Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen has become the endocrine treatment of choice for all stages of breast cancer. Its low incidence of side effects and proven survival advantage observed during adjuvant therapy in postmenopausal women with node-positive disease has encouraged the use of long-term treatment for patients to benefit fully from therapy. The drug has an appropriate level of estrogen-like effects that could be beneficial to maintain bone density and prevent development of coronary heart disease by lowering circulating cholesterol. These effects might be useful in all patients with estrogen receptor-positive breast cancer who currently are receiving no therapy. This antiestrogenic agent could be effective therapy to deter recurrence, and the estrogen-like side effects support the physiologic processes of the patient as hormone-replacement therapy. In the laboratory, a tamoxifen-stimulated breast cancer model has been described in vivo. This form of drug resistance may occur in patients after long-term or indefinite adjuvant therapy. Novel pure antiestrogenic drugs have been discovered that soon will become available as second-line therapy after tamoxifen failure. In addition, tamoxifen is being evaluated in the United Kingdom as chemosuppressive therapy to prevent the development of breast cancer in high-risk women. A similar clinical evaluation is underway in the United States.
 ...
PMID:The strategic use of antiestrogens to control the development and growth of breast cancer. 163 67

The effect of 17 beta-oestradiol on an Ag-specific primary antibody response in cultures of human peripheral blood mononuclear cells (PBMC), stimulated by sheep red blood cells (SRBC) was studied. Addition of 17 beta-oestradiol (2 x 10(-9) to 100 x 10(-7) M final concentration), to PBMC from adult blood donors significantly augments the Ag-specific immune response. PBMC incubated with the anti-oestrogen agent Tamoxifen (10(-6) to 10(-8) M final concentration) prior to culture were no longer stimulated to produce an increased number of anti-SRBC antibodies as compared to control cultures. The augmentation of the immune response to SRBC in treated cultures is due to an inhibiting effect of 17 beta-oestradiol on CD8+ T suppressor (Ts) cells, since preincubation with Tamoxifen, which acts by competitive binding with CD8+ oestrogen receptors reverses such an effect. The antibody response of PBMC X-irradiated with 10 Gy before culture, (in order to decrease the suppressor activity), and then stimulated with SRBC without addition of oestrogen, was increased about 40% as compared to that of unirradiated PBMC. No further increase by addition of 17 beta-oestradiol to PBMC irradiated cultures was obtained. These findings confirm that oestrogen influences the regulatory radiosensitive CD8+ Ts cells subset. T helper (Th) cells and antigen presenting cells (APC) were not modulated by oestrogens. Our study demonstrates direct immunoregulatory effects of oestrogen on human PBMC and suggests that female sex hormones and anti-oestrogens agents may play a role in the pathogenesis and treatment of some autoimmune diseases and tumors, such as breast cancer.
 ...
PMID:Influence of sex steroids on the antigen-specific primary antibody response in vitro. 166 22

Tamoxifen is a well-tolerated palliative and adjuvant treatment for human breast cancer and requires continuous, long-term administration for optimal therapeutic effectiveness. A two-stage model of experimental hepatocarcinogenesis, based upon the natural history of cancer development, has been employed to assess the carcinogenic potential of tamoxifen. In this study, the effectiveness of tamoxifen both as an initiator and a promoter in hepatocarcinogenesis was assessed in female F-344 rats. Tamoxifen was tested as an initiator at a single intragastric dose of 40 mg/kg, followed by promotion with 0.05% phenobarbital. The number and size of the resulting altered hepatic lesions were quantified, and tamoxifen was found to lack initiating action at the dose tested. Other groups of animals were initiated with a nonnecrogenic, subcarcinogenic dose of diethylnitrosamine (10 mg/kg) and were fed tamoxifen at either 250 or 500 mg/kg in the AIN-76A purified diet for 6 months. The livers of these animals showed an increase in the size and number of altered hepatic lesions compared with those animals that were initiated but not exposed to tamoxifen; this indicates that tamoxifen acts as a tumor promoter in the rat liver. The promotion index of tamoxifen, a measure of relative potency, was less than one-tenth that of ethinyl estradiol and more than four times that of phenobarbital, an agent commonly employed as a representative promoting agent in experimental carcinogenesis. Since tamoxifen lacked initiating activity in the rat liver at the dose tested, the mechanism of tumor induction in long-term feeding studies by tamoxifen may be due to its promotion of spontaneously initiated hepatocytes. The chronic therapeutic use of tamoxifen should therefore be limited by the potential carcinogenic risk of this agent as an effective tumor promoter.
 ...
PMID:Tumor promotion as a target for estrogen/antiestrogen effects in rat hepatocarcinogenesis. 167 62

The biological activity of interferons (IFNs) is presumed to be mediated through the induction of a number of IFN-inducible genes. IFN-mediated gene induction was examined in two human breast cancer cell lines, MCF-7 and BT-20. Both these cell lines were remarkably responsive to IFNs as a number of IFN inducible genes were rapidly induced. We examined the sensitivity of these genes towards 2-aminopurine (2-AP), a known inhibitor of double-stranded (ds) RNA dependent protein kinase. 2-AP has also been reported to inhibit the induction of IFN-beta 1 in response to dsRNA and the genes c-myc and c-fos in fibroblasts. In both MCF-7 and BT-20 cell lines, 2-AP selectively inhibited the IFN-induced gene responses. 2-AP did not affect levels of the oncogene, HER-2/neu. Tamoxifen (TAM), an antiestrogenic drug, which is known to inhibit the activity of protein kinase C at high concentrations, did not affect IFN-mediated gene induction. Our data is consistent with the concept that the 2-AP sensitive kinase is primarily associated with the IFN-induced gene systems and that positive and negative growth regulating stimuli in breast cancer may require the participation of distinct kinases.
 ...
PMID:A distinct kinase modulates the expression of IFN-inducible genes in human breast cancer cells. 171 33

Synthetical oestrogens, as well as gestagens may cause metaplastic changes of the endometrial epithelia. While squamous and tubal metaplasia are most often due to oestrogenic stimulation and develop in hyperplastic endometria, mucinous and clear cell metaplasia are stimulated by gestagens and tamoxifen. Tamoxifen seems to act gestagen-like on the endometrium. We present data of 31 patients, who were treated with tamoxifen for breast cancer disease. 3 of these 31 developed endometrial adenocarcinoma.
 ...
PMID:[Role of steroid hormones and related biological substances in the etiology of endometrial carcinomas]. 172 43

We have established a novel human breast carcinoma cell line, HMA-1, derived from ascites of a female breast cancer patient. HMA-1 was shown to be an epithelial cell line with intracytoplasmic duct-like vacuoles, microvilli, desmosomes and tonofibrils in accordance with human breast cancer. The cell line demonstrated a good cell growth ability in monolayer fashion with a doubling time of 46 hr. Based on a whole cell binding assay the cell line contained estrogen receptor (1.45 x 10(-4) sites/cell). Tamoxifen, an anti-estrogen agent induced a dose-dependent decrease in the cell growth rate, but estradiol stimulated the cell growth. HMA-1 could be transplanted subcutaneously into BALB/c nude mice, and was able to cause tumors approximately two months after heteroinoculation. These results indicate that HMA-1 cell line may serve as a new human breast carcinoma cell line which could be utilized in the breast cancer research.
 ...
PMID:Establishment of an estrogen receptor-positive cell line (HMA-1) derived from human breast carcinoma. 175 37

We investigated the ability of high concentrations of oestradiol to reverse the growth inhibitory action of tamoxifen on MCF-7 breast cancer cells in vivo. Tamoxifen inhibits the oestradiol stimulated growth of MCF-7 cells in athymic mice. Using a sustained release preparation of tamoxifen we consistently achieved serum concentrations of the drug in the 40 to 50 ng ml-1 range and much higher levels in tissues. These serum levels are sufficient to inhibit the oestrogen stimulated growth of MCF-7 tumours exposed to physiologic (i.e. 300-600 pg ml-1 serum oestradiol concentrations). However, by administering dosages that increase serum oestradiol concentrations to 900-2000 pg ml-1, mimicking the increase often observed clinically in premenopausal women taking tamoxifen, we show that the growth inhibitory action of tamoxifen can be partially reversed. Serum tamoxifen levels were elevated to nearly 400 ng ml-1 by injecting 1 mg day-1 tamoxifen (IP 3 x weekly); this dosage was more effective at inhibiting oestradiol stimulated tumour growth than subcutaneous tamoxifen capsules alone. Our data suggest that at low serum levels tamoxifen may not act optimally. There may be a need to monitor tamoxifen levels in premenopausal patients to ensure that they are high enough not to be overcome by a tamoxifen induced increase in ovarian steroidogenesis.
 ...
PMID:Reversible control of oestradiol-stimulated growth of MCF-7 tumours by tamoxifen in the athymic mouse. 176 61

The effect of Lonidamine (LND) alone or combined with the antiestrogen Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) on cell proliferation and steroid hormone receptor content of a human estrogen sensitive breast cancer cell line was investigated. LND has a direct growth inhibitory action, even if used at relatively low concentrations (10(-7) M), and shows the maximum effect at 10(-4) M. The combination of LND with the antiestrogen does not produce a potentiation of the TAM-induced reduction of cell number, while the association of the drug with MPA seems more effective with respect to MPA alone, at least at certain concentrations. The negative interference observed between LND and TAM may be due to the LND-induced decrease of estrogen receptor levels.
 ...
PMID:Antitumor effect of lonidamine alone or combined with tamoxifen or medroxyprogesterone acetate in breast cancer cells. 177 46

Tamoxifen is the endocrine treatment of choice for hormone-responsive early and advanced breast cancer. Newly developed biodegradable luteinizing hormone-releasing hormone super agonists represent a practical and effective treatment for metastatic disease in premenopausal women. Progestins or aromatase inhibitors are useful therapies in patients who relapse from antiestrogens. Currently, there is no indication that improved survival can be achieved by combined endocrine therapy or combined chemo-hormonal therapy.
 ...
PMID:Pharmacologic manipulation of steroid hormones. Adjunctive therapies in cancer of the breast. 177 79

Tamoxifen is an important agent for the treatment of breast cancer. Occasionally the drug, which is an antiestrogen, has agonistic estrogenic activity. The authors describe three new cases of endometrial carcinoma developing in breast cancer patients taking tamoxifen and stress the necessity of carefully monitoring the uterine cavity under tamoxifen treatment.
 ...
PMID:Endometrial carcinoma in tamoxifen-treated breast cancer patients. 177 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>