1.Comprehensive therapeutic strategies regarding immune checkpoint
Chinese Journal of Clinical Oncology 2017;44(15):782-786
The rapid development of immunotherapy has exceeded that of standard treatment modes, which include surgery, radio-therapy, chemotherapy, and targeted therapy. Immunotherapy is more durable and less toxic than traditional cancer therapies. More-over, immune checkpoint therapy is an important component of immunotherapy and has been evaluated in preclinical and clinical tri-als and proven to exhibit broad prospects. However, its clinical benefits are limited to a small subset of patients with a subset of tumor types. Therefore, reasonable comprehensive therapeutic strategies are needed to overcome this limitation. Gene targeted therapy, ra-diotherapy, chemotherapy, and tumor vaccine affect the immune system through different mechanisms, and these could provide theo-retical bases for comprehensive treatments. In this review, immune checkpoint therapy and its potential comprehensive therapies with other cancer treatments are introduced.
2.STUDY ON PHARMACOKINETIOS OF AMIODARONE IN RABBIT PLASTER BY MICELLAR ENHARCED FLUORIMETRIC METHOD
Zhigong PANG ; Baoqi WANG ; Guojie WU
Journal of Xi'an Jiaotong University(Medical Sciences) 1982;0(04):-
The authors used high sensitive micellar enhanced fluorimetric method to monitor amiodarone blood-medical concentration. SLS severed as micellar reagent. Under experimental condition,we used 930 fluorophotommeter which made in China as the main analytic instrument,and obtained a series pharmacokinetic parameter ,eg. t_(1/2) (?) was 1.18 h, t_(1/2)(?)was 40.75 h, K_(21) was 0.278 l/h,K_(10) was 0.036 l/h,K_(12) was 0.291 l/h. The linear range of this method was 2 ? 10_(-9)~8 ? 10_(-6) mol/L,determined limit was 1.3 ? 10~(-9)mol/L, average recovery was 99.93%.
3.Reactions of serum Creatine Kinase in Early phase of Spherical steel-bullet Injury
Lichao ZHENG ; Zhigong WANG ; Yinqiu LIU ; Xueyun CHENG
Journal of Third Military Medical University 1984;0(02):-
Through the experiments of producing spherical steel-bullet (4.763mm in caliber and 0,44gm in weight) wound on the hind legs of 17 dogs, the authors re- ported that there was a definite linear relationship between the reactions of the serum creatine kinase and the amount of kintic energy from the high speed of the bullets absorbed by the tissues and also with the weight of dead tissue removed around the bullet-path, Within the first 6 hours after injury, the activity of SCK increased with the rise of the biologic effect values of the amount of the kinetic energy absorbed and the weight of the dead tissue removed.
4.Diagnosis and treatment of rare hepatic tumors
Peikun LI ; Xiaoping GENG ; Yijun ZHAO ; Hongchuan ZHAO ; Fubao LIU ; Guobin WANG ; Zhigong ZHANG
Chinese Journal of General Surgery 2010;25(12):959-962
Objective To sum up our experience on the diagnosis and treatment of rare hepatic tumors. Methods The data of 25 patients with rare liver tumors admitted in our hospital from May 2005 to January 2010 were analyzed retrospectively. Results The final pathologic diagnosis of focal nodular hyperplasia was made in 6 cases, and the diagnosis of vascular leiomyoma, hilar neurilemoma, intrahepatic aneurysm, biliary cystadenoma, hepatic hamartoma, biliary villous adenoma, and hepatic diffuse large B-cell lymphoma was established in one each case, respectively. The diagnosis of angiomyolipoma in 2patients, primary liver gastroimestinal stromal tumor in 2 patients, hepatoblastoma in 5 patients and liver undifferentiated sarcoma in 3 patients was established. Preoperative ultrasonography, CT and MRI were performed in 24, 22 and 6 patients respectively. Preoperative tentative diagnosis was finally confirmed by pathology in only 3 (16.7%) cases, all by CT report. Preoperative diagnosis was consistent with postoperative pathology in 5 patients (20%); All patients underwent liver resection including hemihepatectomy in 7 patients, hepatic lobectomy in 7 patients, segmentectomy in 9 patients and tumor enucleation in 2 patients; There was no recurrence after resection of benign, low malignant tumors and hepatic diffuse large B-cell lymphoma; Postoperative follow-up was made for all the 5 cases of malignant tumours, and there was recurrence in 3 cases. These 3 eases underwent second resection and there were no recurrences after reoperation. The two recurrent patients died with a mean survival of 4 months.Conclusions The preoperative correct imaging diagnostic rate for rare hepatic tumors is low. Surgery is the most effective therapy and reoperation should always be attempted for tumor recurrence in order to prolong survival.
5.FHIT and RASSF1A promoter hypermethylation in plasma and tumor tissues from patients with hepatocellular carcinoma
Dong LI ; Lixin ZHU ; Xiaoping GENG ; Xiaoming LI ; Hongchuan ZHAO ; Fubao LIU ; Guobin WANG ; Yijun ZHAO ; Zhigong ZHANG ; Fan HUANG ; Ping WANG
Chinese Journal of Hepatobiliary Surgery 2012;(11):831-836
Objective To detect aberrant methylation in the promoter of FHIT and RASSF1A genes in peripheral plasma and tumor tissues from patients with hepatocellular carcinoma (HCC) and to determine its clinical significance.Methods The methylation status of FHIT and RASSF1A genes in peripheral plasma and tumor tissues from 36 patients with HCC were detected by methylation-specific polymerase chain reaction(MSP).The correlation between methylation status in plasma and clinicopathological features was analyzed.Results The frequency of promoter methylation of FHIT in tissues was 75% (27/36) and in plasma 52.8% (19/36),and the correlation coefficient was r=0.482 (P=0.003).The frequency of promoter methylation of RASSF1A in tumor tissues was 83.3% (30/36) and in plasma 61.1% (22/36),and the correlation coefficient was r=0.561 (P=0.0004).Aberrant methylation of FHIT,RASSF1A gene in the plasma and tissues had no correlation with the patients' clinicopathological features such as gender,age,HBV/HCV infection,hepatic cirrhosis,tumor size,alpha-fetoprotein (AFP) level,pathological grade,staging,vascular tumour thrombus and recurrence.The sensitivity of AFP ≥400 μg/L was 44.4%,and AFP ≥20 μg/L 69.4%.The sensitivity of FHIT and RASSF1A gene promoter hypermethylation in 36 HCC patients was 72.2%.In 20 patients whose AFP <400 μg/L,the frequency of hypermethylation of the two genes together was 80%.When AFP <20 μg/L,the frequency of hypermethylation of the two genes together was 54.5 %.Conclusions There was a significant concordance between plasma and tumor tissue methylation profiles.The methylation status in plasma and tumor tissues had no correlation with the patients' clinicopathological features.Combining promoter methylation of FHIT and RASSF1A genes was superior to AFP in the diagnosis of HCC.
6.Roles of pancreatic stellate cells and pancreatic cancer cells in angiogenesis of pancreatic cancer: an in vitro study
Zhigong ZHANG ; Tingting CHENG ; Hansjoerg HABISCH ; Marko KORNMANN ; Haoran WANG ; Xiaoping GENG
Chinese Journal of Digestive Surgery 2023;22(5):623-630
Objective:To investigate the role and mechanism of pancreatic stellate cells (PSCs) and pancreatic cancer cells (PCCs) in the angiogenesis of pancreatic cancer.Methods:The experimental study was conducted. The human PSCs and PCCs and human umbilical vein endothelial cells (HUVECs) were cultured in vitro. HUVECs was treated with PSCs/PCCs supernatants and matrix metalloproteinase (MMP) inhibitor of different types and concentrations. As controls, HUVECs treated with complete endoprime medium (C/E) and DMEM/Ham's F12 medium (D/F) were set as the C/E group and the D/F group, respectively. Observation indicators: (1) proliferation of HUVECs under different conditions; (2) tube formation of HUVECs under different conditions; (3) migration of HUVECs under different conditions; (4) expression of MMP-2 in the supernatants of PSCs and PCCs; (5) effect of MMP inhibitor GM6001 on migration of HUVECs. Measurement data with normal distribution were represented as Mean± SD, comparison among groups was conducted using the one way ANOVA and comparison between groups was conducted using the LSD- t test. Results:(1) Proliferation of HUVECs under different conditions. Results of HUVECs proliferation assay using 5-ethynyl-2′-deoxyuridine (EdU) labeling showed that the binding rate of EdU in the HUVECs of D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PSCs was 12.4%±1.0%, 24.5%±2.9%, 25.3%±3.0%, 22.8%±2.0%, 22.9%±2.8%, respectively, showing a significant difference among them ( F=8.60, P<0.05). There were significant differences in the binding rate of EdU between HUVECs in the D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PSCs, respectively ( P<0.05). The binding rate of EdU between HUVECs in the D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PCCs was 12.4%±1.0%, 30.0%±3.2%, 32.1%±1.0%, 32.3%±3.5%, 26.2%±5.6%, respectively, showing a significant difference among them ( F=11.93, P<0.05). There were significant differences in the binding rate of EdU between HUVECs in the D/F group and HUVECs treated with supernatants of different concentration (25%, 50%, 75%, 95%) of PSCs, respectively ( P<0.05). (2) Tube formation of HUVECs under different conditions. Number of tube formation, length of tube in the HUVECs of D/F group and HUVECs treated with PSCs supernatants was 15.2±2.3, (12.1±1.5)mm and 49.7±3.2, (39.8±2.3)mm, respectively, showing significant differences between the two groups of HUVECs ( P<0.05). (3) Migration of HUVECs under different conditions. Results of single cell tracing experiment showed that the migration rate of HUVECs treated with supernatants of different ratio of PSCs and PCCs was faster than that of HUVECs in the D/F group, and the enhancement effect of supernatants of PSCs and PCCs was dose-dependent. The migration rate of HUVECs treated with mix supernatants of different concentration of PSCs and PCCs and supernatants of co-cultured PSCs and PCCs was faster than that of HUVECs in the D/F group. The migration rate of HUVECs treated supernatants of co-cultured PSCs and PCCs was faster than that of HUVECs treated with mix supernatants of different concentration of PSCs and PCCs, showing a synergistic effect in the HUVECs treated supernatants of co-cultured PSCs and PCCs. (4) Expression of MMP-2 in the supernatants of PSCs and PCCs. Results of gelatine zymography showed that the MMP-2 expression levels decreased sequentially in super-natants of co-cultured PSCs and PCCs, supernatants of PSCs, mix supernatants of PSCs and PCCs and supernatants PCCs. (5) Effect of MMP inhibitor GM6001 on migration of HUVECs. Results of single cell tracing experiment showed that the migration rate of HUVECs treated with PSCs supernatants combined with different concentration of GM6001 (0, 1, 10, 25 μmol/L) was (25.70±2.06)μm/h, (18.37±1.61)μm/h, (16.20±0.26)μm/h, (15.99±0.58)μm/h, respectively, showing a significant difference among them ( F=11.39, P<0.05). There were significant differences in the migration rate between HUVECs treated with PSCs supernatants combined with 1, 10, 25 μmol/L GM6001 and HUVECs treated with PSCs supernatants ( P<0.05). The migration rate of HUVECs treated with mix super-natants of PSCs and PCCs combined with different concentration of GM6001 (0, 1, 10, 25 μmol/L) was (30.06±3.70)μm/h, (22.76±1.56)μm/h, (23.87±2.84)μm/h, (22.10±2.35)μm/h, respectively, showing a significant difference among them ( F=4.06, P<0.05). There were significant differences in the migration rate between HUVECs treated with mix supernatants of PSCs and PCCs combined with 1, 10, 25 μmol/L GM6001 and HUVECs treated with mix supernatants of PSCs and PCCs ( P<0.05). Conclusions:Both PSCs and PCCs can promote the proliferation, migration and angiogenesis of HUVECs in vitro experiment. Releasing of MMP-2 by interaction between PSCs and PCCs is an important factor to stimulate endothelial cell migration, which increases the stimulating activity of angiogenesis, especially the migration ability of HUVECs.
7.Selective control of hindlimb movements based on intraspinal functional electronic stimulation.
Xiaoyan SHEN ; Zhigong WANG ; Lei MA ; Xiaoying LU ; Wei DU ; Yi CHEN ; Chunling TAO
Journal of Biomedical Engineering 2018;35(6):860-863
Functional electronic stimulation (FES) may provide a means to restore motor function in patients with spinal cord injuries. The goal of this study is to determine the regions in the spinal cord controlling different hindlimb movements in the rats. Normalization was used for the regions dominating the corresponding movements. It has been verified that FES can be used in motor function recovery of the hindlimb. The spinal cord was stimulated by FES with a three-dimensional scan mode in experiments. The results show that stimulation through the electrodes implanted in the ventral locations of the lumbosacral enlargement can produce coordinated single- and multi-joint hindlimb movements. A variety of different hindlimb movements can be induced with the appropriate stimulation sites, and movement vectors of the hindlimb cover the full range of movement directions in the sagittal plane of the hindlimb. This article drew a map about spinal cord motor function of the rat. The regions in the spinal cord which control corresponding movements are normalized. The data in the study provide guidance about the location of electrode tips in the follow-up experiments.