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)

The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the diagnosis of prostate cancer is made, might inhibit the proliferation of androgen-dependent and -independent cells, improve further the therapeutic response, and increase the survival rate.
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PMID:Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model. 315 90

Seventy-eight patients with cytologically and/or histologically confirmed prostatic cancer were randomly allocated to orchidectomy (ORX, n = 37) or combined intramuscular and oral estrogen treatment (ESTR, n = 41). Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, total estrone (tE1; sum of unconjugated and conjugated estrone, greater than or equal to 85% estrone sulfate), cortisol, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone, sex hormone-binding globulin (SHBG), and albumin were determined prior to treatment and 12, 24, and 36 months after initiation of treatment. Fifty patients responded to treatment or had stable disease, and 28 did not respond (12 in the ORX and 16 in the ESTR group). There was no association between pretreatment hormone or protein levels and outcome of the treatment, neither in the total material nor within either of the two treatment subgroups. Significantly higher pretreatment levels of cortisol and prolactin and significantly lower levels of T, tE1, and albumin and a significantly lower T/SHBG-ratio (index on biologically active T) were found in patients with metastatic disease, compared with the patients without metastases. There was no association between testicular or adrenal androgens, SHBG, T/SHBG, and albumin values during treatment and the clinical outcome. The differences found between metastatic and nonmetastatic disease probably simply reflect the more stressful and catabolic condition and generally poorer health in patients with disseminated malignant disease. Furthermore, the study does not lend any support to the hypothesis that indicates an important role of adrenal "rest androgen" in prostatic cancer tumor growth.
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PMID:Prognostic value of serum hormone concentrations in prostatic cancer. 321 6

Permanent transplantable human tumors in nude mice offer the possibility of studying the impact of different (endocrine) treatment regimens on human cancer tissue. Among the limited number of human tumor models in athymic nude mice developed so far, the PC-82 tumor (which was established in our institution) mimics many of the important properties of clinical prostate cancer. The absence of PC-82 tumor growth in intact female and in castrated male mice indicates the absolute requirement of androgen for the growth of this tumor. Delayed testosterone (T) substitution (up to 70 days after tumor grafting) in PC-82 transplanted female mice resulted in tumor growth. This indicated that after androgen withdrawal at least part of the cells do not die and keep the capability to respond to androgens. Androgen withdrawal from T-implanted tumor-bearing female mice caused a rapid reduction (90% within 1 day) of the tissue T and a slower decline (up to 90% within 7-10 days) of tissue DHT concentrations. By the use of Silastic implants, containing different proportions of T mixed with cholesterol, circulating T levels of 0.2-20 nmol/L were obtained. It was observed that a constant plasma T level between 1 and 2 nmol/L (achieved with 10% T implants) is the threshold below which growth of the PC-82 tumor tissue is no longer stimulated.
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PMID:Androgen-dependent human prostate cancer in nude mice. The PC-82 tumor model. 324 88

Total androgen blockade has been proposed as a better therapeutic technique than castration alone for the management of metastatic prostate cancer. This is based on the theory that links adrenal androgens to tumor growth. We have carefully examined the role of adrenal androgens in prostate cancer. Work done in our laboratory, as well as the work of many others, has demonstrated the following in regard to the role of adrenal androgens in prostate cancer: (1) The adrenal cortex secretes significant amounts of adrenal androgens into the blood. (2) Adrenal androgens are converted into dihydrotestosterone (DHT), as indicated by studies of labeled DHT recovered from prostates resected one-half hour after infusion of 3H-androstenedione or 3H-dehydroepiandrosterone sulfate into patients. We have also shown that biopsies of prostates from patients who were previously castrated may contain significant amounts of DHT, which could only be derived from adrenal androgens. (3) We have quantified DHT derived from adrenal androgens by measuring prostate DHT concentrations in castrates and in patients treated with combined gonadal and adrenal blockade. The mean difference between these two groups, 0.32 ng/g of DHT lower with combined blockade, is statistically significant and represents DHT derived from adrenal androgens. (4) We have also demonstrated that the small amounts of DHT derived from adrenal androgens may be biologically significant in stimulating prostatic epithelial cell protein synthesis in humans; others have reported similar findings in animals. (5) A review of patients in relapse after castration, who are treated with adrenal androgen blockade, indicates that approximately one out of three patients will show an objective remission based on National Prostate Cancer Project (NPCP) criteria. Despite data supporting the importance of adrenal androgens in prostate cancer, clinical trials using combined adrenal and gonadal blockade in prostate cancer have shown only modest benefit over castration. The largest and best study to date is the Southwest Oncology Group (SWOG) study, which did show a near-significant (P less than 0.065) difference between patients treated for 20 months with a luteinizing hormone-releasing hormone (LH-RH) plus flutamide compared with LH-RH alone. The difference in median time to progression was approximately 2 months between the groups. However, when one considers the fact that two out of three patients are probably not responding to the total androgen blockade, the 2 month difference may actually represent 6 or more months in a subset of one-third of patients receiving that therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Advantages of total androgen blockade in the treatment of advanced prostate cancer. 328 84

The effects of feeding menhaden oil (MO), rich in omega-3 fatty acids, or supplemental vitamin A [as retinyl acetate (RA)], on the growth of DU 145 human prostate cancer cells were studied in athymic nude mice. The mice were fed AIN-76A diets containing either 23% corn oil (CO), a mixture of 17% MO and 6% CO, or 23% CO plus RA. After irradiation sterilization, the RA-supplemented diet was found to contain approximately 15 times the amount of vitamin A present in the control diet. There were 24 mice in each dietary group. Three weeks after commencement of feeding the experimental diets, 1 x 10(6) or 5 x 10(6) DU 145 cells were inoculated into subgroups of 12 animals, and the appearance and growth of solid tumors followed over a 6-week period. There was no significant difference in tumor latency between mice fed MO plus CO, and those fed CO alone, regardless of the inoculum size. However, the appearance of palpable tumors was more rapid in mice inoculated with 5 x 10(6) cells and fed the RA-supplemented CO diet (91% after 17 days) compared with mice receiving the same tumor cell load but fed the unsupplemented CO diet (55% after 17 days). Growth of the solid tumors was retarded significantly in mice inoculated with 1 x 10(6) cells and fed the MO-containing diet compared with the CO controls; this effect was not evident in animals who received 5 x 10(6) cells. RA supplementation caused accelerated tumor growth, which, again, only achieved statistical significance in the group inoculated with 1 x 10(6) cells.
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PMID:Effects of dietary menhaden oil and retinyl acetate on the growth of DU 145 human prostatic adenocarcinoma cells transplanted into athymic nude mice. 335 68

In order to determine if intermittent hormonal therapy might prove to be beneficial in the treatment of prostatic cancer, animals bearing the Dunning R3327H prostatic adenocarcinoma were castrated and intermittently subjected to hormonal stimulation by means of indwelling silastic testosterone-filled implants. The growth of these tumors, as measured by increases in volume, was compared to that of a castrate control group, a chronic implant group and an intact control group. By the end of an initial 49 day experimental period there was no significant growth reduction with the intermittent stimulation group as compared to the implanted control or intact groups. The castrate group had a significant lower rate of growth than any other group. The incidence of massive tumor growth or tumor necrosis was significantly lower in the castrate group than the other groups by the end of the 16 week experimental period. Intermittent hormonal therapy is clearly inferior to early castration in preventing tumor growth; furthermore it does not appear to offer any growth-retarding advantages when compared to delayed hormone therapy. The most effective growth-retarding technique for the Dunning R3327H hormone dependent prostatic adenocarcinoma is early castration.
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PMID:Experimental treatment of prostatic cancer by intermittent hormonal therapy. 356 Mar 48

Conventional antiandrogen therapy for prostatic cancer generally results in the death of androgen-dependent cells, resulting in shrinkage of the tumor, followed by regrowth of the tumor as androgen-insensitive cells take over. Because of reported antigonadotropic and antineoplastic effects of the pineal hormone melatonin (MEL), we hypothesized that this indole might provide an effective therapy for prostate cancer, as it would be effective against both populations of tumor cells. We used three sublines of the Dunning R3327 rat prostatic adenocarcinoma to determine whether MEL could suppress the growth of these tumors and, if so, by what mechanisms this occurs. In one experiments, we compared the growth of a well-differentiated slow-growing Dunning tumor in rats given MEL combined with the potentiating procedure olfactory bulbectomy (BULBX), with that in rats pinealectomized (PINX) or untreated. Tumor growth in BULBX-MEL rats was significantly suppressed over that in the other two groups, as were the weights of the gonads and accessory sex glands. Tumor morphology, DNA concentration, and androgen receptor concentration and distribution were identical in untreated controls and in BULBX-MEL rats, suggesting that the treatment affected all populations of tumor cells equally. With another strain of well-differentiated slow-growing Dunning tumor, we examined the effects of MEL in rats with and without BULBX. Reproductive parameters were not suppressed in BULBX-MEL rats and, while there was a trend toward slower tumor growth in this group, this was not significant. Intact rats given MEL grew larger tumors than did control rats but, again, differences were not significant. In a third experiment, we examined a fast-growing androgen-insensitive anaplastic Dunning tumor. PINX was without effect on this tumor, but BULBX-MEL resulted in a significant suppression of one of the constants in the logistic equation fitted to the growth curves. This indicates that there were some direct antitumor effects of BULBX-MEL on this tumor strain. We conclude that MEL suppresses growth of some Dunning tumor strains.
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PMID:Effects of olfactory bulbectomy, melatonin, and/or pinealectomy on three sublines of the Dunning R3327 rat prostatic adenocarcinoma. 362 64

The responsiveness of prostate cancer to treatment with estrogen has been recognized for over 40 years, but whether the effect is mediated by diminished tumor growth or reduction in metastatic spread is not known. To answer this question the authors reviewed the clinical and pathologic features of 89 patients with metastatic prostate cancer after autopsy. Sixty-three percent of the patients studied were black. Patients treated with estrogen survived somewhat longer (0.05 less than P less than 0.10), but they had significantly greater numbers of metastatic sites (P less than 0.001) and greater overall tumor burden (P less than 0.001), with significantly increased frequencies of metastases to the liver, adrenal gland, bone, lymph nodes, large bowel, lungs, serosal surfaces, ureters, and central nervous system (CNS) (all P less than 0.05 or lower) compared with patients who had not been treated with estrogen. However, patients not treated with estrogen more frequently died from other causes (P less than 0.001). When the patients who died from other causes were excluded from the data analysis, there were no significant differences in the number of metastatic sites between patients who received estrogen therapy and those who did not, and the only remaining significant difference in the distribution of metastases was that patients who received estrogen treatment had more frequent metastases to the adrenal cortex and CNS (P less than 0.05). These observations were corroborated by cluster analysis of the metastatic patterns. Cluster analysis also identified a subset of predominantly (67%) black patients who developed distant metastases without much local spread of tumor. This suggests that tumor behavior in this group was less predictable than for the other patients in whom disease appeared to progress from Stage A to Stage D as expected. The authors conclude that estrogen therapy may prolong survival by slowing the rate of tumor growth rather than by inhibiting the metastatic progression of prostate cancer or destroying selective populations of tumor cells.
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PMID:Metastatic behavior of prostate cancer. Cluster analysis of patterns with respect to estrogen treatment. 371 62

A method has been developed to determine the survival of human tumor cells after implantation in athymic nude mice. The method involves the labelling of cells of the prostatic cancer cell line PC-3 with tritiated thymidine after attachment of the cells to Millipore filter disks. The amount of radioactive label incorporated in the cells remained constant for at least 48 hr during in vitro incubation. After s.c. implantation of the filter disks in nude mice, however, the fraction of surviving cells, reflected by the amount of radioactivity persisting on the filters, rapidly decreased with time. Only a relatively small fraction (approx. 10%) of the cells survived for more than 24 hrs under these conditions. Pretreatment of the mice with cyclophosphamide (100 mg/kg, 24 hr prior to implantation) resulted in a 2-fold increase of tumor-cell survival. Likewise, the frequency of tumor takes after injection of PC-3 cells was enhanced following cyclophosphamide pretreatment. These results indicate that immune defense mechanisms might be partly (but not completely) responsible for tumor-cell rejection in nude mice. The technique described here might be a valuable tool for the rapid evaluation of possible effects of various types of pretreatment of the host animal on tumor cell survival and, thereby, on tumor growth.
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PMID:Measurement of the survival of human tumor cells after implantation in athymic nude mice. 372 26

The doubling time (DT) of human prostatic cancer is calculated for the first time; its various parameters and the relative importance of each are reviewed. A crude volume-doubling time (DTcv), a theoretical doubling of the number of cells (DTt), and an annual doubling rate (ADR), are defined and calculated for each of 12 patients who had undergone needling of the prostate for diagnostic purposes and in whom tumor cells were implanted in the track of the biopsy needle and had grown into a subcutaneous perineal nodule. The harmonic average DTcv was six days and DTt eight days, and the average ADR was 45 doublings per year. From the study of the calculated DTs and ADRs, it became obvious that the 12 patients fell into three distinct groups: Group I = slow tumor growth rate, an average ADR of 9 doublings per year, and a harmonic average DTt of forty days; Group II = medium tumor growth rate, an average ADR of 35 doublings/year, and a harmonic average DTt of ten days; and Group III = rapid tumor growth rate, an average ADR of 100 doublings/year, and a harmonic average DTt of four days.
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PMID:Doubling time and annual doubling rate of human prostatic cancer. 379 27


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