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)

Although prostate cancer initially responds well to endocrine therapy, it becomes resistant to the therapy a few years later, and is called hormone-refractory cancer. In general, hormone-refractory prostate cancer is resistant to all kinds of therapy and the prognosis is extremely poor. Here we report an unusual case of a person with hormone-refractory prostate cancer, who has been surviving for more than 5 years after being diagnosed as having this type of cancer. A 75-year-old man was diagnosed with prostate cancer (poorly differentiated adenocarcinoma, T3 N0 M1, stage D2) and initial endocrine therapy combined with castration and estrogen was effective. Four years later, the tumor marker of prostate-specific antigen (PSA) increased and the cancer was thought to be hormone-independent, refractory state. Alteration of antiandrogen from chlormadinone acetate to flutamide was effective and PSA was kept at low levels for 6 months. When PSA rose again, we started oral chemotherapy with tegafur.uracil. PSA decreased to normal range (complete response) and remained stable for 10 months. After that, a rapid increase of PSA was controlled for 7 months by oral chemotherapy with estramustine phosphate sodium and VP-16. This case indicates that alteration of antiandrogens or oral chemotherapy may be useful in some cases with hormone-refractory prostate cancer.
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PMID:[Long-term survival of hormone-refractory prostate cancer: a case report]. 1127 41

The purpose of this study was to determine the effects of interferon-beta (IFN-beta) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN-beta (AdIFN-beta), but not a vector encoding bacterial beta-galactosidase (AdLacZ), suppressed PC3MM2 tumors in a dose-dependent manner. At the highest dose (2x10(9) plaque-forming units, PFU), a single injection of AdIFN-beta (but not AdLacZ) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN-beta-treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN-beta expressed higher levels of IFN-beta and inducible nitric oxide synthase (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). In vitro analysis indicated that expression of bFGF and TGF-beta1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN-beta gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN-beta correlated with up-regulation of iNOS and down-regulation of angiogenesis.
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PMID:Adenovirus-mediated interferon-beta gene therapy suppresses growth and metastasis of human prostate cancer in nude mice. 1149 71

Transport of methotrexate (MTX) into human prostatic PC-3 cells was studied. Uptake of MTX vs concentration was saturable at pH 7.4 in cells grown in normal medium and in cells incubated for 24 h in folate-free medium (Km = 3.24 and 4.84 microM, respectively (P > 0.05, n = 3) and Vmax = 0.64 and 0.92 nmol x min(-1) x 10(-9) cells, respectively (P < 0.05, n = 3)). In contrast, uptake at pH 4.5 showed both a saturable component (Km = 1.03 microM, Vmax = 0.42 nmol x min(-1) x 10(-9) cells) and a nonsaturable, linear component. Uptake was inhibited by the structural analogs 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and folic acid (K(i) = 6.8, 10.9, and 89.6 microM, respectively). Uptake was inhibited by increasing concentrations of chloride ion, suggesting that MTX transport in PC-3 cells may be via an anion-exchange mechanism. Uptake was significantly decreased by high concentrations of sodium cyanide and sodium arsenate but not by sodium azide. Uptake was inhibited by the sulfhydryl inhibitor p-chloromercuriphenylsulfonate and by the anions probenecid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Uptake of MTX was independent of sodium ions in the medium. It is concluded that PC-3 human prostate cancer cells have a carrier-mediated system for the uptake of MTX and other folates.
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PMID:Transport of methotrexate into PC-3 human prostate cancer cells. 1156 25

The recent cloning and molecular characterization of the sodium iodide-symporter (NIS) has inspired novel approaches to the diagnosis and treatment of thyroidal and nonthyroidal malignancies. This article briefly reviews the physiologic regulation of NIS expression by cytokines, the expression in benign and malignant thyroidal diseases, and the expression in extrathyroidal tissues. Current concepts for NIS-based cancer therapy in thyroidal and extrathyroidal tumors are presented. The recent discovery of NIS expression in a majority of breast cancers as well as its promising application for prostate cancer imply potential applications in diagnostic imaging and radioiodine anticancer therapy for these highly common and lethal malignancies.
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PMID:Sodium iodide symporter-based strategies for diagnosis and treatment of thyroidal and nonthyroidal malignancies. 1157 53

The effects of selenium exposure were studied in LNCaP human prostate cancer cells, and this same cell line adapted to selenium over 6 months to compare acute versus chronic effects of sodium selenite, the latter most closely resembling human clinical trials on the effects of selenium in cancer prevention and therapy. Our results demonstrated that oxidative stress was induced by sodium selenite at high concentrations in both acute and chronic treatments, but outcomes were different. After acute exposure to selenite, cells exhibited mitochondrial injury and cell death, mainly apoptosis. After chronic exposure to selenite, cells showed growth inhibition caused by cell cycle arrest, increased numbers of mitochondria and levels of mitochondrial enzymes, and only minimal induction of apoptosis. Immunoblotting analysis revealed that multiple proteins were up-regulated by chronic exposure to selenite. Among them, only up-regulation of manganese superoxide dismutase and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), proteins known to be redox sensitive and to have cell cycle regulatory functions, correlated with cell growth inhibition. Our results in selenite-adapted cells suggest that selenium may exert its effects in human prostate cancer cells by altering intracellular redox state, which subsequently results in cell cycle block.
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PMID:Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. 1158 38

A two-part hypothesis has been tested, which proposes that (1) prostate cancer cells are galvanotactic (i.e. respond to an electric field by moving directionally) and (2) voltage-gated Na+ channel activity, which was shown previously to be expressed specifically by strongly metastatic cells, controls galvanotaxis. Two well-defined rat ('Dunning') cell lines, originally derived from the same prostate tumour but differing markedly in their metastatic ability, were used. Cells were exposed to exogenous direct-current electric fields of physiological strength (0.1-4.0 V cm(-1)), their reactions were recorded by light microscopy and analysed by a quantitative tracking method. Voltage-gated Na+ channel activity was modulated pharmacologically using a range of concentrations of a specific channel blocker (tetrodotoxin) or an opener (veratridine). The results showed that the highly metastatic MAT-LyLu cells responded to the application of the electric field strongly by migrating towards the cathode. By contrast, the weakly metastatic AT-2 cells gave no such response. Tetrodotoxin suppressed the galvanotactic response of the MAT-LyLu cells whereas veratridine enhanced it. Both compounds had little effect on the AT-2 cells. These results are consistent with functional voltage-gated Na+ channel expression occurring specifically in highly metastatic cells. This is also the first demonstration of control of galvanotaxis, in any cell type, by voltage-gated Na+ channel activity. The possible underlying mechanisms and the in vivo relevance of these findings are discussed.
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PMID:Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltagegated Na+ channel activity. 1168 96

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N(G)-monomethyl-L-arginine (1, 2, 4 micromol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.
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PMID:Low-dose estrogen supplementation improves vascular function in hypogonadal men. 1171 90

An 82-year old man received total androgen blockade therapy (bilateral orchiectomy and 375 mg/day flutamide) for the treatment of stage C prostate cancer. Serum PSA levels were undetectable for 13 months and thereafter increased gradually. We administered estramustine phosphate sodium (EPS) instead of flutamide under the diagnosis of hormone refractory prostate cancer. EPS therapy was discontinued after 9 months because serum PSA levels increased again. Then, the patient complained of bilateral breast nodules and pain. Bilateral mammectomies were performed due to bilateral breast cancers which had been diagnosed by aspiration biopsies and radiographic examinations, but he died four months after the operations. Final pathological diagnosis was ductal adenocarcinoma of the breasts. Immunohistochemical study revealed expressions of PSA in the breast cancers. We diagnosed double cancers of the prostate and the breast because of the different expression patterns of progesterone receptor between them. We review the literatures and discuss the differential diagnosis of prostate cancer and PSA-producing breast cancer.
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PMID:[A male case of primary bilateral breast cancers during estrogen therapy for prostate cancer]. 1176 69

Telomerase activity is involved in cellular immortality. We have recently demonstrated that telomerase activity is closely associated with cell proliferation in prostate cancers. Telomerase is composed primarily of the catalytic subunit (hTERT) and the RNA template (hTERC), and hTERT expression is regulated by several factors such as c-MYC and p21(Waf1). Histone deacetylase (HDAC) inhibitors are known to modulate transcription and exhibit antiproliferative effects on cancer cells. The present study was designed to evaluate the effects of HDAC inhibitors on hTERT mRNA expression in prostate cancer cells. LNCaP and PC-3 cells were treated with HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB); mRNA expression and telomerase activity were evaluated by RT-PCR and the TRAP assay, respectively. In LNCaP cells, hTERT mRNA expression was suppressed at 1 and 3 hr after treatment with 1 microM TSA and 4 mM NaB, respectively, followed by inhibition of telomerase activity. The inhibition of hTERT mRNA expression preceded suppression of cell proliferation. In PC-3 cells, TSA and NaB also inhibited cell proliferation, hTERT mRNA expression and telomerase activity. In both cell lines, TSA and NaB had no effect on hTERC expression, or on expression of c-myc and p21(Waf1) mRNA. These effects of TSA and NaB were unlikely to be consequences of cell cycle arrest, apoptosis, or cell differentiation. Thus, HDAC inhibitors down-regulated telomerase activity via suppression of hTERT mRNA expression. Our study identified a novel mechanism for the antiproliferative effects of HDAC inhibitors on prostate cancer cells.
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PMID:Histone deacetylase inhibitors suppress telomerase reverse transcriptase mRNA expression in prostate cancer cells. 1180 87

The activation of soluble guanylate cyclase by bradykinin and sodium nitroprusside (SNP), a direct activator of soluble guanylate cyclase, was evaluated in androgen-sensitive LNCaP and androgen-independent PC3 and DU145 prostate cancer cells. Bradykinin and SNP activated soluble guanylate cyclase in LNCaP cells, but not in PC3 and DU145 cells. Western blot analysis revealed that the bradykinin B2 receptor, Gqalpha, phospholipase Cgamma and endothelial nitric oxide synthase were expressed in LNCaP, PC3 and DU145 cells. However, both Western blotting and reverse transcriptase--polymerase chain reaction indicated that soluble guanylate cyclase was only expressed in LNCaP cells. These results demonstrate that the impaired bradykinin-soluble guanylate cyclase pathway in PC3 and DU145 cells is likely due to lack of expression of soluble guanylate cyclase.
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PMID:The bradykinin/soluble guanylate cyclase signaling pathway is impaired in androgen-independent prostate cancer cells. 1182 65


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