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  2. Matching Content Categories
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We are analyzing https://link.springer.com/article/10.1007/s13402-018-0380-x.

Title:
Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma | Cellular Oncology
Description:
Purpose Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. Methods Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. Results Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. Conclusions Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

  • Health & Fitness
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What CMS is link.springer.com built with?

Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
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The income method remains a mystery to us.

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Keywords {🔍}

pubmed, article, google, scholar, cas, cancer, thyroid, cell, anaplastic, carcinoma, central, azd, resistance, cells, mtor, mtorc, treatment, oncol, inhibitor, paclitaxel, atc, pathways, ptx, target, research, dual, kinase, vivo, clinical, access, inhibitors, privacy, cookies, content, oncology, activity, protein, therapeutic, human, effects, tumor, growth, res, rapamycin, signaling, rev, multidrug, serbia, author, belgrade,

Topics {✒️}

cancer/find-a-clinical-trial/a-trial lung resistance-related protein pi3k-akt-mtor pathway month download article/chapter pi3k/akt/mtor pathways pi3k/pten/akt pathways article  google scholar anaplastic thyroid carcinoma follicular thyroid cancers dramatic antitumor effects miodrag dragoj anaplastic thyroid cancer solid-tumours-tax-torc multidrug resistance proteins atp binding cassette anaplastic tyroid carcinoma medullary thyroid carcinoma papillary thyroid carcinoma chemo-resistant malignancy pi3k-mtor pathways pi3k/akt/mtor targeting ras-mapk-erk chemo-resistance personalized therapy overcome paclitaxel resistance growth signal integration multidrug resistance mediated full article pdf privacy choices/manage cookies phosphatidylinositol 3-kinase/akt p70 s6 kinase refractory indolent lymphoma check access instant access multiple signaling pathways related subjects targeting drug resistance natural products chemistry cancer stem cells human gastric cancer rac1 signaling pathways tubulin-binding agents reduced erk activity p-glycoprotein research nanoemulsion-loaded paclitaxel milica pešić endometrial cancer cells azd2014 versus everolimus author information authors data support results

Questions {❓}

  • Weber, Anaplastic thyroid carcinoma: Palliation or treatment?

Schema {🗺️}

WebPage:
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      headline:Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma
      description:Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate. Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies. Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth. Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
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      dateModified:2018-05-22T00:00:00Z
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         Anaplastic thyroid carcinoma
         mTOR
         AZD2014
         Paclitaxel
         Chemo-resistance
         Targeted therapy
         Cancer Research
         Biomedicine
         general
         Pathology
         Oncology
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               name:Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
               type:PostalAddress
            type:Organization
      name:Marija Stepanović
      affiliation:
            name:University of Belgrade
            address:
               name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
               type:PostalAddress
            type:Organization
      name:Nikola Tanić
      affiliation:
            name:University of Belgrade
            address:
               name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
               type:PostalAddress
            type:Organization
      name:Kostantinos Dimas
      affiliation:
            name:University of Thessaly
            address:
               name:Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
               type:PostalAddress
            type:Organization
      name:Milica Pešić
      url:http://orcid.org/0000-0002-9045-8239
      affiliation:
            name:University of Belgrade
            address:
               name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
      name:Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
      name:Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
      name:Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia
      name:Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
      name:Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
      name:Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
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