Molecular mechanisms of cellular stress responses in cancer and their therapeutic implications

Author: Megan Chircop
Publisher: Frontiers Media SA
ISBN: 2889194965
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In response to stress, cells can activate a myriad of signalling pathways to bring about a specific cellular outcome, including cell cycle arrest, DNA repair, senescence and apoptosis. This response is pivotal for tumour suppression as all of these outcomes result in restriction of the growth and/or elimination of damaged and pre-malignant cells. Thus, a large number of anti-cancer agents target specific components of stress response signalling pathways with the aim of causing tumour regression by stimulating cell death. However, the efficacy of these agents is often impaired due to mutations in genes that are involved in these stress-responsive signalling pathways and instead the oncogenic potential of a cell is increased leading to the initiation and/or progression of tumourigenesis. Moreover, these genetic defects can increase or contribute to resistance to chemotherapeutic agents and/or radiotherapy. Modulating the outcome of cellular stress responses towards cell death in tumour cells without affecting surrounding normal cells is thus one of the ultimate aims in the development of new cancer therapeutics. To achieve this aim, a detailed understanding of cellular stress response pathways and their aberrations in cancer is required. This Research topic aims to reflect the broadness and complexity of this important area of cancer research.

Endoplasmic Reticulum Stress Response and Transcriptional Reprogramming

Author: Kezhong Zhang
Publisher: Frontiers Media SA
ISBN: 2889194361
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Endoplasmic reticulum (ER) is an intracellular organelle responsible for protein folding and assembly, lipid and sterol biosynthesis, and calcium storage. A number of biochemical, physiological, or pathological stimuli can interrupt protein folding process, causing accumulation of unfolded or misfolded proteins in the ER lumen, a condition called “ER stress”. To cope with accumulation of unfolded or misfolded proteins, the ER has evolved a group of signaling pathways termed “Unfolded Protein Response (UPR)” or “ER stress response” to align cellular physiology. To maintain ER homeostasis, transcriptional regulation mediated through multiple UPR branches is orchestrated to increase ER folding capacity, reduce ER workload, and promote degradation of misfolded proteins. In recent years, accumulating evidence suggests that ER stress-triggered transcriptional reprogramming exists in many pathophysiological processes and plays fundamental roles in the initiation and progression of a variety of diseases, such as metabolic disease, cardiovascular disease, neurodegenerative disease, and cancer. Understanding effects and mechanisms of ER stressassociated transcriptional reprogramming has high impact on many areas of molecular genetics and will be particularly informative to the development of pharmacologic avenues towards the prevention and treatment of modern common human diseases by targeting the UPR signaling. For these reasons, ER stress response and transcriptional reprogramming are a timely and necessary topic of discussion for Frontiers in Genetics. The important topics in this area include but not limited to: (1) ER-resident transcription factors and their involvements in ER stress response and cell physiology; (2) Physiologic roles and molecular mechanisms of ER stress-associated transcriptional regulation in lipid and glucose metabolism; (3) In vitro and in vivo models for ER stress-associated transcriptional reprogramming; (4) ER stress-associated transcriptional regulation in human disease; (5) Therapeutic potentials by targeting ER stress response pathways.

Cancer Microenvironment and Therapeutic Implications

Author: Gianfranco Baronzio
Publisher: Springer Science & Business Media
ISBN: 1402095767
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In the post-genomic era, cancer is a genetic disease. However, cancer genotype does not always equal cancer phenotype. Cancers with the same genetic abnormalities don’t always behave the same. Understanding and eradicating cancers will require an appreciation for cancer’s ecology. This book is the first to comprehensively explore and critically appraise cancer microenvironments and host interactions with an eye towards exploiting our understanding for new treatments. The team of contributors share amongst them impressive experiences at the laboratory bench and in the clinic. These physician-scientists have dedicated themselves to the tension between the urgency for cures and the technical challenges of discovery. The target audience includes clinical oncologists, clinical hematologists, research oncologists, research hematologists, immunologists, stem cell researchers, oncology and hematology fellows (trainees), oncology educators (graduate and undergraduate levels), and course book for graduate students and undergraduate students.

Endoplasmic Reticulum Stress in Health and Disease

Author: Patrizia Agostinis
Publisher: Springer Science & Business Media
ISBN: 9400743513
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The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress’. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.

Skin Stress Response Pathways

Author: Georg T. Wondrak
Publisher: Springer
ISBN: 3319431579
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It is now established that the interplay between environmental exposure and molecular stress response pathways plays a critical role in skin health and disease, and a refined mechanistic understanding of this phenomenon at the molecular level promises to open new avenues for targeted therapeutic strategies that may benefit patients in the near future. Coauthored by recognized international leaders in molecular and clinical biomedical sciences, this novel book provides a comprehensive perspective on environmental exposure-induced skin stress response pathways. Focusing on molecular opportunities targeting skin stress response pathways that are involved in cutaneous barrier function and repair, antimicrobial defense, immune regulation, inflammation, and malignant progression, the book is essential reading for students, basic researchers, and biomedical health care professionals interested in skin health and disease with implications for small molecule therapeutic development.

Autophagy Cancer Other Pathologies Inflammation Immunity Infection and Aging

Author: M. A. Hayat
Publisher: Academic Press
ISBN: 0128094281
Format: PDF, Kindle
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Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Volume 10 offer a valuable guide to both cellular processes, while encouraging researchers to explore their potentially important connections. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. This is the tenth volume of the multivolume series that discusses, in detail, almost all aspects of the autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. Volume 10 of the Autophagy series discusses the role of a novel binuclear palladacycle complex that inhibits melanoma growth through apoptosis and autophagy. Presents the most advanced information regarding the role of the autophagic system in life and death Contains a direct focus on the role of a novel binuclear palladacycle complex that inhibits melanoma growth Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation States recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities Edited work with chapters authored by leaders in the field from around the globe—the broadest, most expert coverage available

Lung Cancer An Issue of Clinics in Chest Medicine E Book

Author: Lynn T. Tanoue
Publisher: Elsevier Health Sciences
ISBN: 1455709719
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Carcinoma of the lung is one of the most prevalent and aggressive types of cancer, and rates of lung cancer are on the rise. This issue gives a comprehensive review of the most recent advances in Lung Cancer. Epidemiology, etiology, and prevention of lung cancer is first discussed, followed by articles on pre-invasive evaluation and management, screening, pathology and molecular biology. There is an article on the approach to the ground glass nodule. Of great importance is the revised staging classification of Lung Cancer, which is discussed here in detail. Articles on PET imaging, interventional pulmonary, and functional evaluation before Lung Resection are also included. The issue then focuses on advances in treatment for early stage lung cancer, high risk patients with early stage lung cancer, advances in the treatment of Advanced Stage Lung Cancer, Small Cell Lung Cancer, and gene therapy for lung neoplasms.

Molecular Pathology

Author: William B. Coleman
Publisher: Academic Press
ISBN: 0128027878
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As the molecular basis of human disease becomes better characterized, and the implications for understanding the molecular basis of disease becomes realized through improved diagnostics and treatment, Molecular Pathology, Second Edition stands out as the most comprehensive textbook where molecular mechanisms represent the focus. It is uniquely concerned with the molecular basis of major human diseases and disease processes, presented in the context of traditional pathology, with implications for translational molecular medicine. The Second Edition of Molecular Pathology has been thoroughly updated to reflect seven years of exponential changes in the fields of genetics, molecular, and cell biology which molecular pathology translates in the practice of molecular medicine. The textbook is intended to serve as a multi-use textbook that would be appropriate as a classroom teaching tool for biomedical graduate students, medical students, allied health students, and others (such as advanced undergraduates). Further, this textbook will be valuable for pathology residents and other postdoctoral fellows that desire to advance their understanding of molecular mechanisms of disease beyond what they learned in medical/graduate school. In addition, this textbook is useful as a reference book for practicing basic scientists and physician scientists that perform disease-related basic science and translational research, who require a ready information resource on the molecular basis of various human diseases and disease states. Explores the principles and practice of molecular pathology: molecular pathogenesis, molecular mechanisms of disease, and how the molecular pathogenesis of disease parallels the evolution of the disease Explains the practice of “molecular medicine and the translational aspects of molecular pathology Teaches from the perspective of “integrative systems biology Enhanced digital version included with purchase

The Biology of Tumors

Author: Enrico Mihich
Publisher: Springer Science & Business Media
ISBN: 1489913521
Format: PDF
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The Ninth Annual Pezcoller Symposium entitled "The Biology of Tumors" was held in Rovereto, Italy, June 4-7, 1997. It focused on the genetic mechanisms underlying het erogeneity of tumor cell populations and tumor cell differentiation, on interactions be tween tumor cells and cells of host defenses, and the mechanisms of angiogenesis. With presentations at the cutting edge of progress and stimulating discussions, this symposium addressed issues related to phenomena concerned with cell regulation and cell interactions as determined by activated genes through the appropriate and timely media tion of gene products. Important methodologies that would allow scientists to measure dif ferentially genes and gene products and thus validate many of the mechanisms of control currently proposed were considered, as were the molecular basis of tumor recognition by the immune system, interactions between cells and molecular mechanisms of cell regula tion as they are affected by or implemented through these interactions. The molecular and cellular mechanisms of tumor vascularization were also discussed. It was recognized that angiogenesis provides a potential site of therapeutic intervention and this makes it even more important to understand the mechanisms underlying it. We wish to thank the participants in the symposium for their substantial contribu tions and their participation in the spirited discussions that followed. We would also like to thank Drs.

Oncology of Infancy and Childhood E Book

Author: Stuart H. Orkin
Publisher: Elsevier Health Sciences
ISBN: 1437721389
Format: PDF, Docs
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To address the growing complexities of childhood cancer, Nathan and Oski’s Hematology and Oncology of Infancy and Childhood has now been separated into two distinct volumes. With this volume devoted strictly to pediatric oncology, and another to pediatric hematology, you will be on the cutting edge of these two fields. This exciting new, full-color reference provides you with the most comprehensive, authoritative, up-to-date information for diagnosing and treating children with cancer. It brings together the pathophysiology of disease with detailed clinical guidance on diagnosis and management for the full range of childhood cancers, including aspects important in optimal supportive care. Written by the leading names in pediatric oncology, this resource is an essential tool for all who care for pediatric cancer patients. Offers comprehensive coverage of all pediatric cancers, including less common tumors, making this the most complete guide to pediatric cancer. Covers emerging research developments in cancer biology and therapeutics, both globally and in specific pediatric tumors. Includes a section on supportive care in pediatric oncology, written by authors who represent the critical subdisciplines involved in this important aspect of pediatric oncology. Uses many boxes, graphs, and tables to highlight complex clinical diagnostic and management guidelines. Presents a full-color design that includes clear illustrative examples of the relevant pathology and clinical issues, for quick access to the answers you need. Incorporates the codified WHO classification for all lymphomas and leukemias.