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      Can Aidi injection restore cellular immunity and improve clinical efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy? A meta-analysis of 17 randomized controlled trials following the PRISMA guidelines

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          Abstract

          Background:

          Aidi injection is an adjuvant chemotherapy drug commonly used in China. Can Aidi injection restore the cellular immunity and improve the clinical efficacy in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy? There is a lack of strong evidence to prove it. To further reveal it, we systematically evaluated all related studies. We collected all studies about the clinical efficacy and cellular immunity of Aidi injection plus platinum-based chemotherapy for NSCLC in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China biological medicine database (CBM) (established to June 2015), Cochrane Central Register of Controlled Trials (CCRCT) (June 2015), Chinese clinical trial registry, and US-clinical trials (June 2015). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the patient intervention control group outcomes principles and synthesized the data by meta-analysis. Seventeen (RCTs) with 1390 NSCLC patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR) and disease control rate (DCR) were as follows: 1.26 (1.12, 1.42) and 1.11(1.04, 1.17). The merged standardized mean difference (SMD) values and their 95% CI of meta-analysis for the percentage of CD3 +T cells, CD4 +T cells, CD8 +T cells, natural killer (NK) cells, and CD4 +/CD8 + T cell ratio were as follows: 1.41, (0.89, 1.92), 1.59, (1.07, 2.11), 0.85, (0.38, 1.33), 1.64 (0.89, 2.39) and 0.91, (0.58, 1.24). Compared with platinum-based chemotherapy alone, all differences were statistically significant. These results might be overestimated or underestimated.

          Conclusions:

          Aidi injection plus platinum-based chemotherapy can improve the clinical efficacy of patients with NSCLC. Aidi injection could significantly restore the cellular immunity damaged by platinum-based chemotherapy. It may be an important tumor immune modulator and protector for patients with NSCLC treated with chemotherapy.

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          Most cited references40

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          Reporting results of cancer treatment.

          On the initiative of the World Health Organization, two meetings on the Standardization of Reporting Results of Cancer Treatment have been held with representatives and members of several organizations. Recommendations have been developed for standardized approaches to the recording of baseline data relating to the patient, the tumor, laboratory and radiologic data, the reporting of treatment, grading of acute and subacute toxicity, reporting of response, recurrence and disease-free interval, and reporting results of therapy. These recommendations, already endorsed by a number of organizations, are proposed for international acceptance and use to make it possible for investigators to compare validly their results with those of others.
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            A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb.

            The immunopotentiating effect of the roots of Astragalus membranaceus, a medicinal herb, has been associated with its polysaccharide fractions (Astragalus polysaccharides, APS). We herein demonstrate that APS activates mouse B cells and macrophages, but not T cells, in terms of proliferation or cytokine production. Fluorescence-labeled APS (fl-APS) was able to selectively stain murine B cells, macrophages and a also human tumor cell line, THP-1, as determined in flow cytometric analysis and confocal laser scanning microscopy. The specific binding of APS to B cells and macrophages was competitively inhibited by bacterial lipopolysaccharides. Rabbit-anti-mouse immunoglobulin (Ig) antibody was able to inhibit APS-induced proliferation of, and APS binding to, mouse B cells. Additionally, APS effectively stimulated the proliferation of splenic B cells from C3H/HeJ mice that have a mutated TLR4 molecule incapable of signal transduction. These results indicate that APS activates B cells via membrane Ig in a TLR4-independent manner. Interestingly, macrophages from C3H/HeJ mice were unable to respond to APS stimulation, suggesting a positive involvement of the TLR4 molecule in APS-mediated macrophage activation. Monoclonal Ab against mouse TLR4 partially inhibited APS binding with macrophages, implying direct interaction between APS and TLR4 on cell surface. These results may have important implications for our understanding on the molecular mechanisms of immunopotentiating polysaccharides from medicinal herbs.
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              Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies

              Chemotherapy has historically been thought to induce cancer cell death in an immunogenically silent manner. However, recent studies have demonstrated that therapeutic outcomes with specific chemotherapeutic agents (e.g. anthracyclines) correlate strongly with their ability to induce a process of immunogenic cell death (ICD) in cancer cells. This process generates a series of signals that stimulate the immune system to recognize and clear tumor cells. Extensive studies have revealed that chemotherapy-induced ICD occurs via the exposure/release of calreticulin (CALR), ATP, chemokine (C–X–C motif) ligand 10 (CXCL10) and high mobility group box 1 (HMGB1). This review provides an in-depth look into the concepts and mechanisms underlying CALR exposure, activation of the Toll-like receptor 3/IFN/CXCL10 axis, and the release of ATP and HMGB1 from dying cancer cells. Factors that influence the impact of ICD in clinical studies and the design of therapies combining chemotherapy with immunotherapy are also discussed.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                November 2016
                04 November 2016
                : 95
                : 44
                : e5210
                Affiliations
                [a ]Evidence-based Medicine Center, MOE Virtual Research Center of Evidence-based Medicine at Zunyi Medical College
                [b ]Department of Respiratory Medicine (Center for Evidence-based and Translational Medicine of Major Infectious Diseases), Affiliated Hospital of Zunyi Medical College, Zunyi 563000, Guizhou, China
                [c ]Teaching and Research Group of Evidence-based Medicine, Zhuhai Campus of Zunyi Medical College, Zhuhai, Guangdong, China
                [d ]Department of Immunology, Zunyi Medical College
                [e ]Department of Oncology, Affiliated Hospital of Zunyi Medical College
                [f ]Department of Neurology, First People's Hospital of Zunyi City and Third Affiliated Hospital of Zunyi Medical College
                [g ]Outpatient Department of Psychological Counseling Clinic (Center for Evidence-based and Translational Medicine of Major Infectious Diseases), Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou, China.
                Author notes
                []Correspondence: Prof Zheng Xiao, Evidence-based Medicine Center, MOE Virtual Research Center of Evidence-based Medicine at Zunyi Medical College, Affiliated Hospital of Zunyi Medical College, Zunyi 563003,Guizhou Province, P. R. China (e-mail: zy426f@ 123456163.com ).
                Article
                05210
                10.1097/MD.0000000000005210
                5591112
                27858864
                642f2b5d-c747-474d-bb7c-9cccf1e6466b
                Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 19 May 2016
                : 18 September 2016
                : 4 October 2016
                Categories
                3800
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                adjuvant chemotherapy,aidi injection,cellular immunity,meta-analysis,non-small-cell lung cancer,platinum-based chemotherapy

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