RESUMEN
BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/metabolismo , Proteoma/metabolismo , Anexina A5/metabolismo , Apoptosis , Proliferación Celular , Regulación hacia Abajo , Electroforesis en Gel Bidimensional , Fibroblastos/metabolismo , Genómica , Células Hep G2 , Humanos , Queratinas/metabolismo , Neoplasias de la Boca/genética , Hibridación de Ácido Nucleico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Células del Estroma/metabolismo , Vimentina/metabolismoRESUMEN
The objective of the present study was to analyze a 37-year historical series of patients who had ingested caustic substances, and who were treated in a teaching hospital, to assess the effectiveness of the therapy administered during this period. We studied 239 patients who ingested caustic soda (NaOH) from 1957 to 1994. Data were collected from the medical records of the patients and from interviews with them and analyzed by software and by statistical tests of association. The results showed that more women than men ingested caustic substances (57%, n=153). Ingestion was associated with suicidal intent in 60% of cases and was accidental in 37.2% of cases. The amount of substance ingested ranged from a trace to as much as three tablespoons, with the amount tending to be larger in the suicide attempts. Of the 215 patients for whom information about complications due to ingestion was available, 88.4% (190) presented lesions of the esophagus (73% with stenosis), 1% died during the acute phase, and 10.6% did not present complications. The data revealed that the presence and severity of stenosis were correlated with the amount of caustic substance ingested. The treatment received by the patients in the study sample varied over the years according to the prevailing literature recommendations. Based on our review, we conclude that neither the use of an antidote nor early treatment immediately after ingestion is effective. Treatment with a corticosteroid (1.5-2 mg/kg/day prednisone), an antibiotic, and a high-protein and hypercaloric diet seems to be beneficial for patients who ingest small or medium amounts of caustic soda. When 2-3 tablespoons are ingested, corticosteroids, in addition to being unable to prevent the formation of esophageal stenosis, increase the risk of other complications.
Asunto(s)
Quemaduras Químicas/terapia , Cáusticos/efectos adversos , Estenosis Esofágica/inducido químicamente , Estenosis Esofágica/terapia , Brasil/epidemiología , Quemaduras Químicas/etiología , Quemaduras Químicas/mortalidad , Terapia Combinada , Quimioterapia Combinada , Estenosis Esofágica/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
The objective of the present study was to test the viability of tracheal flaps of different widths and lenghts for tracheal reconstruction in dogs, as well as the location of their pedicles. Six types of single-pedicled tracheal flaps were prepared in 30 dogs as follows: narrow flaps with upper pedicles,wide flaps with upper pedicles, narrow flaps with lower pedicles, wide flaps with lower pedicles, narrow flaps with side pedicles, and wide flaps with side pedicles. Flap condition was determined on the basis of clinical signs and by tracheoscopic, macroscopic and microscopic examination. No statistically significally significant difference in viability was observed between narrow and wide flaps or between flaps with upper and lower pedicles, but all were less viable than side-pedicled flaps. Poor coaptation of the flap borders produced deformities of tracheal architecture, with a significant incidence of necrosis occurring in in poorly postioned flaps. The presence of poor coaptation was statistically significant in narrow flaps. Focal infection appears to influence the development of necrosis. We did not observe fibrosis or granulation tissue in sufficient amounts to cause significant stenosis of the tracheal lumen. We conclude that single-pedicled tracheal flaps are viable and can be used for tracheal reconstruction when they are prepared with a lengh-width ratio of 5 to 10
