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Journal of Cancer Therapy 2012年第4期3卷 269-277页

作者： Andreas Nechansky Stefan Stranner Oliver Scheiber Nicole Halanek Ralf Kircheis Apeiron Biologics AG Igeneon GmbH Vienna Austria Virologik GmbH Erlangen Germany

Purpose: Detailed analysis of a patient with epithelial Lewis Y (LeY) positive cancer who received twice 50 mg of the humanized Lewis Y carbohydrate specific mAb IGN311 and developed a clinically significant human anti-human antibody (HAHA) response (Ab2). Results: Clinical stabilization of the disease was assigned to in this patient. The HAHA response consisted mainly of IgG1 and was found to be directed against the IGN311 binding site. Consistent with the induction of the HAHA response, CDC activity against Lewis Y positive target cells was completely abolished at day 8 and could not be restored by the second 50 mg infusion indicating complete neutralization of applied IGN311. The ADCC reactivity was also significantly reduced and anti-anti idiotype-specific antibodies (Ab3) were detectable at day 65. Conclusions: Induction of Ab3 antibodies should be considered as an additional factor influencing the efficacy of humanized antibodies. In this context, the potential threat of induced HAHA responses against therapeutic mAbs might have to be reconsidered because they might actually have also beneficial immunological long-term effects leading to an active immunization component induced by therapeutic antibodies.

关键词： Lewis Y Carbohydrate Immunotherapy Immunogenicity anti-Idiotype HAHA (human anti-human antibodies)

1-(4-(Pyrrolidin-1-ylsulfonyl)phenyl) ethanone in Heterocyclic Synthesis: Synthesis, Molecular Docking and anti-human Liver Cancer Evaluation of Novel Sulfonamides Incorporating Thiazole, Imidazo[1,2-a]pyridine, Imidazo[2,1-c] [1,2,4]triazole, Imidazo[2,1-b]thiazole, 1,3,4-Thiadiazine and 1,4-Thiazine Moieties

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International Journal of Organic Chemistry 2015年第3期5卷 166-190页

作者： Mahmoud Sayed Bashandy Chemistry Department Faculty of Science (Boys) Al-Azhar University Nasr City Cairo Egypt

This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]thiazole 23, 24, 33, nicotinonitrile 25, 1,3,4-thiadiazine 27, quinoxaline 30 and 1,4-thiazine 31 moieties, starting with 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1). The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and Ms spectral data. All the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 8, 11, 4, 22, 12a, 33, 35, 27 and 24 with selectivity index (SI) values of 33.21, 30.49, 19.43, 14.82, 10.29, 7.3, 6.87, 6.15 and 4.62, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 4.14. Molecular Operating Environment (MOE) performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some synthesized compounds are suitable inhibitors against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.

关键词： Benzenesulfonamide Pyrrolidine Thiazole anti-human Liver Cancer Molecular Docking

Silver nanoparticle labeled immunoresonance scattering spectral assay for trace fibrinogen

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Science China Chemistry 2007年第3期50卷 345-350页

作者： JIANG ZhiLiang CHEN YuanYuan LIANG AiHui TAO HuiLin TANG NingLi ZHONG FuXin School of Environment and Resource Guangxi Normal UniversityGuilin 541004China Department of Material and Chemical Engineering Guilin University of TechnologyGuilin 541004China

Silver nanoparticles in size of 8.0 nm was prepared by the trisodium citrate and used to label goat anti-human fibrinogen. In the pH 5.8 Na2HPO4-NaH2O4 buffer solution (PBS) and in the presence of polyethylene glycol (PEG) and KCl, the immune reaction between silver-labeled goat anti-human fibrinogen and fibrinogen took place and led the resonance scattering intensity at 465 nm (I465) to decreasing. The I465 decreased intensity was linear to the fibrinogen concentration in the range from 0.067 to 1.67 μg/mL, with a detection limit of 0.024 μg/mL. This method was applied to determination of fibrinogen in human plasma, with satisfactory results.

关键词： silver-nanoparticle fibrinogen goat anti-human immune fibrinogen serum resonance scattering spectral assay

Construction of Luffin A Immunotoxin and Its in vitro Inhibition Against human Melanoma Cell M_(21)

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Chinese Science Bulletin 1994年第11期39卷 950-953页

作者：高闻达张茹平曹蕙婷季瑞华张祖传 Shanghai Institute of Biochemistry Academia Sinica Shanghai 200031 PRC

1 Introduction In recent years, significant progress has been made in applying immunotoxin (IT)in the therapy of leukemia and marrow transplantation. By 1990, several ITs havebeen put into clinical trials under the pe... 详细信息

关键词： Luffin A RIP anti-human melanoma McAb immunotoxin human melanoma cell.

An addition of medium-dose ATG to conditioning regimens favours the long-term survival of patients with allogeneic hematopoietic stem cell transplantation

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Stem Cell Discovery 2013年第1期3卷 22-31页

作者： Bingyi Wu Chaoyan Song Zhigang Lu Kunyuan Guo Yingzhi He Sanfan Tu Shaojuan Pan Can Sun Junyong Fang Department of Haematology Zhujiang Hospital Southern Medical University Guangzhou China

Long-term survival of 116 leukemia/MDS patients received allo-SCT conditioned by a regimen with ATG-F or without ATG-F was analysed, together with the impact of ATG-F on the long-term survival, GVHD and disease relapse. Seventy patients received an ATG-F containing conditioning regimen FBCA, and 46 patients received a non-ATG-F FBC regimen. The FBCA regimen was associated with a 5-year survival of 65.4% in the complete HLA-matched group and 39.3% in the HLA-mismatched group. The difference between the two groups was significant (P = 0.012). For the FBC conditioning regimen, the 5-year overall survival of HLA-matched patients and the HLA-mismatched patients was 34.2% and 24.2% respectively (P = 0.216). The incidence of cGVHD was 32.9% and 83.6% in the FBCA and FBC condition regimen group respectively. Only 2.9% of the cases showed extensive cGVHD in the FBCA group while it was 69.4% in the FBC group (P = 0.00). Multivariate analysis indicated that relapse was related to the disease status and HLA typing, but unrelated to the conditioning regimens whether or not ATG-F was used (HR 0.54, P = 0.109). We conclude that the addition of ATG-F to conditioning regimen favours the longterm survival of allo-SCT.

关键词： Hematopoietic Stem Cell Transplantation Long-Term Survival anti-human Lymphocyte Globulin

Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

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World Journal of Gastroenterology 2015年第39期21卷 11016-11026页

作者： Antonio Cuadrado David San Segundo Marcos López-Hoyos Javier Crespo Emilio Fábrega Gastro- enterology and Hepatology Unit Marqués de Valdecilla University Hospital Instituto de Investigación Marqués de Valdecilla Immunology Unit Marqués de Valdecilla University Hospital. Instituto de Investigación Marqués de Valdecilla

antibody-mediated rejection(AMR) caused by donorspecific anti-human leukocyte antigen antibodies(DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant(LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class Ⅱ human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional antirejection therapy, can allow a rational approach to this threat.

关键词： Donor-specific anti-human leukocyte antigen antibo

Autoimmune hepatitis in human immunodeficiency virus infection: Case report and literature review

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World Journal of Clinical Infectious Diseases 2017年第4期7卷 50-57页

作者： Ivan Nore?a Jairo A Morantes-Caballero Andrés Garcés Brian José Gómez Gabriel Rodríguez Carlos Saavedra William Otero Infectious Diseases Section Department of Internal Medicine Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia Department of Internal Medicine Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia Gastroenterology Section Department of Internal Medicine Universidad Nacional de Colombia and Hospital Universitario Nacional de Colombia

The infection due to human immunodeficiency virus(HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. In this context, autoimmune diseases could be considered contradictory, however, cases of autoimmune diseases during this infection have been described, including autoimmune hepatitis(AIH), which is uncommon and has few case reports within medical literature, none of them from Latin America. In this case report where a patient with an HIV infection on combined antiretroviral treatment developed acute elevation of transaminases, hyperbilirubinemia, and deterioration in hepatic synthetic function. Although initially an antiretroviral drug-induced liver injury was suspected, during the study a diagnosis of autoimmune hepatitis was proven, which required treatment with corticosteroid and azathioprine, obtaining a satisfactory response and managing to continue the antiretroviral therapy. Autoimmune diseases in HIV infection must be taken into account. In the case of hepatitis in patients with HIV on antiretroviral treatment, the differentiation between viral hepatitis caused by autoimmune diseases or medications is essential to establish an adequate treatment, and avoid the suspension of the antiretroviral therapy.

关键词： Autoimmunity Autoimmune hepatitis human immunodeficiency virus anti-human immunodeficiency virus agents Drug-induced liver injury