Antibody and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and therapeutic principles.

BACKGROUND: Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis. However, the levels of immunoglobulin (Ig) and complement in patients with hypersplenism associated with cirrhotic portal hypertension remain unclear. This study was undertaken to determine the levels of Ig and complement in these patients, the relationship between these levels and Child-Pugh class and their clinical significance. AIM: To investigate the antibody (Ig) and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and their clinical significance. METHODS: Clinical data of 119 patients with hypersplenism associated with cirrhotic portal hypertension were statistically analyzed and compared with those of 128 control patients. RESULTS: IgA and IgG levels in patients with hypersplenism were significantly higher than controls (P < 0.001). There was no significant difference in IgM between the two groups (P = 0.109). C3 and C4 levels in patients with hypersplenism were significantly lower than controls (P < 0.001). As liver function decreased, IgA and IgG levels increased (P < 0.001), and C3 and C4 levels decreased (P < 0.001). CONCLUSION: Patients with hypersplenism associated with cirrhotic portal hypertension have significantly higher antibody (IgA and IgG) levels and significantly lower complement (C3 and C4) levels, which are both related to liver damage. Clinically, the administration of anti-hepatitis virus agents and protection of liver function should be strengthened.

Gemcitabine resistance induced by interaction between alternatively spliced segment of tenascin-C and annexin A2 in pancreatic cancer cells.

Pancreatic cancer is the fourth leading cause of cancer-related death in the western countries and it is resistant to almost all cytotoxic drugs. In the current study, we explored the gemcitabine resistance induced by the interaction between Annexin A2 (ANXA2) and alternatively spliced segment of tenascin-C (TNfnA-D). In the pancreatic cancer cell culture system in vitro, it was proved that exogenous recombinant TNfnA-D combined with the cell surface ANXA2 specifically and their interaction suppressed gemcitabine-induced cytotoxicity on pancreatic cancer cells in a dose-dependent manner. Meanwhile, the TNfnA-D/ANXA2 interaction increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, inhibitory kappaB (IkappaB) kinase alpha/beta (IKKalpha/beta), IkappaBalpha, and p65 nuclear factor-kappaB (NF-kappaB) significantly. Inhibition of Akt and PI3K with their specific inhibitors partially reversed the suppression of gemcitabine-induced cytotoxicity elicited by TNfnA-D/ANXA2 interaction. Activation of p65 NF-kappaB was dependent on the phosphorylation of PI3K/Akt. The phosphorylated IKKalpha/beta induced the phosphorylation and degradation of IkappaBalpha, the sequential phosphorylation, nuclear translocation and activation of p65 NF-kappaB. Pyrrolidine dithiocarbamate (PDTC) effectively blocked the activity of p65 NF-kappaB in response to TNfnA-D. Down-regulation of p65 NF-kappaB with its specific small interfering RNA (siRNA) restored the gemcitabine-induced cytotoxicity suppressed by TNfnA-D/ANXA2 interaction. For the first time, this study show that ANXA2/TNfnA-D interaction induced gemcitabine resistance via the canonical PI3K/Akt/NF-kappaB signaling pathways in pancreatic cancer cells. Therefore, therapy targeting ANXA2/TNfnA-D and/or p65 NF-kappaB may have potential clinical application for patients with pancreatic cancers.