FGF Expression in HPV16-positive and -negative SCC After Treatment With Small-molecule Tyrosine Kinase Inhibitors and Everolimus.
Identifieur interne : 000121 ( Main/Exploration ); précédent : 000120; suivant : 000122FGF Expression in HPV16-positive and -negative SCC After Treatment With Small-molecule Tyrosine Kinase Inhibitors and Everolimus.
Auteurs : Lena Huber [Allemagne] ; Richard Birk [Allemagne] ; Manuel Knuettel [Allemagne] ; Nicole Rotter [Allemagne] ; Christoph Aderhold [Allemagne] ; Claudia Scherl [Allemagne] ; Anne Lammert [Allemagne] ; Frederic Jungbauer [Allemagne] ; Benedikt Kramer [Allemagne]Source :
- Anticancer research [ 1791-7530 ] ; 2020.
Descripteurs français
- KwdFr :
- Carcinome épidermoïde de la tête et du cou (anatomopathologie), Carcinome épidermoïde de la tête et du cou (génétique), Carcinome épidermoïde de la tête et du cou (traitement médicamenteux), Carcinome épidermoïde de la tête et du cou (virologie), Chlorhydrate d'erlotinib (pharmacologie), Dasatinib (pharmacologie), Facteurs de croissance fibroblastique (antagonistes et inhibiteurs), Facteurs de croissance fibroblastique (génétique), Géfitinib (pharmacologie), Humains (MeSH), Inhibiteurs de protéines kinases (pharmacologie), Lignée cellulaire tumorale (MeSH), Papillomaviridae (effets des médicaments et des substances chimiques), Papillomaviridae (pathogénicité), Papillomavirus humain de type 16 (effets des médicaments et des substances chimiques), Papillomavirus humain de type 16 (pathogénicité), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Sérine-thréonine kinases TOR (génétique), Évérolimus (pharmacologie).
- MESH :
- anatomopathologie : Carcinome épidermoïde de la tête et du cou.
- antagonistes et inhibiteurs : Facteurs de croissance fibroblastique, Sérine-thréonine kinases TOR.
- effets des médicaments et des substances chimiques : Papillomaviridae, Papillomavirus humain de type 16.
- génétique : Carcinome épidermoïde de la tête et du cou, Facteurs de croissance fibroblastique, Sérine-thréonine kinases TOR.
- pathogénicité : Papillomaviridae, Papillomavirus humain de type 16.
- pharmacologie : Chlorhydrate d'erlotinib, Dasatinib, Géfitinib, Inhibiteurs de protéines kinases, Évérolimus.
- traitement médicamenteux : Carcinome épidermoïde de la tête et du cou.
- virologie : Carcinome épidermoïde de la tête et du cou.
- Humains, Lignée cellulaire tumorale.
English descriptors
- KwdEn :
- Cell Line, Tumor (MeSH), Dasatinib (pharmacology), Erlotinib Hydrochloride (pharmacology), Everolimus (pharmacology), Fibroblast Growth Factors (antagonists & inhibitors), Fibroblast Growth Factors (genetics), Gefitinib (pharmacology), Human papillomavirus 16 (drug effects), Human papillomavirus 16 (pathogenicity), Humans (MeSH), Papillomaviridae (drug effects), Papillomaviridae (pathogenicity), Protein Kinase Inhibitors (pharmacology), Squamous Cell Carcinoma of Head and Neck (drug therapy), Squamous Cell Carcinoma of Head and Neck (genetics), Squamous Cell Carcinoma of Head and Neck (pathology), Squamous Cell Carcinoma of Head and Neck (virology), TOR Serine-Threonine Kinases (antagonists & inhibitors), TOR Serine-Threonine Kinases (genetics).
- MESH :
- chemical , antagonists & inhibitors : Fibroblast Growth Factors, TOR Serine-Threonine Kinases.
- chemical , genetics : Fibroblast Growth Factors, TOR Serine-Threonine Kinases.
- chemical , pharmacology : Dasatinib, Erlotinib Hydrochloride, Everolimus, Gefitinib, Protein Kinase Inhibitors.
- drug effects : Human papillomavirus 16, Papillomaviridae.
- drug therapy : Squamous Cell Carcinoma of Head and Neck.
- genetics : Squamous Cell Carcinoma of Head and Neck.
- pathogenicity : Human papillomavirus 16, Papillomaviridae.
- pathology : Squamous Cell Carcinoma of Head and Neck.
- virology : Squamous Cell Carcinoma of Head and Neck.
- Cell Line, Tumor, Humans.
Abstract
BACKGROUND
Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines.
MATERIALS AND METHODS
Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 μmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells.
RESULTS
FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line.
CONCLUSION
Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.
DOI: 10.21873/anticanres.14575
PubMed: 32988886
Affiliations:
- Allemagne
- Bade-Wurtemberg, District de Giessen, District de Karlsruhe, Hesse (Land)
- Mannheim, Marbourg
Links toward previous steps (curation, corpus...)
Le document en format XML
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nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Scherl, Claudia" sort="Scherl, Claudia" uniqKey="Scherl C" first="Claudia" last="Scherl">Claudia Scherl</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Lammert, Anne" sort="Lammert, Anne" uniqKey="Lammert A" first="Anne" last="Lammert">Anne Lammert</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Jungbauer, Frederic" sort="Jungbauer, Frederic" uniqKey="Jungbauer F" first="Frederic" last="Jungbauer">Frederic Jungbauer</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Kramer, Benedikt" sort="Kramer, Benedikt" uniqKey="Kramer B" first="Benedikt" last="Kramer">Benedikt Kramer</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32988886</idno><idno type="pmid">32988886</idno><idno type="doi">10.21873/anticanres.14575</idno><idno type="wicri:Area/Main/Corpus">000022</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000022</idno><idno type="wicri:Area/Main/Curation">000022</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000022</idno><idno type="wicri:Area/Main/Exploration">000022</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">FGF Expression in HPV16-positive and -negative SCC After Treatment With Small-molecule Tyrosine Kinase Inhibitors and Everolimus.</title><author><name sortKey="Huber, Lena" sort="Huber, Lena" uniqKey="Huber L" first="Lena" last="Huber">Lena Huber</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany lena.huber@umm.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Birk, Richard" sort="Birk, Richard" uniqKey="Birk R" first="Richard" last="Birk">Richard Birk</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, University of Marburg, Marburg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, University of Marburg, Marburg</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Giessen</region><settlement type="city">Marbourg</settlement></placeName></affiliation></author><author><name sortKey="Knuettel, Manuel" sort="Knuettel, Manuel" uniqKey="Knuettel M" first="Manuel" last="Knuettel">Manuel Knuettel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Rotter, Nicole" sort="Rotter, Nicole" uniqKey="Rotter N" first="Nicole" last="Rotter">Nicole Rotter</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Aderhold, Christoph" sort="Aderhold, Christoph" uniqKey="Aderhold C" first="Christoph" last="Aderhold">Christoph Aderhold</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Scherl, Claudia" sort="Scherl, Claudia" uniqKey="Scherl C" first="Claudia" last="Scherl">Claudia Scherl</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Lammert, Anne" sort="Lammert, Anne" uniqKey="Lammert A" first="Anne" last="Lammert">Anne Lammert</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Jungbauer, Frederic" sort="Jungbauer, Frederic" uniqKey="Jungbauer F" first="Frederic" last="Jungbauer">Frederic Jungbauer</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Kramer, Benedikt" sort="Kramer, Benedikt" uniqKey="Kramer B" first="Benedikt" last="Kramer">Benedikt Kramer</name><affiliation wicri:level="3"><nlm:affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author></analytic><series><title level="j">Anticancer research</title><idno type="eISSN">1791-7530</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line, Tumor (MeSH)</term><term>Dasatinib (pharmacology)</term><term>Erlotinib Hydrochloride (pharmacology)</term><term>Everolimus (pharmacology)</term><term>Fibroblast Growth Factors (antagonists & inhibitors)</term><term>Fibroblast Growth Factors (genetics)</term><term>Gefitinib (pharmacology)</term><term>Human papillomavirus 16 (drug effects)</term><term>Human papillomavirus 16 (pathogenicity)</term><term>Humans (MeSH)</term><term>Papillomaviridae (drug effects)</term><term>Papillomaviridae (pathogenicity)</term><term>Protein Kinase Inhibitors (pharmacology)</term><term>Squamous Cell Carcinoma of Head and Neck (drug therapy)</term><term>Squamous Cell Carcinoma of Head and Neck (genetics)</term><term>Squamous Cell Carcinoma of Head and Neck (pathology)</term><term>Squamous Cell Carcinoma of Head and Neck (virology)</term><term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term><term>TOR Serine-Threonine Kinases (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Carcinome épidermoïde de la tête et du cou (anatomopathologie)</term><term>Carcinome épidermoïde de la tête et du cou (génétique)</term><term>Carcinome épidermoïde de la tête et du cou (traitement médicamenteux)</term><term>Carcinome épidermoïde de la tête et du cou (virologie)</term><term>Chlorhydrate d'erlotinib (pharmacologie)</term><term>Dasatinib (pharmacologie)</term><term>Facteurs de croissance fibroblastique (antagonistes et inhibiteurs)</term><term>Facteurs de croissance fibroblastique (génétique)</term><term>Géfitinib (pharmacologie)</term><term>Humains (MeSH)</term><term>Inhibiteurs de protéines kinases (pharmacologie)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Papillomaviridae (effets des médicaments et des substances chimiques)</term><term>Papillomaviridae (pathogénicité)</term><term>Papillomavirus humain de type 16 (effets des médicaments et des substances chimiques)</term><term>Papillomavirus humain de type 16 (pathogénicité)</term><term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Évérolimus (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Fibroblast Growth Factors</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Fibroblast Growth Factors</term><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Dasatinib</term><term>Erlotinib Hydrochloride</term><term>Everolimus</term><term>Gefitinib</term><term>Protein Kinase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome épidermoïde de la tête et du cou</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Facteurs de croissance fibroblastique</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Human papillomavirus 16</term><term>Papillomaviridae</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Squamous Cell Carcinoma of Head and Neck</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Papillomaviridae</term><term>Papillomavirus humain de type 16</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Squamous Cell Carcinoma of Head and Neck</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Carcinome épidermoïde de la tête et du cou</term><term>Facteurs de croissance fibroblastique</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Human papillomavirus 16</term><term>Papillomaviridae</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Papillomaviridae</term><term>Papillomavirus humain de type 16</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Squamous Cell Carcinoma of Head and Neck</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chlorhydrate d'erlotinib</term><term>Dasatinib</term><term>Géfitinib</term><term>Inhibiteurs de protéines kinases</term><term>Évérolimus</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Carcinome épidermoïde de la tête et du cou</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Carcinome épidermoïde de la tête et du cou</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Squamous Cell Carcinoma of Head and Neck</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Lignée cellulaire tumorale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines.</p></div><div type="abstract" xml:lang="en"><p><b>MATERIALS AND METHODS</b></p><p>Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 μmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32988886</PMID><DateCompleted><Year>2020</Year><Month>10</Month><Day>07</Day></DateCompleted><DateRevised><Year>2020</Year><Month>10</Month><Day>07</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1791-7530</ISSN><JournalIssue CitedMedium="Internet"><Volume>40</Volume><Issue>10</Issue><PubDate><Year>2020</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Anticancer research</Title><ISOAbbreviation>Anticancer Res</ISOAbbreviation></Journal><ArticleTitle>FGF Expression in HPV16-positive and -negative SCC After Treatment With Small-molecule Tyrosine Kinase Inhibitors and Everolimus.</ArticleTitle><Pagination><MedlinePgn>5621-5630</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.21873/anticanres.14575</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines.</AbstractText><AbstractText Label="MATERIALS AND METHODS" NlmCategory="METHODS">Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 μmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.</AbstractText><CopyrightInformation>Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Huber</LastName><ForeName>Lena</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany lena.huber@umm.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Birk</LastName><ForeName>Richard</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, University of Marburg, Marburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Knuettel</LastName><ForeName>Manuel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rotter</LastName><ForeName>Nicole</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aderhold</LastName><ForeName>Christoph</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scherl</LastName><ForeName>Claudia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lammert</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jungbauer</LastName><ForeName>Frederic</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kramer</LastName><ForeName>Benedikt</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Greece</Country><MedlineTA>Anticancer Res</MedlineTA><NlmUniqueID>8102988</NlmUniqueID><ISSNLinking>0250-7005</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>62031-54-3</RegistryNumber><NameOfSubstance UI="D005346">Fibroblast Growth Factors</NameOfSubstance></Chemical><Chemical><RegistryNumber>9HW64Q8G6G</RegistryNumber><NameOfSubstance UI="D000068338">Everolimus</NameOfSubstance></Chemical><Chemical><RegistryNumber>DA87705X9K</RegistryNumber><NameOfSubstance UI="D000069347">Erlotinib Hydrochloride</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber><NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>RBZ1571X5H</RegistryNumber><NameOfSubstance UI="D000069439">Dasatinib</NameOfSubstance></Chemical><Chemical><RegistryNumber>S65743JHBS</RegistryNumber><NameOfSubstance UI="D000077156">Gefitinib</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000069439" MajorTopicYN="N">Dasatinib</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000069347" MajorTopicYN="N">Erlotinib Hydrochloride</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000068338" MajorTopicYN="N">Everolimus</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005346" MajorTopicYN="N">Fibroblast Growth Factors</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077156" MajorTopicYN="N">Gefitinib</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D052162" MajorTopicYN="N">Human papillomavirus 16</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D027383" MajorTopicYN="N">Papillomaviridae</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D047428" MajorTopicYN="N">Protein Kinase Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077195" MajorTopicYN="N">Squamous Cell Carcinoma of Head and Neck</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">FGF</Keyword><Keyword MajorTopicYN="N">Fibroblast growth factor</Keyword><Keyword MajorTopicYN="N">HNSCC</Keyword><Keyword MajorTopicYN="N">HPV</Keyword><Keyword MajorTopicYN="N">everolimus</Keyword><Keyword MajorTopicYN="N">head and neck squamous cell carcinoma</Keyword><Keyword MajorTopicYN="N">mTOR inhibitors</Keyword><Keyword MajorTopicYN="N">tyrosine kinase inhibitors</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>07</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>08</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>29</Day><Hour>5</Hour><Minute>31</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32988886</ArticleId><ArticleId IdType="pii">40/10/5621</ArticleId><ArticleId IdType="doi">10.21873/anticanres.14575</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li></country><region><li>Bade-Wurtemberg</li><li>District de Giessen</li><li>District de Karlsruhe</li><li>Hesse (Land)</li></region><settlement><li>Mannheim</li><li>Marbourg</li></settlement></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Huber, Lena" sort="Huber, Lena" uniqKey="Huber L" first="Lena" last="Huber">Lena Huber</name></region><name sortKey="Aderhold, Christoph" sort="Aderhold, Christoph" uniqKey="Aderhold C" first="Christoph" last="Aderhold">Christoph Aderhold</name><name sortKey="Birk, Richard" sort="Birk, Richard" uniqKey="Birk R" first="Richard" last="Birk">Richard Birk</name><name sortKey="Jungbauer, Frederic" sort="Jungbauer, Frederic" uniqKey="Jungbauer F" first="Frederic" last="Jungbauer">Frederic Jungbauer</name><name sortKey="Knuettel, Manuel" sort="Knuettel, Manuel" uniqKey="Knuettel M" first="Manuel" last="Knuettel">Manuel Knuettel</name><name sortKey="Kramer, Benedikt" sort="Kramer, Benedikt" uniqKey="Kramer B" first="Benedikt" last="Kramer">Benedikt Kramer</name><name sortKey="Lammert, Anne" sort="Lammert, Anne" uniqKey="Lammert A" first="Anne" last="Lammert">Anne Lammert</name><name sortKey="Rotter, Nicole" sort="Rotter, Nicole" uniqKey="Rotter N" first="Nicole" last="Rotter">Nicole Rotter</name><name sortKey="Scherl, Claudia" sort="Scherl, Claudia" uniqKey="Scherl C" first="Claudia" last="Scherl">Claudia Scherl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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