Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of germline cells with retroviruses initiates permanent proviral colonization of the germline genome. The germline-integrated proviruses, called endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order and belong to the transposable element family. Endogenous retroviruses and other long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse genomes, respectively. It is likely that each individual has a distinct genomic ERV profile. Recent studies have revealed that a substantial fraction of ERVs retains the coding potentials necessary for virion assembly and replication. There are several layers of potential mechanisms controlling ERV expression: intracellular transcription environment (e.g., transcription factor pool, splicing machinery, hormones), epigenetic status of the genome (e.g., proviral methylation, histone acetylation), profile of transcription regulatory elements on each ERV's promoter, and a range of stress signals (e.g., injury, infection, environment). Endogenous retroviruses may exert pathophysiologic effects by infection followed by random reintegration into the genome, by their gene products (e.g., envelope, superantigen), and by altering the expression of neighboring genes. Several studies have provided evidence that ERVs are associated with a range of pathogenic processes involving multiple sclerosis, systemic lupus erythematosus, breast cancer, and the response to burn injury. For instance, the proinflammatory properties of the human ERV-W envelope protein play a central role in demyelination of oligodendrocytes. As reviewed in this article, recent advances in ERV biology and mammalian genomics suggest that ERVs may have a profound influence on various pathogenic processes including the response to injury and infection. Understanding the roles of ERVs in the pathogenesis of injury and infection will broaden insights into the underlying mechanisms of systemic immune disorder and organ failure in these patients.
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PMID:Endogenous retroviruses in systemic response to stress signals. 1831 6

Vitamin D insufficiency has been shown to be associated with a number of conditions including diabetes, multiple sclerosis and the overall risk of cancer. We aimed at studying the association between vitamin D intake and risk of breast cancer in a meta-analysis. We searched Pubmed, Embase, and Web of Science using the MESH terms "vitamin D" and "breast cancer". A total of 1731 studies were identified, but only 6 studies contained original data on the association between intake of vitamin D and risk of breast cancer. Overall there was no association between amount of vitamin D and risk of breast cancer (RR=0.98, 95% CI: 0.93-1.03, test for heterogeneity p<0.01). However, most studies reported on very low intakes of vitamin D (typically in the range 100-400 IU/day). Restricting the analyses to intakes > or =400 IU/day yielded a more homogenous result with a trend towards less breast cancer with > or =400 IU/day vs. the lowest intake (typically <50-150 IU/day), RR=0.92, 95% CI: 0.87-0.97, p for heterogeneity 0.14. In conclusion there may be a trend towards fewer cases of breast cancer with higher intakes of vitamin D (> or =400 IU/day). However, more research is needed, preferably in the form of randomized-controlled trials.
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PMID:Intake of vitamin D and risk of breast cancer--a meta-analysis. 1859 Aug 21

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17) translocation is a well-recognized complication of cancer treatment with agents targeting topoisomerase II. However, cases are emerging after mitoxantrone therapy for multiple sclerosis (MS). Analysis of 12 cases of mitoxantrone-related t-APL in MS patients revealed an altered distribution of chromosome 15 breakpoints versus de novo APL, biased toward disruption within PML intron 6 (11 of 12, 92% vs 622 of 1022, 61%: P = .035). Despite this intron spanning approximately 1 kb, breakpoints in 5 mitoxantrone-treated patients fell within an 8-bp region (1482-9) corresponding to the "hotspot" previously reported in t-APL, complicating mitoxantrone-containing breast cancer therapy. Another shared breakpoint was identified within the approximately 17-kb RARA intron 2 involving 2 t-APL cases arising after mitoxantrone treatment for MS and breast cancer, respectively. Analysis of PML and RARA genomic breakpoints in functional assays in 4 cases, including the shared RARA intron 2 breakpoint at 14 446-49, confirmed each to be preferential sites of topoisomerase IIalpha-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this subtype of leukemia after exposure to this agent.
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PMID:Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis. 1865 Apr 49

Recent large-scale genome-wide association (GWA) studies of SNP variations captured many thousands individual genetic profiles of H. sapiens and facilitated identification of significant genetic traits which are highly likely to influence the pathogenesis of several major human diseases. Here we apply the integrative genomics principles to interrogate relationships between structural features and gene expression patterns of disease-linked SNPs, microRNAs and mRNAs of protein-coding genes in association to phenotypes of 15 major human disorders, namely bipolar disease (BD); rheumatoid arthritis (RA); coronary artery disease (CAD); Crohn's disease (CD); type 1 diabetes (T1D); type 2 diabetes (T2D); hypertension (HT); ankylosing spondylitis (AS); Graves' disease (autoimmune thyroid disease; AITD); multiple sclerosis (MS); breast cancer (BC); prostate cancer (PC); systemic lupus erythematosus (SLE); vitiligo-associated multiple autoimmune disease (VIT); and ulcerative colitis (UC). We selected for sequence homology profiling a set of approximately 250 SNPs which were unequivocally associated with common human disorders based on multiple independent studies of 220,124 individual samples comprising 85,077 disease cases and 129,506 controls. Our analysis reveals a systematic primary sequence homology/complementarity-driven pattern of associations between disease-linked SNPs, microRNAs and protein-coding mRNAs defined here as a human disease phenocode. We utilize this approach to draw SNP-guided microRNA maps of major human diseases and define a consensus disease phenocode for fifteen major human disorders. A consensus disease phenocode comprises 72 SNPs and 18 microRNAs with an apparent propensity to target mRNA sequences derived from a single protein-coding gene, KPNA1. Each of microRNAs in this elite set appears linked to at least three common human diseases and has potential protein-coding mRNA targets among the principal components of the nuclear import pathway. We confirmed the validity of our findings by analyzing independent sets of most significant disease-linked SNPs and demonstrating statistically significant KPNA1-gene expression phenotypes associated with human genotypes of CD, BD, T2D and RA populations. Our analysis supports the idea that variations in DNA sequences associated with multiple human diseases may affect phenotypes in trans via non-protein-coding RNA intermediaries interfering with functions of microRNAs and defines the nuclear import pathway as a potential major target in 15 common human disorders.
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PMID:An SNP-guided microRNA map of fifteen common human disorders identifies a consensus disease phenocode aiming at principal components of the nuclear import pathway. 1871 69

Tamoxifen is a selective oestrogen receptor modulator (SERM) with an established role in the treatment and chemoprevention of hormone-related breast cancer. It is also cardioprotective and increases bone mineral density. However, due to pleiotrophic ligand-receptor properties, its role in a variety of seemingly unrelated disorders, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, systemic lupus erythematosus and urological cancers, has been investigated in many studies. The non-patented drug tamoxifen confers a significant advantage over newer drugs in being inexpensive and well-tolerated with a known side-effect profile. This review highlights the interaction of tamoxifen on oestrogen receptors (ERs) and assesses whether this agent continues to have future applications in a variety of clinical settings, both as a therapy in early and established disease and usage as a prophylactic in those at risk of debilitating conditions. Indeed, it may have as-yet-unknown benefit(s) in a variety of conditions, both as a prophylactic in those at high-risk and also as in novel therapeutic strategies in established disease. Future clinical studies may seek to establish the exact future role and efficacy for SERMs both in men and women. Perhaps a multi-functional SERM such as tamoxifen may be the aspirin of the 21(st) century.
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PMID:The multiple applications of tamoxifen: an example pointing to SERM modulation being the aspirin of the 21st century. 1875 31

Most of the population receive their nutritional vitamin D requirements through exposure to solar ultraviolet (UV) radiation, with cutaneous synthesis estimated to provide 80-100% of the vitamin D requirements of the body. However, little is understood about the basic interaction of sunlight (UV) exposure and the subsequent photobiology and photochemistry of vitamin D production in humans. Low vitamin D (blood serum 25[OH]D) status has been linked to the development of a surprisingly wide range of diseases. Epidemiological data and animal studies indicate that low vitamin D is linked to rickets, bone mass loss, multiple sclerosis, hypertension, breast cancer, prostate cancer, colorectal cancer, insulin dependent diabetes and schizophrenia. Importantly some this emerging research associates such diseases with location and subsequent ultraviolet radiation exposures. This paper overviews concepts important to consider when assessing the impact of location and UV exposure on vitamin D synthesis.
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PMID:Geographic location and vitamin D synthesis. 1878 59

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system frequently complicated by devastating neurologic symptoms and progressive disability. Much progress has been made in the development of immunomodulating drugs to help fight the progression of MS. These drugs are believed to work by interacting with various immune system components to reduce the amount of autoimmune destruction to the nervous system. We report 2 cases of women with MS on immunomodulatory therapy who presented with locally advanced breast cancer with aggressive biologic phenotypes and exceptionally poor outcomes. We consider the potential for an increased risk of developing a poorer-prognosis breast cancer as a result of concomitant immunomodulatory effects of the previous MS treatment, particularly the effects the drugs are reported to have on regulatory T cells, and therefore present these cases and a review of the current literature. Current data in the literature reflect the need for further study in ascertaining the risk of biologically poor-prognosis breast cancer development in patients with MS treated with immunomodulatory therapy.
Clin Breast Cancer 2008 Oct
PMID:Immunomodulatory therapy in multiple sclerosis and breast cancer risk: a case report and literature review. 1895 60

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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PMID:Stem cell transplantation; Iranian experience. 1911 Oct 33

Tamoxifen is a widely known anti-estrogen which has been employed in adjuvant treatment of early-stage, estrogen-sensitive breast cancer for over 20 years. Less well known are the effects of tamoxifen on immune function, which we discuss here. We review the growing body of evidence which demonstrates immunomodulatory effects of tamoxifen, including in vitro and in vivo studies as well as observations made in breast cancer patients treated with tamoxifen. Taken together these studies suggest that tamoxifen is capable of inducing a shift from cellular (T-helper 1) to humoral (T-helper 2) immunity. Interestingly, the immunomodulatory effects of tamoxifen appear to be independent of the estrogen-receptor and may be mediated through the multidrug resistance gene product, Permeability-glycoprotein, for which a role in immunity has recently emerged. We furthermore discuss the clinical implications of the immunomodulatory effects of tamoxifen which are twofold. First, tamoxifen may be useful in the treatment of immune-mediated disorders, particularly of those arising from aberrant T-helper 1 cell activity, including allograft rejection, Crohn's disease, and Th1-mediated autoimmune conditions such as diabetes mellitus, scleroderma, and multiple sclerosis. Second, given that cellular T-helper 1 immunity is targeted against cancer cells, the tamoxifen-induced shift away from cellular immunity represents a significant step in fostering a cancerogenic environment. This may limit the anti-cancer effects of tamoxifen and thus explain why tamoxifen is inferior compared to other anti-estrogens in preventing disease recurrence in early-stage breast tumors.
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PMID:The effects of tamoxifen on immunity. 1968 84

This study evaluated the sociodemographic, clinical and behavioral correlates of post-traumatic growth (PTG) in coronary artery disease (CAD) patients, and the degree of PTG compared to other patient groups. Using a prospective design, 1497 CAD outpatients completed a survey assessing potential PTG correlates. A total of 1268 responded to a nine-month follow-up survey assessing PTG. Significant PTG correlates were being younger, non-white, having lower income, functional status, and depressive symptoms, greater social support, and positive illness perceptions. The degree of PTG was equivalent to that of cardiac patients in other countries, but was lower than that of breast cancer and multiple sclerosis patients.
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PMID:Post-traumatic growth among cardiac outpatients: degree comparison with other chronic illness samples and correlates. 2047 8


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