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        Proof-of-concept study of the caninized anti-canine programmed death antibody in dogs with advanced non-oral malignant melanoma solid tumors

        Masaya Igase,Sakuya Inanaga,Shoma Nishibori,Kazuhito Itamoto,Hiroshi Sunahara,Yuki Nemoto,Kenji Tani,Hiro Horikirizono,Munekazu Nakaichi,Kenji Baba,Satoshi Kambayashi,Masaru Okuda,Yusuke Sakai,Masashi 대한수의학회 2024 Journal of Veterinary Science Vol.25 No.1

        Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

      • SCIESCOPUSKCI등재

        Characterization of Tifton 85 bermudagrass haylage with different layers of polyethylene film and storage time

        Nath, Caroline Daiane,Neres, Marcela Abbado,Scheidt, Kacia Carine,Bersot, Luciano dos Santos,Sunahara, Samantha Mariana Monteiro,Sarto, Jaqueline Rocha Wobeto,Stangarlin, Jose Renato,Gomes, Simone Dam Asian Australasian Association of Animal Productio 2018 Animal Bioscience Vol.31 No.8

        Objective: The objective was to characterize the fermentative and microbiological profile of Tifton 85 bermudagrass haylage with different layers of polyethylene film and storage time. Methods: The experimental design consisted of a randomized block design with four and six wrapping layers (100 and 150 microns in total. respectively) allocated in the main plots, through repeated measures analysis (30, 60, and 90 days of storage) with four replicates. Results: The storage time and number of wrapping layers did not show changes in the population of Clostridium and lactic acid bacteria. A decrease was observed in the enterobacteria population with an increase in the storage period in the two wrapping layers studied. Upon opening of the haylage at 30 days, the population of Bacillus was lower in haylages made with six layers of wrapping (3.63 log colony forming units/g). No growth of Listeria sp. or Salmonella sp. was observed during the experimental period. The fungal genera with a greater occurrence were Penicillium sp. and Fusarium sp. The following mycotoxins were not detected: ochratoxin A, fumonisins, and zearalenone. Relative to the organic butyric, propionic, and acetic acids, the haylages presented a low concentration of lactic acid; this may have prevented a drop in the pH, which was high when the silos were opened (5.4). The levels of ammoniacal nitrogen and soluble carbohydrates presented no variation among the number of wrapping layers, with an overall average of 35.55 and 38.04 g/kg. Conclusion: Tifton 85 bermudagrass haylage wrapped with four and six layers presented adequate fermentation and microbiological characteristics in the evaluated periods.

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        PEGylation of bacterial cocaine esterase for protection against protease digestion and immunogenicity

        Park, J.B.,Kwon, Y.M.,Lee, T.Y.,Brim, R.,Ko, M.C.,Sunahara, R.K.,Woods, J.H.,Yang, V.C. Elsevier Science Publishers 2010 Journal of controlled release Vol.142 No.2

        Enhancing cocaine metabolism by administration of cocaine esterase (CocE) has been considered as a promising treatment strategy for cocaine overdose and addiction, as CocE is the most efficient native enzyme yet identified for metabolizing the naturally occurring cocaine. A major obstacle to the clinical application of CocE, however, lies in its thermo-instability, rapid degradation by circulating proteases, and potential immunogenicity. PEGylation, namely by modifying a protein or peptide compound via attachment of polyethylene glycol (PEG) chains, has been proven to overcome such problems and was therefore exploited in this CocE investigation. The PEG-CocE conjugates prepared in this study showed a purity of greater than 93.5%. Attachment of PEG to CocE apparently inhibited the binding of anti-CocE antibodies to the conjugate, as demonstrated by the enzyme-linked immunosorbent assay (ELISA) assay. In addition, PEGylation yielded protection to CocE against thermal degradation and protease digestion. Furthermore, preliminary in vivo results suggested that, similarly to native CocE, the PEG-CocE conjugates were able to protect animals from cocaine-induced toxic effects. Overall, this study provides evidence that the PEGylation may serve as a tool to prolong CocE functionality in the circulation and reduce its potential immunogenicity.

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