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      Fraction From Lycium barbarum Polysaccharides Reduces Immunotoxicity and Enhances Antitumor Activity of Doxorubicin in Mice

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          Abstract

          The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

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          The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity.

          PHY906, a four-herb Chinese medicine formula first described 1800 years ago, decreases gastrointestinal toxicity induced by the chemotherapeutic drug CPT-11 (irinotecan), as shown in a phase I/II clinical study. Similarly, in a murine colon 38 allograft model, PHY906 increased the antitumor activity of CPT-11 while decreasing animal weight loss caused by CPT-11. Here, we have further examined the effect of PHY906 on the intestinal toxicity caused by CPT-11 in mice. PHY906 did not protect against the initial DNA damage and apoptosis triggered by CPT-11 in the intestine, but by 4 days after CPT-11 treatment, PHY906 had restored the intestinal epithelium by promoting the regeneration of intestinal progenitor or stem cells and several Wnt signaling components. PHY906 also potentiated Wnt3a activity in human embryonic kidney-293 cells. Furthermore, PHY906 exhibited anti-inflammatory effects in mice by decreasing the infiltration of neutrophils or macrophages, tumor necrosis factor-alpha expression in the intestine, and proinflammatory cytokine concentrations in plasma. Chemical constituents of PHY906 potently inhibited nuclear factor kappaB, cyclooxygenase-2, and inducible nitric oxide synthase. Our results show that the herbal medicine PHY906 can counteract the toxicity of CPT-11 via several mechanisms that act simultaneously.
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            Antitumor and immunomodulatory activity of Astragalus membranaceus polysaccharides in H22 tumor-bearing mice.

            In the present study, we investigated the antitumor and immunomodulatory activity of Astragalus membranaceus polysaccharide (AMP) on liver cancer using murine H22 hepatocarcinoma model. The results showed that AMP (100 and 400 mg/kg) could effectively inhibit the solid tumor growth of H22 hepatocarcinoma transplanted in BALB/c mice. Besides, the body weight, spleen/thymus indexes and phagocytotic function of macrophage of H22 tumor bearing mice were also improved in two AMP treated groups. Furthermore, AMP treatment could promote the secretion of IL-2, IL-12 and TNF-α and decreased IL-10 level in serum. Taken together, these findings indicate that AMP has antitumor activity in vivo at least partly via improving immune responses of host organism, and seems to be safe and effective for the use of anti-tumor therapy. Copyright © 2013 Elsevier B.V. All rights reserved.
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              Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy.

              Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.
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                Author and article information

                Journal
                Integr Cancer Ther
                Integr Cancer Ther
                ICT
                spict
                Integrative Cancer Therapies
                SAGE Publications (Sage CA: Los Angeles, CA )
                1534-7354
                1552-695X
                22 January 2018
                September 2018
                : 17
                : 3
                : 860-866
                Affiliations
                [1 ]Guangzhou University of Chinese Medicine, Guangzhou, the People’s Republic of China
                [2 ]Infinitus Chinese Herbal Immunity Research Centre, Guangzhou, the People’s Republic of China
                Author notes
                [*]Lian Zhou, Guangzhou University of Chinese Medicine, No. 232 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 51006, the People’s Republic of China. Email: immunology@ 123456gzucm.edu.cn
                Article
                10.1177_1534735417753544
                10.1177/1534735417753544
                6142073
                29355051
                3ae8a4bf-fe36-4346-9f05-0f2f83015e7b
                © The Author(s) 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 12 September 2017
                : 2 December 2017
                : 4 December 2017
                Funding
                Funded by: China Postdoctoral Science Foundation, FundRef https://doi.org/10.13039/501100002858;
                Award ID: No. 2016M602548
                Categories
                Research Articles

                lycium barbarum polysaccharides,doxorubicin,immunotoxicity,antitumor activity,chemotherapy

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