Objective： To investigate the expression of IL-13Ra2 gene in brain tumors. Methods： Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expre...Objective： To investigate the expression of IL-13Ra2 gene in brain tumors. Methods： Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results： IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion： Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.展开更多
Objective Gliomas are the most common malignant tumors in the central nervous system.Despite multiple therapies including surgery,chemotherapy,and radiotherapy,the prognosis of patients remains poor.Immunotherapy is a...Objective Gliomas are the most common malignant tumors in the central nervous system.Despite multiple therapies including surgery,chemotherapy,and radiotherapy,the prognosis of patients remains poor.Immunotherapy is an alternative method of treating glioma,and the use of dendritic cell vaccines is one of the promising treatment options.However,there is no specific tumor cell antigen that can trigger dendritic cells(DCs).IL-13Ra2 is a specific antigen expressed in glioma cells;in the current study,we have attempted to explore whether IL-13Ra2 could be the antigen that triggers DCs and to envisage its application as potential therapy for glioma.Methods The expression of IL-13Ra2 was detected in U251 glioma cell lines and primary glioma tissues using different methods.DCs from human blood were isolated and pulsed with recombinant IL-13Ra2,following which the cytotoxicity of these DCs on glioma cells was detected and analyzed.Results About 55.9% human glioma tissue cells expressed IL-13Ra2,while normal brain tissue cells did not show any expression.DC vaccines loaded with IL-13Ra2,glioma cell antigen,and brain tumor stem cell(BTSC) antigen could significantly stimulate the proliferation of T lymphocytes and induce cell death in the glioma tissue.Compared to other groups,DC vaccines loaded with BTSC antigen showed the strongest ability to activate cytotoxic T lymphocytes(CTLs),while the glioma cell antigen group showed no significant difference.Conclusion IL-13Ra2,which is expressed in gliomas and by glioma stem cells,as well as IL-13Ra2 could prove to be potential antigens for DC vaccine-based immunotherapy.展开更多
Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease progression.Targeting these rare cancer cells,however,remains challenging with respect to therapeutic benefit.Here,we report...Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease progression.Targeting these rare cancer cells,however,remains challenging with respect to therapeutic benefit.Here,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid cells.The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC.We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients.Biologically,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in vivo.This phenotype could be reversed by knocking down IL-13RA2.Mechanistically,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of IL-13.We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of p53.In conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.展开更多
Glioblastoma(GBM)is one of the most aggressive(grade IV)gliomas characterized by a high rate of recurrence,resistance to therapy and a grim survival prognosis.The long-awaited improvement in GBM patients'survival ...Glioblastoma(GBM)is one of the most aggressive(grade IV)gliomas characterized by a high rate of recurrence,resistance to therapy and a grim survival prognosis.The long-awaited improvement in GBM patients'survival rates essentially depends on advances in the development of new therapeutic approaches.Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnosis and management of brain cancers.In the current review,we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches.Moreover,we willsummarize the main evidence for the potential of the IL-13R alpha 2 receptor(IL13α2R)targeting in GBM early diagnosis and experimental therapy.展开更多
基金This work was supported by National Natural Science Foundation of China (No.303000100) and HYD Educational Foundation (No. 94018).
文摘Objective： To investigate the expression of IL-13Ra2 gene in brain tumors. Methods： Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results： IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion： Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.
文摘Objective Gliomas are the most common malignant tumors in the central nervous system.Despite multiple therapies including surgery,chemotherapy,and radiotherapy,the prognosis of patients remains poor.Immunotherapy is an alternative method of treating glioma,and the use of dendritic cell vaccines is one of the promising treatment options.However,there is no specific tumor cell antigen that can trigger dendritic cells(DCs).IL-13Ra2 is a specific antigen expressed in glioma cells;in the current study,we have attempted to explore whether IL-13Ra2 could be the antigen that triggers DCs and to envisage its application as potential therapy for glioma.Methods The expression of IL-13Ra2 was detected in U251 glioma cell lines and primary glioma tissues using different methods.DCs from human blood were isolated and pulsed with recombinant IL-13Ra2,following which the cytotoxicity of these DCs on glioma cells was detected and analyzed.Results About 55.9% human glioma tissue cells expressed IL-13Ra2,while normal brain tissue cells did not show any expression.DC vaccines loaded with IL-13Ra2,glioma cell antigen,and brain tumor stem cell(BTSC) antigen could significantly stimulate the proliferation of T lymphocytes and induce cell death in the glioma tissue.Compared to other groups,DC vaccines loaded with BTSC antigen showed the strongest ability to activate cytotoxic T lymphocytes(CTLs),while the glioma cell antigen group showed no significant difference.Conclusion IL-13Ra2,which is expressed in gliomas and by glioma stem cells,as well as IL-13Ra2 could prove to be potential antigens for DC vaccine-based immunotherapy.
基金supported by the National Natural Science Foundation of China(No.82173371,82273447,82273069)the project funded by China Postdoctoral Science Foundation(No.2022M711320,2022M711322)+7 种基金Shandong Postdoctoral innovation project(China)(No.SDCX-ZG202201002)Tai Shan Young Scholar Foundation of Shandong Province,China(No.tsqn201909192)Shandong Provincial Natural Science Foundation(China)(No.ZR2020YQ59,ZR2021QH021,ZR202112020099)Youth Innovation Science and Technology Support Plan of Shandong Province’s colleges and universities(China)(No.2021KJ017)the Project of Medicine Health and Technology Development Plan of Shandong Province,China(No.202103030586 and 202103030411)the Miaopu Research of the Affiliated Hospital of Jining Medical University,Shandong,China(No.MP-ZD-2020-005 and MP-ZD-2021-001)Ph.D.Research Foundation of the Affiliated Hospital of Jining Medical University,Shandong,China(No.2022-BS003)Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation in Jining Medical University,Shandong,China(No.JYHL2022FZD04).
文摘Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease progression.Targeting these rare cancer cells,however,remains challenging with respect to therapeutic benefit.Here,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid cells.The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC.We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients.Biologically,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in vivo.This phenotype could be reversed by knocking down IL-13RA2.Mechanistically,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of IL-13.We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of p53.In conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.
基金This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers"Digital Biodesign and Personalized Healthcare"(No.075-15-2020-926).
文摘Glioblastoma(GBM)is one of the most aggressive(grade IV)gliomas characterized by a high rate of recurrence,resistance to therapy and a grim survival prognosis.The long-awaited improvement in GBM patients'survival rates essentially depends on advances in the development of new therapeutic approaches.Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnosis and management of brain cancers.In the current review,we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches.Moreover,we willsummarize the main evidence for the potential of the IL-13R alpha 2 receptor(IL13α2R)targeting in GBM early diagnosis and experimental therapy.
