Investigating Non-apoptotic Cell Death in Cancer PDF Download

Author: Evangelos Giampazolias
Publisher:
ISBN:
Category : Apoptosis
Languages : en
Pages : 0

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Author: Shigekazu Nagata
Publisher: Springer
ISBN: 3319239139
Category : Medical
Languages : en
Pages : 186

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Book Description
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.

Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 228

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The concept of programmed cell death has evolved over the years to include both apoptotic and non-apoptotic death mechanisms. This study describes a novel form of non-apoptotic cell death induced as a result of dysregulated macropinocytosis. We have named this cell death "methuosis". Methuosis is observed when the activated form of Ras GTPase is over-expressed in glioblastoma cells. It is accompanied by the accumulation of large phase-lucent cytoplasmic vacuoles, followed by rounding up, detachment, and disintegration of the cells. The vacuoles quickly take up extracellular fluid-phase tracers, a hallmark of macropinosomes. Our studies also show that the Ras-induced vacuoles are not acidic and are negative for LC3-II (a marker for autophagosomes), transferrin and EEA1 (endosomal markers). These observations rule out the vacuoles originating from autophagosomal, endosomal or lysosomal compartments. Even though caspase activation is observed in dying cells, death is not prevented by zVAD-fmk, a pan caspase inhibitor. Electron microscopy revealed that the dying cells did not show classical signs of apoptosis, like chromatin condensation. These findings indicate that caspase activation is not required for methuosis to occur. Studies performed to decipher the signaling pathway(s) stimulated by Ras revealed that methuosis does not depend on the activation of Raf kinase, PI-3K or RalGDS, the most well-studied Ras signaling intermediates. Interestingly, constitutively active Rac1 induces an identical vacuolar phenotype in glioblastoma cells. Rac1-induced vacuoles are also derived from macropinosomes. We postulate that activated Ras is stimulating Rac GTPase via a unique downstream effector to initiate methuosis in glioblastoma cells. ER stress-initiated apoptosis has recently gained attention as an effective death inducer in cancer cells. This work shows for the first time that the mechanism by which calphostin-C, a photoactivatable inhibitor of protein kinase C, induces apoptosis in cancer cells involves ER stress. Calphostin-C potently reduces the viability of a number of cancer cell lines, including glioblastomas. The cell death induced by cal-C involves accumulation of vacuoles derived from the ER with a concomitant block in the protein trafficking from ER to Golgi. There is a rapid activation of ER stress markers, JNK, PERK, and the induction of pro-apoptotic protein CHOP. Activation of caspases-9 and 7, along with PARP cleavage, is observed following the activation of ER stress signaling. Our studies indicate that apoptosis induced by cal-C has a strong ER-stress component and that this compound has a potential of being exploited as a chemotherapeutic agent for photodynamic therapy.

Author: Holger Kalthoff
Publisher: Springer Science & Business Media
ISBN: 3642030459
Category : Medical
Languages : en
Pages : 286

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Death receptors play a central role in directing apoptosis in mammalian cells. This process of active cell death is important for a number of biological processes, e.g. for the regulation of the immune system. Death receptors are cell surface receptors that transmit apoptotic signals initiated by corresponding death ligands. Many complex signaling pathways are activated and apoptosis is the final result of a complex biochemical cascade of events. Besides their role in the induction of cell death, evidence now exists that death receptors are able to activate several non-apoptotic signaling pathways which, depending on cellular context, may lead to apoptosis resistance, secretion of pro-inflammatory proteins, proliferation and invasive growth of cancer cells. This book looks at the molecular basis of death receptor signaling and the role of death receptors in cancer development.

Author: Douglas R. Green
Publisher:
ISBN: 9781621822141
Category : Science
Languages : en
Pages : 250

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Book Description
One million cells in our bodies die every second--they commit suicide by a mechanism known as apoptosis. Apoptosis is essential for survival of the body as a whole and has critical roles in various developmental processes and the immune system. In Cell Death, Douglas Green provides a clear and comprehensive view of apoptosis and other cell death mechanisms. Taking a bottom-up approach, he starts with the enzymes that perform the execution process (a family of proteases termed caspases) and examines their cellular targets and the ways in which they are activated. He then looks at the molecular machinery that links signals that cause cell death to caspases, emphasizing the importance of the BCL-2 family of proteins and the role of cytochrome c released from mitochondria. The final stage of the process, phagocytic removal of dead or dying cells, is also covered. Green outlines the roles of apoptosis and death mechanisms such as necrosis in embryogenesis, neuronal selection, and the development of self-tolerance in the immune system. In addition, he explains how cell death defends the body against cancer and traces the evolutionary origins of the apoptosis machinery back over a billion years. This new edition contains critical new information on recent exciting advances in the field, such as new forms for cell death and important insights into the mechanisms and control of apoptosis. The book is thus of great use to all biologists interested in how cells function in the context of multicellular organisms and will appeal to everyone from undergraduates encountering the topic for the first time to researchers actively working in the field.

Author: Igor B Roninson
Publisher: CRC Press
ISBN: 9780367386849
Category :
Languages : en
Pages : 376

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Book Description
Addressing a major field of interest for oncologists, cell biologists, and other biomedical researchers, Beyond Apoptosis provides an overview of how different biological mechanisms of cell death, senescence and mitotic catastrophe stop the growth of tumor cells treated with anticancer agents. Written by internationally renowned contributors, this text includes: morphological illustrations, as well as a DVD containing documents and video clips from various time-lapse microscopic studies of cell death and mitotic catastrophe the role and limitations of apoptosis as a determinant of the toxicity of anticancer agents alternative mechanisms of the antiproliferative actions of anticancer drugs and radiation, such as non-apoptotic cell death, cell senescence, and mitotic catastrophe non-apoptotic forms of cell death, such as necrosis, paraptosis, autophagic cell death, and others morphological and kinetic differences of the various forms of cell death

Author: Kazuwa Nakao
Publisher: Springer
ISBN: 4431556516
Category : Science
Languages : en
Pages : 330

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Book Description
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

Author: Han-Ming Shen
Publisher: Springer Science & Business Media
ISBN: 1461482208
Category : Science
Languages : en
Pages : 402

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Book Description
Starting with discussion of basic concepts and the molecular mechanisms of necrosis, this book looks first at several forms of necrotic cell death that have been identified, including necroptosis, autophagic cell death, and PARP-mediated cell death. As necrotic cell death is increasingly known to play a critical role in many physiological processes, the next chapters discuss its effect on metabolism, inflammation, immunity, and development. Necrotic cell death is closely implicated in human diseases like cancer, so the next chapters examine its relevance to human diseases, and final chapters cover methodologies for measuring necrosis. This book presents comprehensive coverage of necrosis from recognized experts from leading academic and medical institutions around the world. ​In contrast to apoptosis, well-defined as a form of programmed cell death, necrosis used to be considered as accidental (i.e., non-programmed) cell death, usually in response to a severe injury. Accumulating evidence now suggests, however, that necrosis is also programmed and controlled by distinctive "death machinery" in response to various stimuli like oxidative stress or DNA damage.

Author: Hanan Dhafer Alqahtani
Publisher:
ISBN:
Category : Cancer
Languages : en
Pages : 87

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Book Description
Cancer is a group of diseases characterized by abnormal features including continuous abnormal growth, uncontrolled cell division, and the ability to spread, invade and destroy surrounding tissues and organs in the body. It is the second most common cause of death in the USA. Therefore, discovering strategies, signaling pathways, and targeted molecules to eliminate cancer cells has been intensively investigated. Cells in multicellular organisms undergo death for many reasons such as senescence and external chemical stimulus. There are many forms of cell death including necrosis, apoptosis, and autophagy, and each form is morphologically, biochemically, and genetically distinct. In addition, each form is activated differently from each other. We are investigating a recently described form of cell death called Ferroptosis that was originally observed in response to the small molecule called Erastin. We hypothesize that Ferroptosis can be exploited to eliminate certain types of tumor cells. In ferroptosis, an iron-dependent form of nonapoptotic cell death, cells die due to the iron-dependent accumulation of Reactive Oxygen Species (ROS). ROS are chemically reactive molecules that contain oxygen, and they are formed naturally as a byproduct of the metabolism of oxygen. We identified a small molecule called 6E that can kill a number of cancer cell lines by Ferroptosis. There are many cellular factors that increase the sensitivity of the cells to be killed by 6E such as activated RAS/MAPK pathway, presence of p53 alleles, iron metal, loss of the epithelial gene E-cadherin, and expressing vimentin the mesenchymal gene. In this thesis we study the mechanism of ferroptosis induced by 6E and related compounds. We tested a number of different cancer cell lines toward 6E. Also we measured the level of glutathione inside the cells, and the level of secreted glutamate after 6E treatment. Also, we tested the effect of the iron chelator CPO and the antioxidant trolox in cell death induced by 6E. Together these experiments suggest that 6E induces ferroptosis by inhibiting XC-, a transport that brings cystine into the cell required to replenish the antioxidant glutathione. We also show that mesenchymal cells are particular sensitive to the 6E precursor molecule. Consistent with these, we find that a number of childhood cancer cell lines derived from mesenchymal tissues are sensitive to 6E.

Author: Michael R. Hamblin
Publisher: Artech House
ISBN: 1596932783
Category : Medical
Languages : en
Pages : 601

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With today's focus on targeted and minimally invasive therapies, photodynamic therapy (PDT) is now being studied and used to combat many disease states and to investigate critical biological questions. This groundbreaking resource brings you the latest advances in photodynamic therapy and offers you a solid understanding of the design, delivery and dosimetry of the three basic ingredients of PDT - photosensitizers, light and oxygen. The book covers novel areas of mechanistic and innovative translational approaches. Moreover, it gives you an overview of the important medical applications of PDT, including approved treatments, clinical trials, and investigated therapies for cancer and non-malignant diseases.