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Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody

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World Journal of Gastroenterology 2018年第48期24卷 5491-5504页

作者： Winn Aung Atsushi B Tsuji Aya Sugyo Hiroki Takashima Masahiro Yasunaga Yasuhiro Matsumura Tatsuya Higashi Department of Molecular Imaging and Theranostics National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and Technology (QST-NIRS) Division of Developmental Therapeutics Exploratory Oncology Research and Clinical Trial CenterNational Cancer Center

AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.3

关键词： Pancreatic cancer Anti-tissue factor antibody Indocyanine green Photoimmunotherapy Near-infrared

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High prevalence of hepatitis B-antibody loss and a case report of de novo hepatitis B virus infection in a child after living-donor liver transplantation

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World Journal of Gastroenterology 2018年第6期24卷 752-762页

作者： Palittiya Sintusek Nawarat Posuwan Piyaporn Wanawongsawad Suttiruk Jitraruch Yong Poovorawan Voranush Chongsrisawat Division of Gastroenterology and Hepatology Department of Pediatrics Faculty of Medicine Chulalongkorn University Center of Excellence in Clinical Virology Chulalongkorn University Excellence Center of Organ Transplantation King Chulalongkorn Memorial Hospital

AIM To assess the seroprevalence of hepatitis B virus(HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation.METHODS This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss. RESULTS In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of nonimmunity(anti-HBs three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs(P = 0.002), serum albumin(P = 0.04), total bilirubin(P = 0.001) and direct bilirubin(P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBs Ag, HBe Ag, and anti-HBc(2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL.CONCLUSION The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, desp

关键词： Hepatitis B vaccine Liver transplantation De novo hepatitis B infection Anti-HBs antibody Immunity

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Hybridization to an Anti-activated Platelet Monoclonal antibody Enhances Fibrinolytic Potency on Urokinase

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Science China Chemistry 1993年第12期36卷 1483-1489页

作者：杜鸰余瑞荣华子春朱德煦吴国新阮长耿 Department of Biochemistry and State Key Laboratory of Biopharmaceutical Technology Nanjing University Nanjing 210008 PRC Thrombosis and Hemostasis Research Unit Suzhou Medical College Suzhou 215007 PRC

The B-chain of urokinase (UK) was covalently linked by disulfide bond to the Fab fragment of an anti-human activated platelet monoclonal antibody(SZ-51). The UKSZ-51 conjugate retained the original binding specificity of its parent antibody, and produced about a 5-fold enhancement in clot lysis in plasma over that of the urokinase in vitro. Whereas UK significantly decreased the concentration of fibrinogen in plasma clot assay supernatants, UK-SZ-51 did not.

关键词： α-granular membrane protein monoclonal antibody urokinase.

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INTERACTION OF ANTIGEN AND antibody ON CORE-SHELL POLYMERIC MICROSPHERES

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Chinese Journal of Polymer Science 2011年第2期29卷 267-273页

作者：李湛勇朱晓夏 Key Laboratory of Functional Polymer Materials Institute of Polymer ChemistryNankai University Departement de Chimie Universite de MontrealC.P.6128Succ.Centre-villeMontrealQCH3C 3J7Canada

Monodispersed microspheres with polystyrene as the core and poly（acrylamide-co-N-acryloxysuccinirnide） as the shell were synthesized by a two-step surfactant-free emulsion copolymerization.The core-shell morphology of the microspheres was shown by scanning electron microscopy and transmission electron microscopy.Rabbit immunoglobulin G （as antigen） was covalently coupled onto the microspheres by the reaction between succinimide-activated ester groups on the shell of the microspheres and amino groups of the antigen molecules.The size of particles was characterized by dynamic light scattering technique and was found to vary upon bioconjugation and interaction with proteins.The binding process was shown to be specific to goat anti-rabbit immunoglobulin G（as antibody） and reversible upon the addition of free antigen into the system.

关键词： Surfactant-free emulsion polymerization Core-shell particles Antigen antibody Bioconjugation

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Helicobacter pylori infection in subjects negative for high titer serum antibody

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World Journal of Gastroenterology 2018年第13期24卷 1419-1428页

作者： Osamu Toyoshima Toshihiro Nishizawa Masahide Arita Yosuke Kataoka Kosuke Sakitani Shuntaro Yoshida Hiroharu Yamashita Keisuke Hata Hidenobu Watanabe Hidekazu Suzuki Department of Gastroenterology Toyoshima Endoscopy Clinic Department of Pathology Pathology and Cytology Laboratory Japan Medical Education Center Keio University School of Medicine

AIM To investigate the clinicopathological features of the patients testing negative for high titer serum antiHelicobacter pylori(H. pylori) antibody.METHODS The antibody titers were measured using antigens derived from Japanese individuals. ^(13)C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and redness.RESULTS Of the 136 subjects enrolled, 23(17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve(0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10^(-20)) for predicting H. pylori infection with a cutoff value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies(89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate analysis.CONCLUSION Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients.

关键词： Kyoto classification Gastritis Helicobacter pylori antibody Endoscopy

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Strategies for Precise Engineering and Conjugation of antibody Targeted-nanoparticles for Cancer Therapy

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Current Medical Science 2020年第3期40卷 463-473页

作者： Yuan-yuan GUO Lu HUANG Zhi-ping ZHANG De-hao FU Department of Pharmacy Liyuan HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430077China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Improvements in the diagnosis and treatment of cancer are urgently needed for use in nanotechnology.Nanoparticles(NPs)can reduce the side effects of traditional chemotherapy by sustained release of loaded drugs and increase therapeutic efficiency.NPs can also enhance endothelial permeation retention by size effect and its accumulation in tumor cells through passive targeting.Furthermore,it is critical to treat cancer with a controlled targeted drug which can be specifically delivered into tumor cells and released there,resulting in a targeted therapy to eradicate tumor cells while sparing normal cells.To this end,antibody-mediated targeting therapy has been developed,but imperfections in antibodies(Abs)limit this therapy.Therefore,the combination of NPs and Abs has been highly valued in recent years,because conjugating special Abs on the surface of NPs can increase targeting efficiency,enabling selective delivery of anti-cancer drugs to tumor cells.In this mini-review,we would like to enumerate the strategies for the conjugation of Abs to the surface of the NPs as well as the precise engineering of targeted NPs.The application of targeting antibody fragments in this drug delivery system will also be discussed.

关键词： cancer drug delivery nanoparticle antibody conjugation

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Synthesis and evaluation of monoclonal antibody against Plasmodium falciparum merozoite surface antigen 2

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Asian Pacific Journal of Tropical Medicine 2013年第10期6卷 798-803页

作者： Afra Khosravi Eghbaleh Asadollahy Sobhan Ghafourian Nourkhoda Sadeghifard Reza Mohebi Immunology Department Faculty of MedicineIlam University of Medical Sciences Food and Drug Department Food and Drug DeputyIlam University of Medical Sciences Clinical Microbiology research Centre Ilam University of Medical Sciences

Objective:To assess the quality of expressed MSP-2 and also to confirm the immune response against different domains of these proteins.Methods:Mice were immunized with a schizont extract to stimulate the immune system to make antibodies against different antigens of the late stage parasite including production of antibodies against different domains of Plasmodium falciparum(P.falciparum)MSP-2.B lymphocytes of immunized mice were extracted from the spleen and the fusion was performed using NS-1 myeloma cells and the hybridoma cells were assayed by ELISA either with a schizont extract or different domains of MSP-2 and/or by IFAT with whole schizont preparation.Fusion of NS-1 and spleen cells was performed.The positive hybrids were cloned and ELISA was applied against different dilutions.The positive clones were transferred to a small tissue culture flask and after developing they were assayed against schizont extract and the different MSP-2 domains.The positive clones were expanded to large(75 cm^2)flask and cultured under the same conditions,checking them using both ELISA and IFAT and the positive cells were frozen as soon as possible.Results:A total number of 7 fusions including 26 plates(2496 wells)were performed,of which 1336 hybrids were produced and the overall efficiency(1336/24%×100)was about 53%.ELISA was performed to detect the positive hybrids against crude schizont extract by which the highest frequency to crude schizont extract was found for the supernatant of the hybrids produced in fusion number 3(66 out of 315 hybrids).The supernatant of both B5 and Ft hybridoma cells were more positive against domain 2 of the MSP-2 recombinant protein in Western blotting test.Western blotting results also showed that different domains of the MSP-2 recombinant protein and also the MSP-2 of the P.falciparum parasite were recognized by some of the positive clones and also immune sera.Conclusions:Bringing together all the results of this study it has been confirmed that some clones have recognized both schizont extract

关键词： MSP-2 Monoclonal antibody Malaria Diagnosis

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Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China

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World Journal of Gastroenterology 2018年第48期24卷 5525-5536页

作者： Ming Lei Lu-Nan Yan Jia-Yin Yang Tian-Fu Wen Bo Li Wen-Tao Wang Hong Wu Ming-Qing Xu Zhe-Yu Chen Yong-Gang Wei Department of Liver Surgery Liver Transplantation CenterWest China Hospital of Sichuan University

BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive(HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of China's Mainland. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal.AIM To evaluate the safety of using hepatitis B virus(HBV) core antibody-positive donors for liver transplantation in Chinese patients.METHODS We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study.RESULTS In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative(HBcAb-) liver grafts. The 1-, 3-and 5-year survival rates in patients and grafts between the two groups were similar(patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3-and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcA b+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surfa

关键词： Liver transplantation Long-term outcome Hepatitis B core antibody Hepatitis B virus infection

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Serum anti-Helicobacter pylori antibody titer and its association with gastric nodularity,atrophy,and age:A cross-sectional study

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World Journal of Gastroenterology 2018年第35期24卷 4061-4068页

作者： Osamu Toyoshima Toshihiro Nishizawa Kosuke Sakitani Tadahiro Yamakawa Yoshiyuki Takahashi Nobutake Yamamichi Keisuke Hata Yasuyuki Seto Kazuhiko Koike Hidenobu Watanabe Hidekazu Suzuki Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Surgical Oncology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Gastrointestinal Surgery Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Pathology and Cytology Laboratory Japan Tokyo 166-0003Japan Medical Education Center Keio University School of MedicineTokyo 160-8582Japan

AIM To clarify the role of serum anti-Helicobacter pylori(H. pylori) antibody titers in gastric cancer.METHODS In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for H. pylori infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers antibody titer in H. pylori-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D.CONCLUSION Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.

关键词： antibody Helicobacter pylori Gastritis Gastric cancer Endoscopy

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EFFECTS OF MONOCLONAL antibody ANTIEGF RECEPTOR ON HUMAN NASOPHARYNGEAL CARCINOMA CELL AND OTHER TUMOR CELLS

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Science China Chemistry 1990年第11期33卷 1334-1340页

作者：管恩南周廷冲王晋海陈勇孙英勋黄培根唐蔚萍赵明伦 Institute of Basic Medical Sciences Academy of Military Medical Sciences CPLA Beijing 100850 PRC Department of Cancer Research Zhanjiang Medical College ZhanJiang 524023 PRC

Three anti-EGF receptor MoAbs were used in these studies. Administration of MoAbs 3 and 176 inhibited tumor formation in nude mice by CNE-2, a poorly differentiated nasopharyngeal carcinoma cell line and A431, an epidermoid carcinoma cell line. When the same MoAbs were used in treatment against HeLa, a cervical carcinoma, tumor growth was not affected. The number of EGF receptors and apparent dissociation constants for 125I-EGF on CNE-2 and A431 was 1.3×10?/cell (Kd 7.7×10-8mol/L) and 1.4×106/cell(Kd 2.4×10-9mol/L), respectively. Both MoAbs 3 and 176, capable of competing with EGF for receptor binding, showed significant tumor growth inhibition. MoAb 101 was incapable of blocking the binding of EGF to its receptor, and not as effective as MoAbs 3 and 176 in tumor growth inhibition. Our observation is that the MoAb anti-EGF receptor is cytostatic rather than cytocidal, in vitro against CNE-2 and A431.

关键词： nasopharyngeal carcinoma EGF receptor monoelonal antibody CNE-2 A431

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