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Metastasis is the main cause of cancer patient mortality. Local tumor invasion is a key step in metastatic dissemination whereby cancer cells dislodge from primary tumors, migrate through the peritumoral stroma and reach the circulation. This is a highly dynamic process occurring in three dimensions that involves interactions between tumor, stromal cells, and the extracellular matrix. Here we describe the organotypic culture system and its utility to study breast cancer cell invasion induced by cancer-associated fibroblasts. This is a three-dimensional model that reproduces the biochemical and physiological properties of real tissue and allows for investigating the molecular and cellular mechanisms involving tumor and its microenvironment, and their contribution to cancer cell invasion. This system provides a robust, accurate, and reproducible method for measuring cancer cell invasion and represents a valuable tool to improve the mechanistic understanding of the initial steps in metastasis.

Organotypic --- Invasion --- Metastasis --- Breast cancer --- Cancer-associated fibroblasts

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This Research Topic is devoted to the understanding of molecular mechanisms of Human Thyroid Cancers. Original research describing functional studies of genetic mutations that shed novel insights into the aetiology and pathogenesis of these cancers, as well as angiogenesis and tumor microenvironment, mouse models studies that describe mechanisms or novel potential therapeutic targets and biomarkers for these endocrine cancers are presented. Scopes: The scope of this Research Topic was to cover the entire field of thyroid cancers: the main focus of this topic is translational, with an emphasis on bench to bedside research. Experimental, pre-clinical and clinical research addressing the following aspects is included in this Research Topic: 1) Investigation of specific molecular patterns of thyroid tumorigenesis, which could allow the development of new directions in the field of pharmacotherapy research; 2) Emphasis on animal studies (preclinical models of human anaplastic thyroid cancers) for the validation of biomarkers with the potential to lead to clinical trials, and studies of targetable mechanisms of oncogenesis, progression of these malignancies, tumor microenvironment and extracellular matrix, and metastatic disease; 3) Assessment of biomarkers to predict the potential response or resistance to drug treatment (targeted cancer therapies) or to guide the follow-up of treated patients; 4) Investigation of new laboratory molecular tests (e.g. molecular techniques and applications of thyroid fine-needle aspiration biopsy) to translate in the clinical practice; In summary, specific areas of interest include: thyroid cancer genetics; genome-wide analysis; clinical and translational research; orthotopic mouse models of metastatic thyroid carcinoma; tumor microenvironment; epigenetic; biological insights of personalized medicine; novel applications of bioinformatics; large scale molecular characterization of tumors; diagnostic or prognostic biomarkers; endocrine pathology studies; thyroid fine-needle aspiration.

Papillary thyroid cancer --- microenvironment --- BRAFV600E --- translational --- epigenetic --- papillary thyroid microcarcinoma --- RET --- beta-Catenin --- anaplastic thyroid cancer --- metastasis

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The Special Issue on high grade serous ovarian cancer (HGSOC) and the contribution of the tumor microenviroment (TME) consists of reviews contributed by leaders in the OC field. As HGSOC metastases have a highly complex TME, there is an urgent need to better understand the TME in general, its distinct components in particular, and the role of the TME in the context of disease recurrence and development of chemoresistance. The Special Issue incorporates the current understanding of the different parts of thd TME components, including the cancer cells themselves, the cells surrounding the cancer cells or stromal cells, and the cells of the immune system, which are attracted to the site of metastases. In addition to these cells of the TME, the role of various cellular factors made by the cells of the TME are also the subject of the reviews. In addition, reviews in this Special Issue cover the complex relationships between the molecular mechanisms of HGSOC progression, including genomic, epigenomic and transcriptomic changes and changes in the immune cell landscape, as these may provide attractive new molecular targets for HGSOC therapy.

ovarian cancer --- tumor microenvironment --- metastasis --- chemoresistance --- recurrence --- stroma --- genomic --- transcriptomic --- epigenetics --- cancer stem cells --- fibroblasts --- immune cells --- immunotherapies

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The analysis of circulating tumor cells (CTCs) as a real-time liquid biopsy approach can be used to obtain new insights into metastasis biology, and as companion diagnostics to improve the stratification of therapies and to obtain insights into the therapy-induced selection of cancer cells. In this book, we will cover all the different facets of CTCs to assemble a huge corpus of knowledge on cancer dissemination: technologies for their enrichment, detection, and characterization; their analysis at the single-cell level; their journey as CTC microemboli; their clinical relevance; their biology with the epithelial-to-mesenchymal transition (EMT); their stem-cell properties; their potential to initiate metastasis at distant sites; their ex vivo expansion; and their escape from the immune system.

circulating tumor cells --- circulating tumor DNA --- liquid biopsy --- metastatic colorectal cancer --- FOLFIRINOX --- circulating tumor cells --- CTC --- liquid biopsy --- CTM --- CTMat --- CTC biology --- CTC capture technology --- metastasis --- circulating tumor cells (CTCs) --- hepatocellular carcinoma (HCC) --- castration resistant prostate cancer (CRPC) --- epithelial-to-mesenchymal transition (EMT) --- fibronectin --- integrin B1 --- SLUG --- major histocompatibility complex class I (MHCI) --- immunomodulation --- bone marrow --- melanoma --- disseminated tumor cells --- solid cancers --- single-cell analysis --- enrichment and detection technologies --- flow cytometry --- tumor stem cells --- HMB-45 --- CD133 --- locally advanced rectal cancer --- circulating tumor cells --- RAD23B --- thymidylate synthase --- chemoradioresistance --- liquid biopsy --- circulating tumor cells --- epithelial–mesenchymal transition --- stem cells --- early breast cancer --- prostate cancer (PCa) --- circulating tumor cells (CTC) --- liquid biopsy --- circulating tumor cells --- metastasis --- xenograft models --- breast cancer --- prostate cancer --- CTC --- AR --- AR-V7 --- ctRNA --- exosome --- circulating tumor cells --- hematological cells --- neutrophils --- platelets --- liquid biopsy --- circulating tumor cells --- melanoma --- liquid biopsy --- EPISPOT --- CellSearch® --- liquid biopsy --- CTCs --- immune checkpoint inhibitors --- PD-L1 expression --- NSCLC --- small-cell lung carcinoma --- circulating tumor cells --- microfluidics --- gene expression analysis --- synaptophysin --- chromogranin A --- rovalpituzumab tesirine --- leukocyte-derived extracellular vesicles --- immunofluorescence imaging --- EpCAM enrichment --- CellSearch --- EasyCount slides --- ACCEPT --- CTC --- heterogeneity --- liquid biopsy --- liquid surgery --- clinical utility --- circulating tumor cells (CTCs) --- glioma --- biomarker --- rVAR2 --- malaria --- enrichment and detection technologies --- prostate cancer --- biomarkers --- circulating tumor cells --- androgen receptor --- ARV7 --- abiraterone --- enzalutamide --- metastasis --- tumor-initiating cells (TICs) --- circulating tumor cells (CTCs) --- CTC-derived xenografts --- CTC-derived ex vivo models --- cerebrospinal liquid biopsy --- in vivo flow cytometry --- tumor biomarkers --- circulating tumor cells --- ctDNA --- miRNA --- exosomes --- emboli --- targeted therapy --- circulating tumor cells --- tumor cell dissemination --- immune system --- microbiome --- circulating tumor cells (CTCs) --- clinical trials --- breast cancer --- CTC-based treatment decisions --- circulating tumour cells --- colorectal cancer --- colorectal surgery --- microsatellite instability --- microfluidics --- immunophenotyping --- fish --- liquid biopsy --- circulating leukemia cells --- circulating plasma cells --- n/a

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Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.

tumor --- metabolism --- carbonic anhydrase --- isoforms IX and XII --- inhibitor --- sulfonamide --- antibody --- bacterial carbonic anhydrases --- inhibitors --- antibiotic --- CO2 capture --- engineered bacteria --- acidity --- hypoxia --- pH --- carbonic anhydrases --- V-ATPases --- proton pump inhibitors --- carbonic anhydrase inhibitors --- carbonic anhydrase IX --- cancer --- hypoxia --- radiation --- resistance --- tumors --- pH --- carbonic anhydrases --- metalloenzymes --- carbonic anhydrase IX --- carbonic anhydrase XII --- cancer therapeutics --- metabolism --- tumor microenvironment --- drug discovery --- hypoxia --- carbonic anhydrase IX --- cancer metabolism --- transporter --- integrin --- MMP14 --- migration --- invasion --- metastasis --- carbonic anhydrases --- CA gene family --- Chlamydomonas reinhardtii --- model alga --- metabolic role --- photosynthesis --- carbonic anhydrase --- hypoxic tumor --- metabolism --- carboxylation --- bicarbonate --- pH regulation --- antitumor agent --- sulfonamide --- bacterial enzymes --- carbonic anhydrase --- enzyme inhibition --- metalloenzymes --- amino acid --- glaucoma --- tumors --- carbonic anhydrase --- human isoform --- sulfonamide --- benzamide --- pathogens --- Entamoeba histolytica --- carbonic anhydrase --- metalloenzymes --- protozoan --- amine --- amino acid --- activator