Cancer Leading Proteases

Cancer Leading Proteases
Author: Satya Prakash Gupta
Publsiher: Academic Press
Total Pages: 526
Release: 2020-02-03
ISBN: 0128181680
Category: Business & Economics
Language: EN, FR, DE, ES & NL

Cancer Leading Proteases Book Excerpt:

Cancer-Leading Proteases: Structures, Functions, and Inhibition presents a detailed discussion on the role of proteases as drug targets and how they have been utilized to develop anticancer drugs. Proteases possess outstanding diversity in their functions. Because of their unique properties, proteases are a major focus of attention for the pharmaceutical industry as potential drug targets or as diagnostic and prognostic biomarkers. This book covers the structure and functions of proteases and the chemical and biological rationale of drug design relating to how these proteases can be exploited to find useful chemotherapeutics to fight cancers. In addition, the book encompasses the experimental and theoretical aspects of anticancer drug design based on proteases. It is a useful resource for pharmaceutical scientists, medicinal chemists, biochemists, microbiologists, and cancer researchers working on proteases. Explains the role of proteases in the biology of cancer Discusses how proteases can be used as potential drug targets or as diagnostic and prognostic biomarkers Covers a wide range of cancers and provides detailed discussions on protease examples

The Cancer Degradome

The Cancer Degradome
Author: Dylan Edwards,Gunilla Hoyer-Hansen,Francesco Blasi,B.F. Sloane
Publsiher: Springer Science & Business Media
Total Pages: 926
Release: 2008-09-16
ISBN: 0387690573
Category: Medical
Language: EN, FR, DE, ES & NL

The Cancer Degradome Book Excerpt:

This book covers recent knowledge of the composition of the Degradome, how it can be studied using modern approaches such as transcriptomics and mass spectrometry; and many other relevant subjects, including new approaches to targeting proteolysis for therapy.

Proteases and Their Inhibitors in Cancer Metastasis

Proteases and Their Inhibitors in Cancer Metastasis
Author: J-M. Foidart,R.J. Muschel
Publsiher: Springer Science & Business Media
Total Pages: 256
Release: 2002
ISBN: 9781402009235
Category: Medical
Language: EN, FR, DE, ES & NL

Proteases and Their Inhibitors in Cancer Metastasis Book Excerpt:

In recent years, serine proteases and matrix metalloproteinases (MMPs) have gained considerable attention in tumor biology. For most of these proteases, their expression is a reliable indication of ongoing tissue remodeling. This book provides a comprehensive evaluation of the mechanisms of action of proteases and their inhibitors in tumor biology. The first part provides the reader with a selective overview of the molecular biology of serine proteases, MMPs and their physiological inhibitors. The most important proteases and their physiological as well as synthetic inhibitors are evaluated in the most relevant models of experimental and human cancer. The clinical aspects are also taken into account. This volume offers an update on this challenging aspect of cancer treatment, its interest bias, and possible clinical implication.

Matrix Proteases in Health and Disease

Matrix Proteases in Health and Disease
Author: Niels Behrendt
Publsiher: John Wiley & Sons
Total Pages: 416
Release: 2012-07-10
ISBN: 3527329919
Category: Science
Language: EN, FR, DE, ES & NL

Matrix Proteases in Health and Disease Book Excerpt:

Presenting a comprehensive overview of the multifaceted field of proteases in the extracellular matrix environment, this reference focuses on the recently elucidated functions of complex proteolytic systems in physiological and pathological tissue remodeling. The proteases treated include both serine proteases such as plasminogen activators and TTSPs, metalloproteases such as MMPs and ADAMS and cysteine protease cathepsins. The text specifically addresses the role of extracellular proteases in cancer cell invasion, stroke and infectious diseases, describing the basic biochemistry behind these disease states, as well as therapeutic strategies based on protease inhibition. With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.

Functional Imaging of Cysteine Proteases in Cancer and Inflammation Using Novel Activity based Probes

Functional Imaging of Cysteine Proteases in Cancer and Inflammation Using Novel Activity based Probes
Author: Laura Elizabeth Edgington
Publsiher: Unknown
Total Pages: 135
Release: 2012
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Functional Imaging of Cysteine Proteases in Cancer and Inflammation Using Novel Activity based Probes Book Excerpt:

Cysteine proteases use a catalytic thiol to cleave amide bonds of protein substrates. This activity serves as an important regulatory mechanism for diverse cellular processes necessary for normal physiology. Dysregulated protease activity is a hallmark of numerous diseases, including atherosclerosis, arthritis, stroke, macular degeneration, neurodegenerative disorders, inflammatory diseases, and cancer. In the last decades, the field of activity-based proteomics has produced a number of tools for dissecting protease function. In the introductory chapter, I will discuss the current state of the field and describe the two main classes of probes for cysteine proteases: substrate-based and activity-based probes. I will then describe my own contribution to the field, which includes the design and characterization of several new and improved activity-based probes. We have applied these probes to optical imaging and biochemical characterization of three families of cysteine proteases: caspases, cathepsins and legumain. In particular, I have used these tools to aid in understanding the regulation of complex signaling pathways associated with cancer and inflammation. Caspases are key mediators of a programmed form of cell death called apoptosis. One of the key features of tumor cells is their ability to evade apoptosis, and therefore, a major therapeutic goal is to reactivate latent death pathways. We have developed fluorescent activity-based probes to image the induction of caspase activity in tumors in response to chemotherapy. In addition to non-invasive optical imaging, we have utilized these new probes to assess the kinetics of caspase activation in response to various death stimuli and identified a unique activation mechanism for the caspase-6 enzyme. Another emerging hallmark of cancer is infiltration of stromal-derived immune cells into the tumor, resulting in an inflammatory microenvironment. Crosstalk between tumor and immune cells can lead to enhanced proliferation, angiogenesis, and metastasis of tumor cells. The cysteine proteases legumain and cathepsins have been shown to play critical roles within the tumor microenvironment. I have developed new tools for optical imaging of their proteolytic activity in several cancer models as well as inflammation associated with pancreatitis. In the future, these new probes will have great value in further dissecting the roles of cysteine proteases in basic biology and disease. Since legumain and cathepsins are used as biomarkers for cancer, the ability to detect their proteolytic activity has much diagnostic and prognostic value in both pre-clinical and clinical settings. Furthermore, these new agents will be integral in validating these enzymes, particularly legumain, as drug targets.

Proteases in Human Diseases

Proteases in Human Diseases
Author: Sajal Chakraborti,Tapati Chakraborti,Naranjan S. Dhalla
Publsiher: Springer
Total Pages: 513
Release: 2017-07-13
ISBN: 9811031622
Category: Medical
Language: EN, FR, DE, ES & NL

Proteases in Human Diseases Book Excerpt:

This book bridges the gap between fundamental research and biomedical and pharmacological applications on proteases. It represents a comprehensive overview of the multifaceted field of proteases in cellular environment and highlights the recently elucidated functions of complex proteolytic systems in different diseases. Several established investigators have elucidated the crucial role of proteases in biological processes, including how proteolytic function and regulation can be combined to develop new strategies of therapeutic interventions. Proteases form one of the largest and most diverse families of enzymes known. It is now clear that proteases are involved in every aspect of life functions of an organism. Under physiological conditions, proteases are regulated by their endogenous inhibitors; however, when the activity of proteases is not regulated appropriately, disease processes can result in. So, there is absolute need for a stringent control of proteolytic activities in cells and tissues. Dysregulation of proteases may cause derangement of cellular signalling network resulting in different pathophysiological conditions such as vascular remodelling, atherosclerotic plaque progression, ulcer and rheumatoid arthritis, Alzheimer disease, cancer metastasis, tumor progression and inflammation. Additionally, many infective microorganisms require proteases for replication or use proteases as virulence factors, which have facilitated the development of protease-targeted therapies for a variety of parasitic diseases.

Determining Gene Expression Substrate Specifically and Natural Substrates for Prostate Associated Proteases

Determining Gene Expression  Substrate Specifically and Natural Substrates for Prostate Associated Proteases
Author: Anonim
Publsiher: Unknown
Total Pages: 26
Release: 2001
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Determining Gene Expression Substrate Specifically and Natural Substrates for Prostate Associated Proteases Book Excerpt:

Numerous studies have shown that proteolytic enzymes play an essential role in tumor invasion, metastasis and angiogenesis (1,2, 3). Proteases may enhance these processes through the release and/or activation of growth factors and the degradation of extracellular matrix. Thus, inhibition of these protease-mediated processes may be a therapeutic strategy for the treatment of metastatic cancer. Indeed, proteases, in general, have proven to be excellent chemotherapeutic targets as evidenced by the HIV protease inhibitors and the large number of successful clinical trials involving protease inhibitors (4). This proposal focused upon serine proteases of the chymotrypsin fold due to the wealth of information that exists on structure-function relationships regarding this class of enzymes and the existence of potent and specific inhibitors that are readily available for their inhibition. In addition, understanding of the function of these proteases may lead to further insight into cancer biology and may lead to possible therapeutics. In particular, we proposed to understand serine protease function by identifying serine protease substrates and substrate specificity. These techniques used and developed should become increasingly useful as the Human Genome Project continues to provide numerous serine protease genes whose products have no known function. These studies should be generalizable to other classes of proteases and to other enzymes such as kinases. In addition, perhaps a greater understanding of prostate and prostate cancer biology can be gained by examining the interaction of the proteases and downstream substrates within a tumor tissue and during various stages of cancer.

Anticancer Agents Based on a New Class of Transition State Analog Inhibitors for Serine and Cysteine Proteases

Anticancer Agents Based on a New Class of Transition  State Analog Inhibitors for Serine and Cysteine Proteases
Author: Anonim
Publsiher: Unknown
Total Pages: 102
Release: 1999
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Anticancer Agents Based on a New Class of Transition State Analog Inhibitors for Serine and Cysteine Proteases Book Excerpt:

In this Final Report we describe our efforts over the last four years to develop a new class of competitive inhibitors for serine and cysteine proteases. These compounds are potential anticancer agents that would act by inhibiting metastasis and angiogenesis. Our work has shown that the 4-heterocyclohexanone pharmacophore can be used to synthesize effective inhibitors of both serine and cysteine proteases. We have rationally designed an inhibitor of the serine protease plasmin, and shown that it has good activity and specificity for plasmin over other proteases. In addition, we have used the 4- heterocyclohexanone pharmacophore to construct a combinatorial library of 400 different protease inhibitors. These compounds are unique in that they are designed to interact with both the S and S' binding sites of proteases; a feature which will increase both their potency and specificity. The library was screened against a variety of cancer-related proteases, which lead us to identify a second, even more potent inhibitor of plasmin. Finally, our investigations into the mechanism of action of these inhibitors has shown that 4-heterocyclohexanones inhibit the proteases be reacting in a reversible covalent manner with the active site nucleophile of the enzymes.

Development of Phosphoramidate Inhibitors for Cell Surface Proteases in Metastatic Cancers

Development of Phosphoramidate Inhibitors for Cell Surface Proteases in Metastatic Cancers
Author: Desiree Ellene Mendes
Publsiher: Unknown
Total Pages: 142
Release: 2016
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Development of Phosphoramidate Inhibitors for Cell Surface Proteases in Metastatic Cancers Book Excerpt:

The development of highly tuned diagnostic agents are critical for the early detection of cancer and are commonly designed to bind cell surface receptors. A small library of first-generation phosphoramidate inhibitors leading to sub-micromolar potency as determined by a FRET-based spectrophotometric assay were generated as peptide mimics with a scaffold designed to interact with the S1, S1` register of the catalytic domain of the cell surface receptor matrix metalloproteinase (MMP-14). Candidate residues were selected for the scaffold using in silico modeling, and synthesized using organophosphate and peptide coupling methodologies. A phosphoramidate inhibitor and fluorescent conjugate were shown to specifically target prostate specific membrane antigen (PSMA) in human cancer cell lines was applied to a canine model of which the expression and enzymatic activity of PSMA were previously unknown. The expression of PSMA was determined by RT-PCR and western blot and found to be in lower abundance when compared to human prostate cancer PSMA expression. The kinetics of PSMA were established and inhibitory potency was determined by an end-point HPLC analysis, and was similar to that of human PSMA enzymatic activity. In addition, a fluorescent-conjugate was successfully used to label canine cancer cells in blood as detected using flow cytometry. Previous studies revealed that both PSMA and androgen receptor (AR) decreased following an extended period of androgen deprivation. When the biomarker expression of c-Met and calpain 2 are upregulated, it indicated a switch to a more aggressive prostate cancer phenotype. The expression of these biomarkers in prostate cancer cell lines subjected to prolonged androgen deprivation in an established in vitro model were investigated. After 10 passages of prolonged androgen deprivation, both c-Met and calpain 2 were found to be upregulated with the concomitant decrease in expression of PSMA and AR. In addition to switching signaling pathways, prostate cancer cells secrete exosomes as long-range cell-to-cell communication vehicles. The exosomes were found to be highly enriched with functionally active PSMA. Insights into inhibitor binding, signaling pathway alterations, and biomarker expression in extracellular vesicles could enable new trajectories for treatment and further the advancement toward powerful development of personalized cancer therapy.

Determining Gene Expression Substrate Specificity and Natural Substrates for Prostate Associated Proteases

Determining Gene Expression  Substrate Specificity and Natural Substrates for Prostate Associated Proteases
Author: Anonim
Publsiher: Unknown
Total Pages: 48
Release: 2000
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Determining Gene Expression Substrate Specificity and Natural Substrates for Prostate Associated Proteases Book Excerpt:

We work on serine proteases of the chymotrypsin fold due to the wealth of information that exists on structure-function relationships regarding this class of enzymes and the existence of potent and specific inhibitors that are readily available for their inhibition. In addition, understanding of the function of these proteases may lead to further insight into cancer biology and may lead to possible therapeutics. We have focused upon an enzyme known as membrane-type serine protease 1 (MT-SPl)that has been implicated in prostate cancer. During our first funding year, we have determined the in vitro cleavage substrate specificity of the enzyme using positional-scanning combinatorial libraries and substrate phage display. The preferred cleavage sequences were found to be ?P4-(Arg/Lys) P3-(X) P2-(Ser) Pl-(Arg) Pl'-(Ala)) and (P4-(X) P3-(Arg/Lys) P2-(Ser) Pi (Arg) Pi (Ala) Z where X is a non-basic amino acid. We have also identified two macromolecular substrates, single-chain urokinase-type plasminogen activator (sc-uPA) and protease activated receptor 2 (PAR2) . The affinity of MT-SPl for these key extracellular targets suggests an important role in pathological and regulatory events such as tumor cell invasion and metastasis.

Proteases in Gastrointestinal Tissues

Proteases in Gastrointestinal Tissues
Author: Uwe Lendeckel,Nigel M. Hooper
Publsiher: Springer Science & Business Media
Total Pages: 343
Release: 2006-01-18
ISBN: 9781402044823
Category: Medical
Language: EN, FR, DE, ES & NL

Proteases in Gastrointestinal Tissues Book Excerpt:

This book is unique for its comprehensive presentation of protease function in the stomach, colon, pancreas and liver under both physiological conditions and major diseases manifesting in these four organs. The individual chapters have been written by leaders in the field who outline in great detail the role of proteases in the pathogenesis, diagnosis and treatment of disease. Animal models and experimental data are discussed in the context of patient-derived data.

Liquid Biopsies of Solid Tumors

Liquid Biopsies of Solid Tumors
Author: Madumali Kalubowilage
Publsiher: Unknown
Total Pages: 135
Release: 2017
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Liquid Biopsies of Solid Tumors Book Excerpt:

Cancer is a group of diseases that are characterized by uncontrolled growth and spread of cells. In order to treat cancer successfully, it is important to diagnose cancers in their early stages, because survival often depends on the stage of cancer detection. For that purpose, highly sensitive and selective methods must be developed, taking advantage of suitable biomarkers. The expression levels of proteases differ from one cancer type to the other, because different cancers arise from different cell types. According to the literature, there are significant differences between the protease expression levels of cancer patients and healthy people, because solid tumors rely on proteases for survival, angiogenesis and metastasis. Development of fluorescence-based nanobiosensors for the early detection of pancreatic cancer and non-small-cell lung cancer is discussed in this thesis. The nanobiosensors are capable of detecting protease/arginase activities in serum samples over a broad range. The functionality of the nanobiosensor is based on Förster resonance energy transfer and surface energy transfer mechanisms. The nanobiosensors for protease detection feature dopamine-coated Fe/Fe3O4 nanoparticles, consensus (cleavage) peptide sequences, meso-tetra(4-carboxyphenyl)porphine (TCPP), and cyanine 5.5. The consensus peptide sequences were synthesized by solid-supported peptide synthesis. In this thesis, improved consensus sequences were used, which permit faster synthesis and higher signal intensities. TCPP, which is the fluorophore of the nanoplatform, was connected to the N-terminal end of the oligopeptides while it was still on the resin. After the addition of TCPP, the TCPP-oligopeptide was cleaved off the resin and linked to the primary amine groups of Fe/Fe3O4-bound via a stable amide bond. In the presence of a particular protease, the consensus sequences attached to the nanoparticle can be cleaved and release TCPP to the aqueous medium. Upon releasing the dye, the emission intensity increases significantly and can be detected by fluorescence spectroscopy or, similarly, by using a fluorescence plate reader. In sensing of arginase, posttranslational modification of the peptide sequence will occur, transforming arginine to ornithine. This changes the conformational dynamics of the oligopeptide tether, leading to the increase of the TCPP signal. This is a highly selective technology, which has a very low limit of detection (LOD) of 1 x 10−16 molL−1 for proteases and arginase. The potential of this nanobiosensor technology to detect early pancreatic and lung cancer was demonstrated by using serum samples, which were collected from patients who have been diagnosed with pancreatic cancer and non-small cell lung cancer at the South Eastern Nebraska Cancer Center (lung cancer) and the University of Kansas Cancer Center (pancreatic cancer). As controls, serum samples collected from healthy volunteers were analyzed. In pancreatic cancer detection, the protease/arginase signature for the detection of pancreatic adenocarcinomas in serum was identified. It comprises arginase, MMPs -1, - 3, and -9, cathepsins -B and -E, urokinase plasminogen activator, and neutrophil elastase. For lung cancer detection, the specificity and sensitivity of the nanobiosensors permit the accurate measurements of the activities of nine signature proteases in serum samples. Cathepsin -L and MMPs-1, -3, and -7 permit detecting non-small-cell lung-cancer at stage 1.

Autophagy

Autophagy
Author: Jessica L. Schwartz-Roberts,Robert Clarke
Publsiher: Elsevier Inc. Chapters
Total Pages: 440
Release: 2013-09-03
ISBN: 0128069449
Category: Medical
Language: EN, FR, DE, ES & NL

Autophagy Book Excerpt:

Autophagy is a major catabolic process used by cells to remove superfluous or damaged proteins and organelles. In the final stages of autophagy, acidic organelles (lysosomes) act to degrade autophagic cargo and to facilitate their recycling. Little is known about how cancer cells undergoing autophagy, often as a consequence of stress, respond when lysosomal function is blocked. To elucidate this mechanism, several recent studies report that lysosomes and their hydrolytic proteases (cathepsins) play a critical role in autophagy and subsequent cancer progression. Our studies in breast cancer suggest that inhibition of cathepsins D and L using the BH3-mimetic, obatoclax, is effective in reducing the cell density of anti-estrogen sensitive and resistant breast cancer cells. Furthermore, blockage of cathepsin protein expression with obatoclax leads to the accumulation of autophagic vacuoles and impairs the ability of cells to use degraded material to restore homeostasis. While cancer cells are dependent on effective lysosomal function, neoplastic transformation induces changes in lysosomal volume, number, and protease activity. Recent reports suggest that pro-oncogenic changes render cancer cells more susceptible to lysosomal-associated death pathways. A number of distinct stimuli have been shown to permeabilize the lysosomal membrane, leading to the release of hydrolases into the cytosol and, ultimately, cell death. Thus, changes in cathepsin and lysosomal membrane permeabilization (LMP) regulation during cancer cell progression suggest that strategies targeting this cellular compartment may be exploited to improve outcomes for cancer patients.

Pathophysiological Aspects of Proteases

Pathophysiological Aspects of Proteases
Author: Sajal Chakraborti,Naranjan S. Dhalla
Publsiher: Springer
Total Pages: 671
Release: 2017-11-15
ISBN: 9811061416
Category: Medical
Language: EN, FR, DE, ES & NL

Pathophysiological Aspects of Proteases Book Excerpt:

This book provides a comprehensive overview of the multifaceted field of protease in the cellular environment and focuses on the recently elucidated functions of complex proteolytic systems in physiology and pathophysiology. Given the breadth and depth of information covered in the respective contributions, the book will be immensely useful for researchers working to identify targets for drug development. Multidisciplinary in scope, the book bridges the gap between fundamental and translational research, with applications in the biomedical and pharmaceutical industry, making it a thought-provoking read for basic and applied scientists engaged in biomedical research. Proteases represent one of the largest and most diverse families of enzymes known, and we now know that they are involved in every aspect of a given organism’s life functions. Under physiological conditions, proteases are regulated by their endogenous inhibitors. However, when the activity of proteases is not correctly regulated, disease processes such as tumour progression, vascular remodelling, atherosclerotic plaque progression, ulcer, rheumatoid arthritis, Alzheimer’s disease and inflammation can result. Many infective microorganisms require proteases for replication or use them as virulence factors, which has facilitated the development of protease-targeted therapies for a variety of parasitic diseases.

Proteases as Targets for Therapy

Proteases as Targets for Therapy
Author: M. Abdel-Meguid,Klaus von der Helm,Bruce D. Korant,John Chris Dion Cheronis
Publsiher: Springer Science & Business Media
Total Pages: 410
Release: 2000
ISBN: 9783540661184
Category: Medical
Language: EN, FR, DE, ES & NL

Proteases as Targets for Therapy Book Excerpt:

This volume is the first to combine latest information on viral, microbial and cellular proteolytic enzymes as potential targets for human therapeutics. Proteases control a large array of physiological reactions, and are involved in a variety of pathological processes for which effective medications are currently needed and/or being sought after. Although protease inhibitors have been investigated for many years, few have been employed therapeutically. Recent break- through by HIV protease inhibitors as therapeutic drugs has re-encouraged the search for inhibitors of other proteolytic enzymes. Klaus von der Helm, who described the first viral protease has brought leading experts together to discuss not only the success and problems of clinical use and continuing prospects, but to review further potential drug targets. This volume provides detailed information and evaluations of key viral, bacterial, fungal, and cellular proteases as potential future drug candidates.

Peptide based Biomaterials

Peptide based Biomaterials
Author: Mustafa O. Guler
Publsiher: Royal Society of Chemistry
Total Pages: 487
Release: 2020-11-26
ISBN: 1839161159
Category: Science
Language: EN, FR, DE, ES & NL

Peptide based Biomaterials Book Excerpt:

Research and new tools in biomaterials development by using peptides are currently growing, as more functional and versatile building blocks are used to design a host of functional biomaterials via chemical modifications for health care applications. It is a field that is attracting researchers from across soft matter science, molecular engineering and biomaterials science. Covering the fundamental concepts of self-assembly, design and synthesis of peptides, this book will provide a solid introduction to the field for those interested in developing functional biomaterials by using peptide derivatives. The bioactive nature of the peptides and their physical properties are discussed in various applications in biomedicine. This book will help researchers and students working in biomaterials and biomedicine fields and help their understanding of modulating biological processes for disease diagnosis and treatments.

Encyclopedia of Cancer

Encyclopedia of Cancer
Author: Manfred Schwab
Publsiher: Springer Science & Business Media
Total Pages: 3235
Release: 2008-09-23
ISBN: 3540368477
Category: Medical
Language: EN, FR, DE, ES & NL

Encyclopedia of Cancer Book Excerpt:

This comprehensive encyclopedic reference provides rapid access to focused information on topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. With an A-Z format of over 7,000 entries, more than 1,000 contributing authors provide a complete reference to cancer. The merging of different basic and clinical scientific disciplines towards the common goal of fighting cancer makes such a comprehensive reference source all the more timely.

The Role of Force Generation in Metastatic Cancer Progression

The Role of Force Generation in Metastatic Cancer Progression
Author: Casey Marie Kraning-Rush
Publsiher: Unknown
Total Pages: 205
Release: 2013
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

The Role of Force Generation in Metastatic Cancer Progression Book Excerpt:

Metastasis, or the process by which cancer cells escape a primary tumor and travel through the body to form secondary tumors, is believed to be responsible for over 90% of the 7.9 million annual cancer-related fatalities reported worldwide. To migrate from the original tumor, cancer cells must navigate an extremely dense and heterogeneous stromal environment to arrive at a blood or lymph vessel, which they can then penetrate to enter the circulatory or lymphatic system. Each of these steps requires cells to pull on its matrix using contractile, or traction, forces. However, the precise relationship of force generation to metastatic cell structure and function remains largely unknown. Herein, I demonstrate that metastatic cells exert increased contractile forces which facilitate the invasion of the extracellular microenvironment (ECM). Using traction force microscopy, I show that human metastatic breast, prostate, and lung cancer cell lines exhibit increased traction stresses compared to non-metastatic counterparts on physiologically-relevant substrates. Additionally, I find that the increased collagen density and matrix stiffness previously shown to be a hallmark of the tumor microenvironment promote increased traction forces through cell spread area-dependent and independent mechanisms. Finally, I develop a novel 3D model for one mode of metastatic migration in which secondary cancer cells follow microtracks that are formed by leading tumor cells secreting proteases and cleaving ECM fibers. iii By using physiologically relevant 3D collagen channels to study cancer cell migration, I specifically assessed the role of force in protease-independent migration, and, surprisingly, found that contractile force was dispensable for this form of protease independent migration. Instead, my results point to focal adhesion, actin filaments, and microtubules being key mediators of protease-independent migration within patterned collagen microtracks. Ultimately, these studies help to define the role that cellular force generation plays in metastatic invasion, and also yield insight into the biophysical mechanisms that tumor cells use to migrate. These insights could potentially lead to a targeted therapeutic approach to combating those mechanisms to delay or prevent metastasis and its subsequent fatal damage. iv.

Redox and Metabolic Circuits in Cancer

Redox and Metabolic Circuits in Cancer
Author: Salvatore Rizza,Andrea Rasola,Danyelle M. Townsend,Giuseppe Filomeni
Publsiher: Frontiers Media SA
Total Pages: 135
Release: 2018-12-21
ISBN: 2889456358
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Redox and Metabolic Circuits in Cancer Book Excerpt:

Living cells require a constant supply of energy for the orchestration of a variety of biological processes in fluctuating environmental conditions. In heterotrophic organisms, energy mainly derives from the oxidation of carbohydrates and lipids, whose chemical bonds breakdown allows electrons to generate ATP and to provide reducing equivalents needed to restore the antioxidant systems and prevent from damage induced by reactive oxygen and nitric oxide (NO)-derived species (ROS and RNS). Studies of the last two decades have highlighted that cancer cells reprogram the metabolic circuitries in order to sustain their high growth rate, invade other tissues, and escape death. Therefore, this broad metabolic reorganization is mandatory for neoplastic growth, allowing the generation of adequate amounts of ATP and metabolites, as well as the optimization of redox homeostasis in the changeable environmental conditions of the tumor mass. Among these, ROS, as well as NO and RNS, which are produced at high extent in the tumor microenvironment or intracellularly, have been demonstrated acting as positive modulators of cell growth and frequently associated with malignant phenotype. Metabolic changes are also emerging as primary drivers of neoplastic onset and growth, and alterations of mitochondrial metabolism and homeostasis are emerging as pivotal in driving tumorigenesis. Targeting the metabolic rewiring, as well as affecting the balance between production and scavenging of ROS and NO-derived species, which underpin cancer growth, opens the possibility of finding selective and effective anti-neoplastic approaches, and new compounds affecting metabolic and/or redox adaptation of cancer cells are emerging as promising chemotherapeutic tools. In this Research Topic we have elaborated on all these aspects and provided our contribution to this increasingly growing field of research with new results, opinions and general overviews about the extraordinary plasticity of cancer cells to change metabolism and redox homeostasis in order to overcome the adverse conditions and sustain their “individualistic” behavior under a teleonomic viewpoint.

The Role of Resveratrol and Its Analogs in Inflammation Preadipocyte Differentiation Neuroblastoma Differentiation

The Role of Resveratrol and Its Analogs in Inflammation  Preadipocyte Differentiation   Neuroblastoma Differentiation
Author: Priti S. Tiwari
Publsiher: Unknown
Total Pages: 149
Release: 2014
ISBN: 1928374650XXX
Category: Cancer
Language: EN, FR, DE, ES & NL

The Role of Resveratrol and Its Analogs in Inflammation Preadipocyte Differentiation Neuroblastoma Differentiation Book Excerpt: