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

Tamoxifen aziridine (TA), an antiestrogen-based affinity label for the estrogen receptor, is highly selective and efficient in its covalent binding to the estrogen receptor (Katzenellenbogen et al., J. biol. Chem. 258 (1983) 3487-3495). Thus, it was of interest to investigate the biological character and potency of this compound and, in particular, to determine if the irreversible attachment of this tamoxifen-derived compound to the estrogen receptor would result in enhanced antiestrogenic properties or in unusual biological activity. The effect of tamoxifen aziridine and tamoxifen (Tam), the parent compound which is an antiestrogen that binds reversibly to the estrogen receptor, were compared with respect to their effects on uterine growth, growth of dimethylbenzanthracene (DMBA)-induced mammary tumors in rats, and proliferation and plasminogen activator activity of MCF-7 human breast cancer cells. In immature (day 20) rats, Tam and TA behaved as weak estrogen agonists and estrogen antagonists in that Tam or TA alone increased uterine weight to levels lower than that evoked by estradiol (E2), and both were able to suppress the stimulation of uterine weight evoked by E2. Administration of Tam and TA via Alzet minipumps (25 or 200 micrograms/rat/day) to mature rats bearing DMBA-induced mammary tumors resulted in marked regression and/or disappearance of most tumors. Uterine weights were also suppressed in these mature rats by Tam and TA. Tam was slightly more potent than TA in evoking tumor regression and in suppressing uterine weights in these in vivo studies. In MCF-7 human breast cancer cells in culture, Tam and TA suppressed cell proliferation and evoked no increase in plasminogen activator activity by themselves, while being very effective in preventing plasminogen activator activity stimulation by E2. Thus, TA displayed a bioactivity profile similar to that of Tam, the reversibly binding ligand, in vitro and in vivo. The covalent attachment of TA to the receptor does not, therefore, markedly alter the biological character or potency of the antiestrogen receptor complex.
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PMID:Biological activities of tamoxifen aziridine, an antiestrogen-based affinity label for the estrogen receptor, in vivo and in vitro. 393 47

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

Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the antiestrogenic agent tamoxifen (Nolvadex) during an 8-12-month period. Computer tomographic, scintigraphic, and clinical evidence of an unspecific tumor response was only encountered in one patient after 4 months of therapy with tamoxifen. The 2-year results did not indicate a favorable response to antiestrogenic treatment. The significance of sex-steroid receptors and their possible prognostic value in endocrine therapy of meningiomas is discussed.
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PMID:Antiestrogenic therapy of meningiomas--a pilot study. 402 3

Variations in cytochrome P-450 levels may influence the responsiveness of uterine and breast tissue as well as carcinomas to endocrine therapy and may be of particular importance with agents such as tamoxifen (Nolvadex) where hydroxylation is known to alter therapeutic activities. Therefore, a sensitive spectrophotometric assay of cytochrome P-450 levels in reproductive tissue microsomes was developed to measure cyclohexane hydroxylase activity. Cyclohexane served as a substrate for several forms of cytochrome P-450. Human uterine leiomyomas (uterine fibroid tumor) contained significantly higher (p less than 0.01) cytochrome P-450 activity than adjacent normal myometrium. Specific activities for both leiomyomas (2.87 +/- 0.26 nmol/min/mg) and normal myometrium (1.60 +/- 0.11 nmol/min/mg) were in the range of those observed for untreated rabbit liver microsomes (1 to 3 nmol/min/mg). The contribution of smooth muscle in the specimen, the phase of the menstrual cycle, and the clinical diagnosis did not influence the level of cytochrome P-450 activity.
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PMID:Cytochrome P-450 activity in human leiomyoma and normal myometrium. 406 17

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


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