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Y have a bias due to small sample size and AZP-531 web incomplete data in most studies. This systematic review only assessed the influence of adoptive transfusion of Tol-DCs on islet allograft survival. However, we have also conducted six systematic reviews on its effect in other organ transplantation models, which has been published [31] or are in preparation.ConclusionsIn conclusion, Tol-DCs induction by different mechanisms prolonged MHC mismatched islet allograft survival to different degrees, but allopeptide-pulsed host DCs performed the best. Immunosuppressive or costimulatory blockade were synergistic with Tol-DC on graft survival, and could even help induce immune tolerance. A single-intrathymic injection of 104 Tol-DCs prolonged survival more than other doses. Multiple injections were not more effective at promoting survival yet increased the risk and cost.2)3)Supporting InformationChecklist S1 PRISMA 2009.(DOC)4)AcknowledgmentsWe would like to thank Lei Luo and Chengwen Li for assistance in gathering articles and providing advice.Author ContributionsConceived and designed the experiments: YL GS JS LF. Performed the experiments: GS JS YZ YG. Analyzed the data: GS YZ YG WW. Contributed reagents/materials/analysis tools: GS WW MX TY. Wrote the paper: GS JS. Data extraction: GS JS TY MX. Critical revision of the manuscript: JS YL LF.Tol-DC therapy in clinical islet transplantationDC vaccines have been applied successfully in clinical cancer therapy [25,28], which highlights the feasibility of the clinical
Lung cancer is the leading cause of cancer deaths in the world, causing more than one million deaths worldwide [1]. Despite advances in early detection and standard treatment, lung cancer is often diagnosed at an advanced stage and has a poor prognosis. Therefore, prevention and treatment of lung cancer are the focus of intensive current research [2]. CDA-2 (cell differentiation agent 2) is a urinary preparation that isolated from healthy human urine in China. It is a novel multifunctional drug that is useful for both the prevention and treatment of several tumors, including leukemia, breast cancer, liver cancer, and pheochromocytoma, in preclinical investigations [3?]. However, the mechanisms of tumor inhibitory action of CDA-2 are far from clear, and especially there was no report on lung cancer. CDA-2 contains multiple active components, including phenylacetylglutamine (PG) (41 ), benzoyl glycocoll (35 ), peptides (MW 400?800) (17 ), 4-OH-phenylacetic acid (6 ), and 5-OH-indoleacetic acid (1 ), which with different mechanisms of anticancer [5]. Although tumor inhibition may be attributed to these components, PG is likely to be a major tumorinhibitory component [3]. Phase I/II/III clinical trials of CDA-2 have been completed in China in 2003. In August 2004, the State Drug Administration (SDA) of China approved the use of CDA-2 as an anticancer drug in solid tumors. Although CDA-2 was suggested to contribute to tumor inhibition through the upregulation of peroxisome proliferator-activated receptor-c (PPARc) and repression of PI3/Akt signaling order AZP-531 pathway in tumor cells, the tumor-inhibiting effect of CDA-2 was so far mainly demonstrated in cancer cells and its action in tumor microenvironments, especially to immune/inflammatory cells in tumor stroma, has not been critically evaluated [6,7]. NF-kB is a key coordinator of inflammatory and immune response 12926553 and has recently been found to play a pivotal role in carcinogenesis of a number of cancers i.Y have a bias due to small sample size and incomplete data in most studies. This systematic review only assessed the influence of adoptive transfusion of Tol-DCs on islet allograft survival. However, we have also conducted six systematic reviews on its effect in other organ transplantation models, which has been published [31] or are in preparation.ConclusionsIn conclusion, Tol-DCs induction by different mechanisms prolonged MHC mismatched islet allograft survival to different degrees, but allopeptide-pulsed host DCs performed the best. Immunosuppressive or costimulatory blockade were synergistic with Tol-DC on graft survival, and could even help induce immune tolerance. A single-intrathymic injection of 104 Tol-DCs prolonged survival more than other doses. Multiple injections were not more effective at promoting survival yet increased the risk and cost.2)3)Supporting InformationChecklist S1 PRISMA 2009.(DOC)4)AcknowledgmentsWe would like to thank Lei Luo and Chengwen Li for assistance in gathering articles and providing advice.Author ContributionsConceived and designed the experiments: YL GS JS LF. Performed the experiments: GS JS YZ YG. Analyzed the data: GS YZ YG WW. Contributed reagents/materials/analysis tools: GS WW MX TY. Wrote the paper: GS JS. Data extraction: GS JS TY MX. Critical revision of the manuscript: JS YL LF.Tol-DC therapy in clinical islet transplantationDC vaccines have been applied successfully in clinical cancer therapy [25,28], which highlights the feasibility of the clinical
Lung cancer is the leading cause of cancer deaths in the world, causing more than one million deaths worldwide [1]. Despite advances in early detection and standard treatment, lung cancer is often diagnosed at an advanced stage and has a poor prognosis. Therefore, prevention and treatment of lung cancer are the focus of intensive current research [2]. CDA-2 (cell differentiation agent 2) is a urinary preparation that isolated from healthy human urine in China. It is a novel multifunctional drug that is useful for both the prevention and treatment of several tumors, including leukemia, breast cancer, liver cancer, and pheochromocytoma, in preclinical investigations [3?]. However, the mechanisms of tumor inhibitory action of CDA-2 are far from clear, and especially there was no report on lung cancer. CDA-2 contains multiple active components, including phenylacetylglutamine (PG) (41 ), benzoyl glycocoll (35 ), peptides (MW 400?800) (17 ), 4-OH-phenylacetic acid (6 ), and 5-OH-indoleacetic acid (1 ), which with different mechanisms of anticancer [5]. Although tumor inhibition may be attributed to these components, PG is likely to be a major tumorinhibitory component [3]. Phase I/II/III clinical trials of CDA-2 have been completed in China in 2003. In August 2004, the State Drug Administration (SDA) of China approved the use of CDA-2 as an anticancer drug in solid tumors. Although CDA-2 was suggested to contribute to tumor inhibition through the upregulation of peroxisome proliferator-activated receptor-c (PPARc) and repression of PI3/Akt signaling pathway in tumor cells, the tumor-inhibiting effect of CDA-2 was so far mainly demonstrated in cancer cells and its action in tumor microenvironments, especially to immune/inflammatory cells in tumor stroma, has not been critically evaluated [6,7]. NF-kB is a key coordinator of inflammatory and immune response 12926553 and has recently been found to play a pivotal role in carcinogenesis of a number of cancers i.