47
views
0
recommends
+1 Recommend
1 collections
    0
    shares

      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Radiosensitivity enhancement by combined treatment of nimotuzumab and celecoxib on nasopharyngeal carcinoma cells

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          In this study, the radiation-enhancing effects of combined treatment with nimotuzumab, a humanized EGFR-blocking antibody, and celecoxib, a COX-2 selective inhibitor, in human nasopharyngeal carcinoma (NPC) cells were investigated.

          Materials and methods

          3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide and clonogenic survival assays were done to evaluate the combined cytotoxic and radiosensitizing effects of nimotuzumab or celecoxib or the combination on CNE1 and CNE2 cells. Western blot analysis was performed to identify the effect of nimotuzumab and/or celecoxib with or without irradiation on the cytoplasmic and nuclear EGFR signaling pathways in CNE2 cells.

          Results

          Our results demonstrated that concurrent administration of nimotuzumab and celecoxib cooperatively enhanced the cytotoxicity and radiosensitivity of CNE2 cells but not CNE1 cells. The combination of both drugs with or without irradiation also cooperatively inhibited cytoplasmic and nuclear EGFR signaling pathways in CNE2 cells.

          Conclusion

          Our results suggest a promising approach for the treatment of poorly differentiated NPC.

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

          To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Nuclear EGFR as a molecular target in cancer.

            The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell's nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial.

              Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC).
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                16 July 2018
                : 12
                : 2223-2231
                Affiliations
                [1 ]Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China, wxsyzfz@ 123456163.com
                [2 ]Department of Radiation Oncology, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, People’s Republic of China
                [3 ]Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China
                [4 ]State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou, People’s Republic of China, fangsh@ 123456suda.edu.cn
                Author notes
                Correspondence: Fuzheng Zhang, Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi 214062, Jiangsu, People’s Republic of China, Tel +86 510 8868 2111, Fax +86 510 8586 0321, Email wxsyzfz@ 123456163.com
                Fenju Liu, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University. Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions. Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, 199 Renai Road, Suzhou 215123, Jiangsu, People’s Republic of China, Tel +86 512 6588 0060, Fax +86 512 6588 4380, Email fangsh@ 123456suda.edu.cn
                [*]

                These authors contributed equally to this work

                Article
                dddt-12-2223
                10.2147/DDDT.S163595
                6052925
                30038488
                37cef97d-9d06-438e-a0d5-8ec3cdf43ac7
                © 2018 Huang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                celecoxib,cyclooxygenase-2,epidermal growth factor receptor,nasopharyngeal carcinoma,nimotuzumab,radiosensitivity

                Comments

                Comment on this article