1.Opportunities and challenges in gene therapy of liver cancer
Cheng QIAN ; Junjie SHEN ; Juanjuan SHAN
Chinese Journal of Digestive Surgery 2010;9(1):12-14
Gene therapy has emerged as an efficient modality to treat human diseases.This method is based on the transfer of genetic material to tissues to induce a curative effect.Gene therapy vectors are molecular constructs used to facilitate the penetration of genomic sequences inside the cells.Viral vectots have however several limitations when administered directly to the patient.They may cause significant toxicity by activating innate immunity or by eliciting an adaptive immune response against viral proteins.In addition,targeting the vector to the desired site is an issue when given systemically.The use of cells as vehicles for gene therapy vectors has many advantages.The combination of cell-viro-gene therapy has been thought as a new and promising strategy for therapy of cancer.The targeting vector to cancer stem cells will become a new direction in the field of gene therapy.In this article,we will introduce progressions,limitations and future directions of gene therapy of liver cancer.
2.Progress in mechanisms of damage induced by hyperkinesis and intervention effect of naturaI poIysaccharides
Feng GU ; Yuxia WANG ; Hao MA ; Hua GUO ; Junjie SHAN
Chinese Journal of Pharmacology and Toxicology 2014;(5):788-793
Physical training induces beneficial adaptations,but long excessive exercise may lead to severe damage to the skeletal muscles,liver,heart,kidneys and immune functions. Over the past few decades,health scholars have been searching for natural components that can prevent or improve the damage induced by hyperkinesis. The mechanisms of organ damage induced by long overtraining include immunosuppression,metabolism disorder,hormone disturbance,oxidative damage, etc. Natural poly-saccharides have interventional effects on these injuries,possibly by improving immunity,regulating metabolism and ameliorating free radical damage.
4.Physicochemical properties of a polysaccharide RAP-B-1 from Rubus amabilis and its immunomodulating effects
Yulin DIAO ; Hao MA ; Jinwei REN ; Guiqiang ZHANG ; Shuai LI ; Junjie SHAN ; Bin LIU
Journal of International Pharmaceutical Research 2014;(4):461-467
Objective To investigate the physicochemica l properties and immunobiological activity of a polysaccharide (RAP-B-1) from stems of Rubus amabilis. Methods The crude polysaccharide (RAP) was obtained successively by boiling, ethanol precipitating and dialyzing. RAP was isolated with DEAE-cellulose and Sephadex G-100 to obtain a polysaccharide RAP-B-1. The physicochemical properties of RAP-B-1 were studied by hydrolysis, periodate oxidation, Smith degradation and methylation, CE, IR, NMR and GC-MS. The immunobiological activities were estimated by the proliferative activity of spleen lymphocytes and phagocytic activity of peritoneal macrophages in mice. Results The molecular weight of RAP-B-1 was 4.80×104 with specific optical rotation value [α] 20D+68.3 (c=1,H2O), and was composed of eight monosaccharides. The molar ratios were as Xyl: Ara: Glc: Rha:Gal: Man: GlcA: GalA = 1.0:6.9:0.8:1.1:6.9:0.3:0.5:3.3. RAP-B-1 was an arabinogalactan. The linkages of arabinose were →1) Ara (2,3→,→1) Ara(5→and→1) Ara, and the linkages of galactose were→1) Gal(4→,→1) Gal(6→and→1) Gal. RAP-B-1 could improve the proliferative activity of spleen T cells(P<0.05) and booste phagocytic activity of peritoneal macrophages at 50μg/ml concentration(P<0.01). Conclusion RAP-B-1 is an arabinogalactan and has immunobiological activity.
5.Extended adjuvant temozolomide for treatment of glioblastoma multiforme:experience of a single institu- tion
Changguo SHAN ; Mingyao LAI ; Weiping HONG ; Junjie ZHEN ; Qingjun HU ; Xuebing LING ; Linbo CAI
The Journal of Practical Medicine 2017;33(16):2743-2746
Objective To assess the impact of additional cycles of temozolomide on the survival of glio-blastoma(GBM)patients after 6 months of maintenance temozolomide(TMZ)following concurrent TMZ chemo-therapy and radiation therapy. Methods Data of 51 GBM patients from 2009 to 2015 were retrospectively studied and the therapeutic effect was assessed according to whether receiving long-term treatment with TMZ. Results Sev-enteen of fifty-one GBM patients received 8 or more cycles and prolonged treatment improved progression-free sur-vival(P=0.011)and overall survival(P=0.004). Conclusions Extended use of TMZ is safe to GBM patients , which may improve response OS and PFS compared to conventional regimen. Prospective studies in larger popula-tions are needed to better-define the population to whom it can be proposed and its optimal duration.
6.Evaluation and prediction by using tissue Doppler imaging on patients with left ventricular dilation and dysfunction secondary to organic mitral regurgitation
Juan ZHANG ; Zhongsheng ZHU ; Junjie ZHANG ; Shoujie SHAN ; Zhizhong LIU ; Yuling MA ; Shaoliang CHEN
Medical Journal of Chinese People's Liberation Army 1981;0(06):-
Grade Ⅲ),preserved LV ejection fraction(EF%≥55%) were involved in present study.TDI and echocardiograms were performed at baseline and during the follow-up period(the time interval between the examinations was 650?362 days).These patients were divided into 2 groups according to the interval LV end-systolic volume(LVESV) with or without 20% increment.Results Corrected by body-surface area,the biplane LVESV,LV end-diastolic volume(LVEDV) and left atrial volume(LAV) increased significantly compared with that of baseline(20?6ml/m2 vs.17?5ml/m2;55?13ml/m2 vs.49?12ml/m2 and 42?11ml/m2 vs.36?14ml/m2,respectively,P
7.Effects of carvedilol at different doses on cardiac myocyte apoptosis and apoptosis-associated gene in rats with pressure overload
Daping YE ; Shoujie SHAN ; Shaoliang CHEN ; Kai ZHOU ; Fe YE ; Junjie ZHAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2004;0(07):-
AIM: To study the effects and mechanism of carvedilol (CAR) at different doses on cardiac myocyte apoptosis in rats with myocardial hypertrophy of CHF. METHODS: Using the animal model of CHF, induced by abdominal aortic constriction in male Wistar rats, hemodyanmics parameters, cardiac myocyte apoptosis, and the expression of Bcl-2 and P53 were investigated in the untreated experimental group (CHF group) at 1 week after operation and treated experimental groups in which rats were treated with CAR at a lower dose (LCAR group, 0.1 mg?kg -1?d -1) and at a higher dose (HCAR group, 10 mg?kg -1?d -1) for 7 weeks since 1 week after operation. The sham-operated rats were as controls (SH group, n=8). RESULTS: Either doses improved heart function and decreased apoptosis index in rats with CHF. The number of myocytes apoptosis and the level of Bcl-2 were significantly higher and P53 was markedly lower in HCAR group than those in LCAR and MCAR groups. CONCLUSION: CAR can effectively decrease myocardiocyte apoptosis, prevent and cure CHF. The effects are dose-dependent, associated with changes of the expression of apoptosis-associated gene.
8.Adjuvant effect of fructooligosaccharide from Achyranthes bidentata on H1N1 influenza vaccine and immunocyte function
Yanyan WANG ; Haixia LI ; Yajun WU ; Xiunan ZHAO ; Hao MA ; Kunlu LIU ; Junhua WU ; Junjie SHAN ; Yuxia WANG ; Hainan WANG
Chinese Journal of Pharmacology and Toxicology 2016;(2):113-121
OBJECTIVE To investigate chemical properties of a fructooligosaccharide (ABP-50-FOS)separated from Achyranthes bidentata and immune response in mice immunized H1N1 influenza vaccine. METHODS The methods of GPC,CE,IR and NMR were used to study chemical properties of ABP-50-FOS. BALB/c mice were immunized intramuscularly twice with H1N1 influenza vaccine (3 μg)plus ABP-50-FOS(200 μg)each mouse. The serum total antibody titer and its isotypes titers were analyzed by ELISA. The populations of CD4+,CD8+,CD3+and CD19+lymphocytes were deter?mined by flow cytometry. The proliferation activities of spleen T and B lymphocytes were determined with MTT method. The levels of cytokines interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),inter?leukin-4(IL-4),IL-12 and NO were measured by ELISA kits. RESULTS ABP-50-FOS was a fructooli?gosaccharide with moleculer mass 1885 u. Its bone linkages contained 1,2-and 1,6-fructose residues. ABP-50-FOS could induce high specific-IgG,IgG1,IgG2a,IgG2b and IgM titers after immunization with H1N1 influenza antigen twice(P<0.01). ABP-50-FOS significantly elevated the percentage of CD3+,CD4+ and CD8+ spleen lymphocytes and IFN-γ secretions(P<0.01)in vitro. It also stimulated peritoneal macrophage of mice and DC2.4 dendritic cells to produce TNF-αand IL-12p70 respectively (P<0.01). However,ABP-50-FOS inhibited secretions of NO in macrophage. CONCLUSION The fruc?tooligosaccharide ABP-50-FOS separated from A. bidentata can exhibit strong adjuvant activity for H1N1 influenza vaccine.
9.Immunogenicity of Poria cocos polysaccharides PCP-Ⅰand PCP-Ⅱas vaccine adjuvants
Haixia LI ; Kunlu LIU ; Wenfei LI ; Peiyuan JIA ; Weili YU ; Junhua WU ; Tao HU ; Yuxia WANG ; Junjie SHAN ; Guohui SUN
Chinese Journal of Pharmacology and Toxicology 2017;31(3):255-261
OBJECTIVE To investigate the immunogenicities of Poria cocos polysaccharides, PCP-Ⅰand PCP-Ⅱ, as a vaccine adjuvant. METHODS ①Keyhole limpet hemocyanin (KLH) was linked to PCP-Ⅰor PCP-Ⅱrespectively to prepare immuno-antigen KLH-PCP-Ⅰor KLH-PCP-Ⅱ. Bovine serum albumin (BSA) was also linked to PCP-Ⅰor PCP-Ⅱrespectively to prepare screening-antigen. Rabbits were immunized with KLH-PCP-Ⅰor KLH-PCP-Ⅱplus Freund adjuvant by intradermal injection twice, and serum specific antibody titers were determined by ELISA. ②BALB/c mice were immunized with PCP-Ⅰ or PCP-Ⅱ alone intramuscularly twice, and serum polysaccharide antibody titers were determined by ELISA.③BALB/c mice were co-immunized intramuscularly or subcutaneously with PCP-Ⅰor PCP-Ⅱplus hepatitis B surface antigen (HBsAg) or porcine reproductive and respiratory syndrome virus inactivated vaccine (PRRSV) twice, and serum polysaccharide-antibody titers were determined by ELISA. RESULTS ①Serum anti-KLH and anti-polysaccharides (PCP-Ⅰor PCP-Ⅱ) antibodies were pro?duced after rabbits were immunized with KLH-PCP-Ⅰor KLH-PCP-Ⅱplus Freund adjuvant twice.②Serum anti-PCP-Ⅰor anti-PCP-Ⅱantibodies were not found after mice were immunized with PCP-Ⅰand PCP-Ⅱalone twice.③After mice were immunized with HBsAg or PRRSV plus PCP-Ⅰor PCP-Ⅱtwice, serum anti-PCP-Ⅰor anti-PCP-Ⅱantibodies were not found. CONCLUSION PCP-Ⅰand PCP-Ⅱshow weak immunogenicity, which may be quite safe as a vaccine adjuvant.
10.Effect of α-glycan isolated from Isatis indigotica on humoral and cellular immunities in mice immunized with H1N1 influenza vaccine
Song WEN ; Qian LL ; Peiyuan JLA ; Xiunan ZHAO ; Junhua WU ; Hao MA ; Yongping ZHANG ; Yuxia WANG ; Junjie SHAN ; Hainan WANG
Chinese Journal of Pharmacology and Toxicology 2014;(6):850-856
OBJECTlVE To investigate the effect of α-glycan isolated from Isatis indigotica on humoral immunity and cellular immunity functions in mice immunized with H1N1 influenza vaccine. METHODS BALB/c mice were immunized intramuscularly once with H1N1 influenza vaccine ( 3 μg) plusα-glycan ( 100μg) each mouse. The serum total antibody titer and its isotype antibody titer of immu-nized mice were analyzed by ELlSA at 5, 8, 10, 12 and 14 d after injection at vaccine. The proliferation activities of spleen T and B lymphocytes were determined with MTT method. The levels of cytokines interferon-γ( lFN-γ) , tumor necrosis factorα( TNF-α) , interleukin-4( lL-4) and lL-12 were measured by ELlSA kits. The populations of CD4+, CD8+, CD3+ and CD19+ lymphocytes were determined by flow cytometry. Furthermore, the proliferation rate of macrophages was studied with MTT method in vitro. RESULTS The α-glycan from I.indigotica could gradually induce high specific-antibody production 5-14 d after immunization with H1N1 influenza antigen plus theα-glycan in mice compared to immunization with antigen alone ( P<0.01) . After injection of antigen withα-glycan for 5 d, the main lgG isotype was lgM, and the titer levels of total lgG, lgG1 , lgG2a and lgG2b were also significantly raised following 5-14 d after immunization. The α-glycan significantly promoted the spleen T and B lymphocytes proliferation ( growth rate 44.2%and 37.8%) , stimulated the secretion of lFN-γand lL-12 of splenocytes ( P<0.01, P<0.05) , and also promoted lL-4 secretion of thymocytes (P<0.01). The polysaccharide significantly raised the percent age of CD3+T cells ( P<0.01) , CD3+/CD19+ T lymphocytes ( P<0.01) , and CD8+ T cells ( P<0.01) but decreased the percentage of CD4+/CD8+ T lymphocytes compared with antigen alone group ( P<0.01) . Furthermore, the α-glycan exhibited significant effects on the proliferation and TNF-α secre-tion of MH-S macrophages. CONCLUSlON Theα-glycan isolated from I.indigotica can improve humoral and cellular immunity response in mice immunized with H1N1 influenza vaccine.