1.Bioactivity of in vitro cultured tumor necrosis factor-alfa transduced tumor-infiltrating lymphocytes and therapeutic effects on human brain glioblastoma infused in different ways
Junhong GUAN ; Hongwei YU ; Weiran PAN ; Yongjie YANG ; Chenglin WANG ; Changshan REN ; Hong CHEN ; Chengguang SUI
Chinese Journal of Tissue Engineering Research 2005;9(26):262-265
BACKGROUND: Tumor-adopted immunity and gene transduction technique are used to introduce tumor necrosis factor-α vector into carrier cells, which are then re-infused into the body so that cancer cells can be killed by tumor necrosis factor-α more directly and effectively with fewer side effects on the other tissues due to high local expression.OBJECTIVE: To study the bioactivity of in vitro cultured tumor necrosis factor-α transduced tumor-infiltrating lymphocytes as well as the inhibitory effects on cancer cells of cancer-loaded rats infused in different ways.DESIGN: A randomized controlled study based on experimental animals.SEETING: Cancer Research Institute of China Medical University.MATERIALS: This study was carried out at the Cancer Research Institute and the Experimental Animal Department, China Medical University,between January 2000 and December 2001. TJ8510 cell line (human brain glioblastoma cell line) was provided by the Neurological Research Institute of Tianjin Medical University Affiliated Hospital. The experimental animals were 36 BALB/C nude mice congenitally having no thymius.METHODS: Based on the establishment of tumor necrosis factor-α retroviral transduction system and the preparation of cartier cells tumor-infil-trating lymphocytes, the monoclonal virus cell line PLC-2 and PLJC-5available were used to introduce marked gene NeoR and targeted gene tumor necrosis factor-α into tumor-infiltrating lymphocytes, respectively.Then cell proliferation, tumor necrosis factor expression and in vitro antitumor activity were examined. After cancer cell inoculation, the 36 nude mice were randomly divided into 6 groups: local infusion control group, local tumor-infiltrating lymphocytes infusion group, local tumor necrosis factor-tumor-infiltrating lymphocytes infusion group, venous infusion control group, venous tumor-infiltrating lymphocytes infusion group and venous tumor necrosis factor-tumor-infiltrating lymphocytes infusion group, and the therapeutic effects on the cancer-loaded mice were observed.proliferation and tumor necrosis factor-α expression in tumor-infiltrating oR-tumor-infiltrating lymphocytes and tumor necrosis factor-tumor-infiltrating lymphocytes was not significantly different from each other (P > 0.05).NeoR-tumor-infiltrating lymphocytes, though not significantly different (P >0.05), significantly differ from that of tumor necrosis factor-tumor-infiltrating lymphocytes (P < 0.01); moreover, tumor necrosis factor-tumor-infiltrating lymphocytes were found to express higher tumor necrosis factor-α conactivity did not significantly differ between tumor-infiltrating lymphocytes and NeoR-tumor-infiltrating lymphocytes (P > 0.05), but obviously increased come of the animal experiment: 40 days after tumor necrosis factor-tumorinfiltrating lymphocytes infusion, cancer size in local tumor necrosis factortumor-infiltrating lymphocytes infusion group was found smaller than that in local infusion control group [(307±42) and (2 048±278) mm3, P < 0.01],and it was also smaller in venous tumor necrosis factor-tumor-infiltrating lymphocytes infusion group than that in venous control group [(954±195)and (1 989±305) mm3 , P < 0.05].CONCLUSION: Tumor necrosis factor-α gene transduced tumor-infiltrating lymphocytes could effectively express tumor necrosis factor, exerting higher and in vivo anti-tumor effects than tumor-infiltrating lymphocytes in cancer-loaded nude mice. No obvious inhibitory effects on the growth of subcutaneous solid carcinoma could be observed in nude mice after venous infusion of human brain glioblastoma tumor-infiltrating lymphocytes, but the inhibitory effects became obvious due to venous infusion of tumor necrosis factor-tumor-infiltrating lymphocytes and significant due to local tumor necrosis factor-tumor-infiltrating lymphocytes infusion, indicating that local infusion is the preferable way in the treatment of glioblastoma by immuno-gene therapy.
2.Relationship between Helicobacter Pylori Infection and Blood Lipid Metabolism and Atherosclerosis
Jie DU ; Wei YANG ; Guixia ZHANG ; Qiuxian HE ; Hongyan LI ; Yongjie SUI
Journal of Modern Laboratory Medicine 2017;32(4):104-106
Objective To investigate the correlation between Helicobacter pylori (Hp) infection and blood lipid metabolism and atherosclerosis.Methods From October 2015 to October 2020,200 cases of Hp positive subjects were observed as observation group and 200 cases of Hp negative subjects as the control group,all subjects were blood lipid levels of vascular ultrasound and other related checks.Results The levels of total cholesterol (TC) (5.68± 1.46 mmol/L),triglyceride (TG) (1.58 ± 0.76 mmol/L) and low density lipoprotein cholesterol (LDL-C),and the difference was statistically significant (t=6.12,7.69,5.64,all P<0.05).The detection rate of carotid atherosclerotic plaque in the observation group was 66.00 %,which was significantly higher than that in the control group (49.50%),the difference was statistically significant (x2=29.61,P<0.05),and the observation group.The detection rate of stable plaque was 44.5 %,which was significantly higher than that of the control group 22.5%,the difference was statistically significant (x2 =21.73,P<0.05).Conclusion Hp infection can affect the level of lipid metabolism in patients,which is an important factor in the occurrence and development of atherosclerosis.
3.Nonlinear relationship between high-density lipoprotein cholesterol and diabetes risk: a secondary analysis based on a Chinese adult cohort study
Jie DU ; Jing NIU ; Hongyan LI ; Yongjie SUI
Chinese Journal of Health Management 2024;18(3):178-184
Objective:To investigate the association between high-density lipoprotein cholesterol (HDL-C) and the risk of diabetes mellitus (DM) in Chinese adults.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study using data from the Chinese health screening program in the DATADRYAD database. Between 2010 and 2016, 211833 Chinese adults aged 20 years or older were screened for diabetes at baseline in 32 sites and 11 cities across the country. Baseline HDL-C level was the target independent variable and the risk of DM at follow-up was the dependent variable. Cox proportional hazards regression analysis assessed the independent association between HDL-C levels and the risk of developing DM. In this paper, the generalized Additive Model (GAM) and the smoothing curve fitting method were used to study the nonlinear relationships. In addition, subgroup analyses were conducted to assess the consistency of the correlations among different subgroup and to further validate the reliability of the results.Results:After adjusting for potential confounding factors such as age, sex and body mass index, HDL-C level was positively correlated with the development of diabetes ( HR=1.43, 95% CI: 1.08-1.90, P=0.012). The level of HDL-C showed a non-linear relationship with the risk of DM, and the inflection point was 1.81 mmol/L. The HR (95% CI) of the left and right sides of the inflection point were 0.94 (0.56-1.55) and 2.54 (1.93-3.30), respectively. When HDL-C>1.81 mmol/L, HDL-C was positively correlated with the occurrence of DM. Each 1.00 mmol/L increase in HDL-C increased the risk of diabetes mellitus by 1.54 times ( P<0.001); when HDL-C<1.81 mmol/L, the risk of diabetes decreased by 6% for every 1.00 mmol/L increase in HDL-C ( P=0.798). Subgroup analysis showed that, in the age, male, BMI 24.5-52.7 kg/m 2 subgroups, all the systolic blood pressure subgroups, diastolic blood pressure 69-77 and 78-164 mmHg (1 mmHg=0.133 kPa) subgroups, total cholesterol 0.02-4.26 and 5.00-17.84 mmol/L subgroups, all the triglyceride subgroups, low-density lipoprotein 0-2.42 and 2.99-12.60 mmol/L subgroups, alanine aminotransferase 23.4-1 508.4 U/L subgroups, aspartate transaminase 0-19.7 and 24.8-1 026.2 U/L subgroups, all the urea nitrogen subgroups, creatinine 61.5-76.9, 77.0-1 116.6 μmol/L subgroups, never smoking subgroup, subgroup with frequent alcohol consumption or family history of diabetes mellitus, the effect values of HDL-C and the risk of diabetes mellitus in Chinese adults showed good stability (all HR>1.00). Conclusions:High levels of HDL-C are associated with an increased risk of DM in Chinese adults. When HDL-C is greater than 1.81 mmol/L, HDL-C is positively correlated with DM.
4.Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression
Yumiao ZHAO ; Jiaxin SUN ; Yin LI ; Xiuman ZHOU ; Wenjie ZHAI ; Yahong WU ; Guanyu CHEN ; Shanshan GOU ; Xinghua SUI ; Wenshan ZHAO ; Lu QIU ; Yongjie YAO ; Yixuan SUN ; Chunxia CHEN ; Yuanming QI ; Yanfeng GAO
Acta Pharmaceutica Sinica B 2021;11(9):2835-2849
Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3