Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current findings and controversies between oral contraceptives (OCs) and cardiovascular disease and cancers. Specifically, venous thromboembolism, stroke, myocardial infarction, (MI), atherosclerosis, breast cancer, cervical cancer, endometrial cancer, and ovarian cancer are reviewed. The concentration in the literature is on higher dose estrogen (at least 50 mg) studies which suggest that there is with current users, particularly older women who smoke, a risk of myocardial infarction, venous thrombosis, and subarachnoid hemorrhage. Of the 11 case control studies and 4 cohort studies it appears that venous thrombosis increases in risk with an increase in estrogen content and remains constant for duration of use. However, definitive studies have not been completed on 50 mg doses of ethinyl estradiol (EE) and mestranol (ME). The actual individual risk may be small, 1/1000 current users/year. Thrombotic and hemorrhagic stroke in the 1970s had a risk of 37/100,000 users per year, mostly among smokers 35 years and older with predisposing medical conditions. It is suggested that although there were mixed findings between current and past users in the 1970s low dose current or past users are not substantially at risk. The pre-mid 1970 risk of MI was 7 and 67 cases/100,000 current users ged 30-39 respectively per year. The risk group is similar to stroke. Thrombosis seems to be responsible for the increased risk, rather than atherosclerosis. More data are needed on low preparations; however limited findings suggest little if any risk. There is no available data on the risk for coronary artery atherosclerosis due to OC use, even though 50% of all women die from atherosclerosis-related processes regardless of OC use. Non human primate studies, however, suggest that there may be a reduced risk, perhaps due to the presence of estrogen receptors in arterial endothelium and smooth muscles. Data clearly indicate that the overall risk of breast cancer pre and post 1950 is the same, but age may be a factor with younger OC users at risk; parity protects. The association for lifetime risk, however, cannot be determined since most use occurred in the 1960s. For cervical cancer, 8 found no increased risk and 9 did, and the suggestion is the 5 years use is related to increased risk. Biases related to sexual behavior confound control and analysis of data. The most common cancer in developing countries is cervical, which warrants greater Pap smear screening to reduce this preventable cancer. Protection from cancer of the endometrium occurs for 15 years following 12 months of OC use at a 40% reduced risk. A protected effect is also found for epithelial ovarian cancer, with a 40% risk reduction. It is concluded that health benefits of OCs far exceed the health risks.
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PMID:Long-term health risks and benefits of oral contraceptive use. 209 41

A review on participation of chlamydiae in the origin of the HIV-infection, carcinoma and atherosclerosis. The antibodies against the newly discovered pgp3 protein of C. trachomatis were found in 83-87% of the seropositive HIV patients. The participation of C. trachomatis in the etiology of cervical and ovarian carcinoma has been discussed in a number of articles. Simultaneous examinations along different lines allow the hypothesis, that C. trachomatis acts as a cofactor in the development of ovarian and cervical carcinoma. Chronic infection by C. pneumoniae appears to be one of the risk factors of pulmonary carcinoma. Many papers dealing with the relation of chlamydiae and atherosclerosis have been published. The relation between the chronic C. pneumoniae-infection and atherosclerosis has been assessed serologically and by direct demonstration of chlamydiae in atheromatous plaques.
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PMID:[Chlamydiae--still new surprises]. 1056 17

The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with reduced enzyme activity, hyperhomocysteinaemia and increased risk for atherosclerosis in homozygotes. We examined the frequency of this mutation and its association with disease pattern in 491 Jewish women with either sporadic (n = 355; 72%) or hereditary (n = 136; 28%) breast and/or ovarian cancer and in 69 asymptomatic BRCA1/2 mutation carriers, genotyped for the three predominant Jewish founder BRCA1/2 mutations (185delAG, 5382insC and 6174delT). 677T homozygotes were equally distributed among women with sporadic breast and/or ovarian cancer (71/355; 20.0%) and among BRCA1/2 mutation carriers (43/205; 21.0%) (P=non-significant). 677T homozygotes were equally distributed among women diagnosed with breast cancer prior to (22/122; 18.0%) and after 42 years of age (42/243; 17.3%). Among BRCA1/2 carriers, the rate of 677T homozygotes in manifesting cancer (32/136; 23.5%) and asymptomatic individuals (11/69; 15.9%) was not significantly different. The rate of 677T homozygotes (24/72; 33.3%) was higher (P=0.0026) among women with bilateral breast cancer and those with both breast and ovarian carcinoma than among those with unilateral breast cancer (64/365; 17.5%). Differences in morbidity (one versus multiple breast/ovarian tumours) are mainly attributed to 677T homozygosity and partly to BRCA1/2 mutations. Confirmation of these data, namely, that the 677T allele is significantly more common in cases of bilateral breast cancer or combined breast and ovarian cancer would have important clinical implications.
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PMID:Association of the C677T polymorphism in the MTHFR gene with breast and/or ovarian cancer risk in Jewish women. 1109 4

ATP-binding cassette (ABC) transporters are a family of proteins that translocate molecules across cellular membranes. Substrates can include lipids, cholesterol and drugs. Mutations in ABC transporter genes can cause human pathologies and drug resistance phenotypes in cancer cells. ABCA2, the second member the A sub-family to be identified, was found at high levels in ovarian carcinoma cells resistant to the anti-cancer agent, estramustine (EM). In vitro models with elevated levels of ABCA2 are resistant to a variety of compounds, including estradiol, mitoxantrone and a free radical initiator, 2,2'-azobis-(2-amidinopropane) (AAPH). ABCA2 is most abundant in the central nervous system (CNS), ovary and macrophages. Enhanced expression of ABCA2 and related proteins, including ABCA1, ABCA4 and ABCA7, is found in human macrophages upon bolus cholesterol treatment. ABCA2 also plays a role in the trafficking of low-density lipoprotein (LDL)-derived free cholesterol and is coordinately expressed with genes involved in cholesterol homeostasis. Additionally, ABCA2 expression has been linked with gene cluster patterns consistent with pathologies including Alzheimer's disease (AD). A single-nucleotide polymorphism (SNP) in exon 14 of the ABCA2 gene was shown to be linked to early onset AD in humans, supporting the observation that ABCA2 expression influences levels of beta-amyloid peptide (Abeta), the primary component of senile plaques. ABCA2 may play a role in cholesterol transport and affect a cellular phenotype conducive to the pathogenesis of a variety of human diseases including AD, atherosclerosis and cancer.
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PMID:The ATP-binding cassette transporter ABCA2 as a mediator of intracellular trafficking. 1702 87

ATP-binding cassette (ABC) transporters comprise a family of critical membrane bound proteins functioning in the translocation of molecules across cellular membranes. Substrates for transport include lipids, cholesterol and pharmacological agents. Mutations in ABC transporter genes cause a variety of human pathologies and elicit drug resistance phenotypes in cancer cells. ABCA2, the second member the A subfamily to be identified, was highly expressed in ovarian carcinoma cells resistant to the anti-cancer agent, estramustine, and more recently, in human vestibular schwannomas. Cells expressing elevated levels of ABCA2 show resistance to variety of compounds, including estradiol, mitoxantrone and a free radical initiator, 2,2'-azobis-(2-amidinopropane). ABCA2 is expressed in a variety of tissues, with greatest abundance in the central nervous system and macrophages. This transporter, along with other proteins that have a high degree of homology to ABCA2, including ABCA1 and ABCA7, are up-regulated in human macrophages during cholesterol import. Recent studies have shown ABCA2 also plays a role in the trafficking of low-density lipoprotein (LDL)-derived free cholesterol and to be coordinately expressed with sterol-responsive genes. A single nucleotide polymorphism in exon 14 of the ABCA2 gene was shown to be linked to early onset Alzheimer disease (AD) in humans, supporting an earlier study showing ABCA2 expression influences levels of APP and beta-amyloid peptide, the primary component of senile plaques. Studies thus far implicate ABCA2 as a sterol transporter, the deregulation of which may affect a cellular phenotype conducive to the pathogenesis of a variety of human diseases including AD, atherosclerosis and cancer.
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PMID:The ABCA2 transporter: intracellular roles in trafficking and metabolism of LDL-derived cholesterol and sterol-related compounds. 1726 23

Guggulsterone is a plant polyphenol traditionally used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, possibly through an anti-inflammatory mechanism. Whether this steroid has any role in cancer is not known. In this study, we found that guggulsterone inhibits the proliferation of wide variety of human tumor cell types including leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian carcinoma. Guggulsterone also inhibited the proliferation of drug-resistant cancer cells (e.g., gleevac-resistant leukemia, dexamethasone-resistant multiple myeloma, and doxorubicin-resistant breast cancer cells). Guggulsterone suppressed the proliferation of cells through inhibition of DNA synthesis, producing cell cycle arrest in S-phase, and this arrest correlated with a decrease in the levels of cyclin D1 and cdc2 and a concomitant increase in the levels of cyclin-dependent kinase inhibitor p21 and p27. Guggulsterone-induced apoptosis as indicated by increase in the number of Annexin V- and TUNEL-positive cells, through the downregulation of anti-apoptototic products. The apoptosis induced by guggulsterone was also indicated by the activation of caspase-8, bid cleavage, cytochrome c release, caspase-9 activation, caspase-3 activation, and PARP cleavage. The apoptotic effects of guggulsterone were preceded by activation of JNK and downregulation of Akt activity. JNK was needed for guggulsterone-induced apoptosis, inasmuch as inhibition of JNK by pharmacological inhibitors or by genetic deletion of MKK4 (activator of JNK) abolished the activity. Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and downregulation of antiapoptotic protein expression.
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PMID:Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. 1747 22

The proto-oncogene Myc serves as a paradigm for understanding the dynamics of transcriptional regulation. Myc protein has been linked to immune dysfunction, cancer development and neoplastic transformation. We review recent research regarding functions of Myc as an important modulator in immune disorders, postallogeneic hematopoietic stem cell transplantation (HSCT) and several cancers. Myc overexpression has been repeatedly linked to immune disorders and specific cancers, such as myasthenia gravis, psoriasis, pemphigus vulgaris, atherosclerosis, long-term allogeneic survival among HSCT patients, (primary) inflammatory breast cancer, (primary) ovarian carcinoma and hematological malignancies: acute myeloid leukemia, chronic myelogenous leukemia, Hodgkin's lymphoma and diffuse large B-cell lymphoma. However, decreased expression of Myc has been observed in HSCT patients who did not survive. Understanding impaired or inappropriate expression of Myc may present a path for the discovery of new targets for therapeutic applications.
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PMID:Is Myc an Important Biomarker? Myc Expression in Immune Disorders and Cancer. 2928 66