Discoveries is a new peer-reviewed, open access, online multidisciplinary and integrative journal publishing high impact reviews, experimental articles, perspective articles, and editorials from all areas related to medicine, biology, and chemistry, including but not limited to: Molecular and Cellular Biology, Biochemistry, Biophysics, Genomics, Proteomics, Biotechnology, Synthetic Biology, Bioengineering, Systems Biology, Bioinformatics, Translational Medicine, Medicine/ Clinical findings, Cognitive Science, Epidemiology, Global Medicine, Family Medicine, Organic/ Inorganic/ Physical Chemistry and Ethics in Science. Discoveries brings to the research community an outstanding editorial board that aims to address several of the innovations proposed above: there is no need to format the manuscript before submission, we have a rapid and efficient submission process, there is no need for a Cover Letter and we support the need for rules for validation of critical reagents, such as antibodies. Discoveries will aim to support high quality research on human subjects materials to provide relevance for non-human studies along with mechanistic insights into human biology and chemistry. We also aim to avoid requesting unnecessary experiments during the review process, without affecting the quality and conclusions of published manuscripts. In addition, we recognize the need of adopting the recommendations made by NCCD and other similar scientific guiding entities.
Publications by Year: 2013
2013
BACKGROUND AND RATIONALE: Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer progression by regulating cell stromal cross-talk in the tumor microenvironment.
GOALS: Our goal was to understand whether TSP-1 could affect protein levels of its integrin receptors (e.g., ITGα3, α6, and β1) and cell morphology in BRAF(V600E)-ATC cells in vitro and in vivo.
EXPERIMENTAL DESIGN: Anaplastic thyroid cancer-derived cell cultures and western blotting were used to assess integrin protein expression upon TSP-1 silencing. Immunohistochemistry was performed on orthotopic primary human ATC and metastatic ATC in lung tissue to compare TSP-1 and integrin protein expression levels.
RESULTS: TSP-1 knock-down down-regulates ITGα3, α6, and β1 in BRAF(V600E)-human ATC cells. BRAF(V600E)-ATC cells with TSP-1 knock-down were rounded compared to control cells, which displayed a spread morphology. TSP-1 knock-down also reduced TSP-1, ITGα3, α6, and β1 protein expression levels in vivo in the ATC microenvironment, which is enriched in stromal and inflammatory cells.
CONCLUSION: TSP-1 silencing causes changes in ITG levels and ATC cell morphology. The assessment of TSP-1 and ITG levels might contribute to earlier metastatic potential of BRAF(V600E)-positive aggressive thyroid cancers, and allow improved patient selection for clinical trials.