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

Molecular mechanisms of cellular stress responses in cancer and their therapeutic implications PDF Author: Megan Chircop
Publisher: Frontiers Media SA
ISBN: 2889194965
Category : Carcinogenesis
Languages : en
Pages : 160

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Book Description
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.

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

Molecular mechanisms of cellular stress responses in cancer and their therapeutic implications PDF Author: Megan Chircop
Publisher: Frontiers Media SA
ISBN: 2889194965
Category : Carcinogenesis
Languages : en
Pages : 160

Get Book Here

Book Description
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.

Stress Response Pathways in Cancer

Stress Response Pathways in Cancer PDF Author: Georg T. Wondrak
Publisher: Springer
ISBN: 9401794219
Category : Medical
Languages : en
Pages : 450

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Book Description
It is now established that dysregulated cell stress response pathways play a critical role in tumorigenesis, and a refined mechanistic understanding of this phenomenon at the molecular level promises to open new avenues for targeted therapeutic strategies that may benefit cancer patients in the near future. Coauthored by recognized leaders in cancer research from five continents, this novel book provides a comprehensive perspective on cell stress response pathways and therapeutic opportunities. Focusing on the role of genotoxic, proteotoxic, oxidative, metabolic, and inflammatory stress in tumorigenesis, the book is essential reading for students, basic researchers, and biomedical health care professionals interested in cancer and therapeutic development.

Inflammation and Cancer

Inflammation and Cancer PDF Author: Bharat B. Aggarwal
Publisher: Springer
ISBN: 3034808372
Category : Medical
Languages : en
Pages : 489

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Book Description
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

Cellular Response to Physical Stress and Therapeutic Application

Cellular Response to Physical Stress and Therapeutic Application PDF Author: Kondo Takashi Shimizu Tadamichi
Publisher:
ISBN: 9781628089219
Category : Medical
Languages : en
Pages : 218

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Book Description
Not all that cannot be seized is an illusion! Many effective powers in nature cannot be seized, including magnetism, electricity and sound. However, they contribute to shaping the quality of human life on a daily basis, transcending health and disease as they interact with the human body. Magnetism is important for stability on earth; however, exposure of the body to magnetic fields is not inert. Such exposure has been reported to alter hormone secretion and stimulate bone formation in vivo. Its coupling with electricity provides light and heat to our planet at certain wavelengths. Yet, the infiltration of shorter or longer wavelengths can be disastrous. For instance, ultraviolet radiation can cause inflammatory skin reactions and carcinogenesis at certain levels. In addition, ionizing radiation is claimed to be the driving force for the origin of power resources on earth, while human exposure to radiation is related to the world's most devastating events. On the other hand, sound, which is a mechanical wave, has been reported to affect cells at inaudible levels, causing alterations in the gene expression and cell death. All these energies as such are identified to exert physical stresses in a biological milieu especially when thresholds of exposure are exceeded. But still "hard times" have significance! Researchers have been accumulating knowledge on the biological effects of these physical stressors and their underlying mechanisms on the molecular and genetic levels, that over years they were able to achieve control over these physical stressors for the benefit of human kind. Nowadays, we see most of these energies employed in diagnosis such as magnetic resonance imaging (MRI) and ultrasound as well as in therapeutics. In our rigorous war against cancer, numerous patients have been cured from tumors by physical means such as ionizing radiation, heating (RF and MW hyperthermia or ablation) or high intensity focused ultrasound (HIFU). Through the chapters of this book, the readers will get introduced to such physical stressors and their biological effects. Recent findings on molecular mechanisms will be thoroughly presented. In addition, perspectives on the modulation of these energies to achieve further therapeutic advantages will be discussed.

Using Phylogenetically Conserved Stress Responses to Discover Natural Products with Anticancer Activity

Using Phylogenetically Conserved Stress Responses to Discover Natural Products with Anticancer Activity PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 214

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Book Description
One unique feature of cancer cells that can be exploited for anticancer drug discovery is their dependence on their own cellular stress responses to survive the stressful acidotic, hypoxic and nutrient-deprived conditions within the tumor. Reasoning that desert organisms surviving under stressful conditions may have evolved to produce small molecule metabolites capable of modulating heat shock protein 90 (Hsp90) function, and/or other cell stress responses, we employed the cellular heat shock response in a moderate-throughput phenotypic assay. This strategy has resulted in the isolation and characterization of a number of small molecule natural products with heat shock induction activity from these organisms. Three such natural products are the subject of this study. In a limited structure-activity relationship (SAR) study, a previously known Hsp90 inhibitor radicicol (RAD), and several structurally related molecules including the fungal metabolite monocillin 1 (MON) were found to interact with Hsp90. In addition, RAD and MON were shown to lead to the degradation of Hsp90 client proteins involved in the cancer cell survival the estrogen receptor (ER) and the insulin-like growth factor receptor 1 (IGF-1R). We further characterized MON and showed that by targeting the molecular chaperone Hsp90, this compound induces components of the heat shock response at the transcriptional and translational levels, and leads to the acquisition of a thermotolerant phenotype in seedlings of the plant Arabidopsis thaliana. These findings support our hypothesis that there is ecological significance to the elaboration of small molecules that target stress responses. A number of extracts active in our phenotypic assay contained small molecules with no apparent Hsp90 activity. One such extract afforded terrecyclic acid A (TCA) with significant anti-tumor activity against a panel of human cancer cell lines. To characterize the biological activities of TCA we examined three key stress responsesthe heat shock, oxidative, and inflammatory responsesand show that TCA destabilizes these pathways associated with cancer cell survival through induction of oxidative stress (ROS), and inhibition of NF-kappaB transactivation. The isolation of RAD, MON and TCA from Sonoran desert organisms provides proof of principle that we have developed an effective strategy for the discovery of small molecule modulators of cellular stress responses that can serve as leads for the development of new anticancer drugs with novel mechanisms of action.

The Unfolded Protein Response in Cancer

The Unfolded Protein Response in Cancer PDF Author: Robert Clarke
Publisher: Springer
ISBN: 303005067X
Category : Medical
Languages : en
Pages : 220

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Book Description
This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.

Holland-Frei Cancer Medicine

Holland-Frei Cancer Medicine PDF Author: Robert C. Bast, Jr.
Publisher: John Wiley & Sons
ISBN: 111900084X
Category : Medical
Languages : en
Pages : 2004

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Book Description
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Mechanisms of Cell Death

Mechanisms of Cell Death PDF Author: Zahra Zakeri
Publisher:
ISBN:
Category : Science
Languages : en
Pages : 236

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Book Description
Contains papers from a July 1998 conference held at the Queens College Campus of the City University of New York. Papers are arranged in sections on mechanisms and general considerations, programmed (developmental) cell death, and cell death and pathological and clinical situations. Specific topics

Heat Shock Proteins in Cancer

Heat Shock Proteins in Cancer PDF Author: Stuart K. Calderwood
Publisher: Springer Science & Business Media
ISBN: 1402064012
Category : Medical
Languages : en
Pages : 399

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Book Description
Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.

Mitochondrial Physiology and Vegetal Molecules

Mitochondrial Physiology and Vegetal Molecules PDF Author: Marcos Roberto de Oliveira
Publisher: Academic Press
ISBN: 0128215836
Category : Science
Languages : en
Pages : 808

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Book Description
Mitochondrial Physiology and Vegetal Molecules: Therapeutic potential of natural compounds on mitochondrial health provides a comprehensive overview of mitochondrial physiology throughout the human life span, as well as the effect of molecules of vegetal origin on mitochondrial health. The editor has lined up a team of worldwide experts to cover the most exciting and high-impact advancements of research in this area. This book is structured into two parts that provide a balance of both foundational and applied content. Part I provides an overview of mitochondrial physiology including its structure, dynamics, biogenesis, membranes, DNA transcription, and translation in the mitochondria. Part I also covers other themes such as apoptosis. Part II then covers the effect of specific vegetable-derived molecules on mitochondrial health, including anthocyanins, caffeine, cannabinoids, carnosic and rosmarinic acids, citrus flavonoids, polyphenols, pterostilbene, resveratrol, and sulforaphane, among others. Mitochondrial Physiology and Vegetal Molecules: Therapeutic potential of natural compounds on mitochondrial health is a complete resource for researchers in this exciting field. Its comprehensive coverage makes it particularly interesting to bioscience researchers willing to understand the foundations of mitochondrial physiology throughout the human life span. Clinician researchers, MDs, nutritionists, pharmacologists, and sports scientists may be attracted to the detailed information on the health effects of vegetal origin molecules on the organelle. Contains detailed information on plant products and their effect on mitochondria Proposes therapies and reviews mechanisms of absorption at the cellular level Discusses the limited bioavailability of plant molecules/compounds in the human organism Includes coverage of specific conditions such as Sports and affective disorders, among others Presents the protective effects of plant products in mitochondrial health through all stages of life