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Sechenov First Moscow State Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012728","name":"Frederick National Laboratory for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012728","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011621","name":"Winship Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Purine nucleoside phosphorylase (PNP) gene transfer represents a promising approach to treatment of head and neck malignancies. We tested recombinant adenovirus already in phase I\/II clinical testing and leading\u2010edge patient\u2010derived xenografts (PDX) as a means to optimize this therapeutic strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our experiments investigated purine base cytotoxicity, PNP enzyme activity following treatment of malignant tissue, tumor mass regression, viral receptor studies, and transduction by tropism\u2010modified adenovirus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Replication deficient vector efficiently transduced PDX cells and mediated significant anticancer effect following treatment with fludarabine phosphate in vivo. Either 6\u2010methylpurine or 2\u2010fluoroadenine (toxic molecules generated by the PNP approach) ablated head and neck cancer cell proliferation. High levels of adenovirus\u20103 specific receptors were detected in human tumor models, and vector was evaluated that utilizes this pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our studies provide the scientific foundation necessary to improve PNP prodrug cleavage and advance a new treatment for head and neck cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.1708","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T03:15:25Z","timestamp":1666062925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluating antitumor activity of <scp><i>Escherichia coli<\/i><\/scp> purine nucleoside phosphorylase against head and neck patient\u2010derived xenografts"],"prefix":"10.1002","volume":"6","author":[{"given":"Regina","family":"Rab","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Ehrhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagelu R.","family":"Achyut","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Disha","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Children's Hospital of Atlanta Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Gilbert\u2010Ross","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunzi","family":"Huang","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Floyd","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton V.","family":"Borovjagin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Alabama at Birmingham; PNP Therapeutics, Inc.  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