Novel syngeneic liver hapten protein compounds play different roles in pathogenesis of autoimmune hepatitis in the C57BL/6 mouse.

BACKGROUND/AIMS: The autoimmune hepatitis (AIH) model in C57BL/6 mice with syngeneic hapten S100 and adjuvant injected intraperitoneally has been designed to elucidate the pathogenesis of AIH. Three separate hapten peak proteins, peak I, peak II and peak III, could be derived from S100, but little is understood their roles on the development of AIH. This study aims to learn more about these roles on pathogenesis of AIH. METHODOLOGY: Novel AIH C57BL/6 mouse models were developed by weekly immunization by intraperitoneal injection with syngeneic S100 liver proteins and the three separated hapten peak proteins emulsified covalently in complete Freund's adjuvant (CFA) for 4 weeks and sacrificed for liver histopathological study. Additionally, TNF-α and INF-γ in culture supernatants of spleen lymphocytes of healthy C57BL/6 mice cultured together with S100 plus CFA for 48 hours were detected, and the T-lymphocytes proliferative response after stimulation with crude S100, peak I, II or III proteins were also assessed. RESULTS: Data showed that hepatitis induced by CFA+S100 was accompanied with more severe inflammation characterized by diffusely distributed liver necrosis and enhanced lymphocyte infiltration in portal tracts, while hepatitis induced by peak I+CFA was characterized by mass lymphocyte infiltration, occasional isolated liver necrosis and many acidophilic bodies, which was more similar to autoimmune hepatitis; hepatitis induced by peak II+CFA was characterized by massive liver necrosis and mild lymphocyte infiltration; hepatitis induced by peak III+CFA was characterized by mild inflammation with isolated acidophilic bodies or dotted hepatocellular necrosis. TNF-α, INF-γ from culture supernatants were increased, and T-lymphocyte proliferative response stimulated with peak I protein significantly increased compared with those stimulated with crude S100, peak II or III proteins. CONCLUSIONS: Syngenic S100 liver protein and its three separated hapten proteins have different roles in the pathogenesis of AIH, and peak I protein may be important in its development.

Clinicopathological significance of expression and amplification of P21-activated kinase 1 gene in colorectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological value of the expression and amplification of P21-activated kinase 1 gene (PAK1) in colorectal carcinoma(CRC).</p><p><b>METHODS</b>Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) methods were used to examine the protein expression, amplification of PAK1 and cell apoptosis in 80 cases of CRC and 30 cases of colorectal adenoma by tissue microarray.</p><p><b>RESULTS</b>IHC showed an overexpression of PAK1 protein in 26% of colorectal adenomas and 62% of CRCs. Significant association was found between expression of PAK1 and tumor histological grade as well as tumor clinical stage(P<0.05). In poor-differentiated(G(3)) CRCs, PAK1 expression in 90% carcinoma was up-regulated, which was significantly higher than that in tumors of G(1/2)(51%). Overexpression of PAK1 was detected in 78% of CRCs in later clinical stages (Dukes C, D), which was significantly higher than that in early clinical stages (Dukes A,B, 53%). In addition, negative correlation between PAK1 overexpression and cell apoptosis was observed in these CRC cohorts(P<0.05). FISH revealed that amplification of PAK1 gene was examined in only 3% CRCs.</p><p><b>CONCLUSIONS</b>Overexpression of PAK1 protein may play an important role in development and progression of colorectal neoplasms and it is closely associated with the malignant histological and invasive phenotype of CRCs. The expression of PAK1 in CRC may be used as one of the new molecular markers in predicting tumors malignant potential and progression.</p>