Kleespies, Axel and Ischenko, Ivan and Eichhorn, Martin E. and Seeliger, Hendrik and Amendt, Christiane and Mantell, Ole and Jauch, Karl-Walter and Bruns, Christiania J. (2008) Matuzumab short-term therapy in experimental pancreatic cancer: Prolonged antitumor activity in combination with gemcitabine. CLINICAL CANCER RESEARCH, 14 (17). pp. 5426-5436. ISSN 1078-0432,
Full text not available from this repository. (Request a copy)Abstract
Purpose: The epidermal growth factor receptor ErbB-1 is commonly expressed in pancreatic cancer and ErbB-1 targeting has shown promising results. We wanted to evaluate matuzumab (EMD72000), a fully humanized ErbB-1-specific monoclonal antibody in combination with gemcitabine in experimental pancreatic cancer. Experimental Design: Using the human pancreatic cancer cell line L3.6pl, we investigated matuzumab in vitro and in vivo. ErbB-1 phosphorylation and downstream pathway activation were evaluated by Western blot. Proliferation and migration assays and fluorescence-activated cell sorting analysis were done. For in vivo studies, we used an orthotopic nude mice model in which 40 mg/kg of matuzumab 100 mg/kg of gemcitabine were administered twice weekly. Different treatment durations (7,14, 21, and 25 days) and varying time points of treatment initiation (days 8,15, 22, and 29) were evaluated. Ki67, CD31, and phosphorylated p44/42 mitogen-activated protein kinase (MAPK) immunohistochemistry were done. Results: ErbB-1 phosphorylation and downstream MAPK and AKT signaling were significantly reduced by matuzumab. Matuzumab significantly inhibited proliferation and migration in vitro, and induced tumor cell apoptosis in a dose-dependant manner. Matuzumab therapy significantly lowered tumor volume in vivo, reduced lymph node and liver metastases, and decreased microvessel density and tumor cell proliferation. These effects were significantly enhanced when gemcitabine was added. A significant and prolonged antitumor activity was even evident with short-term therapy (7 days) and with a late onset of therapy (day 22 after tumor cell injection). Conclusions: Matuzumab is an effective agent with long-lasting antiproliferative, proapoptotic, antiangiogenic, and antimetastatic activity in human pancreatic cancer models. These effects might be potentiated by gemcitabine.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR RECEPTOR; ACTIVATED PROTEIN-KINASES; EGFR MONOCLONAL-ANTIBODY; PHASE-II TRIAL; CONSTITUTIVE ACTIVATION; MEDIATED CYTOTOXICITY; SOLID TUMORS; NUDE-MICE; CARCINOMA; CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 07:53 |
| Last Modified: | 26 Oct 2020 07:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30327 |
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