Journal Title
Title of Journal: Invest New Drugs
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Abbravation: Investigational New Drugs
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Authors: Milica Pešić Ana Podolski Ljubiša Rakić Sabera Ruždijić
Publish Date: 2009/06/18
Volume: 28, Issue: 4, Pages: 482-492
Abstract
The resistant cell line NCIH460/R and its counterpart NCIH460 were used to investigate the ability of purine analogs to overcome multidrug resistance MDR that seriously limit the efficacy of lung cancer regimens with chemotherapeutic agents Two purine analogs sulfinosine SF and 8ClcAMP exerted dosedependent effects on cell growth in both parental and resistant cell lines They significantly decreased mdr1 expression in NCIH460/R cells Low concentrations 1 µM of SF and 8ClcAMP in combination with doxorubicin DOX exerted synergistic growth inhibition in both cell lines Pretreatment with SF and 8ClcAMP improved the sensitivity to DOX more than verapamil VER the standard modulator of MDR The increased accumulation of DOX observed after the treatment with SF and 8ClcAMP was consistent with the results obtained with VER VER stimulated the effect of 8ClcAMP on DOX cytotoxicity and mdr1 expression Combinations of either SF or 8ClcAMP with VER at clinically acceptable concentrations exhibited synergistic effects on cell growth inhibition in the resistant cell line SF and 8ClcAMP modulated MDR in NCIH460/R cells especially when applied before DOX administration This feature together with their ability to reverse MDR renders the purine analogs in combination with VER as potential candidates for improving the clinical activity of existing lung cancer therapeutics
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- Differences in maximum tolerated doses and approval doses of molecularly targeted oncology drug between Japan and Western countries
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- Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer
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- In vitro and in vivo antineoplastic and immunological effects of pterocarpanquinone LQB-118
- A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck
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- A phase I study of S-1 with concurrent radiotherapy in elderly patients with locally advanced non-small cell lung cancer
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- A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma
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