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breast-cancer-derived xenografts triple-negative breast cancer triple-negative breast cancers patient-derived tumor xenografts patient-derived xenograft models month download article/chapter patient-derived xenografts seongmun jeong patient-derived xenograft eun-jung jung ju-yeon kim translational cancer research breast cancer biology her2-targeted agents influence triple negative paradox breast cancer outcome han suk ryu dong-young noh chemotherapy-resistant tumors compared adaptive immune cells myung won seo & dong cancer research institute pdx engraftment-related genes breast cancer subtypes tumor grafts derived breast cancer metastasis engraftment gene signature korea research institute full article pdf triple negative national research foundation related subjects engraftment-related genes privacy choices/manage cookies clin cancer res article moon landis md breast cancer bmc cancer 14 successful tumor engraftment primary tumor chemosensitivity myung won seo check access instant access gyeongsang national university sunchon national university lehmann bd tumor–immune interaction ae kyung park worse survival outcome

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         headline:Prognostic and functional importance of the engraftment-associated genes in the patient-derived xenograft models of triple-negative breast cancers
         description: We aimed to identify the factors affecting the successful tumor engraftment in breast cancer patient-derived xenograft (PDX) models. Further, we investigated the prognostic significance and the functional importance of the PDX engraftment-related genes in triple-negative breast cancers (TNBC). The clinico-pathologic features of 81 breast cancer patients whose tissues were used for PDX transplantation were analyzed to identify the factors affecting the PDX engraftment. A gene signature associated with the PDX engraftment was discovered and its clinical importance was tested in a publicly available dataset and in vitro assays. Nineteen out of 81 (23.4 %) transplanted tumors were successfully engrafted into the PDX models. The engraftment rate was highest in TNBC when compared to other subtypes (p = 0.001) and in recurrent or chemotherapy-resistant tumors compared to newly diagnosed primary tumors (p = 0.024). PDX tumors originated from the TNBC cases showed more rapid tumor growth in mice. Gene expression profiling showed that down-regulation of genes involved in the tumor–immune interaction was significantly associated with the successful PDX engraftment. The engraftment gene signature was associated with worse survival outcome when tested in publicly available mRNA datasets of TNBC cases. Among the engraftment-related genes, PHLDA2, TKT, and P4HA2 showed high expression in triple-negative breast cancer cell lines, and siRNA-based gene silencing resulted in reduced cell invasion and proliferation in vitro. Our results show that the PDX engraftment may reflect the aggressive phenotype in breast cancer. Genes associated with the PDX engraftment may provide a novel prognostic biomarker and therapeutic targets in TNBC.
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      description: We aimed to identify the factors affecting the successful tumor engraftment in breast cancer patient-derived xenograft (PDX) models. Further, we investigated the prognostic significance and the functional importance of the PDX engraftment-related genes in triple-negative breast cancers (TNBC). The clinico-pathologic features of 81 breast cancer patients whose tissues were used for PDX transplantation were analyzed to identify the factors affecting the PDX engraftment. A gene signature associated with the PDX engraftment was discovered and its clinical importance was tested in a publicly available dataset and in vitro assays. Nineteen out of 81 (23.4 %) transplanted tumors were successfully engrafted into the PDX models. The engraftment rate was highest in TNBC when compared to other subtypes (p = 0.001) and in recurrent or chemotherapy-resistant tumors compared to newly diagnosed primary tumors (p = 0.024). PDX tumors originated from the TNBC cases showed more rapid tumor growth in mice. Gene expression profiling showed that down-regulation of genes involved in the tumor–immune interaction was significantly associated with the successful PDX engraftment. The engraftment gene signature was associated with worse survival outcome when tested in publicly available mRNA datasets of TNBC cases. Among the engraftment-related genes, PHLDA2, TKT, and P4HA2 showed high expression in triple-negative breast cancer cell lines, and siRNA-based gene silencing resulted in reduced cell invasion and proliferation in vitro. Our results show that the PDX engraftment may reflect the aggressive phenotype in breast cancer. Genes associated with the PDX engraftment may provide a novel prognostic biomarker and therapeutic targets in TNBC.
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            type:Organization
      name:Ju-Yeon Kim
      affiliation:
            name:Gyeongsang National University
            address:
               name:Department of Surgery, Gyeongsang National University, Jinju, Korea
               type:PostalAddress
            type:Organization
      name:Tae-Kyung Yoo
      affiliation:
            name:Seoul National University College of Medicine
            address:
               name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
            name:Seoul National University College of Medicine
            address:
               name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
      name:Myung Won Seo
      affiliation:
            name:Seoul National University College of Medicine
            address:
               name:Laboratory of Immunology, Interdisciplinary Program of Tumor Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
      name:Ae Kyung Park
      affiliation:
            name:Sunchon National University
            address:
               name:College of Pharmacy, Sunchon National University, Suncheon, Korea
               type:PostalAddress
            type:Organization
      name:Han Suk Ryu
      affiliation:
            name:Seoul National University Hospital
            address:
               name:Department of Pathology, Seoul National University Hospital, Seoul, Korea
               type:PostalAddress
            type:Organization
      name:Eun-Jung Jung
      affiliation:
            name:Gyeongsang National University
            address:
               name:Department of Surgery, Gyeongsang National University, Jinju, Korea
               type:PostalAddress
            type:Organization
      name:Namshin Kim
      affiliation:
            name:Korea Research Institute of Bioscience & Biotechnology
            address:
               name:Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
               type:PostalAddress
            type:Organization
      name:Seongmun Jeong
      affiliation:
            name:Korea Research Institute of Bioscience & Biotechnology
            address:
               name:Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
               type:PostalAddress
            type:Organization
      name:Wonshik Han
      affiliation:
            name:Seoul National University College of Medicine
            address:
               name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
            name:Seoul National University College of Medicine
            address:
               name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
      name:Dong-Sup Lee
      affiliation:
            name:Seoul National University College of Medicine
            address:
               name:Laboratory of Immunology, Interdisciplinary Program of Tumor Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
            name:Seoul National University College of Medicine
            address:
               name:Department of Biomedical Sciences, Laboratory of Immunology and Cancer Biology, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Dong-Young Noh
      affiliation:
            name:Seoul National University College of Medicine
            address:
               name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
            name:Seoul National University College of Medicine
            address:
               name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Immunology, Interdisciplinary Program of Tumor Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Department of Surgery, Gyeongsang National University, Jinju, Korea
      name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Immunology, Interdisciplinary Program of Tumor Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:College of Pharmacy, Sunchon National University, Suncheon, Korea
      name:Department of Pathology, Seoul National University Hospital, Seoul, Korea
      name:Department of Surgery, Gyeongsang National University, Jinju, Korea
      name:Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
      name:Epigenomics Research Center, Genome Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
      name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Immunology, Interdisciplinary Program of Tumor Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
      name:Department of Biomedical Sciences, Laboratory of Immunology and Cancer Biology, Seoul National University College of Medicine, Seoul, Korea
      name:Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
      name:Laboratory of Breast Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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