bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms and Management of Cancer Pain
Authors: Anand Uma 
Published: October 2007

AbstractChronic intractable pain is experienced by an overwhelming majority of cancer patients, compromising their quality of life. The pain can be due to several causes: infiltration by tumours, bone metastases, or a consequence of therapy. The mainstay of analgesia has been opioid treatment of various formulations, but this is limited in efficacy and is not without considerable side effects. Recent advances in understanding the underlying pathophysiological and molecular mechanisms of cancer pain have been derived from animal models and related histopathological findings from chronic pain patients. The identification of novel drug targets, and their imminent clinical trials, provides the prospect of new treatments for alleviating cancer pain in the near future.
Head and Neck Cancer
Authors: Seiwert Tanguy Y. , Vokes Everett E. 
Published: October 2007

AbstractHead and neck cancer (HNC) is the fifth most common cancer worldwide and, in particular, locoregionally (LR) advanced disease continues to be a challenge.HNC treatment has improved dramatically during the past decade owing to advances in radiation and chemotherapy (namely concurrent chemoradiotherapy (CRT)) and improvements in surgical technique. Multiple differing treatment approaches exist. We therefore attempt to give an overview of the field and make recommendations on the basis of available data.In the future the integration of epidermal growth factor receptor (EGFR) inhibitors will further increase efficacy and limit toxicities. In addition, the integration of induction chemotherapy is currently being investigated as a measure to decrease distant metastatic spread.HNC – using an integrated multidisciplinary treatment approach involving chemotherapy and radiation, as well as surgery and novel therapeutics – is a highly curable disease.
Gene Knockouts in Cancer Research
Authors: Merghoub Taha , Pandolfi Pier Paolo 
Published: October 2007

AbstractUnderstanding genetic pathways is a prerequisite for the development of molecular and pharmacological therapies in order to treat and prevent cancer effectively. Transgenic approaches and mouse modelling have been developed as standard techniques for gene targeting that enables the dissection of cancer‐related cellular mechanisms. The possibility of manipulating and culturing pluripotent mouse embryonic stem cells has allowed for the generation of mice with a specific alteration in a chosen target gene. Transgenic mice harbouring activated forms of proto‐oncogenes or dominant negative forms of tumour‐suppressor genes have been generated in order to test the causal relationship between their expression and tumour development. In order to circumvent certain limitations of unspecific genetic alterations, conditional targeting strategies and tissue‐specific expression methods have been created, making it possible to introduce more subtle gene alterations and identify tumour modifiers and cancer‐related signaling networks. This chapter describes basic techniques for the generation of gene alterations in mice, their usefullness, and their limitations.
Introduction to the Diagnosis of Cancer
Authors: Wilczynski Sharon Poltis 
Published: October 2007

AbstractThe diagnosis is a name that is given to a disease process that summarizes its probable natural history, and possible aetiology and is the foundation for all potential treatment. Making a diagnosis of cancer in an individual patient is a complex process that requires the integration of clinical, molecular, and morphologic findings. In this chapter we discuss how cancer is detected in a population by screening as well as the methods that are used to classify tumours including histopathology, immunohistochemistry, and molecular studies. Features of tumours that are important for treatment such as grade, stage, and predictive and prognostic factors as well as the monitoring of response to therapy are also covered.
Models for Genitourinary Cancer – Hereditary Renal Carcinogenesis
Authors: Hino Okio 
Published: October 2007

AbstractThe Eker (Tsc2gene mutant) rat model of hereditary renal carcinoma (RC) is an example of Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. Recently, we discovered a new hereditary RC in the Japanese rat, which was named the “Nihon” rat. The predisposing (Bhd) gene could be a novel renal tumour‐suppressor gene.We present these unique models for the study of problems in renal carcinogenesis.
Models for Human Leukaemias
Authors: Koschmieder Steffen , Serve Hubert L. 
Published: October 2007

Abstract

Animal models for human leukaemias have provided important insight into their molecular pathogenesis. As a consequence, molecularly targeted therapy for several human leukaemias has entered clinical practice, which greatly improves efficacy and lowers toxicity of anti‐leukaemic treatment. Several organisms are being utilized to study the process of leukaemic transformation, including not only
Drosophila
,
Caenorhabditis elegans
, or
Xenopus
but also zebrafish. Most frequently though, spontaneous or induced leukaemias in the mouse are used. Using xenotransplant models of human leukaemic cell lines and leukaemic cells from patients into immunodeficient mouse strains, we have learnt important lessons about the composition of the leukaemic cell population in human disease. In fact, these experiments led to the description of leukaemia‐initiating cells, the first described cancer stem cell. However, animal models have also led to the definition of oncogenes required for leukaemic transformation and are also being used for the evaluation of molecular therapeutic targets. Two strategies for the evaluation of genes in the pathogenesis of human leukaemias are frequently used: (i) transplantation strategies, where genetically modified cell lines or primary bone marrow is injected into recipient animals. (ii) Analyses of genetically modified animals. Both model systems have led to important insights into the role of human oncogenes in leukaemic transformation. Most recently, these model systems are combined to yield sophisticated information about the cooperation of oncogenes, to identify genes that are important for abnormal stem cell functions, and to evaluate the oncogene products as therapeutic targets.
The Role of Epigenetic Alterations in Cancer
Authors: Ballestar Esteban , Esteller Manel 
Published: October 2007

Abstract
Epigenetics has burst into the cancer field. DNA methylation changes, implicated in both silencing of tumour‐suppressor genes and chromosomal instability, were among the first recognized epigenetic alterations. More recently, disruption of the histone modification profile has just started to be unravelled. The impact of epigenetic alterations covers many different aspects of cancer: it provides a context to explain chromosomal rearrangements, inactivation of tumour‐suppressor genes and, in general, aberrant expression of many genes involved in cell differentiation, proliferation, apoptosis, and so on. Moreover, the recognition of epigenetic alterations in all types of cancers has multiple implications: first, it sheds light on the mechanistic insights by which genetic alterations are complemented in the development and progression of cancer; second, epigenetic alterations exhibit a prominent role in the initiation of cancer. In addition, because epigenetic changes are reversible, enzymes involved in their maintenance stand as targets for a variety of compounds used for therapy.
Urinary Tract
Authors: Tamboli Pheroze , Gomez José A. , Jiménez Rafael E. 
Published: October 2007

AbstractThis chapter covers the most common tumours that affect the urinary tract, including tumours arising from the kidney, renal pelvis, ureter, urinary bladder, and urethra. The tumours discussed in this text include Wilms' tumour, renal cell carcinoma, urothelial carcinoma, squamous carcinoma, and adenocarcinoma.
Lymph Nodes
Authors: Müller‐Hermelink Hans Konrad , Ott German , Haralambieva Eugenia 
Published: October 2007

Abstract
The current chapter provides comprehensive data on the tumours derived from the lymphoid tissues that are most commonly affecting the lymph nodes. We discuss the principles of the current classification of lymphoid neoplasia, its clinical relevance, and the possible use of different prognostic factors. For every disease entity, up‐to‐date information on the specific clinical presentation and site of involvement, morphology, including different morphological variants, immunophenotype and genetics is offered. Basically, the lymphoid tumours consist of Hodgkin's disease and non‐ Hodgkin's lymphomas and the latter are subclassified into B‐ and T‐cell lymphomas, according to their putative cell of origin. On the basis of the literature and our own experience we review the relevance of specific lymphoma features for the diagnosis and clinical outcome of lymphoma patients.
Bones
Authors: Klein Michael J. 
Published: October 2007

AbstractBone tumours represent some of the least common malignant and benign human neoplasms. They are classified not only by their cellular contents but also by the extracellular connective tissue matrix they produce. Their accurate diagnosis rests not simply upon the histology but in the correlation of their clinical, radiographic, and pathologic features. This constellation of features is usually fairly reproducible for any given bone tumour. While many of the tumours have no known predispositions, a modest number are associated with genetic predispositions. In addition, some non‐neoplastic diseases and iatrogenic causes may also predispose to the development of certain bone tumours. While untreated malignant bone tumours are highly lethal, the advent of chemotherapy in addition to surgery has made overall survival more favourable.
Neuromuscular System
Authors: Fung Kar‐Ming , Trojanowski John Q. 
Published: October 2007

Abstract
The discussion focuses on tumours of the central and peripheral nervous systems. It starts with a brief discussion on the normal development of the nervous system, followed by a discussion on the epidemiology, aetiology, detection, and prevention of brain tumours. Details of the more commonly encountered tumours of the central and peripheral nervous systems are discussed. The molecular genetics section focuses on hereditary cancer syndromes related to the nervous system and also the pathogenesis and progression of brain tumours. Prognostic factors and clinical management of brain tumours are also briefly discussed.
Eye and Ocular Adnexa
Authors: Burnier Miguel N. , Odashiro Alexandre Nakao , Gregoire François J. 
Published: October 2007

Abstract
Ocular pathology is a subspecialty of both pathology and ophthalmology with few specialists around the world. Like many other pathology specialties, the clinical–pathological correlation is essential for a correct diagnosis. Most of the diseases and tumours affecting the eye and ocular adnexae can be seen in other sites of the body. However, there are some specific tumours that are characteristic of the eye and are rarely found or do not exist anywhere else, like sebaceous carcinoma of the eyelid, conjunctival melanosis, retinoblastoma, and uveal melanoma. Also, the eye can be a source of systemic diseases and disseminated tumours. In this chapter we review the most important tumours in ophthalmic pathology emphasizing the clinical features, pathological diagnosis, and differential diagnosis.
Ear
Authors: Wenig Bruce M. 
Published: October 2007

AbstractThe ear and temporal bone represent a complex anatomic region that includes the organs of hearing and balance. Neoplasms of the ear and temporal bone are uncommon. This chapter details the clinical and pathologic features of the more common neoplasms occurring in the ear and temporal bone. Despite their relative rarity, recognition of the specific clinical and pathologic features should allow for their recognition and differentiation from similar appearing lesions/neoplasms. Treatment is often predicated on the specific tumour type, although the primary mode of the treatment for the more common neoplasms of this anatomic region is surgical resection. Several middle ear/temporal bone neoplasms may be indicators of associated diseases, including acoustic neuromas and meningiomas with neurofibromatosis, and endolymphatic sac papillary tumours with von Hippel‐Lindau syndrome. Knowledge of these unique associations may prompt evaluation and diagnosis of the associated disease and/or syndrome.
Transgenic Technology in the Study of Oncogenes and Tumour‐Suppressor Genes
Authors: Wynshaw‐Boris Anthony 
Published: October 2007

Abstract
Genetic manipulation of the mouse via transgenic or knockout techniques has revolutionized the study of genes that cause cancer. The development of this technology has allowed investigators to examine the biological activity of genes that are important for the formation of cancer. In this chapter, the basic experimental design for the use of genetic manipulation of the mouse for the study of oncogenes and tumour‐suppressor genes will be discussed. Chromosome engineering techniques will be described. More recent strategies that allow investigators to have exquisite control over gene activation and inactivation have refined the use of mouse models to more accurately reflect and model human cancer. However, limitations to the use of mouse models still exist and will be discussed.
Genetic Models: A Powerful Technology for the Study of Cancer
Authors: Wang Ping , Li Suling 
Published: October 2007

Abstract

Transgenics has been proved to be an irreplaceable tool for cancer research. Not only have transgenic models provided the mechanisms of cancer‐related genes, but also models for development of therapeutic strategies. Since cancer is a consequence of genetic events that occur in a permissive epigenetic state influenced by environmental factors, the naturally occurring tumourigenesis in humans is far more complicated than cancer models generated by conventional transgenic technologies. Such a limitation promotes unlimited modification of transgenic technologies for the generation of murine cancer models with latent, conditional, and inducible alleles to better mimic the
in vivo
setting in which sporadic human cancers occur. In these mice, somatic mutations can be induced in a tissue‐specific and time‐controlled fashion, which more faithfully mimics sporadic tumour formation. These conditional models provide opportunities to gain insight into the role of genes in the initiation, progression, and treatment of cancer, and mimic human cancers better than ever before.
Models for Tumour Growth and Differentiation
Authors: Riedel Heimo 
Published: October 2007

AbstractHuman tumour growth can typically be studied only during the last quarter of its development after the tumour has been detected and in the presence of therapeutic interference. The progress of a large tumour does not correlate well with its early, but undetected, stages of cell proliferation. Tumour proliferation is described by (i) the rate of individual cell division, (ii) the growth fraction of the cell population, and (iii) the rate of cell loss from the growing population such as through differentiation or cell death. Cell proliferation and differentiation are largely seen as opposed concepts such that a terminally differentiated cell can no longer proliferate or undergo malignant transformation or such that tumours typically represent a reduced level of cell differentiation. The concept of (proto)oncogenes and the opposed tumour‐suppressor genes, both typically involved in cell proliferation control has been instrumental in defining the series of sequential genetic alterations that result in tumourigenesis. This has been complemented by cell culture, including three‐dimensional models based on primary and immortalized lines. With the available tools of modern molecular biology, primary human cells have been transformed to a malignant phenotype through the sequential introduction of at least four genetic alterations. This phenotype is scored by tumourigenicity in an immunocompromised mouse model and significantly depends on the stromal microenvironment. Aided byin vitromodels a limited number of genetic alterations have now been defined, of which some are found in virtually all human cancers. These can now be specifically targeted by rational drug design with increased selectivity and reduced cytotoxicity. Drugs to exploit the residual capacity of tumour cells to undergo differentiation are under investigation and promise loss of tumourigenesis with minimal impact on normal cell proliferation.
Models for Tumour Metastasis
Authors: Hill Richard 
Published: October 2007

Abstract

Metastasis is a process by which tumour cells establish new growths at sites in the body distinct from the primary tumour. It is complex, involving a number of stages including escape of tumour cells from the primary tumour and arrest, intravasation, and development of a new growth in a distant organ or lymph node. Although some of the individual stages can be modelled
in vitro
, an assessment of the ability of individual tumour cells to complete all stages requires the use of
in vivo
metastasis models. Many different models have been used for studying the multiple aspects of metastasis, but identifying appropriate models that mimic all the characteristics of specific human cancers remains a problem. Metastasis is a very inefficient process with very few tumour cells demonstrating the capacity to grow to form macrometastases, even though they may have initiated the growth of micrometastases. Many specific genetic changes have been identified in tumour cells (and host normal tissue) that can enhance or inhibit metastasis formation but the efficacy of such genetic changes appears to be highly tumour‐cell specific. Recent work developing genetically engineered mouse (GEM) models and models involving human normal tissues transplanted into immune‐deficient mice (SCID‐hu models) is opening up new ways to address some of the many questions remaining about the molecular mechanisms underlying the metastatic process.
Models for Tumour Cell—Endothelial Cell Interactions
Authors: Gassmann Peter , Nicolson Garth L. , Haier Jörg 
Published: October 2007

Abstract

The endothelium is composed of a continuous, semipermeable, and metabolically highly active lining of endothelial cells (ECs) and an underlining basement membrane composed of various extracellular matrix components. The endothelium serves multiple physiologic functions in health and is fundamentally involved in many pathophysiologic conditions like inflammation; wound healing; and cancer, beside others. Endothelial cells mediate the nutritional supply of growing cancerous lesions, are involved in the body's immunologic response to cancer, and mediate initial interactions between circulating tumour cells and metastasis target organs. Endothelial cells and the basement membrane are not uniform throughout the body, but display distinct morphologic and functional characteristics depending on the vascular province they are derived from. Primary derived EC are usually not transformed and lose their endothelial differentiation during
in vitro
culture. Therefore, easily accessible macrovascular ECs like “human umbilical vein endothelial cells” (HUVEC) have been widely used in cancer research. These models are easily reproducible and standardized throughout the literature. Nevertheless, tumour cell–EC interactions are highly dependent on the ECs' origin and microvascular endothelial cells (MECs) show significant differences compared to macrovasular ECs in their morphologic and functional characteristics while interacting with other cell types like tumour cells. Therefore, while analysing tumour cell–EC interactions the ECs' source needs to be carefully selected according to the study's intention and has significant impact on experimental results obtained.
Models for Drug Development and Drug Resistance
Authors: Chou Joseph H. , Chang Tai‐Tsung , Chou Ting‐Chao 
Published: October 2007

AbstractThis chapter describes the drug development process and models in the historical and future perspectives. The features of different models are given and the advantages and disadvantages are elaborated. The focus is at preclinical levels with special emphasis on the evaluation of efficacy and toxicity of candidate antitumour compounds. Methods of overcoming drug resistance are described with special emphasis on drug combinations and computerized, automated data analysis for the quantitation of synergism or antagonism. The theoretical basis of the concept of combination index, dose‐reduction index, isobologram, and polygonogram (i.e., the Chou‐Talalay method) is also given. A specific example for preclinical pharmacological, toxicological, and therapeutic evaluation of a microtubule stabilization antitumour agent—fludelone—that leads tode factotherapeutic cure against human tumour xenografts is provided. Specific examples for the reversal of multidrug resistance by ardeemin or ningalin are illustrated.
Models for Immunotherapy and Cancer Vaccines
Authors: Meisel Roland , Tröger Anja , Moritz Thomas , Dilloo Dagmar 
Published: October 2007

AbstractImmunotherapy of cancer has emerged as a promising new strategy to complement standard anticancer therapies such as chemotherapy, surgery, and radiotherapy. While the currently available data from clinical trials of cancer vaccines provide evidence for the therapeutic benefit of this approach, it is currently confined to a minority of patients. In this chapter, we give an overview on current concepts and experimental models of cancer immunotherapy with a particular focus on cancer cell‐ and dendritic cell–based vaccines. We then proceed to discuss the emerging new data on immune evasion strategies of cancer such as the secretion of paracrine immunoinhibitory factors and the role of regulatory T cells. Exploration of immune escape mechanisms are critical for identification of novel immunotherapy targets to allow for further optimization of cancer immunotherapy. Such strategies hold considerable promise when incorporated into multimodal approaches as exemplified by the combination of chemotherapeutic cytoreduction with tumour vaccination or adoptive transfer of immune effector cells as described in the final part of this chapter. The rapid preclinical evaluation of these novel approaches is today greatly facilitated by the widespread availability of “fully humanized” mouse xenograft models. In addition, good manufacturing practice (GMP)‐grade reagents for immune cell purification support a swift transfer of new experimental insights from bench to bedside. Also targeting patients with low tumour burden instead of bulky or metastasized disease will further the success of clinical immunotherapy.
Models for Gene Therapy
Authors: Sweeney Colin L. , Lin Yuan , Gerson Stanton L. 
Published: October 2007

AbstractThere have been a number of approaches for gene therapy of cancer, directed either at the tumour or at normal host cells. Cancer‐directed strategies include tumour‐suppressor gene transfer, gene knockdown, suicide gene transfer, and oncolytic viruses. Host‐directed strategies include anti‐angiogenic, immunomodulatory, and drug‐resistance gene therapy. In this chapter, preclinical models are discussed for each of these approaches.