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)

Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy expenditure in 10 men with advanced stage C and D prostate cancer receiving a gonadotropin-releasing hormone (GnRH) agonist (Buserelin). Metabolic parameters and nutritional status were determined at 0, 2, 6, and 12 months of therapy. Baseline measurements of plasma leucine appearance (76.2 +/- 5.4 microM/kg/h) and HGP rates (80.1 +/- 2.9 mg/m2/min) were greater than previously reported for normal volunteers. GnRH agonist therapy in prostate cancer patients was associated with a significant reduction in serum testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), and cortisol, and significant increases in triiodothyronine (T3) and free triiodothyronine (free T3). Neither basal energy expenditure nor plasma leucine appearance rates were changed over time, but there were significant linear reductions in HGP rates (80.1 +/- 2.9 mg/m2/min, mean +/- SEM; 79.9 +/- 2.3, 73.7 +/- 3.4, 72.5 +/- 2.3; P less than .01; baseline, 2, 6, and 12 months, respectively, by repeated measures ANOVA). In all patients, significant increases in body weight, triceps skin fold, cholesterol, and fat mass were noted. Total body water content was not significantly increased after the 12-month period; therefore, the weight gain seen in these patients was water-free tissue, ie, fat mass.
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PMID:Nutritional and metabolic effects of gonadotropin-releasing hormone agonist treatment for prostate cancer. 212 81

Chemoprevention trials in prostate cancer would involve excessively long follow-up if conventional endpoints of efficacy are used. Prostatic intraepithelial neoplasia (PIN) may be an appropriate surrogate endpoint for monitoring outcome during prostate cancer chemoprevention studies. To address the question of whether PIN could be stratified into "stable" PIN and PIN likely to progress to invasive cancer, we selected patients with a single focus of peripheral zone cancer with ipsilateral and contralateral high-grade PIN. Sixteen patients met these criteria from a series of 550 patients treated by radical prostatectomy. We examined the rate of apoptosis in PIN and prostate cancer tissues by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on hematoxylin and eosin stained histological sections. Significant differences (ANOVA: p < 0.05) were detected between foci of prostatic intraepithelial neoplasia contralateral to the cancer and the cancer itself. There was no difference in the apoptotic index between a given cancer and a focus of PIN ipsilateral to the tumor in the same section. However, the range of apoptotic indices overlapped in all categories. Apoptotic indices appear to parallel the biological activity of PIN and malignant prostatic tissue, but may be of little benefit when used alone in monitoring the outcome of chemopreventive therapy in an individual patient.
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PMID:Apoptotic index as a biomarker in prostatic intraepithelial neoplasia (PIN) and prostate cancer. 782 93

Paraffin embedded and formalin fixed needle biopsies of prostate cancer (PC) were used to immunocytochemically detect the p120 nucleolar protein in relation to the Gleason histological gradings (GHG), the labelling indices of proliferating nuclear immunocytochemical markers (PCNA/Cyclin, Ki-67/MIB1) and the argyrophilic nucleolar region (AgNOR) rate. The twenty-six cases of PC (6 from large histological samples and 20 from needle biopsies) were equally distributed into low (< or = 6) or high (> or = 7) GHG groups. The p120 nucleolar protein immunocytochemical reaction was randomly expressed in large histological sections but uniformly distributed without gaps in needle biopsy sections. Only on the latter were quantitative values of PCNA/Cyclin (23.2 in low and 45.3 in high GHG), Ki-67/MIB1 (13.8 in low and 43.3 in high GHG) and AgNOR (5.0 in low and 7.5 in high GHG) related to those of p120 nucleolar protein (0.8 in low and 3.8 in high GHG). The values of all these cell cycle markers increased from low to high GHG of PC, all four reaching high statistical significance between the two groups (ANOVA-two tailed p < 0.0001). The PCNA/Cyclin index showed a higher positivity than the Ki-67/MIB1 index in PC with low GHG but not in PC with high GHG. In conclusion, paraffin embedded and formalin fixed PC needle biopsies exhibit a higher diagnostic PCNA/Cyclin than Ki-67/MIB1 index for cases presenting differentiated features, whereas p120 nucleolar protein detection seems to be a suitable marker of poorer outcome of PC.
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PMID:Immunohistochemical detection of cell-cycle associated markers on paraffin embedded and formalin fixed needle biopsies of prostate cancer: correlation of p120 protein expression with AgNOR, PCNA/cyclin, Ki-67/MIB1 proliferation-scores and Gleason gradings. 961 90

The use of cylindrical palladium-cobalt alloy rods has proven effective in the clinical ablation of prostate cancer. In order to thermally destroy tissue, the ferromagnetic implants must heat to temperatures greater than 42 degrees C and produce a power output of at least 400 mW. However, localized cold work such as bending may effect the heating characteristics of these rods and have detrimental clinical effect. Three different types of test devices were manufactured to introduce cold work at one point in the implant: a sharp bend, a curvature, and an MTS three-point bend. After bending, each rod was then restraightened. Rod power output before and after bending was measured by calorimetry. Statistical comparison of power output for prebent and restraightened rods versus degrees bent was performed through the use of the SAS MIXED procedure to fit a mixed-model repeated-measures ANOVA with the use of multivariate models. In vitro testing showed that there was only a small change in the power output before and after rods were cold worked regardless of the type of bending. Therefore, localized cold work does not affect the clinical heating characteristics of rods.
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PMID:The effects of localized cold work on the heating characteristics of thermal therapy implants. 1178 25

We have shown previously that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits survival of PC-3 and LNCaP human prostate cancer cells in culture, whereas proliferation of a normal prostate epithelial cell line is minimally affected by AITC even at concentrations that are highly cytotoxic to the prostate cancer cells. The present studies were designed to test the hypothesis that AITC administration may retard growth of human prostate cancer xenografts in vivo. Bolus i.p. injection of 10 micromol AITC, three times per week (Monday, Wednesday and Friday) beginning the day of tumor cell implantation, significantly inhibited the growth of PC-3 xenograft (P < 0.05 by two-way ANOVA). For example, 26 days after tumor cell implantation, the average tumor volume in control mice (1025 +/- 205 mm3) was approximately 1.7-fold higher compared with AITC-treated mice. Histological analysis of tumors excised at the termination of the experiment revealed a statistically significant increase in number of apoptotic bodies with a concomitant decrease in cells undergoing mitosis in the tumors of AITC-treated mice compared with that of control mice. Western blot analysis indicated an approximately 70% reduction in the levels of anti-apoptotic protein Bcl-2 in the tumor lysate of AITC-treated mice compared with that of control mice. Moreover, the tumors from AITC-treated mice, but not control mice, exhibited cleavage of BID, which is known to promote apoptosis. Statistically significant reduction in the expression of several proteins that regulate G2/M progression, including cyclin B1, cell division cycle (Cdc)25B and Cdc25C (44, 45 and 90% reduction, respectively, compared with control), was also observed in the tumors of AITC-treated mice relative to control tumors. In conclusion, the results of the present study indicate that AITC administration inhibits growth of PC-3 xenografts in vivo by inducing apoptosis and reducing mitotic activity.
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PMID:Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. 1289 4

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are synthetic surfactants used in Japan. An epidemiological study of workers exposed to PFOA revealed a significant increase in prostate cancer mortality. A cross-sectional study of PFOA-exposed workers showed that PFOA perturbs sex hormone homeostasis. We analyzed their concentrations in surface water samples collected from all over Japan by LC/MS with a solid phase extraction method. The lowest limits of detection (LOD) (ng/L) were 0.06 for PFOA and 0.04 for PFOS. The lowest limits of quantification (LOQ) (ng/L) were 0.1 for both analytes. The levels [geometric mean (GM); geometric standard deviation (GS)] (ng/L) of PFOA and PFOS in the surface waters were GM (GS): 0.97 (3.06) and 1.19 (2.44) for Hokkaido-Tohoku (n=16); 2.84(3.56) and 3.69 (3.93) for Kanto (n=14); 2.50 (2.23) and 1.07 (2.36) for Chubu (n=17); 21.5 (2.28) and 5.73 (3.61) for Kinki (n=8); 1.51 (2.28) and 1.00 (3.42) for Chugoku (n=9); 1.93 (2.40) and 0.89 (3.09) for Kyushu-Shikoku (n=15). The GM of PFOA in Kinki was significantly higher than in other areas (ANOVA p<0.01). Systematic searches of Yodo and Kanzaki Rivers revealed two highly contaminated sites, a public-water-disposal site for PFOA and an airport for PFOS. The former was estimated to release 18 kg of PFOA/d. PFOA in drinking water in Osaka city [40 (1.07) ng/L] was significantly higher than in other areas. The present study confirms that recognizable amounts of PFOA are released in the Osaka area and that people are exposed to PFOA through drinking water ingestion.
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PMID:Perfluorooctanoate and perfluorooctane sulfonate concentrations in surface water in Japan. 1496 Aug 30

Our purpose was to compare the three-field and the four-field planning techniques in patients with localized prostate cancer. Twenty patients with localized prostate cancer stage (T1-T2N0M0) were chosen for the analysis of treatment plans. Simulation and CT planning were performed in all cases in the supine position with a "comfortably" full bladder. The planning treatment volume (PTV) was defined as the prostate gland with a 10 mm margins around the clinical target volume (CTV), except for the posterior margin (prostate gland - the anterior part of rectum wall), where a 5 mm margin was applied. The clinical target volume (CTV) was defined as prostate gland. For each patient the following organs at risk (OAR) were outlined: rectum, bladder, and right femoral head. The following three-field and four-field plans were made: 3 field techniques with beam angles orientations 0 degree, 120 degrees, 240 degrees and 0 degree, 90 degrees, 270 degrees, and 4 field technique (0 degree, 90 degrees, 180 degrees, 270 degrees). Two versions of treatment plans were also made including different range of applied energy of photons (6 MV or 20 MV) for the therapeutic machine - Clinac 2300 CD. Beam portals were conformal by shaped by a multileaf collimator (MLC). The daily fractionation dose 1.8 Gy and the total dose 73.8 Gy were applied in each case. One hundred and twenty treatment plans were made and compared according to the following parameters: the mean total dose (MTD) in the target, the tumor control probability (TCP), the mean total dose (MTD) in the OAR (rectum, bladder, and right femoral head), the normal tissue complication probabilities (NTCP), and the volume of OARs which received arbitrary chosen fraction (%) of the total prescribed dose (73.8 Gy=100%). ANOVA statistical methods to verify the significance of differences between the treatment plans were used. There were no significant differences in the distribution of MTD and TCP in the PTV for the evaluated treatment plans. There were no significant differences in the MTD, NTCP, V80, and V90 distribution in bladder. The distribution of MTD, NTCP, and V80 for rectum indicated that lower parameters were achieved in the case of the three-field technique with the orientation of beams 0 degree, 90 degrees, 270 degrees. The distribution of MTD, NTCP, and V70 in right femoral head for each treatment plan was below the tolerance dose. The study has shown that the three-field technique (an anterior and two opposing lateral fields with the portals orientation 0 degree, 90 degrees, 270 degrees) and applied energy photons 20 MV, provides the best rectal protection. All evaluated plans according to the dose distribution in the target (PTV) have not indicated any significant differences. None of the techniques has shown any significant advantages in sparing bladder. The risk of morbidity in the femoral heads for all the applied techniques, in a dose up to 73.8 Gy was not a therapeutic problem. However, the three-field technique with beams orientation 0 degree, 120 degrees, 240 degrees gave the best sparing effect for femoral heads.
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PMID:The comparison of radiotherapy techniques for treatment of the prostate cancer: the three-field vs. the four-field. 1500 63

We assessed the longitudinal alteration of the quality of life (QOL) of patients with localized prostate cancer after radical prostatectomy or hormonoradiotherapy during 3-y follow-up. In addition, we examined the impact on QOL of initiation of second treatment after failure of primary treatment. In all, 135 patients with localized prostate cancer who underwent radical retropubic prostatectomy (RP) (N=84) or external beam radiotherapy with neoadjuvant hormone (XRT) (N=51) at our institute and who had a minimum follow-up of 3 y were included in this study. Data were collected prospectively, at baseline, at 3 months after treatment, at 1 y, and annually thereafter. QOL, generic and disease-targeted was evaluated using the European Organization for Research and Treatment of Cancer Prostate Cancer QOL Questionnaire, the Sapporo Medical University Sexual Function Questionnaire, the International Prostate Symptom Index Quality of Life Score and similar questions regarding bowel function. Repeated-measures ANOVA revealed significantly different patterns of alteration in the domains of QOL, with the exception of several domains, between the RP and XRT groups. Rapid decline of sexual function and increase in sexual bothersomeness were followed by slight amelioration throughout follow-up in the RP group, and did not change thereafter in the XRT group. Overall satisfaction with urinary condition significantly improved after treatment and that with bowel condition was stable during follow-up in both of the groups. Failure of primary treatment and initiation of salvage treatment had no impact on QOL. This prospective study revealed longitudinal alteration of QOL status of patients undergoing treatment for localized prostate cancer, but did not yield any conclusions regarding effect of treatment failure and second treatment on QOL due to small sample size. It should be noted that different instruments for assessment of QOL can generate different outcomes.
Prostate Cancer Prostatic Dis 2004
PMID:A 3-y prospective study of health-related and disease-specific quality of life in patients with nonmetastatic prostate cancer treated with radical prostatectomy or external beam radiotherapy. 1511 81

Disease recurrence following radical prostatectomy is a major concern in prostate cancer patients. Gleason scores are useful in predicting recurrence. Low Gleason scores are usually associated with long disease-free intervals, while high Gleason scores are suggestive of early recurrence. However, prediction of recurrence has been difficult with intermediate Gleason scores. Clusterin is a ubiquitous secretory sulfated glycoprotein. It is also an antiapoptotic mediator in prostate cancer. The objective of the present study is to determine if clusterin can serve as a predictive biomarker for recurrence of prostate cancer with intermediate Gleason scores in patients following radical prostatectomy. Prostatic specimens with Gleason score of 6 (3+3) or 7 (3+4) were obtained from the archival bank. Three groups of specimens were investigated. The first group was from nine patients who developed recurrent disease according to a persistent rise of serum PSA within 3 years following radical prostatectomy. Those in the second group and the third group were from patients who showed no evidence of disease recurrence for at least 5 y (11 patients) and 10 y (eight patients), respectively following the surgery. Histological sections were subjected to immunohistochemical staining using a monoclonal antibody specific for clusterin. The staining intensity was scored as 0, 1, 2, and 3, with 0 being no staining, 1 showing less than 25% positive staining, 2 being 25-50% positive, and 3 showing greater than 75% positive staining. One-way ANOVA with Bonferroni correction was used for statistical analysis. Evaluation of the scores of clusterin staining was carried out according to four specific areas in each specimen. They were (a) benign epithelial cells, (b) malignant epithelial cells (cancer epithelia), (c) stromal cells surrounding benign cells, and (d) stromal cells surrounding malignant cells (cancer stroma). Staining score in prostatic epithelial cells, benign as well as malignant, showed no significant relationship among the three patient groups. However, when staining scores in stromal cells were compared, there was a significant difference between patients with recurrent disease and those showed no evidence of disease recurrence for at least 10 y. Results of this preliminary study support the important role of clusterin in the stromal component for prostate cancer progression. Clusterin immunostaining may be useful to aid the prediction of chance of disease recurrence in patients with Gleason score 6 or 7 prostate cancer following radical prostatectomy. Further studies with a large number of cases are warranted to verify this preliminary finding.
Prostate Cancer Prostatic Dis 2004
PMID:Clusterin as a possible predictor for biochemical recurrence of prostate cancer following radical prostatectomy with intermediate Gleason scores: a preliminary report. 1534 64

To test our hypothesis that Cyclooyxgenase-2 (COX-2) inhibitors would stop the growth of breast and prostate cancer cells in vitro, two breast (MCF-7, ZR75-1) and two prostate cancer cell lines (PC-3, DU145) were treated with rofecoxib (Vioxx) or NS398. Cell growth was measured by MTT at 24 and 72 hours. Statistical analysis was performed by ANOVA. Significant growth inhibition (p < 0.05) was observed in all cell lines in a dose-dependent manner after treatment with COX-2 inhibitors. Rofecoxib inhibited cellular proliferation by inducing (p < 0.001) apoptosis in breast cancer cells. Our study indicates that COX-2 inhibition reduces the growth of human breast and prostate cancer in vitro. Human studies are needed to evaluate the clinical utility of rofecoxib treatment in breast or prostate cancers.
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PMID:COX-2 inhibition and cancer: experimental findings and clinical correlates. 1538 41


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