mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC.
Identifieur interne : 000959 ( Main/Exploration ); précédent : 000958; suivant : 000960mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC.
Auteurs : Joseph D. Coppock [États-Unis] ; Paola D. Vermeer [États-Unis] ; Daniel W. Vermeer [États-Unis] ; Kimberly M. Lee [États-Unis] ; W Keith Miskimins [États-Unis] ; William C. Spanos [États-Unis] ; John H. Lee [États-Unis]Source :
- Oncotarget [ 1949-2553 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Apoptose (effets des médicaments et des substances chimiques), Carcinome épidermoïde (secondaire), Carcinome épidermoïde (traitement médicamenteux), Carcinome épidermoïde (virologie), Cellules cancéreuses en culture (MeSH), Cisplatine (administration et posologie), Humains (MeSH), Infections à papillomavirus (anatomopathologie), Infections à papillomavirus (traitement médicamenteux), Infections à papillomavirus (virologie), Invasion tumorale (MeSH), Marqueurs biologiques tumoraux (métabolisme), Mâle (MeSH), Métastase lymphatique (MeSH), Papillomaviridae (pathogénicité), Prolifération cellulaire (effets des médicaments et des substances chimiques), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Récidive tumorale locale (anatomopathologie), Récidive tumorale locale (traitement médicamenteux), Récidive tumorale locale (virologie), Sirolimus (administration et posologie), Souris (MeSH), Souris de lignée C57BL (MeSH), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Tests d'activité antitumorale sur modèle de xénogreffe (MeSH), Traitement médicamenteux adjuvant (MeSH), Tumeurs de la tête et du cou (anatomopathologie), Tumeurs de la tête et du cou (traitement médicamenteux), Tumeurs de la tête et du cou (virologie).
- MESH :
- administration et posologie : Cisplatine, Sirolimus.
- anatomopathologie : Infections à papillomavirus, Récidive tumorale locale, Tumeurs de la tête et du cou.
- antagonistes et inhibiteurs : Sérine-thréonine kinases TOR.
- effets des médicaments et des substances chimiques : Apoptose, Prolifération cellulaire.
- métabolisme : Marqueurs biologiques tumoraux.
- pathogénicité : Papillomaviridae.
- secondaire : Carcinome épidermoïde.
- traitement médicamenteux : Carcinome épidermoïde, Infections à papillomavirus, Récidive tumorale locale, Tumeurs de la tête et du cou.
- usage thérapeutique : Protocoles de polychimiothérapie antinéoplasique.
- virologie : Carcinome épidermoïde, Infections à papillomavirus, Récidive tumorale locale, Tumeurs de la tête et du cou.
- Animaux, Cellules cancéreuses en culture, Humains, Invasion tumorale, Mâle, Métastase lymphatique, Souris, Souris de lignée C57BL, Tests d'activité antitumorale sur modèle de xénogreffe, Traitement médicamenteux adjuvant.
English descriptors
- KwdEn :
- Animals (MeSH), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), Apoptosis (drug effects), Biomarkers, Tumor (metabolism), Carcinoma, Squamous Cell (drug therapy), Carcinoma, Squamous Cell (secondary), Carcinoma, Squamous Cell (virology), Cell Proliferation (drug effects), Chemotherapy, Adjuvant (MeSH), Cisplatin (administration & dosage), Head and Neck Neoplasms (drug therapy), Head and Neck Neoplasms (pathology), Head and Neck Neoplasms (virology), Humans (MeSH), Lymphatic Metastasis (MeSH), Male (MeSH), Mice (MeSH), Mice, Inbred C57BL (MeSH), Neoplasm Invasiveness (MeSH), Neoplasm Recurrence, Local (drug therapy), Neoplasm Recurrence, Local (pathology), Neoplasm Recurrence, Local (virology), Papillomaviridae (pathogenicity), Papillomavirus Infections (drug therapy), Papillomavirus Infections (pathology), Papillomavirus Infections (virology), Sirolimus (administration & dosage), TOR Serine-Threonine Kinases (antagonists & inhibitors), Tumor Cells, Cultured (MeSH), Xenograft Model Antitumor Assays (MeSH).
- MESH :
- chemical , administration & dosage : Cisplatin, Sirolimus.
- chemical , antagonists & inhibitors : TOR Serine-Threonine Kinases.
- chemical , metabolism : Biomarkers, Tumor.
- drug effects : Apoptosis, Cell Proliferation.
- drug therapy : Carcinoma, Squamous Cell, Head and Neck Neoplasms, Neoplasm Recurrence, Local, Papillomavirus Infections.
- pathogenicity : Papillomaviridae.
- pathology : Head and Neck Neoplasms, Neoplasm Recurrence, Local, Papillomavirus Infections.
- secondary : Carcinoma, Squamous Cell.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- virology : Carcinoma, Squamous Cell, Head and Neck Neoplasms, Neoplasm Recurrence, Local, Papillomavirus Infections.
- Animals, Chemotherapy, Adjuvant, Humans, Lymphatic Metastasis, Male, Mice, Mice, Inbred C57BL, Neoplasm Invasiveness, Tumor Cells, Cultured, Xenograft Model Antitumor Assays.
Abstract
Effective treatments for recurrent/metastatic human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) are limited. To aid treatment development, we characterized a novel murine model of recurrent/metastatic HPV+ HNSCC. Further analysis of the parental tumor cell line and its four recurrent/metastatic derivatives led to preclinical testing of an effective treatment option for this otherwise fatal disease. Reverse phase protein arrays identified key signaling cascades in the parental and recurrent/metastatic cell lines. While protein expression profiles differed among the recurrent/metastatic cell lines, activated proteins associated with the mTOR signaling cascade were a commonality. Based on these data, mTOR inhibition was evaluated as an adjuvant treatment for recurrent/metastatic disease. mTOR activity and treatment response were assessed in vitro by western blot, Seahorse, proliferation, clonogenic, and migration assays. Standard-of-care cisplatin/radiation therapy (CRT) versus CRT/rapamycin were compared in vivo. Low-dose rapamycin inhibited mTOR signaling, decreasing proliferation (43%) and migration (62%) while it enhanced CRT-induced cytotoxicity (3.3 fold) in clonogenic assays. Furthermore, rapamycin re-sensitized CRT-resistant, metastatic tumors to treatment in vivo, improving long-term cures (0-30% improved to 78-100%, depending on the recurrent/metastatic cell line) and limiting lymph node metastasis (32%) and lung metastatic burden (30 fold). Studies using immune compromised mice suggested rapamycin's effect on metastasis is independent of the adaptive immune response. These data suggest a role of mTOR activation in HPV+ HNSCC recurrent/metastatic disease and that adjuvant mTOR inhibition may enhance treatment of resistant, metastatic cell populations at the primary site and limit distant metastasis.
DOI: 10.18632/oncotarget.8286
PubMed: 27015118
PubMed Central: PMC5029697
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term>
<term>Apoptosis (drug effects)</term>
<term>Biomarkers, Tumor (metabolism)</term>
<term>Carcinoma, Squamous Cell (drug therapy)</term>
<term>Carcinoma, Squamous Cell (secondary)</term>
<term>Carcinoma, Squamous Cell (virology)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Chemotherapy, Adjuvant (MeSH)</term>
<term>Cisplatin (administration & dosage)</term>
<term>Head and Neck Neoplasms (drug therapy)</term>
<term>Head and Neck Neoplasms (pathology)</term>
<term>Head and Neck Neoplasms (virology)</term>
<term>Humans (MeSH)</term>
<term>Lymphatic Metastasis (MeSH)</term>
<term>Male (MeSH)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred C57BL (MeSH)</term>
<term>Neoplasm Invasiveness (MeSH)</term>
<term>Neoplasm Recurrence, Local (drug therapy)</term>
<term>Neoplasm Recurrence, Local (pathology)</term>
<term>Neoplasm Recurrence, Local (virology)</term>
<term>Papillomaviridae (pathogenicity)</term>
<term>Papillomavirus Infections (drug therapy)</term>
<term>Papillomavirus Infections (pathology)</term>
<term>Papillomavirus Infections (virology)</term>
<term>Sirolimus (administration & dosage)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
<term>Tumor Cells, Cultured (MeSH)</term>
<term>Xenograft Model Antitumor Assays (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Carcinome épidermoïde (secondaire)</term>
<term>Carcinome épidermoïde (traitement médicamenteux)</term>
<term>Carcinome épidermoïde (virologie)</term>
<term>Cellules cancéreuses en culture (MeSH)</term>
<term>Cisplatine (administration et posologie)</term>
<term>Humains (MeSH)</term>
<term>Infections à papillomavirus (anatomopathologie)</term>
<term>Infections à papillomavirus (traitement médicamenteux)</term>
<term>Infections à papillomavirus (virologie)</term>
<term>Invasion tumorale (MeSH)</term>
<term>Marqueurs biologiques tumoraux (métabolisme)</term>
<term>Mâle (MeSH)</term>
<term>Métastase lymphatique (MeSH)</term>
<term>Papillomaviridae (pathogénicité)</term>
<term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique)</term>
<term>Récidive tumorale locale (anatomopathologie)</term>
<term>Récidive tumorale locale (traitement médicamenteux)</term>
<term>Récidive tumorale locale (virologie)</term>
<term>Sirolimus (administration et posologie)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée C57BL (MeSH)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe (MeSH)</term>
<term>Traitement médicamenteux adjuvant (MeSH)</term>
<term>Tumeurs de la tête et du cou (anatomopathologie)</term>
<term>Tumeurs de la tête et du cou (traitement médicamenteux)</term>
<term>Tumeurs de la tête et du cou (virologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Cisplatin</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Biomarkers, Tumor</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Cisplatine</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à papillomavirus</term>
<term>Récidive tumorale locale</term>
<term>Tumeurs de la tête et du cou</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term>
<term>Cell Proliferation</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
<term>Neoplasm Recurrence, Local</term>
<term>Papillomavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term>
<term>Prolifération cellulaire</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Marqueurs biologiques tumoraux</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Papillomaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Papillomaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Head and Neck Neoplasms</term>
<term>Neoplasm Recurrence, Local</term>
<term>Papillomavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Carcinome épidermoïde</term>
</keywords>
<keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Carcinoma, Squamous Cell</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>Carcinome épidermoïde</term>
<term>Infections à papillomavirus</term>
<term>Récidive tumorale locale</term>
<term>Tumeurs de la tête et du cou</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Protocoles de polychimiothérapie antinéoplasique</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Carcinome épidermoïde</term>
<term>Infections à papillomavirus</term>
<term>Récidive tumorale locale</term>
<term>Tumeurs de la tête et du cou</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
<term>Neoplasm Recurrence, Local</term>
<term>Papillomavirus Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Chemotherapy, Adjuvant</term>
<term>Humans</term>
<term>Lymphatic Metastasis</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Neoplasm Invasiveness</term>
<term>Tumor Cells, Cultured</term>
<term>Xenograft Model Antitumor Assays</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules cancéreuses en culture</term>
<term>Humains</term>
<term>Invasion tumorale</term>
<term>Mâle</term>
<term>Métastase lymphatique</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Tests d'activité antitumorale sur modèle de xénogreffe</term>
<term>Traitement médicamenteux adjuvant</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Effective treatments for recurrent/metastatic human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) are limited. To aid treatment development, we characterized a novel murine model of recurrent/metastatic HPV+ HNSCC. Further analysis of the parental tumor cell line and its four recurrent/metastatic derivatives led to preclinical testing of an effective treatment option for this otherwise fatal disease. Reverse phase protein arrays identified key signaling cascades in the parental and recurrent/metastatic cell lines. While protein expression profiles differed among the recurrent/metastatic cell lines, activated proteins associated with the mTOR signaling cascade were a commonality. Based on these data, mTOR inhibition was evaluated as an adjuvant treatment for recurrent/metastatic disease. mTOR activity and treatment response were assessed in vitro by western blot, Seahorse, proliferation, clonogenic, and migration assays. Standard-of-care cisplatin/radiation therapy (CRT) versus CRT/rapamycin were compared in vivo. Low-dose rapamycin inhibited mTOR signaling, decreasing proliferation (43%) and migration (62%) while it enhanced CRT-induced cytotoxicity (3.3 fold) in clonogenic assays. Furthermore, rapamycin re-sensitized CRT-resistant, metastatic tumors to treatment in vivo, improving long-term cures (0-30% improved to 78-100%, depending on the recurrent/metastatic cell line) and limiting lymph node metastasis (32%) and lung metastatic burden (30 fold). Studies using immune compromised mice suggested rapamycin's effect on metastasis is independent of the adaptive immune response. These data suggest a role of mTOR activation in HPV+ HNSCC recurrent/metastatic disease and that adjuvant mTOR inhibition may enhance treatment of resistant, metastatic cell populations at the primary site and limit distant metastasis. </div>
</front>
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<DateCompleted><Year>2018</Year>
<Month>01</Month>
<Day>17</Day>
</DateCompleted>
<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1949-2553</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>7</Volume>
<Issue>17</Issue>
<PubDate><Year>2016</Year>
<Month>Apr</Month>
<Day>26</Day>
</PubDate>
</JournalIssue>
<Title>Oncotarget</Title>
<ISOAbbreviation>Oncotarget</ISOAbbreviation>
</Journal>
<ArticleTitle>mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC.</ArticleTitle>
<Pagination><MedlinePgn>24228-41</MedlinePgn>
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<ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.8286</ELocationID>
<Abstract><AbstractText>Effective treatments for recurrent/metastatic human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) are limited. To aid treatment development, we characterized a novel murine model of recurrent/metastatic HPV+ HNSCC. Further analysis of the parental tumor cell line and its four recurrent/metastatic derivatives led to preclinical testing of an effective treatment option for this otherwise fatal disease. Reverse phase protein arrays identified key signaling cascades in the parental and recurrent/metastatic cell lines. While protein expression profiles differed among the recurrent/metastatic cell lines, activated proteins associated with the mTOR signaling cascade were a commonality. Based on these data, mTOR inhibition was evaluated as an adjuvant treatment for recurrent/metastatic disease. mTOR activity and treatment response were assessed in vitro by western blot, Seahorse, proliferation, clonogenic, and migration assays. Standard-of-care cisplatin/radiation therapy (CRT) versus CRT/rapamycin were compared in vivo. Low-dose rapamycin inhibited mTOR signaling, decreasing proliferation (43%) and migration (62%) while it enhanced CRT-induced cytotoxicity (3.3 fold) in clonogenic assays. Furthermore, rapamycin re-sensitized CRT-resistant, metastatic tumors to treatment in vivo, improving long-term cures (0-30% improved to 78-100%, depending on the recurrent/metastatic cell line) and limiting lymph node metastasis (32%) and lung metastatic burden (30 fold). Studies using immune compromised mice suggested rapamycin's effect on metastasis is independent of the adaptive immune response. These data suggest a role of mTOR activation in HPV+ HNSCC recurrent/metastatic disease and that adjuvant mTOR inhibition may enhance treatment of resistant, metastatic cell populations at the primary site and limit distant metastasis. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Coppock</LastName>
<ForeName>Joseph D</ForeName>
<Initials>JD</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Vermeer</LastName>
<ForeName>Paola D</ForeName>
<Initials>PD</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Vermeer</LastName>
<ForeName>Daniel W</ForeName>
<Initials>DW</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lee</LastName>
<ForeName>Kimberly M</ForeName>
<Initials>KM</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>W Keith</ForeName>
<Initials>WK</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Spanos</LastName>
<ForeName>William C</ForeName>
<Initials>WC</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Head and Neck Surgery, Sanford Health, Sioux Falls, SD 57105, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>John H</ForeName>
<Initials>JH</Initials>
<AffiliationInfo><Affiliation>Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, SD 57104, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Otolaryngology/Head and Neck Surgery, Sanford Health, Sioux Falls, SD 57105, USA.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>K08 CA149078</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P20 RR024219</GrantID>
<Acronym>RR</Acronym>
<Agency>NCRR NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 CA193522</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DE018386</GrantID>
<Acronym>DE</Acronym>
<Agency>NIDCR NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P20 GM103548</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 CA180033</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
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<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Oncotarget</MedlineTA>
<NlmUniqueID>101532965</NlmUniqueID>
<ISSNLinking>1949-2553</ISSNLinking>
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<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002294" MajorTopicYN="N">Carcinoma, Squamous Cell</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000556" MajorTopicYN="N">secondary</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017024" MajorTopicYN="N">Chemotherapy, Adjuvant</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002945" MajorTopicYN="N">Cisplatin</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006258" MajorTopicYN="N">Head and Neck Neoplasms</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008207" MajorTopicYN="N">Lymphatic Metastasis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009361" MajorTopicYN="N">Neoplasm Invasiveness</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009364" MajorTopicYN="N">Neoplasm Recurrence, Local</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D027383" MajorTopicYN="N">Papillomaviridae</DescriptorName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D030361" MajorTopicYN="N">Papillomavirus Infections</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName>
</MeshHeading>
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<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">head and neck oral cancer</Keyword>
<Keyword MajorTopicYN="N">human papillomavirus</Keyword>
<Keyword MajorTopicYN="N">mTOR</Keyword>
<Keyword MajorTopicYN="N">metastasis</Keyword>
<Keyword MajorTopicYN="N">rapamycin</Keyword>
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<CoiStatement>The authors report no financial or other conflicts of interest relevant to the subject of this article.</CoiStatement>
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</ArticleIdList>
<ReferenceList><Reference><Citation>Mol Cancer Ther. 2009 Aug;8(8):2255-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19625495</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Feb;129(1):26-31</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21944953</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Crit Rev Eukaryot Gene Expr. 2010;20(1):1-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20528734</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Res. 2007 Mar 1;67(5):2160-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17332346</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Neoplasia. 2013 Dec;15(12):1371-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24403859</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Otolaryngol Clin North Am. 2012 Aug;45(4):779-93</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22793852</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Oncol. 2012;2012:450179</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22666248</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Cancer. 2011 Jan;11(1):9-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21160525</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Curr Treat Options Oncol. 2012 Mar;13(1):71-81</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22282394</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Neurooncol. 2013 May;112(3):449-54</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23408186</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Discov. 2013 Jul;3(7):722-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23847349</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Head Neck. 2010 Apr;32(4):417-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19760794</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Arch Otolaryngol Head Neck Surg. 2009 Nov;135(11):1137-46</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19917928</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Mol Med (Berl). 2013 Apr;91(4):411-29</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23515621</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Cancer Res. 2012 May 1;18(9):2558-68</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22409888</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>JAMA. 2012 Feb 15;307(7):693-703</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22282321</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncogene. 2009 Nov 12;28(45):3960-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19734941</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Head Neck Oncol. 2011 Apr 24;3:22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21513566</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Arch Otolaryngol Head Neck Surg. 2007 May;133(5):495-502</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17515506</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ISRN Otolaryngol. 2012 Oct 18;2012:953089</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23762622</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Oncol. 2011;2011:509036</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21234307</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Prev Res (Phila). 2009 Jan;2(1):27-36</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19139015</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2012 Apr 13;149(2):274-93</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22500797</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Res. 2011 Nov 15;71(22):7103-12</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21975930</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Cancer Res. 2007 Sep 1;13(17):4964-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17785546</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Neoplasia. 2013 Jun;15(6):620-30</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23730210</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Expert Opin Ther Targets. 2011 Jan;15(1):63-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21110697</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):409-14</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24367102</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Am J Med Sci. 1986 Jun;291(6):405-15</Citation>
<ArticleIdList><ArticleId IdType="pubmed">3521275</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Cancer. 2010 Apr;10(4):267-77</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20300106</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
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