RESUMEN
Vitamin A is essential to mucosal immunity and cell differentiation. The fact that lack of it might involve chronic inflammation and increased risk of cancer has been reported. Little is known about the mechanism of vitamin A deficiency in the development of colitis and its influence on development of colorectal cancer. To determine the influence of vitamin A deficiency on colitis and colorectal cancer development, an experimental study using a colitis mouse model was performed. Dextran sulfate sodium (DSS) colitis was induced in vitamin A-deficient and vitamin A-supplemented mice. Further, colorectal carcinoma was induced by a combination of azoxymethane preinjection and DSS colitis. Results were compared between the two groups mainly by immunohistochemical analysis. Colitis was more severe and recovery from colitis was slower in vitamin A-deficient mice than in vitamin A-supplemented mice. Compared with vitamin A-supplemented mice, vitamin A-deficient mice had decreases in colonic subepithelial myofibroblasts and the ratio of mucosal IgA(+)/IgG(+) cells, increases in CD11c(+) dendritic cells, and a higher rate of development of colorectal carcinoma with colitis following azoxymethane. Vitamin A lipid droplets in subepithelial myofibroblasts were decreased in vitamin A-deficient mice, suggesting alterations in colonic crypt niche function. Thus, vitamin A inhibited colitis and the development of colorectal cancer.
Asunto(s)
Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/tratamiento farmacológico , Vitamina A/uso terapéutico , Enfermedad Aguda , Animales , Carcinogénesis/patología , Células Dendríticas/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Femenino , Homeostasis/efectos de los fármacos , Inmunohistoquímica , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Gotas Lipídicas/efectos de los fármacos , Gotas Lipídicas/metabolismo , Ratones Endogámicos BALB C , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Vitamina A/farmacologíaRESUMEN
BACKGROUND: Oncocytic L-amino acid transporter (LAT) 1 could be a target of new molecular therapy against malignancies. OBJECTIVE: To assess the correlation between overexpression of LAT1 and local progression (LP) in prostatic carcinoma (PC) patients under expectant management (EM). METHODS: This retrospective study analyzed 109 patients with PC who received EM from 1991 to 2006. The expression of LAT1, LAT2, and CD98, as well as Ki-67 labeling indices (LI), was analyzed immunohistochemically in first biopsy or TUR samples diagnosed as adenocarcinomas. RESULTS: Of the 109 patients, 44 (40%) showed LP on clinical examinations, whereas 65 showed stable disease (SD). LAT1 score and intensity were significantly higher in the LP than in the SD group, as well as among Gleason score (GS)-low (GS < 7) patients who were associated with low-risk. When the LP group was subdivided by D'Amico risk category (low-, intermediate- and high-risk groups), each showed higher LAT1 expression than the SD group. LAT1 expression did not correlate with GS or Ki-67 LI. CONCLUSIONS: Independently of GS, aberrant overexpression of LAT1 in prostatic adenocarcinoma could predict LP under EM. Although prostate biopsy samples are small, LAT1 may be a novel prognostic biomarker of LP.
Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/biosíntesis , Transportador de Aminoácidos Neutros Grandes 1/biosíntesis , Neoplasias de la Próstata/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Sistema de Transporte de Aminoácidos y+/biosíntesis , Sistema de Transporte de Aminoácidos y+/genética , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/biosíntesis , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Antígeno Ki-67/biosíntesis , Transportador de Aminoácidos Neutros Grandes 1/genética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Resección Transuretral de la PróstataRESUMEN
To effectively obtain tumour-specific markers, fractionated proteins obtained using reversed-phase high-performance liquid chromatography for patient-matched pre- and postoperative sera from bladder cancer patients were compared by two-dimensional gel electrophoresis. The usefulness of the identified proteins was confirmed immunohistochemically. S100A8 and S100A9 were identified as tumour-associated proteins. The increased immunoreactive expression of S100A8 protein was associated with bladder wall muscle invasion of the tumour and cancer-specific survival (p<0.05), and the increased immunoreactive expression of S100A9 protein was associated with the tumour grade (p<0.05). In addition, increased expressions of both proteins was associated with recurrence-free survival at a median follow-up of 32.9 months (both p<0.05). On multivariate analysis, the expression of S100A8 was a significant predictor of recurrence (p<0.05). These findings may help to identify biologically aggressive tumors and, thus, patients who might benefit from more intensive adjuvant therapy.