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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen-dependent and androgen-independent (autonomous), cloned, cultured cell lines of the androgen-dependent mouse mammary adenocarcinoma, Shionogi carcinoma 115, have been established. Growth of the dependent cells requires the presence of androgen, provided they are growth in suspension culture in medium containing dextran-charcoal-treated fetal calf serum. The growth rate of autonomous cells in the presence or absence of DHT is similar to that of dependent cells grown in its presence. An agar culture method has been developed that enables the proportion of dependent and autonomous cells in mixed populations to be determined. Autonomous cells appear in dependent clones, and their frequency increases with increasing time of subculture. Dependent cells form tumors preferentially in male animals and dependent cell cytosols contain significant amounts (approximately 300 femtomoles per mg protein) of a specific androgen-binding macromolecule. Autonomous cells formed tumors equally well in both male and female mice, and autonomous cell cytols contain very low levels (less than or equal to 7 femtomoles per mg protein) of the specific androgen-binding macromolecule(s). These studies delineate a system which can be used to investigate the mechanism of steroid hormone-dependent and autonomous tumor growth, and the transitions between the hormone-dependent and autonomous states.
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PMID:Development of methods for the quantitative in vitro analysis of androgen-dependent and autonomous Shionogi carcinoma 115 cells. 83 42

We have demonstrated that differential housing alters the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma (SC115). In the present study we wished to determine if changes in plasma levels of hormones or a shift in the responsiveness of the tumor cells to hormones was responsible for the differential tumor growth rates observed. Plasma testosterone and corticosterone levels were assayed 24 h, 3 days and 1 week post tumor cell/vehicle injection. Also 3 weeks post injection androgen and glucocorticoid receptor binding capacity (Bmax) and binding affinity (Kd) and the in vitro responsiveness of tumor cells to dihydrotestosterone and hydrocortisone were measured. At 24 h post injection, plasma testosterone levels were significantly increased in mice with large tumors, but remained low in mice with small tumors. Plasma corticosterone levels were significantly elevated in mice with small tumors compared to those of mice with large tumors at all time points measured. Androgen and glucocorticoid receptor binding capacity and binding affinity of tumor cells did not differ among groups. Further, all groups tested had the ability to respond to dihydrotestosterone and hydrocortisone in vitro. These data indicate that an effect of housing condition on plasma levels of steroid hormones may, in part, mediate the differential tumor growth rates observed in this model.
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PMID:Endocrine mediation of psychosocial stressor effects on mouse mammary tumor growth. 151 12

The sex hormones of mice have effects on the immune response and the synthesis of epidermal growth factor(EGF). Androgen inhibits the former and enhances the later, whereas estrogen has the opposite effect. EGF is one of the tumor growth factors. In the present study, mice before or after sexual maturation, or gonadectomized adults of both sexes, were subcutaneously inoculated with sarcoma-180 tumor cells. The tumors grew rapidly, with no difference in genders before sexual maturation. However, tumor growth was rapid in adult male mice after sexual maturation, but retarded or inhibited in adult female mice. In orchidectomized male mice, tumor growth slowed down, in ovariectomized female mice, tumor growth accelerated. There was no difference in the rate of tumor growth among gonadectomized mice of either sex.
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PMID:[The relationship between sexual maturation and growth of the subcutaneous sarcoma-180 tumor]. 181 Oct 70

This study addresses, in an animal tumor model, the clinical problem of "escape from castration inhibition." Somatuline (BIM-23014C), an octapeptide analogue of somatostatin with enhanced potency and longer duration of biological activity was administered as a therapeutic agent, over a period of 90 and 197 days, to male Copenhagen rats bearing syngeneic Dunning R-3327-H prostate tumors. Androgen sensitivity was confirmed by the response of tumors to castration and by the significant inhibition of tumor growth in intact animals by treatment with a luteinizing hormone-releasing hormone antagonist (BIM-21009). Inhibition of tumor growth resulting from castration persisted for 102 days, after which progressive regrowth occurred, indicating an escape from castration inhibition. When Somatuline treatment was initiated as an adjuvant therapy 5 days after castration, the rate of tumor regrowth during escape was significantly retarded. During the period of 197 days postcastration, tumors in the vehicle-treated, intact controls grew to an average diameter of 38.6 +/- 7.6 mm and tumors in vehicle-treated castrate controls grew to an average diameter of 23.3 +/- 4.1 mm (60% test/control). Treatment with the luteinizing hormone-releasing hormone antagonist induced no significant additional tumor inhibitory effects in castrated animals which developed tumors having an average diameter of 30.2 +/- 8.2 mm (78% test/control). Treatment of tumors in castrate animals with Somatuline, on the other hand, induced a significant (P less than 0.01) tumor-inhibitory effect that was greater than that produced by castration alone, developing an average tumor diameter of only 14.3 +/- 2.6 mm, (37% test/control). A growth inhibitory effect was also inducible in animals having tumors that had already escaped castration inhibition. The relative nontoxicity of a somatostatin analogue such as Somatuline suggests that chronic or maintenance therapy of slow-growing prostate cancers may be both feasible and acceptable in a clinical setting.
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PMID:Treatment of R-3327 prostate tumors with a somatostatin analogue (somatuline) as adjuvant therapy following surgical castration. 197 Feb 75

A current hypothesis suggests that androgen administration prior to chemotherapy (androgen priming) may potentiate tumor cytotoxicity in prostate cancer. The Dunning R3327G rat prostatic tumor model was used to test this concept experimentally. Control groups without priming included (1) intact untreated, (2) castrate alone and (3) castrate+ chemotherapy (cyclophosphamide, 30 mg/kg/day for 2 days with repeat cycle in 25 days- CTX). Two experimental groups received androgens, one before and one after chemotherapy. Treatment effect was monitored by quantitating tumor volume and animal survival. Control groups receiving castration and chemotherapy had a retardation of tumor growth and a prolongation of survival when compared to untreated animals. Androgen priming before but not after chemotherapy enhanced the degree of tumor suppression. With the androgen-priming protocol, all androgen-primed tumors had regressed, 3/6 tumors had disappeared and 3 were only palpable. At the same time point, tumors in all the other groups were actively growing and had volumes greater than the initial values (P less than 0.01). Median survival was significantly prolonged in primed animals 191 vs 40 days for untreated animals and 150 days for the nonprimed castration + chemotherapy animals (P less than 0.02). These findings have been repeated with several replicate experiments. These observations confirm the hypothesis that androgen priming can potentiate chemotherapy in an experimental system.
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PMID:Androgen-primed chemotherapy-experimental confirmation of efficacy. 228 85

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

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

Mice bearing the androgen-responsive Shionogi mammary carcinoma SC115 were treated with different concentrations of testosterone to determine if regulation of growth by testosterone would affect the susceptibility of the tumor to eradication by drugs. Following s.c. injection of 2 X 10(6) cells, tumors grew to 3 g by 21 +/- 2.1 days in males (n = seven) and 30 +/- 2.4 days in females administered testosterone (n = ten). If androgen was withdrawn, tumors weighing 1 g regressed temporarily but resumed growing after a delay of 19 +/- 1.7 days in males and 6 +/- 3.2 days in females. A combination of cyclophosphamide (100 mg/kg) and Adriamycin (6.5 mg/kg), three i.p. injections 7 days apart, caused a tumor growth delay (TGD) of 5 +/- 3.8 days in males and 26 +/- 3.2 days in females. The combination of endocrine therapy and chemotherapy was superior to either treatment alone in males. Androgen withdrawal plus chemotherapy was additive; a submaximal dose of testosterone for tumor growth plus drugs was more effective, causing a TGD of 40 +/- 2.7 days. There were no significant differences in TGD in females receiving treatments singly or in combination, possibly due to the fact that tumors in females were more sensitive to drugs alone and less sensitive to testosterone alone than were tumors in males. To ascertain if combination therapy would be effective in females in an adjuvant situation, the same treatment regimens were administered 1 day after injection of 10(6) tumor cells. Under these conditions, hormonal manipulations combined with chemotherapy resulted in a longer TGD than either modality alone. Furthermore, submaximal doses of testosterone for growth plus chemotherapy induced a longer disease-free interval (no palpable tumors by 120 days in 12 of 12 mice) than did complete androgen withdrawal plus drugs (palpable tumors in 4 of 5 mice by 104 +/- 2.7 days). The results demonstrate that endocrine regulation of SC115 mammary tumor growth can alter responsiveness of the tumor to chemotherapy.
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PMID:Effects of endocrine regulation of growth of a mouse mammary tumor on its sensitivity to chemotherapy. 670 51

Androgen-stimulated tumors of the dorsal prostate were derived from an estrogen-dependent tumor of Nb rats (Nb-2Pr-E). The change followed repeated androgen treatments in a rat bearing a tumor which had regressed after estrogen removal. The eventual tumor regrowth provided tumor transplant lines, Nb-2Pr-A, which grew in normal or androgenized males, slowly in castrates, but not in estrogenized females. The Nb-2Pr-A growing tumors regressed after treatment with estrogen, and tumors which eventually regrew were autonomous. Slow tumor growth in castrated animals also responded to estrogen treatment. Tamoxifen, an antiestrogen, caused tumors growing in males to become stationary or regress. Regrowth of tumors after they had responded to tamoxifen again responded to castration or estrogen. Tumors which escaped from estrogen treatment or were autonomous did not respond to tamoxifen. The most effective sequence for treatment was tamoxifen followed by castration and, finally, estrogen. Tamoxifen treatment or castration allowed tumors to remain hormone responsive, whereas initial estrogen treatment prevented response to subsequent therapy and led to an autonomous change.
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PMID:Development of androgen-stimulated transplants of Nb rat carcinoma of the dorsal prostate and their response to sex hormones and tamoxifen. 743 42

When the human prostate cancer cell line, LNCaP 104-S, the growth of which is stimulated by physiological levels of androgen, is cultured in androgen-depleted medium for > 100 passages, the cells, now called LNCaP 104-R2, are proliferatively repressed by low concentrations of androgens. LNCaP 104-R2 cells formed tumors in castrated male athymic nude mice. Testosterone propionate (TP) treatment prevented LNCaP 104-R2 tumor growth and caused regression of established tumors in these mice. Such a tumor-suppressive effect was not observed with tumors derived from LNCaP 104-S cells or androgen receptor-negative human prostate cancer PC-3 cells. 5 alpha-Dihydrotestosterone, but not 5 beta-dihydrotestosterone, 17 beta-estradiol, or medroxyprogesterone acetate, also inhibited LNCaP 104-R2 tumor growth. Removal of TP or implantation of finasteride, a 5 alpha-reductase inhibitor, in nude mice bearing TP implants resulted in the regrowth of LNCaP 104-R2 tumors. Within 1 week after TP implantation, LNCaP 104-R2 tumors exhibited massive necrosis with severe hemorrhage. Three weeks later, these tumors showed fibrosis with infiltration of chronic inflammatory cells and scattered carcinoma cells exhibiting degeneration. TP treatment of mice with LNCaP 104-R2 tumors reduced tumor androgen receptor and c-myc mRNA levels but increased prostate-specific antigen in serum- and prostate-specific antigen mRNA in tumors. Although androgen ablation has been the standard treatment for metastatic prostate cancer for > 50 years, our study shows that androgen supplementation therapy may be beneficial for treatment of certain types of human prostate cancer and that the use of 5 alpha-reductase inhibitors, such as finasteride or anti-androgens, in the general treatment of metastatic prostate cancer may require careful assessment.
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PMID:Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride. 887 18


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