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Strategies to Mitigate the Toxicity of Cancer Therapeutics, Volume 155 in the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting interesting chapters, each of which is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Cancer Research series Includes the latest information on Strategies to Mitigate the Toxicity of Cancer Therapeutics
This book provides the first comprehensive overview of a new scientific discipline termed Geroscience. Geroscience examines the molecular and cellular mechanisms that might explain why aging is the main risk factor for most chronic diseases affecting the elderly population. Over the past few decades, researchers have made impressive progress in understanding the genetics, biology and physiology of aging. This book presents vital research that can help readers to better understand how aging is a critical malleable risk factor in most chronic diseases, which, in turn, could lead to interventions that can help increase a healthy lifespan, or ‘healthspan.’ The book begins with an analysis of the Geroscience hypothesis, as well as the epidemiological underpinnings that define aging as a candidate main risk factor for most chronic diseases. Next, each chapter focuses on one particular disease, or group of diseases, with an emphasis on how basic molecular and cellular biology might explain why aging is a major risk factor for it. Coverage in the book includes: cancer, cardiovascular disease, dementias, stroke, Parkinson's and Alzheimer’s diseases, osteoporosis, arthritis, diabetes asthma, emphysema, kidney disease, vision impairment, and AIDS/HIV. It finishes with a chapter on pain in the elderly and an overview of future steps needed to bring the newly acquired knowledge into the clinic and the public at large.
Stereotactic body radiation therapy (SBRT) has emerged as an important innovative treatment for various primary and metastatic cancers. This book provides a comprehensive and up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. It will serve as a detailed resource for this rapidly developing treatment modality. The organ sites covered include lung, liver, spine, pancreas, prostate, adrenal, head and neck, and female reproductive tract. Retrospective studies and prospective clinical trials on SBRT for various organ sites from around the world are examined, and toxicities and normal tissue constraints are discussed. This book features unique insights from world-renowned experts in SBRT from North America, Asia, and Europe. It will be necessary reading for radiation oncologists, radiation oncology residents and fellows, medical physicists, medical physics residents, medical oncologists, surgical oncologists, and cancer scientists.
Rising health care costs are a central fiscal challenge confronting the United States. National spending on health care currently accounts for 18 percent of gross domestic product (GDP), but is anticipated to increase to 25 percent of GDP by 2037. The Bipartisan Policy Center argues that "this rapid growth in health expenditures creates an unsustainable burden on America's economy, with far-reaching consequences". These consequences include crowding out many national priorities, including investments in education, infrastructure, and research; stagnation of employee wages; and decreased international competitiveness.In spite of health care costs that far exceed those of other countries, health outcomes in the United States are not considerably better. With the goal of ensuring that patients have access to high-quality, affordable cancer care, the Institute of Medicine's (IOM's) National Cancer Policy Forum convened a public workshop, Delivering Affordable Cancer Care in the 21st Century, October 8-9, 2012, in Washington, DC. Delivering Affordable Cancer Care in the 21st Century summarizes the workshop.
The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.
The primary goal of this project is to increase specific uptake of anti-cancer therapeutics by nuclei of cancer cells. A lot of research has been done to target therapeutics specifically across plasma membrane of malignant cells. However not much research has been done to deliver them to their target cellular compartment where the drug elicits its pharmacological response. In case of majority of anti-cancer drugs the target is usually nuclei of cancer cells. Hence nuclear delivery of therapeutics is the next frontier of pharmaceutics. In this dissertation work this issue has been investigated. Initially in the first strategy adopted, novel peptide prodrug of doxorubicin was developed which may evade over-expressed efflux pumps on breast cancer cells. This approach may lead to increased uptake and higher drug accumulation in nuclei of cancer cells. L-val-L-val doxorubicin prodrug was synthesized following standard f-moc chemistry. The prodrug was analyzed for stability, cellular and nuclear uptake and interaction with efflux and peptide transporters. Breast cancer cells (T-47D) were grown on polystyrene 12-well plates. The prodrug Val-Val-doxorubicin was found to be very stable in breast cancer cell homogenate. It was able to evade efflux pumps. The prodrug penetrated cytoplasm and nuclei of cancer cells by interacting with peptide transporters over-expressed on plasma and nuclear membrane of T-47D.Uptake of prodrug was found to be 10 fold higher than parent drug. Peptide prodrug derivatization of doxorubicin has potential to evade efflux pumps and increase availability and nuclear accumulation of doxorubcin in breast cancer cells. However due to its stability the prodrug did not biorevert to its parent drug in therapeutic concentration. Hence alternative approaches were investigated. As part of this alternate approach novel nuclear localization signal (NLS) peptide analogues have been designed that can carry therapeutic molecules specifically into nuclei of cancer cells. This strategy might be able to reduce toxicity to non-malignant cells by delivering anticancer drugs to subcellular organelle i.e. nucleus of cancer cells preferentially. Native NLS peptide-conjugated drugs can reach nucleus of any cell non-specifically. However the overarching challenge is to enhance drug uptake across plasma and nuclear membranes to enhance anticancer drug delivery in drug resistant cancer cells. Adenoviral fiber protein (AFP) that encodes for NLS has been known to penetrate both plasma and nuclear membrane nonspecifically. Therefore novel NLS peptide analogues have been synthesized by substitutions of NLS sequence specific amino acids for targeting cancer cells primarily. Specific amino acids of native NLS have been substituted based on hydrophobic interactions between the peptides with plasma membrane and nucleo pore complex (NPC) that can influence cytoplasmic and nuclear transport. These peptides can carry therapeutics selectively to nuclei of cancer cells simultaneously evading normal cells. Five NLS peptides have been synthesized. These peptides were synthesized by AAPtech automated peptide synthesizer. Following synthesis, the peptides were purified by a shimadzu Preparative HPLC which was confirmed by HPLC-MSMS. Confocal and quantitative uptake studies with various cancer and corresponding non-cancerous human cell lines were performed. It was observed that two (NLS3 and NLS5) peptides are specific for targeting cancer cell nucleus. It has led to an unequivocal conclusion that these novel peptide analogues can selectively bind to plasma membranes of cancer cells and target NPC simultaneously. Following screening of peptides which can function as targeting moieties, nanoparticle formulation was developed to deliver anti-cancer drugs. One of the important parameters for nuclear drug delivery is size. The nucleopore complex has a diameter of 30 nm. Cargo with 30-40 nm can enter the NPC passively. However particles higher than 40 nm need to be actively transported across NPC. It has been reported that particles with 60-70 nm with anti cancer drugs can be delivered into nucleus with localization signals. This is the target size which has been achieved for doxorubicin loaded nanoparticle. PLGA-PEG-NH2 was used as polymer for preparation of doxorubicin loaded nanoparticles. This is because of availability of NH2 group at the end of PEG group for conjugation of peptide moiety for targeted delivery following optimization of size. Nanoparticles were prepared by nanoprecipitation method. Parameters like effect of solvent, polymer concentration, effect of aqueous phase volume, drug concentration were optimized to yield a nanoparticle of size range 60-70 nm as this size can be taken up by nucleus if actively aided by nuclear localization signal. Following preparation of nanoparticle of optimized size, screened peptides (NLS3 and NLS5) with maximum affinity for cancer cell nuclei with minimal entry into corresponding non-malignant cells were conjugated to nanoparticles. Targeted nanoparticles were investigated for its active targeting property in a 3D model of breast cancer. It was observed that nanoparticle with NLS conjugated to its surface delivered higher concentration of doxorubicin compared to unconjugated nanoparticle or free doxorubicin.
While a number of books have looked at the intersection between human health in general and other topics, such as climate change or diet, this book focuses specifically on cancer as it impacts and is impacted by social justice issues. The massive explosion of research knowledge of cancer immunology and genomics is holding out great promise of therapeutic advances, yet other human actions—climate change, pollution, business decisions, advertising – are fostering health inequalities as well as increasing risks. Those involved in cancer care and research are in a unique position to let their experiences and knowledge inform the public, yet very often have not taken strong public roles when it comes to discussing issues surrounding tobacco, climate change and health risks, financial toxicity of treatments, and diet choices. Written by a multidisciplinary team of authors and for medical oncologists, cancer researchers, occupational health workers, and related medical students, residents, and fellows, this book encourages oncologists to address public health care and the societal issues associated with cancer risk. This volume discusses the overarching theme of environmental justice and oncology, focuses on business and cancer (such as clinical trials, drug development and profits, and global disparities), as well as animals and cancer.
Since the late 1960s, the survival rate in children and adolescents diagnosed with cancer has steadily improved, with a corresponding decline in the cancer-specific death rate. Although the improvements in survival are encouraging, they have come at the cost of acute, chronic, and late adverse effects precipitated by the toxicities associated with the individual or combined use of different types of treatment (e.g., surgery, radiation, chemotherapy). In some cases, the impairments resulting from cancer and its treatment are severe enough to qualify a child for U.S. Social Security Administration disability benefits. At the request of Social Security Administration, Childhood Cancer and Functional Impacts Across the Care Continuum provides current information and findings and conclusions regarding the diagnosis, treatment, and prognosis of selected childhood cancers, including different types of malignant solid tumors, and the effect of those cancers on childrenâ (TM)s health and functional capacity, including the relative levels of functional limitation typically associated with the cancers and their treatment. This report also provides a summary of selected treatments currently being studied in clinical trials and identifies any limitations on the availability of these treatments, such as whether treatments are available only in certain geographic areas.
The three sections of this volume present currently available cancer gene therapy techniques. Part I describes the various aspects of gene delivery. In Part II, the contributors discuss strategies and targets for the treatment of cancer. Finally, in Part III, experts discuss the difficulties inherent in bringing gene therapy treatment for cancer to the clinic. This book will prove valuable as the volume of preclinical and clinical data continues to increase.