Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of varying the timing of androgen ablation alone and in combination with chemotherapy on tumor growth rate and host survival has been studied using the serially transplantable Dunning R-3327 H rat prostatic adenocarcinoma as a model. These studies have demonstrated three basic points: 1) When either androgen ablation or Cytoxan chemotherapy are given as a single agent treatment, they are both most effective when given as early as possible; 2) when androgen ablation is combined with Cytoxan chemotherapy, it is most effective when both therapies are begun simultaneously and as early as possible; and 3) when androgen ablation and Cytoxan treatment are begun simultaneously and early, it is possible to increase survival above that found for either treatment when given optimally as single modalities (ie, such simultaneous early treatment enhances the individual therapeutic effectiveness of both treatments).
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PMID:The timing of androgen ablation therapy and/or chemotherapy in the treatment of prostatic cancer. 669 14

The LNCaP cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10(5) cells/sq cm; doubling time, 60 hr), form clones in semisolid media, are highly resistant to human fibroblast interferon, and show an aneuploid (modal number, 76 to 91) human male karyotype with several marker chromosomes. The malignant properties of LNCaP cells are maintained. Athymic nude mice develop tumors at the injection site (volume-doubling time, 86 hr). Functional differentiation is preserved; both cultures and tumor produce acid phosphatase. High-affinity specific androgen receptors are present in the cytosol and nuclear fractions of cells in culture and in tumors. Estrogen receptors are demonstrable in the cytosol. The model is hormonally responsive. In vitro, 5 alpha-dihydrotestosterone modulates cell growth and stimulates acid phosphatase production. In vivo, the frequency of tumor development and the mean time of tumor appearance are significantly different for either sex. Male mice develop tumors earlier and at a greater frequency than do females. Hormonal manipulations show that, regardless of sex, the frequency of tumor development correlates with serum androgen levels. The rate of the tumor growth, however, is independent of the gender of hormonal status of the host.
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PMID:LNCaP model of human prostatic carcinoma. 683 20

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

Dunning R3327H prostatic adenocarcinoma was bilaterally transplanted in the flanks of animals at the Papanicolaou Institute in Miami, and the animals were received at the Cross Cancer Institute (Edmonton, Alberta, Canada) each month. The animal flanks were palpated weekly, and when tumor volumes reached a size of approximately 300 mm3 the animals were randomized into treatment groups for the assessment of various therapies. Tumor volumes were determined each week before and after various treatments, and tumor growth was compared to that in untreated controls. Ionizing radiation at relatively small single doses completely inhibits tumor growth for a period of up to 6 months. Some interesting characteristics of this radiation-induced growth arrest are that tumors do not die and shrink away as with some other tumor models but remain static in size and show histologic evidence of viable tumor cells. The hypoxic cell radiosensitizer misonidazole potentiates radiation response in this tumor model. Cisplatin, vincristine, etoposide, and estramustine phosphate administered in drug doses approaching their toxic limits have a partial effect on tumor growth.
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PMID:Response of the Dunning R3327H prostatic adenocarcinoma to radiation and various chemotherapeutic drugs. 688 15

The relative effectiveness of different combinations of estrogen therapy and radiation therapy against the R-3327 prostatic adenocarcinoma of the Copenhagen rat was studied. Because of similar actions of estrogens and radiation in the cell cycle, and possibly antagonistic effects reported in the clinical literature, we looked for an antagonism between these two therapeutic modalities. Radiation therapy consistently showed a greater tumor inhibitory effect than estrogen therapy alone at the dose tested. Combinations of radiation therapy with hormonal manipulation did not appear to show a greater inhibition of tumor growth than radiation therapy alone. There also did not appear to be an antagonistic effect between these two modalities in this system.
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PMID:Investigation of different combinations of estrogen therapy and radiation therapy on prostatic adenocarcinoma (R-3327). 705 7

Two Nb rat prostatic adenocarcinomas, 13 Pr-12, an autonomous tumor, and 2 Pr-128, an androgen-dependent tumor, were transplanted into groups of congenitally athymic nude mice. The agents used for treatment of these tumors are agents characteristically not used in treatment of prostatic adenocarcinoma in humans. However, these have been efficacious in treating other solid malignancies. Both agents, BCNU and Actinomycin-D, were efficacious in producing tumor regression and in causing at least a temporary decrease in tumor growth. The combination of the Nb rat prostatic adenocarcinoma model and nude mouse is presented as an appropriate system to screen therapeutic agents that have proved efficacious in treatment of other solid malignancies but have not been used in treating prostatic adenocarcinoma.
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PMID:Therapy for Nb rat tumor transplanted in athymic mice. 721 11

The Dunning R-3327-H rat prostatic adenocarcinoma is a well-differentiated, slow-growing, serially transplantable tumor of spontaneous origin. When intact male rats bearing such an exponentially growing H-tumor s.c. are castrated, tumor growth abruptly stops, demonstrating the initial androgen sensitivity of this tumor. Eventually, however, after an extended period, the tumor invariably relapses and once again appears to grow exponentially. At the time of relapse, the tumor is no longer androgen sensitive but has irreversibly progressed to a completely insensitive state. The mechanism responsible for this irreversible progression has been demonstrated by fluctuation analysis not to be due to environmentally induced adaptation of initially androgen-dependent H-tumor cells to a new androgen-independent state. Instead, the progression is due to the basic heterogeneity of the original H-tumor (i.e., it is composed of a mixture of preexisting clones of both androgen-dependent and androgen-independent tumor cells). Following castration, only the preexisting clones of androgen-independent tumor cells are able to continue exponential growth; the androgen-dependent tumor cells stop proliferating and die. Thus, androgen ablation creates a host environment in which the androgen-independent tumor cells have a highly selective growth advantage over the androgen-dependent cells. Eventually, with time, this selective growth advantage results in a tumor which is completely composed of androgen-independent cells. It is the continuous proliferative growth of these androgen-independent tumor cells which leads to the relapse phenomenon.
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PMID:Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. 730 8

The Dunning animal model was used to evaluate endocrine management of prostatic adenocarcinoma. Hypophysectomy, alone or in combination, and orchiectomy plus stilbestrol were the most effective means of suppressing tumor growth. Medical adrenalectomy by aminoglutethimide administration was as effective as surgical ablation. Accessary organ weights bore no direct relationship to the inhibition of tumor growth.
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PMID:Endocrine manipulation of the Dunning prostatic adenocarcinoma. 737 43

Nb rat prostatic adenocarcinomas have been successfully transplanted into groups of syngeneic Nb rats, as well as into congenitally athymic (nude) mice, with a high frequency of success. This rate of success is one characteristic of this system that allows for experimentation in vivo in large numbers of animals for statistical considerations such as the following: similarity to human prostatic adenocarcinoma, histopathologic response to appropriate hormonal therapy in the case of androgen-dependent tumors, histochemical characteristics, presence of metastases, presence of acid phosphatase, preliminary data revealing the presence of receptors and autonomous tumor models that are refractory to hormonal manipulation (analogous to patients with prostatic carcinoma no longer sensitive to hormonal manipulation). Additionally, the stability in tumor growth kinetics, as well as the histologic and biochemical parameters, is an important consideration in this tumor model for chemotherapeutic and hormonal studies and the tumor response to such modalities. Of note is the fact that this tumor model rarely occurs spontaneously in aging rats. This animal model has been successfully used in evaluating chemotherapeutic and hormonal treatment protocols (discussed in the Hormonal and Chemotherapeutic Considerations of the Nb Rat Model chapter). Finally, the combination of the Nb prostatic adenocarcinoma model with the transplantation of these tumors to nude mice will enable us to evaluate chemotherapeutic efficacy in the immunocompetent as well as the immunodepressed host.
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PMID:The Nb rat prostatic adenocarcinoma model system. 738 86

Radiation therapy for advanced prostate cancer has dose-limiting complications and often results in limited tumor control. A combination of radiation and taxol, a potential radiation sensitizer, may enhance therapeutic efficacy at currently used individual doses. Human prostatic carcinoma lines in vitro, and Dunning rat prostatic adenocarcinoma in vivo, were treated with taxol and radiation individually, and in combination. Cytotoxicity of taxol was comparable between androgen sensitive and insensitive lines, with 50% growth inhibition at 9.6 to 12.7 nM. Combining agents increased cytotoxicity, with a dose modifying ratio of 1.8 at 0.1% survival. Flow cytometry showed an enhancement of radiation toxicity associated with taxol-induced cell cycle phase arrest at G2/M. Injection of taxol (4 mg/kg/day x 5), radiation dose fractionation (1.5 Gy/day x 5) and their combination significantly delayed Dunning tumor growth. Adverse side effects were minimal. The results imply that combination of these agents may have clinical potential in prostate cancer treatment.
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PMID:Enhancement of radiation response of prostatic carcinoma by taxol: therapeutic potential for late-stage malignancy. 773 49


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