1,735,073 research outputs found

    Targeted Delivery of BMS-1166 for Enhanced Breast Cancer Immunotherapy

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    Zhecheng Yu,1– 4 Zeya Zhou,1– 4 Yunqi Zhao1– 4 1College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang, People’s Republic of China; 2Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou, Zhejiang, People’s Republic of China; 3Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou, Zhejiang, People’s Republic of China; 4Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, Union, NJ, USACorrespondence: Yunqi Zhao, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86 577 5587 0000, Fax +86 577 5587 0101, Email [email protected]: Cancer immunotherapy has achieved great success in breast cancer treatment in recent years. The Programmed Death-1 (PD-1) /Programmed Death-Ligand 1 (PD-L1) immune checkpoint pathway is among the most studied. BMS-1166, a PD-L1 inhibitor, can interfere with PD-1 and PD-L1 interaction. Transferrin Receptor 1 is a transmembrane glycoprotein overexpressed in various cancer cells, including breast cancer, and can specifically interact with the T7 (HAIYPRH) peptide.Purpose: This study hypothesized that BMS-1166-loaded T7-modified poly(ethylene glycol)-poly(ϵ-caprolactone) (PEG-PCL) polymeric micelles (BMS-T7) could block PD-L1 interaction with PD-1, serving as a targeted immunotherapy for TfR1-positive breast cancer.Methods: BMS-1166 was encapsulated in T7-PEG-PCL micelle. Particle size and zeta potential were determined by dynamic light scattering. Particle morphology was studied by transmission electron microscopy. The particles were characterized by Fourier transform infrared, thermogravimetric analysis, and differential scanning calorimetry. Drug encapsulation efficiency, loading degree, and release profile were examined by high-performance liquid chromatography. Human breast cancer MDA-MB-231 was used to test the cytotoxicity. Flow cytometry and immunofluorescence imaging were used to study the PD-L1 inhibition in cell surface and exosomes. MDA-MB-231 and Jurkat co-culture studied T-cell activation and apoptosis.Results: The particle size of the empty and drug-loaded micelles showed a size distribution with an average diameter of 54.62 ± 2.28 nm and 60.22 ± 2.56 nm, respectively. The encapsulation efficiency of BMS-T7 was 83.89 ± 5.59%. The release half-life of drug-loaded micelles was 48h. The IC50 of BMS-1166 was 28.77 μM in MDA-MB-231 cells. In addition, the BMS-T7 showed a better inhibitory effect on PD-L1 expression in breast cancer cells and exosomes than the naked drug. The formulation significantly restored T-cell function compared to the BMS-1166 treatment.Conclusion: These results provide preliminary evidence indicating that BMS-T7 may have the potential to deliver drugs to breast cancer cells via active targeting and hold great promise in cancer immunotherapy drug delivery applications.Keywords: PD-L1, BMS-1166, immunotherapy, breast cancer, micelle

    UMNH:Mamm:1166

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    UMNH:Mamm:1166 Voucher Specimen Study Ski

    RAAPNOTITIE 1166

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    onderzoeksrappor

    EC62-1166 Selection of Lamps

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    EC 62-1166: This circular is about selecting the correct lamp for each area of a house or business

    552. Shunjō (1166-1227)

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    Iwao Seiichi, Iyanaga Teizō, Ishii Susumu, Yoshida Shōichirō, Fujimura Jun'ichirō, Fujimura Michio, Yoshikawa Itsuji, Akiyama Terukazu, Iyanaga Shōkichi, Matsubara Hideichi. 552. Shunjō (1166-1227). In: Dictionnaire historique du Japon, volume 18, 1992. Lettre S (2) p. 113

    552. Shunjō (1166-1227)

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    Iwao Seiichi, Iyanaga Teizō, Ishii Susumu, Yoshida Shōichirō, Fujimura Jun'ichirō, Fujimura Michio, Yoshikawa Itsuji, Akiyama Terukazu, Iyanaga Shōkichi, Matsubara Hideichi. 552. Shunjō (1166-1227). In: Dictionnaire historique du Japon, volume 18, 1992. Lettre S (2) p. 113

    RAAPRAPPORT 1166

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    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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