摘要 :
Japanese encephalitis (JE) is caused by the Japanese encephalitis virus (JEV). It is a major public health problem in Asia. JEV infects swine which results in fatal encephalitis, abortion and stillbirth in pregnant sow, and hyposp...
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Japanese encephalitis (JE) is caused by the Japanese encephalitis virus (JEV). It is a major public health problem in Asia. JEV infects swine which results in fatal encephalitis, abortion and stillbirth in pregnant sow, and hypospermia in boars. Swine is a viral amplifier, and thus plays a critical role in JEV transmission. Thus, development of a rapid method for JEV detection in swine is required for clinical JE diagnosis, as well as to suppress viral spread. In this study, a convenient and rapid immunochromatographic strip (ICS) was developed for detecting JEV in swine using two monoclonal antibodies (MAbs) (2A2 and 4D1) against the E protein of JEV. Results showed that colloidal gold-conjugated MAbs 2A2 (CG-MAb) bond with JEV and the resulting complex was held by the other MAb 4D1 at the test line to give a reddish-purple band. Sensitivity tests demonstrated that ICS can detect 2.5 x 10(5) PFU of JEV. The clinical screening results showed that the specificity and sensitivity of the ICS were 99.3% and 85.7% respectively as compared to that of RT-PCR. This suggests that the MAbs-based ICS test can be used as a convenient method for the rapid detection of JEV in infected swine samples
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Monoclonal antibodies (MAb's) have become one the most powerful therapeutic and diagnostic tools in modern medicine. Some estimates target the worldwide market of MAb's on the order of $125 billion in the next four years. Recent a...
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Monoclonal antibodies (MAb's) have become one the most powerful therapeutic and diagnostic tools in modern medicine. Some estimates target the worldwide market of MAb's on the order of $125 billion in the next four years. Recent advances in molecular biology, immunology, and development of robust production platforms will drive the development of more MAb's suitable to treat an ever increasing number of disease states. This circumstance combined with the fact that many of the original antibody therapies from the 1980s and 1990s will soon be coming off patent will attract a great deal of investment in the development of larger industrial facilities to increase monoclonal antibody to meet increasing demand. In this review, the present state of the science that underlies the development of new antibodies therapies in Chinese hamster ovary cells combined with a description of the present challenges facing the industry in terms of the limitations of output and compliance with current good manufacturing practices and FDA regulations. Also addressed are future challenges to overcome production bottlenecks, description of critical quality control attributes particular to antibodies, and detailed treatment of scale-up considerations.
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Monoclonal antibodies (mAbs) have become one of the largest classes of new therapeutic agents approved for use in oncology, and have revolutionised the treatment of many human malignancies. Clinically useful mAbs can function thro...
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Monoclonal antibodies (mAbs) have become one of the largest classes of new therapeutic agents approved for use in oncology, and have revolutionised the treatment of many human malignancies. Clinically useful mAbs can function through several different mechanisms, including inhibition of tumour-related signalling, induction of apoptosis, inhibition of angiogenesis, enhancing host immune response against cancer and targeted delivery of payloads (such as toxins, cytotoxic agents or radioisotopes) to the tumour site. The increasing knowledge of key molecules and cellular pathways involved in tumour induction and progression has led to a rise in the proportion of therapeutic mAbs entering clinical trials. These mAbs consist of various conventional or recombinant, murine, humanised, chimeric or fully human and fusion constructs. In this review, we provide an overview of mAbs approved for use in clinical oncology and those currently in clinical development. We also discuss the mechanisms of action of anti-cancer mAbs, as well as the antigen targets recognised by these antibodies.
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AIM To directly radiolabel an anti-hepatoma mAb fragment Hab18 F (ab')_2 with 99m Tc by stannous-reduced method, and assess the stability, biodistribution and radioimmun- oimaging (RII). METHODS Immunoreactive fraction was Determi...
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AIM To directly radiolabel an anti-hepatoma mAb fragment Hab18 F (ab')_2 with 99m Tc by stannous-reduced method, and assess the stability, biodistribution and radioimmun- oimaging (RII). METHODS Immunoreactive fraction was Determined according to Lindmo's method. Ellman's reagent was used to determine the Number of thiols in the reduced F9ab)_2. Labeling Efficiency and homogeneity were measured by Paper chromatography, sodium dodecylsulphate Polyacrylamide gel electrophoresis 9SDS-PAGE) And autoradiography.
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Ten different mouse cell lines were examined for Japanese encephalitis virus (JEV) infection in vitro and then tested for their ability to generate virus specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro...
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Ten different mouse cell lines were examined for Japanese encephalitis virus (JEV) infection in vitro and then tested for their ability to generate virus specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro La (a neuroblastoma) was readily infected with JEV as examined by immunofluorescence and viral replication. Among other cells, P388D1, RAW 264.7 (Macrophage origin), Sp2/0 (B-cell Hybridoma), YAC-1 (T-cell lymphoma), and L929 (Fibroblast) were semipermissive to JEV infection. The cytopathic effects caused by progressive JEV infection varied from cell line to cell line. In the case of YAC-1 cells long-term viral antigen expression was observed without significant alterations in cell viability. Intermediate degrees of cytopathicity are seen in RAW 264.7 and L929 cells while infection of PS, Neuro 2a, P388D1 and Sp2/0 caused major viability losses. All infected cell lines were able to prime adult BALB/c (H-2(d)) mice for the generation of secondary JEV specific CTL. In contrast to YAC-1, the permissive neuroblastoma cell line Neuro 2a (H-2K(k)D(d)) was found to be least efficient in its ability to stimulate anti-viral CTL generation. Cold target competition studies demonstrated that both Neuro 2a and YAC-1 (H-2K(k)D(d)) cells expressed similar viral determinants that are recognised by CTL, suggesting that the reason for the lower ability of Neuro 2a to stimulate anti-viral CTL was not due to lack of viral CTL determinants. These findings demonstrate that a variety of mouse cell lines can be infected with Japanese encephalitis virus, and that these infected cells could be utilised to generate virus specific CTL in BALB/c mice.
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Himananto, O., Thummabenjapone, P., Luxananil, P., Kumpoosiri, M., Hongprayoon, R., Kositratana, W., and Gajanandana, O. 2011. Novel and highly specific monoclonal antibody to Acidovorax citrulli and development of ELISA-based det...
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Himananto, O., Thummabenjapone, P., Luxananil, P., Kumpoosiri, M., Hongprayoon, R., Kositratana, W., and Gajanandana, O. 2011. Novel and highly specific monoclonal antibody to Acidovorax citrulli and development of ELISA-based detection in cucurbit leaves and seed. Plant Dis. 95:1172-1178.A novel monoclonal antibody (MAb) specific to the seedborne bacterium Acidovorax citrulli was produced. MAb 11E5 reacted specifically with 19 strains of A. citrulli but not with three closely related bacteria in the family Comamonadaceae (i.e., A. facilis. Comamonas acidovorans, and C. testosteroni) and another seven phytopathogenic bacteria. Moreover, this MAb detected a strain of A. citrulli that was not detected by a commercial enzyme-linked immunosorbent assay (ELISA)-based kit and a commercial immunochromatographic strip test. In Western blot analysis, MAb 11E5 reacted with an A. citrulli protein of a molecular mass >170 kDa. MAb 11E5 was employed to develop two sandwich ELISA systems: MAb captured-sandwich ELISA (MC-sELISA) and polyclonal antibody captured-sandwich ELISA (PC-sELISA). MC-sELISA was 10 times more sensitive than PC-sELISA for detection of A. citrulli in cucurbit leaf and seed extracts. The detection limit of the MC-sELISA was 5 x 10(4) CFU/ml. Detection of A. citrulli in naturally infected cucurbit leaves, fruit, and seed was also feasible using MC-sELISA. The newly established MC-sELISA provides another alternative for specific detection of A. citrulli in cucurbits and can be applied for routine field inspection.
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The human EGF receptor (HER) 2 receptor tyrosine kinase is a survival factor for human cardiomyocytes, and its inhibition may explain the increased incidence of cardiomyopathy associated with the anti-HER2 monoclonal antibody tras...
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The human EGF receptor (HER) 2 receptor tyrosine kinase is a survival factor for human cardiomyocytes, and its inhibition may explain the increased incidence of cardiomyopathy associated with the anti-HER2 monoclonal antibody trastuzumab (Genentech, South San Francisco, CA), particularly in patients with prior exposure to cardiotoxic chemotherapies e.g., anthracyclines. Here, we show that GW2974 (HER2/EGF receptor tyrosine kinase inhibitor), but not trastuzumab, activates AMP-activated protein kinase (AMPK), initiating a metabolic stress response in human cardiomyocytes that protects against TNFα-induced cell death. GW2974 stimulates calcium dependent fatty acid oxidation in vitro and in the myocardium of GW2974-treated rodents. Calcium chelation or siRNA-targeted AMPK knockdown blocks GW2974 induced fatty acid oxidation. In addition, inhibition of AMPK by a specific inhibitor resulted in increased killing of cardiomyocytes. Elucidating the effects of HER2-targeted therapies on AMPK may predict for risk of cardiomyopathy and provide a novel HER2-targeted strategy designed to protect myocardium from the pro-apoptotic effects of pro-inflammatory cytokines released in response to cardiac injury by chemotherapy or acute ischemia.
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A number of therapeutic agents in nuclear medicine are currently attracting considerable interest, including several for the treatment of hematologic and nonhematologic malignancies. A knowledge of the radiation dose received by d...
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A number of therapeutic agents in nuclear medicine are currently attracting considerable interest, including several for the treatment of hematologic and nonhematologic malignancies. A knowledge of the radiation dose received by different organs in the body is essential to the optimization of the therapy for each patient; one wants to maximize the dose to the malignant tissue while minimizing the dose to critical healthy tissues and avoiding any toxic response therein. In this paper, current methods for calculating radiation doses will be discussed and evaluated. In almost all nuclear medicine therapy, and particularly in this application, dose to the active marrow is of paramount concern. Specific focus on current bone marrow dose models and their ability to predict observed marrow toxicity in patient populations to date will be discussed. The paper will focus on current and possible future dosimetry practice in therapeutic nuclear medicine, particularly as regards the treatment of hematologic malignancies.
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摘要 :
Ever since Paul Ehrlich proposed, a century
ago, that antibodies might be used as “magic
bullets” to target and destroy human dis-
eases, scientists have sought to tap the bio-
therapeutic potential of these natural proteins.
Ye...
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Ever since Paul Ehrlich proposed, a century
ago, that antibodies might be used as “magic
bullets” to target and destroy human dis-
eases, scientists have sought to tap the bio-
therapeutic potential of these natural proteins.
Yet only in the past few decades has the ther-
apeutic promise of antibodies begun to be
realized, as advances in immunology
and animal cell culture led to a tech-
nique for the development and pro-
duction of monoclonal antibodies,
an achievement that undoubtedly
ranks as one the foremost advances
in 20th-century medicine
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摘要 :
Background. Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenoma...
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Background. Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. Methods. We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. Results. 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN's identified a group of patients with a superior overall survival (p = 0.027). Conclusion. Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.
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