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

Controversial views exist on the link between prostatic cancer and consumption of high-fat (HF) diet. This topic was examined in experimental prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine (BOP). Groups of Wistar-derived MRC rats were fed a semipurified diet containing either 5% (low fat = LF) or 24.6% (HF) corn oil for life, beginning after weaning. In the short-term study, treatment with testosterone significantly increased the rate of cellular DNA synthesis (as determined by autoradiographs after tritiated thymidine injection) that was not influenced by the level of dietary fat. HF diet alone depressed the rate significantly in the dorsal lobe only. There was a significant increase in the plasma level of estradiol, a decrease in the level of luteinizing hormone, but no changes in the level of follicle-stimulating hormone (FSH) in rats treated with testosterone, with no differences between the HF and LF groups. However, HF in the absence of testosterone depressed the serum FSH level. In the carcinogenicity experiment, all rats fed HF or LF diet developed prostatic cancers (mostly adenocarcinomas). The incidence, however, was significantly higher in testosterone-treated rats. Dietary fat did not influence the incidence, histological patterns, or anatomical distribution of tumors, and there were no differences in the parameters between the HF- and LF-fed groups. Long-term administration of testosterone significantly lowered serum levels of luteinizing hormone but did not change the FSH level and affected estradiol levels to a variable extent. These values were not influenced by dietary fat. However, in the HF-BOP group, significantly higher levels of FSH were found compared with the values in the LF-BOP group. We concluded that (a) under the described experimental conditions, dietary fat, fed ad libitum, does not influence the patterns of prostatic cancer induced in rats by BOP; (b) testosterone alters the serum levels of estradiol and luteinizing hormone; and (c) both testosterone and estradiol could be involved in carcinogenesis.
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PMID:Effects of high-fat diet on the patterns of prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine and testosterone. 190 29

Rectal carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) in male MRC Wistar rats was shown to be inhibited by exogenous testosterone (T) when the hormone was given during, but not after, administration of the carcinogen. This effect was independent of the dose and frequency of BOP, which was given either weekly for 20 weeks orally or daily for 3 days subcutaneously. Since, except for prostatic cancer, the incidence and the patterns of other BOP-induced tumors were not altered by T, this hormone seems to play a specific role in the rectal carcinogenesis of BOP.
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PMID:Prevention of rectal cancer induced by N-nitrosobis(2-oxopropyl)-amine by exogenous testosterone in MRC rats. 280 25

To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.
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PMID:Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells. 283 49

The effect of exogenous testosterone on prostatic carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) in intact and castrated rats was examined in Wistar-derived MRC rats. Daily administration of BOP (either s.c. or i.g.) for 3 days, at a dose of 20 mg/kg b.w. at the heights of prostatic cell proliferation induced by testosterone, led to development of a large number of prostatic tumors, the incidence of which, however, was dependent on the duration of testosterone administration. Testosterone given for life following BOP administration induced prostatic cancer in over 60% of rats, regardless of whether BOP was given orally or s.c., or whether the rats were orchiectomized or not, whereas tumor incidence was significantly lower in rats treated with testosterone for only a short period of time. One (3%) orchiectomized rat, which received testosterone only during BOP treatment, and four (15%) of rats treated with testosterone only for life also developed carcinomas. Histologically, a large number of BOP + testosterone-induced prostatic tumors were adenocarcinomas of various histological patterns and arose primarily from the dorsal lobe, whereas the great majority of squamous cell carcinomas were found in the ventral lobe. Simultaneously induced tumors were papillomas and carcinomas of the urinary bladder and urethra. Testosterone appeared to enhance the incidence of urinary bladder tumors, but not of the urethral tumors, whereas orchiectomy inhibited urethral carcinogenesis, and, to much lesser extent, urinary bladder tumor development. Rats treated weekly for 20 weeks with BOP (10 mg/kg/week i.g.) did not develop any prostatic tumors and all rats died of rectal cancer. Of rats treated similarly with BOP and with testosterone pellets for life following the last injection of BOP, 17% of rats developed prostatic cancer, all of the squamous cell type. Simultaneous testosterone and BOP treatment for 20 weeks followed by testosterone pellets for life resulted in a 39% tumor incidence (three adenocarcinomas, one anaplastic carcinoma, and five squamous cell carcinomas). The overall results suggest that testosterone plays an important role in the initiation of prostatic carcinogenesis, whereas the promotional phase is governed by the interaction of testosterone with other factors.
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PMID:Induction of prostatic carcinomas and lower urinary tract neoplasms by combined treatment of intact and castrated rats with testosterone propionate and N-nitrosobis(2-oxopropyl)amine. 366 75

Weekly intragastric application of N-nitrosobis(2-oxopropyl) amine (BOP) at a dose of 10 mg/kg body wt induced prostatic cancer in 5 out of 15 MRC rats. Hyperplasia and metaplasia of the prostatic gland were found in 13 rats with or without cancer. All tumors had developed in the dorsal lobe, had reached a size of up to 20 mm and were invasive. Distant metastases were not observed. Although hyperplastic lesion were of a glandular type, all carcinomas had squamous cell character. All cases of prostatic cancer were associated with papillomas or carcinomas of the urethral epithelium, which had initially developed in the colliculus seminalis. The induction of prostatic cancer for the first time by a systemic application by a nitrosamine provides a promising model for understanding basic principals of prostatic cancer.
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PMID:A new prostatic cancer model: systemic induction of prostatic cancer in rats by a nitrosamine. 617 36

Weekly intragastric treatment with N-nitrosobis(2-oxopropyl)amine or N-nitrosobis(2-hydroxypropyl)amine induced hyperplastic, preneoplastic and neoplastic prostatic changes in greater than 80% of MRC rats. The lesions initially appeared as focal or multifocal proliferations of alveolar epithelium in a cribriform pattern which, in all but one case, underwent progressive changes, often tending toward squamous cell formation. Tumors, found primarily in the ventral prostate, demonstrated various degrees of differentiation and invasive growth. A few neoplasms developed in the seminal vesicles; however all were of a glandular type. The sequential alteration of induced lesions is described and the possible reasons for the squamous cell character of most tumors discussed. Prostatic cancer induction by systemic application of specific nitrosamines could provide a unique tool for investigating important aspects of the disease.
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PMID:Prostatic cancer induced in MRC rats by N-nitrosobis(2-oxopropyl)-amine and N-nitrosobis(2-hydroxypropyl)amine. 618 48

Increasingly animal and clinical studies suggest that intermittent therapy may improve the duration of hormone dependence in patients with prostate cancer. However there remains uncertainty as to optimal duration of treatment and level of prostate-specific antigen (PSA) before treatment is restarted. The aim of this study was to identify risk factors that predict duration of therapy in prostate cancer patients receiving intermittent hormone therapy. Any patients who had achieved PSA complete remission after hormone therapy for metastatic or locally advanced prostate cancer were included in the study. Fifty patients entered on intermittent hormone therapy after achieving a PSA complete remission. In all, 57% of patients remained off treatment at 12 months and the median time for restarting further hormone therapy was 14 months. At 1 y, 95% of patients retreated are progression free and overall 92% are alive at 3 y. There was some evidence that there was a slower progression to require treatment in older M0 patients and those who had been on treatment for more than 9 months. Although M0 patients receiving radiation concurrently after initial hormone down staging had a slower recurrence rate, 53% of M0 patients treated with hormone alone remained off hormones for more than one year. Clearly selection cannot be excluded as a cause for this good survival. However as overall survival in this study is at least as good as that of patients with M0 disease on hormone therapy in the immediate arm of the MRC immediate vs deferred therapy study, there is a case to extend examination of this approach to a randomized trial. This might also include patients failing to achieve PSA complete remission in order to examine the issue of whether continued androgen withdrawal is required in the terminal treatment phase of hormone-resistant patients to keep the hormone sensitive clone under control. Prostate Cancer and Prostatic Diseases (2000) 3, 286-289
Prostate Cancer Prostatic Dis 2000 Dec
PMID:Potential of intermittent hormone therapy for M+ and M0 prostate cancer patients. 1249 80

Endostatin has been considered a highly specific inhibitor of endothelial cell proliferation and/or migration. To explore the use of endostatin in antiangiogenic gene therapy, we generated a recombinant adenovirus, AdEndo, carrying the gene for mouse endostatin. Injection of 10(9) PFU of AdEndo resulted in a low but significant suppression (25%) of preestablished tumor growth in murine models involving murine Lewis lung carcinoma (LLC) and human breast cancer MDA-MB-231 tumors. Greater anticancer activity was observed when the same dose of AdEndo was injected into two other preestablished murine models involving C51 murine colon cancer and HT29 human colon cancer (55 and 47% tumor growth reduction, respectively). In vitro, endostatin derived from AdEndo-infected MRC-5 fibroblasts inhibited the growth of C51 and HT29 cell lines (72 and 61%, respectively). The extent of this inhibition was comparable to that observed in endothelial cells: 75% for microcapillary endothelial cell line HMEC-1, 52% for human dermal microvascular endothelial cells, 46% for human umbilical vein endothelial cells, and 67% for calf pulmonary arterial endothelial cells. Both endothelial and colon cancer cells showed a clear increase in cell apoptosis (4- to 5-fold for endothelial cells and 5- to 10-fold for colon cancer cells) and an accumulation in the G(1) phase of the cell cycle. This antiproliferative activity was not observed in other tumor cell lines: LLC, MDA-MB-231, murine colon adenocarcinoma MC38, human prostate cancer cell line DU145, and human breast cancer cell line CAL51. Taken together, these results provide evidence that, in addition to its antiangiogenic activity, endostatin exerts a direct anticancer action that appears to be restricted to some tumor cell lines. Thus, endostatin could be used in some colon cancer treatments and its clinical efficacy would depend on the response of tumor cells themselves.
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PMID:Endostatin exhibits a direct antitumor effect in addition to its antiangiogenic activity in colon cancer cells. 1286 17

Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED(50)=14.8, 3.1, 19.4nM compared with 55.5nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer.
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PMID:Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: evaluation of novel conjugates as cytotoxic agents. 1735 Aug 34

Starting from 3beta-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3beta-hydroxy-17-oxa-D-homoandrost-5-ene-16-one (10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, prostate cancer AR-, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC(50) values being 2 microM and 0.55 microM, respectively. Compounds 6 (10 microM) and 14 (9 microM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5.
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PMID:Synthesis and antitumor activity of new D-seco and D-homo androstane derivatives. 1964 59


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