Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triple-negative breast cancer (TNBC) is defined by a lack of expression of estrogen, progesterone, and HER2 receptors, and genetically most of them fall into the basal subgroup of breast cancer. The important issue of TNBC is poorer clinical outcome and absence of effective targeted therapy. In this study, we sought to identify DNA copy number alterations and expression of relevant genes characteristic of TNBC to discover potential therapeutic targets. Frozen tissues from 114 breast cancers were analyzed using high-resolution array comparative genomic hybridization. The classification into subtype was determined by estrogen and progesterone receptor expression, and by the presence or absence of gain on the ERBB2 containing clone. The ACE algorithm was used for calling gain and loss of clones. Twenty-eight cases (25%) were classified as TNBC. Recurrent gains (> or =25%) unique to TNBC were 9p24-p21, 10p15-p13, 12p13, 13q31-q34, 18q12, 18q21-q23, and 21q22. Two published gene expression array data sets comparing basal subtype versus other subtype breast cancers were used for searching candidate genes. Of the genes upregulated in the basal subtype, 45 of 686 genes in one data set and 59 of 1,428 in the second data set were found to be located in the gained regions. Of these candidate genes, gain of NFIB (9p24.1) was specific for TNBC in a validation set by real-time PCR. In conclusion, we have identified recurrently gained regions characteristic of TNBC, and found that NFIB copy number and expression is increased in TNBC across the data sets. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
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PMID:DNA copy number alterations and expression of relevant genes in triple-negative breast cancer. 1831 8

A case of a 36-year old woman with HER2-positive early breast cancer treated with adjuvant trastuzumab left ventricle dysfunction and cardiac arrest in ventricular fibrillation mechanism is presented. After having been successfully resuscitated, trastuzumab therapy was withheld, pharmacotherapy (beta-blocker, ACE-I) implemented and ICD was implanted. Echocardiography performed 6 months later, revealed normal systolic function of the left ventricle. The patient died despite further oncologic treatment due to progression of the disease. The authors discuss the approach to this dramatic but lone cardiac side effect of trastuzumab treatment.
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PMID:[Cardioverter-defibrillator in the treatment of arrhythmia induced by trastuzumab used in the adjuvant setting in a patient with positive human epidermal growth factor receptor type-2 breast cancer]. 2282 58

Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months. The patient was treated with the cardioprotective agent dexrazoxane, and changes in cardiac markers [e.g. decreases in ejection fraction (EF)] were immediately addressed by therapeutic intervention with the ACE inhibitor lisinopril and beta-blocker metoprolol. The patient had a complete response to doxorubicin therapy, with a cumulative dose of 1,350 mg/m2, which is significantly above the recommended limits, and to our knowledge, the highest dose reported in literature. Two and a half years after the last doxorubicin cycle, the patient is asymptomatic with no cardiotoxicity and an excellent quality of life. This case highlights the importance of careful monitoring and management of doxorubicin-mediated cardiotoxicity, and that higher cumulative doses of anthracyclines can be considered in patients with ongoing clinical benefit.
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PMID:Maximizing the Benefit-Cost Ratio of Anthracyclines in Metastatic Breast Cancer: Case Report of a Patient with a Complete Response to High-Dose Doxorubicin. 2862 95