ABSTRACT
The incidence of pancreatic cancer is increasing year by year, but the clinical diagnosis and treatment progress is limited and the prognosis is poor. Tumor microenvironment (TME) is closely related to the invasion, metastasis and chemotherapy resistance of pancreatic cancer. Cancer-associated fibroblasts (CAFs) are fibroblasts in a state of continuous activation, which are the most prominent components in TME. CAFs can promote the malignant biological behavior of pancreatic cancer through a variety of molecule-mediated mechanisms. Moreover, several attempts targeting CAFs for the treatment of pancreatic cancer have been largely unsuccessful. It may be related to the heterogeneity of CAFs in pancreatic cancer. Therefore, in-depth study of its heterogeneity and accurate targeting of some specific phenotypes and functional CAFs subtypes in the matrix on this basis may be more promising in the clinical treatment of pancreatic cancer.
ABSTRACT
ObjectiveTo study the role and mechanism of resisitin in prophylactic and therapeutic treatments of rosiglitazone,a specific peroxisome proliferator-activated receptor-γ(PPARγ) ligand,in rats with severe acute pancreatitis (SAP) and pancreatitis-associated pulmonary injury.MethodsThe levels of amylase ( AMY ),Resistin,TNF-α,IL-1 β and C reactive protein (CRP) in blood plasma,lung myeloperoxidase ( MPO ) activity,pancreas/body weight ratio and lung wet/dry weight ratio were evaluated.Pancreatic and pulmonary pathology were observed.The expression of resistin in pancreas was detected byimmunohistochemistry.The gene expression of resistin mRNA was investigated by real-time PCR.ResultsBoth prophylactic and therapeutic treatments with rosiglitazone could obviously ameliorate the levels of AMY,resistin,TNF-αt,IL-1β and CRP ( all P ＜ 0.01 ).Compared with the control group,both prophylactic and therapeutic treatment groups were higher( all P ＜ 0.01 ).The prophylactic treatment group was not different from the therapeutic treatment group.Both prophylactic and therapeutic treatments with rosiglitazone could significantly reduce pancreas/body weight ratio,pancreatic pathology,MPO,pulmonary pathology ( all P ＜ 0.01 ).Compared with the SAP group,the expression of resistin mRNA in the prophylactic and therapeutic treatment groups were obviously decreased.ConclusionRosiglitazone could obviously ameliorate pancreatitis and pulmonary injury induced by L-arginine.
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Objective To investigate the expression of resistin in rats of acute pancreatitis and the relationship between its expression and pancreatic pathologic changes. Methods Forty Sprague-Dawlev rats were randomly divided into four groups:control group,sham operation group,AEP group and ANP group. AEP model was induced by intraperitoneal injection of cerulein and ANP model was induced bv intrapefitoneal injection of L-arginine while the control group received no treatment,and the sham operation grouD rleceived same volume injections of 0.9%saline solution.The serum amylase,C-reactive protein,TNF-alpha.IL-1 beta were determined by using ELISA,pancreas/body weight(g/kg)ratio was recorded,pancreatic pathology was examinated,the expression of resistin mRNA and protein in pancreas was detected by real-time PCR and immunohistochemistry. Results The levels of amylase,pancreas/body weight ratio.pancreatic pathology score,expression of resistin mRNA,IL-1-beta,TNF-alpha and C-reactive protein in AEP group were(4377±343)U/L,8.67 ±1.43,5.39 ±0.26,2.04 ±0.19,(10.21 ±1.34)ng/ml,(184.18±45.24)pg/ml, (194.24 ±44.81)pg/ml,(3586±63)ng/ml,respectively;and the corresponding value8 in ANP group were (6750±322)U/L.9.33±1.76,7.81±0.28,3.29±0.30,(15.14±0.84)ng/ml,(349.31±94.54)pg/ml,(315.59±37.04)pg/ml,(4345±244)ng/ml,respectively;which were significantly higher than(1442±183)U/L,4.34±0.42,1.10±0.21,0.88±0.08,(5.13±0.74)ng/ml,(108.74±31.03)pg/ml,(106.44±21.31)pg/ml,(2895±165)ng/ml in sham operation group(P<0.01 or P<0.05).Resistin wag positively correlated with the increase of C-reactive protein,TNF-alpha,IL-1 beta and the pathologic score of pancreas,respectively(r=0.711,0.812,0.794,0.812,P<0.01).Conclusions Resistin was correlated with the pathogenesis and development of acute pancreatitis,and may be useful to predict the severity of acute pancreatitis.
ABSTRACT
Objective To investigate the feasibility of induction of experimental chronic pancreatitis rat model with L-arginine.Methods Animals were randomly divided into control group,arginine 12 h group,arginine 24 h group and arginine 7 d group with 10 rats in each group.L-arginine solution was intraperitoneally injected twice with an interval of 1 h.Serum amylase and glucose levels at corresponding time points were detected and histopathological scores of pancreas were evaluated.Collagen in pancreas was stained with Van Gieson method.Results Serum amylase levels were (1 634±890 ) U/L,( 3 872±2 676 ) U/L,( 3 307±2 197)U/L and (1 561±304) U/L in control group,arginine 12 h group,arglnine 24 h group and arginine 7 d group,respectively.The serum amylase level in arginine 7 d group was significantly lower than those in arginine 12 h group and arginine 24 h group (P ＜ 0.05 ).There was no significant difference in serum glucose level among all the groups.Histopathological scores were 0.8±0.4,5.1±2.6,6.5±2.2 and 4.5±1.6,respectively.The histopathological score of arginine 7 d group was significantly lower than those in arginine 24 h group (P ＜ 0.05 ).Obvious collagen could be found in pancreatic parenchyma in arginine 7 d group,while little collagen was found in pancreatic tissue in control,arginine 12 h and arginine 24 h groups.Conclusions Injection of L-arglnine induced fibrosis in pancreatic parenchyma and proliferation of tubular complex 7 days later,and it could be used for chronic pancreatitis model induction.