in aged germfree and conventional Lobund-Wistar (L-W) rats (Pollard Model). Our data documented the presence of IGF-I and glucocorticoid but the absence of IGF-II, insulin and androgen receptors in PA-III cells. Activation of IGF-I receptors by IGF-I, IGF-II and insulin stimulated the proliferation of PA-III cells. Activation of glucocorticoid receptors by dexamethasone inhibited the proliferation of PA-III cells. PA-III cells contained urokinase-like activity and expressed the mRNA for urokinase gene which was negatively regulated by glucocorticoids. The above results suggest that PA-III cells could be a useful model for the study of glucocorticoid effects on prostate cancer cells. In addition, these data are discussed in relationship to the capacity of PA-III cells to produce the osteoblastic reaction when transplanted on L-W rat skeleton. A model outlining the putative paracrine interactions between PA-III cells and rat osteoblasts is proposed.
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PMID:PA-III rat prostate adenocarcinoma cells (review). 132 42

Insulin-like growth factor binding protein-3 (IGFBP-3), the major serum carrier protein for the IGFs, is absent from Western ligand blots of seminal plasma, but is detectable by RIA. IGFBP-3 protease activity has recently been described in pregnancy serum. We investigated the possibility that seminal plasma contains an IGFBP-3 protease, by incubating seminal plasma with 125I-labeled human IGFBP-3. Seminal plasma was found to have potent IGFBP-3 protease activity with a cleavage pattern different from that of pregnancy serum. Prostate-specific antigen (PSA) is a serine protease found in semen. Autoradiographs measuring IGFBP-3 protease activity demonstrated that purified PSA cleaved IGFBP-3, yielding a cleavage pattern identical to that of seminal plasma. IGFBP-2 and -4 in seminal plasma were not degraded by PSA. Cleavage of IGFBP-3 by PSA resulted in a marked reduction in the binding affinity of the fragments to IGF-I, but not IGF-II. We speculate that PSA may serve to modulate IGF function within the reproductive system or in prostate cancer by altering IGF-IGFBP-3 interactions.
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PMID:Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma. 138 55

Four transplantable cell lines (PA-I, II, III, and IV) derived from four Lobund-Wistar (L-W) rats that manifested spontaneous prostate cancer have demonstrated metastatic capacity in visceral organs. Interestingly, PA-III cells, when deposited over the scapula or calvarium of the Lobund-Wistar rat, could produce lytic and blastic reactions on rat skeleton. Since growth factors and growth factor receptors have been implicated in bone remodeling, cancer biology, and metastatic growth of cancer cells, we have examined 1) the effects of insulin and insulin-like growth factors (IGF-I and IGF-II) on the proliferation of PA-III cells; and 2) the presence of specific receptors for these peptides. IGF-I (0.5 to 100 ng/ml), IGF-II (0.5 to 100 ng/ml), and insulin (0.5 to 10 micrograms/ml) stimulated tritiated thymidine uptake and increased the number of PA-III cells in culture. Receptor studies demonstrated the presence of specific bindings sites for IGF-I and II but not for insulin. The number and affinity of the receptor sites were: IGF-I (nb = 675 fmol/100 g protein, Kd = 0.56 nmol) and IGF-II (nb = 225 fmol/100 g protein, Kd = 0.71 nmol). Molecular characterization of IGF binding sites by polyacrylamide gel electrophoresis under denaturing conditions indicated only the presence for the type I IGF receptor. The presence of the IGF-I receptor and the absence of IGF-II and insulin receptors are discussed in relation to the capacity of PA-III cells to produce bone lesions on the L-W rat.
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PMID:Mitogenic effects of insulin and insulin-like growth factors on PA-III rat prostate adenocarcinoma cells: characterization of the receptors involved. 166 15

Tumor growth and metastasis are angiogenesis-dependent. Virtually all solid tumors are neovascularized by the time they are detected. However, there is a prevascular phase during early tumor development where few or no tumor cells are angiogenic and expansion of the tumor is restricted to a few mm3. When enough tumor cells become angiogenic, the tumor can expand progressively and shed metastatic cells. This angiogenic switch has recently been quantitated for human breast cancer, as well as for prostate cancer. We have studied the problem of how tumors switch to the angiogenic phenotype by using transgenic mice in which tumors develop at a predictable time and in discrete prevascular and vascular stages. When the transgene is the bovine papilloma virus (BPV) genome, angiogenic fibrosarcomas develop from non-angiogenic precursors called fibromatoses. The fibrosarcomas secrete growth factors for capillary endothelial cells. In contrast, the fibromatoses do not secrete endothelial cell growth factors. When the transgene consists of the large "T" antigen of SV40 under the control of the rat insulin promoter, 70% of pancreatic islets become hyperplastic and 4-10% of these become angiogenic at 6-7 weeks. Tumors arise from these neovascularized hyperplastic islets and reach > 1000 x the volume of the preangiogenic islets. The onset of angiogenic activity coincides with the secretion of acidic fibroblast growth factor (aFGF) and other growth factors not fully identified at this writing. These studies help to explain the switch to the angiogenic phenotype during tumorigenesis and provide models to discover antiangiogenic therapies directed at the source of angiogenic activity. Such therapy, when developed, may be co-administered with currently available angiogenesis inhibitors which are directed at the target of angiogenic activity, vascular endothelial cells.
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PMID:Switch to the angiogenic phenotype during tumorigenesis. 172 33

Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.
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PMID:Adverse effects of anabolic steroids. 2942 77

Recent advances in culture techniques have enabled routine establishment and propagation of epithelial cells derived from normal and malignant tissues of the human prostate. Comparative studies of the responses of normal and cancer-derived cell populations to various growth and differentiation factors in vitro were undertaken to examine the possibility that cancer cells might respond differentially. Clonal growth assays in serum-free medium demonstrated that optimal proliferation of normal as well as cancer cell strains was generally dependent on the presence of cholera toxin, epidermal growth factor, pituitary extract, hydrocortisone, insulin, and high levels of calcium in the culture medium, and on the use of collagen-coated dishes. Only one cancer strain responded aberrantly to epidermal growth factor and hydrocortisone. Putative differentiation factors (transforming growth factor-beta and vitamin A) inhibited the growth of all normal and cancer strains. The origin of a cancer-derived cell strain that responded similarly to normal strains was verified by positive labeling with a prostate cancer-specific antibody, validating the conclusion from these studies that normal and cancer prostatic epithelial cells are not distinguishable on the basis of responses to the tested factors.
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PMID:In vitro studies of human prostatic epithelial cells: attempts to identify distinguishing features of malignant cells. 269 20

The DU145 human prostate cancer cell line was shown to possess type I insulin-like growth factor receptors (IGFR). The addition of either IGF-I or IGF-II, but not insulin, to serum-free culture medium increases the rate of thymidine incorporation by the cells, a response which is suppressed by specific blockade of the previously described epidermal growth factor (EGF) autocrine growth regulatory loop. The DU145 cells secrete into conditional medium a specific IGF-binding protein (IGFBP) precipitated by an antibody to IGFBP-1, and whose secretion is also suppressed by interruption of the EGF autocrine loop. This IGFBP may modulate the bioactivity of IGFs arising from endocrine or paracrine sources in vivo. After removal of IGFBPs from the conditioned medium, no secretion of either IGF-I or IGF-II by this prostate cancer cell line is detected by radioimmunoassay and radioreceptor assay, respectively.
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PMID:Regulation of DU145 human prostate cancer cell proliferation by insulin-like growth factors and its interaction with the epidermal growth factor autocrine loop. 751 2

Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin growth factor 1 (IGF1). A total of 30 patients with hormone-refractory prostate cancer were treated with a slow-release formulation of lanreotide. The mean age was 71 years. Patients were treated with one intramuscular injection of 30 mg BIM 23014 once a week and were followed for prostate-specific antigen (PSA) level evolution until disease progression or WHO grade 3 or 4 toxicity and for survival. The patients were treated for a mean duration of 12 weeks (range, 2-60 weeks). The performance status and bone pain were improved in 40% and 35% of patients respectively. In all, 20% of the patients had a decrease of > or = 50% in PSA levels and 16% showed a stabilization. The biological response was correlated with clinical improvement. The 1-year global survival rate was 72%, with the rate being 89% in the group of patients who were responders on PSA plasma level and 64% in patients with progressive disease. The response duration ranged from 16 to 60 weeks. Toxicity was minor, with transient grade I digestive side effects being noted in a few patients. Lanreotide given at 30 mg once a week to patients with metastatic hormone-refractory prostate cancer was well tolerated. The response rate was higher than that reported in recent published series. Higher doses of lanreotide should be evaluated.
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PMID:Phase I-II study of the somatostatin analogue lanreotide in hormone-refractory prostate cancer. 754 Jan 20

Insulin-like growth factors (IGFs) are potent mitogens that stimulate the growth of prostate cells. In serum, IGFs circulate bound to IGF-binding proteins (IGFBPs), which modulate their proliferative action. We studied the electrophoretic pattern of IGFBPs in the serum of patients with prostate cancer and in individuals with increased serum levels of prostate-specific antigen (PSA) in the absence of prostate malignancy. Serum IGFBP-2 was dramatically increased in patients with metastatic prostate cancer compared with healthy controls (23.83 +/- 6.93% vs. 2.95 +/- 0.52% of total serum IGFBPs; P < 0.02). A moderate rise in IGFBP-2 was also observed among patients with increased PSA without malignancy. In contrast, a decrease in serum IGFBP-3 was detected in most patients with metastatic prostate cancer (68.2 +/- 9.1% vs. 95.4 +/- 0.9% of total serum IGFBPs; P < 0.02) and was more pronounced in advanced cases. A highly significant correlation between serum IGFBP-2 and PSA levels was found (r = 0.62; P < 0.002), with a significant negative correlation between serum PSA and IGFBP-3 (r = -0.63; P < 0.002). We suggest that IGFBPs may be involved in growth modulation of prostate malignancy and that alterations in their serum levels may serve as a marker for prostate cancer.
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PMID:Serum insulin-like growth factor-binding protein-2 (IGFBP-2) is increased and IGFBP-3 is decreased in patients with prostate cancer: correlation with serum prostate-specific antigen. 768 15

We have established organ cultures of human prostate for in vitro analysis of the hormone responsiveness of prostatic carcinoma. Tissue samples were obtained from total prostatectomies for localized cancer. Normal prostate tissues with age-related hyperplastic changes were obtained from cystoprostatectomies of bladder cancer patients representing the same age group, and they wer cultivated as controls. The explants of prostates were cultured for 7 days in basal medium containing 5% dextran charcoal-treated fetal calf serum, insulin (0.08 IU/ml), and dexamethasone (10(-7) M) with or without dihydrotestosterone (DHT) (10(-7) M) or estradiol (10(-9) M). Control prostates showed involutive changes of morphology when cultured in basal medium. These changes were prevented by DHT, which also maintained a strong epithelial immunostaining for PSA (prostate specific antigen), which was used as a marker for tissue-specific functions. The concentration of PSA in the medium was high. The rate of [3H]thymidine incorporation into DNA was stimulated by DHT in some cultures of control prostates, but no increase was seen in the others. Androgen stimulation of [3H]thymidine incorporation was consistently inhibited by the antihormone cyproterone acetate. The main morphological response of cultured control prostates to estradiol was induction of squamous metaplasia. This was associated with increased incorporation of [3H]thymidine, which was radioautographically localized to the basal layer of epithelium. Estradiol effects were counteracted by the antihormone toremifene. The expression of androgen receptor mRNA and protein in cultured control prostate was demonstrated by Northern blotting and immunohistochemistry, respectively. Also, the expression of estrogen receptor was demonstrated by the polymerase chain reaction analysis of total mRNA from cultured control and cancer prostate. The cultured explants of prostate cancer maintained the overall morphology of the original carcinoma. However, the presence of DHT improved the morphology of cancerous acini in all better differentiated carcinomas (3 grade I and 5 grade II), and corresponding responses to DHT were observed in the rate of DNA labeling with [3H]thymidine. In 2 of 3 grade I carcinomas, DHT increased DNA synthesis, but in grade II cancers the patterns of hormone responses were more variable. The poorly differentiated grade III prostatic carcinomas did not respond to either hormone as measured by [3H]thymidine uptake, and no hormone effects could be seen in morphology. Immunostaining for PSA differed from that in control prostates: besides cancerous acini, the surrounding stroma was also intensively stained, which suggests unpolarized and impaired secretion of PSA by the cancer cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hormone regulation of human prostate in organ culture. 769 34

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