کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10900061 | 1084468 | 2012 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma
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کلمات کلیدی
PDACmAbTdT-mediated dUTP nick end labellingSCIDIgGMRPPancreatic ductal adenocarcinoma - آدنوکارسینوم پانکراس داکتالMonoclonal antibody - آنتی بادی مونوکلونالstandard deviation - انحراف معیارimmunoglobulin G - ایمونوگلوبولین GTUNEL - تونلOvarian cancer - سرطان تخمدانPancreatic cancer - سرطان پانکراسVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)multidrug resistance protein - پروتئین مقاوم در برابر چندین رژیمsevere combined immunodeficiency - کمبود شدید مصدومChemoresistance - کمرویی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma](/preview/png/10900061.png)
چکیده انگلیسی
The adhesion molecule L1CAM (CD171) accounts for enhanced motility, invasiveness and chemoresistance of tumor cells and represents a novel marker for various tumor entities including pancreatic and ovarian carcinoma. Recently, we showed that L1CAM inhibition increases the apoptotic response of tumor cells towards cytostatic drugs pointing to the potential of L1CAM to serve as a chemosensitizer in anti-cancer therapy. Thus, the present study evaluated the therapeutic potential of combined treatment with L1CAM antibodies and chemotherapeutic drugs in pancreatic and ovarian carcinoma model systems in vivo. Two L1CAM-specific antibodies (L1-14.10 and L1-9.3/2a) exhibiting high binding affinity to the L1CAM expressing pancreatic adenocarcinoma cell line Colo357 and the ovarian carcinoma cell line SKOV3ip were used for treatment. The combined therapy of SCID mice with either L1CAM antibody and gemcitabine and paclitaxel, respectively, reduced the growth of subcutaneously grown Colo357 or SKOV3ip tumors more efficiently than treatment with the cytostatic drug alone or in combination with control IgG. This was accompanied by an increased number of apoptotic tumor cells along with an elevated procaspase-8 expression. Furthermore, a lowered activation of NF-κB along with a reduced expression of VEGF and a diminished number of CD31-positive blood vessels were observed in tumors after combined therapy compared to control treatments, while the infiltration of F4/80-positive macrophages increased. Overall, these data provide new insights into the mechanism of the anti-cancer activity of L1CAM-blocking antibodies in vivo and support the suitability of L1CAM as a target for chemosensitization and of L1CAM-interfering antibodies as an appropriate tool to increase the therapeutic response of pancreatic and ovarian carcinoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 319, Issue 1, 1 June 2012, Pages 66-82
Journal: Cancer Letters - Volume 319, Issue 1, 1 June 2012, Pages 66-82
نویسندگان
Heiner Schäfer, Chantal Dieckmann, Olena Korniienko, Gerhard Moldenhauer, Helena Kiefel, Alexey Salnikov, Achim Krüger, Peter Altevogt, Susanne Sebens,