1.Study of the mechanism of anti-tumor effect of Metformin-enhanced radiotherapy in CT26WT cell lines or mouse models with transplanted tumors
Xichao DAI ; Leilei TAO ; Tingting FANG ; Ping CHEN ; Haijun SUN ; Zhifeng WU ; Xichun DAI
Chinese Journal of Radiation Oncology 2020;29(3):203-206
Objective To investigate the inhibitory effect and mechanism of Metformin (Met) combined with irradiation in CT26WT cell lines or mouse models with transplanted tumors.Methods CT26WT cell line was treated with 0.5 μmol/L,1.0 μmol/L,5.0 μmol/L and 10.0 μmol/L Met,and CellTiter Glo kit was used to detect the inhibitory effect of Met at different concentrations on the viability of CT26WT cells.CT26WT cell line was treated with the control,Met (10 pmol/L),15 Gy irradiation and 15 Gy irradiation+Met (10 μmol/L).Clone formation assay was employed to detect the cell proliferation activity.Bablc mouse models of transplanted tumors (tumor size> 150 mm3) were established and randomly divided into the control,15 Gy irradiation,Met and 15Gy irradiation+Met groups.Mice were given with 750 mg/kg Met at 24 h before irradiation.Transplanted tumor volume was measured regularly to delineate the growth curve of transplanted tumors and survival curve.The expression levels of P-H2AX and Sting proteins in CT26WT cells and transplanted tumors were detected by Western blot.The infiltration of CD8a (+) T cells in transplanted tumor tissues was detected by immunohistochemistry.Results The relative cell survival rate was 100%,87.9%,87.8%,87.3% and 76.5% in the 0,0.5,1.0,5.0 and 10.0μmol/L Met groups,respectively (all P<0.05).The inhibitory effect of 10.0 μmol/L was significantly stronger than that of 5.0 μmol/L (P<0.001).The colone formation rate 34.0%,24.0%,22.3% and 14.0% in the control,Met,15 Gy irradiation,Met+ 15Gy irradiation groups,respectively (all P<0.001).Western blot showed that compared with the control group,the expression of Sting protein was increased by 2.99-fold after Met treatment (P<0.001),and increased by 1.37-fold and 4.41-fold in the 15 Gy irradiation and 15Gy irradiation+Met groups (both P<0.01).Compared with the 15 Gy irradiation group,the expression of P-H2AX protein was significantly increased by 1.43 times after treatment with 15Gy+Met (P<0.001).The transplanted tumor growth curve showed that the transplanted tumor growth in the 15 Gy+Met group was slower than that in the control group[(1007.0± 388.5) mm3 vs.(2639.0± 242.9) mm3,P< 0.05)].The overall survival time in the 15 Gy irradiation+Met group was 48 d,significantly longer than 32 d in the control group (P<0.001).Compared with the control group,the expression of P-H2AX and Sting proteins in the 15 Gy+ Met group was increased by 8.8-fold and 1.6-fold (both P<0.001).Immunohistochemical staining showed that the infiltration of CD8a (+) T cells in the 15 Gy irradiation+Met group was significantly higher than that in the control group (P<0.01).Conclusions Met combined with radiotherapy can inhibit the proliferation and clone formation of colon cancer cells,probably by aggravating DNA damage and activating the Sting signaling pathway,eventually leading to the increase of CD8a (+) T cells in tumor tissues and enhancing the killing effect upon transplanted tumor cells.
2.Analysis of risk factors of lymph node metastasis and clinical significance of deep submucosal invasion in 64 cases of T1 stage colorectal cancer
Haiyan JING ; Chunfang TIAN ; Qingshan PEI ; Shulei ZHAO ; Zhigang YAO ; Xichao SUN ; Yejun QIN ; Xiaolong ZHU
Chinese Journal of Digestion 2021;41(11):770-774
Objective:To investigate the risk factors of lymph node metastasis and the clinical significance of deep submucosal invasion in patients with T1 stage colorectal cancer.Methods:From January 30, 2010 to December 31, 2019, at Shandong Provincial Hospital Affiliated to Shandong First Medical University, among patients with T1 stage colorectal cancer, 41 patients underwent radical surgery for colorectal cancer (surgery group) and 23 patients received endoscopic submucosal dissection (ESD) (ESD group) were enrolled. The tumor gross type, maximum diameter, histologically poorly differentiated components, degree of invasion (the type of mucosal muscle destruction, the width and depth of invasion), the budding grade of tumor, and whether with vascular tumor thrombus were recorded. The additional treatment and prognosis of patients were collected by telephone follow-up. The risk factors of lymph node metastasis in stage T1 colorectal cancer, the correlation between the complete muscularis mucosa destruction and the width and depth of invasion in the ESD group, and the effects of additional treatment after operation on the prognosis of patients were analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The rate of lymph node metastasis in patients with poorly differentiated components or vascular tumor thrombus was higher than that in patients without poorly differentiated components or vascular tumor thrombus (3/6 vs. 12.1%, 7/58; 3/4 vs. 11.7%, 7/60), and the differences were statistically significant ( χ2=5.934 and 11.409, both P<0.05). All patients in the surgery group had complete muscularis mucosa destruction. In ESD group, the width of tumor invasion was ≥ 2 mm in 16 cases, including complete destruction of muscularis mucosa in 15 cases and partial destruction in one case; the width of tumor invasion was <2 mm in seven cases, including complete destruction of muscularis mucoa in two cases and partial destruction in five cases; the depth of infiltration was ≥ 2 000 μm in 14 cases, including complete destruction of muscularis mucosa in 13 cases and partial destruction in one case; the depth of infiltration was <2 000 μm in nine cases, including complete destruction of muscularis mucosa in four cases and partial destruction in five cases. The complete muscularis mucosa destruction was related with tumor of invasion width ≥ 2 mm and invasion depth ≥ 2 000 μm (15/16 vs.2/7, 13/14 vs. 4/7), and the differences were statistically significant ( χ2=10.729, 6.659, both P<0.05). Among the 64 patients with T1 stage colorectal cancer in this study, six cases (9.4%) had poor prognosis; five cases (7.8%) died, and three of them (4.7%) were tumor-related deaths. Adjuvant therapy was added in 10 cases in surgery group and 10 cases in ESD group, and there were no poor prognosis in those patients. There were no significant difference in the incidences of poor prognosis of patients without additional treatment and patients with additional treatment of the two groups (9.7% (3/31) vs. 0 (0/10) and 23.1% (3/13) vs. 0 (0/10)) (both P>0.05). Conclusion:When T1 stage colorectal cancer with tumor submucosal invasion, clinicians should comprehensively evaluate the prognostic risk based on various pathological characteristics such as the degree of tumor differentiation, vascular tumor thrombus and mucosal muscle destruction.
3.Research progress of CD73/NT5E in glioblastoma
Jiang SHAO ; Lin LI ; Yansong GUO ; Chengyuan SUN ; Xichao WEN ; Kebin ZHENG ; Yanfang SHI
The Journal of Practical Medicine 2024;40(3):428-431,438
Glioma is the most common primary central nervous system tumor,mainly derived from glial cells,with strong invasiveness,easy recurrence,and poor prognosis.Glioblastoma is a high-grade glioma with the highest degree of malignancy.The clinical treatment method is mainly surgical resection,supplemented by compre-hensive treatment such as radiotherapy,chemotherapy,and electric field therapy,but the treatment effect is not satisfactory.In recent years,with the rapid development of the field of tumor immunotherapy,CD73 is a novel immune checkpoint related to adenosine metabolism,which can promote tumor progression by inhibiting anti-tumor immune responses and promoting angiogenesis.This article systematically reviews the mechanism of action of CD73 and discusses its biological role and application in glioma,aiming to provide potential treatment options for glioma patients.
4.Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition).
Xin YE ; Weijun FAN ; Zhongmin WANG ; Junjie WANG ; Hui WANG ; Jun WANG ; Chuntang WANG ; Lizhi NIU ; Yong FANG ; Shanzhi GU ; Hui TIAN ; Baodong LIU ; Lou ZHONG ; Yiping ZHUANG ; Jiachang CHI ; Xichao SUN ; Nuo YANG ; Zhigang WEI ; Xiao LI ; Xiaoguang LI ; Yuliang LI ; Chunhai LI ; Yan LI ; Xia YANG ; Wuwei YANG ; Po YANG ; Zhengqiang YANG ; Yueyong XIAO ; Xiaoming SONG ; Kaixian ZHANG ; Shilin CHEN ; Weisheng CHEN ; Zhengyu LIN ; Dianjie LIN ; Zhiqiang MENG ; Xiaojing ZHAO ; Kaiwen HU ; Chen LIU ; Cheng LIU ; Chundong GU ; Dong XU ; Yong HUANG ; Guanghui HUANG ; Zhongmin PENG ; Liang DONG ; Lei JIANG ; Yue HAN ; Qingshi ZENG ; Yong JIN ; Guangyan LEI ; Bo ZHAI ; Hailiang LI ; Jie PAN
Chinese Journal of Lung Cancer 2021;24(5):305-322
"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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