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1.
Experimental & Molecular Medicine ; : 293-302, 2012.
Artículo en Inglés | WPRIM | ID: wpr-186640

RESUMEN

Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (K D) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.


Asunto(s)
Animales , Cricetinae , Humanos , Ratones , Anticuerpos Monoclonales/genética , Citotoxicidad Celular Dependiente de Anticuerpos , Conductos Biliares Intrahepáticos/efectos de los fármacos , Células CHO , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Modelos Animales de Enfermedad , Endocitosis/efectos de los fármacos , Inmunoglobulina G/genética , Neoplasias Hepáticas/tratamiento farmacológico , Ratones Desnudos , Trasplante de Neoplasias , Molécula L1 de Adhesión de Célula Nerviosa/genética , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/inmunología
2.
The Korean Journal of Hepatology ; : 97-101, 2008.
Artículo en Coreano | WPRIM | ID: wpr-160185

RESUMEN

Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.


Asunto(s)
Anciano , Humanos , Masculino , Alopurinol/efectos adversos , Antimetabolitos/efectos adversos , Enfermedades de los Conductos Biliares/inducido químicamente , Conductos Biliares Intrahepáticos/efectos de los fármacos , Colestasis/inducido químicamente , Erupciones por Medicamentos/patología , Granuloma/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Fallo Renal Crónico/complicaciones
3.
Asian Pac J Allergy Immunol ; 2002 Mar; 20(1): 57-60
Artículo en Inglés | IMSEAR | ID: sea-36539

RESUMEN

We studied the cytotoxic effects of recombinant TNF-alpha and supernate of phytohemagglutinin stimulated peripheral blood mononuclear cells individually and in combination against a cholangiocarcinoma cell line. Levels of cyclins D1, E and A in the cell line were detected by immunoblotting, and the cell cycle stage was assayed by propidium iodide staining followed by flow cytometry analysis. Viable and apoptotic cells were assessed by trypan blue dye exclusion, DAPI staining, agarose DNA laddering and propidium iodide staining. At the beginning of each experiment, the majority of cholangiocarcinoma cells expressed cyclin A and were in S phase as determined by propidium iodide staining. Treatment of such cells with recombinant TNF-alpha resulted in cytotoxic effects clearly evident at 36 hours post exposure. There was a synergistic killing effect when recombinant TNF-alpha was combined with PHA supernate and this effect could be partly neutralized by monoclonal anti TNF-alpha, interleukin (IL)-2, IL-12 and IFN-gamma.


Asunto(s)
Adulto , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Ciclina A/biosíntesis , Ciclina D1/biosíntesis , Ciclina E/biosíntesis , Citotoxicidad Inmunológica/efectos de los fármacos , Susceptibilidad a Enfermedades , Quimioterapia Combinada , Femenino , Humanos , Immunoblotting , Masculino , Fitohemaglutininas/inmunología , Proteínas Recombinantes/inmunología , Factores de Tiempo , Células Tumorales Cultivadas/efectos de los fármacos , Biomarcadores de Tumor/biosíntesis , Factor de Necrosis Tumoral alfa/inmunología
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