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Childhood leukemias

Anand P. Chokkalingam and Patricia A. Buffler

in Human Genome Epidemiology, 2nd Edition: Building the evidence for using genetic information to improve health and prevent disease

The term “leukemia” refers broadly to cancer of the white blood cells, or leukocytes. As a group, leukemias are the most common cancer among people under 15 years of age, accounting for 32% of all ... More

The term “leukemia” refers broadly to cancer of the white blood cells, or leukocytes. As a group, leukemias are the most common cancer among people under 15 years of age, accounting for 32% of all childhood malignancies. This chapter summarizes the total body of literature on the genetic epidemiology of childhood leukemias, focusing specifically on main effects of gene variants, highlighting conclusions that can be drawn based on the work to date, and emphasizing challenges and future directions.Less

The Leukemias

MARTHA S. LINET, SUSAN S. DEVESA, and GARETH J. MORGAN

in Cancer Epidemiology and Prevention

The leukemias arise from malignant transformation of hematopoietic stem or progenitor cells that originate in the bone marrow, lymph nodes, and/or other lymphoid tissue with immune function. A small ... More

The leukemias arise from malignant transformation of hematopoietic stem or progenitor cells that originate in the bone marrow, lymph nodes, and/or other lymphoid tissue with immune function. A small pool of stem cells, which persists throughout an individual's lifetime, differentiates to early precursors, then divides into multiple subtypes, and ultimately produces large numbers of end-stage cells of myeloid and lymphoid lineage progeny. Because the effector or end-stage cells of each lineage have a finite lifespan and, therefore, cannot transmit mutations, all leukemias are the consequence of derangements of growth and differentiation of the pluripotential early precursors of myeloid or lymphoid progeny. This chapter discusses the epidemiology of the myeloid and lymphoid leukemias.Less

Death and Dignity: A Case of Individualized Decision Making  

Timothy E. Quill

in Caring for Patients at the End of Life: Facing an Uncertain Future Together

This chapter relates a case of individualized decision making in a patient named Diane who was diagnosed with acute leukemia. In the author's conversation with Diane and her family about her ... More

This chapter relates a case of individualized decision making in a patient named Diane who was diagnosed with acute leukemia. In the author's conversation with Diane and her family about her condition and options, she remained very adamant about her wish not to undergo chemotherapy and to live whatever time she had left outside the hospital. Being an advocate of informed patient choice, the author agreed to Diane's wishes despite the possibility of having to face legal and professional problems.Less

Pediatric Oncology: A Medical Overview

David J. Bearison and Raymond K. Mulhern

in Pediatric Psychooncology: Psychological Perspectives on Children with Cancer

This chapter discusses the medical aspects of pediatric cancer, valuable to readers with little or no background in biomedical sciences and medical practice. It considers the etiology, clinical ... More

This chapter discusses the medical aspects of pediatric cancer, valuable to readers with little or no background in biomedical sciences and medical practice. It considers the etiology, clinical symptoms, diagnostic procedures, and different kinds of treatments of childhood cancers, and discusses the characteristics and late effects of the most common kinds of pediatric malignancies, including leukemias, brain tumors, lymphomas, and bone tumors. It helps those who are relatively unfamiliar with medical issues in pediatric oncology to better appreciate the nature of this disease and to establish a context for the discussion of psychological issues in the chapters that follow.Less

Neuropsychological Late Effects

David J. Bearison and Raymond K. Mulhern

in Pediatric Psychooncology: Psychological Perspectives on Children with Cancer

The dramatic improvements in treating childhood cancers also have occasioned a variety of treatment-related toxicities. None are more significant than neuropsychological late effects caused by ... More

The dramatic improvements in treating childhood cancers also have occasioned a variety of treatment-related toxicities. None are more significant than neuropsychological late effects caused by pathological changes in children's central nervous systems that are secondary to cancer and/or its treatment, and which affect children's intellectual abilities and cognitive development. This chapter discusses the evidence for neuropsychological deficits associated with the treatment of pediatric acute lymphoblastic leukemia and brain tumors, the two most prevalent forms of childhood malignancy. It considers critical factors determining neuropsychological function, such as age at treatment and radiation therapy, in terms of modifying medical management, and remedial and rehabilitative programs.Less

Nuclear Energy and Environmental Justice

Kristin Shrader-Frechette

in What Will Work: Fighting Climate Change with Renewable Energy, Not Nuclear Power

Chapter 5 shows that, even when accidents are ignored, fission causes many serious pollution-induced health effects. In addition, atomic energy is ... More

Chapter 5 shows that, even when accidents are ignored, fission causes many serious pollution-induced health effects. In addition, atomic energy is responsible for significant environmental injustice, that is, for disproportionately-higher pollution effects on the weakest, most vulnerable people—children, blue-collar workers, minorities, and members of future generations. The chapter addresses these concerns by arguing for 4 main claims. First, the nuclear fuel cycle imposes unjust and uncompensated radiation burdens on indigenous people and minorities, who are often forced to work for low pay in dangerous uranium mines and processing centers. Second, US commercial reactors are disproportionately sited in the poorest part of the US, the Southeast, and in communities having statistically significantly more people living below the poverty line, unfairly subjecting them to the serious health effects of radiation. Third, even normally operating reactors cause radiation-induced diseases and fatalities. Fourth, the chapter shows that radiation standards themselves are environmentally unjust because they protect some US children almost 200 times less well than adults, and they protect blue-collar radiation workers 50 times less well than members of the public. Children living near normally operating nuclear plants also show statistically significant increases in cancer, especially radiation-related cancers like leukemia, and these cancers decrease in proportion to distance away from the reactor. Likewise, because regulations allow nuclear workers to receive 50 times the annual-radiation dose of the public, they are at especially high risk. Using data from the US National Academy of Sciences and the International Agency for Research on Cancer, the chapter shows that among every 80 workers who receive the annual allowable occupational-radiation dose, that radiation can annually cause 1 fatal, otherwise-avoidable, premature cancer. Moreover, the chapter shows that, because contemporary radiation-protection regulations do not satisfy disclosure and voluntariness requirements, radiation workers cannot give free informed consent to these much-higher occupational risks. Finally, the chapter reveals that, because US radiation standards, for permanent, future, nuclear-waste management, are more than 4 times less protective than for current people, they subject future people to massive environmental injustices.Less

Log-normal distribution—leukemia and pesticide exposure

Steve Selvin

in The Joy of Statistics: A Treasury of Elementary Statistical Tools and their Applications

Like the normal distribution, the log-normal distribution’s properties are useful and often revealing. A short description presents an analysis of log-normal data collected to asses cancer risk ... More

Like the normal distribution, the log-normal distribution’s properties are useful and often revealing. A short description presents an analysis of log-normal data collected to asses cancer risk associated with a specific pesticide.Less

Cancer Survival Is (Mostly) Improving

Michael D. Stein and Sandro Galea

in Pained: Uncomfortable Conversations about the Public's Health

This chapter discusses how the 5-year survival rates for the most common cancers in the United States improved by nearly 20% since the 1970s. While promising overall, low survival rates persist for ... More

This chapter discusses how the 5-year survival rates for the most common cancers in the United States improved by nearly 20% since the 1970s. While promising overall, low survival rates persist for pancreatic, liver, lung, esophageal, brain, and many other cancers. Meanwhile, 5-year survival for uterine and cervical cancers worsened. Pancreatic cancer has the lowest 5-year survival rate at 8.2%. In contrast, prostate cancer had the greatest 5-year survival increase from 67.8% to 98.6%, most likely reflecting a substantial uptick in prostate cancer screening and early detection. Five-year survival with leukemia also improved significantly, from 34.2% to 60.6%, likely resulting from improved treatments. As such, in both detection and treatment, the United States is making progress. For the millions of Americans who face a cancer diagnosis, this is cause for hope.Less

Managing the Future at the Special Virus Leukemia Program

Robin Wolfe Scheffler

in A Contagious Cause: The American Hunt for Cancer Viruses and the Rise of Molecular Medicine

The changing political circumstances discussed in chapter 4 gave the National Cancer Institute unprecedented resources for biomedical research into cancer. However, this windfall also created ... More

The changing political circumstances discussed in chapter 4 gave the National Cancer Institute unprecedented resources for biomedical research into cancer. However, this windfall also created concerns for the accountability of scientific research, particularly that supported by peer reviewed grants. Chapter 5 argues that the leadership of the National Cancer Institute, especially Carl Baker, addressed this crisis in legitimacy by developing new management methods, drawn from Cold War defense planning methods such as systems analysis, for biomedical research. These methods were well suited to the environment of crisis and anticipation surrounding childhood cancer. The methods reframed human cancer viruses from biomedical objects that were best understood in the laboratory into “administrative objects” that could be the objects of large-scale planning—even if they were not yet known to exist.Less

The Drug Discovery Crisis

Brent R. Stockwell

in The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines

This chapter examines the current problem associated with creating new drugs—that so few proteins are considered druggable. It first traces the history of how existing drugs were created. It then ... More

This chapter examines the current problem associated with creating new drugs—that so few proteins are considered druggable. It first traces the history of how existing drugs were created. It then attributes the drug discovery crisis in the United States and the rest of the world to the challenge of the undruggable proteins. To better appreciate the nature of these undruggable proteins and how they might ultimately be used to make medicines, this chapter explains what drugs are and how they function. It then discusses the evolution of kinases from undruggable to druggable, the role of the BCR-ABL kinase in chronic myelogenous leukemia, the discovery of imatinib as a potential cancer drug, and the challenges arising from the concept of druggability.Less

A Landmark Clinical Trial

Peter Keating and Alberto Cambrosio

in Cancer on Trial: Oncology as a New Style of Practice

This chapter discusses the VAMP trial, the clinical trial to test a combination of anticancer drugs on children with acute lymphocytic leukemia (ALL). Four different drugs with different mechanisms ... More

This chapter discusses the VAMP trial, the clinical trial to test a combination of anticancer drugs on children with acute lymphocytic leukemia (ALL). Four different drugs with different mechanisms of action were used: vincristine (V), amethopterin (A), mercaptopurine (M) and prednisone (P). The results of the VAMP protocol were quite spectacular. Of the sixteen patients treated, thirteen achieved complete remission.Less

Magic Bullets? The Gleevec Trials

Peter Keating and Alberto Cambrosio

in Cancer on Trial: Oncology as a New Style of Practice

This chapter discusses the series of clinical trials conducted between 1998 and 2001 to test the efficacy of a compound known as Gleevec. Gleevec (imatinib), one of the first targeted cancer ... More

This chapter discusses the series of clinical trials conducted between 1998 and 2001 to test the efficacy of a compound known as Gleevec. Gleevec (imatinib), one of the first targeted cancer therapies to gain FDA approval, has revolutionized the treatment of chronic myelogenous leukemia.Less

Female Reproductive Function

Sergio R. Ojeda

in Textbook of Endocrine Physiology

The production of germ cells is essential for the continuation of a species. In the female this function is accomplished by the ovaries. In addition, the ovaries secrete steroids and nonsteroidal ... More

The production of germ cells is essential for the continuation of a species. In the female this function is accomplished by the ovaries. In addition, the ovaries secrete steroids and nonsteroidal hormones that not only regulate the secretion of anterior pituitary hormones but also act on various target organs, including the ovaries themselves, the uterus, fallopian tubes, vagina, mammary gland, and bone. Morphologically, the ovary has three regions: an outer cortex that contains the oocytes and represents most of the mass of the ovary; the inner medulla, formed by stromal cells and cells with steroid-producing characteristics; and the hilum, which, in addition to serving as the point of entry of the nerves and blood vessels, represents the attachment region of the gland to the mesovarium. The cortex, which is enveloped by the germinal epithelium, contains the follicles, which are the functional units of the ovary. They are present in different states of development or degeneration (atresia), each enclosing an oocyte. In addition to the oocyte, ovarian follicles have two other cellular components: granulosa cells, which surround the oocyte, and thecal cells, which are separated from the granulosa cells by a basal membrane and are arranged in concentric layers around this membrane. The follicles are embedded in the stroma, which is composed of supportive connective cells similar to that of other tissues, interstitial secretory cells, and neurovascular elements. The medulla has a heterogeneous population of cells, some of which are morphologically similar to the Leydig cells in the testes. These cells predominate in the ovarian hilum; their neoplastic transformation results in excess androgen production. The ovary produces both steroids and peptidergic hormones. Whereas the steroids are synthesized in both interstitial and follicular cells, peptidergic hormones are primarily produced in follicular cells and, after ovulation, by cells of the corpus luteum. The initial precursor for steroid biosynthesis is cholesterol, which derives from animal fats of the diet or from local synthesis. Less

Mechanisms of Hormone Action

Stephen R. Hammes and Carole R. Mendelson

in Textbook of Endocrine Physiology

The capacity of a cell to respond to a particular hormone depends on the presence of cellular receptors specific for that hormone. After binding hormone, the receptor is biochemically and ... More

The capacity of a cell to respond to a particular hormone depends on the presence of cellular receptors specific for that hormone. After binding hormone, the receptor is biochemically and structurally altered, resulting in its activation; the activated receptor then mediates all of the actions of the hormone on the cell. The steroid and thyroid hormones as well as retinoids and 1,25-dihydroxyvitamin D3 diffuse freely through the lipophilic plasma membrane of the cell and interact with receptors that are primarily within the nucleus. On activation, the receptors alter the transcription of specific genes, resulting in changes in the levels of specific messenger RNAs (mRNAs), which are in turn translated into proteins. Hormones that are water soluble, such as the peptide and polypeptide hormones, catecholamines, and other neurotransmitters, as well as the relatively hydrophobic prostaglandins, interact with receptors in the plasma membrane. After hormone binding, the activated membrane receptors initiate signal transduction cascades that result in changes in enzyme activities and alterations in gene expression. In this chapter, the properties of various classes of receptors that are localized within the plasma membranes of target cells and the signal transduction mechanisms that mediate interactions with their ligands will first be addressed. This will be followed by consideration of the structural properties of the nuclear hormone receptors, the events that result in their activation, and the mechanisms whereby the activated nuclear receptors alter the expression of specific genes. Finally, a number of endocrine disorders that are caused by alterations in the number and/or function of plasma membranes and nuclear receptors will be reviewed. The function of a receptor is to recognize a particular hormone among all the molecules in the environment of the cell at a given time and, after binding the hormone, to transmit a signal that ultimately results in a biological response. Hormones are normally present in the circulation in extremely low concentrations, ranging from 10 –9 to 10 –11 M. Less

Dielectric Properties of Blood and Blood Components

Yoshihito Hayashi and Koji Asami

in Dielectric Relaxation in Biological Systems: Physical Principles, Methods, and Applications

An overview of dielectric spectroscopy (DS) studies for erythrocytes, blood coagulation, and leukocytes is provided. Cell suspensions and whole blood show the main dielectric response in the MHz ... More

An overview of dielectric spectroscopy (DS) studies for erythrocytes, blood coagulation, and leukocytes is provided. Cell suspensions and whole blood show the main dielectric response in the MHz region due to interfacial polarization, analysis of which provides important information about the morphology and electric properties of the cells. At first, the dielectric signature of erythrocyte morphology is pointed out by comparing four types of erythrocytes with different shapes, such as discocytes, echinocytes, enlarged erythrocytes, and spherocytes. Subsequently, DS application to monitoring the quality of blood during its preservation is summarized. The glucose effects on the dielectric properties of erythrocytes are also presented. Next, studies of erythrocyte aggregation (rouleaux formation) and blood coagulation are introduced. Dielectric blood coagulometry is a very promising method for the evaluation of the blood coagulability. The chapter concludes with a summary of results on dielectric characterizations of normal and malignant leukocytes.Less

Military Medicine and Cancer Therapy

in Contested Medicine: Cancer Research and the Military

This chapter addresses the intimate relationship between research for cancer therapy and military medicine. It considers the efforts of Donnal Thomas from 1957 to 1977 and his development of a ... More

This chapter addresses the intimate relationship between research for cancer therapy and military medicine. It considers the efforts of Donnal Thomas from 1957 to 1977 and his development of a successful therapy for leukemia with total-body irradiation (TBI) and bone marrow transplantation. Additionally, it evaluates how his work drew on and also contributed to methods for treating the victims of nuclear explosions who were suffering from radiation sickness. Radiation sickness was defined in the period immediately following the atomic bomb attacks on Hiroshima and Nagasaki. The work of Thomas on the treatment of childhood leukemia emphasizes the significance of advances in the diagnosis and treatment of radiation sickness for the development of new strategies in cancer therapy. In general, it has shown the significance of the paradigm problem of radiation injury and how it brought together a range of researchers with interests in military and cancer medicine.Less

A Quiet Revolution: The Legacy of Monoclonal Antibodies

Lara V. Marks

in The Lock and Key of Medicine: Monoclonal Antibodies and the Transformation of Healthcare

This chapter discusses legacy of monoclonal antibodies (Mabs). Mab therapeutics are some of the best-selling drugs in the world today. As of 2012 there were over thirty Mab drugs on the world market. ... More

This chapter discusses legacy of monoclonal antibodies (Mabs). Mab therapeutics are some of the best-selling drugs in the world today. As of 2012 there were over thirty Mab drugs on the world market. Of these, ten had achieved blockbuster status, generating profits of more than $1 billion. These included three marketed for cancer by the Roche Group: bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin), which collectively raised $17 billion in annual revenue in 2009. Mabs have helped advance cancer research and treatment; transformed the management of autoimmune disorders; provided a major tool for understanding the onset and progression of autoimmune diseases and revealed new therapeutic possibilities; and facilitated a paradigm shift in the treatment of autoimmune diseases away from just treating symptoms to targeting and preventing their cause. Mabs were also instrumental historically in the identification and utilization of hematopoietic stem cells (HSCs), immature cells found in bone marrow, to improve the treatment of leukemia.Less

The Biomedical Settlement and the Federalization of the Cancer Problem

Robin Wolfe Scheffler

in A Contagious Cause: The American Hunt for Cancer Viruses and the Rise of Molecular Medicine

Although many assume that the federal government always had a leading role in anticancer efforts, it only gained this status in the middle of the 1950s. Chapter 4 explores how the government ... More

Although many assume that the federal government always had a leading role in anticancer efforts, it only gained this status in the middle of the 1950s. Chapter 4 explores how the government “federalized” cancer as a national problem. This mobilization did not come from within the pre-Second World War community of cancer experts but from new ways of discussing cancer as a curable children’s disease and of understanding the potential impact of biomedical research on national well-being. A key figure for understanding this transition was the New Deal activist Mary Lasker, who reoriented anticancer efforts from opposing to supporting federal intervention, especially in the new field of chemotherapy, where public expectation rapidly exceeded philanthropic capacity.Less

Radiation and Mutation

Soraya de Chadarevian

in Heredity under the Microscope: Chromosomes and the Study of the Human Genome

Chapter 1 substantiates the claim that atomic age anxieties were the driving force for a new interest in human chromosomes. By providing techniques to visualize mutations, karyotyping emerged as the ... More

Chapter 1 substantiates the claim that atomic age anxieties were the driving force for a new interest in human chromosomes. By providing techniques to visualize mutations, karyotyping emerged as the right tool at the right time to address a host of urgent political and scientific questions raised by the development of atomic energy for military and civilian uses. The chapter highlights the development of key techniques in cytogenetics and the early careers of some of the key protagonists (among them Charles Ford, Michael Court Brown, Lionel Penrose, Jérôme Lejeune, Peter Nowell and David Hungerford) and the institutions in which they worked, pointing to multiple connections to the atomic world. It then takes a closer look at two lines of research that defined cytogenetic research agendas while directly responding to atomic age concerns: the chromosomal study of various forms of leukemia, also known as the “pestilence of the atomic age”, and the use of chromosomes for radiodosimetry as well as a tool to measure exposure to other work place pollutants.Less