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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine whether an estrogenic mechanism is involved in dietary fat-modulated tumor development and growth. Female Sprague-Dawley rats were placed on a semipurified low-fat (2% fat), high-saturated fat (20% fat), or high-polyunsaturated fat (20% fat) diet at 21 days of age. A single dose of 7,12-dimethylbenz[a]anthracene (DMBA, 10 mg) was administered intragastrically at 50 days of age. Two studies were performed. One tested the effectiveness of antiestrogen treatment (either tamoxifen or analog II) on tumor development when it was given one week prior to and one week after DMBA treatment in animals consuming a high-polyunsaturated fat diet. The second six-week study tested the antiestrogen effectiveness in arresting tumor growth and in producing regressions of established DMBA-induced tumors in rats consuming various levels and types of fat. The results of these studies indicate that both antiestrogens employed reduced the rate of growth and increased the number of regressions of established DMBA-induced tumors. In general, this was true in animals fed diets with a high content of either saturated or polyunsaturated fats and to a lesser extent in animals fed a low-fat diet. Tamoxifen produced a somewhat greater reduction in the growth of established tumor than did analog II. However, analog II, which is a more biologically "pure" antiestrogen, reduced the incidence of animals with mammary tumors and total tumor burden when administered one week before and one week after DMBA dosing. Tamoxifen, which is a partial estrogen-agonist, did not alter tumor incidence, but it did reduce the total tumor burden under these same experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The interaction of dietary fat and antiestrogen treatment on DMBA-induced mammary tumors in the rat. 393 37

Hepatic hyperplastic nodules (HHNs) induced by the 'resistant hepatocyte method' of Solt and Farber were studied as an experimental prototype of oral contraceptive-related tumors. Cytoplasmic estrogen receptors were present in all HHNs harvested and their concentration was always less than that in normal liver. No specific cytoplasmic progestin receptors could be measured in the above tumor or liver specimens. The long-term administration of estradiol-17 beta (4.8-24.0 micrograms/day) resulted in the death of all but one of 20 animals prior to termination at 10 months. Tamoxifen (0.25-2.5 mg biweekly) which did not lead to excess mortality, decreased HHN grade (proportion of liver slice occupied by HHN) and inhibited malignant transformation. Combination therapy with single-dose estradiol-17 beta (4.8 micrograms/day) and various doses of tamoxifen (0.25-2.5 mg biweekly) in most cases reduced mortality, HHN grade and malignant transformation. Cytoplasmic progestin receptors were absent and estrogen receptors were either undetectable or present in low concentration in hepatic tumors harvested at the time of termination. Our results indicate that HHNs are hormone-dependent and that malignant transformation can be inhibited by tamoxifen alone or in combination with estradiol-17 beta.
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PMID:Tamoxifen alone or in combination with estradiol-17 beta inhibits the growth and malignant transformation of hepatic hyperplastic nodules. 400 11

Hepatic hyperplastic nodules (HHNs) induced by the 'resistant hepatocyte method' of Solt et al. were studied as an experimental prototype of oral contraceptive-related tumors. Cytoplasmic estrogen receptors were present in all HHNs harvested and their concentration was always less than that in normal liver. No specific cytoplasmic progestin receptors could be measured in the above tumor or liver specimens. The long-term administration of estradiol-17 beta (4.8-24.0 micrograms/day) resulted in the death of all but one of 20 animals prior to termination at 10 months. Tamoxifen (0.25-2.5 mg biweekly), which did not lead to excess mortality, decreased HHN grade (proportion of liver slice occupied by HHN) and inhibited malignant transformation. Combination therapy with single-dose estradiol-17 beta (4.8 micrograms/day) and various doses of tamoxifen (0.25-2.5 mg biweekly) in most cases reduced mortality, HHN grade and malignant transformation. Cytoplasmic progestin receptors were absent and estrogen receptors were either undetectable or present in low concentrations in hepatic tumors harvested at the time of termination. Our results indicated that HHNs are hormone-dependent and that malignant transformation can be inhibited by tamoxifen alone or in combination with estradiol-17 beta.
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PMID:Tamoxifen alone or in combination with estradiol-17 beta inhibits the growth and malignant transformation of hepatic hyperplastic nodules. 400 26

Cloned human MCF-7 breast tumor cells were prevented from proliferating when grown in charcoal-dextran stripped human female serum (CDFHS)-supplemented media (40% and 10%); this inhibition was maximally cancelled by estradiol-17, cisTamoxifen, and Metabolite E, whereas Tamoxifen, N-desmethylTamoxifen and Metabolite Y only partially blocked the inhibitory effect of CDFHS. The efficiency of this reversing effect was estradiol-17 greater than Metabolite E greater than cisTAM greater than OHTAM greater than TAM = Metabolite Y. CDFHS at 2% allowed for near maximal cell yield; estradiol-17 at concentrations above 3 X 10(-10) M inhibited cell proliferation whereas at lower concentrations was ineffective. All the triphenylethylenes tested at 2% CDFHS were toxic above 3 X 10(-7) M; beyond these concentrations, these drugs did not significantly affect the cell yield. The proliferative properties of E2 and these triphenylethylenes do not directly correlate with their binding affinities to the intracellular estrophilins. Finally, the control of the proliferation of C7MCF7-173 cells appears to be affected by the interaction among a) estradiol-17 or the triphenylethylenes, b) a specific blood-borne inhibitor of the proliferation of estrogen-sensitive cells (estrocolyones), and c) an inhibitor "receptor"-like structure in these target cells.
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PMID:Estrogenic effect of tamoxifen and its derivatives on the proliferation of MCF7 human breast tumor cells. 401 Apr 80

Tamoxifen (ICI 46474) is the trans-isomer of 1(p-beta-dimethylaminoethoxy-phenyl)-1, 2-diphenylbut-1-ene. In several but not all mammal species it is a potent anti-estrogen. It is thought to act by blocking estrogen receptors. Patients were 68 women with advanced primary carcinoma of the breast, recurrences in the chest wall or soft tissue metastases. The oral dose of tamoxifen was either 10 mg or 20 mg twice daily. Patients were seen and laboratory tests done monthly for 6 months. Side effects were usually trivial and their incidence was the same at both dose levels. Of 26 patients who showed a reduction in tumor size to half or less, 5 had been in remission for over a year and another 10 for over 6 months. Some tumor responses were spectacular. The drug was less effective for bone deposits. In this study 12 of 33 patients (36%) receiving 10 mg of tamoxifen twice daily showed a definite response while a futher 8 (24%) showed a partial response. A definite response was seen in 14 out of 35 (40%) receiving 20 mg twice daily and a partial response in a further 13 (37%). The total response for low dosage was 60% and for high dosage 77%.
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PMID:Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. 456 4

In acid solutions, Tamoxifen is protonized and forms with eosin a fluorescent ionic association (lambda exc 480 nm, lambda em 565 nm). This reaction is quantitatively linked to the concentration of Tamoxifen. Thus the Tamoxifen induced fluorescence observed in hormone-dependent malignant breast tumor cells after Papanicolaou staining procedure, appears as a consequence of the binding of Tamoxifen to eosin.
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PMID:[Tamoxifen fluorescence as a marker of hormone-dependence: physicochemical aspects]. 618 88

Hormonal therapy, surgical and medical ablation procedures, and the use of palliative cytotoxic and adjuvant chemotherapy in the management of breast cancer are reviewed. Breast cancer staging systems are described that use various clinical and histological criteria in choosing the most appropriate therapy and in predicting therapeutic response. Estrogen and progesterone receptor titers now allow for a more reliable prediction of whether palliative hormonal therapy or cytotoxic drug therapy is preferable. Endocrine methods include surgical ablative procedures, additive hormonal therapy, and antiestrogenic therapy with tamoxifen or aminoglutethimide. Aminoglutethimide appears to be at least as efficacious as surgical adrenalectomy and hypophysectomy in treating hormonally sensitive tumors in women with advanced breast cancer, and it is associated with a lower incidence of complications than surgical ablation procedures. Tamoxifen appears to be at least as effective as other forms of endocrine treatment, and it is now preferred to diethylstilbestrol in the treatment of postmenopausal women. Compared with androgens, progestogens, and glucocorticoids, estrogens have the highest rate of objective response in the treatment of advanced breast cancer; however, the use of estrogens has diminished since tamoxifen is associated with similar efficacy and a lower incidence of side effects. Palliative cytotoxic chemotherapy is used for those women who have low titers of hormone receptors, rapidly progressing disease, widespread disease to visceral organs, or tumors that are refractory to hormonal therapy. Combinations of cytotoxic agents yield response rates and durations of response that are superior to single-agent therapy. Attempts are being made to enhance the "cure" rate, postoperative disease-free intervals, and survival times for women who have undergone surgical resection of the breast tumor. The benefits of adjuvant cytotoxic chemotherapy are particularly evident for pre- and postmenopausal women with three or less involved lymph nodes. The potential merits of adjuvant hormonal therapy and combination therapy with hormones and cytotoxic agents are being studied.
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PMID:Management of breast cancer. 619 63

Anti-estrogens and progestagens are synergistically active in the treatment of hormone dependent tumors. The combined action of both compounds in daily treatment schedules are analyzed in rat uterus and in DMBA- induced rat mammary tumors. Tamoxifen in contrast to estradiol does not significantly affect tissue growth, while PgR induction is considerably stimulated by Tamoxifen. It is suggested that the "estrogenic effects" of Tamoxifen and estradiol are separately modulated. When given in sequential combination with anti-estrogens, the anti-tumor response of progestagens is enhanced. Combinations of hormonal treatment based on careful analysis of the regulation processes at target cell level may greatly improve results of anti-tumor therapy.
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PMID:Independent regulation of growth and steroid receptors in uterus and mammary tumors of rats. 623 Sep 84

Methods and evaluation of the human tumor stem cell assay (HTSCA) are described. Advantages and disadvantages of the test system are elaborated. The in vitro/in vivo correlation in the drug screening of human ovarian carcinomas shows that the prediction of sensitivity to a cytotoxic agent is only possible in 64%. Prediction of drug resistance, however, seems to be possible in 95%. The number of patients that profit from the HTSCA seems to be only less than 10%. Our investigations describe the influence of various hormones and antiestrogens on the colony formation of human ovarian carcinoma cells. Tamoxifen and his major metabolite 4-hydroxy-tamoxifen were the most active agents. Both compounds inhibit the colony survival (70% at pharmacological concentrations) of 60% of the screened ovarian carcinomas. A significant correlation to the quantitative level of estrogen or progesterone receptors could not be proved. Colony formation of ovarian carcinoma cells was compared in the HTSCA as described by Hamburger and Salmon and in a methylcellulose-monolayer system. Our results show that the colony formation corresponds to the results of the original HTSCA: Cloning ovarian carcinoma cells in the methylcellulose-monolayer, however, seems to be technically easier and faster.
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PMID:[Significance of the colony formation test in ovarian carcinoma]. 623 68

After ovariectomy DMBA tumor-bearing SD rats were treated with the estrogen DES, a combination of DES plus mammary tumor-inhibiting antiestrogen (tetramethylHES, 3,3'HES and tamoxifen respectively) or with tetramethylHES alone. Small doses of DES led to a stimulation of tumor growth showing a maximum effect at 1 microgram/kg/day, whereas higher doses inhibited tumor growth. In the combination experiment only tetramethylHES reduced, i.e. antagonized, the DES effect. Tamoxifen and 3,3'HES, however, led to an increase of the tumor growth-stimulating and inhibiting effects of DES. Only the dose of 10 mg/kg/day of tetramethylHES led to a slight stimulation of the tumor growth in ovariectomized DMBA tumor-bearing rats. These results indicate that 3,3'HES and tamoxifen possibly unfold their mammary tumor-inhibiting activity by means of their estrogenic potency, whereas tetramethylHES might act as an antiestrogen, though the latter compound does not lack estrogenic activity completely.
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PMID:Tumor growth-stimulating and inhibiting effects of antiestrogens on the DMBA-induced mammary carcinoma of the ovariectomized, diethylstilbestrol-treated SD rat. A study on the mechanism of action of antiestrogens. 630 29


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