| Id |
Subject |
Object |
Predicate |
Lexical cue |
| TextSentencer_T1 |
0-91 |
Sentence |
denotes |
HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance. |
| TextSentencer_T2 |
92-100 |
Sentence |
denotes |
PURPOSE: |
| TextSentencer_T3 |
101-188 |
Sentence |
denotes |
Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. |
| TextSentencer_T4 |
189-331 |
Sentence |
denotes |
The specific role played by HIF-1 and tumor-stromal interactions toward determining tumor resistance to radiation treatment remains undefined. |
| TextSentencer_T5 |
332-501 |
Sentence |
denotes |
We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1-dependent resistance pathways. |
| TextSentencer_T6 |
502-659 |
Sentence |
denotes |
METHODS: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). |
| TextSentencer_T7 |
660-834 |
Sentence |
denotes |
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. |
| TextSentencer_T8 |
835-843 |
Sentence |
denotes |
RESULTS: |
| TextSentencer_T9 |
844-1016 |
Sentence |
denotes |
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. |
| TextSentencer_T10 |
1017-1232 |
Sentence |
denotes |
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. |
| TextSentencer_T11 |
1233-1386 |
Sentence |
denotes |
In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. |
| TextSentencer_T12 |
1387-1611 |
Sentence |
denotes |
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. |
| TextSentencer_T13 |
1612-1721 |
Sentence |
denotes |
Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance. |
| TextSentencer_T14 |
1722-1734 |
Sentence |
denotes |
CONCLUSIONS: |
| TextSentencer_T15 |
1735-2028 |
Sentence |
denotes |
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. |
| T1 |
0-91 |
Sentence |
denotes |
HIF-1-dependent stromal adaptation to ischemia mediates in vivo tumor radiation resistance. |
| T2 |
92-100 |
Sentence |
denotes |
PURPOSE: |
| T3 |
101-188 |
Sentence |
denotes |
Hypoxia-inducible factor 1 (HIF-1) promotes cancer cell survival and tumor progression. |
| T4 |
189-331 |
Sentence |
denotes |
The specific role played by HIF-1 and tumor-stromal interactions toward determining tumor resistance to radiation treatment remains undefined. |
| T5 |
332-501 |
Sentence |
denotes |
We applied a multimodality preclinical imaging platform to mechanistically characterize tumor response to radiation, with a focus on HIF-1-dependent resistance pathways. |
| T6 |
502-659 |
Sentence |
denotes |
METHODS: C6 glioma and HN5 human squamous carcinoma cells were stably transfected with a dual HIF-1 signaling reporter construct (dxHRE-tk/eGFP-cmvRed2XPRT). |
| T7 |
660-834 |
Sentence |
denotes |
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. |
| T8 |
835-843 |
Sentence |
denotes |
RESULTS: |
| T9 |
844-1016 |
Sentence |
denotes |
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. |
| T10 |
1017-1232 |
Sentence |
denotes |
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. |
| T11 |
1233-1386 |
Sentence |
denotes |
In situ ultrasound imaging and dynamic contrast-enhanced (DCE) MRI indicated that HIF-1 signaling followed acute disruption of stromal vascular function. |
| T12 |
1387-1611 |
Sentence |
denotes |
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. |
| T13 |
1612-1721 |
Sentence |
denotes |
Targeted disruption of HIF-1 signaling established this pathway to be a determinant of tumor radioresistance. |
| T14 |
1722-1734 |
Sentence |
denotes |
CONCLUSIONS: |
| T15 |
1735-2028 |
Sentence |
denotes |
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. |