PubMed:23171475 JSONTXT

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":87,"end":115},"obj":"gene:3481"},{"id":"T1","span":{"begin":17,"end":34},"obj":"disease:C1527249"},{"id":"T2","span":{"begin":87,"end":115},"obj":"gene:3481"},{"id":"T3","span":{"begin":17,"end":34},"obj":"disease:C0009402"},{"id":"T4","span":{"begin":251,"end":279},"obj":"gene:3481"},{"id":"T5","span":{"begin":339,"end":359},"obj":"disease:C0009404"},{"id":"T6","span":{"begin":281,"end":285},"obj":"gene:3481"},{"id":"T7","span":{"begin":339,"end":359},"obj":"disease:C0009404"},{"id":"T8","span":{"begin":417,"end":421},"obj":"gene:3481"},{"id":"T9","span":{"begin":469,"end":486},"obj":"disease:C1527249"},{"id":"T10","span":{"begin":417,"end":421},"obj":"gene:3481"},{"id":"T11","span":{"begin":469,"end":486},"obj":"disease:C0009402"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system.\nBACKGROUND: Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.\nRESULTS: We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.\nCONCLUSIONS: Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy."}

{"project":"Allie","denotations":[{"id":"SS1_23171475_3_0","span":{"begin":219,"end":237},"obj":"expanded"},{"id":"SS2_23171475_3_0","span":{"begin":239,"end":242},"obj":"abbr"},{"id":"SS1_23171475_3_1","span":{"begin":251,"end":279},"obj":"expanded"},{"id":"SS2_23171475_3_1","span":{"begin":281,"end":285},"obj":"abbr"},{"id":"SS1_23171475_6_0","span":{"begin":734,"end":749},"obj":"expanded"},{"id":"SS2_23171475_6_0","span":{"begin":751,"end":754},"obj":"abbr"},{"id":"SS1_23171475_6_1","span":{"begin":760,"end":794},"obj":"expanded"},{"id":"SS2_23171475_6_1","span":{"begin":796,"end":800},"obj":"abbr"}],"relations":[{"id":"AE1_23171475_3_0","pred":"abbreviatedTo","subj":"SS1_23171475_3_0","obj":"SS2_23171475_3_0"},{"id":"AE1_23171475_3_1","pred":"abbreviatedTo","subj":"SS1_23171475_3_1","obj":"SS2_23171475_3_1"},{"id":"AE1_23171475_6_0","pred":"abbreviatedTo","subj":"SS1_23171475_6_0","obj":"SS2_23171475_6_0"},{"id":"AE1_23171475_6_1","pred":"abbreviatedTo","subj":"SS1_23171475_6_1","obj":"SS2_23171475_6_1"}],"text":"Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system.\nBACKGROUND: Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.\nRESULTS: We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.\nCONCLUSIONS: Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":158,"end":164},"obj":"HP_0002664"},{"id":"T2","span":{"begin":201,"end":207},"obj":"HP_0002664"},{"id":"T3","span":{"begin":350,"end":359},"obj":"HP_0002664"},{"id":"T4","span":{"begin":480,"end":486},"obj":"HP_0002664"}],"text":"Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system.\nBACKGROUND: Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.\nRESULTS: We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.\nCONCLUSIONS: Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"23171475-0#87#115#gene3481","span":{"begin":87,"end":115},"obj":"gene3481"},{"id":"23171475-0#17#34#diseaseC0009402","span":{"begin":17,"end":34},"obj":"diseaseC0009402"},{"id":"23171475-0#17#34#diseaseC1527249","span":{"begin":17,"end":34},"obj":"diseaseC1527249"},{"id":"23171475-2#32#60#gene3481","span":{"begin":251,"end":279},"obj":"gene3481"},{"id":"23171475-2#62#66#gene3481","span":{"begin":281,"end":285},"obj":"gene3481"},{"id":"23171475-2#120#140#diseaseC0009404","span":{"begin":339,"end":359},"obj":"diseaseC0009404"}],"relations":[{"id":"87#115#gene348117#34#diseaseC0009402","pred":"associated_with","subj":"23171475-0#87#115#gene3481","obj":"23171475-0#17#34#diseaseC0009402"},{"id":"87#115#gene348117#34#diseaseC1527249","pred":"associated_with","subj":"23171475-0#87#115#gene3481","obj":"23171475-0#17#34#diseaseC1527249"},{"id":"32#60#gene3481120#140#diseaseC0009404","pred":"associated_with","subj":"23171475-2#32#60#gene3481","obj":"23171475-2#120#140#diseaseC0009404"},{"id":"62#66#gene3481120#140#diseaseC0009404","pred":"associated_with","subj":"23171475-2#62#66#gene3481","obj":"23171475-2#120#140#diseaseC0009404"}],"text":"Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system.\nBACKGROUND: Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.\nRESULTS: We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.\nCONCLUSIONS: Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy."}