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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.

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

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Somatic stem cells reside in definite compartments, known as “niches”, within developed organs and tissues, being able to renew themselves, differentiate and ensure tissue maintenance and repair. In contrast with the original dogmatic distinction between renewing and non-renewing tissues, somatic stem cells have been found in almost every human organ, including brain and heart. Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective stroma of adult tissues and organs, endowed with outstanding plasticity and trophic features. Strictly-defined MSCs have been originally described as fibroblastoid cells in the bone marrow stroma, able to give rise to differentiated bone cells. Thereafter, additional tissue sources, including adipose tissue, skin, muscle, among others, have been exploited for isolating cell populations that share MSC-like biological features. MSCs are able to differentiate along multiple mesodermal lineages and are believed to represent the key somatic stem cell within the skeletogenic niche, being conceptually able to produce any tissue included within a mature skeletal segment (bone, cartilage, blood vessels, adipose tissue, and supporting connective stroma). Despite this high plasticity, the claim that MSCs could be capable of transdifferentiation along non-mesodermal lineages, including neurons, has been strongly argued. No clear scientific clue has indeed proved the possibility to achieve a functional non-mesordermal phenotype upon MSCs in vitro induction or in vivo inoculation. Adult osteogenic and neurogenic niches display wide differences: embryo origin, microenvironment, progenitors’ lifespan, lineages of supporting cells. Although similar pathways may be involved, it is hard to believe that the osteogenic and neurogenic lineages can share functional features. Beyond embryo stage, neurogenesis persists throughout postnatal life in the subventricular zone (SVZ) of the forebrain lateral ventricles and in the subgranular zone of the hippocampus of adult brain. Here the principal reservoirs of adult neural stem cells reside in specific niches and generate neurons and glial cells to sustain the turnover of selected brain compartments. Studying these reservoirs is useful to gather information on the specialized cellular microenvironments and molecular signals that are needed to maintain neural stem cells in vivo, regulating the fine equilibrium between proliferation and differentiation, acting on the switch between symmetrical and asymmetrical cell division. Based on this contemporary background, this Research Topic wish to provide an in-depth revision of the state of the art on relevant scientific milestones addressing the differences and possible interconnections and overlaps, between the osteogenic and the neurogenic niche, clarifying the questioned issue of neuronal transdifferentiation of somatic stem cells.

Neuroscience. --- Neuropeptide Y --- Stem Cell Niche --- Mesenchymal Stromal Cells --- Neural Stem Cells --- Regenerative Medicine --- Wnt/beta-catenin signaling --- Bone Marrow --- Neural Crest --- RUNX2

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Somatic stem cells reside in definite compartments, known as “niches”, within developed organs and tissues, being able to renew themselves, differentiate and ensure tissue maintenance and repair. In contrast with the original dogmatic distinction between renewing and non-renewing tissues, somatic stem cells have been found in almost every human organ, including brain and heart. Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective stroma of adult tissues and organs, endowed with outstanding plasticity and trophic features. Strictly-defined MSCs have been originally described as fibroblastoid cells in the bone marrow stroma, able to give rise to differentiated bone cells. Thereafter, additional tissue sources, including adipose tissue, skin, muscle, among others, have been exploited for isolating cell populations that share MSC-like biological features. MSCs are able to differentiate along multiple mesodermal lineages and are believed to represent the key somatic stem cell within the skeletogenic niche, being conceptually able to produce any tissue included within a mature skeletal segment (bone, cartilage, blood vessels, adipose tissue, and supporting connective stroma). Despite this high plasticity, the claim that MSCs could be capable of transdifferentiation along non-mesodermal lineages, including neurons, has been strongly argued. No clear scientific clue has indeed proved the possibility to achieve a functional non-mesordermal phenotype upon MSCs in vitro induction or in vivo inoculation. Adult osteogenic and neurogenic niches display wide differences: embryo origin, microenvironment, progenitors’ lifespan, lineages of supporting cells. Although similar pathways may be involved, it is hard to believe that the osteogenic and neurogenic lineages can share functional features. Beyond embryo stage, neurogenesis persists throughout postnatal life in the subventricular zone (SVZ) of the forebrain lateral ventricles and in the subgranular zone of the hippocampus of adult brain. Here the principal reservoirs of adult neural stem cells reside in specific niches and generate neurons and glial cells to sustain the turnover of selected brain compartments. Studying these reservoirs is useful to gather information on the specialized cellular microenvironments and molecular signals that are needed to maintain neural stem cells in vivo, regulating the fine equilibrium between proliferation and differentiation, acting on the switch between symmetrical and asymmetrical cell division. Based on this contemporary background, this Research Topic wish to provide an in-depth revision of the state of the art on relevant scientific milestones addressing the differences and possible interconnections and overlaps, between the osteogenic and the neurogenic niche, clarifying the questioned issue of neuronal transdifferentiation of somatic stem cells.

Neuroscience. --- Neuropeptide Y --- Stem Cell Niche --- Mesenchymal Stromal Cells --- Neural Stem Cells --- Regenerative Medicine --- Wnt/beta-catenin signaling --- Bone Marrow --- Neural Crest --- RUNX2 --- Neuropeptide Y --- Stem Cell Niche --- Mesenchymal Stromal Cells --- Neural Stem Cells --- Regenerative Medicine --- Wnt/beta-catenin signaling --- Bone Marrow --- Neural Crest --- RUNX2

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Dysregulation of Wnt signaling is known to be associated with various cancers. As such, identification of novel Wnt pathway targets in cancer and better characterization of already-known targets present exciting, emerging opportunities for cancer treatment. In this Special Issue, we feature papers which discuss the role of Wnt signaling and associated targets in cancer metabolism, tumor immune response, and tumor microenvironment. Papers discussing a range of Wnt-mediated cancers, including those of the colon, liver, pancreas, synovium, bladder, etc., are included.

Medicine --- Pharmacology --- Wnt signaling --- synovial sarcoma --- TNIK --- NCB-0846 --- MYC --- hepatitis B virus --- HBV --- cancer --- liver cancer --- β-catenin --- TCF/LEF --- pancreatic cancer --- pancreatic stellate cells --- CBP --- p300 --- pancreatitis --- fibrosis --- just-right signaling --- APC --- colorectal cancer --- RNA-binding proteins --- Musashi --- drug discovery --- Notch signaling --- cancer therapy --- fungi secondary metabolite derivative --- microenvironment --- Wnt --- AML --- drug target --- signaling --- colorectal --- porcupine --- R-spondin --- serrated --- immunotherapy --- wnt --- vitamin D --- colon cancer --- L1 --- Wnt target genes --- cell adhesion --- NF-κB --- invasion and metastasis --- cancer stem cells --- EMT --- Lgr5 --- Wnt/beta-catenin signaling --- angiogenesis --- anti-angiogenic therapy --- gastrointestinal cancers --- therapeutic targeting of Wnt signaling --- β-catenin paradox --- molecular targeting --- urothelial cancer --- immune checkpoint inhibitor --- immunotherapy resistance --- IBD --- colitis --- β-catenin mutations --- tumor metabolism --- tumor immunology --- molecular therapeutics --- precision medicine --- astrocytic brain tumors --- DKKs --- GSK3β --- Wnt signaling --- synovial sarcoma --- TNIK --- NCB-0846 --- MYC --- hepatitis B virus --- HBV --- cancer --- liver cancer --- β-catenin --- TCF/LEF --- pancreatic cancer --- pancreatic stellate cells --- CBP --- p300 --- pancreatitis --- fibrosis --- just-right signaling --- APC --- colorectal cancer --- RNA-binding proteins --- Musashi --- drug discovery --- Notch signaling --- cancer therapy --- fungi secondary metabolite derivative --- microenvironment --- Wnt --- AML --- drug target --- signaling --- colorectal --- porcupine --- R-spondin --- serrated --- immunotherapy --- wnt --- vitamin D --- colon cancer --- L1 --- Wnt target genes --- cell adhesion --- NF-κB --- invasion and metastasis --- cancer stem cells --- EMT --- Lgr5 --- Wnt/beta-catenin signaling --- angiogenesis --- anti-angiogenic therapy --- gastrointestinal cancers --- therapeutic targeting of Wnt signaling --- β-catenin paradox --- molecular targeting --- urothelial cancer --- immune checkpoint inhibitor --- immunotherapy resistance --- IBD --- colitis --- β-catenin mutations --- tumor metabolism --- tumor immunology --- molecular therapeutics --- precision medicine --- astrocytic brain tumors --- DKKs --- GSK3β

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Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance