1.In vivo study on IL-37 inhibition of malignant melanoma metastasis.
Jiantang YANG ; Lili FU ; Yanmiao YANG ; Lin LIN
Journal of Central South University(Medical Sciences) 2024;49(12):1885-1890
OBJECTIVES:
Malignant melanoma is highly aggressive, prone to early metastasis, and associated with extremely poor prognosis, posing a serious threat to human health. Identifying molecular mechanisms that inhibit metastasis is of great significance for improving treatment and prognosis. Interleukin-37 (IL-37), an anti-inflammatory cytokine, has not only been linked to various inflammatory diseases but also exhibits anti-tumor properties. This study aims to explore the effect of IL-37 on melanoma metastasis in vivo by establishing a murine model of pulmonary metastasis.
METHODS:
Mouse melanoma B16F1 cells were transfected with either IL-37 overexpression plasmid (IL-37 oe) or empty vector. Three groups were set: An IL-37 oe group (transfection reagent+IL-37 oe plasmid), a Vector group (transfection reagent+vector plasmid), and a Blank group (transfection reagent only). C57 mice were randomly divided into 3 groups (n=3 per group) and injected intravenously with logarithmic-phase B16F1 cells under sterile conditions. Mice were weighed every 3 days. After 1 month, mice were euthanized by cervical dislocation, and organs including lungs, heart, liver, spleen, and kidneys were harvested. Lung metastases were photographed and counted. Organs were fixed in 4% paraformaldehyde, embedded in paraffin, and stained with hematoxylin and eosin (HE).
RESULTS:
Western blotting confirmed successful plasmid transfection. There were no significant differences in body weight among the 3 groups over the 28-day period (P>0.05). Lung tumors were observed upon dissection, indicating successful metastasis modeling. HE staining showed no morphological differences in the heart, liver, spleen, and kidneys between groups. The numbers of lung metastases in the Blank, Vector, and IL-37 oe groups were (24.00±2.08), (24.67±0.88), and (5.33±1.45), respectively. The IL-37 oe group had significantly fewer lung metastases than the other 2 groups (P<0.05), while no difference was observed between the Blank and Vector groups.
CONCLUSIONS
IL-37 significantly inhibits lung metastasis of malignant melanoma cells in mice without affecting body weight or major organs. It may serve as a potential molecular target for gene therapy or immunotherapy of malignant melanoma.
Animals
;
Mice
;
Interleukin-1/genetics*
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Lung Neoplasms/secondary*
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Melanoma, Experimental/pathology*
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Mice, Inbred C57BL
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Cell Line, Tumor
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Transfection
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Melanoma/pathology*
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Female
;
Male
2.Prospective study on the effect of prophylactic octreotide administration in preventing pancreatic fistula after pancreatoduodenectomy
Yu XU ; Xueliang FU ; Dejun LIU ; Yanmiao HUO ; Wei LIU ; Junfeng ZHANG ; Yongwei SUN ; Jianyu YANG ; Rong HUA
Chinese Journal of Pancreatology 2022;22(1):32-38
Objective:To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy (PD)associated postoperative pancreatic fistula (POPF), total complications, peri-operative death and postoperative in-hospital days.Methods:From January 2020 to August 2021, 148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial. Patients were randomly assigned into octreotide group ( n=74) and control group ( n=74). Octreotide group was subcutaneously injected with 0.1 mg (1 ml) octreotide after preoperative anesthesia, and was subcutaneously injected with the same dose every 8 hours for 5 days, with a total of 16 doses. Control group was injected with 1 ml normal saline in the same way, and relevant clinical data and indicators of the two groups were recorded. The primary endpoint was clinically relevant pancreatic fistula, and the secondary endpoints were total complications, perioperative death and postoperative in-hospital days. Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD. Results:120 patients were finally enrolled, including 61 in octreotide group and 59 in control group. There were no significant differences on age, gender ratio, body mass index, preoperative surgery rate of jaundice reduction, preoperative major biochemical indicators, operation time, intraoperative blood loss, pancreatic duct diameter, pancreatic texture and pathological type composition ratio. The total incidence of clinical relevant POPF was 8.3%, and there were no significant differences on biochemical leakage (4.9% vs 8.5%, P=0.435), grade B fistula (4.9% vs 8.5%, P=0.435) and grade C fistula (1.6% vs 1.7%, P=0.981). The total complication incidence (24.5% vs 28.8%, P=0.601), perioperative mortality (0 vs 3.3%, P=0.147) and postoperative in-hospital days (20.6±11.1 d vs 19.5±12.2 d, P=0.633) were not significantly different between two groups. Univariate analysis showed that preoperative serum albumin level <30 g/L( P<0.001) and pathological type of pancreatic ductal adenocarcinoma ( P=0.036) were independent risk factors for POPF after PD, while multivariate analysis found no statistically significant risk factors. Conclusions:Octreotide can neither reduce the incidences of POPF, total complications and postoperative mortality, nor shorten postoperative in-hospital days. However, for patients with preoperative hypoproteinemia and (or) the pathological type of pancreatic duct adenocarcinoma, the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.
3.Kinetic metrics of 68Ga-FAPI-04 in patients with pancreatic cancer identified by total-body PET/CT dynamic imaging
Ruohua CHEN ; Xinlan YANG ; Yanmiao HUO ; Yining WANG ; Xiaofeng YU ; Ling Yee NG ; Chaojie ZHENG ; Haitao ZHAO ; Lianghua LI ; Yun ZHOU ; Gang HUANG ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(12):729-733
Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.
4.Comparison of anti-reflux mucosectomy and endoscopic cardial constriction ligation on treatment of gastroesophageal reflux disease
Dezhi HE ; Yanyan ZHENG ; Xiaotong WANG ; Bingrong LIU ; Jiansheng LI ; Yanmiao HAN ; Haili XU ; Yang CHEN ; Lijuan SONG ; Laifu YUE
Chinese Journal of Digestive Endoscopy 2020;37(8):553-557
Objective:To compare the clinical efficacy of anti-reflux mucosectomy (ARMS) and endoscopic cardial constriction ligation (ECCL) on treatment of gastroesophageal reflux disease.Methods:A retrospective study was conducted on the data of 48 consecutive patients with gastroesophageal reflux disease, who underwent ARMS or ECCL at the First Affiliated Hospital of Zhengzhou University from December 2015 to August 2018. Twenty cases were in the ARMS group and 28 cases in the ECCL group. The short-term and long-term efficacies were compared between the two groups.Results:The success rate of operation was 100.0% in the both groups. The operation time of the ECCL group was significantly shorter than that of the ARMS group (8.43±1.59 min VS 34.05±12.35 min, t=-9.227, P<0.001). After 2 months follow-up, the symptom improvement rate of the ECCL group and the ARMS group was 89.3% (25/28) and 60.0% (12/20), respectively ( χ2=4.128, P=0.042). The GERD Q score of the ECCL group was significantly lower than that of the ARMS group (6.24 ±1.22 VS 7.35±1.79, t=-2.400, P=0.023). One year after operation, there were no significant differences in the symptom improvement rate, GERD Q score, DeMeester score and the time percentage of pH<4 between the two groups ( P>0.05). Conclusion:The long-term clinical effect of ARMS and ECCL is similar, but the short-term clinical effect of ECCL is superior to ARMS.
5.Prognostic factors of survival for patients with duodenal papilla carcinoma after pancreaticoduodenectomy
Xueliang FU ; Jianyu YANG ; Dejun LIU ; Yanmiao HUO ; Wei LIU ; Junfeng ZHANG ; Rong HUA ; Yongwei SUN
Chinese Journal of General Surgery 2019;34(12):1021-1025
Objective To investigate the prognostic factors of survival for patients with duodenal papilla carcinoma (DPC) after pancreaticoduodenectomy.Methods 98 DPC patients undergoing pancreaticoduodenectomy with follow-up from Jan 2010 to Dec 2017 at Renji Hospital,School of Medicine,Shanghai Jiao Tong University were analyzed retrospectively.Results 80 Cases were followed up.The 1,3,and 5 year survival rates of 80 patients were 89.9%,72.4%,and 66.6%,respectively.Univariate analysis showed tumor size,T stage,N stage,TNM stage,tissue differentiation degree were related to postoperative survival(all P <0.05).Multivariate analysis showed that tumor size,N stage,TNM stage,and tissue differentiation degree were independent factors influencing postoperative prognosis(all P < 0.05).Conclusions Tumor size,N stage,TNM stage and tumor tissue differentiation degree were independent factors influencing the prognosis of DPC after pancreaticoduodenectomy,suggesting that early diagnosis,early treatment and radical resection were the key to improve the postoperative prognosis of DPC.
6.Endovascular intervention for late postpancreaticoduodenectomy hemorrhage
Yanmiao HUO ; Jiachang CHI ; Jianyu YANG ; Wei LIU ; Junfeng ZHANG ; Yongwei SUN ; Rong HUA
Chinese Journal of General Surgery 2019;34(3):208-212
Objective To evaluate the safety,efficacy of interventional treatment for late postpancreaticoduodenectomy hemorrhage (LPPH).Methods From Jan 2008 to Dec 2017,678 patients underwent pancreaticoduodenectomy (PD).33 patients (4.9%) suffered from LPPH.30 of these 33 patients underwent diagnostic angiography and endovascular treatment,either transcatheter arterial embolization (TAE,n =21) or covered stent placement (CSP,n =9),and the other 3 underwent laparotomy.Results The incidence of LPPH is 4.9% with a 12% motality.The most common presentation is bleeding from abdominal drainage (24.2%) and melena (24.2%).The incidence of sentinel bleeding (SB) is 45.5% and postoperative pancreatic fistula (POPF) is 69.7%.Intra-abdominal infection were identified in 24 patients (72.7%) and the most common pathogenic bacteria is pseudomonas aeruginosa (11/24,45.8%).The mean time between PD operation and LPPH was 17.4 days.In 21 patients receiving TAE,4 got liver damage and 2 with liver abscesses,1 died.The most common site of LPPH is GDA stump and re-bleeding occurred in 5 patients.9 patients by CSP got bleeding under control.In all 7 re-bleeding patients,2 were saved by CSP,1 was saved by TAE,while the other 4 died.Conclusion Early intervention plays an important role for LPPH.CSP is better than TAE.
7.Long-term efficacy of peroral endoscopic circular myotomy and full-thickness myotomy on treatment of achalasia of cardia
Dezhi HE ; Juan WANG ; Yanmiao HAN ; Jiansheng LI ; Xiaotong WANG ; Pu ZHENG ; Yanyan ZHENG ; Yang CHEN ; Shuguan WANG
Chinese Journal of Digestive Endoscopy 2018;35(5):327-331
Objective To compare the long-term efficacy and complications of peroral endoscopic circular myotomy and full-thickness myotomy for patients with achalasia of cardia. Methods A retrospective analysis was performed on the data of 53 patients with achalasia of cardia, who underwent peroral endoscopic myotomy in the First Affiliated Hospital of Zhengzhou University from June 2012 to December 2014 and were followed-up regularly.Twenty-one patients underwent circular myotomy, and the other 32 patients underwent full-thickness myotomy. The postoperative long-term efficacy and gastroesophageal reflux complications of the two groups were compared. Results The effective rate of the circular myotomy group and the full-thickness myotomy group was 90. 5%( 19/21) and 100. 0%( 32/32), respectively ( P= 0. 152). There were no significant differences between the two groups on postoperative Eckardt scores, lower esophageal sphincter pressure and 4 s integrated relaxation pressure ( P > 0. 05 ). The incidence of clinically relevant gastroesophageal reflux of full-thickness myotomy group was higher than that of circular myotomy group (40. 6% VS 14. 3%, χ2=4. 174, P=0. 041). Conclusion The long-term efficacy of circular myotomy is similar to that of full-thickness myotomy, but the incidence of clinically relevant gastroesophageal reflux is higher in full-thickness myotomy.

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