Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines
Latent infection of Epstein-Barr virus (EBV) is associated with a poor prognosis in patients with B cell malignancy. We examined whether dasatinib, a multi kinase inhibitor, which is broadly used for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia is effect...
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| Veröffentlicht in: | Scientific reports 2020-03, Vol.10 (1), p.4355, Article 4355 |
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| creator | Kotaki, Ryutaro Kawashima, Masaharu Yamamoto, Yuichiro Higuchi, Hiroshi Nagashima, Etsuko Kurosaki, Natsumi Takamatsu, Masako Kikuti, Yara Yukie Imadome, Ken-Ichi Nakamura, Naoya Kotani, Ai |
| description | Latent infection of Epstein-Barr virus (EBV) is associated with a poor prognosis in patients with B cell malignancy. We examined whether dasatinib, a multi kinase inhibitor, which is broadly used for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia is effective on EBV-positive B cell malignancies, using lymphoblastoid cell lines (LCLs)
in vitro
and
in vivo
. As a result,
in vitro
experiments showed that dasatinib induced cell death of the EBV-LCLs which was not accompanied with a lytic reactivation of EBVs. To evaluate the effectiveness in EBV latency type III represented by immunodeficiency lymphoma, LCL-inoculated immunodeficient NOD/shi-
scid
/
Il2rg
nul
(NOG) mice were treated with dasatinib. However,
in vivo
experiments revealed that dasatinib treatment exacerbated tumor cell infiltration into the spleen of LCL-inoculated NOG mice, whereas tumor size at the inoculated site was not affected by the treatment. These results suggest that dasatinib exacerbates the pathogenesis at least in some situations although the drug is effective
in vitro
. Hence, we should carefully examine a possibility of dasatinib repositioning for EBV
+
B cell malignancies. |
| doi_str_mv | 10.1038/s41598-020-61300-y |
| format | Article |
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in vitro
and
in vivo
. As a result,
in vitro
experiments showed that dasatinib induced cell death of the EBV-LCLs which was not accompanied with a lytic reactivation of EBVs. To evaluate the effectiveness in EBV latency type III represented by immunodeficiency lymphoma, LCL-inoculated immunodeficient NOD/shi-
scid
/
Il2rg
nul
(NOG) mice were treated with dasatinib. However,
in vivo
experiments revealed that dasatinib treatment exacerbated tumor cell infiltration into the spleen of LCL-inoculated NOG mice, whereas tumor size at the inoculated site was not affected by the treatment. These results suggest that dasatinib exacerbates the pathogenesis at least in some situations although the drug is effective
in vitro
. Hence, we should carefully examine a possibility of dasatinib repositioning for EBV
+
B cell malignancies.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-61300-y</identifier><identifier>PMID: 32152351</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 13/51 ; 631/326/596/1553 ; 692/699/1541/1990/291/1621/1915 ; 82/80 ; Acute lymphoblastic leukemia ; Animals ; Cell Cycle Checkpoints - drug effects ; Cell death ; Cell Death - drug effects ; Cell Line, Transformed ; Chronic myeloid leukemia ; Dasatinib - adverse effects ; Disease Models, Animal ; Disease Susceptibility ; Enzyme inhibitors ; Epstein-Barr virus ; Epstein-Barr Virus Infections - complications ; Epstein-Barr Virus Infections - virology ; Herpesvirus 4, Human ; Heterografts ; Humanities and Social Sciences ; Humans ; Immunodeficiency ; Latency ; Latent infection ; Leukemia ; Lymphatic leukemia ; Lymphoblastoid cell lines ; Lymphoma ; Malignancy ; Metastases ; Mice ; multidisciplinary ; Myeloid leukemia ; Philadelphia chromosome ; Phosphorylation ; Protein Kinase Inhibitors - adverse effects ; Science ; Science (multidisciplinary) ; Spleen ; Splenomegaly ; Splenomegaly - etiology ; Splenomegaly - pathology</subject><ispartof>Scientific reports, 2020-03, Vol.10 (1), p.4355, Article 4355</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-957bc259c13481d3f052adc54558d3a48c592318b3b84b8208fc3aa50041356f3</citedby><cites>FETCH-LOGICAL-c474t-957bc259c13481d3f052adc54558d3a48c592318b3b84b8208fc3aa50041356f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062761/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062761/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32152351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kotaki, Ryutaro</creatorcontrib><creatorcontrib>Kawashima, Masaharu</creatorcontrib><creatorcontrib>Yamamoto, Yuichiro</creatorcontrib><creatorcontrib>Higuchi, Hiroshi</creatorcontrib><creatorcontrib>Nagashima, Etsuko</creatorcontrib><creatorcontrib>Kurosaki, Natsumi</creatorcontrib><creatorcontrib>Takamatsu, Masako</creatorcontrib><creatorcontrib>Kikuti, Yara Yukie</creatorcontrib><creatorcontrib>Imadome, Ken-Ichi</creatorcontrib><creatorcontrib>Nakamura, Naoya</creatorcontrib><creatorcontrib>Kotani, Ai</creatorcontrib><title>Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Latent infection of Epstein-Barr virus (EBV) is associated with a poor prognosis in patients with B cell malignancy. We examined whether dasatinib, a multi kinase inhibitor, which is broadly used for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia is effective on EBV-positive B cell malignancies, using lymphoblastoid cell lines (LCLs)
in vitro
and
in vivo
. As a result,
in vitro
experiments showed that dasatinib induced cell death of the EBV-LCLs which was not accompanied with a lytic reactivation of EBVs. To evaluate the effectiveness in EBV latency type III represented by immunodeficiency lymphoma, LCL-inoculated immunodeficient NOD/shi-
scid
/
Il2rg
nul
(NOG) mice were treated with dasatinib. However,
in vivo
experiments revealed that dasatinib treatment exacerbated tumor cell infiltration into the spleen of LCL-inoculated NOG mice, whereas tumor size at the inoculated site was not affected by the treatment. These results suggest that dasatinib exacerbates the pathogenesis at least in some situations although the drug is effective
in vitro
. Hence, we should carefully examine a possibility of dasatinib repositioning for EBV
+
B cell malignancies.</description><subject>13/2</subject><subject>13/31</subject><subject>13/51</subject><subject>631/326/596/1553</subject><subject>692/699/1541/1990/291/1621/1915</subject><subject>82/80</subject><subject>Acute lymphoblastic leukemia</subject><subject>Animals</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cell Line, Transformed</subject><subject>Chronic myeloid leukemia</subject><subject>Dasatinib - adverse effects</subject><subject>Disease Models, Animal</subject><subject>Disease Susceptibility</subject><subject>Enzyme inhibitors</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - complications</subject><subject>Epstein-Barr Virus Infections - virology</subject><subject>Herpesvirus 4, Human</subject><subject>Heterografts</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunodeficiency</subject><subject>Latency</subject><subject>Latent infection</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Lymphoblastoid cell lines</subject><subject>Lymphoma</subject><subject>Malignancy</subject><subject>Metastases</subject><subject>Mice</subject><subject>multidisciplinary</subject><subject>Myeloid leukemia</subject><subject>Philadelphia chromosome</subject><subject>Phosphorylation</subject><subject>Protein Kinase Inhibitors - adverse effects</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Spleen</subject><subject>Splenomegaly</subject><subject>Splenomegaly - etiology</subject><subject>Splenomegaly - pathology</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1O3DAUha2KqqApL9BFZYm1i38nzgYJ6LRUGqmbsrYcx5kxcuxgJwN5-3o6QGGDN7Z0vnvukQ8AXwj-RjCT55kTUUuEKUZLwjBG8wdwQjEXiDJKj169j8Fpzne4HEFrTupP4JhRIigT5AQM33XWowuugfZRG5saPdoM8-BtiL3daD_D2MHeGQtdiGbyRW_hgxu3cDXk0bqArnRKcOfSlJELnTV7wM_9sI2N13mMroXGeg-9CzZ_Bh877bM9fboX4PbH6s_1DVr__vnr-nKNDK_4iGpRNYaK2hDGJWlZV8Lr1gguhGyZ5tKImjIiG9ZI3kiKZWeY1gJjTphYdmwBLg6-w9T0tjU2jEl7NSTX6zSrqJ16qwS3VZu4UxVe0qp86QKcPRmkeD_ZPKq7OKVQMivKKsGrul7iQtEDZVLMOdnuZQPBal-UOhSlSlHqX1FqLkNfX2d7GXmupQDsAOQihY1N_3e_Y_sXLqGg7w</recordid><startdate>20200309</startdate><enddate>20200309</enddate><creator>Kotaki, Ryutaro</creator><creator>Kawashima, Masaharu</creator><creator>Yamamoto, Yuichiro</creator><creator>Higuchi, Hiroshi</creator><creator>Nagashima, Etsuko</creator><creator>Kurosaki, Natsumi</creator><creator>Takamatsu, Masako</creator><creator>Kikuti, Yara Yukie</creator><creator>Imadome, Ken-Ichi</creator><creator>Nakamura, Naoya</creator><creator>Kotani, Ai</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20200309</creationdate><title>Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines</title><author>Kotaki, Ryutaro ; Kawashima, Masaharu ; Yamamoto, Yuichiro ; Higuchi, Hiroshi ; Nagashima, Etsuko ; Kurosaki, Natsumi ; Takamatsu, Masako ; Kikuti, Yara Yukie ; Imadome, Ken-Ichi ; Nakamura, Naoya ; Kotani, Ai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-957bc259c13481d3f052adc54558d3a48c592318b3b84b8208fc3aa50041356f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13/2</topic><topic>13/31</topic><topic>13/51</topic><topic>631/326/596/1553</topic><topic>692/699/1541/1990/291/1621/1915</topic><topic>82/80</topic><topic>Acute lymphoblastic leukemia</topic><topic>Animals</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell death</topic><topic>Cell Death - drug effects</topic><topic>Cell Line, Transformed</topic><topic>Chronic myeloid leukemia</topic><topic>Dasatinib - adverse effects</topic><topic>Disease Models, Animal</topic><topic>Disease Susceptibility</topic><topic>Enzyme inhibitors</topic><topic>Epstein-Barr virus</topic><topic>Epstein-Barr Virus Infections - complications</topic><topic>Epstein-Barr Virus Infections - virology</topic><topic>Herpesvirus 4, Human</topic><topic>Heterografts</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Immunodeficiency</topic><topic>Latency</topic><topic>Latent infection</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Lymphoblastoid cell lines</topic><topic>Lymphoma</topic><topic>Malignancy</topic><topic>Metastases</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Myeloid leukemia</topic><topic>Philadelphia chromosome</topic><topic>Phosphorylation</topic><topic>Protein Kinase Inhibitors - adverse effects</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Spleen</topic><topic>Splenomegaly</topic><topic>Splenomegaly - etiology</topic><topic>Splenomegaly - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kotaki, Ryutaro</creatorcontrib><creatorcontrib>Kawashima, Masaharu</creatorcontrib><creatorcontrib>Yamamoto, Yuichiro</creatorcontrib><creatorcontrib>Higuchi, Hiroshi</creatorcontrib><creatorcontrib>Nagashima, Etsuko</creatorcontrib><creatorcontrib>Kurosaki, Natsumi</creatorcontrib><creatorcontrib>Takamatsu, Masako</creatorcontrib><creatorcontrib>Kikuti, Yara Yukie</creatorcontrib><creatorcontrib>Imadome, Ken-Ichi</creatorcontrib><creatorcontrib>Nakamura, Naoya</creatorcontrib><creatorcontrib>Kotani, Ai</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kotaki, Ryutaro</au><au>Kawashima, Masaharu</au><au>Yamamoto, Yuichiro</au><au>Higuchi, Hiroshi</au><au>Nagashima, Etsuko</au><au>Kurosaki, Natsumi</au><au>Takamatsu, Masako</au><au>Kikuti, Yara Yukie</au><au>Imadome, Ken-Ichi</au><au>Nakamura, Naoya</au><au>Kotani, Ai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-03-09</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>4355</spage><pages>4355-</pages><artnum>4355</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Latent infection of Epstein-Barr virus (EBV) is associated with a poor prognosis in patients with B cell malignancy. We examined whether dasatinib, a multi kinase inhibitor, which is broadly used for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia is effective on EBV-positive B cell malignancies, using lymphoblastoid cell lines (LCLs)
in vitro
and
in vivo
. As a result,
in vitro
experiments showed that dasatinib induced cell death of the EBV-LCLs which was not accompanied with a lytic reactivation of EBVs. To evaluate the effectiveness in EBV latency type III represented by immunodeficiency lymphoma, LCL-inoculated immunodeficient NOD/shi-
scid
/
Il2rg
nul
(NOG) mice were treated with dasatinib. However,
in vivo
experiments revealed that dasatinib treatment exacerbated tumor cell infiltration into the spleen of LCL-inoculated NOG mice, whereas tumor size at the inoculated site was not affected by the treatment. These results suggest that dasatinib exacerbates the pathogenesis at least in some situations although the drug is effective
in vitro
. Hence, we should carefully examine a possibility of dasatinib repositioning for EBV
+
B cell malignancies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32152351</pmid><doi>10.1038/s41598-020-61300-y</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 13/2 13/31 13/51 631/326/596/1553 692/699/1541/1990/291/1621/1915 82/80 Acute lymphoblastic leukemia Animals Cell Cycle Checkpoints - drug effects Cell death Cell Death - drug effects Cell Line, Transformed Chronic myeloid leukemia Dasatinib - adverse effects Disease Models, Animal Disease Susceptibility Enzyme inhibitors Epstein-Barr virus Epstein-Barr Virus Infections - complications Epstein-Barr Virus Infections - virology Herpesvirus 4, Human Heterografts Humanities and Social Sciences Humans Immunodeficiency Latency Latent infection Leukemia Lymphatic leukemia Lymphoblastoid cell lines Lymphoma Malignancy Metastases Mice multidisciplinary Myeloid leukemia Philadelphia chromosome Phosphorylation Protein Kinase Inhibitors - adverse effects Science Science (multidisciplinary) Spleen Splenomegaly Splenomegaly - etiology Splenomegaly - pathology |
| title | Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines |
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