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)

There are two distinct phases during prostatic carcinogenesis with regard to tumor blood vessel development. During the first or prevascular phase, which may persist for years, cells that have undergone some but not all of the transformation steps undergo a limited amount of net growth, producing premalignant prostatic intraepithelial neoplastic (PIN) lesions. Most of these PIN lesions do not continue net growth and do not progress to produce histologically detectable cancer. Even the PIN lesions that do progress to cancer remain of limited virulence unless they undergo conversion to the second or angiogenic phase. Once this angiogenic phase is reached, new blood vessel development is greatly enhanced within the cancer. It is this enhanced tumor angiogenesis which allows these cancers both to grow continuously and to metastasize. Thus, inhibition of angiogenesis should be an effective chemopreventive approach for prostatic carcinogenesis. Linomide is a low molecular weight, water-soluble agent with excellent p.o. absorption and bioavailability. We have previously demonstrated that daily p.o. treatment with Linomide has antiangiogenic abilities against a series of rat and human prostatic cancer xenografts growing in vivo. In the present studies, we have demonstrated using Matrigel in in vivo angiogenesis assays that daily p.o. Linomide at 25 mg/kg/day inhibits angiogenesis induced by tumor necrosis factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and vascular endothelial growth factor. Using an N-methylnitrosourea initiation-androgen promotion model, Linomide was given p.o. at a daily dose as high as 25 mg/kg/day for at least 1 year without major toxicity while inhibiting the development of seminal vesicle/prostate cancers in male rats by >50%. Dose-response analysis demonstrated that a Linomide blood level of 50-100 microM is optimal for such chemoprevention. In addition, Linomide treatment at a dose of 25 mg/kg/day was able to inhibit by approximately 60% the incidence of N-methylnitrosourea and approximately 50% of 7,12-dimethyl-benz(a)anthracine-induced mammary carcinogenesis in female rats.
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PMID:Antiangiogenic treatment with linomide as chemoprevention for prostate, seminal vesicle, and breast carcinogenesis in rodents. 875 2

We report 3 cases in which ureteral stents were indwelt to treat hydronephrosis due to retroperitoneal fibrosis, resulting in aggravation of hydronephrosis and renal function. An urodynamic study was carried out to determine the factors that aggravated hydronephrosis. The subjects were a 59-year-old male with prostatic cancer and bilateral hydronephrosis due to intrapelvic lymph node metastasis, a 49-year-old female with retroperitoneal lymph node metastasis and bilateral hydronephrosis following surgery for stomach cancer, and a 65-year-old male with hydronephrosis due to idiopathic retroperitoneal fibrosis. Indwelling of ureteral stents in the 3 patients resulted in aggravation of hydronephrosis and renal function. Stent indwelling models of retroperitoneal fibrosis were produced using adult mongrel dogs. A pressure flow study was carried out through the nephrostomy in each experimental model to determine the intrapelvic pressure and urine volume. In all stent indwelling models, the urine volume showed changes similar to those in the controls. In the stent indwelling models, the intrapelvic pressure showed a significant increase with an increase in the volume of water instilled through the nephrostomy in the stent indwelling models with retroperitoneal fibrosis, unlike the controls and models with ureteral stenosis. In conclusion, the clinical cases and model experiment suggested that unlike partial ureteral stenosis, in ureters in which extensibility was disturbed in an extensive area, the indwelt stent caused an increase in the resistance of the liquid flowing in the ureter, aggravating hydronephrosis.
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PMID:[Three cases of hydronephrosis in which the indwelt ureteral stent was ineffective. Urodynamic studies using a stent indwelling model for retroperitoneal fibrosis]. 880 57

Diffusion NMR spectroscopy was used to study intracellular volume and apparent water diffusion constants in different cell lines (DU145, human prostate cancer; AT3, rat prostate cancer; MCF-7, human breast cancer; RIF-1, mouse fibrosacroma). The cells were grown on various matrices (collagen sponge, collagen beads, polystyrene beads) which enabled continuous growth in perfused high density cell culture suitable for NMR studies. In perfused cell systems, the attenuation of the water signal versus the squared gradient strength was fitted by the sum of two decaying exponentials. For the slowly decaying component the apparent water diffusion constant at 37 degrees C was 0.22 (+/-0.02) x 10(-9) s/m2 for all cell lines at diffusion times > 100 ms. It continuously increased up to 0.47 (+/-0.05) x 10(-9) s/m2 when the diffusion time was decreased to 8 ms, indicating restricted diffusion. No significant effect of the matrices was observed. The fractional volume of the slow component as determined from the biexponential diffusion curve correlated with the relative intracellular volume, as obtained from the cell density in the sample and the cell size as measured by light microscopy. Therefore, this simple NMR approach can be used to determine intracellular volume in perfused cell cultures suitable for NMR studies. Using this information in combination with spectroscopic data, changes in intracellular metabolite concentration can be detected even when the cellular volume is changing during the experiment. The apparent diffusion constant for the fast diffusing component varied with growth matrix, cell density and cell type and also showed the typical characteristics of restricted diffusion (increase of apparent diffusion constant with time).
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PMID:Intracellular volume and apparent diffusion constants of perfused cancer cell cultures, as measured by NMR. 917 32

Urodynamic examinations were performed in 82 patients with clinically localized prostate cancer before and after radical prostatectomy. A significant decrease in bladder capacity (396 ml to 331.9 ml), urethral closure pressure (89.6 cm H2O to 65.2 cm H2O) and functional profile length (61 mm to 25.9 mm) was noted. The continence rate after radical prostatectomy was 33.4% after 1 month, 69.4% after 3 months, 84.7% after 6 months, and 90.9% after 12 months, respectively. A correlation was found between urethral closure pressure and functional profile length and continence. A second urodynamic examination was performed 6 months after radical prostatectomy. Functional profile length and urethral closure pressure increased. These data suggest that restoration of continence is based on sphincteric parameters.
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PMID:[Urodynamic changes after radical prostatectomy]. 948 89

Monolithic microcapsules were designed and developed for controlled release of leuprorelin for one month following a single injection. Copoly (DL-lactic/glycolic) acid (PLGA) of copolymer ratio of 75/25 and average molecular weight of 14,000 was suitable for achieving steady serum leuprorelin levels in rats and dogs for 4 weeks. The clinical efficacy of these injectable microcapsules of leuprorelin has been widely proved for prostate cancer, endometriosis, and other sex hormone dependent diseases in about sixty countries. The interaction between the basic functional group of the drug and the carboxylic end group of PLGA was found to be the most important factor in preparing the microcapsules with a small initial burst, as shown with thyrotropin releasing hormone (TRH) and a water-soluble GPIIb/IIIa antagonist (TAK-029).
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PMID:[Design and development of controlled release of drugs from injectable microcapsules]. 954 55

After almost two decades, the research on LHRH antagonists has produced a number of decapeptides that are currently in clinical studies. The structures of these antagonists, unlike the agonists, differ substantially from that of LHRH. Five of the ten amino acids are unnatural and of D configuration. The structural combination of a hydrophobic N-terminus (residues 1, 2, and 3) and a basic/hydrophilic C-terminus (residues 6 and 8) was thought to be responsible for some HR reactions encountered with the second generation of LHRH antagonists. This side effect was greatly reduced by substituting the appropriate combination of amino acids at positions 5, 6, and 8. The next hurdle in the drug development of LHRH antagonists was solubility and aggregation. In the case of A-75998, water solubility was improved by 12- to 25-fold via substitution of NMeTyr at position 5. However, based on DLS analysis, the aqueous solutions still contained some large aggregates that were not visible to the naked eye. This formation of aggregates was eliminated on formulating A-75998 in Encapsin. In men, a single s.c. dose of 2 mg of A-75998 suppressed T to the castrate levels for over 30 hr. Other LHRH antagonists including ganirelix and cetrorelix are also in phase I/II clinical studies. Clinical studies with cetrorelix in prostate cancer; in vitro fertilization, and benign prostate hypotrophy have been reported.
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PMID:LHRH antagonists. 976 Jun 79

Optimum conditions for the direct reversed-phase LC determination of fluoride based on the ternary M-(F-)-(5-Br-PADAP) complexes [M = ZrIV or HfIV and 5-Br-PADAP = 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol] were evaluated. Chromatographic separation was performed with C18 end-capped column with an eluent consisting of acetonitrile-water (85 + 15 v/v) mixture of pH 4.0 +/- 0.3 (flow rate 1 ml min-1), and the eluate was monitored spectrophotometrically at lambda max = 585 nm. The calibration curves were linear over a wide range of fluoride concentrations: from 1 to 110 and 150 ng ml-1 for the ZrIV-(F-)-(5-Br-PADAP) and HfIV-(F-)-(5-Br-PADAP) systems, respectively (using a 20 microliters loop). Under such conditions the detection limits were 0.8 and 0.7 ng ml-1, respectively, and the quantification limit is 1.0 ng ml-1 for both methods. When a 100 microliters loop was used, the limits of both detection and quantification in the method based on the zirconium system were 0.2 ng ml-1. Using the proposed method, fluoride was determined directly in tap water, saliva and an anti-cancer agent for prostatic cancer (Leuprolid).
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PMID:Sensitive reversed-phase liquid chromatographic determination of fluoride based on its ternary systems with zirconium(IV) or hafnium(IV) and 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol. 983 Jan 65

Localized proton-stimulated echo acquisition mode (STEAM) spectroscopy was performed in seven patients with benign prostatic hyperplasia (BPH), six patients with prostate cancer, and seven healthy volunteers to determine whether citrate levels detected using a saddle-type external-body surface coil (two loops of 13 cm x 17 cm) could reliably discriminate BPH from prostatic cancer. Relative area ratios of citrate level to choline plus creatine or citrate to lipid signal were compared with postoperative pathologic histology findings. The metabolic signals were well detectable as much as the line width of water resonance was ranging from 5 to 9 hz. Average SNRs of citrate in BPH and prostate cancer were 11.4 and 1.9, respectively. The major finding was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate central gland. This was significantly (p < 0.01) reflected by lower mean citrate/[creatine+choline] peak area ratio and citrate/lipid peak area ratio observed for region of cancer (0.446 +/- 0.063, 0.097 +/- 0.030) compared with BPH (1.458 +/- 0.107, 0.786 +/- 0.162) and normal central gland (1.418 +/- 0.129, 0.175 +/- 0.011), respectively. These studies demonstrate the potential of citrate spectrum detected by an external-body surface coil as an in vivo marker for discriminating prostate cancer from BPH.
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PMID:In vivo differential diagnosis of prostate cancer and benign prostatic hyperplasia: localized proton magnetic resonance spectroscopy using external-body surface coil. 985 86

Using data from a case-control study conducted in Group Health Cooperative (GHC) of Puget Sound, we examined the relation between the use of electric blankets or heated water beds and the risk of prostate cancer. Cases were 175 prostate cancer patients ages 40-69 years. Controls were 258 male GHC members frequency matched to cases. The odds ratio (OR) for prostate cancer associated with the use of an electric blanket or heated water bed was 1.4 (95% confidence interval (CI) 0.9-2.2). The risk, however, did not tend to be higher with increasing months per year or years of use. This study did not provide clear evidence on the hypothesized association.
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PMID:Prostate cancer in relation to the use of electric blanket or heated water bed. 1053 2

In select cases of prostatic carcinoma, antikeratin 34betaE12 immunohistochemical analysis is diagnostically useful for specific labeling of basal cells. This antibody, however, is prone to variability in staining, and the optimal conditions were not, to our knowledge, previously defined. We combined steam heat with EDTA buffer (steam-EDTA) and protease digestion (steam-EDTA + protease) to optimize epitope retrieval of antikeratin 34betaE12 in 42 cases of prostatic cancer. Results were judged by the percentage of cells staining and by staining intensity. In benign epithelium, steam-EDTA + protease significantly increased the percentage of immunoreactive cells (from 74 to 93%) and the intensity of staining (from 2.1 to 3.0 on a scale of 0-3+) by comparison with protease alone (all P<.001). In high-grade prostatic intraepithelial neoplasia, the percentage of cells staining increased from 55 to 73% and intensity increased from 1.7 to 2.8 (both P<.001). Steam-EDTA + protease also minimized variability in results between cases, with essentially no background stromal staining. Cancer was negative in all of our cases by both methods. We conclude that steam-EDTA + protease significantly enhances basal cell immunoreactivity compared with protease treatment alone in noncancerous prostatic epithelium. This helps to prevent misinterpretation of histologic mimics of cancer, such as atrophic acini and high-grade prostatic intraepithelial neoplasia, that result from false-negative staining.
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PMID:Steam heat with an EDTA buffer and protease digestion optimizes immunohistochemical expression of basal cell-specific antikeratin 34betaE12 to discriminate cancer in prostatic epithelium. 995 Jan 54


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