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PEP06 polypeptide 30 is a novel clusterdissociating agent inhibiting αv integrin/FAK/Src signaling in oral squamous cell carcinoma cells

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1163-1173页

作者： Gulnara Tuguzbaeva er Yue Xi Chen Lina He Xinlei Li Jiaming Ju Ying Qin Valentin pavlov Yanjie Lu Wenting Jia Yunlong Bai Yumei Niu Baofeng Yang Central Laboratory of Scientific Research Bashkir State Medical UniversityUfa 450008Russian Federation Department of Pharmacology(State-Province Key Laboratories of BiomedicineePharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbin 150081China Department of Endodontics the First Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Department of Orthopedic Dentistry and Maxillofacial Surgery Bashkir State Medical UniversityUfa 450008Russian Federation

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial *** oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be *** to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of *** study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in ***,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human *** study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous *** PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly ***,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC ***06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in ***,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

关键词： Oral squamous cell carcinoma Tumor cell clusters Collective migration Metastasis αv integrin/FAK/RC signaling RGD

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Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels:Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment

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Journal of Innovative Optical Health Sciences 2018年第4期11卷 98-107页

作者： Olga.pavlova alexan.er Shirokov alexan.er Fomin Nikita Navolokin Andrey Terskov alexan.er Khorovodov Anton Namykin Alexey pavlov Valery Tuchin Oxana Semyachkina-Glushkovskaya Interdisciplinary Center of Critical Technologies in Medicine Saratov State University 83 Astrakhanskaya Str.Saratov 410012Russia Institute of Biochemistry and Physiology of Plants and Microorganisms Russian Academy of Sciences13 Entuziastov Ave.Saratov 410049Russia Saratov State Medical University 112 Bolshaya Kazachia Str. Saratov 410012Russia Department of Optics and Biophotonics Saratov State University 83 Astrakhanskaya Str.Saratov 410012Russia Yuri Gagarin State Technical University of Saratov 77 Politechnicheskaya Str. Saratov 410054Russia Laboratory of Laser Diagnostics of Technical and Living Systems Institute of Precision Mechanics and Control of RAS 24 Rabochaya Str.Saratov 410028Russia Laboratory of Biophotonics Tomsk State University 36 Lenin's Ave.Tomsk 634050Russia

Malignant gliomas are highly invasive tumors that 1use the cerebral vessels for invasion due to high vascular fragility of the blood--brain barrier(BBB).On one hand,glioma is characterized by the BBB disruption,on the other hand,drug brain delivery via the BBB is a big challenge in glioma *** limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma ***,we present in vrivo and er vrivo study of the BBB disruption and glioma cells(GCs)migration in rats using fuorescence and confocal *** uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells,where the BBB was impermeable for high weight *** migr ation of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages *** mechanisms underlying glioma progression remain umknown but there is an evidence that the sympathetic nervous system(SNS)via activation of vascular beta2-adrenoreceptors(B2-ADRs)can play an important role in tumor *** results clearly show an increase in the expression of vascular B2-ADRs and production of the beta arrestin-1-co-factor of B2-ADRs signaling pathway in rats with *** blockade of B2-ADRs reduces the BBB disruption,macrophages infiltration,GCs migration and increases survival *** data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis。

关键词： Glioma macrophages blood-brain barrier beta-2 adrenoreceptors bet a arrestin-1

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