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When the fleshy part of the fruit is eaten, this molecule binds to the tongue's taste buds, causing bitter and sour foods (such as lemons and limes) consumed later to taste sweet. This effect lasts between 30 minutes and two hours., delicious.com

Annals of Surgical Oncology, Vol. 15, No. 7. (1 July 2008), pp. 1983-1988.Abstract Background  Few studies have examined breast cancer hormone receptor expression in Africans. We report on the hormone receptor profile of breast cancer in East Africans in the largest prospective study for this region. Methods  Consecutive breast cancer presentations to a hospital in Kijabe (2001?2007) were included. Demographic, clinical, and test data were collected. ER/PR and Her2 testing was based on immunohistochemistry (IHC). Results  There were 129 subjects (median 47 years), most had invasive ductal cancer and locally advanced disease and/or metastases. ER/PR testing was done in 120: 24% had ER-positive tumours, 34% were ER- and/or PR-positive, 10% were ER-negative but PR-positive tumours, and 66% were negative for ER and PR. ER/PR positivity was not associated with stage (P = 0.28) and was not related to age, parity, menopausal status, or node metastases. Increasing tumour grade was associated with PR expression (P = 0.02) with decreasing frequency of PR positive tumours as histological grade increased; there was weak evidence of an association between grade and ER expression (P = 0.06). Of cases tested, 26.5% overexpressed Her2. Conclusions  Breast cancer in Kijabe is an advanced-stage disease, comprised mainly of poorly differentiated cancers that are less likely to be hormone sensitive (across all stages of disease). ER/PR testing of all those affected by breast cancer should be supported as a global priority in cancer control. International and inter-African research collaborations are needed to allow genetic detailing of tumours in indigenous Africans to assess possible racial heterogeneity in the biology of breast cancer.P Bird, A Hill, N Houssami, citeulike.org

J Immunol, Vol. 161, No. 1. (1 July 1998), pp. 27-34.Several observations suggest that sex steroids might participate in steady state regulation of B lymphopoiesis. B cell precursors decline dramatically in bone marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell populations are increased in hypogonadal mice or male castrates. Estrogen treatment of hypogonadal mice reduced precursors to normal. However, questions remain about which hormones and receptors are the most important. Furthermore, these observations need to be reconciled with advances regarding new sex steroid receptors. We have now characterized B lymphopoiesis in androgen receptor-deficient testicular feminization (Tfm) mice. Testicular feminization mice had substantially elevated numbers of B cell precursors in the bone marrow and B cells in the spleen as compared with wild-type mice. The importance of one estrogen receptor (ERalpha) was evaluated in gene-targeted mice, and B cell precursors were found to be within the normal range. Our previous studies indicated that hormone receptors in stromal cells may be important for estrogen-mediated suppression of B lymphopoiesis. We now show that estrogen-mediated inhibition of B cell precursor expansion in culture was blocked by a specific estrogen receptor antagonist (ICI 182,780). Stromal cells derived from ERalpha-targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these stromal cells revealed splice-variant transcripts of ERalpha, as well as message for a recently discovered estrogen-binding receptor, ERbeta. Thus, androgens may normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens might utilize one or more receptors to achieve the same physiologic response.Glennda Smithson, John Couse, Dennis Lubahn, Kenneth Korach, Paul Kincade, citeulike.org

Cancer letters (21 April 2008)Functional role of nuclear receptors and numerous coregulators have been studied in terms of regulating transcriptional control of genes that play critical roles in various pathways. There is growing evidence that nuclear receptors and their coregulators control inflammatory programs of gene expression and progression of hormone-dependent cancer. This review provides a general overview of the interrelationship between nuclear receptor signalling, inflammation and cancer. These insights provide inflammatory genes as attractive targets for the development of cancer therapeutics.Jason S Lee, Keun Il Kim, Sung Hee Baek, citeulike.org

Cancer Res, Vol. 68, No. 21. (1 November 2008), pp. 8908-8917.One-third of all estrogen receptor (ER)-positive breast tumors treated with endocrine therapy fail to respond, and the remainder is likely to relapse in the future. Almost all data on endocrine resistance has been obtained in models of invasive ductal carcinoma (IDC). However, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancers each year and, whereas the incidence of IDC has remained relatively constant during the last 20 years, the prevalence of ILC continues to increase among postmenopausal women. We report a new model of Tamoxifen (TAM)-resistant invasive lobular breast carcinoma cells that provides novel insights into the molecular mechanisms of endocrine resistance. SUM44 cells express ER and are sensitive to the growth inhibitory effects of antiestrogens. Selection for resistance to 4-hydroxytamoxifen led to the development of the SUM44/LCCTam cell line, which exhibits decreased expression of ERalpha and increased expression of the estrogen-related receptor gamma (ERRgamma). Knockdown of ERRgamma in SUM44/LCCTam cells by siRNA restores TAM sensitivity, and overexpression of ERRgamma blocks the growth-inhibitory effects of TAM in SUM44 and MDA-MB-134 VI lobular breast cancer cells. ERRgamma-driven transcription is also increased in SUM44/LCCTam, and inhibition of activator protein 1 (AP1) can restore or enhance TAM sensitivity. These data support a role for ERRgamma/AP1 signaling in the development of TAM resistance and suggest that expression of ERRgamma may be a marker of poor TAM response. 10.1158/0008-5472.CAN-08-2669Rebecca Riggins, Jennifer Lan, Uwe Klimach, Alan Zwart, Luciane Cavalli, Bassem Haddad, Li Chen, Ting Gong, Jianhua Xuan, Stephen Ethier, Robert Clarke, citeulike.org

Breast Cancer Research, Vol. 8 (17 July 2006), R39.Huiyan Ma, Leslie Bernstein, Ronald Ross, Giske Ursin, citeulike.org

BMC Cancer, Vol. 8 (08 May 2008), 130.Background Previous studies and biological mechanisms of carcinogenesis suggest that the steroid receptor content of benign breast epithelium may be related to breast cancer risk. The objective in this study was to compare the levels of estrogen receptor-? (ER) and progesterone receptor (PR) in nonneoplastic breast epithelium between breast cancer cases and biopsy controls. Methods Between 1995 and 1997 at two sites (Women's College Hospital in Toronto and Kingston General Hospital), 667 women who were scheduled for diagnostic excisional breast biopsies completed a questionnaire providing personal information and agreed to allow analysis of routinely resected tissue. Histological slides with nonneoplastic epithelium were available for 101 cancer cases and 200 biopsy controls in Toronto and for 105 cancer cases and 119 controls in Kingston. Nonneoplastic epithelium was examined with immunohistochemical assays to determine the percent of epithelial cells staining for ER and PR. Unconditional logistic regression was used to calculate odds ratios (OR) stratified by study site. Results The ER content of nonneoplastic tissue was higher in cases than biopsy controls in unadjusted analyses; after adjustment for age, however, a weak association remained in only one of the study sites. After adjustment for age, the PR content of nonneoplastic tissue was slightly lower in breast cancer cases than controls in one study site. Furthermore, this inverse association was confined to women with PR negative breast cancer in comparison to the controls. No interaction between ER and PR content of nonneoplastic tissue was observed in relation to the odds of having breast cancer. Conclusion The results of this study are consistent with only a slight indication of increased ER levels in nonneoplastic tissue in breast cancer cases relative to controls. This study contributes to the understanding of breast cancer by examining both ER and PR in nonneoplastic tissue. Limitations remain, however, such as the necessity of using as controls women with benign breast changes, difficulties in selecting the appropriate tissue for analysis, and tissue sampling concurrent to diagnosis.Christy Woolcott, Sandip Sengupta, Wedad Hanna, Kristan Aronson, citeulike.org

Molecular Cancer, Vol. 7 (04 June 2008), 49.BACKGROUND: The transcription factor GATA3 has recently been shown to be necessary for mammary gland morphogenesis and luminal cell differentiation. There is also an increasing body of data linking GATA3 to the estrogen receptor alpha (ERalpha) pathway. Among these it was shown that GATA3 associates with the promoter of the ERalpha gene and ERalpha can reciprocally associate with the GATA3 gene. GATA3 has also been directly implicated in a differentiated phenotype in mouse models of mammary tumourigenesis. The purpose of our study was to compare coexpressed genes, by meta-analysis, of GATA3 and relate these to a similar analysis for ERalpha to determine the depth of overlap. RESULTS: We have used a newly described method of meta-analysis of multiple cancer studies within the Oncomine database, focusing here predominantly upon breast cancer studies. We demonstrate that ERalpha and GATA3 reciprocally have the highest overlap with one another. Furthermore, we show that when both coexpression meta-analysis lists for ERalpha and GATA3 are compared there is a significant overlap between both and, like ERalpha, GATA3 coexpresses with ERalpha pathway partners such as pS2 (TFF1), TFF3, FOXA1, BCL2, ERBB4, XBP1, NRIP1, IL6ST, keratin 18(KRT18) and cyclin D1 (CCND1). Moreover, as these data are derived from human tumour samples this adds credence to previous cell-culture or murine based studies. CONCLUSION: GATA3 is hypothesized to be integral to the ERalpha pathway given the following: (1) The large overlap of coexpressed genes as seen by meta-analysis, between GATA3 and ERalpha, (2) The highest coexpressing gene for GATA3 was ERalpha and vice-versa, (3) GATA3, like ERalpha, coexpresses with many well-known ERalpha pathway partners such as pS2.Brian Wilson, Vincent Giguere, citeulike.org

The Journal of Steroid Biochemistry and Molecular Biology, Vol. 105, No. 1-5. (June 2007), pp. 1-15.Aromatase (CYP19) converts adrenal and ovarian androgens into estrogens, which supports the growth of estrogen-dependent breast cancers. Anti-aromatase agents are displacing antiestrogens as the first-line treatment for estrogen receptor positive breast cancers. Androgens can act as estrogen precursors, but besides this capability they can also directly act on breast cancer cells by binding to androgen receptors, which are present in the majority of breast cancer specimens. Epidemiological and clinical evidences suggest that higher levels of circulating androgen increase the risk of developing breast cancer. Androgen receptor gene polymorphisms which render the more transcriptionally active receptors have been related to a lower risk of breast cancer. It is currently accepted that androgens act as antiproliferative agents in the presence of estrogens in some breast cancer cell lines. However, emerging evidence suggests that direct androgenic activity might also stimulate cell growth in a subset of estrogen-resistant breast tumors. Here we discuss the supporting evidence which proposes that androgens themselves are actively involved in breast carcinogenesis and its clinical behaviour.B Nicolasdiazchico, F Germanrodriguez, A Gonzalez, R Ramirez, C Bilbao, A Cabreradeleon, A Aguirrejaime, R Chirino, D Navarro, J Diazchico, citeulike.org

Annu Rev Pharmacol Toxicol (17 September 2007)blacksquare, square, filled Abstract The chemokine system coordinates leukocyte migration in immunity and inflammation and is implicated in the pathogenesis of many human diseases. Although several successful strategies have been identified to develop drugs targeting chemokines and their receptors, this has not yet resulted in many new therapeutics. This is likely due to a complexity of the chemokine system, which was not initially appreciated, that is characterized by redundancy, pleiotropy, and differences among species. Nevertheless, our understanding of chemokine biology is continuing to grow and several promising drugs are currently being tested in late-stage clinical trials. In this review, we examine the role of chemokines in health and diseases and discuss strategies to target the chemokine system. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 48 is January 6, 2008. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.Antonella Viola, Andrew D Luster, citeulike.org