ArticleThe Journal of clinical endocrinology and metabolism2015
Establishment and characterization of novel human primary and metastatic anaplastic thyroid cancer cell lines and their genomic evolution over a year as a primagraft.
Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
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- Anaplastic Thyroid Carcinoma: Current Issues in Genomics and Therapeutics.Current oncology reports · 2021Review
- The multifaceted role of reactive oxygen species in tumorigenesis.Cellular and molecular life sciences : CMLS · 2020Review
- RAS Subcellular Localization Inversely Regulates Thyroid Tumor Growth and Dissemination.Cancers · 2020Article
- Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy.International journal of molecular sciences · 2020Review
- Immunotherapy in anaplastic thyroid cancer.American journal of translational research · 2020Article
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- Methodology, Criteria, and Characterization of Patient-Matched Thyroid Cell Lines and Patient-Derived Tumor Xenografts.The Journal of clinical endocrinology and metabolism · 2018Article
- Selinexor (KPT-330) has antitumor activity against anaplastic thyroid carcinoma in vitro and in vivo and enhances sensitivity to doxorubicin.Scientific reports · 2017Article
- Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma.Oncotarget · 2017Article
- Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.Blood · 2015Article
- Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models.Hormones & cancer · 2015Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
contextAnaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth.
objectiveThe aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies.
designWe established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC, which was serially xeno-transplanted for more than 1 year in NOD scid gamma mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes, and somatic mutations using RNA array, SNP Chip, and whole exome sequencing.
resultsMice carrying sc (OGK-P and OGK-M) tumors developed splenomegaly and neutrophilia with high expression of cytokines including CSF1, CSF2, CSF3, IL-1β, and IL-6. Levels of HIF-1α and its targeted genes were also elevated in these tumors. The treatment of tumor carrying mice with Bevacizumab effectively decreased tumor growth, macrophage infiltration, and peripheral WBCs. SNP chip analysis showed homozygous deletion of exons 3-22 of the PARD3 gene in the cells. Forced expression of PARD3 decreased cell proliferation, motility, and invasiveness, restores cell-cell contacts and enhanced cell adhesion. Next generation exome sequencing identified the somatic changes present in the primary, metastatic, and primagraft tumors demonstrating evolution of the mutational signature over the year of passage in vivo.
conclusionTo our knowledge, we established the first paired human primary and metastatic ATC cell lines offering unique possibilities for comparative functional investigations in vitro and in vivo. Our exome sequencing also identified novel mutations, as well as clonal evolution in both the metastasis and primagraft.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.