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)

Cell culture systems provide an opportunity to evaluate the effects of carotenoids on molecular and cellular processes involved in proliferation and differentiation of prostate cancer cells. The stability and cellular uptake of beta-carotene (BC) by prostate cancer cells were investigated in vitro by use of various delivery methods and three human prostate adenocarcinoma cell lines: PC-3, DU 145, and LNCaP. Recovery of BC from the media (prepared from water-dispersible BC beadlets) significantly (p < 0.05) decreased after 12 hours in culture and continued to significantly decrease (p < 0.05) after 24, 48, 72, and 96 hours, an observation primarily attributed to BC degradation rather than isomerization, metabolism, or cellular uptake. The uptake of BC by prostate cancer cells was compared when delivered by tetrahydrofuran, BC-enriched bovine serum, water-dispersible BC beadlets, and artificial liposomes. Recovery of BC after three days in culture from enriched bovine serum medium was significantly (p < 0.05) greater than recovery from medium prepared by beadlets, tetrahydrofuran, or artificial liposomes. We conclude that BC is relatively unstable in vitro and that degradation products may contribute to biological responses. Furthermore, our studies indicate that enriched bovine serum provides a stable and physiological approach to carotenoid treatment of cells in culture.
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PMID:beta-Carotene stability and uptake by prostate cancer cells are dependent on delivery vehicle. 1089 29

Permanent prostate implant using 125I or 103Pd sources is a common treatment choice in the management of early prostate cancer. As sources of new designs are developed and marketed for application in permanent prostate implants, it is of paramount importance that their dosimetric characteristics are carefully determined, in order to maintain a high accuracy of patient treatment. This report presents the results of experimental measurements of the dosimetric parameters performed for a newly available 125I seed source, the model MED3631-A/M source (IoGold), manufactured by North American Scientific, Inc. The measurements were performed in a large scanning water phantom, using a diode detector. The positioning of the source and the diode detector was achieved by a computer-controlled positioning mechanism in the scanning water phantom. The dose rate constant in water for the new 125I source was measured in comparison with an existing 125I source of similar design and verified using thermoluminescent dosimetry (TLD) measurement. The radial dose function values for the source were measured using the diode detector. The measurement technique and the results are compared with the dose distribution parameters for the 125I sources discussed in the AAPM TG43 report and elsewhere [Med. Phys. 26, 570-573 (1999)]. For the dose rate constant in water of the new source, it is recommended that a value of 0.950 cGy/U-hr be used based on the NIST 1985 air-kerma strength calibration standard, or 1.060 cGy/U-hr based on the 1999 NIST air-kerma strength standard. The measured radial dose function values for the MED3631-A/M source agree closely with those of the model 6702 source. It is therefore recommended that the radial dose function values for the model 6702 125I source, as recommended by the AAPM TG43 report, be adopted for the new source as well.
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PMID:Experimental measurements of dosimetric parameters on the transverse axis of a new 125I source. 1133 69

Development of effective chemopreventive agents for human consumption requires conclusive evidence of their efficacy in animal models that have relevance to human diseases. Transgenic adenocarcinoma mouse prostate (TRAMP) is an excellent model of prostate cancer that mimics progressive forms of human disease inasmuch as 100% of males develop histological PIN by 8-12 weeks of age that progress to adenocarcinoma with distant site metastases by 24-28 weeks of age. In these animals, ornithine decarboxylase (ODC) activity (>3-fold) as well as protein expression (>4-fold) was found to be markedly higher in the dorsolateral prostate as compared with the nontransgenic littermates, suggesting their suitability to determine the chemopreventive effect of alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ODC, against prostate cancer. Using male TRAMP mice, we studied the effect of oral consumption of DFMO on development of prostate carcinogenesis and surrogate end point biomarkers related to prostate cancer progression. In two independent experiments, each consisting of 8 animals on test, the cumulative incidence of prostatic cancer development at 28 weeks of age in 16 untreated TRAMP mice was 100% (16 of 16), whereas 94% (15 of 16) and 69% (11 of 16) of the animals exhibited distant site metastases to lymph nodes and lungs, respectively. Oral consumption of 1% DFMO (w/v) in the drinking water to TRAMP mice from 8 to 28 weeks of age resulted in a significant decrease in (a) weight (59%) and volume (66%) of prostate, (b) genitourinary weight (63%), and (c) ODC enzyme activity (52%) in the dorsolateral prostate. Importantly, in none of the DFMO-fed TRAMP mice were any distant metastases to lymph node and lungs observed. Furthermore, DFMO treatment resulted in the marked reduction in the protein expression of proliferation cell nuclear antigen, ODC, and probasin in the dorsolateral prostate. The protein expression of antimetastases markers, i.e., E-cadherin and alpha- and beta-catenin, was found to be restored in DFMO-fed animals as compared with the non-DFMO-fed mice. These chemopreventive effects of DFMO were further confirmed by immunohistochemical analysis of the dorsolateral prostate. Histological analysis of the dorsolateral prostate of DFMO-fed animals displayed marginal epithelial stratification, a small number of cribriform structures, elongated hyperchromatic epithelial nuclei, and a significant increase in apoptotic index. Non-DFMO-fed animals, on the other hand, displayed extensive epithelial stratification with profound cribriform structures accompanied with marked thickening, remodeling, and hypercellularity of the fibromuscular stroma. In nontransgenic littermates fed with DFMO, no significant alterations in the above parameters were evident. These data demonstrate that ODC represents a promising and rational target for chemoprevention of human prostate cancer and that TRAMP mice are excellent models for screening of novel drugs and chemopreventive regimens for potential human use.
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PMID:Chemoprevention of prostate carcinogenesis by alpha-difluoromethylornithine in TRAMP mice. 1101 39

The health benefits of fruits and vegetables have been the subject of numerous investigations over many years. Two natural substances, quercetin (a flavonoid) and citrus pectin (a polysaccharide found in the cell wall of plants) are of particular interest to cancer researchers. Two modified versions of these substances - quercetin chalcone (QC) and a pH-modified citrus pectin (MCP) - are the focus of this study. Previous research has confirmed that quercetin exhibits antitumor properties, likely due to immune stimulation, free radical scavenging, alteration of the mitotic cycle in tumor cells, gene expression modification, anti-angiogenesis activity, or apoptosis induction, or a combination of these effects. MCP has inhibited metastases in animal studies of prostate cancer and melanoma. To date, no study has demonstrated a reduction in solid tumor growth with MCP, and there is no research into the antitumor effect of QC. This study examines the effects of MCP and QC on the size and weight of colon-25 tumors implanted in balb-c mice. Fifty mice were orally administered either 1 ml distilled water (controls), low-dose QC (0.8 mg/ml), high-dose QC (1.6 mg/ml), low-dose MCP (0. 8 mg/ml) or high-dose MCP (1.6 mg/ml) on a daily basis, beginning the first day of tumor palpation (usually eight days post-implantation). A significant reduction in tumor size was noted at day 20 in all groups compared to controls. The groups given low-dose QC and MCP had a 29-percent (NS) and 38-percent (p<0.02) decrease in size, respectively. The high-dose groups had an even more impressive reduction in size; 65 percent in the QC group and 70 percent in the mice given MCP (both p<0.001). This is the first evidence that MCP can reduce the growth of solid primary tumors, and the first research showing QC has antitumor activity. Additional research on these substances and their effect on human cancers is warranted.
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PMID:Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice. 1113 77

Assessing prostate metastases is difficult with conventional radiographic modalities as few patients have soft tissue involvement and most have only bone lesions. Even with FDG PET, problems due to decreased avidity compared to other tumor types can occur. We assessed PET's ability to monitor changes in such tumors during an anti-angiogenic therapy. We measured changes in tumor blood flow (15O), blood volume (11CO), 18F-FDG uptake and "metabolic volume" before and during thalidomide treatment, to see if these changes correlated with changes in PSA values.Six patients with androgen-independent prostate cancer were imaged with 18F-FDG, 11CO, and 15O water before and during (mean interval 63 days, range 55-76 days) thalidomide therapy (200-1200mg/day). Lesions were visually identified on FDG images (9 bone, 5 soft tissue lesions). VOI's were generated by 3D region growing, with a 50% maximum pixel threshold. These VOI's were registered with, and applied to, the 11CO and water studies. Correlations with PSA values were done using the Spearman rank test.The change in maximum (r = 0.77, p = 0.06) and mean FDG value (r = 0.83, p = 0.03), functional FDG volume (r = 0.66, p = 0.14), and 11-CO blood volume (r = 0.77, p = 0.06) all correlated with the change in PSA. Changes in blood flow values were smaller than the variance of the method for repeated measures, likely due to low flow values in bone.Changes in blood volume measured by 11CO, and the mean and peak activity and functional volume measured by 18F-FDG, correlate with changes in PSA and may be useful in monitoring anti-angiogenic therapy in prostate cancer.
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PMID:8:45-9:00. Using PET 18F-FDG, 11CO, and 15O-water for Monitoring Prostate Cancer During a Phase II Anti-angiogenic Drug Trial with Thalidomide. 1115 Jul 47

Low-energy photon emitting radionuclides encapsulated for a permanent implant are routinely applied in prostate cancer brachytherapy. Before clinical use, a new source design requires full dosimetric analysis and calibration standardization. The results of one such experimental measurement and analysis are reported here for a new design of 125I source, model I125-SL. Dose measurements were made using standard methods employing thermoluminscent dosimeters in a water equivalent plastic phantom, in accord with the AAPM Task Group #43 recommendation of liquid water reference material. Precision machined bores in the phantom located dosimeters and source(s) in a reproducible fixed geometry providing for transverse-axis and angular dose profiles over a range of distances from 0.17 to 10 cm. The data were analyzed in terms of parameters recommended by AAPM TG43. The dose-rate constant, lambda, was evaluated by two methods, the first with reference to a 60Cobalt standard, accounting for response variation with photon energy spectrum. Second, the dose-rate constant was determined with reference to phantom measurements using NIST traceable calibrated model 6702 and 6711 sources. The radial dose function, g(r), the anisotropy function, F(r,theta), the anisotropy factor, phi(an)(r), and the point-source approximation anisotropy constant, phi(an), were derived from one- and two-dimensional dose distribution data measured in the phantom, accounting for finite dosimeter volume and with attention to interchip effects. The results are compared to TG43 and other existing data for 125I sources. The new source is comparable to the model 6711 source design.
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PMID:Empirical dosimetric characterization of model I125-SL 125iodine brachytherapy source in phantom. 1119 Sep 63

Single-voxel J-resolved spectroscopy with oversampling in the F1 dimension was used to obtain water unsuppressed 1H spectra of in situ human prostate tissue in 40 previously untreated prostate cancer patients. Based on T2-weighted MRI and previous biopsy information, voxels were placed in regions of benign or malignant peripheral zone tissue, or in regions of predominantly glandular or stromal benign prostatic hyperplasia (BPH) within the central gland. The addition of a second J-resolved dimension allowed for the observation of the J-modulation of citrate, as well as the resolution of polyamines from overlapping choline and creatine signals. Regions of healthy peripheral zone tissue and glandular BPH all demonstrated high levels of citrate and polyamines, with consistent coupling and J-modulation patterns. Conversely, regions of malignant peripheral zone tissue and stromal BPH demonstrated low levels of citrate and polyamines consistent with prior in vivo and ex vivo studies. Moreover, water T2 relaxation times determined for healthy peripheral zone tissue (mean 128 +/- 15.2 msec) were significantly different than for malignant peripheral zone tissue (mean 88.0 +/- 14.2 msec, P = 0.005), as well as for predominantly glandular (mean 92.4 +/- 12.2 msec, P = 0.009) and stromal BPH (mean 70.9 +/- 12.1 msec, P = 0.003). This preliminary study demonstrates that J-resolved spectroscopy of the in situ prostate can be acquired, and the information obtained from the second spectral dimension can provide additional physiologic information from human prostate tissue in a reasonable amount of time (< 10 min).
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PMID:Single-voxel oversampled J-resolved spectroscopy of in vivo human prostate tissue. 1137 74

A rapid and highly sensitive method for the detection of formaldehyde utilizing selected ion flow tube-chemical ionization mass spectrometry is reported. Formaldehyde in aqueous biological samples is preconcentrated by distillation and directly analyzed using gas-phase thermal energy proton transfer from H30+; this procedure can be performed in 30 min. The method detection limit for formaldehyde based on seven replicate measurements of reference water samples (2.5 mL) is 80 nM at the 99% confidence level. Detection is linear up to 130 microM. This technique allows the first measurement of natural formaldehyde levels in human cancer cells in vitro. Elevated levels of formaldehyde relative to the reference water are observed for doxorubicin-sensitive cells (MCF-7 breast cancer, K562 leukemia, HeLa S3 cervical cancer) with estimated intracellular formaldehyde concentrations ranging from 1.5 to 4.0 microM, whereas formaldehyde in doxorubicin-resistant MCF-7/Adr breast cancer cells is essentially at reference level. This trend is inverted for prostate cancer cells LNCaP (sensitive) and DU-145 (resistant). Correlation of natural formaldehyde level with doxorubicin cytotoxicity is a function of the expression of enzymes that neutralize oxidative stress and the drug efflux pump, P-170 glycoprotein.
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PMID:Formaldehyde in human cancer cells: detection by preconcentration-chemical ionization mass spectrometry. 1146 45

Development of effective chemopreventive agents against prostate cancer (CaP) for humans requires conclusive evidence of their efficacy in animal models that closely emulates human disease. The autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops metastatic CaP, is one such model that mimics progressive forms of human disease. Employing male TRAMP mice, we show that oral infusion of a polyphenolic fraction isolated from green tea (GTP) at a human achievable dose (equivalent to six cups of green tea per day) significantly inhibits CaP development and increases survival in these mice. In two separate experiments, the cumulative incidence of palpable tumors at 32 weeks of age in 20 untreated mice was 100% (20 of 20). In these mice, 95% (19 of 20), 65% (13 of 20), 40% (8 of 20), and 25% (5 of 20) of the animals exhibited distant site metastases to lymph nodes, lungs, liver, and bone, respectively. However, 0.1% GTP (wt/vol) provided as the sole source of drinking fluid to TRAMP mice from 8 to 32 weeks of age resulted in (i) significant delay in primary tumor incidence and tumor burden as assessed sequentially by MRI, (ii) significant decrease in prostate (64%) and genitourinary (GU) (72%) weight, (iii) significant inhibition in serum insulin-like growth factor-I and restoration of insulin-like growth factor binding protein-3 levels, and (iv) marked reduction in the protein expression of proliferating cell nuclear antigen (PCNA) in the prostate compared with water-fed TRAMP mice. The striking observation of this study was that GTP infusion resulted in almost complete inhibition of distant site metastases. Furthermore, GTP consumption caused significant apoptosis of CaP cells, which possibly resulted in reduced dissemination of cancer cells, thereby causing inhibition of prostate cancer development, progression, and metastasis of CaP to distant organ sites.
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PMID:Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. 1150 10

Nutritional factors, especially phytoestrogens, have been extensively studied for their potential beneficial effects against hormone-dependent and age-related diseases. The present study describes the short-term effects of dietary phytoestrogens on regulatory behaviors (food/water intake, locomotor activity and body weight), prostate weight, prostate 5alpha-reductase enzyme activity, reproductive hormone levels, and testicular steroidogenic acute regulatory peptide (StAR) levels in adult Sprague-Dawley rats. Animals were fed either a phytoestrogen-rich diet containing approximately 600 microg/g isoflavones (as determined by HPLC) or a phytoestrogen-free diet. After 5 weeks of consuming these diets, plasma phytoestrogen levels were 35 times higher in animals fed the phytoestrogen-rich vs phytoestrogen-free diets. Body and prostate weights were significantly decreased in animals fed the phytoestrogen-rich diet vs the phytoestrogen-free fed animals; however, no significant change in prostate 5alpha-reductase enzyme activity was observed between the treatment groups. Locomotor activity levels were higher in the phytoestrogen-rich vs the phytoestrogen-free animals during the course of the treatment interval. Plasma testosterone and androstenedione levels were significantly lower in the animals fed the phytoestrogen-rich diet compared with animals fed the phytoestrogen-free diet. However, there were no significant differences in plasma LH or estradiol levels between the diet groups. Testicular StAR levels were not significantly different between the phytoestrogen-rich vs the phytoestrogen-free fed animals. These results indicated that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels over a relatively short period can significantly alter body and prostate weight and plasma androgen hormone levels without affecting gonadotropin or testicular StAR levels. The findings of this study identify the biological actions of phytoestrogens on male reproductive endocrinology and provide insights into the protective effects these estrogen mimics exert in male reproductive disorders such as benign prostatic hyperplasia and prostate cancer.
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PMID:Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. 1152 39

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