1.Role of heterogeneity of cancer-associated fibroblasts in targeted therapy of pancreatic cancer
Zhiying YAN ; Yifeng MAO ; Yingwei ZHU ; Kequn XU
Journal of International Oncology 2021;48(5):308-312
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.
2.Feasibility study of induction of experimental chronic pancreatitis with L-arginine
Xiaohua MAN ; Hang ZHAO ; Kequn XU ; Yanfang GONG ; Jun GAO ; Yiqi DU ; Aifang XU ; Zhaoshen LI
Chinese Journal of Pancreatology 2009;9(2):109-111
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.
3.Expression of resistin in rats of acute pancreatitis
Kequn XU ; Yunzhi SHEN ; Yanfan GONG ; Xiaohua MAN ; Hongyu WU ; Jin JIN
Chinese Journal of Pancreatology 2009;9(6):402-405
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.
4.The role of resisitin in the prophylactic and therapeutic treatments of rosiglitazone in rats with severe acute pancreatitis
Lening XUE ; Yong TAN ; Ming LIN ; Yanfang GONG ; Hongyu WU ; Jing JIN ; Kequn XU
Chinese Journal of Primary Medicine and Pharmacy 2012;19(1):7-9
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.
5.Analysis on influence of meteorological factors on Oncomelania density
Kequn LIU ; Xingjian XU ; Yuxia CHEN ; Rendong LI ; Yang TANG ; Fenghua WEI
Chinese Journal of Epidemiology 2015;36(11):1274-1278
Objective To understand the influence of meteorological factors on Oncomelania density in natural condition and provide scientific evidence for the control of the spread of schistosomiasis and Oncomelania.Methods Based on the Oncomelania survey data in spring and ground meteorological observation data of Qianjiang from 1990 to 2014, the first-order autoregressive analysis method was used for trend fitting and disassemble, and the correlation between the change rate of Oncomelania density and various meteorological factors in different periods were analyzed.Results The greatest influence of meteorological factors on Oncomelania density was temperature,followed by precipitation.The average minimum temperature in January and from December to February had predominant influence on Oncomelania density and frame occurrence rate of living Oncomelania (FORLO) respectively.The rise (fall) of average minimum temperature in January by 1 ℃ would lead to the increase (decrease) of Oncomelania density by 5.080%-6.710%;The rise (fall) of average minimum temperature from December to February by 1 ℃ would lead to the increase (decrease) of FORLO by 15.521%-15.928%.The period with the biggest influence of precipitation on Oncomelania density was from November to April, as the rainfall declined >20%, drought might occur, which would cause the reduction of Oncomelania density.Sunshine from September to November had some correlations with the change of Oncomelania density and FORLO.Statistical regression models for the change of Oncomelania density, FORLO and meteorological factors based on correlation analysis were established respectively.Conclusion Weed removal in Oncomelania areas before December is beneficial to reduce the surface temperature and soil moisture content, which would result in Oncomelania density reduction in some extent.It' s notable that the winter temperature is in rise in Hubei province along with global climate change, causing the Oncomelania density to increase, to which more attention should be paid.
6.Diagnostic value of combined detection of multiple serum cytokines for gastric adenocarcinoma
QI Yufeng ; XU Kequn ; ZHU Yingwei ; SUN Junning ; SU Wen
Chinese Journal of Cancer Biotherapy 2020;27(4):410-415
[Abstract] Objective:To explore the clinical significance of multiple serumcytokines in early diagnosis and progression assessment of gastric adenocarcinoma. Methods: Peripheral blood samples of 85 healthy subjects (healthy control group) and 81 patients with pathologically confirmed gastric adenocarcinoma (gastric cancer group) were collected from November 2017 to February 2018 at Shanxi Cancer Hospital. Serum levels of 17 cytokines (including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-15, IL-17A, TNF-α, TNF-β, GM-CSF, G-CSF, IFN-γ, IP-10, MCP-1 andVEGF-A) were measured byAimPlex multiplex assay technology.Their diagnostic values were analyzed by receiver operating characteristic (ROC) curve. Results: Serum levels of IL-10, IL-8, IL-6, IP-10, MCP-1, VEGF-Aand IL-12p70 were significantly higher in gastric cancer patients than those in healthy controls (all P<0.01). There were significantly increasedlevelsofIL-8,IL-6and VEGF-Ain advanced-stage gastriccancer(stageI/II)groupoverearly-stage gastric cancer (stage III/IV) group (all P<0.01).AUC (areas under the curve) of IL-8, IL-6, IL-10, IP-10, MCP-1, IL-12p70 and VEGF-Afor distinguishing early-stage gastric cancer patientsfromhealthy controls was0.98,0.92,0.89,0.84,0.76,0.74 and 0.58, respectively. The diagnostic sensitivity of IL-8, IL-6 and IL-10 was 97.4%, 89.5% and 97.4%, respectively, and the specificity was 87.1%, 85.9%and 77.6%, respectively.TheAUCof IL-8, IL-6 andVEGF-Afor distinguishing advanced-stage gastric cancer patients from early-stage gastric cancer patients was 0.82, 0.72 and 0.69, respectively. Thediagnosticsensitivity of IL-8, IL-6 and VEGF-A was 83.7%, 60.5% and 41.9%, respectively, and the specificity was71.1%,76.3%and 92.1%, respectively. Conclusion: ThecombineddetectionofserumIL-8,IL-6andIL-10 may be a potential approach for early screening of gastric adenocarcinoma, which canalsobeusedtoassessthe progression of gastric adenocarcinoma.