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1The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells显示文摘AIM The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722×10-9M (Bmax=12810 sites per cell) and 8.931× 10-SM (Bmax=l19700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.MENG SEN LI, PING FENG LI, FBI YI YANG, SHI PENG HE, Guo GUANG DU, GANG LI1 Department of Biochemistry and Molecular Biology, 2 Department of Biophysics, Health Science Center, Peking University, Beijing 100083, China 2002Cell Research2002,12,2:27
2Preparation and activity of conjugate of monoclonal antibody HAb18 against hepatoma F( ab′ )_2 fragment and staphylococcal enterotoxin A显示文摘AIM To prepare the conjugate of staphylococcal enterotoxin A (SEA) protein which is a bacterial SAg and the F(ab')2 fragment of mAb HAbl8 against human hepatocellular carcinoma (HCC), and identify its activity in order to use SAg in the targeting therapy of HCC.METHODS MAb HAbl8 was extracted from the abdominal dropsy of Balb/ c mice, and was purified through chromatography column SP-40HR with Fast protein liquid chromatography (FPLC) system. The F(ab')2 fragment of mAb HAb18 was prepared by papainic digestion method. The conjugate of mAb HAb18 F(ab')2fragment and SEA was prepared with chemical conjugating reagent N-succinimidyl-3-( 2-pyridyldithio) propionate (SPDP) and purified through chromatography column Superose 12with FPLC system. The molecular mass and purity of each collected peak were identified with SDS-PAGE assay. The protein content was assayed by Lowry's method. The antibody activity of HAb18 F (ab')2 against HCC in the conjugate was identified by indirect immunocytochemical ABC method, and the activity of SEA in the conjugate to activate peripheral blood mononuclear cells (PBMC) was identified with MTT assay.RESULTS The lgG mAb HAb18 was extracted,and purified successfully. Immunocytochemical staining demonstrated that it reacted with most of HHCC cells of human HCC cell line. There were two peaks in the process of purification of the prepared HAb18 F(ab)2-SEA conjugate. SDS-PAGE assay demonstrated that the molecular mass of the first peak was about 130 ku, and the second peak was the mixture of about 45 ku and a little 100 ku proteins. The immunocytochemical staining was similar in HAb18 F (ab ')2-SEAconjugate and HAb18 F (ab ')2, i.e., thecytoplasm and/or cell membranes of most HHCC cells were positively stained. The MTT assay showed that the optical absorbance (A) value at 490 nm of HAb18 F (ab')2-SEA conjugate was 0.182 ± 0.012, that of negative control was 0.033± 0.009, and there was significant difference between them ( P < 0.05).CONCLUSION SPDP is a good proteinconjugating reagent and can be used in preparing protein conjugate. The conjugate of mAb HAb18F(ab')2 fragment and SEA protein was preparedsuccessfully in present study and can be used in the experimental study of HCC targeting therapy with the conjugate of SAg and anti-HCC mAbs or their fragments.Lian Jun Yang Yan Fang Sui Zhi Nan Chen Department of Pathology, Fourth Military Medical University. Xi’an 710032, Shaanxi Province, China 2001World Journal of Gastroenterology2001,7,2:20
3Some recent works on diagnosis and treatment of gastric cancer显示文摘PREPARATIONANDUSESOFMONOCLONALANTIBODIESBymeansofcelfusiontechnicweestablishedseveralhybridomacellinescapableofproducingant...ZHANG Xue Yong 1999World Journal of Gastroenterology1999,5,1:18
4Expression of VEGF_(121)in gastric carcinoma MGC803 cell line显示文摘INTRODUCTIONVascular endothelial growth factor(VEGF)whichis also known as vascular permeability factor(VPF)is a heparin-binding,dimeric polypeptide growthfactor and a potent mitogen for endothelial cells.VEGF can stimulate the endothelial cell growth andenhance the motility through its two knownreceptors flt-1 and KDR.Acting through thesereceptors,VEGF may stimulate angiogenesisXue Jun Tian Jian Wu Lin Meng Zhi Wei Dang Cheng Chao Shou Beijing Institute for Cancer Research,Oncology School of Beijing Medical University,Beijing 100034,China Institute of Cancer Research,Chinese Academy of Medical Sciences,Beijing 100021,China 2000World Journal of Gastroenterology2000,6,2:17
5Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor显示文摘According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.Xiangyu Chen Ren Li Zhiwei Pan Chunfang Qian Yang Yang Renrong You Jing Zhao Pinghuang Liu Leiqiong Gao Zhirong Li Qizhao Huang Lifan Xu Jianfang Tang Qin Tian Wei Yao Li Hu Xiaofeng Yan Xinyuan Zhou Yuzhang Wu Kai Deng Zheng Zhang Zhaohui Qian Yaokai Chen Lilin Ye 2020Cellular & Molecular Immunology2020,17,6:17
6A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers显示文摘Advances in molecular research in cancer have brought new therapeutic strategies into clinical usage.One new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) carcinomas.The concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new drugs.Type I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human malignancies.In this review,we focus on this promising therapeutic target,IGF-IR.The IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI cancers.Preclinical studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer treatments.These results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and pancreas.We also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical experiences.Several mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single agents.We summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug combinations.Thus,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcinomas.Yasushi Adachi Hiroyuki Yamamoto Hirokazu Ohashi Takao Endo David P Carbone Kohzoh Imai Yasuhisa Shinomura 2010World Journal of Gastroenterology2010,16,46:14
7A Novel Combination of Immunoreaction and ICP-MS as a Hyphenated Technique for the Determination of Thyroid-stimulating Hormone (TSH) in Human Serum显示文摘The novel coupling method based on the hyphenation of immunoreaction with ICP-MS is developed and applied to the determination of thyroid-stimulating hormone (TSH) in human serum. In this system, TSH is firstly captured by anti-TSH monoclonal antibodies immobilized on a solid support. Biotinylated anti-TSH monoclonal antibodies and Eu3+-labelled streptavidin are then added to form the complex capturing andbody-TSH-biotinylated anti-TSH antibody-Eu3+-labeled streptavidin. After unbound reactants are washed away, Eu3+ bound to the complex is extractedZHANG Chao, WU Feng-bo, ZHANG Yan-yan, WANG Xin, ZHANG Xin-rong(Department of Chemistry, Tsinghua University, 100084 Third Hospital of Peking University, 100083) 2001Annual Report of China Institute of Atomic Energy2001,,0:14
8Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action显示文摘Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.Hiroaki Itamochi 2010World Journal of Biological Chemistry2010,1,7:13
9Direct technetium-99m labeling of anti-hepatoma monoclonal antibody fragment:a radioimmunoconjugate for hepatocellular carcinoma imaging显示文摘AIM To directly radiolabel an anti-hepatomamAb fragment HAb18 F(ab’)2 with 99mTc bystannous-reduced method,and assess thestability,biodistribution and radioimmun-oimaging(RⅡ).METHODS Immunoreactive fraction wasdetermined according to Lindmo’s method.Ellman’s reagent was used to determine thenumber of thiols in the reduced F(ab’)2.Labelingefficiency and homogeneity were measured bypaper chromatography,sodium dodecylsulphatepolyacrylamide gel electrophoresis(SDS-PAGE)and autoradiography.Challenge assay involvedthe incubation of aliquots of labeled antibody inethylenediaminetetraacetate( EDTA )and L-cysteine(L-cys)solutions with different molarratio at 37℃ for 1h,respectively.Investigationsin vivo utilized nude mice bearing humanhepatocellular carcinoma(HHCC)xenograftswith gamma camera imaging and tissuebiodistribution studies at regular intervals.RESULTS The labeling procedure was finishedwithin 1.5 h compared with the'pretinning'method which would take at least 21h.In vitrostudies demonstrated that the radiolabeled mAbfragment was homogeneous and retained itsimmunoreactivity.Challenge studies indicatedthat 99mTc-labeled HAb18 F(ab’)2 in EDTA is morestable than in L-cys.Imaging and biodistribution showed a significant tumor uptake at 24 h post-injection of 99mTc-labeled HAb18 F(ab’)2.Theblood,kidney,liver and tumor uptakes at 24hwere 0.56±0.09,56.45±11.36,1.43±0.27 and6.57±3.01(%ID/g),respectively.CONCLUSION 99mTc-HAb18 F(ab’)2 conjugateprepared by this direct method appears to be aneffective way to detect hepatoma in nude micemodel.Hui Jie Bian Zhi Nan Chen Jing Lan Deng 2000World Journal of Gastroenterology2000,6,3:13
10Role of P-selectin and anti-P-selectin monoclonal antibody in apoptosis during hepatic/renal ischemia-reperfusion injury显示文摘AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.Pei Wu Xiao Li Tong Zhou Ming Jun Zhang Jin Lian Chen Wei Ming Wang Nan Chen De Chang Dong 2000World Journal of Gastroenterology2000,6,2:10
11Preparation of single chain variable fragment of MG_7 mAb by phage display technology显示文摘AIM To develop the single chain variable fragment of MG7 murine anti-human gastric cancer monoclonal antibody using the phage display technology for obtaining a tumor-targeting mediator.METHODS mRNA was isolated from MG7-producing murine hybridoma cell line and converted into cDNA. The variable fragments of heavy and light chain were amplified separately and assembled into ScFv with a specially constructed DNA linker by PCR. The ScFvs DNA was ligated into the phagmid vector pCANTAB5E and the ligated sample was transformed into competent E. Coli TG1. The transformed cells were infected with M13K07 helper phage to form MG7 recombinant phage antibody library. The volume and recombinant rate of the library were evaluated by means of bacterial colony count and restriction analysis. After two rounds of panning with gastric cancer cell line KATOⅢ of highly expressing MG7binding antigen, the phage clones displaying ScFv of the antibody were selected by ELISA from the enriched phage clones. The antigen-binding affinity of the positive clone was detected by competition ELISA. HB2151 E. Coli was transfected with the positive phage clone demonstrated by competition ELISA for production of a soluble form of the MG7 ScFv. ELISA assay was used to detect the antigenbinding affinity of the soluble MG7 ScFv. Finally, the relative molecular mass of soluble MG7 ScFv was measured by SDS-PAGE.RESULTS The VH, VL and ScFv DNAs were about 340bp,320bp and 750bp, respectively. The volume of the library was up to 2 × 106 and 8 of 11 random clones were recombinants. Two phage clones could strongly compete with the original MG7 antibody for binding to the antigen expressed on KATO Ⅲ cells. Within 2 strong positive phage clones, the soluble MG7 ScFv from one clone was found to have the binding activity with KATO Ⅲ cells.SDS-PAGE showed that the relative molecular weight of soluble MG7 ScFv was 32.CONCLUSION The MG7 ScFv was successfully produced by phage antibody technology, which may be useful for broadening the scope of application of the antibody.Zhao-Cai Yu Jie Ding Yong-Zhan Nie Dai-Ming Fan Xue-Yong Zhang Department of Gastroenterology,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,Shaanxi Province,China 2001World Journal of Gastroenterology2001,7,4:9
12^(99m)Tc-labeled HAb18 McAb Fab fragment for radioimmunoimaging in nude mice bearing human hepatocellular carcinoma显示文摘99mTclabeledHAb18McAbFabfragmentforradioimmunoimaginginnudemicebearinghumanhepatocelularcarcinomaQIUKai1,2,WANGBoChen1,CHE...Qiu K Wang BC Chen ZN Fang P Liu CG Wan WX Liu YF 1998World Journal of Gastroenterology1998,4,2:8
13Seeing is believing:anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy显示文摘Structural immunology,focusing on structures of host immune related molecules,enables the immunologists to see what the molecules look like,and more importantly,how they work together.Antibody-based PD-1/PD-L1 blockade therapy has achieved brilliant successes in clinical applications.The recent breakthrough of the complex structures of checkpoint blockade antibodies with their counterparts,pembrolizumab with PD-1 and avelumab with PD-L1,have made it clear how these monoclonal antibodies compete the binding of PD-1/PD-L1 and function to blockade the receptor-ligand interaction.Herein,we summarize the structural findings of these two reports and look into the future for how this information would facilitate the development of more efficient PD-1/PD-L1 targeting antibodies,small molecule drugs,and other protein or non-protein inhibitors.Shuguang Tan Catherine W-H Zhang George F Gao 2016Signal Transduction and Targeted Therapy2016,1,1:8
14Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice显示文摘Objective:Cryoglobulinemia often causes systemic vasculitis,thereby damaging to skin and internal organs including kidneys,even life-threatening.This review aimed to introduce the advances in understanding,detection,and treatment of this disease in recent years,with a particular concern to clinical practice.Data sources:All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.Study selection:This review selected important original articles,meaningful reviews,and some reports on cryoglobulinemia published in recent years and in history,as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.Results:Diagnosis of cryoglobulinemia relies on serum cryoglobulin test,in which to ensure that the blood sample temperature is not less than 37℃ in the entire pre-analysis phase is the key to avoid false negative results.Cryoglobulinemic vasculitis (Cryo Vas),including cryoglobulinemic glomerulonephritis (Cryo GN),usually occurs in types Ⅱ and Ⅲ mixed cryoglobulinemia,and can also be seen in type Ⅰ cryoglobulinemia caused by monoclonal IgG3 or IgG1.Skin purpura,positive serum rheumatoid factor,and decreased serum levels of C4 and C3 are important clues for prompting types Ⅱ and Ⅲ Cryo Vas.Renal biopsy is an important means for diagnosis of Cryo GN,while membranous proliferative GN is the most common pathological type of Cryo GN.In recent years,great advances have been made in the treatment of Cryo Vas and its underlying diseases,and this review has briefly introduced these advances.Conclusions:Laboratory examinations of serum cryoglobulins urgently need standardization.The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.Yi-Pu Chen Hong Cheng Hong-Liang Rui Hong-Rui Dong 2019Chinese Medical Journal2019,,14:8
15Effect of anti-P-selectin monoclonal antibody on renal ischemia/reperfusion injury in rats显示文摘To explore the effect of anti-P-selectin monoclonal antibody (mAb) on renal ischemia/reperfusion (I/R) injury in rats Methods Renal function, renal histopathological changes, plasma P-selectin levels and renal P-selectin protein and mRNA expression were studied in a renal I/R injury rat models Biochemical measurement, ELISA, Immunohistochemistry and Nested RT-PCR were used Results Renal function insufficiency and renal histopathological damage were much less in the anti-P-selectin mAb-treated group than the saline-treated group Plasma P-selectin levels were lower and renal P-selectin protein and mRNA expression were down-regulated in the former group Conclusion Anti-P-selectin mAb might be an efficient approach for the treatment of renal I/R周同 李晓 吴佩 张东华 张明钧 陈楠 董德长 2000Chinese Medical Journal2000,,9:8
16Antitumor effects of the molecule-downsized immunocon-jugate composed of lidamycin and Fab' fragment of monoclonal antibody directed against type IV collagenase显示文摘Type IV collagenase plays an important role in tumor invasion and metastasis through cleaving type IV collagen in the basement membrane and extracellular matrix. In this study a molecule-downsized immunoconjugate (Fab′-LDM) was constructed by linking lidamycin (LDM), a highly potent antitumor antibiotic, to the Fab′ fragment of a monoclonal antibody directed against type IV collagenase and its antitumor effect was investigated. As assayed in 10% SDS-PAGE gel, the molecular weight of Fab′-LDM conjugate was 65 kD with a 1:1 molecular ratio of Fab′ and LDM. The Fab′-LDM conjugate maintained most part of the immunoreactivity of Fab′ fragment to both type IV collagense and mouse hepatoma 22 cells by ELISA. By MTT assay, Fab′-LDM conjugate showed more potent cytotoxicity to hepatoma 22 cells than that of LDM. Administered intravenously, Fab′-LDM conjugate proved to be more effective against the growth of subcutaneously transplanted hepatoma 22 in mice than free LDM in two experiment settings. In Experiment I, the drugs were given intravenously on day 1 and day 8. Fab′-LDM at the doses of 0.025 mg/kg, 0.05 mg/kg and 0.1 mg/kg inhibited tumor growth by 76.7%, 93.3% and 94.8%, while free LDM at 0.05 mg/kg inhibited tumor growth by 76.1%, respectively. In experiment II, the drugs were given intravenously on day 4 and day 11, Fab′-LDM at the doses of 0.025 mg/kg and 0.05 mg/kg inhibited tumor growth by 74.2%, 80.9%, while free LDM at 0.05 mg/kg inhibited tumor growth by 60.5%, respectively. In terms of survival time, Fab′-LDM was more effective than free LDM. The results suggest that the molecule-downsized immunoconjugate directed against type IV collagenase is of high efficacy in experimental cancer therapy.WANG Fengqiang SHANG Boyang ZHEN Yongsu 2004Science China(Life Sciences)2004,47,1:7
17Matrix Interference in Serum Total Thyroxin (T_4) Time-resolved Fluorescence Immunoassay (TRFIA) and Its Elimination With the Use of Streptavidin-biotin Separation Technique显示文摘In development of serum total thyroxin TRFIA using the surface second-antibody (S-Ab) as separation agent, a significant bias of measurement caused by matrix interference when the surface S-Ab shows a relatively low binding capacity for primary anti-T4 monoclonal antibody (McAb) is studied. The bias ranges from 10% to 78%, depending on the matrix of individual samples and the binding capacity of the surface S-Ab prepared. So, a new separation system based on the use of a highly active surface streptavidin and biotinylated anti-T4 McAb is employed. The resultsWU Feng-bo, HE You-feng, HAN Shi-quan 2001Annual Report of China Institute of Atomic Energy2001,,0:7
18Interleukin-17 plays a critical role in the acute rejection of intestinal transplantation显示文摘AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.Jian-Jun Yang Fan Feng Liu Hong Li Sun Meng-Bin Li Ran Zhuang Feng Pan Ying-Mei Wang Wei-Zhong Wang Guo-Sheng Wu Hong-Wei Zhang 2013World Journal of Gastroenterology2013,19,5:7
19Current applications and future prospects of nanotechnology in cancer immunotherapy显示文摘Cancer immunotherapy is an artificial stimulation of the immune system to recognize cancer cells and activate specific immune cells to target and attack cancer cells.In clinical trials, immunotherapy has recently shown impressive results in the treatment of multiple cancers.Thus, cancer immunotherapy has gained a lot of attention for its unique advantages and promising future.With extensive research on cancer immunotherapy, its safety and effectiveness has gradually been revealed.However, it is still a huge challenge to expand and drive this therapy while maintaining low toxicity, high specificity, and long-lasting efficacy.As a unique technology, nanotechnology has been applied in many fields, the advantages of which will promote the development of cancer immunotherapies.Researchers have tried to apply nanomaterials to cancer immunotherapy due to their advantageous properties,such as large specific surface areas, effective drug delivery, and controlled surface chemistry, to improve treatment efficacy.Here,we briefly introduce the current applications of nanomaterials in cancer immunotherapy, including adoptive cell therapy(ACT),therapeutic cancer vaccines, and monoclonal antibodies, and throw light on future directions of nanotechnology-based cancer immunotherapy.Sen Yan Peng Zhao Tingting Yu Ning Gu 2019Cancer Biology & Medicine2019,16,3:6
20Appearance of an inhibitory cell nuclear antigen in rat and human serum during variable degrees of hepatic regenerative activity显示文摘METHODSInanimalstudies,adultmaleSpragueDawleyrats(n=3-4/group)weresacrificedat0,12,24,36,48,72and96hoursfollowing70%partia...N Assy 1,2 ,YW Gong 3,M Zhang 3 and GY Minuk 3,4 1999World Journal of Gastroenterology1999,5,2:6
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