New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse
Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experime...
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| Veröffentlicht in: | Clinical cancer research 2008-10, Vol.14 (20), p.6564-6573 |
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| container_title | Clinical cancer research |
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| creator | STARKEY, Jean R REBANE, Aleksander K DROBIZHEV, Mikhail A FANQING MENG AIJUN GONG ELLIOTT, Aleisha MCINNERNEY, Kate SPANGLER, Charles W |
| description | Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption
in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions
at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation
on normal tissues and characterized the response of xenograft tumors to our PDT protocols.
Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were
induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth
of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these
new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon
activated PDT.
Results: Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal,
changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes
in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation.
Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was
consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the
maximal achievable depth of treatment. |
| doi_str_mv | 10.1158/1078-0432.CCR-07-4162 |
| format | Article |
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in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions
at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation
on normal tissues and characterized the response of xenograft tumors to our PDT protocols.
Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were
induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth
of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these
new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon
activated PDT.
Results: Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal,
changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes
in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation.
Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was
consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the
maximal achievable depth of treatment.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-07-4162</identifier><identifier>PMID: 18927297</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Apoptosis - radiation effects ; Biological and medical sciences ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic - radiation effects ; Hematoporphyrins - chemical synthesis ; Hematoporphyrins - chemistry ; Hematoporphyrins - therapeutic use ; Humans ; Infrared Rays ; Lasers ; Male ; Medical sciences ; Mice ; Mice, SCID ; Microarray ; Neoplasms - drug therapy ; Neoplasms - metabolism ; Neoplasms - pathology ; Oxidative Stress - radiation effects ; Oxygen - metabolism ; Pharmacology. Drug treatments ; Photochemotherapy ; Photodynamic therapy ; Photons ; Photosensitizing Agents - chemical synthesis ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - therapeutic use ; Phototherapeutic window ; Tumor Cells, Cultured ; Whole-Body Irradiation ; Xenograft Model Antitumor Assays</subject><ispartof>Clinical cancer research, 2008-10, Vol.14 (20), p.6564-6573</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-85bf70eb799ce54fb9ecaa995b068f1478f680b5cf40eface95020cc36b081693</citedby><cites>FETCH-LOGICAL-c484t-85bf70eb799ce54fb9ecaa995b068f1478f680b5cf40eface95020cc36b081693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3358,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20842097$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18927297$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>STARKEY, Jean R</creatorcontrib><creatorcontrib>REBANE, Aleksander K</creatorcontrib><creatorcontrib>DROBIZHEV, Mikhail A</creatorcontrib><creatorcontrib>FANQING MENG</creatorcontrib><creatorcontrib>AIJUN GONG</creatorcontrib><creatorcontrib>ELLIOTT, Aleisha</creatorcontrib><creatorcontrib>MCINNERNEY, Kate</creatorcontrib><creatorcontrib>SPANGLER, Charles W</creatorcontrib><title>New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption
in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions
at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation
on normal tissues and characterized the response of xenograft tumors to our PDT protocols.
Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were
induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth
of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these
new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon
activated PDT.
Results: Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal,
changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes
in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation.
Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was
consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the
maximal achievable depth of treatment.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Apoptosis - radiation effects</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic - radiation effects</subject><subject>Hematoporphyrins - chemical synthesis</subject><subject>Hematoporphyrins - chemistry</subject><subject>Hematoporphyrins - therapeutic use</subject><subject>Humans</subject><subject>Infrared Rays</subject><subject>Lasers</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Microarray</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Oxidative Stress - radiation effects</subject><subject>Oxygen - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Photochemotherapy</subject><subject>Photodynamic therapy</subject><subject>Photons</subject><subject>Photosensitizing Agents - chemical synthesis</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - therapeutic use</subject><subject>Phototherapeutic window</subject><subject>Tumor Cells, Cultured</subject><subject>Whole-Body Irradiation</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkcuO0zAUhiMEYi7wCCBvQJpFBjuxHXs5VMBUKgMqQWJnOe5xY9TExXaoyrvwrrgXYHUu-s5F_18ULwi-JYSJNwQ3osS0rm5ns2WJm5ISXj0qLgljTVlXnD3O-V_moriK8TvGhBJMnxYXRMiqqWRzWfx-gB1qd7783PvkR3RnkvupE6zQsbHaj3pwBrU9BL3doy8wRpfcLwgRzcfVZAB9g9Gvg7YJtdPgA1rCOkCMzo8R5S4E9AA6lPMlWuiYqzaATgOMCaU--Gnd5wjobT6FvD3m9z4m9NFPEZ4VT6zeRHh-jtfF1_fv2tl9ufj0YT67W5SGCppKwTrbYOgaKQ0wajsJRmspWYe5sIQ2wnKBO2YsxWC1AclwhY2peYcF4bK-Ll6f9m6D_zFBTGpw0cBmo0fIfyguOZdS4AyyE2iCjzGAVdvgBh32imB18EUdNFcHzVX2ReFGHXzJcy_PB6ZugNX_qbMRGXh1BnQ0emODHo2L_7gKC1rhI3dz4nq37ncugDKZhJAlzyqbXhGaYcUZp_Ufx5OnNQ</recordid><startdate>20081015</startdate><enddate>20081015</enddate><creator>STARKEY, Jean R</creator><creator>REBANE, Aleksander K</creator><creator>DROBIZHEV, Mikhail A</creator><creator>FANQING MENG</creator><creator>AIJUN GONG</creator><creator>ELLIOTT, Aleisha</creator><creator>MCINNERNEY, Kate</creator><creator>SPANGLER, Charles W</creator><general>American Association for Cancer Research</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>20081015</creationdate><title>New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse</title><author>STARKEY, Jean R ; REBANE, Aleksander K ; DROBIZHEV, Mikhail A ; FANQING MENG ; AIJUN GONG ; ELLIOTT, Aleisha ; MCINNERNEY, Kate ; SPANGLER, Charles W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-85bf70eb799ce54fb9ecaa995b068f1478f680b5cf40eface95020cc36b081693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Apoptosis - radiation effects</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic - radiation effects</topic><topic>Hematoporphyrins - chemical synthesis</topic><topic>Hematoporphyrins - chemistry</topic><topic>Hematoporphyrins - therapeutic use</topic><topic>Humans</topic><topic>Infrared Rays</topic><topic>Lasers</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Microarray</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Oxidative Stress - radiation effects</topic><topic>Oxygen - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Photochemotherapy</topic><topic>Photodynamic therapy</topic><topic>Photons</topic><topic>Photosensitizing Agents - chemical synthesis</topic><topic>Photosensitizing Agents - chemistry</topic><topic>Photosensitizing Agents - therapeutic use</topic><topic>Phototherapeutic window</topic><topic>Tumor Cells, Cultured</topic><topic>Whole-Body Irradiation</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STARKEY, Jean R</creatorcontrib><creatorcontrib>REBANE, Aleksander K</creatorcontrib><creatorcontrib>DROBIZHEV, Mikhail A</creatorcontrib><creatorcontrib>FANQING MENG</creatorcontrib><creatorcontrib>AIJUN GONG</creatorcontrib><creatorcontrib>ELLIOTT, Aleisha</creatorcontrib><creatorcontrib>MCINNERNEY, Kate</creatorcontrib><creatorcontrib>SPANGLER, Charles W</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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STARKEY, Jean R</au><au>REBANE, Aleksander K</au><au>DROBIZHEV, Mikhail A</au><au>FANQING MENG</au><au>AIJUN GONG</au><au>ELLIOTT, Aleisha</au><au>MCINNERNEY, Kate</au><au>SPANGLER, Charles W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-10-15</date><risdate>2008</risdate><volume>14</volume><issue>20</issue><spage>6564</spage><epage>6573</epage><pages>6564-6573</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption
in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions
at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation
on normal tissues and characterized the response of xenograft tumors to our PDT protocols.
Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were
induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth
of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these
new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon
activated PDT.
Results: Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal,
changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes
in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation.
Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was
consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the
maximal achievable depth of treatment.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18927297</pmid><doi>10.1158/1078-0432.CCR-07-4162</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic agents Apoptosis - radiation effects Biological and medical sciences Female Gene Expression Profiling Gene Expression Regulation, Neoplastic - radiation effects Hematoporphyrins - chemical synthesis Hematoporphyrins - chemistry Hematoporphyrins - therapeutic use Humans Infrared Rays Lasers Male Medical sciences Mice Mice, SCID Microarray Neoplasms - drug therapy Neoplasms - metabolism Neoplasms - pathology Oxidative Stress - radiation effects Oxygen - metabolism Pharmacology. Drug treatments Photochemotherapy Photodynamic therapy Photons Photosensitizing Agents - chemical synthesis Photosensitizing Agents - chemistry Photosensitizing Agents - therapeutic use Phototherapeutic window Tumor Cells, Cultured Whole-Body Irradiation Xenograft Model Antitumor Assays |
| title | New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse |
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