1.Effects of MMI-166 on apoptosis and apoptosis-related protein expression in human pancreatic cancer SW1990 cells
Chongchong GAO ; Bengang GONG ; Xiuliang XIA ; Dekun SONG ; Huaiyong XU
Chinese Journal of Pancreatology 2013;(1):24-27
Objective To investigate the effects of MMI-166 on apoptosis and apoptosis-related protein expression of human pancreatic cancer SW1990 cells and its transplanted tumor,and explore possible mechanism.Methods The human pancreatic cancer xenograft model was constructed by using human pancreatic cancer SW1990 cells.Tumor-bearing nude mice were randomly divided into control and MMI-166 groups,and they were treated with normal saline or MMI-166 (200 mg · kg-1 · d-1) for 28 days.Apoptosis index (AI),p53,c-Myc,Bax,Bcl-2,Survivin,Caspase-1,Fas proteins were detected by deoxynucl-eotidyl transferase-mediated nick end labeling (TUNEL method) and Western blot.MMI-166 of different concentrations (0,50,100 μg/ml) were used to treat human pancreatic cancer SW1990 cell for 24 h.The c-Myc,Survivin proteins expressions were measured by Western blotting.Results Apoptosis index in MMI-166 group was 81.1 ±7.9,which was significantly higher than that in control group (21.3 ±2.2,P =0.000) ; the expressions of c-Myc,Survivin were 7715 ± 2229,4594 ± 1240,which were significantly higher than those in control group (16870 ± 2446,15208 ± 1903,P =0.000) ; the expressions of p53,Bax,Bcl-2,Caspase-1,Fas were not significantly different from those in control group.After 50,100 μg/ml MMI-166 treatment,the expression of c-Myc was significantly down-regulated (0.098 ± 0.003,0.073 ± 0.008 vs.0.169 ± 0.007,F =189.361,P < 0.05) ; and the expression of Survivin was not significantly changed.Conclusions MMI-166 may induce cell apoptosis of SW1990 by down-regulating the expression of c-Myc.
2.Mechamism of PAUF in pancreatic cancer pathogenesis and progression
Chongchong GAO ; Diangang LIU ; Feng CAO ; Fei LI
Chinese Journal of Hepatobiliary Surgery 2014;20(4):317-320
Pancreatic adenocarcinoma up-regulated factor(PAUF),a newly discovered gene,is highly expressed in pancreatic cancer.PAUF promotes the metastasis and progression of pancreatic cancer through many ways,such as the activation of signal pathway (CXCR4,β-catenin,TPL2/MEK/ERK,FAK/Scr),increasing the adhesiveness of pancreatic cancer cells,promoting angiogenesis and vascular permeability.Simultaneously,CXCR4,β-catenin,TPL2/MEK/ERK and FAK/Scr are closely related with gemcitabine-resistance.Based on this theory,we infer that PAUF plays a role in gemcitabine-resistance of pancreatic cancer cells.So far,no related research has been done domestic and overseas.The research may find a clue for the mechanism of chemotherapy-resistance and provide a new target spot for the therapy of pancreatic cancer.
3.Effects of MMI-166 on proliferation and apoptosis in human pancreatic cancer SW1990 cell
Bengang GONG ; Huaiyong XU ; Piguang CHENG ; Chongchong GAO ; Junben WU
Chinese Journal of Pancreatology 2012;12(2):100-102
ObjectiveTo investigate the effects of MMI-166 on the proliferation and apoptosis of human pancreatic cancer SW1990 cells.MethodsMMI-166 of different concentrations (25,50,100 μg/ml) were used to treat human pancreatic cancer SW1990 cell for 24,48 h.Effect of MMI-166 on cell proliferation wasdetected by 3- (4,5-dimethyl-2-thiazole) -2-5-biphenly-tetrazole bromide ( MTT ) method and effect on cell apoptosis was tested by Annexin V-PI method and flow cytometry (FCM).ResultsTwenty-four hours after MMI-166 treatment of different concentrations (25,50,100 μg/ml),the inhibitory rates of the cells were (34.23±3.87)%,(44.81 ±2.01)%,(53.91 ±1.74)%,and the corresponding values were (39.95 ± 1.83) %,( 52.26 ± 3.46 ) %,( 63.20 ± 2.48 ) % at 48 h,which suggested a time-and concentrationdependent manner.The cell's apoptosis rates were (11.19 ±0.47)%,(23.01 ±0.53)%,(28.10 ± 0.52) % at 24 h,and the corresponding values were ( 11.19 ± 0.47 ) %,( 23.01 ± 0.53 ) %,( 28.10 ± 0.52)% at 48 h,which were significantly higher than those in control group [ (0.09 ±0.12)%,P <0.05].ConclusionsMMI-166 can inhibit proliferation and induce apoptosis of human pancreatic SW1990 cell in a time- and concentration-dependent manner.
4.Effects of a new matrix metalloproteinase inhibitor, MMI-166, in nude mouse xenografts of human pancreatic cancer
Huaiyong XU ; Bengang GONG ; Chongchong GAO ; Mengyu LI ; Junben WU ; Tinghai XIANG ; Piguang CHENG
Chinese Journal of Hepatobiliary Surgery 2012;(11):859-862
Objective To investigate of the MMI-166 on the expression of MMP-2,MMP-9 and the cell apoptosis of nude mouse xenografts of SW1990 human pancreatic cancer cells.Methods Establishment of control and experimental groups,randomly,the human pancreatic cancer xenograft model of SW1990 was constructed.The control group was treated with normal saline,and experimental group was treated with MML-166 (200 mg · kg-1 · d-1).The tumor volume and tumor inhibition rate was measured by vernier caliper through length and short diameter.The expression of MMP-2 and MMP-9 protein was observed using immunohistochemistry in the tumor tissues.Apoptosis index was detected by deoxynucleotidyl transferase-mediated nick end labeling (TUNEL method).Results The tumor volume of MMI-166 group (1252.30± 464.84) mm3 was less than the control group (2241.82±208.06) mm3,significantly.The inhibition rate was 34.47% between the experimental groups (treat with MMI-166) (1.42±0.15) g and control group (2.17±0.20) g.The expression of MMP-2 (2.80 ± 1.10) % and MMP-9 (2.60 ± 1.52) % protein was significantly downregulated in MMI-166 group,compared with the control group.Apoptotic index in the experimental group (75.60±9.71) % was higher than the control group (17.40 ± 10.14) %,significantly.Conclusion The mechanism of MMI-166 inhibiting pancreatic tumor growth and inducing apoptosis may be related to the suppression of MMP-2 and MMP-9 protein expression.
5.Imaging Features Multi-slice Spiral CT and PET/CT in Lymphoma with Pulmonary Lesions as the Initial Presentation
Xiaomei WANG ; Jinghong WANG ; Chongchong WU ; Shaohong ZHAO ; Jie GAO ; Zhiwei GUAN
Chinese Journal of Medical Imaging 2015;(9):677-681
PurposeTo discuss the imaging features of multi-slice spiral CT (MSCT) and PET/CT in lymphoma with pulmonary lesions as the initial presentation.Materials and Methods Eighteen cases of lymphoma with pulmonary lesions as initial presentation confirmed by operation and pathology were retrospectively analyzed including Hodgkin lymphoma (HL) in 3 cases and non-Hodgkin lymphoma (NHL) in 15 cases. All 18 patients underwent MSCT, of which 11 also underwent PET/CT. The MSCT manifestations included number of lesions, morphology, density and bronchial change. PET/CT evaluated lesions in other body parts and SUVmax of lung lesions.Results MSCT showed single lung lesion in 6 cases, multiple lung lesions in 12 cases. Masses were seen in 9 cases, non-masses in 7 cases, and mixed type in 2 cases. There was single consolidation in 3 cases and mixed consolidation in 15 cases. Air bronchogram was identified in 15 cases. CT predictive diagnosis was lymphoma in 3 cases, lung cancer in 5 cases, pneumonia in 7 cases, granuloma in 1 patient, and indeterminate in 2 cases. PET/CT showed hypermetabolic lung lesions in 11 patients, mediastinal lymph node in 3 cases, and unilateral supraclavicular lymphadenopathy in 1 case. One patient showed pancreatic tail masses, gastric wall thickening and haunch masses. All 11 patients were diagnosed as malignant tumor, of which 8 cases as lymphoma.Conclusion MSCT manifestations of lymphoma with pulmonary lesions as initial presentation include multiple lesions, polymorphic type and heterogeneity with air bronchogram. PET/CT has better accuracy than MSCT.
6.Multi-slice Spiral CT Features of Lung Primary Invasive Mucinous Adenocarcinoma
Xiaomei WANG ; Jinghong WANG ; Chongchong WU ; Yongkang NIE ; Shaohong ZHAO ; Jie GAO
Chinese Journal of Medical Imaging 2015;(9):691-694
PurposeTo investigate the multi-slice spiral CT features of lung primary invasive mucinous adenocarcinoma, a rare malignancy with few relevant literature. Materials and Methods Forty-one patients with pathology proven primary invasive mucinous adenocarcinoma of the lungs underwent MSCT examination, of which 27 patients received intravenous contrast. Imaging features were analyzed, and the patients were divided into groups according to morphology, density and enhancement.Results For 41 patients, 40 cases had one lesion, and one case had more than one lesion; the lesions were in the right upper lobe in 5 cases, right middle lobe in one case, right lower lobe in 17 cases, left upper lobe in 5 cases, and left lower lobe in 12 cases. There was solitary lesion in 40 cases. The other patient had multiple lesions. 29 cases showed nodules/masses, while non-mass lesions in 12 cases. Ground glass opacity was seen in 4 cases, single consolidation in 11 cases, and mixed consolidation in 26 cases. There was significant contrast enhancement in nodules/masses compared to non-mass lesions (t=5.00, 6.51 and 14.06,P<0.05).Conclusion MSCT shows a diversity of imaging features of primary invasive mucinous adenocarcinom, including single round lesion, lower lobe in both side; the density is lower than muscle on CT scan, and presents mild to moderate enhancement on enhancement scan round lesions has high density and enhancement range than irregular-shaped lesions.
7.Laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis
Chongchong GAO ; Fei LI ; Feng CAO ; Xiaohui WANG ; Ang LI ; Zhe WANG ; Chao ZHANG ; Zhe JIANG
Chinese Journal of Hepatobiliary Surgery 2021;27(5):354-357
Objective:To study the clinical application of laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis (CIPN).Methods:The clinical data of 34 patients with CIPN who were treated at the Department of General Surgery, Xuanwu Hospital, Capital Medical University from August 2017 to December 2019 were retrospectively studied. Based on the different video methods used, these patients were divided into 3 groups: the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group. The number of operations, operation time, blood loss, postoperative complication rates, mortality rates and total length of hospital stay were compared.Results:There were 13 patients in the laparoscopic combined with intraoperative ultrasound group, with age of (56.4±13.4) years. There were 7 patients in the laparoscopic combined with choledochoscopy group, with age of (48.0±8.4) years. There were 14 patients in the laparoscopic group with age of (51.4±15.6) years. The number of operations of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (2.2±1.1), (1.6±0.8), (2.9±1.4), respectively. The number of operations of the laparoscopic combined with choledochoscopy group were significantly less than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). The operation time of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (70.5±22.9) min, (65.7±19.9) min, (51.5±15.4) min, respectively. The operation time of the laparoscopic combined with intraoperative ultrasound group was significantly longer than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). There were no differences in blood loss, postoperative complication rate, mortality rates and total lengths of hospital stay among the three groups ( P>0.05). Conclusion:Laparoscopic combined with multi-video debridement after making full use of the advantages of each of the video methods, can be used to improve treatment outcomes of patients with CIPN.
8. Re-exploration of minimally invasive surgery for infected pancreatic necrosis
Chinese Journal of Surgery 2019;57(10):730-732
The application of minimally invasive technique in infected pancreatic necrosis has been matured gradually but has controversy and challenges in the same time. This paper further discusses the advantages, timing, combination of multi-video-assisted debridement and post-operative management of minimally invasive surgery. The greatest advantage of minimally invasive surgery lies in "No intervention for normal abdominal space" which not only can reduce unnecessary injury and complication but also promote intestinal function recovery after operation. The principle of delayed operation is controversial. Early PCD and "one-step" minimally invasive laparoscopic debridement and drainage have both achieved good results. The combination of multi-video-assisted minimally invasive technique can make up for the shortage of single technique to shorten the operation time and improve the debridement efficiency of patients with complicated infected pancreatic necrosis and provide new ideas for video-assisted debridement. Fully debridement and drainage are the key points and standardization for post-operative management. It′s a difficult problem and an important research direction to apply minimally invasive technique for patients with infected pancreatic necrosis reasonably and scientifically.
9.Silencing pancreatic adenocarcinoma up-regulated factor increases the sensitivity of pancreatic cancer cell line to gemcitabine
Chongchong GAO ; Xiaolan XU ; Fei LI ; Shuang LIU ; Yeqing CUI ; Haichen SUN ; Yuduo WU
Chinese Journal of Hepatobiliary Surgery 2017;23(1):44-47
Objective To observe the influence on the sensitivity of pancreatic cancer cell line BxPC-3 to gemcitabine of silencing PAUF gene.Methods BxPC-3 cells,which overexpress PAUF,was stably transfected with PAUF-shCtrl and PAUF-shRNA to establish BxPC-3_shCtrl and BxPC-3_shPAUF cells as control and experiment group.Then the mRNA and protein expression level of PAUF in these two cell lines were detected by RT-PCR and western blot,respectively.The growth inhibition rates of these two cell lines treated with different concentrations of gemcitabine (0,3.1,6.25,12.5,25,50,100,200 nmol/L) were detected by MTT.Apoptosis rates in the cells treated with different concentrations of gemcitabine (0,75,100 nmol/L) were then observed by flow cytometry.Results The relative PAUF mRNA expression level in BxPC-3_shCtrl and BxPC-3 cells were 1.00 ± 0.06 and 0.83 ± 0.07,which were significantly high er than that in BxPC-3_shPAUF cells (0.25 ± 0.02;both P < 0.05).The relative PAUF protein expression level in BxPC-3_shCtrl and BxPC-3 cells were 0.89 ± 0.07 and 0.95 ± 0.04,which were significantly high er than that in BxPC-3_shPAUF cells (0.31 ± 0.03;both P < 0.05).The IC50 value of gemcitabine to BxPC-3_shCtrl cell was (22.88 ± 2.43) nmol/L,which was significantly higher than that of BxPC-3_shPAUF cells [(1.06 ± 0.02) nmol/L;P < 0.05];apoptosis rate of BxPC-3_shPAUF cells treated by gemcitabine increased faster than that of BxPC-3_shCtrl cells.Conclusion PAUF silencing could greatly enhance the sensitivity of BxPC-3 cells to gemcitabine.
10.Abnormal air bronchogram within pure ground glass opacity lung adenocarcinoma: value for predicting histopathologic subtypes
Yueqing YANG ; Jie GAO ; Mei JIN ; Chuncai LUO ; Chongchong WU ; Shaohong ZHAO
Chinese Journal of Radiology 2017;51(7):489-492
Objective To analyze the value of abnormal air bronchogram for predicting the invasiveness of lung adenocarcinoma with pure ground-glass nodule (pGGN).Methods From April 2014 to February 2016,157 patients with 165 pGGN lung adenocarcinomas confirmed by surgical pathology were selected.There were 30 pre-invasive lesions (AAH+AIS),39 minimally invasive adenocarcinoma (MIA),and 96 invasive adenocarcinoma (IAC).CT characteristics including lesion size,density,abnormal air bronchogram were recorded.All lesions were divided into two groups:normal group (no air bronchogram or normal air bronchogram) and abnormal air bronchogram group.Chi-square test was used to analyze the difference of pathological subtypes between the two groups.Mann-Whitney rank test was used to analyze the size difference of pGGN between the two groups.Two-independent samples t-test was used to analyze the lesion density difference of pGGN between the two groups.Results Of the 165 lesions,85 were found to have air bronchogram,there were 12 lesions in 30 pre-invasive lesions (AAH+AIS),17 in 39 MIAs,56 in 96 IACs.Abnormal air bronchogram were demonstrated in 61 lesions which was 1 in 30 pre-invasive lesions (IACs+AIS),13 in 39 MIAs and 47 in 96 IACs,significant differences were found between two groups (x2=25.943,P<0.01).The mean size of the IACs were (10.8±4.2) mm for normal group,(17.0±6.7) mm for abnormal air bronchogram group,the mean density were (-519± 118) HU and (-518± 124) HU,respectively.There was a significant difference in lesion diameter between two groups (Z=-6.197,P<0.01),but not in density (t=-0.042,P=-0.966).Conclusions Abnormal air bronchogram can be used to predict the invasiveness of pGGN lung adenocarcinoma,and is correlated with lesion size,but not with density.