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ABSTRACT Iridociliary ring melanoma is an uncommon type of uveal melanoma. Clinical manifestation varies from asymptomatic cases to masquerade syndromes mimicking refractory glaucoma. Treatment options include radiotherapy and enucleation. Management of metastatic uveal melanoma remains discouraging. Novel therapies using immune checkpoint inhibitors are currently under study. We present a case of a 54-year-old Hispanic woman with progressive vision loss due to metastatic ring melanoma with anterior chamber seeding treated with pembrolizumab.
RESUMO O melanoma iridociliar em anel é um tipo incomum de melanoma uveal. As manifestações clínicas variam desde casos assintomáticos até síndromes mascaradas que mimetizam um glaucoma refratário. As opções de tratamento incluem radioterapia e enucleação. O manejo do melanoma uveal metastático continua desanimador. Novas terapias usando inibidores de checkpoint imunológico estão atualmente em estudo. Apresentamos o caso de uma mulher hispânica de 54 anos com perda progressiva da visão por um melanoma metastático em anel, com semeadura de câmara anterior, tratada com pembrolizumabe.
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Objective To evaluate the effect of anti-myosin monoclonal antibodies-nuclear factor kappa B (NF-κB) decoy oligodeoxynucleotides-lipofectamine compound (mAb2G4-ODN-lip) on myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty clean-grade healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 240-260 g,were divided into 4 groups (n=10 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),ODN-lip group (group ODN) and mAb2G4-ODN-lip group (group mAb2G4).Myocardial I/R was induced by occlusion of the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion.In ODN and mAb2G4 groups,ODN-lip (100 μg ODN) and mAb2G4-ODN-lip (100 μg ODN) compounds were injected via the femoral vein,respectively,immediately after onset of ischemia.The left anterior descending branch of coronary artery was only occluded but not ligated in group S.The animals were sacrificed at 120 min of reperfusion and myocardial specimens of the left ventricle on the ischemic side were obtained for examination of the pathological changes (using haematoxylin and eosin staining) and for determination of the expression of NF-κB (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay).Results Compared with group S,the expression of NF-κB was significantly up-regulated,and the contents of TNF-α and IL-6 were increased in I/R,ODN and mAb2G4 groups (P＜ 0.05).Compared with group I/R,the expression of NF-κB was significantly down-regulated,and the contents of TNF-α and IL-6 were decreased in ODN and mAb2G4 groups (P＜0.05).Compared with group ODN,the expression of NF-κB was significantly down-regulated,and the contents of TNF-α and IL-6 were decreased in group mAb2G4 (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group I/R,group ODN and group mAb2G4 in turn.Conclusion mAb2G4-ODN-lip can mitigate myocardial I/R injury in rats.
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Glucagon regulates glucolipid metabolism and body weight through binding to and activating glucagon receptor ( GCGR ), which is predominantly expressed in liver and pancreas. In the diabetic state, inappropriately increased glucagon secretion leads to elevated hepatic glucose output, while GCGR blockage restores blood glucose homeostasis. Various approaches including GCGR monoclonal antibodies ( mAbs ), antagonists, antisense oligonucleotides, and gene knockout can block GCGR signaling. It has shown that GCGR mAbs improve hyperglycemia in diabetic mice and humans without severe adverse effects, since they can specifically antagonize the action of glucagon. Therefore, GCGR signaling plays a critical role in the pathophysiology of diabetes and GCGR mAbs represent innovative approaches in the management of diabetes.
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Lung cancer is characterized by high malignancy and the majority of patients are diagnosed at the advanced or late stage.Chemoradiotherapy has insufficient effect on this malignant tumor.At present the immune therapy has become a new choice for lung cancer treatment.Ipilimumab,antibody to programmed death-1 ,immune cells,cytokines,melanoma-associated antigen A3 vaccine,liposomal BLP25,belagen-pumatucel-L and polypeptide vaccine have been proved effective for lung cancer through various clinical trials. Futhermore,most of them have been moved forward to phase Ⅲ clinical trials in order to get more strong evidence to support the immunotherapy incorporated into the multidisciplinary treatment of lung cancer.
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Objective To evaluate the efficacy and safety of infliximab and traditional disease modifying antirheumatic drugs (DMARDs) in the treatment of ankylosing spondylitis (AS). Methods Sixty patients with definite AS were treated with infliximab 5 mg/kg infusion at 0, 2, 6, 12 weeks and were followed up for 12 weeks. The primary endpoint was proportion of ASAS 20 responders at week 12. The secondary endpoints were the proportion of ASAS 50, the change from baseline in Bath AS functional index (BASFI).The improvement of signs and symptoms of AS and physical function were evaluated. The statistical treatments were used t-test andA2 test. Results The proportion of ASAS 20 responders at 2, 6, 12 week was 70%, 83% and 93% respectively. The proportion of ASAS50 responders at patients at 2, 6, 12 week was 13%, 37% and 57% respectively. Results for other secondary efficacy endpoints showed that infliximab could provide substantial benefits to patients with AS by reducing clinical signs and symptoms and improving range of motion, physical function and quality of life. Ten percent of the subjects reported treatment- related adverse events. The most frequently occurred were upper respiratory tract infection, followed by gastrointestinal adverse events and infusion reaction. Most treatment-related adverse events were mild to moderate in severity and disappeared after drug withdrawal. Conclusion Infliximab has been demonstrated to be effective and is well tolerated in the treatment of AS.
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objectlve To investigate the efficacy of continuous low-dose fluorouracil with cetuximab for antiangiogenic effect on colon carcinoma xenograft,and test its antitumor effect and toxicity.Methods Balb/c mice bearing CT-26 colon carcinoma xenograft were randomly divided into five groups,receiving low-dose metronomic(LDM)fluorouracil,maximum tolerated dose(MTD)fluorouracil,cetuximab,LDM fluorouracil with cetuximab therapy and saline respectively.Tumor growth,weight loss,peripheral white blood cell counts and survival of mice were monitoted.At the end of experiment,tumors were resected for tumor microvascular density(MVD)by immunofluorescence staining. Results Tumor growth inhibition was found in mice receiving LDM fluorouracil therapy and combined therapy,without significant body weight loss or leukopenia,and the survival of mice was remarkably prolonged,compared with mice receiving MTD fluorouracil or cetuximab therapy,and the antitumor effects of the combined therapy was stronger than that of the fluorouracil LDM therapy.LDM treatment and combine treatment led to statistically significant(P＜0.05)55%and 71%reduction in tumor growth,as well as 73%and 77% reduction in tumor microvessel density compared with the control respectively.Additonally,tunnel staining shows no significant difference between these treatment groups. Conclusion Continuous low-dose regimen of fluorouracil with cetuximab can significantly increase the therapeutic activity with decreased toxicity and prolonged animal survival bearing implanted colon cancer.
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Objective: To prepare the monoclonal antibody of G protein coupled receptor 48 (GPR48) and investigate the expression in colorectal cancers. Methods: The monoclonal antibody of GPR48 was produced by cell fusion technology and identified by Western blotting and flow cytometry (FCM). The expression of GPR48 was studied in colorectal cancer by using the immunohistochemical method. Results: The specific monoclonal antibody of GPR48 was prepared. No expression of GPR48 was detected in normal colorectal tissues. The positive rate of GPR48 was significantly higher in colorectal cancer patients with lymph node metastasis than that in patients without lymph node metastasis (85.7% vs 34.6% P <0.05); it was significantly lower in well-differentiated colorectal cancer than that in moderately- and poorly-differentiated colorectal cancer (22.2% vs 77.3%, P <0.05). GPR48 expression had no correlation with the sex and tumor size of patients. Conclusion: The monoclonal antibody of GPR48 is a specific antibody. It can be used as a new index for predicting tumor differentiation and lymph node metastasis.
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Objective To evaluate the effects of radioimmunoimaging with 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb or combined application of both on nude mice bearing lung adenocarcinoma. Methods Animal model of nude mice bearing lung adenocarcinoma was established. The direct labeling method of 99Tcm was applied to labeling monoclonal antibodies for EGFR and CD44, and then the properties of the labeling antibodies purified by SephadexG50 Column were identified. The radio-immuno-image as well as body distribution concerning nude mice bearing lung adenocarcinoma was studied by application of 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb alone or combined application of both. Results The labeling rates of 99Tcm for EGFR-McAb and CD44-McAb were (91.5?3.8)% and (92.3?4.1)% respectively. Specific activities of the labeled antibodies were (2.8?0.3)MBq/g and (2.9?0.5)MBq/g, respectively. The rates of radiochemical purity were (96.5?2.8)% and (96.2?3.1)%, respectively. The tumor tissue had high intake of the two labeled antibodies according to radioimmunoimaging result. The radioactivity concentration of the combined application of the two labeled antibodies was obviously higher than that of the single application. The T/NT relative values measured through ROI technique were 5.58?0.46, 2.72?0.22, and 2.30?0.18, respectively. The body distribution result of the labeled antibodies and their imaging results were basically identical. Conclusion The optimal target and non-target ratios could be obtained by application of 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb alone in nude mice bearing lung adenocarcinoma. The target and non-target ratios could be enhanced through the combined application of the two antibodies.
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Objective Clinical significance of using ELISA to determine ?-amyloid(A?)_(1-42) antibody levels in the sera of patients with Alzheimer's disease(AD).Methods 96 wells PVC plate was coated with A?_(1-42)peptide.Serum of AD patient was competing with mouse A?_(1-42)monoclonal antibody in this assay.The second antibody was horseradish peroxidase(HRP)conjugated goat anti-mouse IgG.Serum A?_(1-42)antibody levels were determined by ELISA.Results The sensitivity of this assay was about 1 ng/ml.The recovery rate of this test was between 96.5% and 104.7%.The residual A?_(1-42)antibody levels in human serum or horse serum after A?_(1-42)antibody was removed by absorption were less than 1 ng/ml. Serum A?_(1-42)antibody levels in 37 AD patients[(5.1?1.9)ng/ml]were remarkably lower than those in normal people[(12.6?3.3)ng/ml,P
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Objective To clone human asparagine synthetase(ASNS)gene,express the MS2- ASNS fusion protein through gene engineering and use the purified target protein to immune BALB/C mice, prepare and identify the monoclonal antibody(McAb),which forms the base for studying mechanism of L- asparaginase used as salvage regimen in midline NK/T cell lymphoma nasal type.Methods ASNS gene fragment was amplified by RT-PCR from HepG2 cell line and constructed into prokaryocytic expression vector.Fusion-protein of MS2-ASNS was expressed and used for immunizing BALB/C mice to prepare McAbs against ASNS.Identified the McAb and detected the expression of ASNS in tumor.Results Part of the ASNS reading frame(NCBI,M27396:179-1 420 bp)was cloned and product length of RT-PCR was 1 263 bp.Molecular weight of MS2-ASNS was about 54 700 Da.Two strains of hybridoma secreting ASNS McAbs were obtained.The subtype of the ASNS McAb was IgG2a.Western-blot showed that the McAbs could specifically react with MS2-ASNS fusion protein and ASNS protein in tumor cell lines.ASNS expression was detected by immunocytochemistry and Immunohistochemisrry.Conclusion We have cloned human ASNS gene,obtained the anti-ASNS McAb and examined the expression of ASNS in tumor.
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To evaluate the effect of delayed treatment with monoclonal antibody to tumor necrosis factor-alpha (TNF-? MAb) on systemic hemodynamics and multiple organ dysfunction following prolonged hemorrhagic shock and resuscitation. Method: Adult male Sprague-Dawley rats were subjected to prolonged hemorrhagic shock (MAP of 4.00-4.66 kPa for 180 rain)followed by resuscitation over 50 min. The animals were treated intravenously with either TNF-? MAb (20.0 mg/kg) or the control protein(albumin,20.0 mg/kg)15 rain after the end of resuscitation(65 min after shock). Result: Compared to the albumin controls, delayed treatment with TNF-? MAh significantly reduced the total peripheral resistance index (P
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To observe the effect and its potential mechanism of monoclonal antibody to tumor necrosis factor-alpha(TNF? MoAb)on systemic hemodynamics and survival rate after intestinal ischemia/reperfusion (Ⅱ/R). Method: SD rats were subjected to 75 rain of superior mesenteric artery occlusion followed by 6 hours of reperfusion. The animals were treated intravenously with either TNF? MoAb(20mg/kg)or the control protein(albumin, 20mg/kg) 30 min prior to the onset of ischemia. Result: Pretreatment with TNF? MoAb significantly attenuated the decrease in blood pressure and cardiac index compared to controls throughout the 6-hour period of observation(P
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Rats were immersed into boiling water for 15 seconds with scalded area about 23 cm~2 and decapitated at 0.5,1 and 6 hours after scalding. The changes of immunoreactive glueocorticoid receptor (GR_(IR)) and glucocorticoid receptor binding (GR_B) of hepatic cytosol after scalding were studied by both monoclonal antibody method and radioligand binding assay. The results showed that GR_(IR) and GR_B decreased markedly in parallel manner after scalding. Comparing with the controls (100%), the values of GRIR of 0.5,1 and 6 hours after scalding decreased to 64.76?13.320% (n=4),59.55?13.18% (n=5) and 42.64?4.24% (n=4)respectively; and relevent GR_B decreased to 50.24?9.71% (n=4), 51.11?11.31% (n=5) and 30.43?3.03% (n=4). The amplitude of decrease of GR_B was about 10% more than that of GR_(IR). Thus it might be concluded that the reduction of GR_B after stress was mainly due to the decrease of GR protein molecules but 10% of that was due to the change of GR binding activity. The mechanisms of these changes were discussed.
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Apolipoprotein E (ApoE) was purified from human serum and used as the antigen to immunize BALB/C mice. The splenic cells of the mice fused with NS-1 mouse myeloma cells. Three hybridoma cell lines(E3C3, E6C3 and E4C2)secreting anti-human ApoE McAb were established. The immunological property of the McAb was studied. The ascites fluids titer were 8?10~(-5)2?10~(-6). The McAbs did not cross react with the other apolipoprotins. ApoE was purified by immunoaffinity chromatography prepared by using the ApoE McAb. McAbs recognized two distinct respective epitopcs on ApoE. The subclass of immunoglabulin of three McAbs were IgG_1. A double McAb sandwich EL1SA was developed to evaluate ApoE levels in normal and hyperlipidemia human serum.
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By using antr-ras P21 mouse monoclonal (MoAb), SCI-Oncogema 1, the authors examined immunohistochemica! staining in pancreatc adeocarcinoma. The percentage of positive staining was 24/43 (558%). Furthermore it was indicated that the positive staining rate of antr-ras P21 MoAb was related to either histopathological grade or clinical stage. Upon statistical analysis of the correlation between the staining of anti-ras P21 and patient prognosis with Kaplan-Meier curve and Log-rant test, the positive staining cases showed comparatively better prognosis than the negative ones. Our study suggests that ras P21 expression may be important in the early stage of pancreatic carcinoma.
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In this study, 5'-CMP was sulfonated, and then the modified 5'-CMP was connected to a protein carrier as an immunogen to immunize BALB/c mice. After cell hybridization, screening and recloning , a McAb (B10) with high sensitivity and specificity was selected. In a dot Hot using the McAb B10, less than 0.05 pg of sulfonated DNA could be detected while 10 ng of DNA was not coloured The result showed that the sensitivity of McAb B10 was higher than that of the McAb from "Chemiprobe" kit