The tumor-bearing state is associated with an increase in gluconeogenesis which may contribute to the development of cancer cachexia. The purpose of this study was to determine if tolbutamide, a drug ...known to decrease gluconeogenesis in diabetes, could decrease gluconeogenesis in hepatocytes isolated from tumor-bearing rats. Hepatocytes from 24-hr fasted normal and methylcholanthrene-induced sarcoma-bearing rats (5-10% tumor burden) were isolated by in situ collagenase liver perfusion. Hepatocytes (n = 12 samples) from non-tumor-bearing (NTB) controls and tumor-bearing (TB) rats were incubated with lactate (10 mM) and alanine (10 mM) with and without 1 mM tolbutamide. Supernatant glucose concentration was measured at 30-min intervals for 2 hr. Rates of gluconeogenesis (+/- standard error) were calculated by linear regression and are expressed as nmole glucose/10(6) cells/min. Comparisons were made by two-way analysis of variance and significance defined as P < 0.05. TB hepatocytes had an increased rate of gluconeogenesis (P < 0.0001) from alanine and lactate (3.8 +/- 0.30 and 2.2 +/- 0.10, respectively) compared with NTB hepatocytes (0.66 +/- 0.10 and 1.2 +/- 0.04, respectively). TB hepatocytes treated with tolbutamide had a decreased (P < 0.0001) rate of gluconeogenesis from alanine and lactate (3.1 +/- 0.10 and 1.1 +/- 0.10, respectively) compared with untreated TB hepatocytes (5.3 +/- 0.10 and 2.1 +/- 0.10, respectively). Tolbutamide inhibits gluconeogenesis from lactate and alanine in tumor-influenced hepatocytes.
Background. About half the patients involved in the current study were born outside of the United States. Epidemiologic and histologic features and survival estimates were compared with persons born ...in the United States. Results of gastrectomy with lymph node dissection were studied.
Methods. Records of 187 patients with adenocarcinoma of the stomach were reviewed. Seventy‐six with a curative gastrectomy were staged retrospectively. Univariate and multivariate analyses were done.
Results. Seventy‐six percent of histologically reviewed curative resections had the intestinal subtype with the same frequency in U.S.‐born and foreign‐born patients. Fewer patients with proximal third lesions were foreign born. Thirty‐six percent had complications. The overall 5‐year Kaplan‐Meier survival estimate was 46%: 77% for patients with negative nodes and 33% for patients with positive nodes. N1 survival estimate was 44%; N2, 25%; N3(M1), 0%. All six patients with early gastric cancer are alive 50–147 months after surgery. Other Stage I patients had estimated survival of 65%; Stage II, 52%; Stage III, 40%; and Stage IV, 0%. Multivariate analysis revealed four significant prognostic variables: nativity, histologic subgroup, presence of complications, and number of positive nodes.
Conclusions. Proximal gastric cancer was more common in U.S.‐born persons. Gastric cancer may be more malignant in U.S.‐born persons than in foreign‐born persons because their survival was significantly poorer. Complications, a significant adverse factor, were more common in U.S. series. Pancreatectomy with gastrectomy is rarely indicated, because microscopic involvement is rare and complications frequent. The prognostic advantage of a regional lymphadenectomy remains unclear.
The proximal tubule (PT) is a nephron segment that is responsible for the majority of solute and water reabsorption in the kidney. Each of its sub-segments have specialized functions; however, little ...is known about the genes and proteins that determine the oxidative phosphorylation capacity of the PT sub-segments. This information is critical to understanding kidney function and will provide a comprehensive landscape of renal cell adaptations to injury, physiologic stressors, and development. This study analyzed three immortalized murine renal cell lines (PT S1, S2, and S3 segments) for protein content and compared them to a murine fibroblast cell line. All three proximal tubule cell lines generate ATP predominantly by oxidative phosphorylation while the fibroblast cell line is glycolytic. The proteomic data demonstrates that the most significant difference in proteomic signatures between the cell lines are proteins known to be localized in the nucleus followed by mitochondrial proteins. Mitochondrial metabolic substrate utilization assays were performed using the proximal tubule cell lines to determine substrate utilization kinetics thereby providing a physiologic context to the proteomic dataset. This data will allow researchers to study differences in nephron-specific cell lines, between epithelial and fibroblast cells, and between actively respiring cells and glycolytic cells.
Proteomic analysis of proteins expressed in immortalized murine renal proximal tubule cells was compared to a murine fibroblast cell line proteome. The proximal tubule segment specific cell lines: S1, S2 and S3 are all grown under conditions whereby the cells generate ATP by oxidative phosphorylation while the fibroblast cell line utilizes anaerobic glycolysis for ATP generation. The proteomic studies allow for the following queries: 1) comparisons between the proximal tubule segment specific cell lines, 2) comparisons between polarized epithelia and fibroblasts, 3) comparison between cells employing oxidative phosphorylation versus anaerobic glycolysis and 4) comparisons between cells grown on clear versus opaque membrane supports. The data finds major differences in nuclear protein expression and mitochondrial proteins. This proteomic data set will be an important baseline dataset for investigators who need immortalized renal proximal tubule epithelial cells for their research.
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•Immortalized murine proximal S1, S2, and S3 cells have large differences in nuclear and mitochondria protein expression.•.Fibroblast proteome differs from renal epithelial cells proteomes, with major differences in glycolytic enzymes.•Changes in filter substrates, transparent versus opaque, lead to substantial changes in proteomic profiles in S2 cells.•Substrate utilization assays identify substrates with high kinetic metabolic rates by S1, S2, S3 cells and a fibroblast line.
Desde 1999, quando comecaram as pesquisas para o informe apresentado esta semana, duas mil variedades locais foram identificadas como em situacao de risco. Um exemplo da dependencia excessiva em uma ...variedade particular e a vaca leiteira Holstein-Friesian (tambem chamada Holandesa ou Frisona), branca e preta, originaria da Holanda, que agora e encontrada em 128 paises e em todas as regioes do mundo. Alem disso, 90% do gado nos paises industrializados procedem de apenas seis variedades muito especificamente definidas. Para o informe, com o qual contribuiram o Instituto Internacional de Pesquisa em Pecuaria (Ilri) e outros centros academicos, foram analisada racas de gado em 169 paises e descobriu-se que 70% das que existem em todo o mundo se encontram no Sul em desenvolvimento. Cientistas do Grupo Consultivo para a Pesquisa Agricola Internacional (CGIAR), organizacao que apoia o Ilri, exigiram a rapida criacao de bancos de esperma e ovulos de animais-chave par a sobrevivencia da populacao no futuro. "Esse e o primeiro passo", disse Sere, que fez o discurso inaugural da conferencia de Interlaken. "Nos Estados Unidos, na Europa, China e America do Sul ha bancos geneticos bem estabelecidos que preservam ativamente a diversidade pecuaria regional", afirmou Sere. "A Africa ficou na vontade, e essa ausencia e sentida muito precisamente agora, porque e uma das regioes com a diversidade mais rica e e provavel que sejam um dos principais focos de perda de racas neste seculo", acrescentou. Em todo o mundo, um bilhao de pessoas estao envolvidas na criacao de animais e para 70% dos pobres das zonas rurais o gado e chave em seu sustento. "No futuro imediato, os animais continuarao gerando meios para que centenas de milhoes de pessoas escapem da pobreza absoluta", afirmou Sere. Conservarf as variedades de gado locais no mundo em desenvolvimento e crucial tambem porque os animais nesses paises precisam adaptar-se ao meio ambiente, e nao o inverso. "Se nao ha atencao veterinaria, as racas locais podem sobreviver, mas nao as importadas", afirmou.
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