Nitric oxide–mediated increase in tumor blood flow and oxygenation of tumors implanted in muscles stimulated by electric pulses
Oxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities. We tested the hypothesis that electrical stimulation of the sciatic nerve could modify the oxygenation status and the blood flow of tumors implanted in the thigh of mice. The sciatic nerve was electrically stimulat...
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| Veröffentlicht in: | International journal of radiation oncology, biology, physics biology, physics, 2003-03, Vol.55 (4), p.1066-1073 |
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| container_title | International journal of radiation oncology, biology, physics |
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| creator | Jordan, Bénédicte F Sonveaux, Pierre Feron, Olivier Grégoire, Vincent Beghein, Nelson Gallez, Bernard |
| description | Oxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities. We tested the hypothesis that electrical stimulation of the sciatic nerve could modify the oxygenation status and the blood flow of tumors implanted in the thigh of mice.
The sciatic nerve was electrically stimulated at 5 Hz. Local transplantable liver tumor (TLT) and fibrosarcoma (FSaII) tumor oxygen pressure (pO
2) and perfusion measurements were carried out using electron paramagnetic resonance (EPR) oximetry and the OxyLite/OxyFlo technique. The radiosensitizing effect of the protocol was assessed by irradiating FSaII tumors with X-rays.
Tumor pO
2 increased from ∼3 mm Hg to ∼8 mm Hg, and relative tumor blood flow was increased by 241% and 162% for TLT and FSaII tumor models, respectively. The effect on the tumor oxygenation was inhibited by a nitric oxide synthase (NOS) inhibitor, and an increase in the tumor nitric oxide (NO) content was observed using EPR spin-trapping. The tumor oxygen consumption rate was decreased after the stimulation protocol. In addition, the electrical stimulation of the host tissue increased regrowth delays by a factor of 1.65.
This increase in tumor oxygenation is due to the temporary increase in tumor blood flow, but particularly to a decrease in the tumor oxygen consumption rate (inhibition of respiration) that is mediated by a local production of NO during the protocol. Those tumor hemodynamic changes resulted in a radiosensitizing effect. |
| doi_str_mv | 10.1016/S0360-3016(02)04505-4 |
| format | Article |
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The sciatic nerve was electrically stimulated at 5 Hz. Local transplantable liver tumor (TLT) and fibrosarcoma (FSaII) tumor oxygen pressure (pO
2) and perfusion measurements were carried out using electron paramagnetic resonance (EPR) oximetry and the OxyLite/OxyFlo technique. The radiosensitizing effect of the protocol was assessed by irradiating FSaII tumors with X-rays.
Tumor pO
2 increased from ∼3 mm Hg to ∼8 mm Hg, and relative tumor blood flow was increased by 241% and 162% for TLT and FSaII tumor models, respectively. The effect on the tumor oxygenation was inhibited by a nitric oxide synthase (NOS) inhibitor, and an increase in the tumor nitric oxide (NO) content was observed using EPR spin-trapping. The tumor oxygen consumption rate was decreased after the stimulation protocol. In addition, the electrical stimulation of the host tissue increased regrowth delays by a factor of 1.65.
This increase in tumor oxygenation is due to the temporary increase in tumor blood flow, but particularly to a decrease in the tumor oxygen consumption rate (inhibition of respiration) that is mediated by a local production of NO during the protocol. Those tumor hemodynamic changes resulted in a radiosensitizing effect.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/S0360-3016(02)04505-4</identifier><identifier>PMID: 12605986</identifier><identifier>CODEN: IOBPD3</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cell Hypoxia - physiology ; Cyclic GMP - metabolism ; Electric pulse ; Electric Stimulation ; Flow Cytometry - methods ; Laser-Doppler Flowmetry ; Medical sciences ; Mice ; Muscle, Skeletal - blood supply ; Muscle, Skeletal - metabolism ; Neoplasm Transplantation ; Neoplasms - blood supply ; Neoplasms - metabolism ; Neoplasms - radiotherapy ; Nitric oxide ; Nitric Oxide - biosynthesis ; Nitric Oxide - physiology ; Oximetry ; Oxygen Consumption - physiology ; Oxygenation ; Partial Pressure ; Perfusion ; Physical Exertion - physiology ; Radiation Tolerance - physiology ; Regional Blood Flow - physiology ; Sciatic Nerve - physiology ; Spin Trapping - methods ; Tumor</subject><ispartof>International journal of radiation oncology, biology, physics, 2003-03, Vol.55 (4), p.1066-1073</ispartof><rights>2003 Elsevier Science Inc.</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-19f95617f37b969fa05721fe3ce77a008a4ecb75d2315c8f8d42102412d0a3db3</citedby><cites>FETCH-LOGICAL-c443t-19f95617f37b969fa05721fe3ce77a008a4ecb75d2315c8f8d42102412d0a3db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0360-3016(02)04505-4$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14590384$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12605986$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jordan, Bénédicte F</creatorcontrib><creatorcontrib>Sonveaux, Pierre</creatorcontrib><creatorcontrib>Feron, Olivier</creatorcontrib><creatorcontrib>Grégoire, Vincent</creatorcontrib><creatorcontrib>Beghein, Nelson</creatorcontrib><creatorcontrib>Gallez, Bernard</creatorcontrib><title>Nitric oxide–mediated increase in tumor blood flow and oxygenation of tumors implanted in muscles stimulated by electric pulses</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Oxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities. We tested the hypothesis that electrical stimulation of the sciatic nerve could modify the oxygenation status and the blood flow of tumors implanted in the thigh of mice.
The sciatic nerve was electrically stimulated at 5 Hz. Local transplantable liver tumor (TLT) and fibrosarcoma (FSaII) tumor oxygen pressure (pO
2) and perfusion measurements were carried out using electron paramagnetic resonance (EPR) oximetry and the OxyLite/OxyFlo technique. The radiosensitizing effect of the protocol was assessed by irradiating FSaII tumors with X-rays.
Tumor pO
2 increased from ∼3 mm Hg to ∼8 mm Hg, and relative tumor blood flow was increased by 241% and 162% for TLT and FSaII tumor models, respectively. The effect on the tumor oxygenation was inhibited by a nitric oxide synthase (NOS) inhibitor, and an increase in the tumor nitric oxide (NO) content was observed using EPR spin-trapping. The tumor oxygen consumption rate was decreased after the stimulation protocol. In addition, the electrical stimulation of the host tissue increased regrowth delays by a factor of 1.65.
This increase in tumor oxygenation is due to the temporary increase in tumor blood flow, but particularly to a decrease in the tumor oxygen consumption rate (inhibition of respiration) that is mediated by a local production of NO during the protocol. Those tumor hemodynamic changes resulted in a radiosensitizing effect.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Hypoxia - physiology</subject><subject>Cyclic GMP - metabolism</subject><subject>Electric pulse</subject><subject>Electric Stimulation</subject><subject>Flow Cytometry - methods</subject><subject>Laser-Doppler Flowmetry</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Muscle, Skeletal - blood supply</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms - blood supply</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - radiotherapy</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Nitric Oxide - physiology</subject><subject>Oximetry</subject><subject>Oxygen Consumption - physiology</subject><subject>Oxygenation</subject><subject>Partial Pressure</subject><subject>Perfusion</subject><subject>Physical Exertion - physiology</subject><subject>Radiation Tolerance - physiology</subject><subject>Regional Blood Flow - physiology</subject><subject>Sciatic Nerve - physiology</subject><subject>Spin Trapping - methods</subject><subject>Tumor</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuFDEQRS0EIkPgE0DegGDRUG7b_VhFKAoPKYIFILGz3HYZGbnbg90NmV34Bv6QL8EzPUqWrHwXp26Vjgl5zOAlA9a8-gS8gYqX-BzqFyAkyErcIRvWtX3Fpfx6l2xukBPyIOfvAMBYK-6TE1Y3IPuu2ZDfH_ycvKHxylv8e_1nROv1jJb6ySTUGUug8zLGRIcQo6UuxF9UT7ZM7L7hpGcfJxrdymTqx23Q01pAxyWbgJnm2Y9LONQOO4oBzWHndgkZ80Nyz-kSHh3fU_LlzcXn83fV5ce3789fX1ZGCD5XrHe9bFjreDv0Te80yLZmDrnBttUAnRZohlbamjNpOtdZUTOoBastaG4Hfkqerb3bFH8smGc1-mwwlHMxLlm1HCRjHRRQrqBJMeeETm2TH3XaKQZq714d3Ku9WAW1OrhXosw9OS5YhqLxduoouwBPj4DORgeX9GR8vuWE7IF3-6KzlcOi46fHpLLxOJnyNamoUzb6_5zyD3fSo7E</recordid><startdate>20030315</startdate><enddate>20030315</enddate><creator>Jordan, Bénédicte F</creator><creator>Sonveaux, Pierre</creator><creator>Feron, Olivier</creator><creator>Grégoire, Vincent</creator><creator>Beghein, Nelson</creator><creator>Gallez, Bernard</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20030315</creationdate><title>Nitric oxide–mediated increase in tumor blood flow and oxygenation of tumors implanted in muscles stimulated by electric pulses</title><author>Jordan, Bénédicte F ; Sonveaux, Pierre ; Feron, Olivier ; Grégoire, Vincent ; Beghein, Nelson ; Gallez, Bernard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-19f95617f37b969fa05721fe3ce77a008a4ecb75d2315c8f8d42102412d0a3db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Hypoxia - physiology</topic><topic>Cyclic GMP - metabolism</topic><topic>Electric pulse</topic><topic>Electric Stimulation</topic><topic>Flow Cytometry - methods</topic><topic>Laser-Doppler Flowmetry</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Muscle, Skeletal - blood supply</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Neoplasm Transplantation</topic><topic>Neoplasms - blood supply</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - radiotherapy</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Nitric Oxide - physiology</topic><topic>Oximetry</topic><topic>Oxygen Consumption - physiology</topic><topic>Oxygenation</topic><topic>Partial Pressure</topic><topic>Perfusion</topic><topic>Physical Exertion - physiology</topic><topic>Radiation Tolerance - physiology</topic><topic>Regional Blood Flow - physiology</topic><topic>Sciatic Nerve - physiology</topic><topic>Spin Trapping - methods</topic><topic>Tumor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jordan, Bénédicte F</creatorcontrib><creatorcontrib>Sonveaux, Pierre</creatorcontrib><creatorcontrib>Feron, Olivier</creatorcontrib><creatorcontrib>Grégoire, Vincent</creatorcontrib><creatorcontrib>Beghein, Nelson</creatorcontrib><creatorcontrib>Gallez, Bernard</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jordan, Bénédicte F</au><au>Sonveaux, Pierre</au><au>Feron, Olivier</au><au>Grégoire, Vincent</au><au>Beghein, Nelson</au><au>Gallez, Bernard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric oxide–mediated increase in tumor blood flow and oxygenation of tumors implanted in muscles stimulated by electric pulses</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2003-03-15</date><risdate>2003</risdate><volume>55</volume><issue>4</issue><spage>1066</spage><epage>1073</epage><pages>1066-1073</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><coden>IOBPD3</coden><abstract>Oxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities. We tested the hypothesis that electrical stimulation of the sciatic nerve could modify the oxygenation status and the blood flow of tumors implanted in the thigh of mice.
The sciatic nerve was electrically stimulated at 5 Hz. Local transplantable liver tumor (TLT) and fibrosarcoma (FSaII) tumor oxygen pressure (pO
2) and perfusion measurements were carried out using electron paramagnetic resonance (EPR) oximetry and the OxyLite/OxyFlo technique. The radiosensitizing effect of the protocol was assessed by irradiating FSaII tumors with X-rays.
Tumor pO
2 increased from ∼3 mm Hg to ∼8 mm Hg, and relative tumor blood flow was increased by 241% and 162% for TLT and FSaII tumor models, respectively. The effect on the tumor oxygenation was inhibited by a nitric oxide synthase (NOS) inhibitor, and an increase in the tumor nitric oxide (NO) content was observed using EPR spin-trapping. The tumor oxygen consumption rate was decreased after the stimulation protocol. In addition, the electrical stimulation of the host tissue increased regrowth delays by a factor of 1.65.
This increase in tumor oxygenation is due to the temporary increase in tumor blood flow, but particularly to a decrease in the tumor oxygen consumption rate (inhibition of respiration) that is mediated by a local production of NO during the protocol. Those tumor hemodynamic changes resulted in a radiosensitizing effect.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>12605986</pmid><doi>10.1016/S0360-3016(02)04505-4</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0360-3016 |
| ispartof | International journal of radiation oncology, biology, physics, 2003-03, Vol.55 (4), p.1066-1073 |
| issn | 0360-3016 1879-355X |
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| subjects | Animals Biological and medical sciences Cell Hypoxia - physiology Cyclic GMP - metabolism Electric pulse Electric Stimulation Flow Cytometry - methods Laser-Doppler Flowmetry Medical sciences Mice Muscle, Skeletal - blood supply Muscle, Skeletal - metabolism Neoplasm Transplantation Neoplasms - blood supply Neoplasms - metabolism Neoplasms - radiotherapy Nitric oxide Nitric Oxide - biosynthesis Nitric Oxide - physiology Oximetry Oxygen Consumption - physiology Oxygenation Partial Pressure Perfusion Physical Exertion - physiology Radiation Tolerance - physiology Regional Blood Flow - physiology Sciatic Nerve - physiology Spin Trapping - methods Tumor |
| title | Nitric oxide–mediated increase in tumor blood flow and oxygenation of tumors implanted in muscles stimulated by electric pulses |
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