Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen ablation induces an energy-dependent process of programmed death in nonproliferating androgen-dependent prostatic cancer cells which involves fragmentation of genomic DNA into nucleosomal oligomers catalyzed by nuclear Ca2+, Mg(2+)-dependent endonuclease enzymes activated following a sustained elevation in intracellular free Ca2+ (Cai). In contrast, androgen-independent prostatic cancer cells are not induced to undergo such programmed cell death by androgen ablation. One explanation for the inability of androgen ablation to induce programmed death of androgen-independent prostatic cancer cells is that such ablation does not result in a sustained elevation in Cai in these cells. This raises the issue of whether androgen-independent prostatic cancer cells can be induced to undergo programmed death if an elevation in the Cai is sufficiently sustained by nonhormonal means. To test this possibility, androgen-independent, highly metastatic Dunning R-3327 AT-3 rat prostatic cancer cells were chronically exposed in vitro to the calcium ionophore ionomycin to sustain an elevation in their Cai. These studies demonstrated that an elevation of Cai as small as only 3-6-fold above baseline can induce the death of these cells if sustained for greater than 12 h. Temporal analysis demonstrated that the death of these cells does not require cell proliferation and involves Ca(2+)-induced fragmentation of genomic DNA into nucleosome-sized pieces as the commitment step in this process. These results demonstrate that even nonproliferating androgen-independent prostatic cancer cells can be induced to undergo programmed cell death if a modest elevation in the Cai is sustained for a sufficient time. These observations identify Cai as a potential target for therapy for androgen-independent prostatic cancer cells.
Cancer Res 1991 Sep 01
PMID:Programmed death of nonproliferating androgen-independent prostatic cancer cells. 187 14

Evidence supporting a broad role for the inactivation of the p53 gene in human tumorigenesis has been provided by studies showing that the p53 gene is mutated in many human cancers. In this study, we report on the mutational status of the p53 gene in prostate cancer cells and provide functional evidence that the wild-type p53 gene may have a role in suppressing prostatic tumorigenesis. Sequence analysis of exons 5-8 of the p53 gene reveals that three of five prostate cancer cell lines (TSUPr-1, PC3, DU145) contain mutations which alter the amino acid sequence of this most highly conserved portion of the gene. One of two primary prostatic cancer specimens examined also contained a mutation in this region. Transfection of the wild-type p53 gene versus a mutated p53 gene into two cell lines with p53 mutations results in reduced colony formation. Wild-type p53 gene expression is apparently incompatible with continued growth of these tumor cells inasmuch as none of the colonies which formed after wild-type transfections retain the transfected p53 sequences. Immunocytochemical data indicate that prostate carcinoma cells expressing the transfected wild-type p53 gene are growth arrested because they exhibit a reduced level of thymidine incorporation into DNA. This study is the first report of p53 gene mutations in prostate cancer cells and suggests a functional role for the p53 gene in suppressing prostatic tumorigenesis.
Cancer Res 1991 Sep 01
PMID:Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. 187 16

A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer.
J Urol 1991 Sep
PMID:Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). 187 19

From 1970 through 1983, 107 patients with newly diagnosed adenocarcinoma of the prostate were treated with radiotherapy with curative intent at Duke University Medical Center. Forty-five patients (42%) underwent transurethral resection of the prostate (TURP) for diagnostic and/or therapeutic purposes prior to beginning radiotherapy. Sixty-one patients (57%) were diagnosed by needle biopsy. TURP and needle biopsy groups were comparable (age, elevated acid phosphatase, early [A2, B] and late [C, D1] disease stages, and follow-up). TURP patients were more likely to have poorly differentiated tumors and were more often given concurrent hormonal therapy. Both univariate and multivariate analyses to study the effect of TURP on patients with prostate cancer treated with radiotherapy were done. We were unable to demonstrate any adverse impact of TURP on the outcome of radiation therapy for prostate cancer. This issue remains controversial and should be addressed in a prospective, randomized trial.
Urology 1991 Sep
PMID:Transurethral resection of prostate prior to definitive irradiation for prostate cancer. Lack of correlation with treatment outcome. 188 32

The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.
Am J Hematol 1991 Sep
PMID:A glycosaminoglycan inhibitor of thrombin: a new mechanism for abnormal hemostatic assays in cancer. 189 11

We reviewed the treatment morbidity associated with definitive high energy external beam radiotherapy in 289 consecutive patients with clinically localized prostate cancer (stages A2 to C) treated from 1984 to 1988 inclusively. All patients were treated with 18 mv. photon beams via a 4-field box technique. Radiation doses ranged from 5,858 to 6,900 cGy., with a mean dose of 6,456 cGy. and a median dose of 6,400 cGy. A total of 65 patients underwent extraperitoneal pelvic staging lymphadenectomy before radiotherapy. Complications noted in 42 patients were mild (generally trivial) in 23 and moderate in 19 (6.6%). There were no severe complications. The actuarial incidence of moderate complications was 9% at 5 years. Only 6 patients experienced symptoms for longer than 6 months. The risk of complications was not increased in patients who had undergone prior lymph node dissection, and only 2 of 65 had mild lymphedema, which resolved in both cases. We conclude that high energy external beam radiation for prostate cancer can be delivered with a low risk of serious complications, even in patients who have undergone extraperitoneal staging pelvic lymphadenectomy, provided the patients are treated to limited fields with high energy photons and at doses limited to 6,800 cGy. or less.
J Urol 1991 Sep
PMID:Complications following external beam radiation therapy for prostate cancer: an analysis of patients treated with and without staging pelvic lymphadenectomy. 190 30

A sensitive method for the determination of leuprorelin (TAP-144), a luteinizing hormone-releasing hormone analogue, and its C-terminal metabolite, M-I, in serum and urine has been developed. Leuprorelin and M-I were extracted from serum or urine samples with Sep-Pak C18 cartridges, and separated completely by high-performance liquid chromatography and determined by radioimmunoassay using [125I]leuprorelin as the labelled antigen. The detection limit of the method was 0.05 ng/ml for leuprorelin and M-I, and the recovery of the compounds added to serum and urine was over 88% with a coefficient of variation (within-assay) of less than 5%. The method was applied to the determination of leuprorelin and M-I-like immunoreactivity in serum or urine after administration of once-a-month injectable microspheres of leuprorelin acetate (TAP-144-SR) to patients with prostate cancer.
 ...
PMID:High-performance liquid chromatography followed by radioimmunoassay for the determination of a luteinizing hormone-releasing hormone analogue, leuprorelin, and its metabolite. 190 42

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.
Cancer Res 1991 Sep 15
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

We analysed ploidy and S-phase fraction (SPF) from 78 paraffin-embedded primary prostatic carcinomas by DNA flow cytometry. DNA aneuploidy and above median (4.2%) SPF were both associated with high tumour grade, large size of prostate and presence of distant metastases. Both aneuploidy and high SPF (greater than 4.2%) indicated short 10-year progression-free (P = 0.01 for ploidy and P = 0.0002 for SPF), overall (P = 0.004 and P less than 0.0001) as well as prostate cancer survival (P = 0.002 and P less than 0.0001). Ten-year overall survival rate was 45% in cases with SPF below 4.2% and 0% in those with higher values, whereas the corresponding prostate cancer-specific survival rates were 80% and 11%, respectively. None of the seven tumours with SPF above 12% showed an objective response to endocrine therapy, whereas 26/49 (52%) of those with lower SPF values responded (P = 0.01). DNA ploidy, tumour grade, T-stage or M-stage did not significantly correlate with endocrine responsiveness. SPF was also the best predictor of progression free survival in patients treated hormonally. In conclusion, detection of high SPF in prostate cancer may indicate lack of hormonal responsiveness and poor prognosis.
Br J Cancer 1991 Sep
PMID:Flow cytometric analysis of DNA ploidy and S-phase fraction from prostatic carcinomas: implications for prognosis and response to endocrine therapy. 191 Dec 1

One hundred four patients with stage T-1b, T-2 N-O M-O prostate cancer were treated with external beam irradiation as part of RTOG 77-06. Lymph nodes were negative by lymph node dissection in 16 patients with T-1b and 88 patients with T-2 cancers. Survival exceeds age matched expected survival for the 10 years of observation (63% vs 59% at 10 years). Patterns of failure at 10 years show 87% of patients were free of isolated local recurrence, 79% free of metastatic failure, 67% free of any failure, and cause specific survival shows 86% free of cancer death at 10 years. The outcome of this group is equal or superior to reports of radical prostatectomy in similar stage patients.
Int J Radiat Oncol Biol Phys 1991 Sep
PMID:Outcome for lymph node dissection negative T-1b, T-2 (A-2,B) prostate cancer treated with external beam radiation therapy in RTOG 77-06. 191 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>