1.Antibody-drug conjugates as targeted cancer therapeutics.
Yu SUN ; Fei YU ; Bai-Wang SUN
Acta Pharmaceutica Sinica 2009;44(9):943-952
Traditional chemotherapy has become one of the essential treatments of cancer. However, cytotoxic agents are not tumor specific, which would cause serious side effects. Antibody-drug conjugates (ADCs), also called immunoconjugates, belong to the "targeted chemotherapeutics" category of anti-cancer drugs. ADCs are composed of three components including the cytotoxic drug, the monoclonal antibody, and the linker connecting the drug to the antibody. With the special-binding between antibody and antigen expressed on the surface of targeted cancer cells, ADCs provide a method to achieve excellent localization of the drug at the desired site in the body. The internalization and formation of ADCs are crucial in designing and applying an antibody conjugate to a particular disease model. In this review, we summarize three distinct internalization routes of ADCs and analysis the structure of ADCs. We also discuss in detail the categories and interaction of every component, as well as their influence to targeting property, liability and activity.
Antibodies, Monoclonal
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administration & dosage
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Antineoplastic Agents
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administration & dosage
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Drug Delivery Systems
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Immunotoxins
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chemistry
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therapeutic use
2.A new thought of compound compatibility mechanism based on active small molecules monoclonal antibodies in herbs.
Hui-hua QU ; Yan ZHAO ; Qing-Guo WANG
Chinese Journal of Integrated Traditional and Western Medicine 2012;32(10):1416-1419
Compatibility mechanism study of Chinese herbal compound (CHC) has been one of key contents in Chinese medical research, but the present research methods are not suitable for its own features due to its complexity, which has restricted the process of modernization and intemationalization of Chinese medicine. In this paper, we addressed that the compatibility is closely correlated to their in vivo metabolic processes. The preparation of active small molecules monoclonal antibodies in herbs and testing a variety of effective compositions simultaneously using immunoassay can clarify the in vivo metabolism and mutual interactions of Chinese herbs, which is a new thought of studying the compound compatibility mechanisms.
Antibodies, Monoclonal
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administration & dosage
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Drug Combinations
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Drug Incompatibility
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Drugs, Chinese Herbal
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administration & dosage
3.Development of polymeric nanoparticles in the targeting drugs carriers.
Journal of Biomedical Engineering 2004;21(3):495-497
This review presents the most outstanding contribution in the field of polymeric nanoparticles used as targeting drugs delivery systems. Nanoparticles barrier is a novel kind of controlled release system for drugs which can effectively deliver the drug to a target site and increase the bioavailability and therapeutic benefit, while minizing the side effects. In this paper the applications of nanoparticles in the active, passive and physical targeting drugs carriers are reviewed.
Albumins
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administration & dosage
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Antibodies, Monoclonal
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administration & dosage
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Biological Availability
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Cyanoacrylates
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administration & dosage
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Drug Carriers
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Drug Delivery Systems
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Humans
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Nanotechnology
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Particle Size
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Polymers
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administration & dosage
4.Intraocular avastin (bevacizumab) for neovascularisation of the iris and neovascular glaucoma.
Jacob Y C CHENG ; Doric W K WONG ; Chong Lye ANG
Annals of the Academy of Medicine, Singapore 2008;37(1):72-74
INTRODUCTIONThe aim of this study was to determine the effectiveness of intraocular injections of bevacizumab for neovascularisation of the iris and neovascular glaucoma.
CLINICAL PICTUREThree patients with neovascularisation of the iris due to various causes were recruited.
TREATMENTPatients were treated with intraocular bevacizumab.
OUTCOMENeovascularisation of the iris was noted to have completely regressed as early as 3 days after the injection and in all the patients (100%) within 8 days after injection. They were followed up for at least 1 month with no clinical evidence of recurrence. Visual acuity remained stable or improved, and the intraocular pressure was controlled in all the 3 patients' eyes. Vitreous haemorrhage also cleared. No signs of inflammation or complications were observed.
CONCLUSIONIntraocular injection of bevacizumab is effective and safe for patients with neovascularisation of the iris and neovascular glaucoma with or without vitreous haemorrhage.
Adult ; Aged ; Angiogenesis Inhibitors ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Glaucoma, Neovascular ; drug therapy ; Humans ; Iris ; blood supply ; Male
5.Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin radioimmunoimaging.
Yi-xiang FAN ; Rong-cheng LUO ; Mei-ju GAO ; Qing-zhu LIU ; Ke-bin LI ; Ji-zhen WU ; Wei-min SHI
Journal of Southern Medical University 2009;29(12):2477-2484
OBJECTIVETo study the mechanism of cardiotoxicity associated with Herceptin.
METHODSHerceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues.
RESULTSThe O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172).
CONCLUSIONMyocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.
Animals ; Antibodies, Monoclonal ; administration & dosage ; pharmacokinetics ; toxicity ; Antibodies, Monoclonal, Humanized ; Female ; Iodine Radioisotopes ; administration & dosage ; pharmacokinetics ; Male ; Myocardium ; metabolism ; Rabbits ; Radioimmunodetection ; Receptor, ErbB-2 ; metabolism ; Tissue Distribution ; Trastuzumab
6.Intravitreal bevacizumab injection for chronic central serous chorioretinopathy.
Chinese Medical Journal 2010;123(15):2145-2147
7.A Case of Refractory Pediatric Crohn's Disease with a Successful Treatment by Infliximab Therapy.
Sang Hoon PARK ; Yoon Tae JEEN ; Hwang Rae CHUN ; Dong Il KIM ; Chang Won BAECK ; Yong Sik KIM ; Hoon Jai CHUN ; Hong Sik LEE ; Soon Ho UM ; Jai Hyun CHOI ; Chang Duck KIM ; Ho Sang RYU ; Jin Hai HYUN
The Korean Journal of Gastroenterology 2005;46(4):297-301
Crohn's disease is a chronic inflammatory bowel disease which affects mainly children and young adults, and its cause remains unknown so far. Infliximab, a monoclonal antibody to the pivotal cytokine tumor necrosis factor-alpha, has been approved as a drug for both induction and maintenance therapy for moderately to severely active, or fistula-complicated Crohn's disease. The authors report a 12-year-old male patient diagnosed as Crohn's disease complicated with a perianal fistula, which was refractory to the conventional therapy. After the 0, 2, and 6 week scheduled intravenous infusion of infliximab, the patient reached to clinical remission in both subjective symptoms and objective manifestations. For children or young adults who develop Crohn's disease in a refractory course, infliximab may serve as a drug which leads to a clinical improvement or even to an extent of remission.
Antibodies, Monoclonal/*administration & dosage
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Child
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Crohn Disease/*drug therapy
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Drug Administration Schedule
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English Abstract
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Gastrointestinal Agents/*administration & dosage
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Humans
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Infusions, Intravenous
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Male
8.Description of the Efficacy and Safety of Three New Biologics in the Treatment of Rheumatoid Arthritis.
Steven S STORAGE ; Harsh AGRAWAL ; Daniel E FURST
The Korean Journal of Internal Medicine 2010;25(1):1-17
English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were thirteen articles on abatacept, four on golimumab, and seven on tocilizumab. All three drugs were effective in methotrexate-naive, methotrexate-incomplete responders, and tumor-necrosis-factor-failure rheumatoid arthritis patients. Of the three, only abatacept has been tested in a head-to-head trial with infliximab, in which it was found to be equivalent to infliximab. Golimumab resulted in a more modest improvement than the others in methotrexate-naive patients, although no direct comparisons among the three drugs were possible or appropriate. Descriptive analysis of adverse events showed that patients receiving abatacept, golimumab, and tocilizumab were subject to more adverse events than controls overall, as expected. In the abatacept studies, a few cases of tuberculosis, more cardiovascular events and gastrointestinal bleedings and more basal cell carcinoma were seen. Golimumab was associated with more skin rashes and pneumonia, while tocilizumab was associated with increased lipids, more liver-function abnormalities, and neutropenia. These new medications are useful additions to the rheumatologic armamentarium and represent greater convenience (golimumab) or different mechanisms of action (abatacept and tocilizumab) than tumor-necrosis-factor inhibitors for treating rheumatoid arthritis. As expected, some adverse events occur when using these drugs and patients need to be watched carefully.
Antibodies, Monoclonal/*administration & dosage/adverse effects
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Antirheumatic Agents/*administration & dosage/adverse effects
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Arthritis, Rheumatoid/*drug therapy
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Biological Therapy
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Humans
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Immunoconjugates/*administration & dosage/adverse effects
9.The study on the 0, 12 month vaccination schedule' of Healive inactivated hepatitis A vaccine in children.
Yin-hai REN ; Jiang-ting CHEN ; Wen-ting WU ; Xue-jie GONG ; Yu-cheng ZHANG ; Wei-hua XUE ; Yi-feng REN ; Lian-jun HAN ; Wen-xue KANG ; Sheng-ping LI ; Chong-bai LIU
Chinese Journal of Epidemiology 2003;24(11):1013-1015
OBJECTIVETo evaluate the safety, immunogenicity and fit dosage of Healive inactivated hepatitis A vaccine (HAV) in children.
METHODSA total of 85 susceptible aged 4 - 10 years with HAV seronegative children, had been enrolled from two adjacent villages in a county. The volunteers were randomized allocated into two groups and to receive a priming dose of 250 U/0.5 ml/dose or 500 U/1.0 ml/dose of Healive vaccine, produced by Sinovac Biotech Co, Ltd. A booster of the same dose was given at 12th month. Local and systemic side effects were examined and seroconversion rate as well as geometric mean titers of anti-HAV antibody were tested at 3-week, 12-month after the primary dose and at 1 month after the booster dose.
RESULTSThe vaccine was well tolerated in both groups. At 21 days after the primary dose, the seroconversion rates were 94.4%, 100.0% and geometric mean titers (GMT) were 195 mIU/ml and 370 mIU/ml in 250 U and 500 U groups respectively. At 12 months after the primary dose, the seroconversion rate of anti-HAV was 100.0%, and GMT raised to 361 mIU/ml, 456 mIU/ml (P > 0.05) respectively. One month after the booster dose, GMT raised to 14 893 mIU/ml, 21 696 mIU/ml.
CONCLUSIONGMT of the 0, 12 month schedule was higher than other schedule after the booster vaccination. The Healive inactivated vaccine can be used for emergency vaccination. The Healive inactivated vaccine produced by Sinovac Company Ltd was safe and highly immunogenic. Two hundred and fifty U/dose was considered appropriate for children.
Child ; Child, Preschool ; Dose-Response Relationship, Immunologic ; Drug Administration Schedule ; Hepatitis A ; immunology ; prevention & control ; Hepatitis A Antibodies ; analysis ; Hepatitis A Vaccines ; administration & dosage ; immunology ; Humans ; Vaccines, Inactivated ; administration & dosage ; immunology
10.Local production of specific IgE antibody to house dust mite in nasal polyp tissues.
Ji Won KANG ; Dong Ho NAHM ; Kyung Sik SUH ; Hee Yeon KIM ; Hae Sim PARK
Journal of Asthma, Allergy and Clinical Immunology 1998;18(3):426-433
OBJECTIVE: In order to confirm the local production of total and specific IgE antibodies in the nasal polyp tissues. MATERIAL AND METHOD: We measured total IgE and house dust mite(Dermatophagoides pteronpssinus .' DP)-specific IgE antibody using enzyme-linked immunosorbent assay(ELISA) in the supernatant of nasal polyp homogenates from 72 subjects undergoing nasal polypectomy. The subjects were divided into three groups according to skin reactivity to DP: 20 strongly atopic subjects to group I(mean wheal diameter) 3mm), 19 weakly atopic subjects to group II (mean wheal diameter 1-3mm) and 33 negative skin responders to group III. RESULT: Group I showed significantly higher levels of total and DP-specific IgE levels in the nasa
Antibodies
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Dust*
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Immunoglobulin E*
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Nasal Polyps*
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Pyroglyphidae*
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Skin
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United States National Aeronautics and Space Administration