Study of efficacy and toxicity profile of gemcitabine and erlotinib based chemotherapy regimen in locally advanced (inoperable) and metastatic (LA/M) carcinoma pancreas

Abstract

Objective: This study investigated the different outcomes between alcohol-based and hypertriglyceridemia-based acute pancreatitis and then tried to find out the key factors that would aggravate the pathophysiological course of the disease. Methods: Feeding rats with alcohol or high-fat diet for 4 weeks, we induced acute pancreatitis models under the etiology-based conditions. Results: We found alcohol abuse caused firm fibrosis thus aggravated the lobule hypoxia and caused hypoxia inducible factor-1a activation of acinar cells. Moreover, alcohol led to intracellular lipid droplet accumulation and mitochondrial stress under acute pancreatitis while high-fat diet only caused slight endoplasmic reticulum stress. Alcohol also caused higher level of nuclear factor-kappaB DNA-binding activity and activation than HTG thus aggravated the inflammatory reaction. The alcohol or highfat diet pretreatment did not influence the amylase, interleukin-6, tumor necrosis factor-a production and secretion, however, alcohol pretreatment increased the serum macrophage inflammatory protein 1a and monocyte chemotactic protein 1 comparing with control group. Alcohol induced more extensive oxidative stress than HTG which was shown by the level of serum myeloperoxidase and lipid peri-oxidant. Conclusions: In conclusion, we speculated that alcohol aggravated the acute pancreatitis and led to more severe disease than HTG by the fact that alcohol caused firm fibrosis along the interlobular area and more severe intracellular stress, and all these contributed to the higher level of hypoxia inducible factor and nuclear factor kappaB than HTG. The activated hypoxia inducible factor and nuclear factor kappaB caused the more severe