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      Drug Design, Development and Therapy (submit here)

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      Effect Of Bevacizumab On Growth Of Human Nasal Polyposis In Vitro; An Off-Label Use Of Anti-Angiogenic Agent For Nasal Polyposis Treatment

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          Abstract

          Introduction

          Nasal polyposis (NP) is a frequent problem during adulthood. Treatment of NP is primarily based on drugs, such as oral or topical steroids and in some types, by surgery. Despite of available therapeutic options for NP, recurrence after polypectomy is found. Vascular endothelial growth factor (VEGF) is a known factor involved in NP. Bevacizumab is a monoclonal antibody, which acts against VEGF.

          Aim

          Regarding the availability of bevacizumab and its use in ophthalmic off-label application, in this study, we hypothesized that it could be a choice of non-invasive treatment. The researchers aimed at evaluating the use of bevacizumab in vitro on the growth of NP.

          Materials and methods

          In this experimental study, the researchers used eight non-allergic NP tissues from patients admitted for polypectomy clinic of Imam Reza Hospital, Mashhad. Tissues were cultured in DMEM medium based on standard protocols in the presence or absence of bevacizumab (10 to 250 μM) then incubated. The mean of the responses was reported. The level of VEGF and MTT test for NP epithelial cell viability were determined for each group. Data were analyzed using the SPSS software.

          Results

          The researchers demonstrated that bevacizumab leads to a decrease in the level of VEGF (the most common cause of angiogenesis in NP) in media culture of NP, dose-dependently (P<0.001). The highest mean was related to the 10-μM group and the least mean was related to the 250-μM group. In MTT test after 5 days, it was shown that the percentage of viable epithelial NP cells (due to apoptosis) was decreased dose-dependently and could lead to resolving NP tissue (P<0.001), significantly.

          Conclusion

          This study showed that bevacizumab could help decrease the growth of NP tissue dose-dependently in organ culture in vitro by inhibiting VEGF. It seems that bevacizumab could be a good candidate for the treatment of non-allergic NP.

          Most cited references35

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          Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy.

          Napoleone Ferrara, Kenneth J Hillan, William E Novotny (2005)
          Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in vivo. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high affinity VEGF receptors. VEGF plays an essential role in developmental angiogenesis and is important also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with VEGF inhibitors in a variety of malignancies are ongoing. Recently, a humanized anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the FDA as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.
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            Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro.

            Martin Vanderlaan, Yaning Wang, David Fei … (2003)
            Bevacizumab (Avastin, Genentech) is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), a critical angiogenic factor involved in both physiological and pathological conditions. It has been recently approved by the US FDA as a first-line therapy for widespread metastatic colorectal cancer. This report is a detailed biological characterization of bevacizumab in a variety of in vitro models. It is shown that bevacizumab potently neutralizes VEGF and blocks its signal transduction through both the VEGFR-1 and VEGFR-2 receptors, as demonstrated by the inhibition of VEGF-induced cell proliferation, survival, permeability, nitric oxide production, as well as migration and tissue factor production. Although bevacizumab retains the ability to bind to human Fcgamma receptors and complement protein C1q, it does not demonstrate cell or complement-mediated cytotoxicity in either VEGF producing or targeting cells. Thus the mechanism of anti-tumor activity of bevacizumab is most likely due to its anti-angiogenesis effect through binding and neutralization of secreted VEGF.
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              Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis.

              Claus Bachert, Luo Zhang, Phillippe Gevaert (2015)
              Chronic rhinosinusitis (CRS) affects more than 10% of the population in the United States and Europe. Recent findings point to a considerable variation of inflammatory subtypes in patients with CRS with nasal polyps and patients with CRS without nasal polyps. According to current guidelines, glucocorticosteroids and antibiotics are the principle pharmacotherapeutic approaches; however, they fail in a group of patients who share common clinical and laboratory markers. Several clinical phenotypes often leading to uncontrolled disease, including adult nasal polyposis, aspirin-exacerbated respiratory disease, and allergic fungal rhinosinusitis, are characterized by a common endotype: a TH2 bias is associated with a higher likelihood of comorbid asthma and recurrence after surgical treatment. As a consequence, several innovative approaches targeting the TH2 bias with humanized mAbs have been subjected to proof-of-concept studies in patients with CRS with nasal polyps with or without comorbid asthma: omalizumab, reslizumab, mepolizumab, and recently dupilumab. Future concepts using upstream targets, such as GATA-3, also focus on this endotype. This current development might result in advantages in the treatment of patients with the most severe CRS.
              Article 0 comments Cited 82 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): DDDT
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 24 September 2019
                Publication date Collection: 2019
                Volume: 13
                Pages: 3383-3389
                Affiliations
                [1 ]Rhino-sinus, Ear, and Skull Base Diseases Research Center, Guilan University of Medical Sciences , Rasht, Iran
                [2 ]Cardiology Department, Imam Reza & Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences , Mashhad, Iran
                [3 ]Pharmaceutical Research Division, Booali Research Center, Mashhad University of Medical Sciences , Mashhad, Iran
                [4 ]Faculty of Medicine, Guilan University of Medical Sciences , Rasht, Iran
                [5 ]Pharmaceutical Research Division, Booali Research Center, Mashhad University of Medical Sciences , Mashhad, Iran
                [6 ]Faculty of Medicine, Ear, Nose and Throat Department, Mashhad University of Medical Sciences , Mashhad, Iran
                Author notes
                Correspondence: Amin Saeidinia Faculty of Medicine, Mashhad University Complex , Azadi Square, Mashhad9177948564, IranTel +98 511 9119451607 Email saeidiniaa971@mums.ac.ir
                Article
                Publisher ID: 219724
                DOI: 10.2147/DDDT.S219724
                PMC ID: 6767760
                SO-VID: fb7e9ed5-253c-40e7-a8fb-37d5bc0a10b9
                Copyright © © 2019 Nemati et al.
                License:

                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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 19 June 2019
                Date accepted : 11 September 2019
                Page count
                Figures: 3, Tables: 3, References: 38, Pages: 7
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: nasal polyposis,non-allergic polyps,bevacizumab,avastin,in vitro study
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: nasal polyposis, non-allergic polyps, bevacizumab, avastin, in vitro study

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