1.Expression of human interferon-?gene in colon cancer cell
Qiang DING ; Lizong SHEN ; Wenxi WU
Chinese Journal of General Surgery 2001;0(07):-
Objective This study was to investigate the expression of human interferon ?(huIFN ?) gene in colon cancer cells. MethodsThe whole length cDNA of huIFN ? was subcloned into the expression vector pcDNA 3 after sequence measurement. Lipofectamine was used to transfer huIFN ? gene into three colon cancer cell lines(LOVO?SW620?HCT116BG) .The integration and expression of huIFN ? were identified by PCR and RT PCR respectively, the activity of IFN ? expressed in different cell lines was measured by ELISA. Results PCR and RT PCR showed successful integration and sustained expression of huIFN ? in 3 colon cancer cell lines. Conclusion The huIFN ? can be effectively transduced into human colon cancer cells, and sustained expression was obtained.
2.In vitro effect of cytosine deaminase gene therapy and chemical reagents on colon cancer cell line
Lizong SHEN ; Qiang DING ; Wenxi WU
Chinese Journal of General Surgery 2001;0(07):-
ObjectiveTo evaluate the effect of combined cytosine deaminase(CD) gene therapy and chemical reagents on colon cancer cell line.MethodsLovo cells transducted with CD gene in a recombinant adenovirus AdCMVCD vector were treated with 5 fluorocytosine(5 FC) and ciplatin(CDDP) or mitomycine C(MMC). Cytotoxic effect was assayed with MTT method. ResultsLow dose of CDDP or MMC reduces the IC 50 of 5 FC significantly on Lovo cells transducted with CD gene and enhances the bystander effect of AdCMVCD/5 FC system.ConclusionCombined therapy with CD/5 FC system and chemical reagents may have a potential application in the treatment of colon cancer.
3.The anti-tumor effect of lipofectamine mediated interferon-? gene therapy on experimental colon cancer model
Qiang DING ; Wenxi WU ; Lizong SHEN ; Ping FAN ; Dehua XU ; Xinyuan LIU
Chinese Journal of General Surgery 2001;0(08):-
Objective To investigate the anti-tumor effect of interferon-?(IFN-?) gene therapy on colon cancer. Methods BALB/c mice were inoculated subcutaneously with CT26 (murine colon carcinoma cell line) cells to prepare an in vivo tumor model. Eight days after tumor inoculation,the tumor-bearing mice were divided into 3 groups and injected intra-tumorally with one of the following preparations: pcDNA3-IFN-?/Lipofectamine,pcDNA3 /Lipofectamine,and PBS respectively. The expression of IFN-?,the immunity function of mice,the histological changes of the tumor,the tumor volume in tumor-bearing mice were tested after gene therapy. ResultsThe level of IFN-? in the serum and the CTL activity increased significantly( P
4.Oncologic outcomes of early stage cervical cancer performed operation by different laparoscopic surgical procedures: analysis of clinical data from mutiple centers
Kaijian LING ; Yanzhou WANG ; Hui ZHANG ; Xuyin ZHANG ; Junjun YANG ; Chengyan LUO ; Bin SONG ; Wenxi ZHANG ; Li DENG ; Gongli CHEN ; Yudi LI ; Qunying HU ; Yong CHEN ; Xin WANG ; Jun ZHANG ; Jingxin DING ; Tong REN ; Shan KANG ; Keqin HUA ; Yang XIANG ; Wenjun CHENG ; Zhiqing LIANG
Chinese Journal of Obstetrics and Gynecology 2020;55(9):617-623
Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH ( P=0.010). Stratify analysis, including stage of disease (Ⅰb1 and Ⅱa1), histologic subtypes (squamous-cell carcinoma, adenocarcinoma), lymph node metastasis, revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group (98.6% vs 93.6%, P=0.012). In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% ( P=0.007). ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference ( P=0.046); for adenocarcinoma, the OS at five years were 91.0% and 88.6%, and there was no difference between two groups ( P=0.230). ③ Lymph node metastasis: the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156, P=0.093). (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group (88.2% vs 75.8%, P=0.074). Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.
5.Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer.
Yu ZHOU ; Wenxi ZHOU ; Xinli CHEN ; Qingbing WANG ; Chao LI ; Qinjun CHEN ; Yu ZHANG ; Yifei LU ; Xiaoyi DING ; Chen JIANG
Acta Pharmaceutica Sinica B 2020;10(8):1563-1575
Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy and , plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.
6. Therapeutic and immunomodulatory effects of human umbilical cord-derived mesenchymal stem cells on adjuvant arthritis in rats
Run CHENG ; Wenxi DING ; Zhuoyu CHENG ; Jichen HE ; Yingjie ZHAO ; Shangxue YAN ; Wei WEI
Chinese Journal of Primary Medicine and Pharmacy 2019;26(19):2327-2331
Objective:
To investigate the therapeutic and immunomodulatory effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on adjuvant arthritis(AA) rats.
Methods:
Twenty-four male Sprague-Dawley(SD) rats were established with AA by complete Freund's adjuvant method.They were randomly divided into model group and hUC-MSCs group (2×106 cells/mL, 5×106 cells/mL, tail vein injection), and the Yisaipu group (2.8mg/kg, subcutaneous injection), 6 rats in each group.Another 6 male SD rats were used as the control group.After the model was established, the body weight and paw volume were recorded weekly, the whole body score and the arthritis index score were calculated, and the joint swelling number was calculated.The animals were sacrificed after d35, the weight of thymus and spleen were weighed, and the corresponding index was calculated, the histopathological changes of the ankle joint were observed by HE staining.The percentages of CD4+ CD44+ T cell and CD4+ CD62L+ T cell were detected by flow cytometry.The levels of TNF-α, IL-1β in the serum of AA rats were detected by ELISA.
Results:
hUC-MSCs relieved paw volume, the whole body score and arthritis index score, and the joint swelling number in AA rats (