کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10911636 | 1088386 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The retinoid X receptor agonist bexarotene (Targretin) synergistically enhances the growth inhibitory activity of cytotoxic drugs in non-small cell lung cancer cells
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کلمات کلیدی
ICNRARMTDRetinoid X receptorRXRAP-1ATCCCDK4CTCLWST-1FAMSAPKNMUN-nitrosomethylureaJnkCmaxNF-κB6-carboxy-fluorescein - 6-کربوکسی فلورسینc-Jun N-terminal kinase - C-Jun N-terminal kinaseDMSO - DMSOQuantitative PCR - PCR کمیq-PCR - Q-PCRBexarotene - بکساروتنTamra - تامراMaximum tolerated dose - حداکثر دوز قابل تحملmaximum concentration - حداکثر غلظتDimethyl sulfoxide - دیمتیل سولفواکسیدNSCLC - سرطان ریوی غیر سلول کوچکNon-small cell lung cancer - سرطان غیر سلول کوچک ریهcombination index - شاخص ترکیبیnuclear factor kappa B - فاکتور هسته ای کاپا BCutaneous T cell lymphoma - لنفوم بدن انسان TAmerican Type Culture Collection - مجموعه فرهنگی نوع آمریکاییDrug synergy - همکاری با مواد مخدرpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازretinoblastoma protein - پروتئین رتینوبلاستوماactivator protein-1 - پروتئین فعال کننده-1Stress-activated protein kinase - پروتئین کیناز فعال شده با استرسcyclin-dependent kinase 4 - کییناز وابسته به سیکلین 4Retinoic acid receptor - گیرنده اسید رتینوئیک
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This study was designed to evaluate, using preclinical models of non-small cell lung cancer (NSCLC), the growth inhibitory effects of the retinoid X receptor (RXR) agonist bexarotene (LGD1069, Targretin) in combination with cytotoxic agents currently used as standard first-line therapy in advanced disease. Although single-agent bexarotene had modest growth inhibitory effects in several cell lines, efficacy was observed only in the micromolar range (>1 μM), which approximates the plasma Cmax measured in pharmacokinetic studies in patients. However, when combined with paclitaxel or vinorelbine, bexarotene produced a concentration-dependent enhancement of the growth inhibitory activities of paclitaxel and vinorelbine. Formal synergy analysis using the Calu3 cell line demonstrated that the combination of bexarotene with either cytotoxic agent produced synergistic activity (combination index, CI < 1). The in vitro observations were confirmed in vivo in a NSCLC xenograft tumor model (Calu3), where both bexarotene/paclitaxel and bexarotene/vinorelbine combinations produced significantly greater antitumor effects than the single agents. These results demonstrate that bexarotene can cooperate with widely used cytotoxic agents to decrease the growth of NSCLC tumor cells both in vitro and in vivo, and suggest the potential benefit of adding a RXR-selective agonist in combination with chemotherapy for NSCLC treatment. Furthermore, the data support the clinical observation from phase I/IIa trials suggesting that bexarotene has beneficial effects on survival when used in combination with cytotoxic agents in advanced NSCLC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Lung Cancer - Volume 50, Issue 1, October 2005, Pages 9-18
Journal: Lung Cancer - Volume 50, Issue 1, October 2005, Pages 9-18
نویسندگان
Thomas W. Hermann, Wan-Ching Yen, Patricia Tooker, Bingqi Fan, Karen Roegner, Andrés Negro-Vilar, William W. Lamph, Reid P. Bissonnette,