PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.
Identifieur interne : 000780 ( Main/Exploration ); précédent : 000779; suivant : 000781PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.
Auteurs : Simona Ultimo [Italie] ; Carolina Simioni [Italie] ; Alberto M. Martelli [Italie] ; Giorgio Zauli [Italie] ; Camilla Evangelisti [Italie] ; Claudio Celeghini [Italie] ; James A. Mccubrey [États-Unis] ; Giorgia Marisi [Italie] ; Paola Ulivi [Italie] ; Silvano Capitani [Italie] ; Luca M. Neri [Italie]Source :
- Oncotarget [ 1949-2553 ] ; 2017.
Descripteurs français
- KwdFr :
- Apoptose (effets des médicaments et des substances chimiques), Benzamides (administration et posologie), Benzamides (pharmacologie), Humains (MeSH), Inhibiteurs de protéines kinases (administration et posologie), Inhibiteurs de protéines kinases (pharmacologie), Isoenzymes (antagonistes et inhibiteurs), Isoquinoléines (administration et posologie), Isoquinoléines (pharmacologie), Leucémie myéloïde chronique BCR-ABL positive (anatomopathologie), Leucémie myéloïde chronique BCR-ABL positive (traitement médicamenteux), Lignée cellulaire tumorale (MeSH), Mésilate d'imatinib (administration et posologie), Mésilate d'imatinib (pharmacologie), Prolifération cellulaire (effets des médicaments et des substances chimiques), Protocoles de polychimiothérapie antinéoplasique (pharmacologie), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Protéines de fusion bcr-abl (antagonistes et inhibiteurs), Purines (administration et posologie), Purines (pharmacologie), Pyrazoles (administration et posologie), Pyrazoles (pharmacologie), Pyrimidines (administration et posologie), Pyrimidines (pharmacologie), Résistance aux médicaments antinéoplasiques (effets des médicaments et des substances chimiques), Synergie des médicaments (MeSH), Thiazoles (administration et posologie), Thiazoles (pharmacologie), Triazines (administration et posologie), Triazines (pharmacologie).
- MESH :
- administration et posologie : Benzamides, Inhibiteurs de protéines kinases, Isoquinoléines, Mésilate d'imatinib, Purines, Pyrazoles, Pyrimidines, Thiazoles, Triazines.
- anatomopathologie : Leucémie myéloïde chronique BCR-ABL positive.
- antagonistes et inhibiteurs : Isoenzymes, Protéines de fusion bcr-abl.
- effets des médicaments et des substances chimiques : Apoptose, Prolifération cellulaire, Résistance aux médicaments antinéoplasiques.
- pharmacologie : Benzamides, Inhibiteurs de protéines kinases, Isoquinoléines, Mésilate d'imatinib, Protocoles de polychimiothérapie antinéoplasique, Purines, Pyrazoles, Pyrimidines, Thiazoles, Triazines.
- traitement médicamenteux : Leucémie myéloïde chronique BCR-ABL positive.
- usage thérapeutique : Protocoles de polychimiothérapie antinéoplasique.
- Humains, Lignée cellulaire tumorale, Synergie des médicaments.
English descriptors
- KwdEn :
- Antineoplastic Combined Chemotherapy Protocols (pharmacology), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), Apoptosis (drug effects), Benzamides (administration & dosage), Benzamides (pharmacology), Cell Line, Tumor (MeSH), Cell Proliferation (drug effects), Drug Resistance, Neoplasm (drug effects), Drug Synergism (MeSH), Fusion Proteins, bcr-abl (antagonists & inhibitors), Humans (MeSH), Imatinib Mesylate (administration & dosage), Imatinib Mesylate (pharmacology), Isoenzymes (antagonists & inhibitors), Isoquinolines (administration & dosage), Isoquinolines (pharmacology), Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy), Leukemia, Myelogenous, Chronic, BCR-ABL Positive (pathology), Phosphoinositide-3 Kinase Inhibitors (MeSH), Protein Kinase Inhibitors (administration & dosage), Protein Kinase Inhibitors (pharmacology), Purines (administration & dosage), Purines (pharmacology), Pyrazoles (administration & dosage), Pyrazoles (pharmacology), Pyrimidines (administration & dosage), Pyrimidines (pharmacology), Thiazoles (administration & dosage), Thiazoles (pharmacology), Triazines (administration & dosage), Triazines (pharmacology).
- MESH :
- chemical , administration & dosage : Benzamides, Imatinib Mesylate, Isoquinolines, Protein Kinase Inhibitors, Purines, Pyrazoles, Pyrimidines, Thiazoles, Triazines.
- chemical , antagonists & inhibitors : Fusion Proteins, bcr-abl, Isoenzymes.
- drug effects : Apoptosis, Cell Proliferation, Drug Resistance, Neoplasm.
- drug therapy : Leukemia, Myelogenous, Chronic, BCR-ABL Positive.
- pathology : Leukemia, Myelogenous, Chronic, BCR-ABL Positive.
- pharmacology : Antineoplastic Combined Chemotherapy Protocols, Benzamides, Imatinib Mesylate, Isoquinolines, Protein Kinase Inhibitors, Purines, Pyrazoles, Pyrimidines, Thiazoles, Triazines.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Cell Line, Tumor, Drug Synergism, Humans, Phosphoinositide-3 Kinase Inhibitors.
Abstract
B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein.We studied the effects of anti Bcr-Abl drugs Imatinib, Nilotinib and GZD824 associated with PI3K isoform inhibitors. We used a panel of six compounds which specifically target PI3K isoforms including the pan-PI3K inhibitor ZSTK474, p110α BYL719 inhibitor and the dual p110γ/p110δ inhibitor IPI145. The effects of single drugs and of several drug combinations were analyzed to assess cytotoxicity by MTS assays, apoptosis and autophagy by flow cytometry and Western blot, as well as the phosphorylation status of the pathway.ZSTK474, BYL719 and IPI145 administered in combination with imatinib, nilotinib and GZD824 for 48 h, decreased cell viability, induced apoptosis and autophagy in a marked synergistic manner.These findings suggest that selected PI3K isoform inhibitors used in combination with anti Bcr-Abl drugs may be an attractive novel therapeutic intervention in Ph+ B-ALL.
DOI: 10.18632/oncotarget.15542
PubMed: 28390196
PubMed Central: PMC5410298
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.</title><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="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="Evangelisti, Camilla" sort="Evangelisti, Camilla" uniqKey="Evangelisti C" first="Camilla" last="Evangelisti">Camilla Evangelisti</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Genetics, Rizzoli Orthopedic Institute, National Research Council, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Molecular Genetics, Rizzoli Orthopedic Institute, National Research Council, Bologna</wicri:regionArea><wicri:noRegion>Bologna</wicri:noRegion></affiliation></author><author><name sortKey="Celeghini, Claudio" sort="Celeghini, Claudio" uniqKey="Celeghini C" first="Claudio" last="Celeghini">Claudio Celeghini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Sciences, University of Trieste, Trieste, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Life Sciences, University of Trieste, Trieste</wicri:regionArea><wicri:noRegion>Trieste</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 and 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 and 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="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="2017">2017</date><idno type="RBID">pubmed:28390196</idno><idno type="pmid">28390196</idno><idno type="doi">10.18632/oncotarget.15542</idno><idno type="pmc">PMC5410298</idno><idno type="wicri:Area/Main/Corpus">000835</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000835</idno><idno type="wicri:Area/Main/Curation">000835</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000835</idno><idno type="wicri:Area/Main/Exploration">000835</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.</title><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="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="Evangelisti, Camilla" sort="Evangelisti, Camilla" uniqKey="Evangelisti C" first="Camilla" last="Evangelisti">Camilla Evangelisti</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Genetics, Rizzoli Orthopedic Institute, National Research Council, Bologna, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Molecular Genetics, Rizzoli Orthopedic Institute, National Research Council, Bologna</wicri:regionArea><wicri:noRegion>Bologna</wicri:noRegion></affiliation></author><author><name sortKey="Celeghini, Claudio" sort="Celeghini, Claudio" uniqKey="Celeghini C" first="Claudio" last="Celeghini">Claudio Celeghini</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Sciences, University of Trieste, Trieste, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Life Sciences, University of Trieste, Trieste</wicri:regionArea><wicri:noRegion>Trieste</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 and 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 and 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="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="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols (pharmacology)</term><term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term><term>Apoptosis (drug effects)</term><term>Benzamides (administration & dosage)</term><term>Benzamides (pharmacology)</term><term>Cell Line, Tumor (MeSH)</term><term>Cell Proliferation (drug effects)</term><term>Drug Resistance, Neoplasm (drug effects)</term><term>Drug Synergism (MeSH)</term><term>Fusion Proteins, bcr-abl (antagonists & inhibitors)</term><term>Humans (MeSH)</term><term>Imatinib Mesylate (administration & dosage)</term><term>Imatinib Mesylate (pharmacology)</term><term>Isoenzymes (antagonists & inhibitors)</term><term>Isoquinolines (administration & dosage)</term><term>Isoquinolines (pharmacology)</term><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)</term><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (pathology)</term><term>Phosphoinositide-3 Kinase Inhibitors (MeSH)</term><term>Protein Kinase Inhibitors (administration & dosage)</term><term>Protein Kinase Inhibitors (pharmacology)</term><term>Purines (administration & dosage)</term><term>Purines (pharmacology)</term><term>Pyrazoles (administration & dosage)</term><term>Pyrazoles (pharmacology)</term><term>Pyrimidines (administration & dosage)</term><term>Pyrimidines (pharmacology)</term><term>Thiazoles (administration & dosage)</term><term>Thiazoles (pharmacology)</term><term>Triazines (administration & dosage)</term><term>Triazines (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Apoptose (effets des médicaments et des substances chimiques)</term><term>Benzamides (administration et posologie)</term><term>Benzamides (pharmacologie)</term><term>Humains (MeSH)</term><term>Inhibiteurs de protéines kinases (administration et posologie)</term><term>Inhibiteurs de protéines kinases (pharmacologie)</term><term>Isoenzymes (antagonistes et inhibiteurs)</term><term>Isoquinoléines (administration et posologie)</term><term>Isoquinoléines (pharmacologie)</term><term>Leucémie myéloïde chronique BCR-ABL positive (anatomopathologie)</term><term>Leucémie myéloïde chronique BCR-ABL positive (traitement médicamenteux)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Mésilate d'imatinib (administration et posologie)</term><term>Mésilate d'imatinib (pharmacologie)</term><term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term><term>Protocoles de polychimiothérapie antinéoplasique (pharmacologie)</term><term>Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique)</term><term>Protéines de fusion bcr-abl (antagonistes et inhibiteurs)</term><term>Purines (administration et posologie)</term><term>Purines (pharmacologie)</term><term>Pyrazoles (administration et posologie)</term><term>Pyrazoles (pharmacologie)</term><term>Pyrimidines (administration et posologie)</term><term>Pyrimidines (pharmacologie)</term><term>Résistance aux médicaments antinéoplasiques (effets des médicaments et des substances chimiques)</term><term>Synergie des médicaments (MeSH)</term><term>Thiazoles (administration et posologie)</term><term>Thiazoles (pharmacologie)</term><term>Triazines (administration et posologie)</term><term>Triazines (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Benzamides</term><term>Imatinib Mesylate</term><term>Isoquinolines</term><term>Protein Kinase Inhibitors</term><term>Purines</term><term>Pyrazoles</term><term>Pyrimidines</term><term>Thiazoles</term><term>Triazines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Fusion Proteins, bcr-abl</term><term>Isoenzymes</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Benzamides</term><term>Inhibiteurs de protéines kinases</term><term>Isoquinoléines</term><term>Mésilate d'imatinib</term><term>Purines</term><term>Pyrazoles</term><term>Pyrimidines</term><term>Thiazoles</term><term>Triazines</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Leucémie myéloïde chronique BCR-ABL positive</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Isoenzymes</term><term>Protéines de fusion bcr-abl</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Cell Proliferation</term><term>Drug Resistance, Neoplasm</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term><term>Prolifération cellulaire</term><term>Résistance aux médicaments antinéoplasiques</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Benzamides</term><term>Inhibiteurs de protéines kinases</term><term>Isoquinoléines</term><term>Mésilate d'imatinib</term><term>Protocoles de polychimiothérapie antinéoplasique</term><term>Purines</term><term>Pyrazoles</term><term>Pyrimidines</term><term>Thiazoles</term><term>Triazines</term></keywords><keywords scheme="MESH" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term><term>Benzamides</term><term>Imatinib Mesylate</term><term>Isoquinolines</term><term>Protein Kinase Inhibitors</term><term>Purines</term><term>Pyrazoles</term><term>Pyrimidines</term><term>Thiazoles</term><term>Triazines</term></keywords><keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie myéloïde chronique BCR-ABL positive</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Protocoles de polychimiothérapie antinéoplasique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Humans</term><term>Phosphoinositide-3 Kinase Inhibitors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Synergie des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein.We studied the effects of anti Bcr-Abl drugs Imatinib, Nilotinib and GZD824 associated with PI3K isoform inhibitors. We used a panel of six compounds which specifically target PI3K isoforms including the pan-PI3K inhibitor ZSTK474, p110α BYL719 inhibitor and the dual p110γ/p110δ inhibitor IPI145. The effects of single drugs and of several drug combinations were analyzed to assess cytotoxicity by MTS assays, apoptosis and autophagy by flow cytometry and Western blot, as well as the phosphorylation status of the pathway.ZSTK474, BYL719 and IPI145 administered in combination with imatinib, nilotinib and GZD824 for 48 h, decreased cell viability, induced apoptosis and autophagy in a marked synergistic manner.These findings suggest that selected PI3K isoform inhibitors used in combination with anti Bcr-Abl drugs may be an attractive novel therapeutic intervention in Ph+ B-ALL.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28390196</PMID><DateCompleted><Year>2018</Year><Month>01</Month><Day>12</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>8</Volume><Issue>14</Issue><PubDate><Year>2017</Year><Month>Apr</Month><Day>04</Day></PubDate></JournalIssue><Title>Oncotarget</Title><ISOAbbreviation>Oncotarget</ISOAbbreviation></Journal><ArticleTitle>PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.</ArticleTitle><Pagination><MedlinePgn>23213-23227</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.15542</ELocationID><Abstract><AbstractText>B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein.We studied the effects of anti Bcr-Abl drugs Imatinib, Nilotinib and GZD824 associated with PI3K isoform inhibitors. We used a panel of six compounds which specifically target PI3K isoforms including the pan-PI3K inhibitor ZSTK474, p110α BYL719 inhibitor and the dual p110γ/p110δ inhibitor IPI145. The effects of single drugs and of several drug combinations were analyzed to assess cytotoxicity by MTS assays, apoptosis and autophagy by flow cytometry and Western blot, as well as the phosphorylation status of the pathway.ZSTK474, BYL719 and IPI145 administered in combination with imatinib, nilotinib and GZD824 for 48 h, decreased cell viability, induced apoptosis and autophagy in a marked synergistic manner.These findings suggest that selected PI3K isoform inhibitors used in combination with anti Bcr-Abl drugs may be an attractive novel therapeutic intervention in Ph+ B-ALL.</AbstractText></Abstract><AuthorList CompleteYN="Y"><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>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>Evangelisti</LastName><ForeName>Camilla</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Molecular Genetics, Rizzoli Orthopedic Institute, National Research Council, Bologna, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Celeghini</LastName><ForeName>Claudio</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Life Sciences, University of Trieste, Trieste, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McCubrey</LastName><ForeName>James A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.</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="C579813">3-((1H-pyrazolo(3,4-b)pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C498826">4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001549">Benzamides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007527">Isoenzymes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007546">Isoquinolines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000081082">Phosphoinositide-3 Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011687">Purines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011720">Pyrazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011743">Pyrimidines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013844">Thiazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014227">Triazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C510150">ZSTK474</NameOfSubstance></Chemical><Chemical><RegistryNumber>08W5N2C97Q</RegistryNumber><NameOfSubstance UI="C585539">Alpelisib</NameOfSubstance></Chemical><Chemical><RegistryNumber>610V23S0JI</RegistryNumber><NameOfSubstance UI="C586691">duvelisib</NameOfSubstance></Chemical><Chemical><RegistryNumber>8A1O1M485B</RegistryNumber><NameOfSubstance UI="D000068877">Imatinib Mesylate</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.2</RegistryNumber><NameOfSubstance UI="D016044">Fusion Proteins, bcr-abl</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001549" MajorTopicYN="N">Benzamides</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019008" MajorTopicYN="N">Drug Resistance, Neoplasm</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004357" MajorTopicYN="N">Drug Synergism</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016044" MajorTopicYN="N">Fusion Proteins, bcr-abl</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000068877" MajorTopicYN="N">Imatinib Mesylate</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007527" MajorTopicYN="N">Isoenzymes</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007546" MajorTopicYN="N">Isoquinolines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015464" MajorTopicYN="N">Leukemia, Myelogenous, Chronic, BCR-ABL Positive</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000081082" MajorTopicYN="Y">Phosphoinositide-3 Kinase Inhibitors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D047428" MajorTopicYN="N">Protein Kinase Inhibitors</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011687" MajorTopicYN="N">Purines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011720" MajorTopicYN="N">Pyrazoles</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011743" MajorTopicYN="N">Pyrimidines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013844" MajorTopicYN="N">Thiazoles</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014227" MajorTopicYN="N">Triazines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Bcr-Abl</Keyword><Keyword MajorTopicYN="N">PI3K isoforms</Keyword><Keyword MajorTopicYN="N">Ph+ B-acute lymphoblastic leukemia</Keyword><Keyword MajorTopicYN="N">autophagy</Keyword><Keyword MajorTopicYN="N">tyrosine kinase inhibitors</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>12</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>02</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>1</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28390196</ArticleId><ArticleId IdType="pii">15542</ArticleId><ArticleId IdType="doi">10.18632/oncotarget.15542</ArticleId><ArticleId IdType="pmc">PMC5410298</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Biochem Biophys Res Commun. 2014 Nov 21;454(3):423-8</Citation><ArticleIdList><ArticleId IdType="pubmed">25451263</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2015 Apr 30;6(12):10399-414</Citation><ArticleIdList><ArticleId IdType="pubmed">25871383</ArticleId></ArticleIdList></Reference><Reference><Citation>Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8</Citation><ArticleIdList><ArticleId IdType="pubmed">23726034</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Lett. 2006 Sep 28;241(2):184-96</Citation><ArticleIdList><ArticleId IdType="pubmed">16412571</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2016 Jul 19;7(29):45186-45198</Citation><ArticleIdList><ArticleId IdType="pubmed">27286256</ArticleId></ArticleIdList></Reference><Reference><Citation>Leuk Res. 2012 Apr;36(4):509-13</Citation><ArticleIdList><ArticleId IdType="pubmed">22285507</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Drug Discov. 2014 Feb;13(2):140-56</Citation><ArticleIdList><ArticleId IdType="pubmed">24481312</ArticleId></ArticleIdList></Reference><Reference><Citation>Med Oncol. 2016 Apr;33(4):32</Citation><ArticleIdList><ArticleId IdType="pubmed">26927447</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer. 2011 Apr 15;117(8):1583-94</Citation><ArticleIdList><ArticleId IdType="pubmed">21472706</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Med. 2005 Sep;11(9):936-43</Citation><ArticleIdList><ArticleId IdType="pubmed">16127437</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Cell. 2005 Feb;7(2):129-41</Citation><ArticleIdList><ArticleId IdType="pubmed">15710326</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 2000 Nov 15;96(10):3343-56</Citation><ArticleIdList><ArticleId IdType="pubmed">11071626</ArticleId></ArticleIdList></Reference><Reference><Citation>J Clin Invest. 2008 Sep;118(9):3038-50</Citation><ArticleIdList><ArticleId IdType="pubmed">18704194</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 2005 Aug 1;106(3):1063-6</Citation><ArticleIdList><ArticleId IdType="pubmed">15840695</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Genet. 2006 Aug;7(8):606-19</Citation><ArticleIdList><ArticleId IdType="pubmed">16847462</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Drug Discov. 2005 Dec;4(12):988-1004</Citation><ArticleIdList><ArticleId IdType="pubmed">16341064</ArticleId></ArticleIdList></Reference><Reference><Citation>J Clin Invest. 2014 Apr;124(4):1794-809</Citation><ArticleIdList><ArticleId IdType="pubmed">24569456</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2016 Oct 4;7(40):64766-64777</Citation><ArticleIdList><ArticleId IdType="pubmed">27074568</ArticleId></ArticleIdList></Reference><Reference><Citation>Immunology. 2014 Jan;141(1):1-8</Citation><ArticleIdList><ArticleId IdType="pubmed">23991647</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>Cancer Treat Rev. 2004 Feb;30(1):37-51</Citation><ArticleIdList><ArticleId IdType="pubmed">14766125</ArticleId></ArticleIdList></Reference><Reference><Citation>FASEB J. 2014 Feb;28(2):524-35</Citation><ArticleIdList><ArticleId IdType="pubmed">24196588</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2014 Mar 13;370(11):1061-2</Citation><ArticleIdList><ArticleId IdType="pubmed">24620870</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Sci. 2012 Nov;103(11):1955-60</Citation><ArticleIdList><ArticleId IdType="pubmed">22925034</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Cancer Res. 2017 Jan 1;23 (1):26-34</Citation><ArticleIdList><ArticleId IdType="pubmed">27126994</ArticleId></ArticleIdList></Reference><Reference><Citation>Leukemia. 2005 Oct;19(10):1774-82</Citation><ArticleIdList><ArticleId IdType="pubmed">16136169</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Res. 2010 Jun 15;70(12 ):4982-94</Citation><ArticleIdList><ArticleId IdType="pubmed">20530683</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Treat Rev. 2016 Apr;45:87-96</Citation><ArticleIdList><ArticleId IdType="pubmed">26995633</ArticleId></ArticleIdList></Reference><Reference><Citation>Pharmacol Ther. 2015 Feb;146:53-60</Citation><ArticleIdList><ArticleId IdType="pubmed">25240910</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2013 Nov 14;8(11):e80070</Citation><ArticleIdList><ArticleId IdType="pubmed">24244612</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Transl Med. 2013 Jul 31;5(196):196ra99</Citation><ArticleIdList><ArticleId IdType="pubmed">23903756</ArticleId></ArticleIdList></Reference><Reference><Citation>Acta Pharmacol Sin. 2010 Sep;31(9):1189-97</Citation><ArticleIdList><ArticleId IdType="pubmed">20729870</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>Eur J Clin Pharmacol. 2016 Feb;72 (2):185-93</Citation><ArticleIdList><ArticleId IdType="pubmed">26507546</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 2004 Apr 15;103(8):3167-74</Citation><ArticleIdList><ArticleId IdType="pubmed">15070699</ArticleId></ArticleIdList></Reference><Reference><Citation>Mol Cancer Ther. 2012 Aug;11(8):1747-57</Citation><ArticleIdList><ArticleId IdType="pubmed">22653967</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Chem. 2013 Feb 14;56(3):879-94</Citation><ArticleIdList><ArticleId IdType="pubmed">23301703</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2014 Jul 30;5(14):5381-91</Citation><ArticleIdList><ArticleId IdType="pubmed">25026292</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>Mol Cancer Ther. 2014 May;13(5):1117-29</Citation><ArticleIdList><ArticleId IdType="pubmed">24608574</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Cell. 2012 Apr 17;21(4):459-72</Citation><ArticleIdList><ArticleId IdType="pubmed">22516257</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2016 Mar 29;7(13):16996-7008</Citation><ArticleIdList><ArticleId IdType="pubmed">26959738</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Cancer. 2010 May;10(5):342-52</Citation><ArticleIdList><ArticleId IdType="pubmed">20414202</ArticleId></ArticleIdList></Reference><Reference><Citation>Cancer Sci. 2008 Sep;99(9):1734-40</Citation><ArticleIdList><ArticleId IdType="pubmed">18616528</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur J Cancer. 2010 Apr;46(6):1111-21</Citation><ArticleIdList><ArticleId IdType="pubmed">20129775</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2014 Apr 08;9(4):e94374</Citation><ArticleIdList><ArticleId IdType="pubmed">24714637</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 2011 Jan 13;117(2):591-4</Citation><ArticleIdList><ArticleId IdType="pubmed">20959606</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2002 May 31;296(5573):1655-7</Citation><ArticleIdList><ArticleId IdType="pubmed">12040186</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur J Haematol. 2014 Feb;92(2):111-20</Citation><ArticleIdList><ArticleId IdType="pubmed">24112092</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2015 Apr 08;5:9465</Citation><ArticleIdList><ArticleId IdType="pubmed">25853938</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2006 Dec 7;355(23):2408-17</Citation><ArticleIdList><ArticleId IdType="pubmed">17151364</ArticleId></ArticleIdList></Reference><Reference><Citation>Haematologica. 2013 Sep;98(9):1335-43</Citation><ArticleIdList><ArticleId IdType="pubmed">24006406</ArticleId></ArticleIdList></Reference><Reference><Citation>Leuk Lymphoma. 2007 Dec;48(12):2310-22</Citation><ArticleIdList><ArticleId IdType="pubmed">18067005</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2016 Aug 23;7(34):55690-55703</Citation><ArticleIdList><ArticleId IdType="pubmed">27494886</ArticleId></ArticleIdList></Reference><Reference><Citation>Ther Adv Med Oncol. 2014 Mar;6(2):43-51</Citation><ArticleIdList><ArticleId IdType="pubmed">24587830</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 2014 Jun 19;123(25):3999-4000</Citation><ArticleIdList><ArticleId IdType="pubmed">24948623</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2015 Mar 30;6(9):6597-610</Citation><ArticleIdList><ArticleId IdType="pubmed">25788264</ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2014 Feb 28;5(4):894-900</Citation><ArticleIdList><ArticleId IdType="pubmed">24658595</ArticleId></ArticleIdList></Reference><Reference><Citation>Bioorg Med Chem Lett. 2004 Dec 6;14(23):5793-7</Citation><ArticleIdList><ArticleId IdType="pubmed">15501042</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Italie</li><li>États-Unis</li></country><region><li>Caroline du Nord</li></region></list><tree><country name="Italie"><noRegion><name sortKey="Ultimo, Simona" sort="Ultimo, Simona" uniqKey="Ultimo S" first="Simona" last="Ultimo">Simona Ultimo</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="Celeghini, Claudio" sort="Celeghini, Claudio" uniqKey="Celeghini C" first="Claudio" last="Celeghini">Claudio Celeghini</name><name sortKey="Evangelisti, Camilla" sort="Evangelisti, Camilla" uniqKey="Evangelisti C" first="Camilla" last="Evangelisti">Camilla Evangelisti</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="Zauli, Giorgio" sort="Zauli, Giorgio" uniqKey="Zauli G" first="Giorgio" last="Zauli">Giorgio Zauli</name></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 000780 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000780 | 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:28390196
|texte= PI3K isoform inhibition associated with anti Bcr-Abl drugs shows in vitro increased anti-leukemic activity in Philadelphia chromosome-positive B-acute lymphoblastic leukemia cell lines.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:28390196" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a RapamycinFungusV1
| This area was generated with Dilib version V0.6.38. |  |