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)

Hypofibrinogenemia and disseminated intravascular coagulation are common events in patients with metastatic prostate carcinoma. This study tests the hypothesis that prostate tumor growth and metastasis is associated with sustained activation of fibrinolysis secondary to increased release of plasminogen activator. We implanted an androgen-insensitive prostate tumor into an inbred strain of rats and serially measured plasminogen, plasminogen activator, plasmin and fibrinogen. Control groups included animals without tumor and a group implanted with transitional cell bladder carcinoma, a locally infiltrating tumor not usually associated with hemostatic complications. Our results showed a significant and steady rise in plasma plasminogen activator, plasmin and fibrinogen levels in animals implanted with prostate cancer. This, however, is not specific for prostate tumor. Similar, perhaps more profound changes were noted in animals implanted with the transitional cell carcinoma.
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PMID:The fibrinolytic system in experimental prostate tumor. 381 May 52

The effect of 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase has been evaluated on tumor growth in the Noble rat model of prostatic adenocarcinoma. The growth characteristics of the tumor line 2Pr-121D(1) were consistent with heterogeneity of cell types, composed of androgen-sensitive and androgen-insensitive malignant cells. Both sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20 (s)-carboxylate and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one significantly retarded tumor progression. Each agent increased tumor volume doubling time by approximately 62%. On the basis of their similarities to female rats and male castrate group, in terms of growth rate, tumor doubling time, and histologic characteristics, the treatments with the 4-methyl-4-aza-steroids appeared to produce effects common to both castration and estrogenization (chronic administration of pharmacologic doses of estrogen). The failure of 5 alpha-reductase inhibitors to be active as antiprostatic agents in vivo has hitherto detracted from their use of therapeutic agents. Present studies demonstrate that the 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase may represent an alternative to orchiectomy and chronic estrogen therapy for the management of the hormone-dependent phase of prostate cancer.
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PMID:Retardation of prostate tumor progression in the Noble rat by 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase. 385 54

Preliminary evidence suggests that the sensitivity of endocrine-dependent neoplasms to chemotherapy may be enhanced by transient hormonal stimulation of tumor growth. To test this concept, we are conducting a prospective controlled trial in men with stage D2 prostate cancer who have relapsed following orchiectomy. All patients are continuously treated with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion plus cyclic chemotherapy. Patients in the stimulation arm receive, in addition, the synthetic androgen fluoxymesterone for 3 days before and on the day of chemotherapy. Of 41 patients entered to date, 26 are evaluable. Twenty-one (81%) obtained either an objective remission or stabilization of disease with a mean duration of 9+ months and 10 patients still responding. Thus far, the response rate is similar in the control and stimulation groups. Androgen administration was associated with a rise in acid phosphatase and usually a modest flare of symptoms except for 2 patients who developed spinal cord compression. These preliminary data indicate that the combination of aminoglutethimide and chemotherapy has a potent antitumor effect on advanced prostate cancer refractory to orchiectomy. A large number of patients and a longer follow up are needed to assess whether transient androgen administration potentiates the effect of chemotherapy.
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PMID:Hormone stimulation and chemotherapy in advanced prostate cancer: preliminary results of a prospective controlled clinical trial. 388 46

The polyamine metabolism is pathologically changed in tumor tissues, and especially putrescine and spermidine demonstrate abnormally high values in kidney, bladder, and prostate cancer. The inductive processes which activate the biosynthetic polyamine enzymes in cancer are completely unknown. Of therapeutic interest is the fact that increased enzyme activities through irreversible inhibitors become significantly reduced, which consequently slows the tumor growth. Experimental therapy, especially in transplantable bladder and prostate cancer, displayed a 50% tumor destruction. In clinical studies using inhibitors of the polyamine biosynthesis, the dose had to be significantly reduced because of expressed toxicity. Additional investigations which tried a combination of reversible and irreversible inhibitors proved a similar antitumor activity, but less severe side effects.
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PMID:[Polyamines, polyamine antimetabolites and urogenital tumors. State of research and clinical results]. 393 27

The relative efficacy of hormonal, chemical, or combined therapy was investigated in a prostate cancer animal model. 96 Copenhagen-Fischer hybrid rats were implanted with equal-sized fragments of the Dunning H strain transplantable prostatic adenocarcinoma. These animals were randomly assigned to 1 of 6 treatment groups: (1) control, (2) testosterone, (3) testosterone followed by cyclophosphamide, (4) cyclophosphamide, (5) orchiectomy or (6) orchiectomy followed by cyclophosphamide. Animals in the control group had the shortest survival, fastest tumor growth rate, and largest tumor size. Testosterone, when compared to the control group, did not accelerate tumor growth. Cyclophosphamide alone, orchiectomy alone, cyclophosphamide plus orchiectomy, and testosterone plus cyclophosphamide were each equally effective in decreasing tumor growth rate. Tumor size in the testosterone plus cyclophosphamide-treated animals was equivalent to that in orchiectomized animals. The survival of all groups treated with cyclophosphamide was reduced because of toxicity. Testosterone administered prior to cyclophosphamide eliminated and shortened survival from cyclophosphamide. The best overall results were obtained by orchiectomy alone, orchiectomy plus cyclophosphamide, and testosterone plus cyclophosphamide. Although chemotherapy alone was effective in shrinking tumor size, it was highly toxic.
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PMID:Hormonal and chemotherapeutic treatment of prostatic carcinoma; Dunning adenocarcinoma of the prostate in Copenhagen-Fischer rats. 396 57

Standard initial therapy for metastatic prostatic cancer involves surgical or chemically induced castration. Castration lowers the serum testosterone level by over 90% but does not completely eliminate all potential serum androgens (i.e., it induces a partial androgen withdrawal). This has led some investigators to suggest that a more complete form of androgen withdrawal in which the very low levels of serum androgens remaining after castration are neutralized by the simultaneous treatment with a direct acting antiandrogen (i.e., complete androgen withdrawal) might be more effective than simply castration alone. To determine whether complete androgen withdrawal is any more effective than partial androgen withdrawal therapy, the slow growing, well differentiated H and the fast growing, poorly differentiated G sublines of the serially transplantable Dunning R-3327 system of rat prostatic adenocarcinomas were used as a test system since both of these cancers are androgen responsive. These studies demonstrated that: (a) complete androgen withdrawal consisting of surgical castration in combination with daily treatment with the potent antiandrogen, cyproterone acetate, was no more effective in terms of tumor growth retardation or overall host survival than was partial androgen withdrawal induced by castration alone; (b) serum testosterone levels must be maintained below 0.5 ng/ml but do not have to be completely eliminated to produce the maximum therapeutic response; and (c) prostatic cancers are more sensitive than is the normal prostate to growth stimulation by serum testosterone.
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PMID:Effectiveness of complete versus partial androgen withdrawal therapy for the treatment of prostatic cancer as studied in the Dunning R-3327 system of rat prostatic adenocarcinomas. 406 63

Preliminary clinical trials indicate that transient stimulation of breast and prostate cancer growth by hormonal means may enhance tumor sensitivity to chemotherapy. In none of these studies, however, has an attempt been made to measure parameters that might reflect perturbations in cell kinetics induced by the treatment schedules. While conducting two, controlled, randomized clinical trials in advanced breast cancer and prostate cancer using a similar approach, we have measured plasma levels of two tumor markers, carcinoembryonic antigen (CEA) and breast gross cystic disease fluid protein (GCDFP-15). These served as a possible means of monitoring hormonal stimulation of tumor growth. Both markers failed to increase following administration of estrogens to patients with breast cancer and of androgens to men with prostatic carcinoma. In contrast, transient stimulation of tumor growth probably occurred as shown by exacerbation of symptoms and, in patients with prostate cancer, rise in acid phosphatase. We conclude that CEA and GCDFP-15 are not useful for monitoring pertubations in tumor cell kinetics induced by hormone stimulative protocols.
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PMID:Evaluation of CEA and GCDFP-15 plasma level during hormonally induced cancer stimulation. 638 Mar 98

The polyamines, putrescine, spermidine, and spermine, are fundamentally related to both normal and neoplastic cell proliferation. The prostate gland and prostatic tumors in man and rodents contain large amounts of polyamines. This suggests that inhibition of polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosyl-methionine decarboxylase (SAMDC) may retard the growth of prostatic cancer. Since alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) are irreversible and competitive inhibitors of ODC and SAMDC, respectively, they were tested as single agents and in combination on a transplantable rapidly growing and hormone-resistant G subline of the Dunning R-3327 rat prostatic adenocarcinoma. Groups of rats bearing tumors were treated with various regimens of DFMO, MGBG, and DFMO plus MGBG, daily for 21 days. Analysis of differences in tumor growth between treatment groups and controls showed DFMO had no antitumor effect but was well tolerated, MGBG retarded growth rate significantly but resulted in drug deaths in over 50% of the animals, and the combination of DFMO and MGBG resulted in rapid decline in tumor growth rates after 5 to 9 days of treatment with reduced toxicity. At 21 days, or death, 38 of 60 (63%) rats had no viable tumor on histologic study, whereas tumor was present in each of the animals in the other groups. Alpha-difluoromethylornithine increased the intracellular uptake of MGBG and potentiated the antigrowth activity of MGBG on a hormone refractory rat prostatic tumor with less toxicity than MGBG alone.
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PMID:Potentiation of methylglyoxal-bis-guanylhydrazone by alpha-difluoromethylornithine in rat prostate cancer. 642 41

Difluoromethylornithine (DFMO) and methylglyoxal-bis(guanyl-hydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested in two experimental prostatic cancer models. DFMO resulted in a reduction in tumor size in both the rapidly growing R-3327 rat prostatic adenocarcinoma (30.5 +/- 15 versus 61 +/- 9.5 in control animals) and the human DU-145 adenocarcinomas (1.7 ml versus 3.3 ml in control animals) in nude mice. MGBG was tested only in the rat tumor, where it induced a reduction of 22.9 +/- 9.5 ml versus 61 +/- 9.5 in control animals in tumor size but was highly toxic. Flutamide or 9-B-D-arabinofuranosyladenine (Ara-A) proved ineffective per se in reducing tumor growth of the human DU-145 or of the R-3327-G strain, respectively, but increased the efficacy of DFMO against the DU-145 tumor had a high level of ODC which was reduced by DFMO of by Ara-A; the R-3327 tumor had a low level of ODC which was too low to be decreased by DFMO.
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PMID:Some effects of inhibitors of polyamine synthesis on experimental prostatic cancer. 642 51

The purpose of this pilot study was to determine if biogenetic precursors of estrone such as 4-androstene-3,17-dion-19-al, which is virtually devoid of thrombotic potential as well as androgenic and uterotrophic activity, could replace estrogen in the treatment of the hormone-sensitive Dunning R3327 prostatic adenocarcinoma in the male Copenhagen rat. If such were the case, the way would be open to an improved form of palliative therapy of prostatic cancer with the potential for decreased estrogenic side effects and cardiovascular complications. To this end, the R3327 tumor was transplanted (Day 0) into the flank of 10-week-old male Copenhagen rats, and treatment was begun 20 weeks later at which time the tumors reached a mean volume of 2160 cu cm. In addition to 4-androstene-3,17-dion-19-al (1 and 10 mg/day), diethylstilbestrol (33 micrograms/day) and 17 beta-estradiol (3.3 and 33 micrograms/day) were studied (daily for 60 days). At 1 mg/day, 4-androstene-3,17-dion-19-al produced a 43% inhibition of tumor growth (Day 203) while, in the 10 mg/day group, a 72% inhibition of tumor growth was measured on Day 196 (roughly equivalent to that produced by estradiol at 3.3 micrograms/day), with a 50% inhibition on Day 231. It is concluded that the tumor-inhibiting activity of 4-androstene-3,17-dion-19-al, coupled with its very low thrombotic potential, indicated that orally active analogues of this steroid may offer advantages over estrogens in the palliative treatment of prostatic cancer.
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PMID:Effect of the preestrogen 4-androstene-3,17-dion-19-al on the Dunning R3327 prostatic adenocarcinoma. 686 Nov 38


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