1.Strategy of antibody-drug conjugates in preclinical safety evaluation
Min HONG ; Xiaoping ZHAO ; Jing MA
Chinese Journal of Pharmacology and Toxicology 2016;(1):7-12
Recently,increasing cancer researches focus on antibody-drug conjugates(ADCs) which can improve the anti-tumor potency with less adverse effect while benefiting patients in the future. However,safety evaluation of ADCs is a big challenge because of complex components as well as in experience in preclinical studies. In this review,the authors reviewed the mode of action,hazard risks,and toxicity observed in preclinical/clinical studies of ADCs,summarized the preclinical studies of Adcetris(brentuximab vedotin)and Kadcyla(ado-trastuzumab emtansine),and suggested a better strategy of ADCs in preclinical safety evaluation.
2.Blocking efficacy of 23 cases of mother to child transmission of acquired immunodeficiency syndrome in the First Hospital of Changsha
Chun LIU ; Min WANG ; Xiaoping LI
Chinese Journal of Infection Control 2017;16(4):355-358
Objective To observe the blocking efficacy of mother to child transmission (MTCT) in pregnant women with positive human immunodeficiency virus(HIV), and explore proper MTCT blocking mode for acquired immunodeficiency syndrome.Methods Clinical data of 23 HIV-positive pregnant women in a hospital from 2005 to 2015 were retrospectively analyzed.Results All 23 HIV-positive pregnant women received highly active antiretroviral therapy (HAART) and comprehensive intervention for blocking MTCT of HIV.Among these women, 12 got pregnant after receiving HAART, 10 were detected positive HIV in early pregnancy (within 28 weeks) and then received HAART, 1 was detected positive HIV 28 weeks after pregnancy and then received HAART.23 HIV-positive pregnant women all delivered normal newborns, follow-up observation of babies found no HIV infection.Conclusion HAART for HIV-positive pregnant women is the key to block MTCT of HIV, combined with preventive medication and artificial feeding of newborns, HAART can effectively prevent MTCT.Mutual blocking mode, such as HAART for HIV-positive pregnant women by specialists, pregnancy check-up, and preventive medicine for infants provided by maternity and child care hospital, is highly efficiency.
3.The research on composite radix sophora flavescentis injection combined with oxaliplatin inhibiting angiogenesis
Min LI ; Xiaoping QIAN ; Baorui LIU
China Oncology 2001;0(03):-
Background and purpose:The growth,metastasis,relapse and the prognosis of tumor are correlated with tumor angiogenesis.Therefore,target to angiogenesis and antiangiogenic therapy has become one of the hot points in cancer research field.Some chemotherapeutic drugs can inhibit the growth of new vascular endothelial cell markedly in the way of low-dose and high time administration.This is metronomic chemotherapy or antiangiogenic chemotherapy.Traditional Chinese medicine has an effect on tumor control.In recent years,we discovered that some traditional Chinese medicine have an antiangiogenic effect.This experiment aimed to study the antiangiogenetic ability of oxaliplatin combined with composite radix sophora flavescentis injection(CRSFI) in vitro and in vivo. Methods :We used MTT method to observe the influence of oxaliplatin and composite radix sophora flavescentis injection on human umbilical vein endothelial cells(HUVEC) or LoVo proliferation.The influence of oxaliplatin and composite radix sophora flavescentis injection on HUVEC migration was evaluated by transwell.Chick embryo chorioallantoic membrane(CAM)model was used to check whether the neovascularization of CAM could be suppressed in vivo by them. Results :The survival rate of LoVo within the same doses of oxaliplatin and composite radix sophora flavescentis injection were higher than HUVEC.Oxaliplatin(2 ?g/ml) and composite radix sophora flavescentis Injection(25 ?l/ml) could inhibit the prolifetation of HUVEC;the rate of inhibition were 31.6%,32.1% respectively;the rate of the two drugs combination was 54.4%.So when combined,they had synergistic effect.There was coordinate repression to migration of HUVEC in vitro when we used oxaliplatin(0.5 ?g/ml) and composite radix sophora flavescentis injection(6.25 ?l/ml).They also suppressed angiogenesis of CAM in vivo. Conclusions :This experiment showed that low dose oxaliplatin combined with composite radix sophora flavescentis injection has anti-angiogenic synergetic ability in vivo and the ability of inhibiting the growth of the cells in vitro.
4.Relationship between carotid stiffness and coronary angiography in elderly patients with coronary heart disease
Xiaoping HUANG ; Min XIAO ; Shaolan XU ; Yuping GUO
Chinese Journal of Geriatrics 2008;27(5):327-329
Objective To investigate the relationship between carotid stiffness and coronary angiography in elderly patients with coronary heart disease(CHD). Methods Thirty-five elderly patients with CHD who underwent coronary angiography were enrolled in the study. The carotid stiffness was measured by ultrasound, the results were compared with those in hypertension group,hyperlipemia group and healthy elderly group. Results There were significant differences in carotid tensity (8.15 ± 1.54), arteriectasis ( 0.34 ± 0.07 ) and carotid stiffness ( 640.51 ± 150.98 ) of elderly patients with CHD compared to other groups (all P<0.05 or P < 0. 01 ). There was significant correlation between coronary angiography score and carotid stiffness in elderly patients of CHD(P<0.05 or P<0.01). Conclusions There is close relationship between carotid atherosclerosis and coronary atherosclerosis in elderly patients with CHD.
5.Introduction of a new model for prediction and evaluationof research capability of high-level scientific research personnels
Yun PENG ; Peng RUAN ; Min ZHANG ; Xiaoping YU
Chinese Journal of Medical Science Research Management 2014;27(2):187-190
High-level researchers,who can efficiently enhance the research strength of the college,are often brought in at high cost.Therefore there is often the need to scientifically evaluate these researchers when introduce them.We here discuss the main indicators for the evaluation of High-level researchers.Taking into consideration of their age,research span,et al.,we propose a model for the quantitative evaluation of research capability based on research achievement and prediction of future achievement,
6.Prognostic value of initial arterial lactate and 6-h lactate clearance rate in acute paraquat poisoning
Min CHEN ; Feng CHEN ; Rijin ZHU ; Xiaoping WANG ; Haiyang SONG
Chinese Journal of Emergency Medicine 2014;23(11):1204-1208
Objective To investigate the correlation of the initial arterial lactate (Lac) and 6-h lactate clearance rate (LCR) with prognosis in patients with acute paraquat poisoning (APP).Methods The included 132 APP patients (70 males and 62 females,age ranging 15-71,30 (18) [M (IQR)]treated at a single center between January 2009 and December 2013.Patients were divided into two groups:group A,survivors > 28 days after admission (n =64); and group B,those died ≤ 28 days after admission (n =68).The prognostic values of arterial Lac and 6-h LCR during the acute stage of poisoning were evaluated.Results Paraquat dose ranged from 5-200 mL,20 mL (37.25 mL) [M (IQR)].The average time from poisoning to arrival at the emergency department was ranging 4-312 h,6 h (8.75h) [M (IQR)].Total mortality was 51.51%.There were no differences in age,gender,and length of time elapsed from poisoning to diagnosis between two groups.Survivors had a significantly lower dose of paraquat ingested compared with nonsurvivors (P < 0.05).An ROC curve analysis determined that the dose had an area of 0.86 (95% CI:0.80-0.92) and the volume cut-off point was 27.5 mL to predict the prognosis in patients with acute paraquat poisoning (75% sensitivity,85.9% specificity,Youden index 0.609).The initial arterial lactate level was higher in nonsurvivors than that in survivors.The ROC curve analysis indicated that the initial arterial lactate level had an area of 0.99 (95% CI:0.99-1.00) and the concentration cut-off point was 5.050 mmoL/L to predicti prognosis in patients with acute paraquat poisoning (sensitivity 98.5%,specificity 100%,Youden index 0.985).The 6 h LCR was lower in nonsurvivors than that in survivors.ROC curve analysis showed that the 6-h LCR had an area of 0.99 (95 % CI:0.97-1.00) and the concentration cut-off point was 17.28% to predict prognosis in APP patients (sensitivity 100%,specificity 97.1%,Youden index 0.971).Conclusions In the early stages of APP,initial arterial Lac and 6-h LCR are closely related to prognosis and may serve as prognostic factors.
7.In vitro anti-tumor effect of autologous mixed lymphocyte primed by BCG activated dendritic cells based PANC1 lysate
Dehong YANG ; Wenjia LIU ; Min CHEN ; Yumei WU ; Xiaoping ZOU
Chinese Journal of Pancreatology 2010;10(4):267-271
Objective To evaluate in vitro anti tumor effect of host lymphocyte primed by CalmetteGuerin bacillus (CGB) activated dendritic cells (DC) based PANC1 lysate. Methods DCs were obtained from peripheral blood mononuclear cells of healthy volunteer and cuitured by rhGM CSF and rhIL 4. DC vaccines for pancreatic cancer were loaded with PANC1 tumor lysate (TL) and were further maturated by CGB.CD1a, CD83, CD86 and HLA-DR phenotype was characterized by flow cytometer, and IL-12p70 and TNF-α concentration in DC culture supernatant were measured by ELISA. Autologous mixed lymphocyte proliferation and the cytotoxicity of cytotoxic T lymphocytes primed by activated DCs to PANC1, PaTu8988 and SCG7901 tumor cells was measured by CCK 8 test. Results When DCs based PANC1 lysate were activated by CGB,the expression rates of CD83 and CD86 were increased from (3.7±0.3)% and (38.6±5.0)% to (16.5±0.6)% and (76.6±2.5)% (P <0.05 ). The concentrations of cytokines ILpl2p70 and TNF-α were increased from (20.18±2.06 ) pg/mland (61.38±1.19) pg/mlto (62.48±3.80) pg/mland (592.53±17.96)pg/ml (P<0. 01 ). When co-cultured with CGB activated DCs based PANC1 lysate in proportion of 0.40)% , (3.39±1.05)% , (2.82±0.39)% significantly increased to (55.38±3.58)% , (75.0±2.54) % , (77.07±3.4)% , (99.07±2.4)% (P<0.01) , respectively. The killing effects of lymphocytes 2.77)%, (19.03±3.04) %; but the killing effects on PaTu8988 and SCG7901 were significantly decreased.Conclusions DC vaccines for pancreatic cancer could be more maturated when activated by CGB, and could show a high capability of anti-tumor in vitro.
8.Evaluation of endothelium function in left anterior descending coronary artery by transesophageal echocardiography in subjects with angiographically normal coronary arteries
Ping FANG ; Zuo HUANG ; Min FAN ; Xiaotao WANG ; Xiaoping NIU ;
Academic Journal of Second Military Medical University 1999;0(12):-
Objective: To establish a mini invasive way to evaluate endothelium function. Methods: Group 1 consisted of 10 subjects with no risk factors for coronary artery disease, group 2 consisted of 11 subjects with risk factors for coronary artery disease and angiographically normal coronary arteries. Two groups of patients underwent transesophageal echocardiography(TEE) for assessment of LAD diastolic blood flow velocity (V) and time velocity integral (VTI) at rest (B 1), 2 min after immersion of the hand in cold water (CPT), 5 min after rewarming of the extremity (B 2), and 5 min after administered nitroglycerin. The percent change in V and VTI were calculated between B 1 and CTP and B 2 and nitroglycerin. Results: After CPT the percent increase in V and VTI were significant in group 1 than group 2 ( P
9.Research progress of effect and mechanism of protein arginine methyltransferase in tumors
Jun WEN ; Xuejie MIN ; Li ZHAO ; Xiaoping ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(6):842-846
Protein arginine methyltransferase (PRMT) can methylate a variety of proteins,including histones and non-histones,affecting a variety of cellular processes such as transcription,RNA splicing,DNA repair,and cell cycle control.The activity of PRMT is affected by a variety of regulatory mechanisms,and its abnormal expression plays an important role in the development of the diseases,especially in tumors such as breast cancer and leukemia.PRMT has a unique value in the diagnosis or treatment of tumors.With the further exploration of PRMT methylation mechanism,PRMT selective inhibitors have made some progress.PRMT-specific inhibitors are expected to be targeted drugs for the treatment of tumors.
10.Clinical Observation of Acupoint Thread-embedding for Premature Ovarian Failure
Min CHEN ; Lihua CHEN ; Xiaoping TIAN ; Xingliang CHEN
Shanghai Journal of Acupuncture and Moxibustion 2017;36(6):697-701
Objective To observe the clinical efficacy of acupoint thread-embedding in treating premature ovarian failure.Method By following the visiting or admission sequence, 35 patients were randomized into a treatment group (acupoint thread-embedding group) and a control group (Western medication group). The therapeutic efficacy, and the levels of follicle stimulation hormone (FSH), luteinizing hormone (LH) and estradiol (E2) before and after the treatment were observed.Result After the treatment, the recovery rate and total effective rate were respectively 44.4% and 72.2% in the treatment group, significantly different from 0.0% and 52.9% in the control group (P<0.05). The level of serum E2increased significantly in both groups after the treatment (P<0.01); the serum FSH dropped significantly in both groups with a more significant efficacy in the treatment group, and the change after the treatment was extremely statistically significant in the treatment group (P<0.01) and the change after the treatment in the control group was statistically significant (P<0.05); after the treatment, the serum LH presented a tendency to decline but without a statistical significance (P>0.05).Conclusion Acupoint thread-embedding can produce a satisfactory efficacy in treating premature ovarian failure.