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dc.contributor.author Márk, Ágnes
dc.contributor.author Hajdu, Melinda
dc.contributor.author Varadi Z
dc.contributor.author Sticz TB
dc.contributor.author Nagy, Noémi
dc.contributor.author Csomor, Judit
dc.contributor.author Berczi L
dc.contributor.author Varga V
dc.contributor.author Csóka, Monika
dc.contributor.author Kopper, László
dc.contributor.author Sebestyén, Anna
dc.date.accessioned 2016-05-04T13:21:37Z
dc.date.available 2016-05-04T13:21:37Z
dc.date.issued 2013
dc.identifier 84878008302
dc.identifier.citation pagination=1-12; journalVolume=13; journalTitle=BMC CANCER;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2663
dc.identifier.uri doi:10.1186/1471-2407-13-250
dc.description.abstract BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response.
dc.relation.ispartof urn:issn:1471-2407
dc.title Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease - a combined tissue microarray, in vitro and in vivo study.
dc.type Journal Article
dc.date.updated 2015-11-24T14:29:36Z
dc.language.rfc3066 en
dc.identifier.mtmt 2338473
dc.identifier.wos 000319514800001
dc.identifier.pubmed 23693095
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.department SE/AOK/I/IISZPI/MTA-SE Molekuláris Onkológia Kutatócsoport
dc.contributor.department SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote PMC PMC3665449


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