2.Clinical Progress in the Targeted Therapy for Renal Cell Carcinoma
Yanhui ZHANG ; Xusheng CHEN ; Xin YAO
Chinese Journal of Clinical Oncology 2010;37(5):297-300
Renal cell carcinoma(RCC)is currently one of treatment-resistant malignancies and is not sensitive to conventional radiotherapy or chemotherapy.The effective rate of high dose of recombinant human interleukin-2(IL-2)and recombinant human interferon-α(IFN-α)was only 10%-15%.Advances in the understanding of cancer at molecular level have led to more progress in the development of anti-cancer agents.Recently,mutation of Von Hippel-Lindau(VHL),Ras,PTEN genes have been observed in RCC and the mutation can result in different expression levels of RTK.Among the newly invented medications for targeted cancer therapy,protein kinase inhibitors target intracellular molecules crucial in sighaling pathways of cancer cell survival and proliferation.Compared with conventional chemotherapy and immune therapy,targeted therapy is effective,with fewer adverse effects.According to 2009 NCCN Clinical Practice Guidelines in oncology,this article reviewed the clinical application of sunitinib,sorafenib,temsirolimus,and bevacizumab in the targeted therapy for renal cell carcinoma.
3.Study on the HBV specific CD3~+ T cells in the peripheral blood of chronic hepatitis B patients using Dimer X I A_2:Ig reagent
Jiming ZHANG ; Xin YAO ; Shuhui SUN
Chinese Journal of Infectious Diseases 2001;0(05):-
Objective To study the percentage of HBV specific CD3 + T cells in the peripheral blood of chronic hepatitis B patients. Methods HLA A 2 patients were screened by MHC:Ig dimer reagent. HLA A 2 restricted HBV core, polymerase, and surface peptides were added to T cells of chronic hepatitis B patients, followed by double staining with anti CD3 antibodies and antibodies reactive with the heavy chain of Ig. FACS was used for monitoring HBV specific T cell percentage. Results 23/54 (42.6%) patients belonged to HLA A 2. Fifteen of them were reacted with HBV peptides. CD3 + T cells of five patients showed higher percentage of binding with the HBV peptides than that in the controls. Four patients showed CD3 + T cells binding with S peptide, one with P peptide and one binding with both S and P peptide. Conclusions The percentage of T cells which could bind with HBV peptide was low in chronic hepatitis B and the binding efficiency was low as well. The MHC:Ig dimer reagent is convenient for counting the number of HBV specific T cells, but the nonspecific staining background seems to be relatively high. However, this technology is useful to monitor changes of immune responses in chronic hepatitis B patients during immuno therapy.
4.The Effect of Schisandraceae on SOD and OFR Level of in Female Rats Ovary of Experimental Kidney Yin deficiency
Tao ZHANG ; Ning YAO ; Xin WANG
Chinese Journal of Information on Traditional Chinese Medicine 2006;0(02):-
Objective To approach the medicine-Schisandraceae-protective actions to the mice of experimental Kidney Yin deficiency from different angles. Method To observe the level of SOD and OFR in the female rats ovary tissue in order to prove the medicine’s curative effect. Result Schisandraceae can obviously increase the SOD and decrease the OFR to experimental Kidney Yin deficiency mice. Conclusion Schisandraceae has very obviously protective action to experimental Kidney Yin deficiency by influencing content of SOD and OFR of female mice ovary tissue.
5.The value of contrast-enhanced ultrasound in diagnosis of renal cell carcinoma subtyping
Chunxiang LI ; Xiaojie XIN ; Xin YAO ; Sheng ZHANG ; Yong XU
Chinese Journal of Urology 2015;36(5):329-332
Objective The purpose of this study was to evaluate the value of contrast-enhanced ultrasound in diagnosis of renal cell carcinoma subtyping.Methods 206 cases with renal tumors were confirmed by pathology and surgery from June 2012 to June 2014,including 113 male cases and 93 female cases.The mean age was 54 years (range 23-80 years).The subtype of renal tumor included clear cell carcinoma in 147 cases,papillary cell carcinoma in 32 cases,chromophobe cell carcinoma in 27 cases.All patients were received the CEUS before operation.The enhancement patterns,degree of enhancement,the appearance of necrosis and the time-intensity curve by contrast-enhanced ultrasound were analyzed.Results Enhancement patterns of CEUS were showed by fast in and fast out in 63.9% (94/147)cases with clear cell carcinoma,59.4% (19/32) cases with papillary cell carcinoma,51.9% (14/27) cases with chromophobe cell carcinoma.Statistical significant diference was shown among those subtype groups (P < 0.05).Most of the clear cell carcinomas (127/147,86.4%) showed hyperenhancing.While,the papillary renal cell carcinoma (22/32,68.8%) and chromophobe cell carcinoma (15/27,55.6%) showed hypoenhancing (P < 0.05).The rate of necrosis in clear renal cell carcinoma was 62.6% (92/147),and 59.4% (19/32) in papillary cell carcinoma.necrosis area accounted for only 18.5% (5/27)in chromophobe cell carcinoma (P < 0.05).In the time-intensity curve analysis,the initial time,the average arrival time,the time to peak and area under the curve in renal cortex was (11.06 ± 2.75) s,(23.42 ± 2.79) s,(27.47 ± 3.02) dB,(35.01 ± 2.94)dB,respectively.Significant differences in those items were found in clear cell carcinoma,which was(8.01 ± 1.89) s,(20.05 ± 3.01) s,(30.03 ± 2.98) dB,(37.64 ± 4.01) dB respectively,compared with those in cortex (P < 0.05).The arrival time,time to peak,peak intensity and area under the curve in papillary cell carcinoma were (1 1.12 ± 2.43) s,(27.29 ± 3.54) s,(20.13 ± 2.67) dB,(34.67 ±3.24) dB,respectively.The curve showed the time to peak was higher and the peak intensity were lower than those of renal cortex (P <0.05).The arrival time,time to peak,peak intensity and area under the curve in chromophobe cell carcinoma were (11.32 ± 2.90) s,(22.21 ± 3.62) s,(22.02 ± 2.52) dB,(28.67 ± 3.65) dB,respectively.The curve demonstrated peak intensity and area under the curve were lower than those of surrounding renal cortex (P < 0.05).The increase of tumor diameter after contrast-enhanced ultrasound in clear cell carcinoma was about (0.35 ± 0.11)cm and in nonclear cell carcinoma was about (0.23 ± 0.10) cm (P < 0.05).Conclusion The contrast-enhanced ultrasound played an important role in diagnosis and subtype renal cell carcinoma.
6.Security Experiment of 2-Methoxyestradiol Nanosuspension
Xin JIA ; Chaofeng ZHANG ; Qingqing ZHANG ; Shanshan GAO ; Hanchun YAO
Herald of Medicine 2016;35(9):934-937
Objective To evaluate the preclinical safety of 2-methoxyestradiol nanosuspension. Methods The safety of 2-methoxyestradiol nanosuspension for injection was observed through vascular stimulation test of the ear vein on rabbits, hemolytic test using rabbit erythrocytes, active systemic anaphylaxis (ASA) test on guinea pigs and acute toxicity test on mice. Results 2-Methoxyestradiol nanosuspension injection had no irritating effects on vessels, and no haemocytolysis, agglutination and ASA occurred.ASA test showed no allergy symptoms such as piloerection, nose rubbing and dyspnea in guinea pigs 30 min after sensitization.Acute toxicity test revealed that no pathological changes, including black spots and hyperaemia, were visually observed on the heart, liver and lungs after 14 days of intravenous administration. Conclusion 2-Methoxyestradiol nanosuspension injection is relatively safe, with low toxicity, and no hemolytic, anaphylactic and irritating effects. It may be clinically used for injection.
10.The structure-function relationship analysis of VEGI: Y111 is an important residue in biological activity
Min ZHANG ; Jingjuan YAO ; Xin PAN ; Wei PAN ; Zhongtian QI
Chinese Pharmacological Bulletin 1987;0(03):-
Aim Vascular endothelial cell growth inhibitor(VEGI) is a recently discovered novel member of the TNF superfamily,which is expressed predominantly in endothelial cells.As an endothelial cell-specific negative regulator of angiogenesis,the relationship between structure and function of VEGI is not understood at present.Methods In order to explore the functional key amino acids of VEGI,four mutants of VEGI(E45→R,G47→A,Y111→F,Y111→T) were construced by site-directed mutagenesis,and recombinant proteins were generated from E.coli.Four mutant proteins behaved similar to the wild type VEGI in various physico-chemical assays.The proliferation of HUVEC and chick choriallantic membrane assay were performed to study the activity of four mutants.Results The mutant E45→R significantly decreased the biological activity,and the mutant G47→A caused a slight drop on activity,but the mutants Y111→F,Y111→T almost completely abolished biological activity.Conclusion It suggests that Y111 is an important residue in biological activity,which may play a direct role in receptor recognition.Moreover,the tyrosine ring and hydroxy group of the amino acid are important determinant of biological activity.Additionally,E45 also plays an important role in biological activity of VEGI.