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Chemical and Molecular Approach to Tumor Metastases

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ISBN: 9783038428954 9783038428961 Year: Pages: VIII, 256 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Oncology --- Biology
Added to DOAB on : 2018-07-05 12:45:05
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Dear Colleagues, Malignant tumors develop distant metastases, e.g., small clusters of cells that detach from the primitive site and colonize distant organs and tissues. Unlike the primary masses, metastases are often difficult to fully eradicate by surgery ablation and are almost always the primary object of chemo- and/or immune-therapies. The presence of metastases at tumor diagnosis is responsible for the unfavorable prognosis and of relapses even after initially successful tumor therapies. The lack of success of chemo- and immune-therapy approaches depends on many factors among which, the inadequate capacity of the anti-tumor drugs of reaching appropriate concentrations in the organs and tissues involved in the metastatic growth is a major concern. Another factor is the complexity of the metastasis biology and of their molecular behavior, evidencing a population of tumor cells with a genetic compartment different from that of the tumor of origin. The involvement of host cells and factors recruited by the metastatic cells and committed to support the metastatic growth is also an event crucial for the lack of success of the anti-tumor therapy. The knowledge of the molecular biology of metastases is mandatory to support the search for chemical agents to treat the metastatic determinants and to control of the neoplastic disease. This Special Issue on “Chemical and Molecular Approach to Tumor Metastases” will explore the impact of biology, molecular medicine and chemistry on all aspects related to tumor metastases from the biological and molecular aspects of the metastatic growth, including the relationships between the metastatic cells and the host environment, and the search for druggable determinants useful for the chemical analysis of agents selectively active against tumor metastases. With the combination of invited reviews and original papers from prominent scientists working on all aspects of molecular medicine and cancer therapy, such as, but not limited to: drug delivery, genomics, chemoprevention, drug discovery, we aim to sample recent progress in molecular and chemical aspects of therapy of malignant tumors. Clinical success studies and evidences of novel compounds are particularly welcome.

Chapter: 'Analysis of Breast Cancer Cell Invasion Using an Organotypic Culture System' from book: 3D Cell Culture: Methods and Protocols (Book chapter)

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Book Series: Methods in Molecular Biology ISSN: 1064-3745 / 1940-6029 ISBN: 9781493970193 9781493970216 Year: Volume: 1612 Pages: 13 DOI: https://doi.org/10.1007/9781493970216_15 Language: English
Publisher: Springer Nature
Subject: Oncology
Added to DOAB on : 2017-07-19 15:44:38
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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.

Cancer Metabolism: Molecular Targeting and Implications for Therapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453221 Year: Pages: 114 DOI: 10.3389/978-2-88945-322-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-02-27 16:16:45
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Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists. “Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies.

Targeting thyroid cancer microenvironment and epigenetic signalling: new frontiers in cancer endocrinology basic and clinical research

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192403 Year: Pages: 131 DOI: 10.3389/978-2-88919-240-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
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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.

Physiology and Pathophysiology of the Extracellular Calcium-Sensing Receptor

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455126 Year: Pages: 189 DOI: 10.3389/978-2-88945-512-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2019-01-23 14:53:42
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Calcium is vital for human physiology; it mediates multiple signaling cascades, critical for cell survival, differentiation, or death both as first and as second messenger. The role of calcium as first messenger is mediated by the G-protein coupled receptor, the extracellular calcium-sensing receptor (CaSR). The CaSR is a multifaceted molecule that senses changes in the concentration of a wide variety of environmental factors including di- and trivalent cations, amino acids, polyamines, and pH. In calcitropic tissues with obvious roles in calcium homeostasis such as parathyroid, kidney, and bone it regulates circulating calcium concentrations. The germline mutations of the CaSR cause parathyroid disorders demonstrating the importance of the CaSR for the maintenance of serum calcium homeostasis. The CaSR has an important role also in a range of non-calcitropic tissues, such as the intestine, lungs, central and peripheral nervous system, breast, skin and reproductive system, where it regulates molecular and cellular processes such as gene expression, proliferation, differentiation and apoptosis; as well as regulating hormone secretion and lactation.This Research Topic is an overview of the CaSR and its molecular signaling properties together with the various organ systems where it plays an important role. The articles highlight the current knowledge regarding many aspects of the calcitropic and non-calcitropic physiology and pathophysiology of the CaSR.

The Tumor Microenvironment of High Grade Serous Ovarian Cancer

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ISBN: 9783038975540 9783038975557 Year: Pages: 434 DOI: 10.3390/books978-3-03897-555-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology --- Oncology
Added to DOAB on : 2019-02-06 09:22:42
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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.

The Epithelial-to-Mesenchymal Transition (EMT) in Cancer

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ISBN: 9783038427933 9783038427940 Year: Pages: VI, 254 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-04-27 16:09:54
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The epithelial-to-mesenchymal transition (EMT) is a highly dynamic process with multiple transitional states, by which epithelial cells can convert into a mesenchymal phenotype. This process involves loss of cellular adhesion and cellular polarity, and an improvement in migratory and invasive properties. It occurs during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing. It is also involved in tumor progression with metastatic expansion, and plays a major role in resistance to cancer treatment. In cancers, EMT inducers are hypoxia, cytokines and growth factors secreted by the tumor microenvironment, stroma crosstalk, metabolic changes, innate and adaptive immune responses, and treatment with antitumor drugs. Switch in gene expression from epithelial to mesenchymal phenotype is triggered by complex regulatory networks involving transcriptional control, non-coding RNAs, chromatin remodeling and epigenetic modifications, alternative splicing, post-translational regulation, protein stability and subcellular localization. Reversion of EMT, the mesenchymal-to-epithelial transition (MET), affects circulating cancer cells when they reach a desirable metastatic niche to develop secondary tumors. More knowledge and control of EMT to MET is necessary and will be beneficial for patients for cancer treatment. This current Special Issue entitled “Epithelial to Mesenchymal Transition in Cancer” will address these questions.

Circulating Tumor Cells: Finding Rare Events for A Huge Knowledge of Cancer Dissemination

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ISBN: 9783039286980 / 9783039286997 Year: Pages: 366 DOI: 10.3390/books978-3-03928-699-7 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2020-06-09 16:38:57
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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.

Keywords

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

Micro- and Nanofluidics for Bionanoparticle Analysis

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ISBN: 9783039215942 9783039215959 Year: Pages: 138 DOI: 10.3390/books978-3-03921-595-9 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: General and Civil Engineering --- Technology (General)
Added to DOAB on : 2019-12-09 11:49:16
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Bionanoparticles such as microorganisms and exosomes are recoganized as important targets for clinical applications, food safety, and environmental monitoring. Other nanoscale biological particles, includeing liposomes, micelles, and functionalized polymeric particles are widely used in nanomedicines. The recent deveopment of microfluidic and nanofluidic technologies has enabled the separation and anslysis of these species in a lab-on-a-chip platform, while there are still many challenges to address before these analytical tools can be adopted in practice. For example, the complex matrices within which these species reside in create a high background for their detection. Their small dimension and often low concentration demand creative strategies to amplify the sensing signal and enhance the detection speed. This Special Issue aims to recruit recent discoveries and developments of micro- and nanofluidic strategies for the processing and analysis of biological nanoparticles. The collection of papers will hopefully bring out more innovative ideas and fundamental insights to overcome the hurdles faced in the separation and detection of bionanoparticles.

Carbonic Anhydrases and Metabolism

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ISBN: 9783038978008 9783038978015 Year: Pages: 184 DOI: 10.3390/books978-3-03897-801-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-04-25 16:37:17
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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.

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