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

In order to investigate the mechanisms of the endocrine therapeutic agents and the applicability of combined endocrine therapies for breast cancers, we studied the effects of estrogen and the endocrine therapeutic agents on estrogen receptor (ER), progesterone receptor (PgR), and DNA synthesis in MCF-7 human breast cancer cells, which is known to be sensitive to estrogen. ER and PgR of MCF-7 cells were determined by whole cell uptake method. In brief, intact MCF-7 cells cultured in the multi-well plates were incubated with various concentrations of tritiated estradiol (E2) or promegestone (R5020) at 37 degrees C for 1 hour. The characteristics of the hormone binding were analyzed by Scatchard plots. MCF-7 cells had single class of ER (Kd: 2.1 +/- 0.2 X 10(-10) M, MBC: 9.0 +/- 1.5 X 10(3) sites/cell) and PgR (Kd: 7.2 +/- 1.1 X 10(-10) M, MBC: 3.1 +/- 0.5 X 10(4) sites/cell). When cultured in the presence of 10(-8) M or 10(-6) M of E2, tamoxifen (TAM), R5020 or medroxyprogesterone acetate (MPA) for 48 hrs, the numbers of binding sites of ER and PgR altered, but the affinities of either of them did not change. E2(10(-8) or 10(-6) M) increased about twice the number of PgR. Although treatment of 10(-8) M TAM, a non-steroidal antiestrogen, slightly increased the number of PgR, 10(-6) M TAM significantly decreased the number of PgR. Both of R5020 (10(-8) or 10(-6) M) and MPA (10(-8) or 10(-6) M), synthetic progestins, decreased the number of ER dose-dependently. On the other hand, E2 (10(-8) and 10(-6) M) and R5020 (10(-8) M) enhanced DNA synthesis, but 10(-6) M TAM or MPA inhibited DNA synthesis. The effects of single, sequential and coincidental treatment of these agents were compared. The sequential treatment of 10(-8) M E2 for 36 hrs and followed 10(-6) M MPA for 36 hrs ("10(-8) M E2----10(-6) M MPA") and "10(-6) M TAM----10(-6) M MPA" inhibited DNA synthesis of MCF-7 cells more efficiently than 10(-6) M TAM alone or 10(-6) M MPA alone for 72 hrs. However, "10(-6) M MPA----10(-6) M TAM" inhibited DNA synthesis less than "10(-6) M TAM----10(-6) M MPA".(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Effects of estrogen and endocrine therapeutic agents on the estrogen receptor, progesterone receptor and DNA synthesis in MCF-7 human breast cancer cells using the whole cell uptake method]. 296 35

Klinefelter's syndrome (KS, XXY) as a risk factor for developing breast cancer was evaluated in a retrospective study of 93 unselected male breast cancer patients from the Healthcare region of Western Sweden. Archival normal material from lymph nodes or skin and subcutaneous tissue was examined using the FISH (fluorescence in situ hybridisation)-technique. The best yield of intact nuclei was obtained from lymph node tissue. The prevalence rate of KS in males with breast cancer was found to be 7.5 per cent, a much higher rate than previously reported (approximately 3 per cent). Methodological differences are suggested to cause the increased prevalence rate. Based on our finding and on the prevalence of KS in the normal population as well as on the incidence of MBC, a 50-fold increased risk of developing breast cancer in males with KS relative to normal males was found. The same median age at diagnosis, 72 years, was established for both groups of patients. No differences in survival were seen.
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PMID:Prevalence of Klinefelter's syndrome in male breast cancer patients. 949 23

Ultraviolet (UV) screens are increasingly used as a result of growing concern about UV radiation and skin cancer; they are also added to cosmetics and other products for light stability. Recent data on bioaccumulation in wildlife and humans point to a need for in-depth analyses of systemic toxicology, in particular with respect to reproduction and ontogeny. We examined six frequently used UVA and UVB screens for estrogenicity in vitro and in vivo. In MCF-7 breast cancer cells, five out of six chemicals, that is, benzophenone-3 (Bp-3), homosalate (HMS), 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC), and octyl-dimethyl-PABA (OD-PABA), increased cell proliferation with median effective concentrations (EC(50)) values between 1.56 and 3.73 microM, whereas butyl-methoxydibenzoylmethane (B-MDM) was inactive. Further evidence for estrogenic activity was the induction of pS2 protein in MCF-7 cells and the blockade of the proliferative effect of 4-MBC by the estrogen antagonist ICI 182,780. In the uterotrophic assay using immature Long-Evans rats that received the chemicals for 4 days in powdered feed, uterine weight was dose-dependently increased by 4-MBC (ED(50 )309mg/kg/day), OMC (ED(50) 935 mg/kg/day), and weakly by Bp-3 (active at 1,525 mg/kg/day). Three compounds were inactive by the oral route in the doses tested. Dermal application of 4-MBC to immature hairless (hr/hr) rats also increased uterine weight at concentrations of 5 and 7.5% in olive oil. Our findings indicate that UV screens should be tested for endocrine activity, in view of possible long-term effects in humans and wildlife.
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PMID:In vitro and in vivo estrogenicity of UV screens. 1176 7

Preliminary randomized studies have failed to show a survival benefit of high-dose chemotherapy with alkylators in advanced breast cancer. Idarubicin is an active agent in breast cancer and is suitable for dose escalation. We designed a dose finding study with escalating high-dose idarubicin (HD-Ida) followed by fixed high-dose thiotepa+melphalan (HD-TM) with peripheral blood progenitor cells (PBPC) in MBC patients with stable disease or in partial response after six courses of induction chemotherapy with gemcitabine 1000 mg/m(2) days 1 and 4, epirubicin 90 mg/m(2) day 1, taxol 175 mg/m(2) day 1 (GET). Aims of the study were to identify the maximum tolerated dose (MTD) of idarubicin, to evaluate the cardiac safety and activity of HD-Ida and HD-TM after GET and to study the pharmacokinetic profile of idarubicin and idarubicinol. A total of 14 patients were treated. Idarubicin was administered as a 48 h continuous i.v. infusion at the following dose levels: 40 mg/m(2) (three patients), 50 mg/m(2) (three patients), 60 mg/m(2) (five patients) and 70 mg/m(2) (three patients). Mucositis was the dose-limiting toxicity and the MTD was 60 mg/m(2). C(max) of Idarubicin and idarubicinol were 7.7+/-2.0 and 26.3+/-9.7 ng/ml at 40 mg/m(2) and increased to 14.8+3.0 and 47.4+12.6 ng/ml at 70 mg/m(2). AUCt(0-264) of idarubicin and idarubicinol increased from 423.2+/-111.6 and 2581+/-606 hng/ml at 40 mg/m(2) to 732.8+/-140.2 and 4590+/-1258 hng/ml at 70 mg/m(2). Conversion rates after HD-Ida and HD-TM were 28.6 and 38.5%, respectively. No episodes of cardiac toxicity were observed. We conclude that HD-Ida followed by HD-TM is feasible and devoid of cardiac toxicity. Moreover, the activity of HD-Ida after a epirubicin-containing regimen suggests incomplete cross-resistance between the two drugs.
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PMID:High-dose consolidation chemotherapy with Idarubicin and alkylating agents following induction with gemcitabine-epirubicin-paclitaxel in metastatic breast cancer: a dose finding study. 1262 62

Breast cancer was the focus of several presentations during the 27th European Society of Medical Oncology (ESMO) Congress held in Nice. Fulvestrant seems to be equally effective to tamoxifen as a first-line therapy in hormone-sensitive advanced breast cancer in postmenopausal women. However, it may be more effective than tamoxifen in ER- and PgR-positive disease. The addition of tamoxifen to epirubicin containing regimens was found to significantly increase PFS and OS in patients with MBC according to a multivariate analysis of 640 patients. BRCA-1 linked breast cancer was reported to be more sensitive to anthracycline-based CT than sporadic and BRCA-2 linked disease. VEGF was found to be an independent prognostic factor in patients with node-negative breast cancer. The implications and limitations of these findings are discussed.
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PMID:Recent advances in breast cancer: the 27th ESMO Congress 2002. 1275 50

Carcinoma of the male breast (MBC) is an uncommon phenomenon, accounting for <1% of all malignancies in man. It represents a biologically heterogeneous disorder, and its clinical course may vary from indolent and slowly progressive to rapidly metastatic disease. Most of our current knowledge regarding its biology, natural history, and treatment strategies has been extrapolated from its female counterpart. Information regarding prognostic relevance of new molecular markers is limited. At the European Institute of Oncology we performed a study showing data in which p21Waf1 and p27Kip1 proteins were evaluated in a series of male breast cancer patients. Our data suggest that the immunohistochemical evaluation of p21Waf1 and p27Kip1 expression in male breast carcinomas may be a further useful marker for selecting patients who express functional proteins that can be predictive for the most efficient endocrine response. Moreover, searching for more conservative treatment, we introduced in our clinical practice sentinel node biopsy, and if present, sentinel node biopsy of the internal mammary chain. The potential clinical implications of complete nodal staging are far-reaching, and give us a major new opportunity to stratify male patients with breast cancer for appropriate surgery as well as giving valuable prognostic information. Male breast cancer has biological differences compared with female breast cancer. It responds to hormonal manipulation and chemotherapy, but optimal treatment regimens in males are unknown. By analogy to the female breast cancer, post-mastectomy radiotherapy should be proposed in case of advanced T stage and/or lymph node positivity (considering the small volume of the male mammary gland, we suggest post-mastectomy irradiation in case of T >1 cm and/or presence of >1 metastatic axillary lymph node). Breast conserving surgery, performed in selected cases of male breast cancer, should be always followed by radiotherapy. Despite a wealth of small retrospective studies on MBC, its rarity means there is a lack of prospective randomized controlled treatment trials, which needs to be addressed if significant advances are to be made in the treatment of this unusual challenging disease.
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PMID:Male breast cancer: a special therapeutic problem. Anything new? (Review). 1476 51

Multi-drug resistance (MDR) in MCF7 breast cancer cells and multi-xenobiotic resistance (MXR) in mussel (Mytilus edulis) blood cells (MBC) are well known mechanisms that contribute to the decrease in intracellular concentrations of many unrelated but cytotoxic compounds. In the present work, we have carried out comparative investigations of the MDR/MXR protective mechanisms using a rapid colorimetric assay for cell viability and calcein accumulation for MDR/MXR activities. These studies were performed using cultured MCF7 and MBC before and after in vitro exposure to xenobiotics. Our results indicate that a 5-day exposure to doxorubicin or vincristine decreased calcein accumulation in MBC which is consistent with an induction of multi-xenobiotic resistance. The increase in calcein accumulation provoked by 1-h treatment with 50 microM verapamil was much lower in MBC when compared to the P-glycoprotein overexpressing MCF7 cell line. We conclude that such microplate assays could be used in primary cultures of MBC to estimate the effects of various chemicals on MXR activity.
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PMID:Cell responses to xenobiotics: comparison of MCF7 multi-drug- and mussel blood cell multi-xenobiotic-defense mechanisms. 1517 34

We tested the ultraviolet screen 3-(4-methylbenzylidene)-camphor (4-MBC; Eusolex 6300), which has been implicated as a potential endocrine disruptor, for its potential to bind to and activate endogenous estrogen receptors (ER) and to mediate ER-dependent changes in gene transcription, in hepatocytes of the water-dwelling South African clawed frog Xenopus laevis. We were able to confirm previous findings that 4-MBC accelerates cell proliferation in estrogen-dependent human breast cancer cells (MCF-7). Results of competitive binding assays of [3H]17beta-estradiol and 4-MBC using cytosolic protein preparations from Xenopus hepatocytes indicated that 4-MBC weakly binds to the ER. 4-MBC at a concentration of 100 micromol/L is not able to completely replace estradiol from the receptor. However, when 4-MBC was tested in a gene induction assay using the relative amount of ER transcript as a marker for ER-dependent transcriptional activation, we found that micromolar concentrations of this substance produced an increase in the amount of ER mRNA that was not different from the amount of mRNA that was observed upon activation of cells with 17beta-estradiol in concentrations above 1 nmol/L. The results indicate that 4-MBC has the potential to change physiological and developmental processes mediated by ER signaling mechanisms. It may therefore be a potentially harmful substance for water-dwelling animals when present in the environment at micromolar concentrations.
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PMID:Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor (Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells. 1558 35

Forty-six previously untreated patients with advanced breast cancer were eligible for the present randomised phase I study. It aimed to evaluate the toxicity and activity of a therapeutic sequence with epirubicin on day 1 followed by paclitaxel on day 2 (sequence A) or the reverse sequence, ie., paclitaxel on day 1 followed by epirubicin on day 2 (sequence B). The starting doses of epirubicin and paclitaxel, administered either according to sequence A or B, (level 1 cohort) were 90 mg/m2 and 175 mg/m2, respectively. Per cohort of 3 patients, the dose of paclitaxel was increased by 25 mg/m2 (levels 2 and 4) and of epirubicin by 10 mg/m2 (levels 3 and 5). Treatment was repeated with 3-week intervals. The maximal tolerated dose (MTD) was achieved at level 1 in sequence B (paclitaxel first) and level 3 (epirubicin 100 mg/m2 followed by paclitaxel 200 mg m2) in sequence A. Dose limiting toxicity (DLT) was neutropenia (+/- febrile) in both sequences. Cardiac events occurred in 28% of the patients; significant decrease in left ventricular ejection function (LVEF) was observed in 8/33 and in 2/13 patients in sequence A and B, respectively. This was associated with 5 and 1 cardiac heart failure (CHF), respectively. In 43 evaluable patients, 10 CR and 25 PR were observed (overall response rate 81%). In the 20 patients with locally advanced disease (LABC), the respective numbers were 7 CR and 11 PR; in the 23 metastatic (MBC) patients, 3 CR and 14 PR were recorded. The median survival of the both groups was not reached at 33 + months. In conclusion , the combination of epirubicin and paclitaxel has significant activity in breast cancer. The recommended sequence of both drugs in combination therapy, mainly to avoid neutropenia, is epirubicin day 1 followed by paclitaxel on day 2. Cardiac toxicity remains problematic in either sequence of administration.
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PMID:Sequential administration of epirubicin and paclitaxel for advanced breast cancer. A phase I randomised trial. 1586 68

Availability of effective treatment has been shown to have a profound, positive impact on survival of breast cancer patients. However, with passing of time treatment of breast cancer has become more complex and associated with increase of costs that puts an enormous burden on health care resources. In order to compare the costs and outcomes of different treatments, we have made our own assessment of costs of breast cancer treatment based on the existing situation in Bosnia & Herzegovina (B&H) and data available from the relevant literature. In B&H costs of breast cancer therapy constitute about one third of the total cost for all tumor types therapies, and this is proportional to the relative number of the treated patients. Prices of overall treatment vary predominantly according to the use of specific adjuvant chemotherapy (CT) and hormonal therapy (HT). FAC (5 fluorouracil/doxorubicin/cyclophosphamide/methotrexate/5 fluorouracil), higher doses of epirubicin in FE(100)C are twice as high compared with FAC. Inclusion of taxanes further increases costs (40-fold for AC[(doxorubicin/cyclophosphamide) + paclitaxel x 4]; 60-fold for TAC with docetaxel; 70-fold for dense-dose regimens in relation to FEC). Treatment with aromatase inhibitors is 11-13 times more expensive compared to tamoxifen. Therapy of metastatic disease is heterogeneous, and it is likely to prolong median survival by 14 months on average. Overall costs vary according to specific treatment modalities used. From CMF and FEC to trastuzumab and docexatel prices have increased 300 times. All health care systems have a limited budget, but wise use of health care resources is of special importance in countries in transition with evident weakness in economy. In the early breast cancer (EBC) setting, therapy should be individualised according to evidence-based data and respecting available resources. In metastatic disease (MBC) it should be based on risk factors, predictive factors, toxicity, preference of the patient herself and available resources, and weighted against effect on quality of life and treatment costs.
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PMID:How to make the best use of limited resources in breast cancer treatment--experiences in Bosnia & Herzegovina. 1731 48


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