RESUMO
Expression of estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) can subdivide breast carcinomas into clinically meaningful classes. Cancers lacking expression of all three of these receptors (triple-negative breast cancer; TNBC) is of particular interest for molecular research because these tumors currently have no effective targets for therapy. Furthermore, TNBCs are relatively more prevalent among African-American women and can account for some of the health disparities associated with breast cancer. We approached a molecular understanding of how TNBC differs from ER(+) breast cancer through a comprehensive gas chromatography (GC)-mass spectrometry (MS) and liquid chromatography (LC)/MS/MS-based and unbiased metabolomic analysis of a series of breast carcinomas from African-American patients. Remarkably, global metabolomic profiling of tumor tissues identified a total of 418 distinct metabolites, out of which 133 (31.8%) were shown to differ between the ER(+) and TNBC tumors with statistical probability of p<0.05. Specific biochemical pathways affected included those reflecting general increases in energy metabolism and transmethylation in the TNBC tumors when compared to ER(+) tumors. Additionally, biochemicals associated with increased proliferation, redox balance and the recently proposed oncometabolites, sarcosine and 2-hydroxyglutarate, were also detected at higher levels in the TNBC versus ER(+) tumors. These studies demonstrate that TNBC tumors have metabolic signatures that distinguish them from ER(+) tumors and suggest that distinctive metabolic characteristics of these tumors might offer new targets for treatment.
Assuntos
Biomarcadores Tumorais/metabolismo , Negro ou Afro-Americano , Metabolômica/métodos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Aminoácidos/metabolismo , Dipeptídeos/metabolismo , Metabolismo Energético , Feminino , Glutationa/metabolismo , Humanos , Redes e Vias Metabólicas , Metaboloma , Metilação , Pessoa de Meia-Idade , NAD/metabolismo , Invasividade Neoplásica , OxirreduçãoRESUMO
OBJECTIVE: We undertook this study to determine the outcomes of upper extremity arterial reconstruction for chronic ischemia. METHODS: The National Surgical Quality Improvement Program Database was queried to identify all patients who had undergone an upper extremity bypass for chronic ischemia between 2005 and 2007. RESULTS: A total of 55 patients were identified in a primarily female population (71% women). Mean age was 57. The most common preoperative diagnoses included ischemia resulting from prior arterial thromboembolism in 16 (29%) patients and atherosclerotic upper extremity arterial disease in 11 (20%) patients. The most common procedures performed included axillo-brachial bypass in 17 (31%) patients, brachial-brachial bypass in 11 (20%) patients, and carotid-brachial bypass in 11 (20%) patients. There were no perioperative deaths and no acute graft failures. CONCLUSION: Although upper extremity bypass remains rare, the procedures appear to be safe with excellent 30-day results. Indications differ from those for lower extremity bypass.