Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local formation of oestrogens from androgens by aromatase cytochrome P-450 within brain cells is crucial for the sexual differentiation of the mammalian CNS. Aromatase activity has been detected in several brain regions of the developing rodent brain. In the present study, we used a mouse-specific, peptide-generated, polyclonal aromatase antibody to determine whether neurones and/or glial cells in the developing brain are involved in androgen aromatization and if aromatase-immunoreactive (Arom-IR) cells exhibit a sex-specific distribution and regional-specific morphological characteristics. For these experiments, gender-specific cell cultures were prepared from embryonic day 15 mouse hypothalamus and cortex. Specificity of the immunoreaction was confirmed by Western-blot analysis and by inhibition of aromatase activity using tissue homogenates from mouse ovaries and male newborn hypothalamus and from male hypothalamic cultures with known aromatase activity, respectively. Arom-IR cells were found in both hypothalamic and cortical cultures. Double-labeling experiments revealed that Arom-IR cells co-stained only for the neuronal marker MAP II, but never for glial markers. Therefore aromatase immunoreactivity is specifically neuronal. Regional differences in the morphology of Arom-IR neurones were observed between both brain regions. In hypothalamic cultures, IR-neurones represented a heterologous population of phenotypes (magnocellular, small bipolar and multipolar neurones with long processes showing varicose-like structures or without processes). Cortical Arom-IR neurones were always oval in shape with short or no IR-processes. Sexual dimorphisms in numbers of Arom-IR neurones were found in the hypothalamus with significantly higher cell numbers in male cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Aromatase-immunoreactivity is localised specifically in neurones in the developing mouse hypothalamus and cortex. 819 60

Pre-clinical, molecular and epidemiological evidence supports a role for estrogen in both the initiation and promotion of breast cancer. Antagonizing estrogen has therefore been proposed as one way of reducing risk. Tamoxifen, which competes with estrogen at the estrogen receptor, has been shown in four phase III clinical trials to reduce tumour occurrence substantially. Aromatase inhibitors are superior to tamoxifen in terms of both efficacy and toxicity in advanced disease and in the neoadjuvant and adjuvant setting. Exemestane may be distinct because its steroidal structure potentially protects bone and lipid metabolism from estrogen ablation. Phase three trials are ongoing to test the efficacy of the inhibitors, including the IBIS 2 trial which randomizes anastrozole against placebo and the NCIC CTG MAP.3 study of exemestane with or without celecoxib against placebo. The efficacy and toxicity results of these studies, and the identification of risk profiles from them, are awaited with interest.
 ...
PMID:Aromatase inhibitors for chemoprevention. 1468 1

Aromatase (estrogen synthetase) inhibitors are superior to tamoxifen in terms of both efficacy and toxicity in the treatment of advanced breast cancer and also in the neoadjuvant setting. Recent results from the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial showed a marked reduction in contralateral primary breast cancer with anastrozole, an apparent prevention effect. A similar effect was seen in the MA.17 adjuvant trial comparing letrozole with placebo after 5 years of adjuvant tamoxifen. This has accelerated interest in aromatase inhibitors as primary preventive therapy. Two studies being conducted by the National Cancer Institute of Canada's Clinical Trials Group select women by virtue of mammographic breast density. The International Breast Cancer Intervention Study 2 trial randomizes women at elevated risk to anastrozole or placebo. Because of its steroidal structure, exemestane may be more effective than the nonsteroidal aromatase inhibitors and may protect bone and lipid metabolism from the effects of estrogen ablation. Elevated prostaglandin E2 levels from cyclooxygenase-2 induction by preinvasive and invasive breast lesions increase a number of tumor-promoting pathways, including aromatase, as well as angiogenetic, antiapoptotic, and others. Additive or synergistic effects between celecoxib, a cyclooxygenase-2 inhibitor, and exemestane have been demonstrated and have led to the National Cancer Institute of Canada's Clinical Trials Group MAP.3 trial, which will randomize women at elevated risk to placebo or to exemestane with or without celecoxib. The efficacy and long-term toxicity data from the aromatase inhibitor prevention trials, and the identification of risk profiles from trial results, are awaited with interest.
 ...
PMID:Prevention strategies with aromatase inhibitors. 1473 94

Aromatase inhibitors are well-established therapies in the neoadjuvant, adjuvant and metastatic settings for breast cancer. In adjuvant trials, this class of drugs has shown preventative properties by decreasing the rate of contralateral breast cancer. Recently, the National Cancer Institute of Canada Clinical Trials Group MAP.3 study evaluated exemestane as a breast cancer prevention agent for women with specified higher risks of developing breast cancer. We review the history of exemestane and evaluate the available evidence of its use for breast cancer prevention.
 ...
PMID:Exemestane in the prevention setting. 2259 Apr 84

Purpose Aromatase inhibitors are established breast cancer chemoprevention interventions. However, nonadherence remains a significant challenge. We investigated the association between worsening menopause-specific quality of life, baseline participant characteristics, and early treatment discontinuation within the Mammary Prevention.3 (MAP.3) breast cancer prevention trial. Methods In the MAP.3 randomized, placebo-controlled trial evaluating exemestane, participants completed the Menopause-Specific Quality of Life Questionnaire (MENQOL) at entry and at 6 months. Multivariable log-binomial regression was used to assess the associations of baseline participant characteristics and clinically meaningful worsening in menopause-specific quality of life (QOL) with treatment discontinuation at 1 year. Results Of the 4,501 participants eligible for this analysis, 724 (17%) discontinued assigned treatment within the first year of random assignment of treatment (19% of the exemestane group and 13% of the placebo group). Between 19% and 35% of women experienced a clinically meaningful worsening in the vasomotor, sexual, physical, and psychosocial domains of the MENQOL within 6 months of treatment initiation. Regardless of receiving exemestane or not, experiencing a worsening in any MENQOL domain or, especially, overall menopause-specific QOL, was associated with early treatment discontinuation (relative risk, 1.79; 95% CI, 1.53 to 2.10 for overall worsening). Assignment to exemestane, having a smoking history, and current employment also were significantly associated with early discontinuation. Conclusion Negative changes in menopause-specific QOL influence a woman's decision to stop chemoprevention therapy. Attention to such symptoms may improve QOL and potentially improve chemoprevention adherence.
 ...
PMID:Factors Associated With Early Discontinuation of Study Treatment in the Mammary Prevention.3 Breast Cancer Chemoprevention Trial. 2806 70