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Article ; Online: Pediatric Medical Countermeasures: Antidotes and Cytokines for Radiological and Nuclear Incidents and Terrorism.

Maciulewicz, Thom S / Kazzi, Ziad / Navis, Irene L / Nelsen, Gregory J / Cieslak, Theodore J / Newton, Christopher / Lin, Anna / West, Doneen J / Walter, Frank G

Disaster medicine and public health preparedness

2024 Volume 18, Page(s) e76

Abstract: The war in Ukraine raises concerns for potential hazards of radiological and nuclear incidents. Children are particularly vulnerable in these incidents and may need pharmaceutical countermeasures, including antidotes and cytokines. Searches found no ... ...

Abstract	The war in Ukraine raises concerns for potential hazards of radiological and nuclear incidents. Children are particularly vulnerable in these incidents and may need pharmaceutical countermeasures, including antidotes and cytokines. Searches found no published study comparing pediatric indications and dosing among standard references detailing pediatric medications for these incidents. This study addresses this gap by collecting, tabulating, and disseminating this information to healthcare professionals caring for children. Expert consensus chose the following references to compare their pediatric indications and dosing of medical countermeasures for radiation exposure and internal contamination with radioactive materials:
MeSH term(s)	Humans ; Terrorism/statistics & numerical data ; Medical Countermeasures ; Antidotes/therapeutic use ; Child ; Cytokines ; Radioactive Hazard Release ; Ukraine ; Pediatrics/methods ; Pediatrics/standards ; Disaster Planning/methods
Chemical Substances	Antidotes ; Cytokines
Language	English
Publishing date	2024-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2375268-3
ISSN	1938-744X ; 1935-7893
ISSN (online)	1938-744X
ISSN	1935-7893
DOI	10.1017/dmp.2024.35
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Article ; Online: An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver.

Fernández Moro, Carlos / Geyer, Natalie / Harrizi, Sara / Hamidi, Yousra / Söderqvist, Sara / Kuznyecov, Danyil / Tidholm Qvist, Evelina / Salmonson Schaad, Media / Hermann, Laura / Lindberg, Amanda / Heuchel, Rainer L / Martín-Bernabé, Alfonso / Dhanjal, Soniya / Navis, Anna C / Villard, Christina / Del Valle, Andrea C / Bozóky, Lorand / Sparrelid, Ernesto / Dirix, Luc /

Strell, Carina / Östman, Arne / Schmierer, Bernhard / Vermeulen, Peter B / Engstrand, Jennie / Bozóky, Béla / Gerling, Marco

Nature communications

2023 Volume 14, Issue 1, Page(s) 5024

Abstract: A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to ...

Abstract	A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR
MeSH term(s)	Animals ; Mice ; Liver Neoplasms ; Hepatocytes ; Aggression ; Clinical Relevance
Language	English
Publishing date	2023-08-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40688-x
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Article ; Online: UHRF1 Licensed Self-Renewal of Active Adult Neural Stem Cells.

Blanchart, Albert / Navis, Anna C / Assaife-Lopes, Natalia / Usoskin, Dmitry / Aranda, Sergi / Sontheimer, Jana / Ernfors, Patrik

Stem cells (Dayton, Ohio)

2018 Volume 36, Issue 11, Page(s) 1736–1751

Abstract: Adult neurogenesis in the brain continuously seeds new neurons throughout life, but how homeostasis of adult neural stem cells (NSCs) is maintained is incompletely understood. Here, we demonstrate that the DNA methylation adapter ubiquitin-like, ... ...

Abstract	Adult neurogenesis in the brain continuously seeds new neurons throughout life, but how homeostasis of adult neural stem cells (NSCs) is maintained is incompletely understood. Here, we demonstrate that the DNA methylation adapter ubiquitin-like, containing PHD and RING finger domains-1 (UHRF1) is expressed in, and regulates proliferation of, the active but not quiescent pool of adult neural progenitor cells. Mice with a neural stem cell-specific deficiency in UHRF1 exhibit a massive depletion of neurogenesis resulting in a collapse of formation of new neurons. In the absence of UHRF1, NSCs unexpectedly remain in the cell cycle but with a 17-fold increased cell cycle length due to a failure of replication phase entry caused by promoter demethylation and derepression of Cdkn1a, which encodes the cyclin-dependent kinase inhibitor p21. UHRF1 does not affect the proportion progenitor cells active within the cell cycle but among these cells, UHRF1 is critical for licensing replication re-entry. Therefore, this study shows that a UHRF1-Cdkn1a axis is essential for the control of stem cell self-renewal and neurogenesis in the adult brain. Stem Cells 2018;36:1736-1751.
MeSH term(s)	Adult Stem Cells/metabolism ; Animals ; Humans ; Mice ; Neural Stem Cells/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism
Chemical Substances	Nuclear Proteins ; Uhrf1 protein, mouse
Language	English
Publishing date	2018-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.2889
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Article ; Online: p120-catenin-dependent collective brain infiltration by glioma cell networks.

Gritsenko, Pavlo G / Atlasy, Nader / Dieteren, Cindy E J / Navis, Anna C / Venhuizen, Jan-Hendrik / Veelken, Cornelia / Schubert, Dirk / Acker-Palmer, Amparo / Westerman, Bart A / Wurdinger, Thomas / Leenders, William / Wesseling, Pieter / Stunnenberg, Hendrik G / Friedl, Peter

Nature cell biology

2020 Volume 22, Issue 1, Page(s) 97–107

Abstract: Diffuse brain infiltration by glioma cells causes detrimental disease progression, but its multicellular coordination is poorly understood. We show here that glioma cells infiltrate the brain collectively as multicellular networks. Contacts between ... ...

Abstract	Diffuse brain infiltration by glioma cells causes detrimental disease progression, but its multicellular coordination is poorly understood. We show here that glioma cells infiltrate the brain collectively as multicellular networks. Contacts between moving glioma cells are adaptive epithelial-like or filamentous junctions stabilized by N-cadherin, β-catenin and p120-catenin, which undergo kinetic turnover, transmit intercellular calcium transients and mediate directional persistence. Downregulation of p120-catenin compromises cell-cell interaction and communication, disrupts collective networks, and both the cadherin and RhoA binding domains of p120-catenin are required for network formation and migration. Deregulating p120-catenin further prevents diffuse glioma cell infiltration of the mouse brain with marginalized microlesions as the outcome. Transcriptomics analysis has identified p120-catenin as an upstream regulator of neurogenesis and cell cycle pathways and a predictor of poor clinical outcome in glioma patients. Collective glioma networks infiltrating the brain thus depend on adherens junctions dynamics, the targeting of which may offer an unanticipated strategy to halt glioma progression.
MeSH term(s)	Adherens Junctions/metabolism ; Animals ; Brain/metabolism ; Brain/pathology ; Cadherins/metabolism ; Catenins/metabolism ; Cell Adhesion/physiology ; Cell Line, Tumor ; Down-Regulation/physiology ; Glioma/metabolism ; Glioma/pathology ; Phosphoproteins/metabolism ; Phosphorylation ; Delta Catenin
Chemical Substances	Cadherins ; Catenins ; Phosphoproteins ; Delta Catenin
Language	English
Publishing date	2020-01-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-019-0443-x
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Legomedicine-A Versatile Chemo-Enzymatic Approach for the Preparation of Targeted Dual-Labeled Llama Antibody-Nanoparticle Conjugates.

van Lith, Sanne A M / van Duijnhoven, Sander M J / Navis, Anna C / Leenders, William P J / Dolk, Edward / Wennink, Jos W H / van Nostrum, Cornelus F / van Hest, Jan C M

Bioconjugate chemistry

2017 Volume 28, Issue 2, Page(s) 539–548

Abstract: Conjugation of llama single domain antibody fragments (Variable Heavy chain domains of Heavy chain antibodies, VHHs) to diagnostic or therapeutic nanoparticles, peptides, proteins, or drugs offers many opportunities for optimized targeted cancer ... ...

Abstract	Conjugation of llama single domain antibody fragments (Variable Heavy chain domains of Heavy chain antibodies, VHHs) to diagnostic or therapeutic nanoparticles, peptides, proteins, or drugs offers many opportunities for optimized targeted cancer treatment. Currently, mostly nonspecific conjugation strategies or genetic fusions are used that may compromise VHH functionality. In this paper we present a versatile modular approach for bioorthogonal VHH modification and conjugation. First, sortase A mediated transPEGylation is used for introduction of a chemical click moiety. The resulting clickable VHHs are then used for conjugation to other groups employing the Cu
MeSH term(s)	Alkynes/chemistry ; Aminoacyltransferases/metabolism ; Animals ; Azides/chemistry ; Bacterial Proteins/metabolism ; Camelids, New World/immunology ; Click Chemistry/methods ; Cycloaddition Reaction/methods ; Cysteine Endopeptidases/metabolism ; Immunoconjugates/chemistry ; Immunoconjugates/immunology ; Immunoconjugates/metabolism ; Immunoglobulin Heavy Chains/chemistry ; Immunoglobulin Heavy Chains/immunology ; Immunoglobulin Heavy Chains/metabolism ; Nanoparticles/chemistry ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/metabolism ; Single-Domain Antibodies/chemistry ; Single-Domain Antibodies/immunology ; Single-Domain Antibodies/metabolism
Chemical Substances	Alkynes ; Azides ; Bacterial Proteins ; Immunoconjugates ; Immunoglobulin Heavy Chains ; Single-Domain Antibodies ; Polyethylene Glycols (30IQX730WE) ; Aminoacyltransferases (EC 2.3.2.-) ; sortase A (EC 2.3.2.-) ; Cysteine Endopeptidases (EC 3.4.22.-)
Language	English
Publishing date	2017-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.6b00638
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Article ; Online: IDH1 R132H mutation generates a distinct phospholipid metabolite profile in glioma.

Esmaeili, Morteza / Hamans, Bob C / Navis, Anna C / van Horssen, Remco / Bathen, Tone F / Gribbestad, Ingrid S / Leenders, William P / Heerschap, Arend

Cancer research

2014 Volume 74, Issue 17, Page(s) 4898–4907

Abstract: Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several ... ...

Abstract	Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed (31)P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation. (31)P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by (31)P high-resolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro (31)P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma.
MeSH term(s)	Animals ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Ethanolamines/metabolism ; Female ; Glioma/genetics ; Glioma/metabolism ; Humans ; Isocitrate Dehydrogenase/genetics ; Magnetic Resonance Spectroscopy/methods ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mutation/genetics ; Phospholipids/genetics ; Phospholipids/metabolism
Chemical Substances	Biomarkers, Tumor ; Ethanolamines ; Phospholipids ; phosphorylethanolamine (78A2BX7AEU) ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.)
Language	English
Publishing date	2014-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-14-0008
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Article ; Online: Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma.

Sol, Nik / In 't Veld, Sjors G J G / Vancura, Adrienne / Tjerkstra, Maud / Leurs, Cyra / Rustenburg, François / Schellen, Pepijn / Verschueren, Heleen / Post, Edward / Zwaan, Kenn / Ramaker, Jip / Wedekind, Laurine E / Tannous, Jihane / Ylstra, Bauke / Killestein, Joep / Mateen, Farrah / Idema, Sander / de Witt Hamer, Philip C / Navis, Anna C /

Leenders, William P J / Hoeben, Ann / Moraal, Bastiaan / Noske, David P / Vandertop, W Peter / Nilsson, R Jonas A / Tannous, Bakhos A / Wesseling, Pieter / Reijneveld, Jaap C / Best, Myron G / Wurdinger, Thomas

Cell reports. Medicine

2020 Volume 1, Issue 7, Page(s) 100101

Abstract: Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined ... ...

Abstract	Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Algorithms ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Blood Platelets/metabolism ; Blood Platelets/pathology ; Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Brain Neoplasms/mortality ; Brain Neoplasms/surgery ; Case-Control Studies ; Disease Progression ; Glioblastoma/diagnosis ; Glioblastoma/genetics ; Glioblastoma/mortality ; Glioblastoma/surgery ; Humans ; Middle Aged ; Monitoring, Physiologic/methods ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/genetics ; Multiple Sclerosis/pathology ; Neoplasm Metastasis ; RNA Splicing ; RNA, Neoplasm/genetics ; RNA, Neoplasm/metabolism ; ROC Curve ; Survival Analysis ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers, Tumor ; RNA, Neoplasm
Language	English
Publishing date	2020-10-20
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2020.100101
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Article: Effects of targeting the VEGF and PDGF pathways in diffuse orthotopic glioma models

Navis, Anna C / Hamans, Bob C / Claes, An / Heerschap, Arend / Jeuken, Judith WM / Wesseling, Pieter / Leenders, William PJ

Journal of pathology. 2011 Apr., v. 223, no. 5

2011

Abstract: Currently available compounds that interfere with VEGF-A signalling effectively inhibit angiogenesis in gliomas, but influence diffuse infiltrative growth to a much lesser extent. Development of a functional tumour vascular bed not only involves VEGF-A ... ...

Abstract	Currently available compounds that interfere with VEGF-A signalling effectively inhibit angiogenesis in gliomas, but influence diffuse infiltrative growth to a much lesser extent. Development of a functional tumour vascular bed not only involves VEGF-A but also requires platelet-derived growth factor receptor-β (PDGFRβ), which induces maturation of tumour blood vessels. Therefore, we tested whether combined inhibition of VEGFR and PDGFRβ increases therapeutic benefit in the orthotopic glioma xenograft models E98 and E473, both displaying the diffuse infiltrative growth that is characteristically observed in most human gliomas. We used bevacizumab and vandetanib as VEGF(R) inhibitors, and sunitinib to additionally target PDGFRβ. We show that combination therapy of sunitinib and vandetanib does not improve therapeutic efficacy compared to treatment with sunitinib, vandetanib or bevacizumab alone. Furthermore, all compounds induced reduction of vessel leakage in compact E98 tumour areas, resulting in decreased detectability of these mostly infiltrative xenografts in Gd-DTPA-enhanced MRI scans. These data show that inhibition of VEGF signalling cannot be optimized by additional PDGFR inhibition and support the concept that diffuse infiltrative areas in gliomas are resistant to anti-angiogenic therapy. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Language	English
Dates of publication	2011-04
Size	p. 626-634.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.2836
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Targeting Cyclin-Dependent Kinases in Synovial Sarcoma: Palbociclib as a Potential Treatment for Synovial Sarcoma Patients.

Vlenterie, Myrella / Hillebrandt-Roeffen, Melissa H S / Schaars, Esther W M / Flucke, Uta E / Fleuren, Emmy D G / Navis, Anna C / Leenders, William P J / Versleijen-Jonkers, Yvonne M H / van der Graaf, Winette T A

Annals of surgical oncology

2016 Volume 23, Issue 9, Page(s) 2745–2752

Abstract: Background: In synovial sarcomas alterations in the cyclin D1-CDK4/6-Rb axis have been described. Also, β-catenin, a cyclin D1 regulator, is often overexpressed. Additionally, studies have shown that the t(X;18) translocation influences tumor behavior ... ...

Abstract	Background: In synovial sarcomas alterations in the cyclin D1-CDK4/6-Rb axis have been described. Also, β-catenin, a cyclin D1 regulator, is often overexpressed. Additionally, studies have shown that the t(X;18) translocation influences tumor behavior partly through cyclin D1 activation. We investigated how alterations in the cyclin D1-CDK4/6-Rb axis impact prognosis and studied effects of targeting this axis with the CDK4/6 inhibitor palbociclib. Methods: Synovial sarcoma samples (n = 43) were immunohistochemically stained for β-catenin, cyclin D1, p16, p21, p27, Rb, and phospho-Rb. Fluorescent in situ hybridization (FISH) was performed to detect CCND1 amplification or translocation. In 4 synovial sarcoma cell lines sensitivity to palbociclib was investigated using cell viability assays, and effects on the sensitive cell lines were evaluated on protein level and by cell cycle arrest. Results: Expression of nuclear phospho-Rb and nuclear β-catenin in the patient samples was associated with poor survival. FISH showed a sporadic translocation of CCND1 in a subset of tumors. An 8-fold CCND1 amplification was found in 1 cell line, but not in the patient samples investigated. Palbociclib effectively inhibited Rb-phosphorylation in 3 cell lines, resulting in an induction of a G1 arrest and proliferation block. Conclusions: In this series nuclear phospho-Rb and nuclear β-catenin expression were negative prognostic factors. In vitro data suggest that palbociclib may be a potential treatment for a subset of synovial sarcoma patients. Whether this effect can be enhanced by combination treatment deserves further preclinical investigations.
MeSH term(s)	Adolescent ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin D1/genetics ; Cyclin-Dependent Kinase 4/antagonists & inhibitors ; Cyclin-Dependent Kinase 6/antagonists & inhibitors ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Female ; G1 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Immunohistochemistry ; Male ; Phosphorylation/drug effects ; Piperazines/pharmacology ; Piperazines/therapeutic use ; Pyridines/pharmacology ; Pyridines/therapeutic use ; Retinoblastoma Protein/metabolism ; Sarcoma, Synovial/drug therapy ; Sarcoma, Synovial/genetics ; Sarcoma, Synovial/metabolism ; Survival Rate ; Young Adult ; beta Catenin/metabolism
Chemical Substances	Antineoplastic Agents ; CCND1 protein, human ; CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21 ; Piperazines ; Pyridines ; Retinoblastoma Protein ; beta Catenin ; Cyclin D1 (136601-57-5) ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22) ; palbociclib (G9ZF61LE7G)
Language	English
Publishing date	2016-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-016-5341-x
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Article ; Online: Selective MET Kinase Inhibition in MET-Dependent Glioma Models Alters Gene Expression and Induces Tumor Plasticity.

van den Heuvel, Corina N A M / Navis, Anna C / de Bitter, Tessa / Amiri, Houshang / Verrijp, Kiek / Heerschap, Arend / Rex, Karen / Dussault, Isabelle / Caenepeel, Sean / Coxon, Angela / Span, Paul N / Wesseling, Pieter / Hendriks, Wiljan / Leenders, William P J

Molecular cancer research : MCR

2017 Volume 15, Issue 11, Page(s) 1587–1597

Abstract: The receptor tyrosine kinase (RTK) MET represents a promising tumor target in a subset of glioblastomas. Most RTK inhibitors available in the clinic today, including those inhibiting MET, affect multiple targets simultaneously. Previously, it was ... ...

Abstract	The receptor tyrosine kinase (RTK) MET represents a promising tumor target in a subset of glioblastomas. Most RTK inhibitors available in the clinic today, including those inhibiting MET, affect multiple targets simultaneously. Previously, it was demonstrated that treatment with cabozantinib (MET/VEGFR2/RET inhibitor) prolonged survival of mice carrying orthotopic patient-derived xenografts (PDX) of the MET-addicted glioblastoma model E98, yet did not prevent development of recurrent and cabozantinib-resistant tumors. To exclude VEGFR2 inhibition-inflicted blood-brain barrier normalization and diminished tumor distribution of the drug, we have now investigated the effects of the novel MET-selective inhibitor Compound A in the orthotopic E98 xenograft model.
MeSH term(s)	Aminopyridines/administration & dosage ; Aminopyridines/pharmacology ; Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic/drug effects ; Glioma/drug therapy ; Glioma/genetics ; HT29 Cells ; Humans ; Mice ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/pharmacology ; Pyrazoles/administration & dosage ; Pyrazoles/pharmacology ; Sequence Analysis, RNA/methods ; Small Molecule Libraries/administration & dosage ; Small Molecule Libraries/pharmacology ; Xenograft Model Antitumor Assays
Chemical Substances	1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide ; Aminopyridines ; Protein Kinase Inhibitors ; Pyrazoles ; Small Molecule Libraries
Language	English
Publishing date	2017-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-17-0177
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