{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:53:55Z","timestamp":1789437235825,"version":"build-2803163510"},"reference-count":24,"publisher":"Frontiers Media SA","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:p>Paclitaxel is a chemotherapeutic agent used for the treatment of metastatic breast cancer. 2,5,7,8-Tetramethyl-2R-(4R, 8R-12-trimethyltridecyl) chroman-6-yloxyacetic acid (\u03b1-TEA) is an analog of vitamin E that inhibits primary tumor growth and the incidence of lymphatic and pulmonary metastases in preclinical animal models. Here, the efficacy of sequential treatment with paclitaxel and \u03b1-TEA was tested in the BALB\/c syngeneic 66cl-4-GFP mammary cancer model. Both agents were formulated into liposomes and delivered by inhalation in an effort to increase anti-tumor efficacy and minimize paclitaxel toxicity. Combination treatment consisting of twelve days of every-other-day treatment with aerosolized paclitaxel (approximately 0.46 \u03bcg\/mouse\/treatment) followed by a daily regimen of aerosolized \u03b1-TEA (36 \u03bcg\/mouse\/treatment) significantly decreased primary tumor burden when compared to untreated or liposome control groups and was significantly better than individual treatments ( P &lt; 0.05). Importantly, combination treatment was significantly better at reducing lung and lymph node micrometastatic foci when compared to control and individual treatment groups ( P &lt; 0.05). Immunohistochemical analyses of tumor sections showed combination treatment when compared to liposome control or individual treatments to significantly decrease total number of cells staining positive for the endothelial cell marker CD31 or for the Ki67 marker of cellular proliferation and increase the number of apoptotic (TUNEL positive) tumor cells ( P &lt; 0.001). Studies addressing the toxicity of \u03b1-TEA demonstrated that \u03b1-TEA formulated in liposomes and delivered by aerosol (72 \u03bcg\/mouse\/day) or gavage (5 mg\/mouse\/day) for 25 days did not cause blood, liver, or kidney toxicity. In conclusion, sequential inhalation delivery of liposomal-formulated paclitaxel and \u03b1-TEA produces significantly better anti-tumor outcomes than single treatments.<\/jats:p>","DOI":"10.3181\/0901-rm-8","type":"journal-article","created":{"date-parts":[[2009,8,5]],"date-time":"2009-08-05T21:46:17Z","timestamp":1249508777000},"page":"1244-1252","source":"Crossref","is-referenced-by-count":40,"title":["Aerosol Delivery of Liposomal Formulated Paclitaxel and Vitamin E Analog Reduces Murine Mammary Tumor Burden and Metastases"],"prefix":"10.3389","volume":"234","author":[{"given":"Paul","family":"Latimer","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla","family":"Menchaca","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob G.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Kline","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, and the Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, Texas 78712; and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2009,10,1]]},"reference":[{"key":"bibr-R1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(01)02149-3"},{"key":"bibr-R2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/5.suppl_5.3"},{"key":"bibr-R3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970328)71:1<103::AID-IJC17>3.0.CO;2-J"},{"key":"bibr-R4","doi-asserted-by":"crossref","unstructured":"Cabanes A, Briggs KE, Gokhale PC, Treat JA, Rahman A. Comparative in vivo studies with paclitaxel and liposome-encapsulated paclitaxel. Int J Oncol 12:1035\u20131040, 1998.","DOI":"10.3892\/ijo.12.5.1035"},{"key":"bibr-R5","unstructured":"Lawson KA, Anderson K, Menchaca M, Atkinson J, Sun L, Knight V, Gilbert BE, Conti C, Sanders BG, Kline K. Novel vitamin E analogue decreases syngeneic mouse mammary tumor burden and reduces lung metastasis. Mol Cancer Ther 2:437\u2013444, 2003."},{"key":"bibr-R6","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2403"},{"key":"bibr-R7","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422901112"},{"key":"bibr-R8","doi-asserted-by":"crossref","unstructured":"Jia L, Yu W, Wang P, Sanders BG, Kline K. In vivo and in vitro studies of anticancer actions of \u03b1-TEA for human prostate cancer cells. Prostate 68:849\u2013860, 2007.","DOI":"10.1002\/pros.20750"},{"key":"bibr-R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(07)76017-X"},{"key":"bibr-R10","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422900913"},{"key":"bibr-R11","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005938428456"},{"key":"bibr-R12","unstructured":"Koshkina NV, Waldrep JC, Roberts LE, Golunski E, Melton S, Knight V. Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases in murine renal carcinoma model. Clin Cancer Res 7:3258\u20133262, 2001."},{"key":"bibr-R13","doi-asserted-by":"publisher","DOI":"10.1007\/s002800000230"},{"key":"bibr-R14","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050966"},{"key":"bibr-R15","doi-asserted-by":"publisher","DOI":"10.1023\/B:BREA.0000041593.69178.57"},{"key":"bibr-R16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1630"},{"key":"bibr-R17","doi-asserted-by":"publisher","DOI":"10.1593\/neo.08302"},{"key":"bibr-R18","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2007-0204"},{"key":"bibr-R19","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1634"},{"key":"bibr-R21","unstructured":"Wu Y, Zu K, Ni J, Yeh S, Kasi D, James NS, Chemler S, Ip C. Cellular and molecular effects of alpha-tocopheryloxybutyrate: lessons for the design of vitamin E analog for cancer prevention. Anticancer Res 24: 395\u2013302, 2004."},{"key":"bibr-R22","doi-asserted-by":"publisher","DOI":"10.2174\/1568009043332943"},{"key":"bibr-R23","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23689"},{"key":"bibr-R24","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2007.02.004"},{"key":"bibr-R26","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0817-y"}],"container-title":["Experimental Biology and Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.3181\/0901-RM-8","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.3181\/0901-RM-8","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.3181\/0901-RM-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:55:32Z","timestamp":1777571732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ebm-journal.org\/journals\/experimental-biology-and-medicine\/articles\/10.3181\/0901-rm-8\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2009,10]]}},"alternative-id":["10.3181\/0901-RM-8"],"URL":"https:\/\/doi.org\/10.3181\/0901-rm-8","relation":{},"ISSN":["1535-3702","1535-3699"],"issn-type":[{"value":"1535-3702","type":"print"},{"value":"1535-3699","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10]]}}}