bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraviolet Radiation Carcinogenesis
Authors: Cleaver James E. , Ortiz‐Urda Susana , Gulhar Radhika , T. Arron Sarah , Brookes Lionel , Mitchell David L. 
Published: March 2017

Overview
Skin carcinogenesis from solar ultraviolet (UV) exposure is initiated by UV photoproducts formed in the DNA of precursor cells that give rise to squamous cell carcinomas, basal cell carcinomas, and melanomas. These photoproducts consist of dimers between adjacent pyrimidines that are repaired by nucleotide excision repair (NER). Two branches of NER differ in mechanisms of damage recognition: in global genome repair (GGR), damage is recognized in nontranscribed DNA by the DDB2 and XPC proteins; in transcription‐coupled repair (TCR), damage is recognized by arrest of the transcribing RNA polymerase at damaged sites. The T = C photoproduct is the predominant mutagenic product which, if unrepaired, gives rise to C to T or CC to TT mutations through replication by the low‐fidelity polymerase Pol H. TCR reduces the mutation frequency in regions of transcription, in comparison to the rest of the genome subject to GGR. Deficiencies in GGR in the human disease xeroderma pigmentosum cause earlier onset and increased rates of skin cancer, which often contain UV‐type mutations in genes that are rarely mutated in the general population. Deficiencies in TCR in the human disease Cockayne syndrome are associated with photosensitivity, developmental, and neurological disorders, but no cancer has been reported.
Parasites
Authors: El Azzouni Mervat Z. , Diab Radwa G. 
Published: March 2017

OverviewMany parasites were studied for a possible role in oncogenesis.Schistosoma haematobiumwas proved to play an important role in developing urinary bladder cancer. OtherSchistosomaspecies,Schistosoma japonicumis classified as a colorectal carcinogen especially in the Far East. Other helminthsClonorchisandOpisthorchisare proved to induce hepatobiliary cancer. In Africa, a strong correlation between Ebstein–Barr virus infection and Burkitt lymphoma is present, with an evident enhancing role forPlasmodium falciparum. Chronic inflammation was incriminated to be the most accepted mechanism for parasite‐induced cancer; however, the roles of certain carcinogens, oncogenes, DNA mutations, and others were all approved as mechanisms enhancing carcinogenesis in parasitic infections. Strikingly, despite the above‐mentioned data, it seemed that certain parasites can modulate the host immune response in a manner that could lead to cancer regression or prevention. This is in the prospect of revaluation of the clinical importance of infectious agents; an issue that requires future concern.
Chemoprevention of Cancer
Authors: William William N. , Hong Waun Ki , Lippman Scott M. 
Published: March 2017

OverviewThe field of cancer chemoprevention is underpinned by two phenomena of neoplasia: field carcinogenesis and multistep carcinogenesis. Accurate cancer risk models are critical to chemoprevention and may accelerate drug development in this setting. The Food and Drug Administration has approved several chemoprevention strategies. This chapter describes completed chemoprevention clinical trials focused on the four major cancer sites in the Western world (lung, colon and rectum, prostate, and breast), as well as site‐agnostic chemoprevention studies. The contributions of vaccines to cancer prevention are also discussed.
Principles of Medical Oncology
Authors: Hait William N. , Holland James F. , Frei Emil , Kufe Donald W. , Bast Robert C. , Hong Waun Ki 
Published: March 2017

Overview
The practice of medical oncology is evolving more rapidly than any field in medicine. The uncovering of the molecular basis of the numerous malignancies and their subtypes created a seemingly bewildering collection of new information that confronts the practicing physician. Since the principles that underlie the practice of this subspecialty, by definition, should remain constant, they can provide the scaffolding on which new information can be attached. To that end, this chapter attempts to define those immutable areas that apply to the care of the oncology patient, and through their understanding the massive amount of new information presented in this text can be organized.
Principles of Psycho‐Oncology
Authors: Holland Jimmie C. , Wiesel Talia W. 
Published: March 2017

Overview
This chapter provides oncologists with the present state of the art in psycho‐oncology, a subspecialty that has evolved over the past 30 years. The basic treatment, particularly pharmacologic, is outlined for anxiety, depression, and delirium, as well as the psychotherapeutic interventions which are based on evidence. The field has come of age since it received the Institute of Medicine blessing in 2008 stating that quality cancer care must integrate the psychosocial domain in routine care. This was given a strong boost from the American College of Surgeons Commission on Cancer which made screening for distress a quality standard for accreditation in 2015, requiring that all cancer centers have in place—or in development—an on‐site program to identify and triage patients who are distressed. This has resulted in a strong effort to develop routine screening of all new patients to assure that they are recognized early and treated appropriately. Implementation of programs is in progress across the country with assistance available from the American Psychosocial Oncology Society (APOS) which has organized training, consultation, and ongoing mentoring for cancer staff. Indeed, thanks to these changes in national policy related to cancer, it is a different experience for patients today to cope with cancer. Attention has turned to providing patient‐centered care which encompasses care of the whole person.
Preclinical and Early Clinical Development of Chemotherapeutic Drugs, Mechanism‐Based Agents and Biologics
Authors: Hanauske Axel‐R. , Von Hoff Daniel D. 
Published: March 2017

OverviewOver the past 10 years, the approach to drug development has changed considerably. Owing to the enormous increase in insights into the molecular biology of cancer cells, a largely empirical approach has been mostly abandoned and replaced with a biology‐driven, hypothesis‐based, and translational approach. Notwithstanding this dramatic development, the hierarchical sequence of clinical drug‐development trials basically remained unchanged and is divided into three phases. This chapter provides an overview of the various steps of early clinical development with milestones of the drug‐development process, the role of the National Cancer Institute, and the switch to mechanism‐based drug development. It outlines challenges in the clinical development of these new agents and provides a fundamental understanding of the complexity involved in early clinical drug development.
Cytokines, Interferons, and Hematopoietic Growth Factors
Authors: Ekmekcioglu Suhendan , Grimm Elizabeth A. 
Published: March 2017

OverviewCytokines are important mediators of immune responses and produced by almost every cell in the body. Growth stimulatory or inhibitory cytokines could be subclassified as interleukins (ILs), lymphokines, monokines, chemokines, and hematopoietic growth factors. In cancer, certain cytokines act directly on the growth, differentiation, or survival of endothelial cells, whereas others act by attracting inflammatory cell types affecting angiogenesis or by inducing secondary cytokines or other mediators regulating angiogenesis. Proinflammatory and chemotactic cytokines influence the tumor environment and control the quantity and nature of infiltrating hematopoietic effector cells, with inhibiting or enhancing effects on tumor growth. The important role of cytokines in regulating immune responses may permit an effective immune response against the tumors or suppress the function of antigen‐presenting cells (APC).The understanding of cytokines has now emerged as complex picture of interacting stimulatory and inhibitory factors. Many of the molecules that govern this process have been cloned and have entered clinical trials. It is now clear that regulatory cytokines are characteristically pleiotropic and, at the same time, exhibit significant functional redundancy.The biologic characterization of the known clinically relevant ILs, interferons and selected growth factors, the rationale for their use in therapy for patients with cancer, and the accumulated clinical experience represent the subjects of this chapter.
Cancer Gene Therapy
Authors: Tashiro Haruko , Brenner Malcolm 
Published: March 2017

OverviewGene therapy of cancer has shown increasingly encouraging results and now is ready to enter mainstream oncological practice. Gene transfer can modify the cellular phenotype and behavior of malignant cells or host immune cells in order to modulate tumor responses. In this chapter, we discuss both of the above approaches and describe the vector systems that are able to produce the intended genetic modifications. We describe current clinical successes of gene therapy and outline the challenges it has yet to overcome. The success of either approach depends on efficient, safe gene transfer with vectors that can either integrate (e.g., retroviral, lentiviral, or adeno‐associated viral, or transposons) or not integrate (e.g., adenoviral, herpesviral, or nonviral) into the human genome. To date, reversing the phenotype of all stem cells within a cancer has not proven feasible, and infectious cytolytic viral therapy has not yet had a significant impact in the clinic. Enhancement of active cancer immunotherapy with forced expression of antigens and cytokines or the enhancement of adoptive immunotherapy by engineering T lymphocytes with specific T‐cell receptors and chimeric antigen receptors shows greater immediate promise, although ultimately a combination of multiple approaches will prove optimal.
Principles of Pediatric Oncology
Authors: Bhatla Teena , Carroll William L. 
Published: March 2017

OverviewPediatric malignancies differ from those that occur in adults in their relative incidence, pathological type, clinical presentation, and prognosis. The last several decades of the twentieth century have been a period of enormous accomplishment in the field of pediatric cancer research and outcomes have steadily improved largely due to results from large well‐controlled clinical trials conducted by various cooperative groups at the national and international level. This chapter seeks to provide a broad overview of pediatric oncology, outlining the several common cancer types that are unique to the pediatric age group.
Cancer and Aging
Authors: Hurria Arti , Muss Hyman B. , Cohen Harvey J. 
Published: March 2017

OverviewCancer is a disease of aging. Approximately sixty percent of all cancers and seventy percent of cancer mortality occurs in people >/= age 65. The number of older adults with cancer is on the rise as the US population is aging. However, there is great heterogeneity in the health status of older adults which may impact cancer treatment decisions and outcomes. This chapter will review the principles of geriatric assessment and frailty, the biology of cancer and aging, as well as the unique issues and considerations in caring for older patients with cancer during treatment and into the survivorship years.
Disparities in Cancer Care
Authors: Brawley Otis W. 
Published: March 2017

Overview
Differences in healthcare outcome have become increasingly apparent over the past 50 years. It is especially apparent in cancer, a discipline that has had tremendous advancement. Ironically, the more progress that is made, the greater the disparities become. There are populations that do not enjoy the progress usually because of socioeconomic differences. The field of health disparities has grown into its own discipline within epidemiology. It involves population categorization by race, area of geographic origin, socioecomic status, and so on. The discipline looks at differences in risk of cancer, risk of death, survival, and the survival experience.
A number of well‐designed studies show that equal treatment yields equal outcome among equal patients whether one categorizes population by race, socioeconomics, or other major factors. If people with the same genetic markers are compared, race for example is not a factor in outcome unless it is allowed to be. Numerous patterns of care studies demonstrate that there is not equal treatment by race in the United States. The discipline of health disparities has progressed to include assessment of interventions to reduce disparities.
The advent of precision medicine and tailored therapy will make categorization using genes and polymorphisms more important. The crude categories of race and ethnicity and even socioeconomic status will only be important in terms of social issues such as access to care and equality of treatment.
Social interventions to overcome disparities and bring about equity include efforts to (1) increase cultural competence and understanding of the patient among healthcare providers; (2) increase access to care; and (3) improve communications and educate those needing service.
Primary and Metastatic Neoplasms of the Brain in Adults
Authors: DeAngelis Lisa M. 
Published: March 2017

OverviewPrimary brain tumors are uncommon but aggressive neoplasms even when histology is low grade. Secondary, or metastatic, tumors are at least 3 times more common than all primary tumors combined. Diagnosis is easily established by magnetic resonance imaging (MRI), and surgical resection provides histologic confirmation and decompression; surgery alone may suffice for low‐grade tumors and most extra‐axial tumors such as meningiomas. Treatment of parenchymal brain tumors, primary or metastatic, often requires a combination of radiotherapy and chemotherapy, which may improve patient function and control disease but rarely achieves cure.
Cancer of the Lung
Authors: Lu Charles , Morgensztern Daniel , Chiang Anne , Onn Amir , Sepesi Boris , Vaporciyan Ara A. , Chang Joe Y. , Komaki Ritsuko K. , Wistuba Ignacio I. , Herbst Roy S. 
Published: March 2017

OverviewWorldwide, lung cancer is responsible for the largest number of cancer‐related deaths, and reducing tobacco consumption is the most effective way to reduce lung cancer mortality. Standard therapy options continue to include surgery, radiotherapy, and/or chemotherapy. As lung cancer is a heterogeneous disease, it is hoped that translational proteomic and genomic research will advance our understanding of driver molecular pathways and allow development of more effective, less toxic, targeted therapies. Recent developments in immunotherapy have generated significant excitement and represent a novel therapeutic strategy, which has already impacted current standard of care.
Malignant Pleural Mesothelioma
Authors: Gomez Daniel R. , Tsao Anne S. , Yang Haining , Pass Harvey I. 
Published: March 2017

OverviewMalignant pleural mesothelioma is an aggressive malignancy with an incidence that may be peaking worldwide in the next 5–10 years. While the majority of patients do ultimately die of this disease, there have been substantial treatment and diagnostic shifts over the past decade that may improve long‐term outcomes. These changes include worldwide interest in defining early detection biomarkers for the disease, a debate as to the optimal surgical approach (extrapleural pneumonectomy vs lung‐sparing methods such as pleurectomy/decortication), further refinement of radiation techniques that allow for conformal treatment fields and the delivery of radiation with the involved lung intact, and the emergence of systemic therapies that are targeted in nature and allow for the increased individualization of care. Indeed, prospective clinical trials assessing the safety and efficacy of novel treatment approaches will be essential to the standardization of paradigms that improve the outcomes. It is hoped that the maturation of these efforts will lead to an optimal approach in which earlier‐stage patients will benefit from multiple modalities that will provide synergistic control while limiting toxicity, thereby increasing the number of long‐term survivors over the next one to two decades.
Neoplasms of the Prostate
Authors: Logothetis Christopher J. , Kim Jeri , Davis John W. , Chapin Brian F. , Kuban Deborah , Efstathiou Eleni , Aparicio Ana 
Published: March 2017

OverviewCancer of the prostate is the most commonly diagnosed nonskin neoplasm and the second leading cause of cancer‐related mortality in men in the United States. Considerable advances have been made in screening, diagnosis, and therapy options, particularly in advanced disease, but controversies about the diagnosis and management of prostate cancer, especially in the areas of screening and choice of therapy, continue to evolve. Controversies in advanced disease states have shifted from prognostication to prediction, and current treatment considerations are focused on optimization of sequence or combinations of therapy, determining the role of local control and bone targeting. It is anticipated that addressing these knowledge gaps will lead to an integrated and more effective treatment strategies. Further advances in therapy can be achieved by development of new agents with unique mechanisms of action and rational integration into combination therapies.Prostate cancer awareness, clinical application of improved biopsy schemes, and advances in imaging combined with the widespread use of prostate‐specific antigen (PSA) have resulted in increased detection of prostate cancer. The evolving use of the serum PSA concentration and its change over time have not been paralleled by studies that tested the relevance of those findings until the results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were first published in 2009. Though many of the apparent discrepancies between these trials can be accounted for by trial design and patient cross‐contamination, they brought to the forefront the dilemma of overdiagnosis and overtreatment and the urgent need to improve the accuracy of clinically significant prostate cancer. It is hoped that replacement of the current morphologic and anatomic classification of prostate cancer with one based on improved understanding of biology will lead to molecular classification and bring closer a personalized management of this complex disease.Salient features that distinguish prostate cancer from other malignancies and that frame the dilemmas surrounding it are its striking age‐dependent incidence, with progressively increasing frequency with increasing age; the variable lethality of morphologically identified cancers; the central role of androgen signaling; and the preponderance of bone‐forming metastases on its lethal progression. The important advances made in each of these areas will, in the near future, modify the approaches currently used to prevent, prognosticate, and treat prostate cancer.
Tumors of the Penis and the Urethra
Authors: Holland James F. , Lance Raymond S. , Lynch Donald F. 
Published: March 2017

OverviewCarcinoma of the penis, predominantly squamous, some related to human papilloma virus, is rare in the developed world and among circumcised men, but of major importance elsewhere. Surgery early can be curative. Other modalities are less robust. Voluntary adult circumcision to diminish susceptibility to human immunodeficiency virus infection is being observed as possibly preventive. Urethral cancer, rare, usually of transitional epithelium, is often detected too late for cure.
Nonepithelial Ovarian Malignancies
Authors: Berek Jonathan S. , Friedlander Michael L. , Bast Robert C. 
Published: March 2017

OverviewCompared with epithelial ovarian cancers, nonepithelial ovarian tumors are uncommon, constituting <10% of all ovarian malignancies. They include germ cell malignancies, sex‐cord–stromal tumors, carcinomas metastatic to the ovary, and a variety of extremely rare ovarian cancers, including sarcomas and lipoid cell tumors. Although there are many similarities in the presentation, evaluation, and management of patients, these tumors also have unique features that require special approaches to management. Germ cell malignancies are derived from primordial germ cells of the ovary and can be distinguished by histotype and expression of the biomarkers alpha‐fetoprotein (AFP) and/or human chorionic gonadotropin (hCG). They include dysgerminomas (AFP−hCG−), embryonal carcinomas (AFP+hCG+), immature teratomas (AFP−hCG−), endodermal sinus (yolk sac) tumors (AFP+hCG−), and ovarian choriocarcinomas (AFP−hCG+). Germ cell tumors occur in premenarchal girls and young women, grow rapidly, and can present with a symptomatic pelvic mass. As preservation of fertility is often an important priority, unilateral salpingo‐oophorectomy can often be performed followed by adjuvant platinum‐based therapy. Among the germ cell tumors, dysgerminomas can be bilateral in 10–15% of cases and are associated with gonadal dysgenesis in 5% of cases. Metastatic germ cell cancers can be quite sensitive to chemotherapy and the long‐term survival rate is high, even in advanced stages. At some institutions, young patients with stage IA germ cell tumors are followed carefully after resection and chemotherapy given only if there is recurrence with excellent outcomes. Sex‐Cord‐Stromal tumors include Granulosa‐Stromal tumors, Juvenile Granulosa tumors, and Sertoli–Leydig cell tumors. Granulosa‐Stromal tumors can occur at all ages and produce estrogen resulting in pseudoprecocious puberty in a small fraction of girls, amenorrhea in pre‐menopausal women, and endometrial hyperplasia in postmenopausal adults. Granulosa‐Stromal tumors are indolent and often confined to one ovary where surgery can cure stage I disease in more than 75% of cases. Adjuvant chemotherapy is generally not given after complete resection. Late recurrence has, however, been observed. Persistent or recurrent disease has responded to platinum based and hormonal therapy, including progestational agents, luteinizing hormone‐releasing hormone agonists, and aromatase inhibitors. Inhibin B has been a useful biomarker. Sertoli–Leydig cell tumors generally present in the third or fourth decade, produce androgens, and induce virilization in more than 70% of patients. As many Sertoli–Leydig cell tumors are in early stage and rarely bilateral, unilateral salpingo‐oophorectomy is often performed with 70–90% 5‐year survival.