RESUMO
The estrogen receptor plays a critical role in the pathogenesis and clinical behavior of breast cancer. To better understand the molecular basis of estrogen-dependent forms of this disease we studied gene expression profiles from 53 primary breast cancer biopsies. Gene expression data for more than 7000 genes were generated from each tumor sample with oligo microarrays. A standard correlation-clustering algorithm identified 18 genes that co-clustered with estrogen receptor alpha. Eleven of these genes had previously been associated with estrogen regulation or breast tumorigenesis including trefoil factor 1 and estrogen regulated LIV-1. Additional study of these 18 genes may further delineate the role of estrogen receptor in breast cancer, generate new predictive biomarkers for response to endocrine therapies and identify novel therapeutic targets.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Família Multigênica/genética , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Estrogênio/genética , Animais , Biópsia , Células Cultivadas , Receptor alfa de Estrogênio , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , RNA Neoplásico/química , RNA Neoplásico/genéticaRESUMO
The first German patient with achalasia-microcephaly syndrome is described. The mother was exposed to the anti-malarial drug Mefloquine during the first 8 weeks of pregnancy.
Assuntos
Anormalidades Induzidas por Medicamentos , Acalasia Esofágica/induzido quimicamente , Microcefalia/induzido quimicamente , Antimaláricos/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Mefloquina/efeitos adversos , GravidezRESUMO
The beta-synuclein protein is highly homologous to the alpha-synuclein protein for which two mutations were reported in some familial cases of Parkinson disease. It has been shown that both alpha- and beta-synucleins may be able to inhibit phospholipase D2 selectively. We have observed that the beta-synuclein gene (HGMW-approved symbol, SNCB) is highly expressed in brain including the substantia nigra, the main region of neuronal degeneration in patients with Parkinson disease. We have determined the intron-exon structure of the beta-synuclein gene and established sequencing assays that will facilitate the search for mutations in the beta-synuclein gene in patients with Parkinson disease or other neurodegenerative disorders.
Assuntos
Encéfalo/metabolismo , Proteínas do Tecido Nervoso/genética , Sequência de Aminoácidos , Sequência de Bases , DNA Complementar , Éxons/genética , Expressão Gênica , Humanos , Íntrons/genética , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/química , Reação em Cadeia da Polimerase/métodos , Sinucleínas , alfa-Sinucleína , beta-SinucleínaRESUMO
We have identified and characterized a new member of the human synuclein gene family, gamma-synuclein (SNCG). This gene is composed of five exons, which encode a 127 amino acid protein that is highly homologous to alpha-synuclein, which is mutated in some Parkinson's disease families, and to beta-synuclein. The gamma-synuclein gene is localized to chromosome 10q23 and is principally expressed in the brain, particularly in the substantia nigra. We have determined its genomic sequence, and established conditions for sequence analysis of each of the exons. The gamma-synuclein gene, also known as BCSG1, was recently found to be overexpressed in advanced infiltrating carcinoma of the breast. Our survey of the EST database indicated that it might also be overexpressed in an ovarian tumor.
Assuntos
Encéfalo/metabolismo , Cromossomos Humanos Par 10 , Proteínas do Tecido Nervoso/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Mapeamento Cromossômico , Bases de Dados Factuais , Éxons , Feminino , Humanos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/química , Neurônios/metabolismo , Neoplasias Ovarianas/genética , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Substância Negra/metabolismo , Sinucleínas , alfa-Sinucleína , beta-Sinucleína , gama-SinucleínaRESUMO
The objective of this prospective study was to assess the prognostic value of dynamic and static liver function tests and clinical symptoms in pediatric patients with chronic end-stage liver disease in a serial examination including three evaluations at 3-month intervals. Of the 24 patients entering the study, six were given transplants within the observation period of 10 months. Of the remaining 18 patients who were considered in the final evaluation, five died before transplantation was possible. The variables included in the analysis were monoethylglycinexylidide (MEGX) formation from lidocaine, bilirubin, albumin, and creatinine serum concentrations, catalytic serum concentration of cholinesterase (CHE), prothrombin time (PT), factors II and V, serum amino acids, body weight, and presence of ascites. In nonsurvivors (n = 5), MEGX serum concentrations 30 min after intravenous administration of lidocaine (1 mg/kg body weight) were < 10 micrograms/L at the first examination. Statistically significant differences between nonsurvivors and survivors were observed for initial MEGX test results (p = 0.0089) and serum bilirubin concentrations (p = 0.009), as well as for the last available MEGX and bilirubin data from each patient (p = 0.017 and 0.016, respectively). At a diagnostic sensitivity of 100%, the corresponding diagnostic specificities for MEGX and bilirubin from the first examination were 77 and 62%, respectively. These data show that consistently low MEGX test results < 10 micrograms/L, obtained 30 min after intravenous administration of lidocaine (1 mg/kg body weight), are a prognostically unfavorable sign in pediatric transplant candidates.