دورية أكاديمية
أعرض في EDS

Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells.

التفاصيل البيبلوغرافية
العنوان: Recombinant Vaccinia Viruses Coding Transgenes of Apoptosis-Inducing Proteins Enhance Apoptosis But Not Immunogenicity of Infected Tumor Cells.
المؤلفون: Koval O; Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.; Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia., Kochneva G; Department of Viral Hepatitis, State Research Center of Virology and Biotechnology 'Vector', Rospotrebnadzor, Koltsovo, Russia., Tkachenko A; Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia., Troitskaya O; Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.; Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia., Sivolobova G; Department of Viral Hepatitis, State Research Center of Virology and Biotechnology 'Vector', Rospotrebnadzor, Koltsovo, Russia., Grazhdantseva A; Department of Viral Hepatitis, State Research Center of Virology and Biotechnology 'Vector', Rospotrebnadzor, Koltsovo, Russia., Nushtaeva A; Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia., Kuligina E; Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia., Richter V; Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.
المصدر: BioMed research international [Biomed Res Int] 2017; Vol. 2017, pp. 3620510. Date of Electronic Publication: 2017 Aug 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Hindawi Pub. Co.
مواضيع طبية MeSH: Apoptosis/*genetics , Apoptosis Regulatory Proteins/*genetics , Transgenes/*genetics , Vaccinia virus/*genetics, Animals ; Antineoplastic Agents ; Biomarkers, Tumor/genetics ; Caspase 3/genetics ; Caspase 7/genetics ; Cell Death/genetics ; Cell Line, Tumor ; Chlorocebus aethiops ; DNA Fragmentation ; Female ; Genetic Vectors/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; HSP70 Heat-Shock Proteins/genetics ; Humans ; Membrane Potential, Mitochondrial/genetics ; Mice ; Mice, SCID ; Neoplasms/genetics ; Oncolytic Viruses/genetics ; Phosphatidylserines/genetics ; Up-Regulation/genetics ; Virus Replication/genetics ; bcl-2-Associated X Protein/genetics
مستخلص: Genetic modifications of the oncolytic vaccinia virus (VV) improve selective tumor cell infection and death, as well as activation of antitumor immunity. We have engineered a double recombinant VV, coding human GM-CSF, and apoptosis-inducing protein apoptin (VV-GMCSF-Apo) for comparing with the earlier constructed double recombinant VV-GMCSF-Lact, coding another apoptosis-inducing protein, lactaptin, which activated different cell death pathways than apoptin. We showed that both these recombinant VVs more considerably activated a set of critical apoptosis markers in infected cells than the recombinant VV coding GM-CSF alone (VV-GMCSF-dGF): these were phosphatidylserine externalization, caspase-3 and caspase-7 activation, DNA fragmentation, and upregulation of proapoptotic protein BAX. However, only VV-GMCSF-Lact efficiently decreased the mitochondrial membrane potential of infected cancer cells. Investigating immunogenic cell death markers in cancer cells infected with recombinant VVs, we demonstrated that all tested recombinant VVs were efficient in calreticulin and HSP70 externalization, decrease of cellular HMGB1, and ATP secretion. The comparison of antitumor activity against advanced MDA-MB-231 tumor revealed that both recombinants VV-GMCSF-Lact and VV-GMCSF-Apo efficiently delay tumor growth. Our results demonstrate that the composition of GM-CSF and apoptosis-inducing proteins in the VV genome is very efficient tool for specific killing of cancer cells and for activation of antitumor immunity.
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المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Apoptosis Regulatory Proteins)
0 (Biomarkers, Tumor)
0 (HSP70 Heat-Shock Proteins)
0 (Phosphatidylserines)
0 (bcl-2-Associated X Protein)
83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
EC 3.4.22.- (Caspase 3)
EC 3.4.22.- (Caspase 7)
تواريخ الأحداث: Date Created: 20170928 Date Completed: 20180523 Latest Revision: 20240327
رمز التحديث: 20240327
مُعرف محوري في PubMed: PMC5603130
DOI: 10.1155/2017/3620510
PMID: 28951871
قاعدة البيانات: MEDLINE
الوصف
تدمد:2314-6141
DOI:10.1155/2017/3620510