1.Progress on glioblastoma multiforme treatment with chimeric antigen receptor T-cells
Yue BAI ; Xiaosong ZHONG ; Wenbin LI
Chinese Journal of Clinical Oncology 2017;44(16):794-799
Glioblastoma multiforme (GBM) is the most malignant form of glioma, and its treatment through traditional surgery combined with chemotherapy and radiotherapy has limited efficacy. Chimericantigen receptor T-cells (CAR-T) are recombinant receptors for antigen, which, in a single molecule, redirect and mediateantigen recognition, T-cell activation, and, in the case of second-generation chimeric antigen receptors (CARs) costimulation (CD28 or 4-BB), augment T-cell functionality and persistence. CARs are the focus of attention in emerging treatment options for GBM. This article mainly introduces the development process of CAR-T therapy and the recent success of adoptive transfer of CAR-T cells. Effective targets of the treatment of GBM with CAR-T according to this research are discussed as well. Some of the most extensively studied targets on GBM, especially interleukin-13 receptor α chain variant 2, epidermal growth factor receptor-Ⅷ(EGFRⅧ), human epidermal growth factor receptor 2 (ErbB2), and ephrinA2 receptor (ErbA2), and the different characteristics of each kind of alloantigen-specific CAR-T cells, are the basis for CAR-T therapy and indicate their different characteristics or utilities and the prospect of further clinical research. The discovery of selective expression of interleukin-13 receptor alpha 2 in glioma cells more than 20 years ago prompted the clinical trial of CAR-T therapy in stage I GBM tumors, and the therapy was proven safe and effective. EGFRⅧ is a neoantigen presenting only in cancer cells and glioblastoma stem cells. Its presence is correlated with poor prognosis, and a phase Ⅰ/Ⅱ trial is ongoing at different institutes. ErbB2-specific CARs were also expressed in human Tcells.Adoptive transfer of EphA2 (or ErbB2)-specific T cells resulted in the regression of glioma xenografts. Thus, target-specific CAR-T immunotherapy may be a promising approach for the treatment of different target-positive GBM. Finally, we summarize the application value and challenge of CAR-T cell therapy in the treatment of GBM.
2.Expression of HPV L1 protein and p16 in cervical lesions
Li LI ; Wenbin HUANG ; Yue HUANG ; Youcai ZHAO ; Xiaobin YANG ; Jinsong WANG ; Jianhua ZHAO
Chinese Journal of Clinical and Experimental Pathology 2009;(6):576-579
Purpose To study the expression of HPV L1 protein and p16 in various cervical lesions and to explore the value of HPV L1 protein and p16 immunostaining in predicting the progression from CIN1 to CIN3 and squamous cell carcinoma (SCC).Methods Expression of HPV L1 protein and p16 in 18 cases of CIN1, 9 cases of CIN2, 8 cases of CIN3 and 6 cases of SCC was detected by immunohistochemistry.Results The average positive rates of HPV L1 protein in cervical lesions were 26.8%, and HPV L1 protein was positive in 38.9% of CIN1 and 44.4% of CIN2, but in 0 of CIN3 and SCC. In contrast, the average positive rate of p16 protein in cervical lesions was 68.3%, p16 protein was positive in 38.9% of CIN1and 77.8% of CIN2, but in 100% of CIN3 and SCC. p16-/HPV L1+ and p16-/HPV L1- cases represented 61.1% of CIN1, but 0 of CIN3 and SCCs, whereas p16+/HPV L1- cases represented 100% of CIN3 and SCC.Conclusions Expression of HPV L1 protein decreases whereas p16 protein increases with lesion progression. p16+/HPV L1- cases have the potential for progression, whereas p16-/HPV L1+ and p16-/HPV L1- cases may not be progressive lesions or potentially in remission.
3.Diagnostic value of radionuclide salivagram in pediatric pulmonary aspiration
Liang CAI ; Yue CHEN ; Zhanwen HUANG ; Li ZHANG ; Qiang WAN ; Wenbin DONG ; Zedong BIAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(4):287-290
Objective To evaluate the diagnostic value of radionuclide salivagram in children with pulmonary aspiration.Methods From March 2012 to June 2015,a total of 62 patients (37 males,25 females;age range:2 d-14 years) with suspected pediatric aspiration pneumonia were enrolled in this retrospective study.All patients underwent gastroesophageal reflux (GER) imaging and(or) radionuclide salivagram.Detection rate of pulmonary aspiration by the two imaging techniques was compared with x2 test.Results Of 62 patients,14 were diagnosed as pulmonary aspiration,including 1 detected by GER imaging,and 13 detected by salivagram.The detection rate for pulmonary aspiration by radionuclide salivagram (26.0%,13/50) was significantly higher than that by GER imaging (3.1%,1/32;x2=7.211,P<0.05).Eight of the 13 cases with pulmonary aspiration diagnosed by radionuclide salivagram underwent upper gastrointestinal radiography,and 5 cases had visible contrast agent in the airway.Conclusion Radionuclide salivagram has a higher detection rate for pulmonary aspiration compared to GER imaging,and has good concordance with the traditional upper gastrointestinal radiography.
4.99Tcm-EHIDA SPECT combined with planar hepatobiliary scintigraphy for the differentiation between infant biliary atresia and neonatal hepatitis
Wenlu ZHENG ; Yue CHEN ; Zhanwen HUANG ; Liang CAI ; Wenbin DONG ; Bin LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(4):296-299
Objective To evaluate the value of 99Tcm-EHIDA SPECT combined with planar hepatobiliary scintigraphy (combined scintigraphy) in the differentiation of infant biliary atresia (BA) from neonatal hepatitis (NH).Methods This is a retrospective study on 32 infants with cholestasis (18 males,14 females;age:28-83 d) from June 2013 to June 2014.All infants underwent sequential 99Tcm-EHIDA hepatobiliary planar scintigraphy and combined scintigraphy,and the diagnostic efficacy of the 2 methods for differentiating infant BA from NH was analyzed by x2 test.Results In sequential planar scintigraphy,the diagnostic sensitivity,specificity,accuracy,positive predictive value and negative predictive value were 76.2% (16/21),6/11,68.8% (22/32),76.2% (16/21) and 6/11,respectively.In combined scintigraphy,the diagnostic parameters were 95.2% (20/21),8/11,87.5% (28/32),87.0% (20/23) and 8/9,respectively.Combined scintigraphy correctly identified 4 BA cases that were misdiagnosed as NH by planar scintigraphy.The sensitivity of combined scintigraphy was significantly higher than that of planar scintigraphy (x2 =4.285,P<0.05),while no significant difference was found in the other diagnostic parameters (x2 =0.061-0.405,all P>0.05).Conclusions Combined scintigraphy has incremental value for the differentiation of infant BA from NH.
5.Comparation of efficacy between percutaneous decortication and ureteroscopic decompression in treating simple renal cyst
Wenbin YANG ; Ci ZHANG ; Huijun QIAN ; Yue XIA ; Guang SHAN ; Ming ZHENG
International Journal of Surgery 2015;42(8):523-526
Objective To compare the efficacy and complications of percutaneous nephroscope decortication of cystic renal disease with transureteroscopic decompression of cystic renal disease.Methods Retrospectively analyze the clinical data of 42 simple renal cyst cases,who under treatment of surgical in Zhongnan Hospital of Wuhan University from Sep.2010 to Sep.2014 via percutaneous nephrolithotomy as well as ureteroscope.There were 21 patients in each group.Comparisons were made between the two groups on operation time,peripheral tissue injury,blood loss,postoperative infection,hospitalzation time.Postoperative recurrence were followed up.Results For the percutaneous nephroscope decortication of cystic renal disease group and transureteroscopic decompression of cystic renal disease group,the operation time were (38.43 ± 9.76) minutes,(28.95 ± 8.67) minutes,the number of tissue injury were 8,6;the blood loss were (28.62 ± 9.82) mL,(23.48 ± 7.65) mL;the number of postoperative infection was 4,10;the postoperative recurrence were 2,5;the hospitalzation time were 2 days and 8 days.Compared with the transureteroscopic decompression group,the percutaneous nephroscope decortication group had a less postoperative infection and fewer postoperative recurrence (P < 0.05).But the operation time was longer in the percutaneous nephroscope decortication group (P < 0.05).Conclusions The therapeutic effect of percutaneous nephroscope decortication is much better than that of transureteroscopic decompression,but also has a little disadvantage.
6.Evaluation of synchronous bilateral primary breast cancer by MRI and pathology
Yue YANG ; Yuping PAN ; Chungen WU ; Zhuhua ZHU ; Wenbin LI ; Qin HUANG
Journal of Practical Radiology 2016;32(3):358-361
Objective To analyze the magnetic resonance imaging (MRI)and histologic features of the synchronous bilateral primary breast cancer (sBPBC).Methods MRI findings and pathologic types of sBPBC in 20 patients in our institute were reviewed retrospectively. The MRI features of sBPBC were compared with the pathologic types,respectively.Results 20 sBPBC patients with 41 lesions were found with the most common pathological type of invasive ductal carcinoma in 26 (26/41 ).Bilateral lesions had the same pathological types in 1 1 patients(1 1/20),and different types in 9(9/20).The MRI features of invasive breast cancer were more characteristic than that of early breast cancer.In 20 patients,the first and second primary breast cancers with similar MRI findings were found in 6(6/20).In 10 patients with sBPBC,the first cancer was advanced breast cancer,and the second was early or low grade breast cancer.Conclusion (1)The most common pathological type of sBPBC is invasive ductal carcinoma,and the pathological types of bilateral lesions are not similar. (2)The MRI features of the first and the second lesions in bilateral primary breast cancer showed lower similarity,and the bilateral lesions should be diagnosed independently.(3)In patients with sBPBC,some cancers are advanced breast cancers,and the second ones are early cancers,suggesting the lesion should be followed up if the contralateral one is diagnosed as breast cancer.
7.A new multiplex-polymerase chain reaction-single strand conformation polymorphism assay for simultaneous detection of isoniazid and rifampin resistance in Mycobacterium tuberculosis
Xiaodong CHENG ; Liu YANG ; Jiayun LIU ; Qiaohong YUE ; Xiuli XU ; Yueyun MA ; Daorong PENG ; Wenbin YU ; Mingquan SU ; Xiaoke HAO
Chinese Journal of Laboratory Medicine 2008;31(11):1240-1244
Objective To detect the isoniazid (INH) and rifampin (RIF) resistance of Mycohaeterium tuberculosis isolates in the single tube with multiplex-polymerase chain reaction-single strand conformation polymorphism(muhi-PCR-SSCP) system. Methods According to the sequences of inhA, katG and rpoB genes of the Mycohacterium tuberculosis, three pairs of oligonucleotide primes were designed to examine the INH and RIF resistance with the multi-PCR-SSCP. The validity of the newly developed method was evaluated with 116 clinical isolates of Mycohacterium tuberculosis( 70 isolates that were INH-resistant and 66 isolates that were RIF-resistant). Results The validity of the method was assessed with multiplex PCR-SSCP with the bacteria culture with susceptibility test as golden standard. The three genes, katG, inhA and rpoB, in the 116 clinical isolates and H37Rv strain were amplified successfully in single PCR reactions,except 4 isolates with katG deletion mutants. Compared with strain H37Rv, forty-six isolates had katG gene mutations, thirteen had inhA mutations and fifty-eight had rpoB mutations. Thirty-eight isolates had simultaneous katG and rpoB mutations and 4 isolates had both inhA and rpoB mutations. Four isolates had inhA and katG mutations and 2 isolates had mutations in all three genes simultaneously. The sensitivity of the newly developed multiplex-PCR-SSCP assay was 80% and 82% for INH and RIF, respectively. The specificity of the assay was 100% and 92% for INH and RIF, respectively. Conclusion Muhiplex-PCRSSCP provides a rapid, specific and cost-effective method of detecting multidrug-resistant TB. It laid a solid foundation for the further study of drug resistant gene.
8.Isolation and biological properties of avian infectious bronchitis virus isolated from Shanxi province
Fang YAN ; Wenbin YUE ; Juan LIU ; Xuying LI ; Yujun ZHAO ; Wenhui JI ; Fengbo LIU ; Qian WU ; Jiayan REN ; Lizhen HUA
Chinese Journal of Veterinary Science 2009;29(7):845-848
Five field strains of infectious bronchitis virus (IBV) were isolated from suspected flocks from different time and different regions of Shanxi province,respectively,and characterized by a series of systematic identification assays,such as morphological observation by electron-microscope,interfering with the propagation of NDV,virus pathological role to chicken embryo,virus pathological role to SPF chickens,hemagglutination activity,physiscochemical,and reverse transcription polymerase chain reaction(RT-PCR).The results showed:The typical coronavirus which the spherical virions 60-120 nm in diameter and surface covered with spike like corona were observed under electron-microscope)The propagation of NDV strain was seriously interfered by the 5 isolates respectively;The embryonated chicken egg passages of the 5 isolates could dwarf with chicken embryos;The five isolates had no hemagglutination activity,but after treatment with 1% trypsin,it can agglutinate chicken red blood cell.The strains are sensitive to chloroform and ethyl ether.The SPF chickens which inoculated with the 5 isolates showed clinical sign and result in respiratory and kidney diseases,flower-steak,and swollen with severe urate deposition.The specific fragments of N gene of the 5 isolates were amplified by RT-PCR,respectiveiy.On the basis of all above mentioned results,the 5 isolates were classified as IBV.The study got a good preparedness for further study on molecular epidemioogy of the 5 IBV isolates.
9.Influence of Alismatis Combined with Bifendateon Cytochrome P450 in Rat
Yue XU ; Libin WANG ; Pei LI ; Yunyun YUAN ; Wenbin LIU
Herald of Medicine 2017;36(11):1249-1252
Objective To research the influence of Alismatis combined with bifendate on cytochrome P 450 in rat liver microsomes. Methods Twenty four healthy male SD rats were randomly divided into four groups:the experimental groups were given Alismatis at 140 mg·kg-1 , bifendateat 2.18 mg·kg-1 , and Alismatis plus bifendate at 140 mg+2.18 mg·kg-1 ,while the blank control group was given 0. 9% sodium chloride at 5 Ml · kg-1 . The liver microsomes were prepared upon differential centrifugation 7 days after administration.The microsomal protein concentration, cytochrome P450 content, Cytb5 content, NADPH cytochrome C reductase activity and amino pyrine N removal of methyl enzyme activity, erythromycin demethylase activity were determined by UV respectively. Results Compared with the normal control group, the combination use of Alismatis and bifendate redued the microsome content and cytochrome P450 content, while it increased the NADPH cytodrome C activity. The concentrations of cytochrome P450 were both increased by Alismatis and bifendate. Conclusion In contrast, combination ofAlismatis and bifendate reduces cytochrome P450 content which has a negative effect on phase I drug metabolism.Moreover, the combination of Alismatis and bifendate induced NADPH- cytochrome C reductase, accelerated the reduction of cytochrome P450 and inhibited cytochrome P450 isoform CYP2E1 activity.
10.Diagnostic value of dynamic monitoring of C-reactive protein in drain drainage to predict early anastomotic leakage after colorectal cancer surgery.
Jia LU ; Lei ZHENG ; Runtian LI ; Chunmin HAO ; Wenbin GAO ; Ziwei FENG ; Guangya YIN ; Yue WANG ;
Chinese Journal of Gastrointestinal Surgery 2017;20(9):1055-1059
OBJECTIVETo evaluate the diagnostic value of dynamic monitoring of C-reactive protein (CRP) in drainage fluid in predicting early anastomotic leakage after colorectal surgery.
METHODSThis study enrolled 172 patients, who were diagnosed as colorectal cancer before operation and underwent radical surgery, without residual tumor tissues by postoperative pathology and perioperative infection, at the Tianjin Medical University Cancer Hospital between July 2015 and January 2016. The C-reactive(CRP) protein level in drainage fluid was continuously monitored from postoperative days (POD) 1 to 5. CRP level was compared between anastomotic leakage (AL) group and non-anastomotic leakage (NAL) group. Receiver operating characteristics (ROC) curve was used to estimate the value of monitoring CRP in drainage fluid to predict anastomotic leakage after colorectal surgery.
RESULTSAmong 172 patients, 101 cases were male and 71 cases were female, with age of (59.9±10.3) years. Anastomotic leakage occurred after colorectal surgery in 24 cases(14.0%, AL group ) and other 148 cases were defined as NAL group. Other than body mass index (BMI), differences in baseline data were not statistically significant between two groups. The CRP lever in AL group and NAL group showed rising trend from POD1 to POD4 [Day 1: (6.7±8.4) g/L vs. (8.0±10.6) g/L; Day 2: (24.8±14.6) g/L vs. (28.3±21.1) g/L, Day 3: (54.8±26.5) g/L vs. (53.8±27.6)g/L, Day 4: (62.0±32.2) g/L vs. (58.4±30.7) g/L], while the differences were not significant (all P>0.05). At POD 5, the CRP lever of AL group increased continuously, while that of NAL group decreased with significant difference [(65.3±38.9) g/L vs. (44.7±39.5) g/L, t=-2.85, P=0.005]. Further stratification analysis on AL group revealed CRP level in early AL (AL occurrence
CONCLUSIONContinuous increase of CRP level in abdominal drainage fluid from POD 1 to POD 5 indicates the occurrence of AL after colorectal cancer operation, especially the detection of CRP level at POD 5 is important.