Download or read book Regulation of Human Breast Cancer Cell Death by Sphingolipids written by Chi Zhang and published by . This book was released on 1998 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Sphingolipids in Cancer written by and published by Academic Press. This book was released on 2018-07-27 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sphingolipids in Cancer, Volume 140, the latest release in the Advances in Cancer Research series, provides invaluable information on the exciting and fast-moving field of cancer research. Topics discussed in this updated volume include Mechanisms of ceramide-dependent cancer cell death, Sphingolipids as regulators of autophagy and endocytic trafficking, The role and function of sphingomyelin biosynthesis in the development of cancer, Neutral sphingomyelinases in cancer: Friend or foe?, Sphingolipid rendezvous at the crossroad of NAFLD and senescence, Ceramide signaling and p53 pathways, Sphingolipid regulation of RNA Biology in cancer phenotypes, The role of ceramide-1-phosphate in tumor cell survival and dissemination, and more. Provides information on cancer research, with this release focusing on sphingolipids Offers outstanding and original reviews on a range of cancer research topics Serves as an indispensable reference for researchers and students alike

Download or read book Bioactive Sphingolipids in Cancer Biology and Therapy written by Yusuf A. Hannun and published by Springer. This book was released on 2015-08-28 with total page 491 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents information on both the basic and clinical aspects of sphingolipid-metabolizing enzymes in various cancers. The volume also includes discussions of the innovative techniques and approaches for quantitative analysis and imaging that could significantly impact the general understanding of this topic, and the potential benefit of targeting sphingolipid enzymes to develop novel cancer therapeutics. As well, the volume includes a critical examination of the specific pathways and pathobiologies associated with the altered regulation of sphingolipid metabolism as a contributor to the development and/or maintenance of pathological conditions such as cancer.

Download or read book The Role of Sphingolipids in Cancer Development and Therapy written by and published by Academic Press. This book was released on 2012-12-31 with total page 313 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. This thematic volume looks at "The Role of Sphingolipids in Cancer Development and Therapy" Provides invaluable information on the exciting and fast-moving field of cancer research This thematic volume looks at "The Role of Sphingolipids in Cancer Development and Therapy" Outstanding and original reviews

Download or read book Regulatory Role of Sphingolipid Metabolites in Immunogenic Cancer Cell Death written by Asvelt Nduwumwami and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ability of cancer cells to elicit an antitumor immunity relies on two determining features of immunogenicity: antigenicity and adjuvanticity. Antigenicity, which arises mainly from somatic mutations that form neoantigens, allows endogenous T cells to recognize tumors. Adjuvanticity on the other hand is a consequence of endogenous alarm signals emitted by malignant cells succumbing to immunogenic cell death (ICD) induced by chemotherapeutic or physical agents. These alarm entities include various immunostimulatory molecules such as extracellular ATP and cell surface exposure of the endoplasmic reticulum resident protein calreticulin. They communicate damage or stress and are therefore termed damage associated molecular patterns (DAMPs). DAMPs interact with their cognate receptors on antigen presenting cells (APCs) to drive the maturation and recruitment of APCs to tumor microenvironment, and to promote phagocytosis of dying cancer cells and antigen cross-presentation to naïve T cells, thereby paving the way for adaptive antitumor immunity. The findings presented in this dissertation demonstrate that bioactive sphingolipid metabolites including sphingosine-1-phosphate (S1P) and ceramide regulate processes that are integral to the emission of ICD-associated DAMPs. We show that inhibition of the oncogenic sphingosine kinase (SphK) enhances mitoxantrone-induced ceramide production and results in increased ATP secretion and cell surface exposure of calreticulin. Examination of the isolated plasma membrane lipid raft fraction demonstrated that cell surface calreticulin exists as a disulfide linked dimer in response to ICD induction, suggesting that this structural modification of calreticulin may underlie its ICD-associated immunological function. Pharmacological inhibition and genetic manipulation of enzymes in the sphingolipid metabolic pathway coupled with LC/MS-based sphingolipidomic analyses identified ceramide synthase 6-derived C16 ceramide to be required for the translocation of dimerized calreticulin to the lipid raft microdomain at the plasma membrane. Importantly, we show that agents that induce intracellular ceramide accumulation convert cancer cells into a "vaccine" that elicits an antitumor protection against inoculation of live cancer cells in syngeneic immunocompetent murine models. This ability of ceramide to induce ICD provides an attractive complement to its established direct cytotoxic effects on tumors. While intracellular ceramide accumulation is required for the ICD-associated production of the cell surface calreticulin, we show that SphK1-derived S1P is a stress-induced pro-survival lipid that suppresses ICD. Mechanistically, under ER stress conditions, S1P stabilizes the cellular FADD-like IL-1[beta]-converting enzyme-inhibitory protein (c-FLIP), which suppresses caspase 8-mediated initiation of ICD signaling pathways. These findings indicate that inhibition of sphingosine kinase may represent a means to enhance the therapeutic efficacy of immunogenic cell death-inducing agents, such as mitoxantrone, while reducing their overt toxicity and immunosuppressive effects, leading to better therapeutic outcomes for patients.

Download or read book Chemotherapeutic and Chemopreventive Roles of Sphingolipids in Human Breast Cancer written by Hong Yang and published by . This book was released on 1999 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Regulation of Cell Survival and Motility in Human Breast Cancer Cells by Sphingosine Kinase written by Sarah Spiegel and published by . This book was released on 2002 with total page 104 pages. Available in PDF, EPUB and Kindle. Book excerpt: The sphingolipid metabolite, sphingosine-1-phosphate (S1P) formed by phosphorylation of sphingosine, has been implicated in cell growth, suppression of apoptosis, and angiogenesis. We have examined where increased intracellular S1P produced by overexpression of sphingosine kinase contributes to tumorigenesis of breast adenocarcinoma MCF-7 cells. Sphingosine kinase type 1 (SPHK1) blocks MCF-7 cell death induced by anti-cancer drugs, sphingosine and TNF-alpha. The cytoprotectie effect of SPHK1 was reversed by N, N'-dimethylsphingosine, a specific inhibitor of SPHKs. Enforced expression of SPHK1 in MCF-7 cells also conferred a growth advantage as determined by proliferation and growth in soft agar. Although no changes in estrogen receptor levels could be detected, estrogen antagonists eliminated this growth advantage. EDG-1 is a GPCR for S1P that mediates S1P-directed cell migration and vascular maturation. Cell migration toward PDGF, which stimulates sphingosine kinase and increases S1P levels, was dependent on expression of S1P1/EDG-1, and conversely, deletion of S1P1/EDG-1, inhibition of sphingosine kinase of treatment with pertussis toxin to uncouple Gi-linked receptors suppressed chemotaxis toward PDGF. PDGF indusced tykrosine phosphorylation of focal adhesion proteins, including FAK and Src whereas tyrosine phosphorylation of the PDGFR and ERK activation was unaltered.

Download or read book Starving Cancer written by Manuel U. Ramirez and published by . This book was released on 2017 with total page 177 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sphingolipids are found in all kingdoms of life. In mammals, sphingolipids regulate multiple cellular processes. Ceramide is a sphingolipid of interest to cancer biologists due to its regulation of cell cycle, membrane morphology, cell migration, differentiation, and cell death. Disruptions in ceramide metabolism are associated with disease. Reduced ceramide in cancer cells leads to increased malignancy and metastasis. Conversely, increasing cellular ceramide leads to differentiation, proliferative arrest, and cell death. Our lab has developed synthetic sphingolipids that effectively and selectively induce cancer cell death in vivo. We have recently described one such synthetic sphingolipid, SH-BC-893 (893), that is selective and effective in murine cancer models without notable toxicity to the animal.Our publications show that the selectivity of sphingolipids for cancer cells is due to oncogene-driven constitutive anabolism of cancer cells. Highly anabolic TSC2 knockout cells are resistant to sphingolipid-induced death but are sensitized by expression of oncogenic KRAS.893 inhibits multiple, parallel cellular nutrient acquisition mechanisms. One mechanism is by decreasing surface nutrient transporter expression, an activity shared with the endogenous sphingolipid ceramide. However, 893 further limits nutrient acquisition by reducing lysosomal fusion to prevent access to intracellular metabolites from LDL, autophagosomes, and macropinosomes. These phenotypes were not observed with ceramide.The molecular mechanism through which ceramide and synthetic sphingolipids induce loss of surface nutrient transporters is not yet known. The work presented here suggests that recycling of nutrient transporter proteins is inhibited. We show that actin remodeling, ARF6 inactivation, PKC and Rac1 activation all appear to contribute to sphingolipid-induced nutrient transporter loss. ARF6 inactivation may be downstream of sphingolipid-induced PP2A activation similar to other effects. Preliminary data suggests ARF6 inactivation may result from PP2A-mediated de-phosphorylation of the ARF6 guanine nucleotide exchange factor Grp1, which activates ARF6. Both endogenous sphingolipids and 893 inactivate ARF6. Interestingly, ARF6 activation is associated with tumor progression, grade, and metastasis in multiple cancer classes. We found that combining sphingolipid with ARF6 inhibitors synergistically and selectively kill cancer cells. These findings clarify the mechanism of sphingolipid-induced cell death and identify inactivation of ARF6 playing a role in nutrient transporter loss.

Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Download or read book Sphingolipids as Signaling and Regulatory Molecules written by Charles Chalfant and published by Springer Science & Business Media. This book was released on 2011-01-12 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book attempts to analyze the latest discoveries in sphingolipid biology and how the alteration of their metabolism leads to altered signaling events and to the development of pathobiological disorders, such as cancer, cardiovascular diseases, asthma, diabetes, inflammation and infectious diseases.

Download or read book Sphingolipid Biology written by Y. Hirabayashi and published by Springer Science & Business Media. This book was released on 2007-12-31 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sphingolipids are fundamental to the structures of cell membranes, lipoproteins, and the stratum cornea of the skin. Many complex sphingolipids, as well as simpler sphingoid bases and derivatives, are highly bioactive as extra- and intracellular regulators of growth, differentiation, migration, survival, senescence, and numerous cellular responses to stress. This book reviews exciting new developments in sphingolipid biology/sphingolipidology that challenge our understanding of how multicellular organisms grow, develop, function, age, and die.

Download or read book Apoptotic and Non apoptotic Cell Death written by Shigekazu Nagata and published by Springer. This book was released on 2017-04-07 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on apoptotic and non-apoptotic programmed cell death, including necroptosis, pyroptosis, and ferroptosis, and presents recent findings in the field. It discusses the crucial role that apoptotic and non-apoptotic cell death play in various pathological conditions, such as skin diseases, inflammatory bowel diseases, and virus infections. Further, it highlights the mechanisms underlying the recognition and clearance of dead cells, and the subsequent biological responses triggered by phagocytosed macrophages and factors released from dying cells. Offering insights into cell death, it is a valuable resource for researchers and clinicians developing novel strategies to treat various diseases that are closely associated with cell death.

Download or read book Sphingolipids Basic Science and Drug Development written by Erich Gulbins and published by Springer Science & Business Media. This book was released on 2013-04-11 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sphingolipids are lipid components of the plasma membrane in eukaryotic cells. They have an important function in signaling mechanisms in the cell. This book on sphingolipids provides insights into the basics of sphingolipid biology and drug development, with a particular emphasis on the sphingolipid derivative ceramide. In the first part basic functions of sphingolipids are described, as well as the genetics of important enzymes, sphingolipid metabolism and synthesis. The second part of this first volume focuses on drug development and pharmacology. The book is intended for scientists in pharmacology, biochemistry and cell biology with a focus on biomedical research as well as for clinicians working in pharmacology, oncology, cardiology, neurology and infectious disease. Together with Volume 216 by the same editors, the collection represents a unique, comprehensive work on sphingolipids, providing information on both sphingolipids’ basic biology (including synthesis, metabolism and cell biology) and their important function in a (patho-)physiological context.

Download or read book Ceramide Signaling written by Anthony H. Futerman and published by Springer. This book was released on 2012-11-06 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ceramide Generation 127 Ceramide Targets 129 Ceramide Function 129 Therapeutic Implications 130 Concluding Remarks 130 14. Ceramide Glycosylation and Chemotherapy Resistance 133 Myles C. Cabot 15. Ceramide in Serum Lipoproteins: Function and Regulation of Metabolism 141 Mariana N. Nikolova-Karakashian Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Int roduction 141 Ceramide is a Component ofSerum Lipoproteins 142 Secretion of Ceramide in the Form ofVLOL by the Liver 142 Generation of Ceramide in LOL Particles 143 Biological Consequences of Elevation of Ceramide Concentrations in LDL 145 Conclusions and Future Directions 147 16. T herapeutic Implications of Ceramide-Regulated Signaling Cascades 149 Mark Kester, fongK Yun, Tom Stover andLakshman Sandirasegarane Abstract 149 The Bench-Ceramides and Signaling Cascades 149 The Bedside-Ceramides and Cardiovascular Disease 150 The Bedside-Ceramides and Cancer 153 The Bedside-Other Potential Applications for Ceramide-Based Therapeutics 155 Conclusions-Back to the Bench 155 Index 161 EDITOR ====================;-t Anthony H. Futerman, PhD Department of Biological Chemistry Weizmann Institute of Science Rehovot, Israel email: tony. futerman@Weizmann. ac. iI Chapter 11 I===========CONTRIBUTORS==========~ JeremyC. Allegood Myles C. Cabot Schoolof Biology John Wayne Cancer Institute Petit Institute for Bioengineering SantaMonica, California, U. S. A. and Biosciences email: cabot@jwci. org GeorgiaInstitute of Technology Chapter 14 Atlanta, Georgia, U. S. A. Chapter 1 Charles E. Chalfant Department of Biochemistry Lindsay Andras and Molecular Biology Schoolof Biology Medical University of South Carolina Petit Institute for Bioengineering Charleston, South Carolina, U. S. A. and Biosciences email: chalfant@musc. edu Georgia Institute of Technology Chapter 6 Atlanta, Georgia, U. S. A.

Download or read book Lipids in Health and Disease written by Peter Quinn and published by Springer Science & Business Media. This book was released on 2008-08-27 with total page 603 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lipids are functionally versatile molecules. They have evolved from relatively simple hydrocarbons that serve as depot storages of metabolites and barriers to the permeation of solutes into complex compounds that perform a variety of signalling functions in higher organisms. This volume is devoted to the polar lipids and their constituents. We have omitted the neutral lipids like fats and oils because their function is generally to act as deposits of metabolizable substrates. The sterols are also outside the scope of the present volume and the reader is referred to volume 28 of this series which is the subject of cholesterol. The polar lipids are comprised of fatty acids attached to either glycerol or sphingosine. The fatty acids themselves constitute an important reservoir of substrates for conversion into families of signalling and modulating molecules including the eicosanoids amongst which are the prostaglandins, thromboxanes and leucotrienes. The way fatty acid metabolism is regulated in the liver and how fatty acids are desaturated are subjects considered in the first part of this volume. This section also deals with the modulation of protein function and inflammation by unsaturated fatty acids and their derivatives. New insights into the role of fatty acid synthesis and eicosenoid function in tumour progression and metastasis are presented.

Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.

Download or read book Natural Products for Cancer Prevention and Therapy written by Anupam Bishayee and published by MDPI. This book was released on 2018-11-07 with total page 285 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Natural Products for Cancer Prevention and Therapy" that was published in Nutrients