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Sentinel Lymph Node Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model.

Abstract

In clinical N0 cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)-targeted therapy using the urokinase-type plasminogen activator (uPA)-dependent oncolytic Sendai virus "BioKnife". The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its anti-tumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue SCC cells, in the tongue of the nude mice, and after two weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imaging system. We also examined its anti-tumor effects and mechanisms through serial section analysis of LNs. GFP reporter expression was clearly visible in the LNs of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and LNs in the virus groups compared to that in the control groups (p < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant anti-tumor effect against LNM compared to the control groups (p < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in clinical N0 patients with HNSCC.

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  • Authors+Show Affiliations

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    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College.

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    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College kojaraki@ndmc.ac.jp.

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    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College.

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    Department of Otorhinolaryngology - Head and Neck Surgery, National Defense Medical College.

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    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College.

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    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College.

    ,

    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College.

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    Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College.

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    Department of Otolaryngologyl-Head & Neck Surgery, National Defense Medical College.

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    Department of Otorhinolaryngology - Head and Neck Surgery, Kitasato University School of Medicine.

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    Department of Gene Medicine, DNAVEC Corporation.

    Otorhinolaryngology-Head & Neck Surgery, National Defense Medical College.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31171582

    Citation

    Tanaka, Yuya, et al. "Sentinel Lymph Node Targeted Therapy By Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model." Molecular Cancer Therapeutics, 2019.
    Tanaka Y, Araki K, Tanaka S, et al. Sentinel Lymph Node Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model. Mol Cancer Ther. 2019.
    Tanaka, Y., Araki, K., Tanaka, S., Miyagawa, Y., Suzuki, H., Kamide, D., ... Shiotani, A. (2019). Sentinel Lymph Node Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model. Molecular Cancer Therapeutics, doi:10.1158/1535-7163.MCT-18-1372.
    Tanaka Y, et al. Sentinel Lymph Node Targeted Therapy By Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model. Mol Cancer Ther. 2019 Jun 6; PubMed PMID: 31171582.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Sentinel Lymph Node Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model. AU - Tanaka,Yuya, AU - Araki,Koji, AU - Tanaka,Shingo, AU - Miyagawa,Yoshihiro, AU - Suzuki,Hiroshi, AU - Kamide,Daisuke, AU - Tomifuji,Masayuki, AU - Uno,Kosuke, AU - Kimura,Eiko, AU - Yamashita,Taku, AU - Ueda,Yasuji, AU - Shiotani,Akihiro, Y1 - 2019/06/06/ PY - 2019/05/30/accepted PY - 2018/12/16/received PY - 2019/04/11/revised PY - 2019/6/8/entrez PY - 2019/6/7/pubmed PY - 2019/6/7/medline JF - Molecular cancer therapeutics JO - Mol. Cancer Ther. N2 - In clinical N0 cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)-targeted therapy using the urokinase-type plasminogen activator (uPA)-dependent oncolytic Sendai virus "BioKnife". The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its anti-tumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue SCC cells, in the tongue of the nude mice, and after two weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imaging system. We also examined its anti-tumor effects and mechanisms through serial section analysis of LNs. GFP reporter expression was clearly visible in the LNs of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and LNs in the virus groups compared to that in the control groups (p < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant anti-tumor effect against LNM compared to the control groups (p < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in clinical N0 patients with HNSCC. SN - 1538-8514 UR - https://www.unboundmedicine.com/medline/citation/31171582/Sentinel_Lymph_Node_Targeted_Therapy_by_Oncolytic_Sendai_Virus_Suppresses_Micrometastasis_of_Head_and_Neck_Squamous_Cell_Carcinoma_in_an_Orthotopic_Nude_Mouse_Model L2 - http://mct.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=31171582 DB - PRIME DP - Unbound Medicine ER -