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

The effects of two hormonal agents with different mechanisms of action, medroxyprogesterone acetate (MPA) and tamoxifen (TAM), on the tumor growth and hormone receptor status were evaluated in rat mammary tumors induced by 7,12-dimethylbenz[alpha]anthracene (DMBA). All estrogen receptor-positive (ER(+)) tumors became ER-negative (ER(-)), and 3 out of 4 progesterone receptor-negative (PgR(-)) and ER(+) tumors became PgR-positive (PgR(+)) after daily, oral administration of TAM for 2 weeks. In contrast, ER and PgR remained unchanged after daily administration of MPA for 2 to 4 weeks. All the ER(+) and PgR(-) tumors were transformed into PgR(+) after daily treatment with MPA for 2 weeks and then with TAM for another 2 weeks, but tumor regression was modest and none disappeared completely. In contrast, complete remission was achieved in all ER(+) tumors in the group treated with TAM for 2 weeks and then with MPA for another 2 weeks. The results suggest that the antitumor activity of the latter treatment regimen was significantly higher than that of the former. The possible mechanisms of antitumor activity of two hormonal agents are discussed.
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PMID:Effective sequential administration of tamoxifen and medroxyprogesterone acetate for 7,12-dimethylbenz[a-anthracene-induced rat mammary tumors in relation to hormone receptors. 293 17

A-ring substituted estrogens have been examined as growth inhibitors of the hormone dependent MXT murine mammary tumor. Certain of these estrogen analogues inhibited the growth of newly implanted as well as established MXT tumors when administered either by s.c. or i.p. injections or by intubation. These compounds were nontoxic over a broad range of active levels. Amino and nitro groups, introduced at position-4 of estrone 3-methyl ether were particularly carcinostatic, a property not shared by 4-bromoestrone 3-methyl ether. In addition tumor inhibition was greatly diminished by placing the nitro group at the other ortho position (i.e., carbon-2). Evidence indicates that the A-ring substituted estrogens may function as growth inhibitors via the estrogen receptor mechanism in the case of 4-nitro- and 4-aminoestrone. The 3-methyl ethers of these compounds also blocked tumor growth, possibly through in vivo dealkylation leading to the free phenolic A-ring substituted estrogens. On the other hand, A-ring substituted 3-deoxyestrogens (particularly 4-nitro- and 4-aminoestratrien-17 beta-ol), which do not bind to receptor, were also excellent inhibitors of hormone dependent MXT breast tumors and therefore must express their activity by mechanisms other than that mediated by receptor. The A-ring substituted estrogens are unlike tamoxifen and diethylstilbestrol which (a) display toxicity at optimum inhibitory doses and (b) are inactive or marginally active in rodent breast cancer models.
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PMID:A-ring substituted estrogens as inhibitors of the MXT transplantable mammary ductal carcinoma. 304 Feb 28

The historical development of carcinogen-induced rat mammary tumors is reviewed. Most work has been done with the polycyclic hydrocarbon dimethylbenz[a]anthracene (DMBA). Huggins was the first to describe a protocol for the routine production of DMBA-induced mammary tumors and demonstrated their ovarian dependency. Pearson found that DMBA-induced tumors could not grow during estrogen administration in hypophysectomized rats, and it was subsequently shown that estrogen-stimulated prolactin release is responsible for tumor growth. The antiestrogen tamoxifen has been used in the treatment of breast cancer and has been studied extensively in the DMBA-induced rat mammary carcinoma model. The complexities of tamoxifen's pharmacology in vivo suggested that the development of estrogen-responsive systems in vitro might facilitate an understanding of tamoxifen's mode of action. The description of estrogen-stimulated prolactin synthesis by primary culture of pituitary gland cells provided an opportunity to study the structure-activity relationships of antiestrogens. A model ("crocodile model") to describe the interaction of estrogens and antiestrogens is proposed. An estrogen will permit the conformation change in the receptor that is necessary to translate into prolactin synthesis. An antiestrogen wedges into the binding site on the receptor to prevent changes in protein conformation. As a result prolactin synthesis is inhibited. An extensive study of structure-activity relationships has been used to describe the nature of the ligand binding site of the estrogen receptor. The model can be used to predict the pharmacology of new agents.
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PMID:Laboratory models of breast cancer to aid the elucidation of antiestrogen action. 310 56

The transplantable mouse mammary tumor, TPDMT-4, is pregnancy-dependent and requires prolactin (PRL), estradiol (E2) and progesterone (Pg) for growth. To examine the role of PRL in regulating tissue growth and the levels of estrogen receptor (ER) and progesterone receptor (PgR), tumor-bearing mice were ovariectomized, hysterectomized and then injected with ergocornine hydrogenmaleate (ERG), ERG + PRL, or ERG + PRL + E2 + Pg. Total (nuclear + cytoplasmic) ER and PgR in normal and neoplastic mammary tissues were measured. In addition, tumor size and tritium-labeled thymidine [( 3H]dThd) incorporation into nuclei of the tumor and mammary gland were determined. PRL alone caused a 2- to 3-fold increase in ER and PgR levels in normal mammary gland but not in the tumor. PRL alone caused a modest increase in the number of 3H-thymidine-labeled nuclei in both tissues. PRL combined with E2 and Pg increased the percent of labeled nuclei 5- to 10-fold in both tissues, and increased the PgR levels in normal but not in tumor tissue. Thus, PRL alone can increase ER in normal mammary tissue but this increase is not required for growth since ER levels are unchanged when PRL + E2 + Pg are injected and mammary cell growth is stimulated. The ability of PRL to up-regulate ER has been lost in the tumor. Since basal levels of ER and PgR are not altered in the tumor when PRL + E2 + Pg are given, an increase in ER and PgR levels is not required for the three hormones to stimulate tumor growth.
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PMID:Prolactin regulation of estrogen and progesterone receptors in normal and neoplastic mouse mammary tissue. 311 44

Four human breast carcinoma strains serially transplanted into nude mice were used for the experimental chemotherapy and combination chemoendocrine therapy. Whereas three of these strains (MCF-7, Br-10, TM-61) possessed cytosol estrogen receptor (ERc) and were dependent on estradiol for the tumor growth, the other strain (MX-1) without ERc was hormone independent. For the chemotherapy, mitomycin C (MMC), adriamycin (ADM), cyclophosphamide (CPM) and 5-fluorouracil (5-FU) were administered 3 times every 4 days. To know the stability of ERc after chemotherapy, binding sites of ERc were measured 4 days after MMC administration at doses of 1, 2 and 4.5 mg/kg. For the chemoendocrine therapy, 1 or 2 mg/kg of MMC was administered once followed by treatment by tamoxifen (TAM). The effect of treatment was evaluated by T/C ratio of the tumor weight. MMC showed the most excellent antitumor effect and CPM and ADM showed a moderate effect. As ERc was found to be stable by MMC treatment, TAM was used after MMC, and this combination of MMC and TAM revealed an additive effect against ERc positive strains and no combination effect was observed in MX-1 without ERc. The dose response curves of 4 strains to MMC alone against 4 strains were made and the effect of combination chemoendocrine therapy was converted to the effect of MMC alone, showing the dose of MMC could be significantly reduced. Binding sites of ERc which were measured 4 days after MMC administration (1, 2 and 4.5 mg/kg) was found to be stable, suggesting TAM treatment after MMC might be reasonable. From these results, chemoendocrine therapy of MMC followed by TAM was considered to be beneficial modality for clinical treatment of the cytotoxic agent and increasing the antitumor effect.
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PMID:[Experimental chemo- and chemoendocrine therapy of human breast carcinomas serially transplanted into nude mice]. 312 45

Physiochemical properties of an estrogen binding protein were characterized in three human melanoma cell lines, UISO-MEL-1, UISO-MEL-2, and UISO-MEL-4. Estrogen binding to melanoma cytosol was saturable, specific for estrogens, and represented by a single class of high-affinity, limited-capacity binding sites (Kd 5.5 x 10(-10) M, 2.7 +/- 0.5 fmol/mg of cytosol protein, UISO-MEL-2; 2.2 x 10(-10) M, 7.8 +/- 3.3, UISO-MEL-4) (SEM). UISO-MEL-1 cytosols did not bind estradiol. The binding protein in UISO-MEL-2 and -4 sedimented at 8.5S and 9.2S, respectively, in the presence of 10 mM sodium molybdate. Solid-phase radioimmunoassay with a monoclonal antibody specific for human estrogen receptor (H222 sp lambda) showed good correlation (r = 0.84) with a hydroxyapatite biochemical assay of identical melanoma cytosols. Exposure of UISO-MEL-2 to estradiol produced a time- and temperature-dependent increase in total nuclear receptor for estrogen in vitro. Estradiol treatment of athymic mice also significantly increased cytosol progesterone receptor content in UISO-MEL-2 and UISO-MEL-4 xenografts. Estradiol had no effect on the plating efficiency or growth of any melanoma cell line or normal melanocytes in vitro. Tamoxifen also had no effect on melanoma growth in vitro. In contrast, chronic exposure of athymic mice carrying estrogen receptor-positive UISO-MEL-2 to estradiol resulted in a sex-dependent increase in tumor latency and overall inhibition of tumor growth. Taken together, these observations suggest that a subset of human melanomas contains limited amounts of an estrogen binding protein similar to that observed in other estrogen-responsive tissues. The lack of effect of estradiol on melanocyte and melanoma growth in vitro, coupled with a decrease in tumor growth in athymic mice, suggests that, while inhibition may be receptor mediated, possible indirect actions of estradiol must also be considered.
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PMID:Effect of 17 beta-estradiol on the growth of estrogen receptor-positive human melanoma in vitro and in athymic mice. 319 86

Estrogens have previously been shown to induce covalent DNA modifications specifically in the hamster kidney, the target organ of estrogen-inducible and -dependent renal carcinoma. The DNA adducts, formed by yet unknown mechanisms, have been postulated to mediate hormonal carcinogenesis in this animal model. In an attempt to study a possible involvement of estrogen receptor mechanisms in the formation of DNA adducts, 17 beta-estradiol and the antihormone tamoxifen were concomitantly administered as s.c. implants to male Syrian hamsters. 17 beta-Estradiol-treated and tamoxifen-treated animals served as positive and negative controls, respectively. The tumor incidence decreased from 100% in 17 beta-estradiol-treated controls to 25% in the group receiving tamoxifen in addition to hormone. Tamoxifen-treated animals did not develop kidney tumors and did not show any detectable DNA damage. DNA adduct levels were comparable in hamsters treated with 17 beta-estradiol and 17 beta-estradiol plus tamoxifen for 5 or 7 months. In hamsters inoculated with H-301 cells, which are derived from the estrogen-induced hamster renal carcinoma and are estrogen dependent for growth, tamoxifen decreased estrogen-dependent H-301 tumor growth. However, in cell culture, neither 17 beta-estradiol nor tamoxifen influenced H-301 cell division. It was concluded that tamoxifen inhibited the growth of estrogen-induced renal carcinoma but did not interfere with tumor initiation since it did not inhibit the formation of DNA adducts. Moreover, receptor mechanisms were most probably not involved in the induction of DNA modifications by estrogens.
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PMID:Inhibition of estrogen-induced renal carcinogenesis in male Syrian hamsters by tamoxifen without decrease in DNA adduct levels. 333 75

A rat transplantable pituitary tumor, MtT/F84, grows much faster in E2 treated rats than in normal females, but is much retarded in thyroidectomized rats. Triiodothyronine (T3) administration in a drinking water increased the tumor growth by the dose dependent manner. The tumor contained both estrogen receptor (ER) and T3 receptor. ER levels both in the nuclei and cytosols elevated 2 to 3 times by the T3 administration compared to those of control. E2 administration promotes the growth of MtT/F84 through elevation of nuclear ER level. T3 may directly elevate cellular ER level and thus it may enhance estrogenic actions including the tumor growth.
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PMID:Increase of estrogen receptor level by thyroxine in estrogen dependent pituitary tumor (MtT/F84) in rats. 335 70

Epidermal growth factor receptor (EGFR) expression was determined on 88 primary breast carcinomas immunohistochemically. These results were compared with growth fractions (Ki-67 immunoreactivity and Transferrin receptor (TrfR) expression), histologic tumor type, tumor grading, axillary lymph node status and estrogen receptor (ER) status. 60.2% were EGFR positive. Cytomorphology predominantly revealed a fine granular staining pattern. Sometimes a concentrated immunoreaction on the intercellular and basal oriented cell poles could be observed. EGFR expression in relation to growth fractions, grading, tumor diameter and lymph node status showed no correlation, suggesting that EGFR status seems to be independent to tumor growth and morphological prognostic parameters. ER status revealed an inverse correlation to EGFR expression (Kendall's tau: -0.22804, p = 0.012). In this context, it stands to reason to investigate further how far determination of EGFR expression justifies the existence of different subpopulations of breast cancer cells with respect to prognostic value.
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PMID:Expression of epidermal growth factor receptors (EGFR) on breast carcinomas in relation to growth fractions, estrogen receptor status and morphological criteria. An immunohistochemical study. 336 49

The purpose of this study was to investigate if the local effects of estradiol on the Dunning R3327 prostatic adenocarcinoma were estrogen-receptor mediated. All rats with the transplantable Dunning R3327 prostatic adenocarcinoma were castrated on the first day of treatment and were supplemented with daily s.c. injections of testosterone propionate (0.1 mg) during the treatment period, lasting for 6 weeks. The following treatment groups were studied: castration + testosterone supplementation (C + T, control group), C + T and estradiol-17 beta (50 micrograms/daily s.c.), C + T and tamoxifen (1 mg twice a week s.c.), and C + T and estradiol-17 beta in combination with tamoxifen. Tumor volumes were measured every week. At the end of the treatment period, pieces of the tumors were taken for morphological studies and estrogen-receptor analysis. In the groups of rats given tamoxifen treatment no estrogen-receptor binding was detectable in prostatic tumors, but, despite this, tamoxifen did not prevent either the inhibitory effect of estradiol-17 beta on the tumor growth rate or the estrogen-induced decrease of volume density of prostatic glandular epithelium. In contrast, the estrogen-induced increase of volume density of the stroma was abolished by tamoxifen, suggesting that this effect may be mediated by the estrogen receptor. A morphometrical method for estimating the growth of different tumor compartments is presented. Treatment with estradiol-17 beta, both with or without combined treatment with tamoxifen, reduced the growth of both the tumor epithelium and stroma. The direct effect of estradiol-17 beta on the growth and morphology of the Dunning R3327 prostatic adenocarcinoma seemed not to be mediated by the estrogen receptor.
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PMID:Antiestrogens do not counteract the inhibitory effect of estradiol-17 beta on the growth of the Dunning R3327 prostatic adenocarcinoma. 339 91


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