Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) is a multifunctional cytokine that plays important roles in the immune system, hematopoiesis, and acute phase reactions. Estrogens have significant roles in a variety of biological events, such as the development and maintenance of female reproductive organs, and bone and lipid metabolism. Previous studies demonstrated that estrogens suppress IL-6-induced osteoporosis and the growth of multiple myeloma cells by repressing IL-6 and IL-6 receptor gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on IL-6 function. IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) activity and STAT3-mediated gene expression were suppressed by 17beta-estradiol (E2) in breast cancer cells. E2-mediated inhibition of STAT3 activation was reversed by tamoxifen, an estrogen receptor (ER) antagonist. We provide evidence that the inhibitory action of ER on STAT3 activity was due to direct physical interactions between STAT3 and ER which represents a novel form of cross-talk between STAT3 and ER signaling pathways.
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PMID:Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling. 1111 55

Estrogens are essential for human health. Their physiological effects are primarily mediated by two types of intracellular estrogen receptors (ER alpha and ER beta) that function as DNA-binding transcription factors. However, estrogens are also involved in the development and progression of breast cancers. Endocrine therapy aims to reduce the availability of the hormone or to counteract its action. This can be achieved by preventing estrogen production or administrating antiestrogens (AEs), synthetic drugs belonging to several distinct structural categories. Selective estrogen receptor modulators (or SERMs) bind ERs but have a mixed agonist/antagonist profile. Selective estrogen receptor downregulators (or SERDs) are pure antiestrogens, acting by decreasing the level of ERs through their ubiquitinylation and subsequent targeting to the proteasome. We review most of the usual antiestrogenic therapies for estrogen-dependent and estrogen-independent solid cancers and present our recent results on the use of AEs against multiple myeloma. In breast cancer treatments, the most commonly used antiestrogen, tamoxifen, has major limitations: side effects due to its partial agonist activity and constitutive or acquired resistance. We propose that novel AE drug delivery systems may enhance the overall beneficial effects by targeting tumoral cells.
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PMID:Antiestrogenic therapies in solid cancers and multiple myeloma. 1690 Jun 59

Estrogens are important immunomodulators, exerting significant effects on cell proliferation, apoptosis, cytokine production and differentiation of hematopoietic cells. Estrogen receptors are expressed on normal B and T lymphocytes, bone marrow and in leukemia and lymphoma cell lines. Epidemiologic evidence for the association of menopausal hormone use with risk of non-Hodgkin's lymphoma (NHL) has been mixed; however, all of the investigations have been observational. We analyzed the data from Women's Health Initiative hormone therapy trials where conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 16,654) or CEE alone (women with prior hysterectomy) (n = 10,685) were tested against placebos and the intervention lasted a median of 5.6 years in the CEE + MPA trial and 7.2 years in the CEE alone trial. During 13 years of follow-up through September 20, 2013 383 incident NHL cases were identified. We used the intent-to-treat approach to calculate incidence rates of NHL, hazards ratios (HR) and 95% confidence intervals (CI) by treatment group. Incidence of NHL was virtually the same in the treatment and placebo groups. The HR was 1.02 (95%CI 0.74-1.39) for CEE alone, 0.98 (95% CI 0.76-1.28) for CEE+MPA, and 1.00 (95% CI 0.82-1.22) for both combined. There were no specific NHL subtypes associated with either type of the treatment, except a marginally decreased risk of plasma cell neoplasms (HR= 0.53 95% CI 0.27-1.03) in the CEE-alone group. These results do not support a role of estrogen alone or combined with progestin in the development of NHL among postmenopausal women.
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PMID:Menopausal estrogen therapy and non-Hodgkin's lymphoma: A post-hoc analysis of women's health initiative randomized clinical trial. 2636 26