Browsing by Subject "NSCLC"
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Item PREPARATION OF A CISPLATIN PRODRUG FOR USE AGAINST NON-SMALL CELL LUNG CANCER(2014-03) Redfearn, Warren; Shi, Yi; Koneru, Bhuvaneswari; Di Pasqua, AnthonyBackground: Lung cancer is the leading cause of cancer-related death in the United States, and non-small cell lung cancer (NSCLC) the most common type. NSCLC is extremely difficult to treat, resulting in a poor prognosis for patients. Platinum (Pt) anti-cancer agents, such as cisplatin, remain a mainstay in the clinic; however, these Pt complexes act nonspecifically, and thus result in serious side-effects. Development and delivery of a Pt complex with an improved therapeutic index would be highly advantageous to the fight against NSCLC. We prepared trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV), referred to here as PtC, and studied its DNA binding and toxicity toward normal lung and NSCLC cells. Methods: A lipophilic Pt(IV) complex, PtC, was synthesized and characterized, and its binding to DNA and toxicity toward various cancer and normal cell lines determined. Results: We confirmed that the synthesized Pt complex binds to DNA in a manner similar to that of cisplatin, which suggests that it is cisplatin prodrug; however, probably due to its lipophilic nature and improved stability, PtC is much more toxic toward NSCLC cell lines than is cisplatin, and has a much improved therapeutic index. Conclusions: PtC shows promise as a therapeutic agent against NSCLC, and, furthermore, its lipophilic nature allows for us to incorporate it into mesoporous silica nanoparticles for fine-controlled release and the targeting of tumors.Item Properties of a Human Metastatic Variant Lung Cancer Model(2003-05-01) Poirot, Julie E.; Mart Hart; Robert Wordinger; Rick KitsonPoirot, J. Properties of a Human Metastatic Variant Lung Cancer Model. Master of Science (Molecular Biology and Immunology). May 2003. 44 pp., 11 illustrations, 1 table, 39 bibliography titles. A model of non-small cell lung cancer (NSCLC) has been developed for screening and preclinical drug evaluation by implanting the A549 lung cancer cell line orthotopically into immunocompromised (SCID) mice. Aggressive metastatic sublines were then derived from metastases from the primary implant. The purpose of this project is to elucidate some of the cellular properties involved in the tumor aggressiveness of the metastatic variant cell lines. In vitro migration and invasion assays produced data showing no significant differences between the rates of migration or invasion of parental and metastatic sublines. In vivo tumor burden experiments, however, produced data showing significant differences in the numbers and sizes of metastatic tumors formed when the three cell lines were compared in SCID mice. RT-PCR analysis has indicated that there are differences in the mRNA levels of certain matrix metalloproteinases. The A549 parental cells have matrix metalloproteinase-2 (MMP-2) but not MMP-9, while both metastatic variants show MMP-9 mRNA but no MMP-2. Western blots and gelatin zymographies also confirm these findings. RT-PCR analysis and casein zymography experiments have also shown no differences in the message or activity of urokinase plasminogen activator *uPA0 among the cell lines. Multidrug resistance studies were done on the tumor cell lines in order to compare their resistance to various classes of antineoplastic drugs. These studies indicate that there is no significant difference in the resistance to doxorubicin or paclitaxel, but the parental cell line is substantially more resistant to cisplatin than either of the metastatic sublines.