کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10915436 | 1090056 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models
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کلمات کلیدی
i.pMTDIVMIFPOrthotopic tumor modelImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیMaximum tolerated dose - حداکثر دوز قابل تحملPancreatic cancer - سرطان پانکراسInterstitial fluid pressure - فشار مایع بینابینیDorsal skinfold chamber - محفظه پوست پشتی پشتیVascular targeting - هدف قرار دادن عروقCytoskeleton - چارچوب یاخته، سیتواسکلتون، اسکلت سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 7, Issue 10, October 2005, Pages 957-966
Journal: Neoplasia - Volume 7, Issue 10, October 2005, Pages 957-966
نویسندگان
Axel Kleespies, Gudrun Köhl, Michael Friedrich, Anderson J. Ryan, Alan Barge, Karl-Walter Jauch, Christiane J. Bruns,