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The cancer stem cell (CSC) paradigm represents one of the most prominent breakthroughs of the last decades in tumor biology. CSCs are that subpopulation within a tumor that can survive conventional therapies and as a consequence are able to fuel tumor recurrence. Nevertheless, the biological characteristics of CSCs and even their existence, remain the main topic among tumor biologists debates. The difficulty in achieving a better definition of CSC biology may actually be explained by the plasticity of such a cell subpopulation. Indeed, the emerging view is that CSCs represent a dynamic “state” of tumor cells that can acquire stemness-related properties under specific circumstances, rather than referring to a well-defined group of cells. Regardless of their origin, it is clear that designing novel antitumor treatments based on the eradication of CSCs will only be possible upon unraveling the biological mechanisms that underlie their pathogenic role in tumor progression and therapy resistance. The Special Issue on “New aspects of cancer stem cell biology: implications for innovative therapies” aims at highlighting recent insights into CSC features that can make them an attractive target for novel therapeutic strategies.

Cadherin 11 --- WNT signaling --- β-catenin --- cancer stem cells --- TNBC --- early breast cancer --- bevacizumab --- neoadjuvant chemotherapy --- ALDH1 --- solid cancer --- chemo-resistance --- HDAC inhibitors --- head and neck squamous cell carcinoma --- SRC --- dasatinib --- saracatinib --- EC-8042 --- Ovarian cancer --- Wnt signaling --- tumor progression --- therapy resistance --- exosomes --- oral cancer risk --- oral epithelial dysplasia --- SOX2 --- immunohistochemistry --- oral squamous cell carcinoma --- genome-wide --- transcriptome --- lung cancer --- ATAC-seq --- RNA-seq --- CSCs --- NSCLC --- B4GALT1 --- LUAD --- breast cancer --- lipid --- metabolism --- therapeutic resistance --- bowel cancer --- organoid --- tumoroid --- colorectal --- colon --- stem cell --- chemotherapy resistance --- ovarian cancer --- cancer stem cell --- genetic heterogeneity --- SNP array --- L1CAM --- chemoresistance --- epithelial-mesenchymal transition --- cancer therapy --- cell adhesion molecule

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Tissue engineering and regenerative medicine is a rapidly evolving research field which effectively combines stem cells and biologic scaffolds in order to replace damaged tissues. Biologic scaffolds can be produced through the removal of resident cellular populations using several tissue engineering approaches, such as the decellularization method. Indeed, the decellularization method aims to develop a cell-free biologic scaffold while keeping the extracellular matrix (ECM) intact. Furthermore, biologic scaffolds have been investigated for their in vitro potential for whole organ development. Currently, clinical products composed of decellularized matrices, such as pericardium, urinary bladder, small intestine, heart valves, nerve conduits, trachea, and vessels, are being evaluated for use in human clinical trials. Tissue engineering strategies require the interaction of biologic scaffolds with cellular populations. Among them, stem cells are characterized by unlimited cell division, self-renewal, and differentiation potential, distinguishing themselves as a frontline source for the repopulation of decellularized matrices and scaffolds. Under this scheme, stem cells can be isolated from patients, expanded under good manufacturing practices (GMPs), used for the repopulation of biologic scaffolds and, finally, returned to the patient. The interaction between scaffolds and stem cells is thought to be crucial for their infiltration, adhesion, and differentiation into specific cell types. In addition, biomedical devices such as bioreactors contribute to the uniform repopulation of scaffolds. Until now, remarkable efforts have been made by the scientific society in order to establish the proper repopulation conditions of decellularized matrices and scaffolds. However, parameters such as stem cell number, in vitro cultivation conditions, and specific growth media composition need further evaluation. The ultimate goal is the development of "artificial" tissues similar to native ones, which is achieved by properly combining stem cells and biologic scaffolds and thus bringing them one step closer to personalized medicine. The original research articles and comprehensive reviews in this Special Issue deal with the use of stem cells and biologic scaffolds that utilize state-of-the-art tissue engineering and regenerative medicine approaches.

nerve conduit --- tissue engineering --- regenerative medicine --- mixed lymphocyte reaction --- histological images --- future scaffold engineering --- multiparameter --- 3DPVS --- MSCs --- Wnt signaling --- Mesenchymal Stromal Cells --- factorial design --- novel scaffold --- Wharton’s Jelly tissue --- stem cells --- umbilical arteries --- SDS --- platelet rich plasma --- TGF? signaling --- traditional scaffold --- pluripotency and commitment --- tissue engineered construct --- HLA-G --- CHAPS --- platelets --- proteomic analysis --- vibrating nature of universe. --- VS55 --- cell culture --- FGF signaling --- evolution of scaffold --- dynamicity and dimensionality --- fibrin gel --- scaffold classification --- decellularization --- vitrification --- seven-folder logics --- IIEF-5 questionnaire --- TGF-?1 --- erectile dysfunction --- human induced pluripotent stem cells --- iPSCs --- scaffolds --- Barret’s esophagus --- nerve regeneration --- long term storage --- laws of system evolution --- scaffold categorization --- platelet lysate --- 3D scaffold --- esophagus --- language of relativity --- cord blood units

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The scientific community has made significant progress in our molecular understanding of sporadic and hereditary colorectal carcinogenesis and progression. Thie pertains to, e.g., the discovery of (mutated) oncogenes and tumor suppressor genes, microsatellite instabilities, modifications in DNA repair, cellular aging, signaling cascades, genomic, epigenetic, transcriptional, translational, and protein modifications, as well as microbiotic factors and further parameters. Progression and metastasis have been more intensively studied, especially during recent years, leading to an intensified knowledge on molecular protagonists and microenvironmental interactions contributing to invasion, dissemination, and metastasis; still, more concerted efforts need to be made to better understand issues such as metastasis to different sites or the metastatic heterogeneity of single cells. Nevertheless, based on actual discoveries, personalized medicine, together with highly interdisciplinary therapeutic strategies combining advanced levels of surgical techniques, oncology, and radiation in neoadjuvant, adjuvant, or palliative settings, has started to improve the clinical prognosis of individual patients with colorectal cancer. The present Special Issue features articles of excellent international experts with the latest data in the fields mentioned. With this Special Issue, we aim to deepen discussions amongst colleagues in all kinds of disciplines working on this disease and to intensify interdisciplinary collaborations aimed at an ultimate understanding of strategies to defeat and prevent, colorectal cancer, and its progression.

Phage --- bacteriophages --- diet --- infection --- colorectal --- cancer --- nutrition --- circulating tumor cells --- colorectal cancer --- EPISPOT assay --- CellSearch® system --- predictive value --- chromatin density --- nanoscale --- tumour cell heterogeneity --- microRNAs --- metastasis --- super-resolution microscopy --- early onset --- cohort --- epidemiology --- liquid biopsy --- biomarker --- indirect carcinogenesis --- bovine meat and milk factors (BMMF) --- chronic zoonosis --- multiplex --- tumor immunology --- immune landscape --- spontaneous feline intestinal tumors --- comparative oncology --- tumor budding --- CTNNB1 --- genome-wide methylation array --- methylation --- miRNA --- colon cancer --- personalized treatment --- drug combinations --- Matrix Metalloproteinases (MMPs) --- polyp --- TIMPs --- MMP polymorphisms --- MMP targeting --- S100A4 --- DKK1 --- Wnt signaling --- patient survival --- gender --- rectal cancer --- radiochemotherapy --- radiosensitivity --- DNA double-strand breaks --- deposited energy --- quality of life --- blood values --- (molecular) carcinogenesis --- cancer progression --- (single) cancer cell heterogeneity --- models --- infectious agents --- (targeted) therapy --- personalized medicine

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The Wnt pathway is an evolutionarily conserved signaling network that is critical for mammalian development and adult tissue maintenance, and, importantly, hyperactivated in most human cancers. Almost two decades of study has confirmed that Wnt signaling is necessary and sufficient for cancer pathogenesis in multiple in vitro and in vivo models systems, suggesting that the pathway represents an attractive therapeutic target.  Recent efforts have focused on innovative strategies to antagonize Wnt signaling at various levels of the pathway – from attenuating the extracellular signaling through the Wnt receptors to modulating the catenin destruction complex to blocking catenin-mediated transcription. Many of these approaches have been largely successful in preclinical validation studies and have been met with considerable enthusiasm to move forward into clinical trials. In this book, we highlight the recent advances in our understanding of the complexity of the Wnt pathway, particularly its intricate regulation and cross-talk with other key signal transduction pathways in normal and tumor cells. As a way to comprehend the role of Wnt pathway activation in tumor initiation and progression, we discuss the importance of Wnt signaling in embryonic and tissue development and stem cell maintenance and self-renewal. The evidence for aberrant Wnt pathway activation in human solid and hematopoietic cancers, as well as a few of the genetic mouse models that mimic the Wnt pathway deregulation observed in some of these tumor types, is reviewed. Lastly, we summarize the current status of the development of Wnt pathway inhibitors, their efficacy in preclinical models and their potential as therapeutic agents for cancer. It is an exciting time in the Wnt signaling field – one that represents a key crossroad between dissecting the molecular details of the pathway and translating that work into promising targeted tumor therapies – that is likely to profoundly impact this research area for years to come.

Cancer -- Genetic aspects. --- Neoplasms -- genetics. --- Neoplasms -- therapy. --- Signal Transduction. --- Targeted Gene Repair -- methods. --- Wnt genes. --- Intercellular Signaling Peptides and Proteins --- Cell Physiological Processes --- Biology --- Biochemical Processes --- Gene Therapy --- Investigative Techniques --- Mutagenesis, Site-Directed --- Diseases --- Proteins --- Cell Physiological Phenomena --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Chemical Processes --- Genetic Engineering --- Protein Engineering --- Biological Therapy --- Biochemical Phenomena --- Biological Factors --- Peptides --- Biological Science Disciplines --- Chemical Phenomena --- Therapeutics --- Amino Acids, Peptides, and Proteins --- Phenomena and Processes --- Chemicals and Drugs --- Natural Science Disciplines --- Genetic Techniques --- Disciplines and Occupations --- Wnt Proteins --- Neoplasms --- Signal Transduction --- Genetics --- Targeted Gene Repair --- Methods --- Medicine --- Health & Biological Sciences --- Oncology --- Cellular signal transduction. --- Wnt proteins. --- Cancer. --- Cancers --- Carcinoma --- Malignancy (Cancer) --- Malignant tumors --- Cellular information transduction --- Information transduction, Cellular --- Signal transduction, Cellular --- Medicine. --- Cancer research. --- Pharmacology. --- Oncology. --- Medicine & Public Health. --- Pharmacology/Toxicology. --- Cancer Research. --- Tumors --- Glycoproteins --- Growth factors --- Bioenergetics --- Cellular control mechanisms --- Information theory in biology --- Oncology  . --- Toxicology. --- Chemicals --- Pharmacology --- Poisoning --- Poisons --- Toxicology --- Wnt pathway. --- Pathway, Wnt --- Signal transduction pathway, Wnt --- Signaling pathway, Wnt --- Wnt signal transduction pathway --- Wnt signaling pathway --- Cellular signal transduction --- Cancer research --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemotherapy --- Drugs --- Pharmacy --- Physiological effect

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The Book covers this whole field, from the discovery of structurally new and bioactive natural products (including biomacromolecules), from marine macro-/micro-organisms, to the pharmacodynamics, pharmacokinetics, metabolisms, and mechanisms of marine-derived lead compounds, both in vitro and in vivo, along with the synthesis and/or structural optimization of marine-derived lead compounds and their structure–activity relationships. Taken together, this Special Issue reprint not only provides inspiration for the discovery of marine-derived novel bioactive compounds, but also sheds light on the further research and development of marine candidate drugs.

Antarctic krill (Euphausia superba) --- peptide --- antioxidant activity --- stability --- oyster --- plasma --- peptidome --- antimicrobial peptides --- cytotoxicity --- actinomycete --- piericidins --- absolute configuration --- Pestalotiopsis heterocornis --- heterocornols --- anti-inflammatory activity --- sponge-derived fungus --- sclerotides --- lipodepsipeptide --- Aspergillus sclerotiorum --- nasopharyngeal carcinoma --- AChE inhibitory --- vascular endothelial cell --- flavonoid --- oxidized low-density lipoprotein --- Nrf2 --- apoptosis --- butyrolactone I --- food allergy --- metabolism --- pharmacokinetics --- actinomycin X2 --- microbial pigments --- dyeing --- silk --- antibacterial properties --- PD-L1 --- virtual screening --- pharmacophore modeling --- ADME --- molecular dynamics --- xanthones --- ascidian-derived fungus --- Diaporthe sp. --- anti-glioma activity --- antiaging --- Sonneratia apetala --- signaling pathway --- Caenorhabditis elegans --- mutants --- coral-derived fungi --- Aspergillus hiratsukae --- meroterpenoids --- antibacterial activity --- cytotoxic activity --- deep-sea-derived fungus --- Aspergillus puniceus --- isoquinoline alkaloid --- protein tyrosine phosphatase inhibitor --- antibacterial --- Aspergillus sp. --- geodin --- semisynthesize --- insecticidal activity --- Arca inflata --- antitumor peptide --- MAPK signaling --- calmodulin --- colorectal cancer --- methicillin-resistant Staphylococcus aureus --- actinomycin D --- Streptomyces parvulus --- mechanism --- mangrove endophytic Pestalotiopsis --- Sdy-1 --- antitumor activity --- Wnt signaling --- β-catenin --- eremophilane sesquiterpenoids --- mangrove-derived fungus --- Penicillium sp. --- Oceanapia --- sponge --- secondary metabolites --- biological activities --- drug design --- anticancer --- cyclic pentapeptide --- galaxamide analogues --- skipjack tuna (Katsuwonus pelamis) muscle --- angiotensin-I-converting enzyme (ACE) peptide --- molecular docking --- nitric oxide (NO) --- endothelin-1 (ET-1) --- Trichoderma longibrachiatum --- sesquiterpene glycoside --- antimicrobial activity --- marine fungi --- Aspergillus unguis --- depsides --- depsidones --- osteoclast differentiation --- soft-coral-derived fungus --- pyranodipyran derivatives --- tyrosyl DNA phosphodiesterase 1 inhibitory activities --- fluorescent properties --- butenolides --- enantiomers --- Aspergillus terreus --- pancreatic lipase --- NAFLD --- fucoxanthin --- adenosine monophosphate-activated protein kinase (AMPK) --- nuclear factor erythroid-2-related factor 2-mediated (Nrf2) --- Toll-like receptor 4-mediated (TLR4) --- Aspergillus flavipes HN4-13 --- emodin --- macroporous resin XAD-16 --- adsorption kinetics and isotherms --- enrichment --- tetramic acid derivatives --- deep-sea fungus --- clavipitacae --- Lecanicillium fusisporum --- chronic kidney disease --- fucoidan --- cognitive dysfunction --- neuroinflammation --- oxidative stress --- GSK3β-Nrf2-HO-1 signaling --- microglial polarization --- deep-sea actinomycetes --- aromatic acids --- oximes --- antihyperlipidemic --- phycocyanin --- microbiota --- transcriptome --- IL-17 pathway --- Hahella --- prodiginine --- chejuenlide --- genome mining --- LC-MS/MS --- CDK4/6 --- marine compounds --- pharmacophore construction --- ADMET --- mm-pbsa