mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma
Background: Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models. Methods: Human and murine HCC cells, endothelial c...
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| Veröffentlicht in: | British journal of cancer 2015-03, Vol.112 (5), p.841-850 |
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| creator | Scheller, T Hellerbrand, C Moser, C Schmidt, K Kroemer, A Brunner, S M Schlitt, H J Geissler, E K Lang, S A |
| description | Background:
Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models.
Methods:
Human and murine HCC cells, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), hepatic stellate cells (HSCs), human HCC samples, FGFR inhibitor BGJ398 and mammalian target of rapamycin (mTOR) inhibitor rapamycin were used. Effects on growth, motility, signalling and angiogenic markers were determined.
In vivo
subcutaneous and syngeneic orthotopic tumour models were used.
Results:
In tumour cells and ECs, targeting FGFR showed significant inhibitory effects on signalling and motility. Minor effects of FGFR inhibition were observed on VSMCs and HSCs, which were significantly enhanced by combining FGFR and mTOR blockade.
In vivo
daily (5 mg kg
−1
) treatment with BGJ398 led to a significant growth inhibition in subcutaneous tumour models, but only a combination of FGFR and mTOR blockade impaired tumour growth in the orthotopic model. This was paralleled by reduced tumour cell proliferation, vascularisation, pericytes and increased apoptosis.
Conclusions:
Targeting FGFR with BGJ398 affects tumour cells and ECs, whereas only a combination with mTOR inhibition impairs recruitment of VSMCs and HSCs. Therefore, this study provides evidence for combined FGFR/mTOR inhibition in HCC. |
| doi_str_mv | 10.1038/bjc.2014.638 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4453944</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3613102901</sourcerecordid><originalsourceid>FETCH-LOGICAL-c520t-fd9699a5954fde31b84f92e4720e5548e052427962e6ccfaed51cf800a9b343</originalsourceid><addsrcrecordid>eNptkd9LHDEQx0Ox6Kl963NZ8NU983M3eRFE1BYEofqeZnOTvRy7m22Ss_S_b45TseDTzDCf-c4wX4S-ErwkmMmLbmOXFBO-bJj8hBZEMFoTSdsDtMAYtzVWFB-h45Q2pVRYtofoiIpGypazBfo1Pj38rPy09p3PPkyVH-cYniFVzncxdINJuepj-JPXlTM2h1hFsDDvkmxiD9lPfZmv1jCbHCwMw3YwsbImWj-F0Zyiz84MCb68xBP0eHvzdP29vn-4-3F9dV9bQXGu3Uo1ShmhBHcrYKST3CkKvKUYhOASsKCctqqh0FjrDKwEsU5ibFTHODtBl3vVeduNsLIw5WgGPUc_mvhXB-P1_53Jr3UfnjXngim-Ezh7EYjh9xZS1puwjVO5WJOmwayVhOJCne8pG0NKEdzbBoL1zg1d3NA7N3Rxo-Df3l_1Br--vwD1HkilNfUQ3239SPAfdw6XPQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1660378120</pqid></control><display><type>article</type><title>mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma</title><source>MEDLINE</source><source>Nature</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><source>SpringerLink Journals - AutoHoldings</source><creator>Scheller, T ; Hellerbrand, C ; Moser, C ; Schmidt, K ; Kroemer, A ; Brunner, S M ; Schlitt, H J ; Geissler, E K ; Lang, S A</creator><creatorcontrib>Scheller, T ; Hellerbrand, C ; Moser, C ; Schmidt, K ; Kroemer, A ; Brunner, S M ; Schlitt, H J ; Geissler, E K ; Lang, S A</creatorcontrib><description>Background:
Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models.
Methods:
Human and murine HCC cells, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), hepatic stellate cells (HSCs), human HCC samples, FGFR inhibitor BGJ398 and mammalian target of rapamycin (mTOR) inhibitor rapamycin were used. Effects on growth, motility, signalling and angiogenic markers were determined.
In vivo
subcutaneous and syngeneic orthotopic tumour models were used.
Results:
In tumour cells and ECs, targeting FGFR showed significant inhibitory effects on signalling and motility. Minor effects of FGFR inhibition were observed on VSMCs and HSCs, which were significantly enhanced by combining FGFR and mTOR blockade.
In vivo
daily (5 mg kg
−1
) treatment with BGJ398 led to a significant growth inhibition in subcutaneous tumour models, but only a combination of FGFR and mTOR blockade impaired tumour growth in the orthotopic model. This was paralleled by reduced tumour cell proliferation, vascularisation, pericytes and increased apoptosis.
Conclusions:
Targeting FGFR with BGJ398 affects tumour cells and ECs, whereas only a combination with mTOR inhibition impairs recruitment of VSMCs and HSCs. Therefore, this study provides evidence for combined FGFR/mTOR inhibition in HCC.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2014.638</identifier><identifier>PMID: 25688743</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/80/86/2368 ; 692/699/1503/1504/1610/4029 ; 692/699/67/1059/602 ; Angiogenesis ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - pathology ; Cell culture ; Cell growth ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Drug Resistance ; Drug Synergism ; Epidemiology ; Fibroblasts ; Gene Expression Regulation, Neoplastic - drug effects ; Hep G2 Cells ; Hospitals ; Humans ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Medical prognosis ; Mice ; Mice, Nude ; Molecular Medicine ; Motility ; Neoplasm Transplantation ; Oncology ; Phenylurea Compounds - administration & dosage ; Phenylurea Compounds - pharmacology ; Pyrimidines - administration & dosage ; Pyrimidines - pharmacology ; Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors ; Signal Transduction - drug effects ; Sirolimus - administration & dosage ; Sirolimus - pharmacology ; Surgery ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; Translational Therapeutics ; Vascular endothelial growth factor ; Xenograft Model Antitumor Assays</subject><ispartof>British journal of cancer, 2015-03, Vol.112 (5), p.841-850</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Mar 3, 2015</rights><rights>Copyright © 2015 Cancer Research UK 2015 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-fd9699a5954fde31b84f92e4720e5548e052427962e6ccfaed51cf800a9b343</citedby><cites>FETCH-LOGICAL-c520t-fd9699a5954fde31b84f92e4720e5548e052427962e6ccfaed51cf800a9b343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453944/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453944/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25688743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scheller, T</creatorcontrib><creatorcontrib>Hellerbrand, C</creatorcontrib><creatorcontrib>Moser, C</creatorcontrib><creatorcontrib>Schmidt, K</creatorcontrib><creatorcontrib>Kroemer, A</creatorcontrib><creatorcontrib>Brunner, S M</creatorcontrib><creatorcontrib>Schlitt, H J</creatorcontrib><creatorcontrib>Geissler, E K</creatorcontrib><creatorcontrib>Lang, S A</creatorcontrib><title>mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models.
Methods:
Human and murine HCC cells, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), hepatic stellate cells (HSCs), human HCC samples, FGFR inhibitor BGJ398 and mammalian target of rapamycin (mTOR) inhibitor rapamycin were used. Effects on growth, motility, signalling and angiogenic markers were determined.
In vivo
subcutaneous and syngeneic orthotopic tumour models were used.
Results:
In tumour cells and ECs, targeting FGFR showed significant inhibitory effects on signalling and motility. Minor effects of FGFR inhibition were observed on VSMCs and HSCs, which were significantly enhanced by combining FGFR and mTOR blockade.
In vivo
daily (5 mg kg
−1
) treatment with BGJ398 led to a significant growth inhibition in subcutaneous tumour models, but only a combination of FGFR and mTOR blockade impaired tumour growth in the orthotopic model. This was paralleled by reduced tumour cell proliferation, vascularisation, pericytes and increased apoptosis.
Conclusions:
Targeting FGFR with BGJ398 affects tumour cells and ECs, whereas only a combination with mTOR inhibition impairs recruitment of VSMCs and HSCs. Therefore, this study provides evidence for combined FGFR/mTOR inhibition in HCC.</description><subject>631/80/86/2368</subject><subject>692/699/1503/1504/1610/4029</subject><subject>692/699/67/1059/602</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Drug Resistance</subject><subject>Drug Synergism</subject><subject>Epidemiology</subject><subject>Fibroblasts</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Hep G2 Cells</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - pathology</subject><subject>Medical prognosis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Molecular Medicine</subject><subject>Motility</subject><subject>Neoplasm Transplantation</subject><subject>Oncology</subject><subject>Phenylurea Compounds - administration & dosage</subject><subject>Phenylurea Compounds - pharmacology</subject><subject>Pyrimidines - administration & dosage</subject><subject>Pyrimidines - pharmacology</subject><subject>Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors</subject><subject>Signal Transduction - drug effects</subject><subject>Sirolimus - administration & dosage</subject><subject>Sirolimus - pharmacology</subject><subject>Surgery</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Translational Therapeutics</subject><subject>Vascular endothelial growth factor</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkd9LHDEQx0Ox6Kl963NZ8NU983M3eRFE1BYEofqeZnOTvRy7m22Ss_S_b45TseDTzDCf-c4wX4S-ErwkmMmLbmOXFBO-bJj8hBZEMFoTSdsDtMAYtzVWFB-h45Q2pVRYtofoiIpGypazBfo1Pj38rPy09p3PPkyVH-cYniFVzncxdINJuepj-JPXlTM2h1hFsDDvkmxiD9lPfZmv1jCbHCwMw3YwsbImWj-F0Zyiz84MCb68xBP0eHvzdP29vn-4-3F9dV9bQXGu3Uo1ShmhBHcrYKST3CkKvKUYhOASsKCctqqh0FjrDKwEsU5ibFTHODtBl3vVeduNsLIw5WgGPUc_mvhXB-P1_53Jr3UfnjXngim-Ezh7EYjh9xZS1puwjVO5WJOmwayVhOJCne8pG0NKEdzbBoL1zg1d3NA7N3Rxo-Df3l_1Br--vwD1HkilNfUQ3239SPAfdw6XPQ</recordid><startdate>20150303</startdate><enddate>20150303</enddate><creator>Scheller, T</creator><creator>Hellerbrand, C</creator><creator>Moser, C</creator><creator>Schmidt, K</creator><creator>Kroemer, A</creator><creator>Brunner, S M</creator><creator>Schlitt, H J</creator><creator>Geissler, E K</creator><creator>Lang, S A</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20150303</creationdate><title>mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma</title><author>Scheller, T ; Hellerbrand, C ; Moser, C ; Schmidt, K ; Kroemer, A ; Brunner, S M ; Schlitt, H J ; Geissler, E K ; Lang, S A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-fd9699a5954fde31b84f92e4720e5548e052427962e6ccfaed51cf800a9b343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/80/86/2368</topic><topic>692/699/1503/1504/1610/4029</topic><topic>692/699/67/1059/602</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Drug Resistance</topic><topic>Drug Synergism</topic><topic>Epidemiology</topic><topic>Fibroblasts</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Hep G2 Cells</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - pathology</topic><topic>Medical prognosis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Molecular Medicine</topic><topic>Motility</topic><topic>Neoplasm Transplantation</topic><topic>Oncology</topic><topic>Phenylurea Compounds - administration & dosage</topic><topic>Phenylurea Compounds - pharmacology</topic><topic>Pyrimidines - administration & dosage</topic><topic>Pyrimidines - pharmacology</topic><topic>Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors</topic><topic>Signal Transduction - drug effects</topic><topic>Sirolimus - administration & dosage</topic><topic>Sirolimus - pharmacology</topic><topic>Surgery</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Translational Therapeutics</topic><topic>Vascular endothelial growth factor</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scheller, T</creatorcontrib><creatorcontrib>Hellerbrand, C</creatorcontrib><creatorcontrib>Moser, C</creatorcontrib><creatorcontrib>Schmidt, K</creatorcontrib><creatorcontrib>Kroemer, A</creatorcontrib><creatorcontrib>Brunner, S M</creatorcontrib><creatorcontrib>Schlitt, H J</creatorcontrib><creatorcontrib>Geissler, E K</creatorcontrib><creatorcontrib>Lang, S A</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scheller, T</au><au>Hellerbrand, C</au><au>Moser, C</au><au>Schmidt, K</au><au>Kroemer, A</au><au>Brunner, S M</au><au>Schlitt, H J</au><au>Geissler, E K</au><au>Lang, S A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2015-03-03</date><risdate>2015</risdate><volume>112</volume><issue>5</issue><spage>841</spage><epage>850</epage><pages>841-850</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models.
Methods:
Human and murine HCC cells, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), hepatic stellate cells (HSCs), human HCC samples, FGFR inhibitor BGJ398 and mammalian target of rapamycin (mTOR) inhibitor rapamycin were used. Effects on growth, motility, signalling and angiogenic markers were determined.
In vivo
subcutaneous and syngeneic orthotopic tumour models were used.
Results:
In tumour cells and ECs, targeting FGFR showed significant inhibitory effects on signalling and motility. Minor effects of FGFR inhibition were observed on VSMCs and HSCs, which were significantly enhanced by combining FGFR and mTOR blockade.
In vivo
daily (5 mg kg
−1
) treatment with BGJ398 led to a significant growth inhibition in subcutaneous tumour models, but only a combination of FGFR and mTOR blockade impaired tumour growth in the orthotopic model. This was paralleled by reduced tumour cell proliferation, vascularisation, pericytes and increased apoptosis.
Conclusions:
Targeting FGFR with BGJ398 affects tumour cells and ECs, whereas only a combination with mTOR inhibition impairs recruitment of VSMCs and HSCs. Therefore, this study provides evidence for combined FGFR/mTOR inhibition in HCC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25688743</pmid><doi>10.1038/bjc.2014.638</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; Nature; PubMed Central; EZB Electronic Journals Library; SpringerLink Journals - AutoHoldings |
| subjects | 631/80/86/2368 692/699/1503/1504/1610/4029 692/699/67/1059/602 Angiogenesis Animals Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - pathology Cell culture Cell growth Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Drug Resistance Drug Synergism Epidemiology Fibroblasts Gene Expression Regulation, Neoplastic - drug effects Hep G2 Cells Hospitals Humans Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - pathology Medical prognosis Mice Mice, Nude Molecular Medicine Motility Neoplasm Transplantation Oncology Phenylurea Compounds - administration & dosage Phenylurea Compounds - pharmacology Pyrimidines - administration & dosage Pyrimidines - pharmacology Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors Signal Transduction - drug effects Sirolimus - administration & dosage Sirolimus - pharmacology Surgery TOR Serine-Threonine Kinases - antagonists & inhibitors Translational Therapeutics Vascular endothelial growth factor Xenograft Model Antitumor Assays |
| title | mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T15%3A51%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=mTOR%20inhibition%20improves%20fibroblast%20growth%20factor%20receptor%20targeting%20in%20hepatocellular%20carcinoma&rft.jtitle=British%20journal%20of%20cancer&rft.au=Scheller,%20T&rft.date=2015-03-03&rft.volume=112&rft.issue=5&rft.spage=841&rft.epage=850&rft.pages=841-850&rft.issn=0007-0920&rft.eissn=1532-1827&rft.coden=BJCAAI&rft_id=info:doi/10.1038/bjc.2014.638&rft_dat=%3Cproquest_pubme%3E3613102901%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1660378120&rft_id=info:pmid/25688743&rfr_iscdi=true |