PubMed:21364021 JSON TXT

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DisGeNET

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":145,"end":151},"obj":"HP_0002664"},{"id":"T2","span":{"begin":170,"end":175},"obj":"HP_0002664"},{"id":"T3","span":{"begin":227,"end":232},"obj":"HP_0002664"},{"id":"T4","span":{"begin":273,"end":278},"obj":"HP_0002664"},{"id":"T5","span":{"begin":420,"end":425},"obj":"HP_0002664"}],"text":"HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance.\nPURPOSE: Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor-stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1-dependent resistance pathways.\nMETHODS: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). Reporter cells were serially interrogated in vitro before and after irradiation as monolayer and multicellular spheroid cultures and as subcutaneous xenografts in nu/nu mice.\nRESULTS: In vitro, single-dose irradiation of C6 and HN5 reporter cells modestly impacted HIF-1 signaling in normoxic monolayers and inhibited HIF-1 signaling in maturing spheroids. In contrast, irradiation of C6 or HN5 reporter xenografts with 8 Gy in vivo elicited marked upregulation of HIF-1 signaling and downstream proangiogenic signaling at 48 hours which preceded recovery of tumor growth. In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. High-resolution positron emission tomography and dual-contrast DCE-MRI of immobilized dorsal skin window tumors confirmed postradiotherapy HIF-1 signaling to spatiotemporally coincide with impaired stromal vascular function. Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance.\nCONCLUSIONS: Our results illustrate that tumor radioresistance is mediated by a capacity to compensate for stromal vascular disruption through HIF-1-dependent proangiogenic signaling and that clinically relevant vascular imaging techniques can spatially define mechanisms associated with tumor irradiation."}

Allie

{"project":"Allie","denotations":[{"id":"SS1_21364021_2_0","span":{"begin":101,"end":127},"obj":"expanded"},{"id":"SS2_21364021_2_0","span":{"begin":129,"end":134},"obj":"abbr"},{"id":"SS1_21364021_11_0","span":{"begin":1264,"end":1289},"obj":"expanded"},{"id":"SS2_21364021_11_0","span":{"begin":1291,"end":1294},"obj":"abbr"}],"relations":[{"id":"AE1_21364021_2_0","pred":"abbreviatedTo","subj":"SS1_21364021_2_0","obj":"SS2_21364021_2_0"},{"id":"AE1_21364021_11_0","pred":"abbreviatedTo","subj":"SS1_21364021_11_0","obj":"SS2_21364021_11_0"}],"text":"HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance.\nPURPOSE: Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor-stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1-dependent resistance pathways.\nMETHODS: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). Reporter cells were serially interrogated in vitro before and after irradiation as monolayer and multicellular spheroid cultures and as subcutaneous xenografts in nu/nu mice.\nRESULTS: In vitro, single-dose irradiation of C6 and HN5 reporter cells modestly impacted HIF-1 signaling in normoxic monolayers and inhibited HIF-1 signaling in maturing spheroids. In contrast, irradiation of C6 or HN5 reporter xenografts with 8 Gy in vivo elicited marked upregulation of HIF-1 signaling and downstream proangiogenic signaling at 48 hours which preceded recovery of tumor growth. In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. High-resolution positron emission tomography and dual-contrast DCE-MRI of immobilized dorsal skin window tumors confirmed postradiotherapy HIF-1 signaling to spatiotemporally coincide with impaired stromal vascular function. Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance.\nCONCLUSIONS: Our results illustrate that tumor radioresistance is mediated by a capacity to compensate for stromal vascular disruption through HIF-1-dependent proangiogenic signaling and that clinically relevant vascular imaging techniques can spatially define mechanisms associated with tumor irradiation."}

DisGeNET5_gene_disease

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"21364021-1#28#33#gene3091","span":{"begin":129,"end":134},"obj":"gene3091"},{"id":"21364021-1#28#33#gene29072","span":{"begin":129,"end":134},"obj":"gene29072"},{"id":"21364021-1#69#86#diseaseC0178874","span":{"begin":170,"end":187},"obj":"diseaseC0178874"},{"id":"21364021-2#28#33#gene3091","span":{"begin":217,"end":222},"obj":"gene3091"},{"id":"21364021-2#28#33#gene29072","span":{"begin":217,"end":222},"obj":"gene29072"},{"id":"21364021-2#38#51#diseaseC0879615","span":{"begin":227,"end":240},"obj":"diseaseC0879615"}],"relations":[{"id":"28#33#gene309169#86#diseaseC0178874","pred":"associated_with","subj":"21364021-1#28#33#gene3091","obj":"21364021-1#69#86#diseaseC0178874"},{"id":"28#33#gene2907269#86#diseaseC0178874","pred":"associated_with","subj":"21364021-1#28#33#gene29072","obj":"21364021-1#69#86#diseaseC0178874"},{"id":"28#33#gene309138#51#diseaseC0879615","pred":"associated_with","subj":"21364021-2#28#33#gene3091","obj":"21364021-2#38#51#diseaseC0879615"},{"id":"28#33#gene2907238#51#diseaseC0879615","pred":"associated_with","subj":"21364021-2#28#33#gene29072","obj":"21364021-2#38#51#diseaseC0879615"}],"text":"HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance.\nPURPOSE: Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor-stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1-dependent resistance pathways.\nMETHODS: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). Reporter cells were serially interrogated in vitro before and after irradiation as monolayer and multicellular spheroid cultures and as subcutaneous xenografts in nu/nu mice.\nRESULTS: In vitro, single-dose irradiation of C6 and HN5 reporter cells modestly impacted HIF-1 signaling in normoxic monolayers and inhibited HIF-1 signaling in maturing spheroids. In contrast, irradiation of C6 or HN5 reporter xenografts with 8 Gy in vivo elicited marked upregulation of HIF-1 signaling and downstream proangiogenic signaling at 48 hours which preceded recovery of tumor growth. In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. High-resolution positron emission tomography and dual-contrast DCE-MRI of immobilized dorsal skin window tumors confirmed postradiotherapy HIF-1 signaling to spatiotemporally coincide with impaired stromal vascular function. Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance.\nCONCLUSIONS: Our results illustrate that tumor radioresistance is mediated by a capacity to compensate for stromal vascular disruption through HIF-1-dependent proangiogenic signaling and that clinically relevant vascular imaging techniques can spatially define mechanisms associated with tumor irradiation."}

DisGeNet-2017-sample

{"project":"DisGeNet-2017-sample","denotations":[{"id":"T1559","span":{"begin":129,"end":134},"obj":"gene:3091"},{"id":"T1560","span":{"begin":170,"end":187},"obj":"disease:C0178874"},{"id":"T1561","span":{"begin":217,"end":222},"obj":"gene:3091"},{"id":"T1562","span":{"begin":227,"end":240},"obj":"disease:C0879615"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T1559","obj":"T1560"},{"id":"R2","pred":"associated_with","subj":"T1559","obj":"T1560"},{"id":"R3","pred":"associated_with","subj":"T1561","obj":"T1562"},{"id":"R4","pred":"associated_with","subj":"T1561","obj":"T1562"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance.\nPURPOSE: Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. The specific role played by HIF-1 and tumor-stromal interactions toward determining tumor resistance to radiation treatment remains undefined. We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1-dependent resistance pathways.\nMETHODS: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). Reporter cells were serially interrogated in vitro before and after irradiation as monolayer and multicellular spheroid cultures and as subcutaneous xenografts in nu/nu mice.\nRESULTS: In vitro, single-dose irradiation of C6 and HN5 reporter cells modestly impacted HIF-1 signaling in normoxic monolayers and inhibited HIF-1 signaling in maturing spheroids. In contrast, irradiation of C6 or HN5 reporter xenografts with 8 Gy in vivo elicited marked upregulation of HIF-1 signaling and downstream proangiogenic signaling at 48 hours which preceded recovery of tumor growth. In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. High-resolution positron emission tomography and dual-contrast DCE-MRI of immobilized dorsal skin window tumors confirmed postradiotherapy HIF-1 signaling to spatiotemporally coincide with impaired stromal vascular function. Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance.\nCONCLUSIONS: Our results illustrate that tumor radioresistance is mediated by a capacity to compensate for stromal vascular disruption through HIF-1-dependent proangiogenic signaling and that clinically relevant vascular imaging techniques can spatially define mechanisms associated with tumor irradiation."}