RapamycinFungusV1, Main, Exploration, bibRecord, 000A97

Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.

Identifieur interne : 000A97 ( Main/Exploration ); précédent : 000A96; suivant : 000A98

Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.

Auteurs : Ayman A M. Alameen [Italie, Soudan] ; Carolina Simioni [Italie] ; Alberto M. Martelli [Italie] ; Giorgio Zauli [Italie] ; Simona Ultimo [Italie] ; James A. Mccubrey [États-Unis] ; Arianna Gonelli [Italie] ; Giorgia Marisi [Italie] ; Paola Ulivi [Italie] ; Silvano Capitani [Italie] ; Luca M. Neri [Italie]

Source :

Oncotarget [ 1949-2553 ] ; 2016.

RBID : pubmed:27494886

Descripteurs français

KwdFr :
- Activation des lymphocytes (MeSH), Autophagie (effets des médicaments et des substances chimiques), Humains (MeSH), Imidazoles (pharmacologie), Leucémie-lymphome lymphoblastique à précurseurs T (anatomopathologie), Leucémie-lymphome lymphoblastique à précurseurs T (immunologie), Leucémie-lymphome lymphoblastique à précurseurs T (traitement médicamenteux), Lignée cellulaire tumorale (MeSH), Lymphocytes T CD4+ (effets des médicaments et des substances chimiques), Lymphocytes T CD4+ (immunologie), Naphtyridines (pharmacologie), Protéines proto-oncogènes c-akt (antagonistes et inhibiteurs), Quinoléines (pharmacologie), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Thérapie moléculaire ciblée (MeSH), Transduction du signal (effets des médicaments et des substances chimiques).
MESH :
- anatomopathologie : Leucémie-lymphome lymphoblastique à précurseurs T.
- antagonistes et inhibiteurs : Protéines proto-oncogènes c-akt, Sérine-thréonine kinases TOR.
- effets des médicaments et des substances chimiques : Autophagie, Lymphocytes T CD4+, Transduction du signal.
- immunologie : Leucémie-lymphome lymphoblastique à précurseurs T, Lymphocytes T CD4+.
- pharmacologie : Imidazoles, Naphtyridines, Quinoléines.
- traitement médicamenteux : Leucémie-lymphome lymphoblastique à précurseurs T.
- Activation des lymphocytes, Humains, Lignée cellulaire tumorale, Thérapie moléculaire ciblée.

English descriptors

KwdEn :
- Autophagy (drug effects), CD4-Positive T-Lymphocytes (drug effects), CD4-Positive T-Lymphocytes (immunology), Cell Line, Tumor (MeSH), Humans (MeSH), Imidazoles (pharmacology), Lymphocyte Activation (MeSH), Molecular Targeted Therapy (MeSH), Naphthyridines (pharmacology), Phosphoinositide-3 Kinase Inhibitors (MeSH), Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy), Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (immunology), Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (pathology), Proto-Oncogene Proteins c-akt (antagonists & inhibitors), Quinolines (pharmacology), Signal Transduction (drug effects), TOR Serine-Threonine Kinases (antagonists & inhibitors).
MESH :
- chemical , antagonists & inhibitors : Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases.
- chemical , pharmacology : Imidazoles, Naphthyridines, Quinolines.
- drug effects : Autophagy, CD4-Positive T-Lymphocytes, Signal Transduction.
- drug therapy : Precursor T-Cell Lymphoblastic Leukemia-Lymphoma.
- immunology : CD4-Positive T-Lymphocytes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma.
- pathology : Precursor T-Cell Lymphoblastic Leukemia-Lymphoma.
- Cell Line, Tumor, Humans, Lymphocyte Activation, Molecular Targeted Therapy, Phosphoinositide-3 Kinase Inhibitors.

Abstract

An attractive molecular target for novel anti-cancer therapies is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway which is commonly deregulated in many types of cancer. Nevertheless, the effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune responses, have been seldom explored. In this study we investigated the effects on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK-2206, and ZSTK474. We also assessed their efficacy against two acute leukemia T cell lines. T lymphocytes were stimulated with phytohemagglutinin. Inhibitor effects on cell cycle and apoptosis were analyzed by flow cytometry, while cytotoxicity was assessed by MTT assays. In addition, the activation status of the pathway as well as induction of autophagy were analyzed by Western blotting. Quiescent healthy T lymphocytes were unaffected by the drugs whereas mitogen-stimulated lymphocytes as well as leukemic cell lines displayed a cell cycle block, caspase-dependent apoptosis, and dephosphorylation of key components of the signaling pathway. Autophagy was also induced in proliferating lymphocytes and in JURKAT and MOLT-4 cell lines. When autophagy was inhibited by 3-methyladenine or Bafilomycin A1, drug cytotoxicity was increased, indicating that autophagy is a protective mechanism. Therefore, our findings suggest that PI3K/Akt/mTOR inhibitors preserve lymphocyte viability. This is a valuable result to be taken into account when selecting drugs for targeted cancer therapy in order to minimize detrimental effects on immune function.

DOI: 10.18632/oncotarget.10984
PubMed: 27494886
PubMed Central: PMC5342446

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000A03
to stream Main, to step Curation: 000A03

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.</title>
<author><name sortKey="Alameen, Ayman A M" sort="Alameen, Ayman A M" uniqKey="Alameen A" first="Ayman A M" last="Alameen">Ayman A M. Alameen</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.</nlm:affiliation>
<country xml:lang="fr">Soudan</country>
<wicri:regionArea>Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum</wicri:regionArea>
<wicri:noRegion>Khartoum</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Simioni, Carolina" sort="Simioni, Carolina" uniqKey="Simioni C" first="Carolina" last="Simioni">Carolina Simioni</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Martelli, Alberto M" sort="Martelli, Alberto M" uniqKey="Martelli A" first="Alberto M" last="Martelli">Alberto M. Martelli</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna</wicri:regionArea>
<wicri:noRegion>Bologna</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zauli, Giorgio" sort="Zauli, Giorgio" uniqKey="Zauli G" first="Giorgio" last="Zauli">Giorgio Zauli</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ultimo, Simona" sort="Ultimo, Simona" uniqKey="Ultimo S" first="Simona" last="Ultimo">Simona Ultimo</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mccubrey, James A" sort="Mccubrey, James A" uniqKey="Mccubrey J" first="James A" last="Mccubrey">James A. Mccubrey</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gonelli, Arianna" sort="Gonelli, Arianna" uniqKey="Gonelli A" first="Arianna" last="Gonelli">Arianna Gonelli</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marisi, Giorgia" sort="Marisi, Giorgia" uniqKey="Marisi G" first="Giorgia" last="Marisi">Giorgia Marisi</name>
<affiliation wicri:level="1"><nlm:affiliation>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola</wicri:regionArea>
<wicri:noRegion>Meldola</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ulivi, Paola" sort="Ulivi, Paola" uniqKey="Ulivi P" first="Paola" last="Ulivi">Paola Ulivi</name>
<affiliation wicri:level="1"><nlm:affiliation>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola</wicri:regionArea>
<wicri:noRegion>Meldola</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Capitani, Silvano" sort="Capitani, Silvano" uniqKey="Capitani S" first="Silvano" last="Capitani">Silvano Capitani</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>LTTA Center, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>LTTA Center, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Neri, Luca M" sort="Neri, Luca M" uniqKey="Neri L" first="Luca M" last="Neri">Luca M. Neri</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2016">2016</date>
<idno type="RBID">pubmed:27494886</idno>
<idno type="pmid">27494886</idno>
<idno type="doi">10.18632/oncotarget.10984</idno>
<idno type="pmc">PMC5342446</idno>
<idno type="wicri:Area/Main/Corpus">000A03</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000A03</idno>
<idno type="wicri:Area/Main/Curation">000A03</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000A03</idno>
<idno type="wicri:Area/Main/Exploration">000A03</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.</title>
<author><name sortKey="Alameen, Ayman A M" sort="Alameen, Ayman A M" uniqKey="Alameen A" first="Ayman A M" last="Alameen">Ayman A M. Alameen</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.</nlm:affiliation>
<country xml:lang="fr">Soudan</country>
<wicri:regionArea>Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum</wicri:regionArea>
<wicri:noRegion>Khartoum</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Simioni, Carolina" sort="Simioni, Carolina" uniqKey="Simioni C" first="Carolina" last="Simioni">Carolina Simioni</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Martelli, Alberto M" sort="Martelli, Alberto M" uniqKey="Martelli A" first="Alberto M" last="Martelli">Alberto M. Martelli</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna</wicri:regionArea>
<wicri:noRegion>Bologna</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zauli, Giorgio" sort="Zauli, Giorgio" uniqKey="Zauli G" first="Giorgio" last="Zauli">Giorgio Zauli</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ultimo, Simona" sort="Ultimo, Simona" uniqKey="Ultimo S" first="Simona" last="Ultimo">Simona Ultimo</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mccubrey, James A" sort="Mccubrey, James A" uniqKey="Mccubrey J" first="James A" last="Mccubrey">James A. Mccubrey</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gonelli, Arianna" sort="Gonelli, Arianna" uniqKey="Gonelli A" first="Arianna" last="Gonelli">Arianna Gonelli</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marisi, Giorgia" sort="Marisi, Giorgia" uniqKey="Marisi G" first="Giorgia" last="Marisi">Giorgia Marisi</name>
<affiliation wicri:level="1"><nlm:affiliation>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola</wicri:regionArea>
<wicri:noRegion>Meldola</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ulivi, Paola" sort="Ulivi, Paola" uniqKey="Ulivi P" first="Paola" last="Ulivi">Paola Ulivi</name>
<affiliation wicri:level="1"><nlm:affiliation>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola</wicri:regionArea>
<wicri:noRegion>Meldola</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Capitani, Silvano" sort="Capitani, Silvano" uniqKey="Capitani S" first="Silvano" last="Capitani">Silvano Capitani</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>LTTA Center, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>LTTA Center, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Neri, Luca M" sort="Neri, Luca M" uniqKey="Neri L" first="Luca M" last="Neri">Luca M. Neri</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara</wicri:regionArea>
<wicri:noRegion>Ferrara</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Oncotarget</title>
<idno type="eISSN">1949-2553</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Autophagy (drug effects)</term>
<term>CD4-Positive T-Lymphocytes (drug effects)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>Cell Line, Tumor (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Imidazoles (pharmacology)</term>
<term>Lymphocyte Activation (MeSH)</term>
<term>Molecular Targeted Therapy (MeSH)</term>
<term>Naphthyridines (pharmacology)</term>
<term>Phosphoinositide-3 Kinase Inhibitors (MeSH)</term>
<term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)</term>
<term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (immunology)</term>
<term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (pathology)</term>
<term>Proto-Oncogene Proteins c-akt (antagonists & inhibitors)</term>
<term>Quinolines (pharmacology)</term>
<term>Signal Transduction (drug effects)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (MeSH)</term>
<term>Autophagie (effets des médicaments et des substances chimiques)</term>
<term>Humains (MeSH)</term>
<term>Imidazoles (pharmacologie)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs T (anatomopathologie)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs T (immunologie)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs T (traitement médicamenteux)</term>
<term>Lignée cellulaire tumorale (MeSH)</term>
<term>Lymphocytes T CD4+ (effets des médicaments et des substances chimiques)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Naphtyridines (pharmacologie)</term>
<term>Protéines proto-oncogènes c-akt (antagonistes et inhibiteurs)</term>
<term>Quinoléines (pharmacologie)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Thérapie moléculaire ciblée (MeSH)</term>
<term>Transduction du signal (effets des médicaments et des substances chimiques)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Proto-Oncogene Proteins c-akt</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Imidazoles</term>
<term>Naphthyridines</term>
<term>Quinolines</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs T</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines proto-oncogènes c-akt</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term>
<term>CD4-Positive T-Lymphocytes</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Autophagie</term>
<term>Lymphocytes T CD4+</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs T</term>
<term>Lymphocytes T CD4+</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Imidazoles</term>
<term>Naphtyridines</term>
<term>Quinoléines</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs T</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term>
<term>Humans</term>
<term>Lymphocyte Activation</term>
<term>Molecular Targeted Therapy</term>
<term>Phosphoinositide-3 Kinase Inhibitors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Thérapie moléculaire ciblée</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">An attractive molecular target for novel anti-cancer therapies is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway which is commonly deregulated in many types of cancer. Nevertheless, the effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune responses, have been seldom explored. In this study we investigated the effects on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK-2206, and ZSTK474. We also assessed their efficacy against two acute leukemia T cell lines. T lymphocytes were stimulated with phytohemagglutinin. Inhibitor effects on cell cycle and apoptosis were analyzed by flow cytometry, while cytotoxicity was assessed by MTT assays. In addition, the activation status of the pathway as well as induction of autophagy were analyzed by Western blotting. Quiescent healthy T lymphocytes were unaffected by the drugs whereas mitogen-stimulated lymphocytes as well as leukemic cell lines displayed a cell cycle block, caspase-dependent apoptosis, and dephosphorylation of key components of the signaling pathway. Autophagy was also induced in proliferating lymphocytes and in JURKAT and MOLT-4 cell lines. When autophagy was inhibited by 3-methyladenine or Bafilomycin A1, drug cytotoxicity was increased, indicating that autophagy is a protective mechanism. Therefore, our findings suggest that PI3K/Akt/mTOR inhibitors preserve lymphocyte viability. This is a valuable result to be taken into account when selecting drugs for targeted cancer therapy in order to minimize detrimental effects on immune function.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27494886</PMID>
<DateCompleted><Year>2018</Year>
<Month>02</Month>
<Day>05</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>12</Month>
<Day>10</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1949-2553</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>7</Volume>
<Issue>34</Issue>
<PubDate><Year>2016</Year>
<Month>Aug</Month>
<Day>23</Day>
</PubDate>
</JournalIssue>
<Title>Oncotarget</Title>
<ISOAbbreviation>Oncotarget</ISOAbbreviation>
</Journal>
<ArticleTitle>Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.</ArticleTitle>
<Pagination><MedlinePgn>55690-55703</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.10984</ELocationID>
<Abstract><AbstractText>An attractive molecular target for novel anti-cancer therapies is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway which is commonly deregulated in many types of cancer. Nevertheless, the effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune responses, have been seldom explored. In this study we investigated the effects on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK-2206, and ZSTK474. We also assessed their efficacy against two acute leukemia T cell lines. T lymphocytes were stimulated with phytohemagglutinin. Inhibitor effects on cell cycle and apoptosis were analyzed by flow cytometry, while cytotoxicity was assessed by MTT assays. In addition, the activation status of the pathway as well as induction of autophagy were analyzed by Western blotting. Quiescent healthy T lymphocytes were unaffected by the drugs whereas mitogen-stimulated lymphocytes as well as leukemic cell lines displayed a cell cycle block, caspase-dependent apoptosis, and dephosphorylation of key components of the signaling pathway. Autophagy was also induced in proliferating lymphocytes and in JURKAT and MOLT-4 cell lines. When autophagy was inhibited by 3-methyladenine or Bafilomycin A1, drug cytotoxicity was increased, indicating that autophagy is a protective mechanism. Therefore, our findings suggest that PI3K/Akt/mTOR inhibitors preserve lymphocyte viability. This is a valuable result to be taken into account when selecting drugs for targeted cancer therapy in order to minimize detrimental effects on immune function.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alameen</LastName>
<ForeName>Ayman A M</ForeName>
<Initials>AA</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Simioni</LastName>
<ForeName>Carolina</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Martelli</LastName>
<ForeName>Alberto M</ForeName>
<Initials>AM</Initials>
<AffiliationInfo><Affiliation>Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zauli</LastName>
<ForeName>Giorgio</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ultimo</LastName>
<ForeName>Simona</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McCubrey</LastName>
<ForeName>James A</ForeName>
<Initials>JA</Initials>
<AffiliationInfo><Affiliation>Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gonelli</LastName>
<ForeName>Arianna</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marisi</LastName>
<ForeName>Giorgia</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ulivi</LastName>
<ForeName>Paola</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Capitani</LastName>
<ForeName>Silvano</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>LTTA Center, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Neri</LastName>
<ForeName>Luca M</ForeName>
<Initials>LM</Initials>
<AffiliationInfo><Affiliation>Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Oncotarget</MedlineTA>
<NlmUniqueID>101532965</NlmUniqueID>
<ISSNLinking>1949-2553</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C570852">8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-piperazin-1-yl-3-trifluoromethylphenyl)-1,3-dihydroimidazo(4,5-c)quinolin-2-one</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C558529">9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo(h)(1,6)naphthyridin-2(1H)-one</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D009287">Naphthyridines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000081082">Phosphoinositide-3 Kinase Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011804">Quinolines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007093" MajorTopicYN="N">Imidazoles</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058990" MajorTopicYN="N">Molecular Targeted Therapy</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009287" MajorTopicYN="N">Naphthyridines</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000081082" MajorTopicYN="Y">Phosphoinositide-3 Kinase Inhibitors</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054218" MajorTopicYN="N">Precursor T-Cell Lymphoblastic Leukemia-Lymphoma</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011804" MajorTopicYN="N">Quinolines</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">PI3K/Akt/mTOR signaling</Keyword>
<Keyword MajorTopicYN="N">T lymphocytes</Keyword>
<Keyword MajorTopicYN="N">T-acute lymphoblastic leukemia</Keyword>
<Keyword MajorTopicYN="N">autophagy</Keyword>
<Keyword MajorTopicYN="N">targeted therapies</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>05</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>07</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>8</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2018</Year>
<Month>2</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>8</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">27494886</ArticleId>
<ArticleId IdType="pii">10984</ArticleId>
<ArticleId IdType="doi">10.18632/oncotarget.10984</ArticleId>
<ArticleId IdType="pmc">PMC5342446</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>Curr Opin Oncol. 2006 Jan;18(1):77-82</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16357568</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2016 Mar 22;7(12):14781-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26895379</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Cycle. 2011 Dec 15;10(24):4330-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22134238</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2013 Sep;4(9):1496-506</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24036604</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2015 Jul 10;6(19):17147-60</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26003166</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Autophagy. 2011 Jul;7(7):707-15</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21460633</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2015 Apr 30;6(12):10399-414</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25871383</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Cancer. 2012 Mar 22;12(4):237-51</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22437869</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Immunol. 2004 Aug 15;173(4):2236-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15294934</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Leukemia. 2010 Jan;24(1):13-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19865108</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Med Oncol. 2016 Apr;33(4):32</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26927447</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Front Oncol. 2014 May 16;4:108</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24904824</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Cell Biochem. 2016 Aug;117(8):1745-52</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27018341</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Blood. 2010 Mar 18;115(11):2203-13</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20081091</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2016 May 31;7(22):33004-15</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27105509</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Res. 2011 Apr 1;71(7):2654-63</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21307130</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Leukemia. 2011 May;25(5):781-91</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21331075</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2016 Oct 4;7(40):64766-64777</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27074568</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2005 Feb 18;307(5712):1098-101</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15718470</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncol Lett. 2014 Sep;8(3):1355-1359</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25120723</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Natl Cancer Inst. 2006 Apr 19;98 (8):545-56</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16622124</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Drug Discov. 2012 Sep;11(9):709-30</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22935804</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Lancet Oncol. 2013 May;14(6):e205-17</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23639321</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2014 Jun 10;9(6):e99486</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24915189</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2016 Apr 19;7(16):21064-75</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27027448</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Int Immunopharmacol. 2015 Sep;28(1):675-85</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26256696</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2011 Mar 4;144(5):646-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21376230</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Cell. 2009 Dec 8;16(6):463-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19962665</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cancer. 2013 May 24;12:46</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23705826</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Radiat Res. 2014 Oct;182(4):363-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25184372</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2012 Aug;3(8):811-23</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22885370</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS Pathog. 2016 Jun 09;12(6):e1005663</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27280548</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Cycle. 2011 Dec 1;10(23):4090-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22101339</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Treat Rev. 2016 Apr;45:87-96</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26995633</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Autophagy. 2016;12 (2):223-4</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26902583</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2016 Feb 9;7(6):7207-15</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26769852</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2016 Apr 12;7(15):19897-909</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26918351</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Leukemia. 2011 Jun;25(6):960-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21455214</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Leukemia. 2012 Nov;26(11):2336-42</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22614243</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2014 Oct 30;5(20):10034-47</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25296981</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Clin Invest. 2008 Nov;118(11):3762-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18830414</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Anticancer Drugs. 2012 Jan;23(1):131-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21959532</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Res. 2013 Apr 15;73(8):2574-86</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23436801</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2010 Nov;1(7):530-43</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21317449</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Blood. 2010 Sep 23;116(12):2078-88</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20522708</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Cycle. 2014;13(14):2237-47</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24874015</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Leukemia. 2013 Mar;27(3):586-94</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23090679</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Res. 2010 Oct 15;70(20):8097-107</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20876803</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Biol Med. 2015 Jun;12(2):126-39</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26175928</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Anticancer Res. 2011 Apr;31(4):1115-23</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21508354</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Ann Oncol. 2012 Sep;23 (9):2399-408</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22357447</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Blood. 2010 Aug 19;116(7):1083-91</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20442367</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Lett. 2014 Jun 1;347(2):196-203</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24614285</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Med Chem Lett. 2013 Feb 14;4(2):206-210</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23795239</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Cell Int. 2015 Sep 29;15:91</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26421002</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cancer Ther. 2010 Jul;9(7):1956-67</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20571069</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Immunol Res. 2015 Jun;62(2):175-88</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25869396</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2011 Mar 10;54(5):1473-80</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21322566</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2013 Feb 22;288(8):5718-31</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23275335</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2011 Mar;2(3):135-64</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21411864</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Cancer Res. 2011 Nov 15;17(22):7116-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21976531</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncogene. 2008 Sep 18;27(41):5497-510</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18794884</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2015 Mar 30;6(9):6597-610</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25788264</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochem J. 2011 Apr 15;435(2):539-44</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21348862</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Italie</li>
<li>Soudan</li>
<li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
</region>
</list>
<tree><country name="Italie"><noRegion><name sortKey="Alameen, Ayman A M" sort="Alameen, Ayman A M" uniqKey="Alameen A" first="Ayman A M" last="Alameen">Ayman A M. Alameen</name>
</noRegion>
<name sortKey="Capitani, Silvano" sort="Capitani, Silvano" uniqKey="Capitani S" first="Silvano" last="Capitani">Silvano Capitani</name>
<name sortKey="Capitani, Silvano" sort="Capitani, Silvano" uniqKey="Capitani S" first="Silvano" last="Capitani">Silvano Capitani</name>
<name sortKey="Gonelli, Arianna" sort="Gonelli, Arianna" uniqKey="Gonelli A" first="Arianna" last="Gonelli">Arianna Gonelli</name>
<name sortKey="Marisi, Giorgia" sort="Marisi, Giorgia" uniqKey="Marisi G" first="Giorgia" last="Marisi">Giorgia Marisi</name>
<name sortKey="Martelli, Alberto M" sort="Martelli, Alberto M" uniqKey="Martelli A" first="Alberto M" last="Martelli">Alberto M. Martelli</name>
<name sortKey="Neri, Luca M" sort="Neri, Luca M" uniqKey="Neri L" first="Luca M" last="Neri">Luca M. Neri</name>
<name sortKey="Simioni, Carolina" sort="Simioni, Carolina" uniqKey="Simioni C" first="Carolina" last="Simioni">Carolina Simioni</name>
<name sortKey="Ulivi, Paola" sort="Ulivi, Paola" uniqKey="Ulivi P" first="Paola" last="Ulivi">Paola Ulivi</name>
<name sortKey="Ultimo, Simona" sort="Ultimo, Simona" uniqKey="Ultimo S" first="Simona" last="Ultimo">Simona Ultimo</name>
<name sortKey="Zauli, Giorgio" sort="Zauli, Giorgio" uniqKey="Zauli G" first="Giorgio" last="Zauli">Giorgio Zauli</name>
</country>
<country name="Soudan"><noRegion><name sortKey="Alameen, Ayman A M" sort="Alameen, Ayman A M" uniqKey="Alameen A" first="Ayman A M" last="Alameen">Ayman A M. Alameen</name>
</noRegion>
</country>
<country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Mccubrey, James A" sort="Mccubrey, James A" uniqKey="Mccubrey J" first="James A" last="Mccubrey">James A. Mccubrey</name>
</region>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Bois/explor/RapamycinFungusV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A97 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000A97 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Bois
   |area=    RapamycinFungusV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:27494886
   |texte=   Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:27494886" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a RapamycinFungusV1

This area was generated with Dilib version V0.6.38.
Data generation: Thu Nov 19 21:55:41 2020. Site generation: Thu Nov 19 22:00:39 2020

	Serveur d'exploration sur la rapamycine et les champignons
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur la rapamycine et les champignons

Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.

Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki