{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:48:31Z","timestamp":1791071311756,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,9,8]],"date-time":"2004-09-08T00:00:00Z","timestamp":1094601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2004,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Nonsmall cell lung carcinomas (NSCLCs) are associated with very dismal prognoses, and adjuvant chemotherapy, including irinotecan, taxanes, platin, and vinca alkaloid derivatives, offer patients only slight clinical benefits. Part of the chemoresistance of NSCLC results from the expression in NSCLC cells of a very large set of endogenous proteins, which antagonize chemotherapy\u2010mediated attacks on these tumor cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The authors set up an orthotopic model of a human NSCLC by grafting A549 cells into the lungs of nude mice. They tried treating these A549 NSCLC orthotopic xenograft\u2013bearing nude mice on the basis of various chemotherapeutic protocols, including chronic administrations of taxol, oxaliplatin, and irinotecan. A cyclooxygenase\u20102 (COX\u20102) inhibitor (NS\u2010398) also was assayed in combination with taxol. The immunohistochemical expression levels of COX\u20102, prostaglandin E synthetase (PGES), ornithine decarboxylase (ODC), the lung\u2010related resistance protein (LRP), and glutathione\u2010S\u2010transferase\u2010\u03b1 (GST\u2010\u03b1), GST\u2010\u03bc, and GST\u2010\u03c0 were quantitatively determined by means of computer\u2010assisted microscopy in control and drug\u2010treated NSCLC orthotopic xenografts.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The orthotopic A549 xenograft model developed in 100% of the grafted mice, leading to brain metastases in approximately 61% mice and to liver metastases in approximately 40% of mice. The model was resistant to taxol and oxaliplatin and was only weakly sensitive to irinotecan. High levels of chemoresistant markers (i.e., COX\u20102, PGES, ODC, LRP, GST\u2010\u03b1, GST\u2010\u03bc, and GST\u2010\u03c0) were observed in the nontreated A549 xenografts, although with dramatic variations in individual expression. Taxol and oxaliplatin significantly increased the levels of expression of COX\u20102, PGES, GST\u2010\u03bc, and GST\u2010\u03c0 in a number of different experimental protocols.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The A549 orthotopic xenograft model could be used to evaluate investigational chemotherapeutic agents to identify drugs rapidly that are more active than the drugs currently in use in hospitals. Cancer 2004. \u00a9 2004 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.20571","type":"journal-article","created":{"date-parts":[[2004,9,14]],"date-time":"2004-09-14T04:32:39Z","timestamp":1095136359000},"page":"1908-1918","source":"Crossref","is-referenced-by-count":92,"title":["Development of a chemoresistant orthotopic human nonsmall cell lung carcinoma model in nude 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