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      Chitosan oligosaccharides in combination with Agaricus blazei Murill extract reduces hepatoma formation in mice with severe combined immunodeficiency

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          Abstract

          Chitosan and Agaricus blazei Murill (ABM) extracts possess antitumor activities. The aim of the present study was to investigate whether chitosan, ABM extract or the two in combination were effective against tumors in tumor-bearing mice. The mice were subcutaneously injected with SK-Hep 1 cells and were then were divided into the following six groups: Group 1, control group; group 2, chitosan 5 mg/kg/day; group 3, chitosan 20 mg/kg/day; group 4, ABM (246 mg/kg/day) and chitosan (5 mg/kg/day) combined; group 5, ABM (984 mg/kg/day) and chitosan (20 mg/kg/day) combined; and group 6, ABM (984 mg/kg/day). The mice were treated with the different concentrations of chitosan, ABM or combinations of the two for 6 weeks. The levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and vascular endothelial growth factor (VEGF), and tissue histopathological features were examined in the surviving animals. Based on the results of the investigation, the treatments performed in groups 2, 3 and 4 were identified as being capable of reducing the weights of the tumors, however, group 4, which was treated with chitosan (5 mg/kg/day) in combination with ABM (246 mg/kg/day) was able to reduce the levels of GOT and VEGF. As a result, treatment with chitosan in combination with ABM may offer potential in cancer therapy and requires further investigation.

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          Most cited references44

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          Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases.

          Vascular endothelial growth factors (VEGFs) belong to the platelet-derived growth factor supergene family, and they play central roles in the regulation of angiogenesis and lymphangiogenesis. VEGF-A, the major factor for angiogenesis, binds to two tyrosine kinase (TK) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and regulates endothelial cell proliferation, migration, vascular permeability, secretion and other endothelial functions. VEGFR-2 exhibits a strong TK activity towards pro-angiogenic signals, whereas the soluble VEGFR-1 (sFlt-1) functions as an endogenous VEGF inhibitor. sFlt-1 is abnormally overexpressed in the placenta of preeclampsia patients, resulting in the major symptoms of the disease due to abnormal trapping of VEGFs. The VEGF-VEGFR system is crucial for tumour angiogenesis, and anti-VEGF-VEGFR molecules are now widely used in the clinical field to treat cancer patients. The efficacy of these molecules in prolonging the overall survival of patients has been established; however, some cancers do not respond well and reduced tumour sensitivity to anti-VEGF signals may occur after long-term treatment. The molecular basis of tumour refractoriness should be determined to improve anti-angiogenic therapy.
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            Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis.

            The VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates. VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). VEGFR1, which occurs in transmembrane and soluble forms, negatively regulates vasculogenesis and angiogenesis during early embryogenesis, but it also acts as a positive regulator of angiogenesis and inflammatory responses, playing a role in several human diseases such as rheumatoid arthritis and cancer. The soluble VEGFR1 is overexpressed in placenta in preeclampsia patients. VEGFR2 has critical functions in physiological and pathological angiogenesis through distinct signal transduction pathways regulating proliferation and migration of endothelial cells. VEGFR3, a receptor for the lymphatic growth factors VEGF-C and VEGF-D, but not for VEGF-A, regulates vascular and lymphatic endothelial cell function during embryogenesis. Loss-of-function variants of VEGFR3 have been identified in lymphedema. Formation of tumor lymphatics may be stimulated by tumor-produced VEGF-C, allowing increased spread of tumor metastases through the lymphatics. Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases.
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              Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation.

              Chitin is a surface component of parasites and insects, and chitinases are induced in lower life forms during infections with these agents. Although chitin itself does not exist in humans, chitinases are present in the human genome. We show here that acidic mammalian chitinase (AMCase) is induced via a T helper-2 (Th2)-specific, interleukin-13 (IL-13)-mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma. AMCase neutralization ameliorated Th2 inflammation and airway hyperresponsiveness, in part by inhibiting IL-13 pathway activation and chemokine induction. AMCase may thus be an important mediator of IL-13-induced responses in Th2-dominated disorders such as asthma.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                July 2015
                09 March 2015
                09 March 2015
                : 12
                : 1
                : 133-140
                Affiliations
                [1 ]Department of Medical Education and Research, Cheng Hsin General Hospital, Taipei 112, Taiwan, R.O.C.
                [2 ]Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 112, Taiwan, R.O.C.
                [3 ]Departments of Clinical Pathology, Cheng Hsin General Hospital, Taipei 112, Taiwan, R.O.C.
                [4 ]Departments of Anatomical Pathology, Cheng Hsin General Hospital, Taipei 112, Taiwan, R.O.C.
                [5 ]Division of Gastroenterology, Cheng Hsin General Hospital, Taipei 112, Taiwan, R.O.C.
                [6 ]Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu 300, Taiwan, R.O.C.
                [7 ]Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan, R.O.C.
                [8 ]Department of Biology, Ching Cheng High School, Changhua 500, Taiwan, R.O.C.
                [9 ]School of Chinese Medicine for Post Baccalaureate, I Shou University, Kaohsiung 840, Taiwan, R.O.C.
                [10 ]Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
                [11 ]Department of Biotechnology, Asia University, Taichung 404, Taiwan, R.O.C.
                Author notes
                Correspondence to: Professor Jing Gung Chung, Department of Biological Science and Technology, China Medical University, 91 Hsueh Shih Road, Taichung 404, Taiwan, R.O.C., E mail: jgchung@ 123456mail.cmu.edu.tw
                Professor Lung Yuan Wu, School of Chinese Medicine for Post Baccalaureate, I Shou University, 8 Yida Road, Yanchao, Kaohsiung 840, Taiwan, R.O.C., E mail: dr.wuly@ 123456gmail.com
                [*]

                Contributed equally

                Article
                mmr-12-01-0133
                10.3892/mmr.2015.3454
                4438976
                25760985
                c81154b3-95d8-4a0e-9b06-5b11f9ac086e
                Copyright © 2015, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 08 April 2014
                : 30 January 2015
                Categories
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                chitosan,agaricus blazei murill,vascular endothelial growth factor

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