bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Cavity and Major and Minor Salivary Glands
Authors: Tilakaratne Wanninayake M. 
Published: October 2007

Abstract
Cancer of the oral cavity is almost synonymous with squamous cell carcinoma as 90% of cancers in the oral mucosa appear to be of this type. The sixth most common oral malignancy is the different types of adenocarcinoma arising from salivary glands. A small proportion of cancers in the oral cavity are composed of melanoma, lymphoma, and various types of sarcomas. Oral squamous cell carcinoma is the sixth common malignancy and is a major cause of cancer morbidity and mortality worldwide. Although the aetiology is thought to be multifactorial, tobacco use in many different forms appears to play a major role. It is clear that various other factors such as genetic susceptibility, alcohol, nutritional deficiencies, viruses, fungi, and ultraviolet light have either a synergistic role or direct effect on oral carcinogenesis. A significant number of cases occur in a background of either a precancerous lesion or a precancerous condition. Molecular markers which have been investigated for determining different aspects of oral cancer can be classified into DNA content (ploidy), loss of heterozygosity, expression of oncogenes and onco‐suppressor genes, proliferation markers, and differentiation markers. However, prediction of malignant transformation of precancers and prognosis of oral cancers with the help of molecular markers need further research. Despite the advancement in treatment involving surgery, chemotherapy, and radiotherapy, the long‐term survival has been less than 50% with no significant improvement in prognosis over the last four decades. Salivary neoplasms account for up to 2% of all neoplasms in the head and neck. Although the exact aetiology of salivary gland tumours is far from clear, various aetiological factors such as radiation, viruses, occupational, hormonal, nutritional, and smoking have been suggested. Unlike most cancers, salivary tumours do not show any evidence of familial predisposition. Surprisingly, only a few studies have been carried out on salivary tumours in order to investigate molecular aspects. Prognosis of salivary tumours mostly depends on microscopical grade and tumour type. Surgery is the treatment of choice for a large majority of both benign and malignant salivary tumours. Chemotherapy and radiotherapy are used mostly as palliative measures.
Respiratory System
Authors: Hasleton Phillip S. , Sloan Philip 
Published: October 2007

AbstractThe respiratory tract is a common site for cancer. Exposure to inhaled industrial and environmental particles, particularly those associated with smoking, is a major cause. Viruses also play a part, particularly the Epstein‐Barr virus (EBV) in nasopharyngeal carcinoma and human papillomavirus in squamous carcinomas of oropharynx, larynx, and bronchus. We focus on the more common and important cancers of the respiratory tract and give differential diagnoses where relevant. The World Health Organization has recently produced revised classifications of tumours of the respiratory tract (2004) and head and neck (2005). Sarcomatoid carcinoma has been added to the previously recognized squamous cell carcinoma, small cell carcinoma, adenocarcinoma, and large cell undifferentiated carcinoma of the lung in the new classification. Sinonasal undifferentiated carcinoma is also included as a recognized entity. It is increasingly recognized that precursor and early lesions are the best targets for interventions. Detection, biology, and current practice regarding assessment of precursor lesions are covered. It is increasingly recognized that many respiratory cancers arise in a field and second primaries with similar molecular features to the original tumour are being described.
Upper Gastrointestinal Tract
Authors: Stemmermann Grant N. , Noffsinger Amy E. , Fenoglio‐Preiser Cecilia M. 
Published: October 2007

AbstractBackgrounds of different types of oesophageal and gastric cancers are well known. Each of these cancers associates with known environmental exposures and carries a poor prognosis if sufficiently advanced to cause symptoms. A diet that provides fresh vegetables and fruit on a year‐round basis to all members of the society, the correction of tobacco and alcohol abuse, and the prevention ofHelicobacter pylorigastritis should prevent all but the small number of these cancers that arise from inherited germ‐line mutations. Knowing the clinical and anatomic precursors of these cancers enables us to find them at an early, treatable stage.
Lower Gastrointestinal Tract
Authors: Jass Jeremy R. 
Published: October 2007

AbstractThis chapter provides an overview of benign and malignant neoplasms affecting the lower intestinal tract, but the main focus in on the commonest epithelial malignancy, namely, colorectal cancer. The multifactorial causation of colorectal cancer including both genetic and environmental factors is emphasized. Classical pathology is now supplemented by the application of molecular markers that allow colorectal cancers to be subclassified into new groups with their own clinical, pathological, and molecular features. Additionally, prognostic and predictive markers are becoming better established in clinical management, though their ultimate potential is yet to be fully realized. Surgical management remains the main therapeutic option, but adjuvant and neoadjuvant therapy are showing increasing clinical benefit with respect to both local recurrence and survival.
Models for Liver Cancer
Authors: Feo Francesco , Pascale Rosa M. , Calvisi Diego F. 
Published: October 2007

Abstract

Primary liver tumours include hepatocellular carcinomas (HCCs), cholangiocarcinomas, and hepatoblastomas. HCC is the most frequent liver tumour, whose development is preceded, both in humans and rodents, by the appearance in the liver of foci of altered hepatocytes (FAHs) and dysplastic nodules. Bipotential hepatic progenitor cells (HPCs), which may differentiate into hepatocytes or cholangiocytes, are liver tumour precursors. Several rodent models have been developed to study the aetiology, evolution, and pathogenesis of preneoplastic and neoplastic liver lesions. They include the woodchuck hepatitis model, chemical models in which hepatocyte initiation by a carcinogen is followed by a growth stimulus inducing clonal expansion of initiated cells, diet‐linked models based on induction of methyl donor deficiency, and transgenic/knockout models, particularly useful to study
in vivo
role(s) of genes favouring or suppressing neoplastic cell growth. Furthermore,
in vitro
growing liver tumour cell lines have been used to study the role of single genes or signal transduction pathways, the effect of inhibitor compounds and genome engineering on tumour growth, and gene expression profiles. Transplants of
in vitro
growing cells are currently used for chemopreventive and therapeutic approaches to hepatocarcinogenesis. Animal models of liver cancer allowed investigation of the molecular alterations involved in early stages and in the progression phase of hepatocarcinogenesis, thus evidencing the interspecies commonalties of the basic mechanisms of hepatocarcinogenesis, and strongly contributing to understanding the molecular bases of the disease. Finally, animal models allowed investigation of genetic predisposition to liver cancer and contributed to map predisposition genes, understanding the genetic model, and some effector mechanisms of cancer modifier genes.
Models for Skin Cancer
Authors: Philpott Michael P. , Bergamaschi Daniele , Storey Alan 
Published: October 2007

AbstractMalignant melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) are the three most common types of skin cancer. Malignant melanoma commonly arises from melanocytes in the epidermis and is the most lethal of skin cancers. BCC arises from keratinocytes and is the commonest cancer. There is considerable debate as to whether BCC arises from hair follicle keratinocytes and also because of the association of BCC with mutations that activate the sonic hedgehog (SHH) pathway, whether BCC may reflect failed organogenesis. SCC also arises from keratinocytes and is a more aggressive tumour than BCC and can form lethal metastases, whereas BCC rarely metastasize. All three skin cancers lend themselves to bothin vivoandin vitromodels and these are discussed in this chapter.
Liver, Gallbladder, and Extrahepatic Bile Ducts
Authors: Kanel Gary C. 
Published: October 2007

Abstract
Both benign and malignant hepatic neoplasms and tumourlike lesions provide interesting clues in tumour pathogenesis. This chapter discusses these tumours, with special emphasis on the two most common primary neoplasms, hepatocellular carcinoma and cholangiocarcinoma. The epidemiology, the various aetiologic factors, pathophysiologic concepts, and pathology are presented with brief mention on clinical presentations and treatment options and outcomes. Additionally, a brief discussion of tumours of the gallbladder and extrahepatic biliary system is also included.
Breast
Authors: Gudi M. , Stamp G. W. H. 
Published: October 2007

Abstract

This chapter gives an overview of the pathological changes in the breast and the current approaches to treatment and diagnosis. The micro‐anatomical structure of the breast is described in relation to pathogenesis of common benign diseases of the breast which may simulate cancer clinically. The generation of epithelial hyperplasias and definition of atypical hyperplasias (ADH and ALH) is addressed with updated classification. Emphasis is placed on the evolution of lobular and ductal
in situ
neoplasia and their relationships to invasive carcinoma in the main types of breast cancers are described together with the parameters used for pathological assessment. The molecular genetic and biological alterations in breast cancers are listed, and the relationship of these factors to potential diagnostic and therapeutic approaches to breast cancer are outlined.
Female Reproductive System
Authors: Aguilera‐Barrantes Irene , Euscher Beth , Morisson Carl , Nuovo Gerard J. 
Published: October 2007

Abstract
The study of the female reproductive system is an excellent example of the importance of molecular pathology to diagnosis and treatment. The classic example is infection of the uterine cervix by human papillomavirus (HPV). The recent FDA approval of vaccines against HPVs 6, 11, 16, and 18 mark the culmination of years of work where HPV detection has increased the accuracy of the Pap smear. These vaccines, which have little to no side effects, most likely are the harbingers of less toxic and effective therapies against cervical cancer that invariably contains HPV. Similarly, molecular testing for targets such as p16 is becoming more useful in the diagnosis and more accurate characterization of endometrial cancers and may also herald changes in the treatment of these cancers. Ovarian tumours represent another fertile area for molecular clinical‐pathology correlation. This is because of the very well characterized ovarian cystadenomas of low malignant potential where histologic markers are usually a poor indicator of clinical behaviour. It is very likely that additional research will identify protein and/or RNA targets that differentiate the aggressive from benign acting tumours in this group and lead to more effective treatment. This chapter will combine the classic histopathology of the female reproductive system with clinical correlates and add to this important mixture newer insights provided by molecular diagnostics.
Heart
Authors: Virmani Renu , Burke Allen 
Published: October 2007

Abstract
Cardiac tumours are rare. In children, the most common are rhabdomyoma and cardiac fibroma, non‐neoplastic growths that are associated with extracardiac malformations. True neoplasms occur primarily in adults. Most are benign (cardiac myxoma), but malignant heart tumours (cardiac sarcomas) may also occur, and clinically mimic myxoma. Any cardiac tumour, whether biologically malignant or truly neoplastic may cause morbidity or mortality by obstructing blood flow or compressing vital structures.
Advantages and Limitations of Models for Cancer and Malignant Cell Progression
Authors: Haier Jörg , Nicolson Garth L. 
Published: October 2007

AbstractModelling of cancer is one of the most difficult tasks in cancer research. The establishment and choice of appropriate models for certain topics, aspects, and questions in cancer development and progression requires a knowledge of the advantages and limitations, possible results, and impossible interpretations of the available models. The initial section of this chapter provides general remarks about models in cancer research. This section focuses on the description of model characteristics, based on overviews of the biological background of many aspects of cancer. In the first part, general techniques that are frequently used in cancer research are explained. The second part of this section describes options for the investigation of certain cancer characteristics, whereas the last part summarizes the available models for different tumour entities.
Models for Angiogenesis
Authors: Kassis Jareer N. , Cohen Joshua G. , Rasool Nabila , Kohn Elise C. 
Published: October 2007

AbstractThe study of angiogenesis has produced a plethora of creative assays through which various aspects of vascular formation and growth are observed, measured, evaluated, and inhibited. A basic theme of angiogenesis investigation is that multiple models are needed to prove a hypothesis. Thus, different aspects are tested in separate models in order to circumscribe those selected effects on the vasculature. Traditional models of the study of angiogenesis have generally been categorized into eitherin vitroorin vivoassays.In vitromodels allow for more strict control over the local microenvironment, sometimes at the expense of authenticity to thein vivoevent, whereas in vivo models enable more accurate observations in a simulated live environment at the expense of optimizing certain variables. A balance of various techniques involving bothin vitroandin vivomodels has led to a better understanding of the overall process of angiogenesis, and thus enabled the development of more effective targeting and therapeutic agents.
Models for Tumour Cell Adhesion and Invasion
Authors: Fisch Katja M. , Haier Jörg 
Published: October 2007

AbstractThe localization of tumour metastasis in distant organs is not determined solely by anatomical considerations. Adhesion of metastatic cells to and migration through the microvascular vessel walls of host organs require specific interactions between the tumour cells and endothelial cells, (EC) the extracellular matrix, or surrounding cells. This chapter describesin vitroandin vivomethods to investigate these specific interactions, their principles, applications, and biological and technical limitations. The cell detachment assay, microtitre plate–based adhesion assay, flow or dynamic cell adhesion assay, spreading assay, migration, invasion, and motility assays (Boyden chamber and microscopy–based techniques), as well as intravital microscopy are explained in detail. These methods are increasingly being used for a detailed study on the involvement of complex interactions of signalling cascades in the metastatic behaviour.
Models for Tumour Cell—Stromal Cell Interactions
Authors: Eble Johannes A. 
Published: October 2007

AbstractStromal cells in the vicinity of tumour cells are not an inert component of an organ. Cancer cells induce the fibroblasts of the surrounding connective tissue to develop into carcinoma‐associated fibroblasts (CAFs), also termedreactive stroma cells, which have biosynthetic capacities similar to fibrotic cells or fibroblasts in granulation tissue during wound healing. By producing growth factors, extracellular matrix (ECM) proteins, and proteinases, the CAFs generate an environment that supports tumour proliferation and progression. Understanding these communication pathways between reactive stroma cells and the cancer cell is the basis for intervening in the tumour‐stroma relationship and preventing stromal cells from promoting cancer cells.
Models for Sarcomas
Authors: Hotfilder Marc , le Viseur Christoph , Vormoor Josef 
Published: October 2007

AbstractSarcomas are rare tumours in patients under the age of 20. Because of their characteristic chromosomal translocations Ewing's sarcomas have been a paradigm for understanding the biology of sarcomas. Since the survival rates in Ewing's sarcoma patients with metastasis and relapse are still unsatisfactory, new therapeutic options have to be developed. Model systems based on fibroblast cell lines have helped in understanding the biology of the transforming protein EWS/FLI1. Cell lines established from primary Ewing's sarcoma are now in use to test new therapeutic options. Since these models only poorly reflect the conditions within the patients, xenograft mouse models have recently been developed to study the biology of Ewing's sarcoma in a more relevantin vivoenvironment. These new model systems will help define novel therapeutic targets and support the preclinical evaluation of new treatments.
Models forCNSMalignancies
Authors: Pilkington Geoffrey J. , Parker Katharine A. 
Published: October 2007

AbstractPrimary or intrinsic central nervous system (CNS) tumours, which affect the brain, spinal cord, and cranial nerves, are derived from the CNS substance itself, with the majority of them emanating from neuroglial cells or their progenitors. These tumours are, generally, collectively known asgliomas. Although such neoplasms are quite amenable to cell culture and the established cell lines are numerous, the original tumours display a high degree of cellular heterogeneity, while resultant high‐passage cultures suffer from homogeneity due toin vitroselection, thereby limiting their value in biological studies. Monolayer cultures have, however, been used extensively for drug chemosensitivity and multidrug resistance studies, as well as for studies of adhesion, motility, and invasiveness. The use of three‐dimensional (3D) multicellular tumour spheroids (MCTSs) has gained much support in recent years often in the context of “confrontation” cultures, where a 3D “target” tissue of precultured heart fragment or re‐aggregated brain cells is juxtaposed with the tumour spheroid in order to study interaction between neoplastic and non‐neoplastic cell populations. Local invasiveness is frequently monitored by such means. Animal models of primary brain tumour suffer from a number of problems related to their biological differences with spontaneous brain tumours in man. Such animal models may be developed either by exposure to ionizing radiation, chemical carcinogens, or oncogenic viruses or by genetic manipulation. Alternatively, tumour cells or tissues may be either syngeneically transplanted into same‐species hosts or xenografted, such as when human biopsy tissue is implanted into immunologically deprived host animals. In addition to hosting primary, intrinsic brain and spinal tumours, the CNS plays host to many secondary or metastatic cancers, which originate in different, distant organs and tissues. Indeed, around a quarter of all cancers spread into the CNS, with seeding into the CNS generally bringing with it a poorer prognosis. Animal models of metastasis into the CNS are rare, as arein vitromodels. This is probably a reflection of the underinvestment of time and resources in this branch of oncology. The interaction between metastatic cancer cells and the modified blood vascular system of the brain, which incorporates the structural and physiological blood‐brain barrier (B‐BB), may be considered an interesting area for further investigation as may the direct interaction between metastatic cancer cells and the brain substance, which provides a “fertile soil” for their growth, but seems to provide a barrier to their invasive behaviour and, hence, growth is essentially proliferative in nature.
Antibody Therapy for Cancer
Authors: Wilkins Duncan K. , Begent Richard H. J. 
Published: October 2007

Abstract
Monoclonal antibodies (mAbs) are being explored as an anticancer therapy of growing importance and formidable potential. The exquisite specificity of antibodies provides an ideal mechanism for targeted cancer therapy. Using hybridoma technology, antibody libraries, or transgenic mice, high‐affinity antibodies can be generated against an extensive range of targets. Recombinant technology is enabling the production of fully human mAbs, smaller mAb‐based molecules, and multifunctional fusion proteins. mAbs can target a growth factor or its receptor, initiate an immunological assault, activate apoptosis, or deliver a cytotoxic payload such as a radioisotope. Several antibody‐based therapies are now licensed to treat haematological or solid tumour malignancies. This chapter explores the structure and function of antibodies, the application of recombinant technology to mAbs and the therapeutic effects of mAbs on cancer.
Cancer Chemoprevention
Authors: Kim Edward S. , Lippman Scott M. 
Published: October 2007

AbstractChemoprevention—the use of natural or synthetic chemical agents to reverse, suppress, or prevent progression to invasive cancer—is a major approach comprising laboratory and clinical research and practice for improving control of the worldwide epidemic of cancer. Chemoprevention is based on the concepts of field “cancerization” (cancer can develop in multiple foci within a field (e.g., the lung) exposed to a carcinogen (e.g., cigarette smoke)) and multistep carcinogenesis (the stepwise accumulation of genotypic and phenotypic alterations progressing through premalignant stages to cancer). Biomarkers are essential to chemoprevention research (e.g., as molecular targets for identifying new agents, markers of cancer risk for selecting trial patients, and endpoints of phase II trials). Major sites of clinical/translational chemoprevention include the lung, head and neck, breast, prostate, colorectal region, and cervix. Important clinical outcomes and advances include reducing the risks of breast cancer with tamoxifen and raloxifene, prostate cancer with finasteride, cervical intraepithelial neoplasia with HPV vaccine, and familial adenomatous polyposis with celecoxib. Major current and/or future directions of chemoprevention include molecular‐targeted research, novel imaging and other technologies aimed at developing personalized chemoprevention, and convergent development of molecular‐targeted drugs for preventing and treating precancer and cancer.
Rational Drug Design of Small Molecule Anticancer Agents: Preclinical Discovery
Authors: Collins Ian , Molife Rhoda , Kaye Stan B. , Workman Paul 
Published: October 2007

AbstractIn this chapter we review the development of small molecule inhibitors that act on targets involved in the causation and progression of human cancer. Considerable success has been achieved with drugs like imatinib and erlotinib that demonstrate the clinical utility of the molecular targeted approach. However, the success rate for cancer drugs in clinical development is only 1 in 20. We review the technologies that are being implemented to improve the success rate and increase the speed of preclinical oncology drug development. Topics covered include the selection and validation of drug targets, with emphasis on the genetics and biology of the disease, as well as on “druggability”; the generation of chemical “leads”, including various high‐throughput screening approaches; the use of structure‐based drug design, particularly using X‐ray crystallography; the value of chemical biology approaches; and the importance of biomarkers for patient selection and rational drug development. The integrated use of these technologies is illustrated using selected case histories. The chapter concludes with a look into the future and an assessment of the likely progress towards the development of bespoke cancer medicine. This chapter is followed by a companion chapter in which we review the clinical development of targeted molecular therapeutics.