Radioprotection from radiation-induced lymphedema without tumor protection.
Identifieur interne : 002918 ( PubMed/Corpus ); précédent : 002917; suivant : 002919Radioprotection from radiation-induced lymphedema without tumor protection.
Auteurs : S K Daley ; M J Bernas ; B D Stea ; F. Bracamonte ; M. Mckenna ; A. Stejskal ; E D Hirleman ; M H WitteSource :
- Lymphology [ 0024-7766 ] ; 2010.
English descriptors
- KwdEn :
- Amifostine (therapeutic use), Animals, Colony-Forming Units Assay, Female, Humans, Incidence, Lymphatic Vessels (radiation effects), Lymphedema (etiology), Lymphedema (prevention & control), Male, Mammary Neoplasms, Experimental (metabolism), Mammary Neoplasms, Experimental (radiotherapy), Mice, Mice, Nude, Radiation Tolerance, Radiation-Protective Agents (therapeutic use), Rats, Rats, Wistar, Tumor Cells, Cultured, Wound Healing, Xenograft Model Antitumor Assays.
- MESH :
- chemical , therapeutic use : Amifostine, Radiation-Protective Agents.
- etiology : Lymphedema.
- metabolism : Mammary Neoplasms, Experimental.
- prevention & control : Lymphedema.
- radiation effects : Lymphatic Vessels.
- radiotherapy : Mammary Neoplasms, Experimental.
- Animals, Colony-Forming Units Assay, Female, Humans, Incidence, Male, Mice, Mice, Nude, Radiation Tolerance, Rats, Rats, Wistar, Tumor Cells, Cultured, Wound Healing, Xenograft Model Antitumor Assays.
Abstract
Lymphedema or tissue swelling from impaired lymph drainage commonly occurs after regional nodal dissection and/or radiation therapy for cancer control. Treatment options for this disabling and life-altering complication involve long-term labor-intensive commitments. Sentinel node biopsy can forestall removal of negative regional nodes, offering some protection against lymphedema, however, most preventive measures are elusive, ineffective, or unproven. Our goal was to determine whether the radioprotectant amifostine could prevent or retard the development of lymphedema in a rodent radiation therapy-dependent model yet not offer tumor protection from the therapeutic effects of radiation therapy. We pre-treated rats after unilateral radical groin dissection with the organic thiophosphate radioprotectant amifostine or placebo prior to single dose post-operative groin radiation therapy and monitored hindlimb volumes, wound scores, and tissue lymphostasis. In addition, we determined whether amifostine protected human MCF7 breast cancer cells exposed to a range of radiation therapy doses in an in vitro clonogenic assay and an in vivo MCF7 tumor xenograft model. Our findings indicate that amifostine markedly reduced the volume of limb lymphedema and dramatically improved wound healing and tissue lymphostasis in the rodent lymphedema model. The in vivo and in vitro studies further demonstrated that amifostine offered no MCF7 tumor protection from radiation therapy. These pre-clinical findings provide proof-of-principle to further delineate specific mechanisms underlying amifostine's beneficial effects, determine optimal amifostine-radiation therapy dosing regimens, and thereby expedite translation into clinical trials to reduce lymphedema incidence and severity in cancer patients at high lymphedema risk in whom radiation therapy is the recommended therapy.
PubMed: 20848992
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Radioprotection from radiation-induced lymphedema without tumor protection.</title><author><name sortKey="Daley, S K" sort="Daley, S K" uniqKey="Daley S" first="S K" last="Daley">S K Daley</name><affiliation><nlm:affiliation>Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona 85724-5200, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bernas, M J" sort="Bernas, M J" uniqKey="Bernas M" first="M J" last="Bernas">M J Bernas</name></author><author><name sortKey="Stea, B D" sort="Stea, B D" uniqKey="Stea B" first="B D" last="Stea">B D Stea</name></author><author><name sortKey="Bracamonte, F" sort="Bracamonte, F" uniqKey="Bracamonte F" first="F" last="Bracamonte">F. Bracamonte</name></author><author><name sortKey="Mckenna, M" sort="Mckenna, M" uniqKey="Mckenna M" first="M" last="Mckenna">M. Mckenna</name></author><author><name sortKey="Stejskal, A" sort="Stejskal, A" uniqKey="Stejskal A" first="A" last="Stejskal">A. Stejskal</name></author><author><name sortKey="Hirleman, E D" sort="Hirleman, E D" uniqKey="Hirleman E" first="E D" last="Hirleman">E D Hirleman</name></author><author><name sortKey="Witte, M H" sort="Witte, M H" uniqKey="Witte M" first="M H" last="Witte">M H Witte</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:20848992</idno><idno type="pmid">20848992</idno><idno type="wicri:Area/PubMed/Corpus">002918</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002918</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Radioprotection from radiation-induced lymphedema without tumor protection.</title><author><name sortKey="Daley, S K" sort="Daley, S K" uniqKey="Daley S" first="S K" last="Daley">S K Daley</name><affiliation><nlm:affiliation>Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona 85724-5200, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bernas, M J" sort="Bernas, M J" uniqKey="Bernas M" first="M J" last="Bernas">M J Bernas</name></author><author><name sortKey="Stea, B D" sort="Stea, B D" uniqKey="Stea B" first="B D" last="Stea">B D Stea</name></author><author><name sortKey="Bracamonte, F" sort="Bracamonte, F" uniqKey="Bracamonte F" first="F" last="Bracamonte">F. Bracamonte</name></author><author><name sortKey="Mckenna, M" sort="Mckenna, M" uniqKey="Mckenna M" first="M" last="Mckenna">M. Mckenna</name></author><author><name sortKey="Stejskal, A" sort="Stejskal, A" uniqKey="Stejskal A" first="A" last="Stejskal">A. Stejskal</name></author><author><name sortKey="Hirleman, E D" sort="Hirleman, E D" uniqKey="Hirleman E" first="E D" last="Hirleman">E D Hirleman</name></author><author><name sortKey="Witte, M H" sort="Witte, M H" uniqKey="Witte M" first="M H" last="Witte">M H Witte</name></author></analytic><series><title level="j">Lymphology</title><idno type="ISSN">0024-7766</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amifostine (therapeutic use)</term><term>Animals</term><term>Colony-Forming Units Assay</term><term>Female</term><term>Humans</term><term>Incidence</term><term>Lymphatic Vessels (radiation effects)</term><term>Lymphedema (etiology)</term><term>Lymphedema (prevention & control)</term><term>Male</term><term>Mammary Neoplasms, Experimental (metabolism)</term><term>Mammary Neoplasms, Experimental (radiotherapy)</term><term>Mice</term><term>Mice, Nude</term><term>Radiation Tolerance</term><term>Radiation-Protective Agents (therapeutic use)</term><term>Rats</term><term>Rats, Wistar</term><term>Tumor Cells, Cultured</term><term>Wound Healing</term><term>Xenograft Model Antitumor Assays</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Amifostine</term><term>Radiation-Protective Agents</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mammary Neoplasms, Experimental</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Lymphedema</term></keywords><keywords scheme="MESH" qualifier="radiation effects" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="radiotherapy" xml:lang="en"><term>Mammary Neoplasms, Experimental</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Colony-Forming Units Assay</term><term>Female</term><term>Humans</term><term>Incidence</term><term>Male</term><term>Mice</term><term>Mice, Nude</term><term>Radiation Tolerance</term><term>Rats</term><term>Rats, Wistar</term><term>Tumor Cells, Cultured</term><term>Wound Healing</term><term>Xenograft Model Antitumor Assays</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lymphedema or tissue swelling from impaired lymph drainage commonly occurs after regional nodal dissection and/or radiation therapy for cancer control. Treatment options for this disabling and life-altering complication involve long-term labor-intensive commitments. Sentinel node biopsy can forestall removal of negative regional nodes, offering some protection against lymphedema, however, most preventive measures are elusive, ineffective, or unproven. Our goal was to determine whether the radioprotectant amifostine could prevent or retard the development of lymphedema in a rodent radiation therapy-dependent model yet not offer tumor protection from the therapeutic effects of radiation therapy. We pre-treated rats after unilateral radical groin dissection with the organic thiophosphate radioprotectant amifostine or placebo prior to single dose post-operative groin radiation therapy and monitored hindlimb volumes, wound scores, and tissue lymphostasis. In addition, we determined whether amifostine protected human MCF7 breast cancer cells exposed to a range of radiation therapy doses in an in vitro clonogenic assay and an in vivo MCF7 tumor xenograft model. Our findings indicate that amifostine markedly reduced the volume of limb lymphedema and dramatically improved wound healing and tissue lymphostasis in the rodent lymphedema model. The in vivo and in vitro studies further demonstrated that amifostine offered no MCF7 tumor protection from radiation therapy. These pre-clinical findings provide proof-of-principle to further delineate specific mechanisms underlying amifostine's beneficial effects, determine optimal amifostine-radiation therapy dosing regimens, and thereby expedite translation into clinical trials to reduce lymphedema incidence and severity in cancer patients at high lymphedema risk in whom radiation therapy is the recommended therapy.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20848992</PMID><DateCreated><Year>2010</Year><Month>09</Month><Day>20</Day></DateCreated><DateCompleted><Year>2010</Year><Month>10</Month><Day>07</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0024-7766</ISSN><JournalIssue CitedMedium="Print"><Volume>43</Volume><Issue>2</Issue><PubDate><Year>2010</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Lymphology</Title><ISOAbbreviation>Lymphology</ISOAbbreviation></Journal><ArticleTitle>Radioprotection from radiation-induced lymphedema without tumor protection.</ArticleTitle><Pagination><MedlinePgn>48-58</MedlinePgn></Pagination><Abstract><AbstractText>Lymphedema or tissue swelling from impaired lymph drainage commonly occurs after regional nodal dissection and/or radiation therapy for cancer control. Treatment options for this disabling and life-altering complication involve long-term labor-intensive commitments. Sentinel node biopsy can forestall removal of negative regional nodes, offering some protection against lymphedema, however, most preventive measures are elusive, ineffective, or unproven. Our goal was to determine whether the radioprotectant amifostine could prevent or retard the development of lymphedema in a rodent radiation therapy-dependent model yet not offer tumor protection from the therapeutic effects of radiation therapy. We pre-treated rats after unilateral radical groin dissection with the organic thiophosphate radioprotectant amifostine or placebo prior to single dose post-operative groin radiation therapy and monitored hindlimb volumes, wound scores, and tissue lymphostasis. In addition, we determined whether amifostine protected human MCF7 breast cancer cells exposed to a range of radiation therapy doses in an in vitro clonogenic assay and an in vivo MCF7 tumor xenograft model. Our findings indicate that amifostine markedly reduced the volume of limb lymphedema and dramatically improved wound healing and tissue lymphostasis in the rodent lymphedema model. The in vivo and in vitro studies further demonstrated that amifostine offered no MCF7 tumor protection from radiation therapy. These pre-clinical findings provide proof-of-principle to further delineate specific mechanisms underlying amifostine's beneficial effects, determine optimal amifostine-radiation therapy dosing regimens, and thereby expedite translation into clinical trials to reduce lymphedema incidence and severity in cancer patients at high lymphedema risk in whom radiation therapy is the recommended therapy.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Daley</LastName><ForeName>S K</ForeName><Initials>SK</Initials><AffiliationInfo><Affiliation>Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona 85724-5200, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bernas</LastName><ForeName>M J</ForeName><Initials>MJ</Initials></Author><Author ValidYN="Y"><LastName>Stea</LastName><ForeName>B D</ForeName><Initials>BD</Initials></Author><Author ValidYN="Y"><LastName>Bracamonte</LastName><ForeName>F</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>McKenna</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Stejskal</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Hirleman</LastName><ForeName>E D</ForeName><Initials>ED</Initials></Author><Author ValidYN="Y"><LastName>Witte</LastName><ForeName>M H</ForeName><Initials>MH</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Lymphology</MedlineTA><NlmUniqueID>0155112</NlmUniqueID><ISSNLinking>0024-7766</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011837">Radiation-Protective Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>M487QF2F4V</RegistryNumber><NameOfSubstance UI="D004999">Amifostine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004999" MajorTopicYN="N">Amifostine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003114" MajorTopicYN="N">Colony-Forming Units Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015994" MajorTopicYN="N">Incidence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D042601" MajorTopicYN="N">Lymphatic Vessels</DescriptorName><QualifierName UI="Q000528" MajorTopicYN="N">radiation effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008209" MajorTopicYN="N">Lymphedema</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008325" MajorTopicYN="N">Mammary Neoplasms, Experimental</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000532" MajorTopicYN="Y">radiotherapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008819" MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011836" MajorTopicYN="N">Radiation Tolerance</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011837" MajorTopicYN="N">Radiation-Protective Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014945" MajorTopicYN="N">Wound Healing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>9</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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