Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy
Abstract Xenograft models are suitable for in vivo study of leukemia’s pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unkn...
Gespeichert in:
| Veröffentlicht in: | Biomedicine & pharmacotherapy 2016-04, Vol.79, p.62-70 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 70 |
|---|---|
| container_issue | |
| container_start_page | 62 |
| container_title | Biomedicine & pharmacotherapy |
| container_volume | 79 |
| creator | Valiulienė, Giedrė Treigytė, Gražina Savickienė, Jūratė Matuzevičius, Dalius Alksnė, Milda Jarašienė-Burinskaja, Rasa Bukelskienė, Virginija Navakauskas, Dalius Navakauskienė, Rūta |
| description | Abstract Xenograft models are suitable for in vivo study of leukemia’s pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all -trans -retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism. |
| doi_str_mv | 10.1016/j.biopha.2016.01.044 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1779021263</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0753332215301736</els_id><sourcerecordid>1779021263</sourcerecordid><originalsourceid>FETCH-LOGICAL-c417t-fa467ed9a79ddfd404fa4556d080b0b0fcba0748fb55132e4199e3d80b6c735e3</originalsourceid><addsrcrecordid>eNqFUkGP1iAQJUbjfq7-A2M4emkdSlu-XkzMRl2TTTyoZ0Jh2OXbFipQY_-Gv1iab_XgxXBgBt57k5k3hLxkUDNg_ZtTPbqw3Km6KVkNrIa2fUQObOig6gHEY3IA0fGK86a5IM9SOgFA1_PjU3LRiAI-Mn4gv65dysEjnYNx1mmVXfCJLipnjCVwnmaX0oqJKm9oXuewxkRtDDNVes1IlxJuOAW9ZafphOs9zk7Rn-jDbVQ278o47UIR01LEkeZAdZhH59FQXNwtety5-Q6jWrbn5IlVU8IXD_cl-fbh_der6-rm88dPV-9uKt0ykSur2l6gGZQYjLGmhba8dF1v4AhjOVaPCkR7tGPXMd5gy4YBuSmfvRa8Q35JXp91SwffS4NZzi5pnCblMaxJMiEGaFjT8wJtz1AdQ0oRrVyim1XcJAO5uyFP8uyG3N2QwGQZcKG9eqiwjjOav6Q_4y-At2cAlj5_OIwyaYdeo3ERdZYmuP9V-FdAT84XG6d73DCdilm-zFAymRoJ8su-EftCsI4DE7znvwH5brZ7</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779021263</pqid></control><display><type>article</type><title>Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Valiulienė, Giedrė ; Treigytė, Gražina ; Savickienė, Jūratė ; Matuzevičius, Dalius ; Alksnė, Milda ; Jarašienė-Burinskaja, Rasa ; Bukelskienė, Virginija ; Navakauskas, Dalius ; Navakauskienė, Rūta</creator><creatorcontrib>Valiulienė, Giedrė ; Treigytė, Gražina ; Savickienė, Jūratė ; Matuzevičius, Dalius ; Alksnė, Milda ; Jarašienė-Burinskaja, Rasa ; Bukelskienė, Virginija ; Navakauskas, Dalius ; Navakauskienė, Rūta</creatorcontrib><description>Abstract Xenograft models are suitable for in vivo study of leukemia’s pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all -trans -retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism.</description><identifier>ISSN: 0753-3322</identifier><identifier>EISSN: 1950-6007</identifier><identifier>DOI: 10.1016/j.biopha.2016.01.044</identifier><identifier>PMID: 27044813</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>3-DZNeaplanocin A ; Acute promyelocytic leukemia ; Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Belinostat ; Brain - drug effects ; Brain - metabolism ; Cell Line, Tumor ; Epigenesis, Genetic - drug effects ; Female ; Histone modifications ; Histones - metabolism ; Humans ; Hydroxamic Acids - pharmacology ; Hydroxamic Acids - therapeutic use ; Internal Medicine ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - genetics ; Leukemia, Promyelocytic, Acute - metabolism ; Liver - drug effects ; Liver - metabolism ; Male ; Medical Education ; Mice ; Organ Specificity - drug effects ; Protein Processing, Post-Translational - drug effects ; Sulfonamides - pharmacology ; Sulfonamides - therapeutic use ; Tretinoin - pharmacology ; Tretinoin - therapeutic use ; WT1 ; WT1 Proteins - metabolism ; Xenograft Model Antitumor Assays</subject><ispartof>Biomedicine & pharmacotherapy, 2016-04, Vol.79, p.62-70</ispartof><rights>Elsevier Masson SAS</rights><rights>2016 Elsevier Masson SAS</rights><rights>Copyright © 2016 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-fa467ed9a79ddfd404fa4556d080b0b0fcba0748fb55132e4199e3d80b6c735e3</citedby><cites>FETCH-LOGICAL-c417t-fa467ed9a79ddfd404fa4556d080b0b0fcba0748fb55132e4199e3d80b6c735e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopha.2016.01.044$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27044813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valiulienė, Giedrė</creatorcontrib><creatorcontrib>Treigytė, Gražina</creatorcontrib><creatorcontrib>Savickienė, Jūratė</creatorcontrib><creatorcontrib>Matuzevičius, Dalius</creatorcontrib><creatorcontrib>Alksnė, Milda</creatorcontrib><creatorcontrib>Jarašienė-Burinskaja, Rasa</creatorcontrib><creatorcontrib>Bukelskienė, Virginija</creatorcontrib><creatorcontrib>Navakauskas, Dalius</creatorcontrib><creatorcontrib>Navakauskienė, Rūta</creatorcontrib><title>Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy</title><title>Biomedicine & pharmacotherapy</title><addtitle>Biomed Pharmacother</addtitle><description>Abstract Xenograft models are suitable for in vivo study of leukemia’s pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all -trans -retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism.</description><subject>3-DZNeaplanocin A</subject><subject>Acute promyelocytic leukemia</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Belinostat</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Epigenesis, Genetic - drug effects</subject><subject>Female</subject><subject>Histone modifications</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Hydroxamic Acids - therapeutic use</subject><subject>Internal Medicine</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Leukemia, Promyelocytic, Acute - genetics</subject><subject>Leukemia, Promyelocytic, Acute - metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Medical Education</subject><subject>Mice</subject><subject>Organ Specificity - drug effects</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Sulfonamides - pharmacology</subject><subject>Sulfonamides - therapeutic use</subject><subject>Tretinoin - pharmacology</subject><subject>Tretinoin - therapeutic use</subject><subject>WT1</subject><subject>WT1 Proteins - metabolism</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0753-3322</issn><issn>1950-6007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUkGP1iAQJUbjfq7-A2M4emkdSlu-XkzMRl2TTTyoZ0Jh2OXbFipQY_-Gv1iab_XgxXBgBt57k5k3hLxkUDNg_ZtTPbqw3Km6KVkNrIa2fUQObOig6gHEY3IA0fGK86a5IM9SOgFA1_PjU3LRiAI-Mn4gv65dysEjnYNx1mmVXfCJLipnjCVwnmaX0oqJKm9oXuewxkRtDDNVes1IlxJuOAW9ZafphOs9zk7Rn-jDbVQ278o47UIR01LEkeZAdZhH59FQXNwtety5-Q6jWrbn5IlVU8IXD_cl-fbh_der6-rm88dPV-9uKt0ykSur2l6gGZQYjLGmhba8dF1v4AhjOVaPCkR7tGPXMd5gy4YBuSmfvRa8Q35JXp91SwffS4NZzi5pnCblMaxJMiEGaFjT8wJtz1AdQ0oRrVyim1XcJAO5uyFP8uyG3N2QwGQZcKG9eqiwjjOav6Q_4y-At2cAlj5_OIwyaYdeo3ERdZYmuP9V-FdAT84XG6d73DCdilm-zFAymRoJ8su-EftCsI4DE7znvwH5brZ7</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Valiulienė, Giedrė</creator><creator>Treigytė, Gražina</creator><creator>Savickienė, Jūratė</creator><creator>Matuzevičius, Dalius</creator><creator>Alksnė, Milda</creator><creator>Jarašienė-Burinskaja, Rasa</creator><creator>Bukelskienė, Virginija</creator><creator>Navakauskas, Dalius</creator><creator>Navakauskienė, Rūta</creator><general>Elsevier Masson SAS</general><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>20160401</creationdate><title>Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy</title><author>Valiulienė, Giedrė ; Treigytė, Gražina ; Savickienė, Jūratė ; Matuzevičius, Dalius ; Alksnė, Milda ; Jarašienė-Burinskaja, Rasa ; Bukelskienė, Virginija ; Navakauskas, Dalius ; Navakauskienė, Rūta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-fa467ed9a79ddfd404fa4556d080b0b0fcba0748fb55132e4199e3d80b6c735e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3-DZNeaplanocin A</topic><topic>Acute promyelocytic leukemia</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Belinostat</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Epigenesis, Genetic - drug effects</topic><topic>Female</topic><topic>Histone modifications</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Hydroxamic Acids - therapeutic use</topic><topic>Internal Medicine</topic><topic>Leukemia, Promyelocytic, Acute - drug therapy</topic><topic>Leukemia, Promyelocytic, Acute - genetics</topic><topic>Leukemia, Promyelocytic, Acute - metabolism</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Medical Education</topic><topic>Mice</topic><topic>Organ Specificity - drug effects</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Sulfonamides - pharmacology</topic><topic>Sulfonamides - therapeutic use</topic><topic>Tretinoin - pharmacology</topic><topic>Tretinoin - therapeutic use</topic><topic>WT1</topic><topic>WT1 Proteins - metabolism</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valiulienė, Giedrė</creatorcontrib><creatorcontrib>Treigytė, Gražina</creatorcontrib><creatorcontrib>Savickienė, Jūratė</creatorcontrib><creatorcontrib>Matuzevičius, Dalius</creatorcontrib><creatorcontrib>Alksnė, Milda</creatorcontrib><creatorcontrib>Jarašienė-Burinskaja, Rasa</creatorcontrib><creatorcontrib>Bukelskienė, Virginija</creatorcontrib><creatorcontrib>Navakauskas, Dalius</creatorcontrib><creatorcontrib>Navakauskienė, Rūta</creatorcontrib><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>Biomedicine & pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valiulienė, Giedrė</au><au>Treigytė, Gražina</au><au>Savickienė, Jūratė</au><au>Matuzevičius, Dalius</au><au>Alksnė, Milda</au><au>Jarašienė-Burinskaja, Rasa</au><au>Bukelskienė, Virginija</au><au>Navakauskas, Dalius</au><au>Navakauskienė, Rūta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy</atitle><jtitle>Biomedicine & pharmacotherapy</jtitle><addtitle>Biomed Pharmacother</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>79</volume><spage>62</spage><epage>70</epage><pages>62-70</pages><issn>0753-3322</issn><eissn>1950-6007</eissn><abstract>Abstract Xenograft models are suitable for in vivo study of leukemia’s pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all -trans -retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>27044813</pmid><doi>10.1016/j.biopha.2016.01.044</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0753-3322 |
| ispartof | Biomedicine & pharmacotherapy, 2016-04, Vol.79, p.62-70 |
| issn | 0753-3322 1950-6007 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1779021263 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 3-DZNeaplanocin A Acute promyelocytic leukemia Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Belinostat Brain - drug effects Brain - metabolism Cell Line, Tumor Epigenesis, Genetic - drug effects Female Histone modifications Histones - metabolism Humans Hydroxamic Acids - pharmacology Hydroxamic Acids - therapeutic use Internal Medicine Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - genetics Leukemia, Promyelocytic, Acute - metabolism Liver - drug effects Liver - metabolism Male Medical Education Mice Organ Specificity - drug effects Protein Processing, Post-Translational - drug effects Sulfonamides - pharmacology Sulfonamides - therapeutic use Tretinoin - pharmacology Tretinoin - therapeutic use WT1 WT1 Proteins - metabolism Xenograft Model Antitumor Assays |
| title | Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T10%3A49%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Histone%20modifications%20patterns%20in%20tissues%20and%20tumours%20from%20acute%20promyelocytic%20leukemia%20xenograft%20model%20in%20response%20to%20combined%20epigenetic%20therapy&rft.jtitle=Biomedicine%20&%20pharmacotherapy&rft.au=Valiulien%C4%97,%20Giedr%C4%97&rft.date=2016-04-01&rft.volume=79&rft.spage=62&rft.epage=70&rft.pages=62-70&rft.issn=0753-3322&rft.eissn=1950-6007&rft_id=info:doi/10.1016/j.biopha.2016.01.044&rft_dat=%3Cproquest_cross%3E1779021263%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1779021263&rft_id=info:pmid/27044813&rft_els_id=1_s2_0_S0753332215301736&rfr_iscdi=true |