{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:22:29Z","timestamp":1792707749649,"version":"4.5.0"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,11,20]]},"abstract":"<jats:p>\n                    No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2\u20133 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 \u00d7 10\n                    <jats:sup>7<\/jats:sup>\n                    to 5.8 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses &lt;5.8 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1210662109","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T00:57:15Z","timestamp":1352163435000},"page":"19403-19407","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":178,"title":["Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction"],"prefix":"10.1073","volume":"109","author":[{"given":"Bruce J.","family":"Baum","sequence":"first","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Alevizos","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana P.","family":"Cotrim","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Liu","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"McCullagh","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne M.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Burbelo","sequence":"additional","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah E.","family":"Citrin","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesl K.","family":"Nottingham","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Branch, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan F.","family":"Rudy","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Branch, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter","family":"Van Waes","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Branch, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Millie A.","family":"Whatley","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Section and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime S.","family":"Brahim","sequence":"additional","affiliation":[{"name":"Department of Oral-Maxillofacial Surgery, University of Maryland, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Chiorini","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatina","family":"Danielides","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. James","family":"Turner","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Patronas","sequence":"additional","affiliation":[{"name":"Section on Neuroradiology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Section and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay P.","family":"Nikolov","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor G.","family":"Illei","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Therapeutics Branch, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,11,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20006"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(95)00060-C"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-010-0837-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2010.06.052"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.1o816.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-010-0827-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb18338.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2009.09.004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3268"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.11.007"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2006.17.1122"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1416"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340152712647"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340152712638"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.128"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2006.17.167"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7935"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2002.0638"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.5.468"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1996.7.17-2177"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.476"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.034"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345000790020201"},{"key":"e_1_3_3_24_2","volume-title":"Fields\u2019 Virology","author":"Wold WSM","year":"2007","unstructured":"WSM Wold, MS Horwitz, Adenoviruses. 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