Serum cholesterol reduction with tamoxifen

Schapira, David V.; Kumar, Nagi B.; Lyman, Gary H.

doi:10.1007/bf01812678

Cited by 31 publications

(10 citation statements)

References 17 publications

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“…Based on the cell types and tissues, tamoxifen can function either as an agonist or an antagonist of estrogen receptor (ER) [12]. Tamoxifen also has atheroprotective effects which have been determined in both animal models and humans [13][14][15][16]. We previously reported that tamoxifen increased expression of type BI scavenger receptor (SR-BI), a receptor for high-density lipoprotein, in macrophages isolated from female but not male mice [17].…”

Section: Introductionmentioning

confidence: 97%

Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Liu

Wang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Hernia is a disease with defects in collagen synthesis/metabolism. However, the underlying mechanisms for hernia formation have not been fully defined. Tamoxifen is a selective estrogen receptor modulator and used for patients with breast cancer. Tamoxifen also has pleiotropic and side effects. Herein, we report that tamoxifen treatment resulted in an appearance of a large bulge in the low abdomen between the hind legs in male but not in female mice. The autopsy demonstrated that the low abdominal wall was broken and a large amount of intestine herniated out of the abdominal cavity. Histological analysis indicated that tamoxifen caused structural abnormalities in the low abdominal wall which were associated with decreased type II collagen content. Furthermore, we determined increased matrix metalloproteinase-2 (MMP-2) and MMP-13 expression in the tissue. In vitro, tamoxifen induced MMP-2 and MMP-13 expression in fibroblasts. The promoter activity analysis and ChIP assay demonstrate that induction of MMP-13 expression was associated with activation of JNK-AP-1 and ERK1/2 signaling pathways while induction of MMP-2 expression was related to activation of the ERK1/2 signaling pathway. Taken together, our study establishes a novel murine hernia model, defines a severe side effect of tamoxifen, and suggests a caution to male patients receiving tamoxifen treatment.

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Section: Introductionmentioning

confidence: 97%

Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Liu

Wang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…[17][18][19] Interestingly, Tamoxifen exerts an antagonistic effect on mammary tissues, but adversely acts as an agonist on other tissues such as skeletal 20,21) and cardiovascular systems. [22][23][24] This unexpected discovery provided the impetus for pursuit of tissue-selective agonistic estrogen alternatives, which have beneficial effects on osteoporosis and cardiovascular diseases, and minimal effects on mammary and uterine tissues. Following extensive investigation, novel types of nonsteroidal, estrogen receptor partial agonists, termed as selective estrogen receptor modulators (SERMs), have been identified.…”

mentioning

confidence: 99%

A New Series of Estrogen Receptor Modulators: Effect of Alkyl Substituents on Receptor-Binding Affinity

Kamada

Sasaki

Kitazawa

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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New types of selective estrogen receptor modulators (SERMs) were synthesized and evaluated for their binding affinity and biological effect on reproductive cells. A proposed lead structure (B) was derivatized to provide compounds 30 and 44, which showed good estrogen-receptor binding affinity (K i values: 6.3 and 10 nM, respectively), as well as minimal impact on mammary and uterine carcinoma cells. Introduction of an alkyl group in the core structure considerably enhanced receptor-binding affinity of the compounds tested. Synthesis and structure-activity relationships of these compounds are described.

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“…Animal and human studies since have attempted to provide biologic evidence to support a cardioprotective effect. It also has been shown that tamoxifen reduces total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, [13][14][15][16][17][18][19][20][21][22] both of which are known risk factors for coronary artery disease. [23][24][25][26][27] Tamoxifen also reduces circulating levels of lipoprotein(a), 22 which is a potentially more atherogenic lipiprotein than LDL.…”

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confidence: 99%

Tamoxifen‐treated breast carcinoma patients and the risk of acute myocardial infarction and newly‐diagnosed angina

Bradbury

Lash

Kaye

et al. 2005

Cancer

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BACKGROUNDIt is known that tamoxifen therapy favorably affects blood cholesterol levels and other cardiovascular disease risk factors; however, to our knowledge, few studies to date have reported a lower risk of heart disease for breast carcinoma patients who are treated with tamoxifen.METHODSA nested, matched, case–control study design was used with data from the General Practice Research Database to examine whether patients with breast carcinoma who had been treated with tamoxifen were at reduced risk of having a first acute myocardial infarction (MI) or of developing angina compared with unexposed women. All women between age 30 years and age 85 years who had been diagnosed with breast carcinoma and treated with tamoxifen, or who had been diagnosed with carcinoma of the bladder or colorectum, or nonmelanoma skin cancer between January 1991 and December 1999 were identified. From this population, all women were identified who had newly diagnosed acute MI or angina that occurred at least 1 year after their cancer diagnosis. Four female control participants were matched to each case based on age (± 1 year), date of MI or angina diagnosis (corresponding date for matched controls), and date of cancer diagnosis (± 6 months). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using conditional logistic regression, controlling for the matching factors, and adjusting for important risk factors, including body mass index, use of hormone replacement therapy, smoking status, and treated hypertension.RESULTSCurrent users of tamoxifen had a reduced rate ratio of acute MI or angina (adjusted OR, 0.4; 95% CI, 0.2–0.7) compared with nonusers. The effect persisted with increasing cumulative dose and length of use.CONCLUSIONSThe treatment of breast carcinoma with tamoxifen was found to reduce a woman's risk of acute MI or angina during the 5 years of recommended therapy. Cancer 2005. © 2005 American Cancer Society.

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Serum cholesterol reduction with tamoxifen

Cited by 31 publications

References 17 publications

Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

A New Series of Estrogen Receptor Modulators: Effect of Alkyl Substituents on Receptor-Binding Affinity

Tamoxifen‐treated breast carcinoma patients and the risk of acute myocardial infarction and newly‐diagnosed angina

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