bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNATumour Viruses
Authors: Edwards Dustin C. , Marriott Susan J. 
Published: October 2007

AbstractIt is estimated that 15% of all cancer cases are aetiologically linked to viral infection. In these cancers, genomic instability and subsequent multi‐step tumourigenesis is associated with the expression of viral oncoproteins. Human T‐cell leukaemia virus type‐I (HTLV‐I), a prototypic representative of the RNA tumour viruses, is linked to the development of adult T‐cell leukaemia. The HTLV‐I oncoprotein, Tax, targets the regulators of cell cycle progression and DNA repair, leading to cellular transformation.
Genomic Instability and
DNA
Repair
Authors: Gagos Sarantis 
Published: October 2007

Abstract
There is growing evidence that genomic instability is both an epiphenomenon and a leading cause of cancer. Chromosomal instability in neoplasia (CIN) is the most frequent type of genomic instability in solid tumours. For more than a century, chromosomal rearrangements and aneuploidy in neoplasia have been extensively studied and a vast number of genes and pathways, directly or indirectly implicated in CIN, have been described. Chromosomal abnormalities in cancer generate huge genomic imbalances and tumour heterogeneity. This chapter addresses the role of genes, chromosome structure, and telomere dysfunction in the initiation and perpetuation of CIN. The biological consequences of large chromosomal imbalances are discussed and the long‐standing hypotheses for the generation of chromosomal anomalies in neoplasia are re‐examined under the context of telomere dysfunction and restoration.
Apoptosis
Authors: Williamson Kate E. , El Din Osama Sharaf , O'Kane Hugh F. 
Published: October 2007

Abstract
Apoptosis plays a key role in homeostasis and its inhibition results in diseases, including cancer. Multiple genes control apoptosis at the level of stimuli, sensitivity, and execution of the process. Apoptosis can be stimulated by diverse factors including cytotoxic immune cells, radiation, chemotherapy, absence of growth factors, and cytokine deprivation. The life/death balance in cells is controlled by the Bcl‐2 and inhibitor of apoptosis protein (IAP) families whose complex interactions seal the fate of the cell. The execution of apoptosis, the demolition of the cell, is undertaken by caspases. Advances in our understanding of the apoptotic process have led to the search for targets in the pathway that can be manipulated therapeutically to enhance response to treatment in cancer cells.
Clinical Trial Design for Anticancer Therapies
Authors: Lee J. Jack 
Published: October 2007

Abstract
Clinical trials, which are prospective studies to evaluate the effect of interventions in humans under pre‐specified conditions, have become a standard and integral part in the development of new cancer therapies. A properly planned and executed clinical trial is the most definitive tool for evaluating the effect and applicability of new anticancer therapies. Basic elements of clinical trial design are discussed, including study objective, population, design, randomization and blinding, primary and secondary end points, power and sample size calculation, study accrual, interim monitoring plan, and data analysis plan. The paradigm and essence of phase I, II, III, and IV trials are reviewed and illustrated with examples of commonly used designs. Novel study designs for the development of targeted agents, designs using biomarker and genomic end points, and Bayesian methods are introduced and reviewed. Finally, information on clinical trial conduct and reporting is provided and practical considerations and useful links are given.
Multidisciplinary Team Management of Upper Gastrointestinal, Hepatic, Pancreatic, and Biliary Cancers
Authors: Kristeleit Rebecca , Chua Yujo , Cunningham David 
Published: October 2007

Abstract
Despite recent advances in the management of gastrointestinal cancer and the development of more effective treatment paradigms there is still much scope for improvement. The multidisciplinary team is a vital part of clinical management as treatment pathways are becoming increasingly multimodal and complex and in some tumour types the expertise of the treatment team has been shown to be a major determinant of outcome. In addition to optimising the combination of surgery, radiotherapy and conventional cytotoxics in the treatment of these cancers, the role of molecular targeted therapy is also being established. These newer agents are likely to be integrated into future treatment protocols. In addition, improvements in tumour staging with imaging techniques such as PET (positron emission tomography) and the identification of new prognostic markers will enable more accurate tailoring of treatment according to disease extent and biological behaviour. This chapter summarizes the current status of multidisciplinary treatment for upper gastrointestinal, hepatic, pancreatic and biliary cancer.
Transforming Growth Factor‐β and Cancer
Authors: Zhu Beibei , Kyprianou Natasha 
Published: October 2007

Abstract
Members of the TGF‐β super‐family regulate differentiation, proliferation, growth arrest, and apoptosis. TGF‐β mediated signalling proceeds via binding of the ligand to membrane receptor kinases, phosphorylation of TβRII receptor to the TβRI receptor kinase, and subsequently Smad activation, resulting in gene transcription. Dysfunctional TGF‐β signalling is associated with cancer development and progression, while TGF‐β ligand secretion and activation enhances tumour aggressiveness and correlates with metastatic behaviour in human tumours. Molecular exploitation of defective signalling effectors of this pathway is of major significance in detection and therapeutic targeting of human cancers. The present chapter summarizes the current knowledge on the contribution of dysfunctional TGF‐β1 signalling in tumour development and progression and its relevance in cancer prognosis and therapy.
WntSignal Transduction
Authors: Ilyas Mohammad 
Published: October 2007

AbstractDisruption of Wnt signalling is commonly found in a wide range of cancers and thus can possibly be regarded as a “generic” step in the process of carcinogenesis. Recent advances in the understanding of the Wnt signalling pathway have given insight into how inappropriate activation of this pathway may facilitate the neoplastic conversion of a normal cell. In addition, identification of the mechanisms which regulate Wnt signalling has led to the possibility of manipulating these mechanisms in order to down‐regulate Wnt signalling as a therapeutic strategy. In this chapter, the role of aberrant Wnt signalling in the mechanics of tumour development is discussed together with its implications for anti‐tumour therapy.
The Biology of Tumour Stroma
Authors: Guyot Christelle , Lepreux Sébastien , Darby Ian A. , Desmoulière Alexis 
Published: October 2007

AbstractThe cooperation between epithelial and mesenchymal cells is essential for embryonic development and certainly plays an important role in pathological phenomena such as wound healing and tumour progression. Many epithelial tumours are characterised by the local accumulation of connective tissue cells and extracellular material; this phenomenon has been calledstroma reaction, which shows many similarities in its organisation and evolution with the granulation tissue that develops during tissue repair. One of the cellular components of stroma reaction is the myofibroblast, a modified fibroblast that has become capable of expression of α‐smooth muscle actin, the actin isoform typical of vascular smooth muscle cells, and also capable of synthesis of significant amounts of collagen and other extracellular matrix components. The myofibroblast is a key cell for connective tissue remodelling that takes place during wound healing and fibrosis development. Myofibroblasts are also capable of interaction with epithelial cells and other connective tissue cells and may thus control such phenomena as tumour invasion and angiogenesis. In this chapter, we discuss the mechanisms of myofibroblast evolution during normal and malignant conditions, and the interaction of myofibroblasts with other cells in order to control tumour progression. On this basis, we suggest that the myofibroblast may represent a new and important target for anti‐tumour therapy.
Angiogenesis
Authors: Billioux Alexander C. , Modlich Ute , Bicknell Roy 
Published: October 2007

Abstract

Angiogenesis is the process in which new blood vessels are produced by extending the existing vasculature. This process is a part of embryonic development, following directly after vasculogenesis, or the development of blood vessels
de novo
. Angiogenesis after embryogenesis is rare in the adult, occurring largely only during menstruation and wound healing. Nevertheless, many disorders result in the stimulation of angiogenesis, with this aberrant vascular development often playing a key role in the disorder's pathology. This phenomenon is especially relevant in cancer.

Most solid tumours are dependant on angiogenic vascular development for invasive growth and metastasis. Non‐vascularized tumours remain small, rarely growing beyond a few millimetres in diameter. However, after the stimulation of local vascular development – termed the “
angiogenic switch
” – the cancer is able to grow substantially in size and make use of the vascular and lymphatic systems for the systemic dispersal of cells.

Tumour angiogenesis, though stimulated by aberrant growth patterns and modulated growth factor expression, takes place in much the same manner as physiological angiogenesis during development. Thus, understanding the normal process and function of angiogenesis has proved valuable to understanding the ways in which tumours exploit this phenomenon and how this exploitation may be therapeutically abrogated. In this chapter, the physiological process of angiogenesis – stimulation of the quiescent vasculature, breakdown of the extracellular matrix, migration, proliferation, and vascular maturation – is presented, followed by a description of aspects of tumour angiogenesis peculiar to this phenomenon. Finally, a discussion of the role of angiogenic markers in cancer diagnostics is provided.
Epidemiology in the Identification of Cancer Causes
Authors: Lagiou Pagona , Trichopoulos Dimitrios , Adami Hans‐Olov 
Published: October 2007

Abstract
Primary prevention represents the most promising strategy for effective cancer control and requires identification of carcinogenic agents and of the conditions that favour the exposure of susceptible individuals to these agents. An agent is judged to be “conclusively” carcinogenic in humans when there is sufficient evidence of carcinogenicity derived from epidemiological studies; only rarely does evidence from non‐human systems suffice. This chapter addresses conceptual and practical issues in assessing cancer aetiology, outlines the descriptive epidemiology of cancer, gives an overview of the available analytic epidemiologic study designs, examines the role of chance, confounding, and bias, and introduces principles of causal inference in cancer epidemiology.
The Formation of
DNA
Adducts
Authors: Phillips David H. 
Published: October 2007

Abstract
Genotoxic carcinogens initiate the carcinogenic process in mammalian cells by damaging DNA. Where the damage results in attachment of the carcinogen, or its activated metabolite(s) to DNA, the resulting DNA adducts can lead to errors in replication and a permanent alteration in the genetic code. Mutations in critical genes can result in malignant transformation. Several techniques are available with sufficient sensitivity to detect DNA adducts formed as a consequence of occupational or environmental exposure to carcinogens. Detection and identification of DNA adducts in human DNA can provide important clues to the aetiology of cancer. Strategies that inhibit the formation of DNA adducts may have utility in chemoprevention of cancer, and monitoring of DNA adduct formation and removal offers an intermediate biomarker for the assessment of carcinogen exposure and risk of cancer.
The Links between Inflammation and Cancer
Authors: Balkwill Frances , Charles Kellie A. , Mantovani Alberto 
Published: October 2007

AbstractInflammation is a crucial function of the innate immune system that protects against pathogens and initiates specific immunity. Acute inflammation is a tightly controlled process that normally resolves via active repair processes, but this does not always happen. Many of the diseases of middle and old age may be driven, at least in part, by chronic, “smouldering”, unresolved and often subclinical inflammation. In the past 5 years or so there has been great interest in the role of chronic inflammatory processes in malignant disease. It appears that neoplastic tissue selects for the type and extent of inflammation most favourable to tumour growth and progression. There is accumulating evidence that the cells and the chemical mediators of chronic inflammation are found in cancers; general or cell‐specific gene inactivation of key inflammatory mediators influences neoplastic progression, and population‐based studies link inflammatory disease or non‐steroidal anti‐inflammatory drug (NSAID) use with risk of some cancers. If genetic damage isthe match that lights the fireof cancer, inflammation can be considered as afuel that feeds the flame.
Regulation of Translation in Malignant Transformation
Authors: Clemens Michael J. 
Published: October 2007

Abstract
Gene expression is regulated at the level of translation by a number of mechanisms that are susceptible to aberrant control in malignant cells. In particular, polypeptide chain initiation factor eIF4E is often overexpressed in tumours. The availability and/or activity of eIF4E and other initiation factors can be regulated by signal transduction pathways that modulate the state of phosphorylation of these factors (or of proteins that interact with them). The key rate‐limiting steps in such pathways may thus constitute targets for therapeutic intervention. A promising example is the use of rapamycin and its derivatives to inhibit the activity of the protein kinase mammalian target of rapamycin (mTOR), an enzyme that directly influences the ability of the 4E binding proteins to sequester eIF4E and thus control translation. The effects of initiation factor overexpression can be mRNA selective, because such effects are influenced by the structures of the untranslated regions (UTRs) of mRNA molecules. Increased understanding of the regulatory mechanisms involved in the control of translation of specific mRNAs is likely to lead to the development of novel strategies for cancer treatment.
The Retinoblastoma Tumour Suppressor
Authors: Dirlam Alexandra , Macleod Kay F. 
Published: October 2007

Abstract
The retinoblastoma tumour suppressor (pRB) is functionally inactivated in most human cancers. pRB regulates cell cycle checkpoints, cell death, cellular senescence, and terminal differentiation through interactions with members of the E2F family of transcription factors, chromatin‐remodelling factors and with tissue‐restricted transcription factors. The RB‐related “pocket proteins”, p107 and p130 also interact with E2Fs to regulate cell cycle, although neither p107 nor p130 are known tumour suppressors in human cancer, despite data from mouse models indicating their ability to compensate for Rb loss under certain circumstances. This chapter discusses the latest findings on the role of pRB in development and tumourigenesis to help determine which functions of pRB contribute most to its tumour‐suppressor activity, why certain tumours select against RB but others do not, and what kind of additional mutations are likely to cooperate with RB loss in cancer as a function of tissue type.
Development and Cancer: TheHOXGene Connection
Authors: James Jacqueline A. , Grier David G. , Thompson Alexander , Lappin Terry R. J. 
Published: October 2007

AbstractHomeobox genes nave been identified in the genomes of all animals mapped so far. The Human Class 1 homeobox (HOX) genes are clustered on four different chromosomes, 7p15, 17q21, 12q123 and 2q31. The proteins encoded by these genes act as master regulators of transcription. During embryogenesis they define axial patterning and developmental cues. The discovery that genes initially expressed in embryogenesis are often re‐expressed in neoplasia has led to the concept that ‘Oncology recapitulates Ontogeny’. IndividualHOXgenes have been identified in specific developmetal processes,e.g.downregulation ofHOXB5appears necessary for normal lung development. In other processes such as haematopoiesis sub‐sets ofHOXgenes are associated with lineage commitment and differentiation. Generally higherHOXgene expression is associated with a more primitive phenotype. The oncogenic potential of HOX proteins has been linked with leukaemia and solid tumours. Chromosomal translocations involving severalHOXgenes indicate they play a direct role in leukaemogenesis. Known regulators ofHOXexpression such as MLL are also directly involved in the onset and maintenance of leukaemia. Current investigations ofHOXgene expression in various cancers indicate their potential for disease classification and prediction of clinical outcome. Model systems of dysregulated HOX expression suggest a functional role for these master regulators in cancer, often associated with a more aggressive phenotype, such as high metastatic potential. Future work to test the concept that ‘Oncology recapitulates Ontogeny’ will involve elucidation of the upstream regulators and downstream targets within the HOX‐axis.
Infectious Agents and Cancer
Authors: Duensing Stefan , Moore Patrick S. , Parsonnet Julie 
Published: October 2007

AbstractInfection is second only to smoking as a cause of human cancer. Microbial agents implicated in carcinogenesis run the gamut from simple viruses to complex parasites. Mechanisms of carcinogenesis imputed to these agents are as diverse as the agents themselves. These mechanisms provide important insights into cancer more generally, including the role of proto‐oncogenes in tumour development and the effects of inflammation on host cells. Because infections can often be prevented through vaccines or public health measures, or can be treated with anti‐microbial agents, they provide a promising arena for cancer control.
Cancer Bioassays
Authors: Maronpot Robert R. 
Published: October 2007

AbstractRodent cancer bioassays have a long history of identifying carcinogenic potential of synthetic and natural chemicals, chemical mixtures, and a variety of commercial products including drugs. The rodent cancer bioassay is a reliable approach to hazard identification with a primary goal of identifying potential human carcinogens. The emphasis here is on the word potential. Human exposure scenarios are highly variable; typically involve simultaneous exposure to multiple dietary, occupational, and environmental agents; and any subsequent disease burden is influenced by age at exposure, lifestyle, and socioeconomic situations. Further, the rodent physiology, metabolism, and detoxification processes and exactly how they handle specific chemicals will frequently have important similarities and differences from those processes in humans. Consequently, the long‐term rodent cancer bioassay will never be completely accurate in identifying agents that cause human cancer. Amongin vivoanimal carcinogenicity testing strategies, the long‐term rodent cancer bioassay remains the standard against which alternative approaches are compared.
Unknown Primary
Authors: Oien Karin A. , Stewart Ian , Evans T. R. Jeffry 
Published: October 2007

Abstract

Ten percent to 15% of all cancer patients present with metastatic disease, of initially unknown origin. In one‐third, a primary site cannot be identified, which is called
metastatic cancer of unknown primary
(
CUP
). CUPs may present in solid organs, for example, liver, or in lymph nodes or serous cavities. CUP generally has a poor prognosis but there are so‐called “favourable” subsets of patients whose tumours are sensitive to therapy. To predict the patient's outcome and provide optimal treatment, it is therefore important to identify the type and subtype of the metastatic cancer, and, depending on the cancer type, to identify or predict its most likely site of origin. This can be achieved through clinical assessment, because different cancers tend to metastasize in characteristic patterns, and through investigations including radiology, serum tumour markers, and pathology. For the latter, microscopic examination of a biopsy of the metastasis itself enables tumour typing through morphology and immunohistochemistry. Lymphoma, melanoma, and sarcoma are first considered and excluded, because the diagnosis of CUP is usually limited to carcinomas; 90% of CUPs are adenocarcinomas, from lung, pancreas, stomach, colon, ovary, breast, prostate, and so on. Adenocarcinomas from different primary sites are sensitive to different chemotherapeutic agents and so it is important to identify or predict the site of origin and this can now be achieved through immunohistochemical profiling. The diagnostic and therapeutic nihilism of the past in CUP patients is thus disappearing; continued improvement in their outcome depends ultimately on the development of novel therapies.
Dietary Genotoxins and Cancer
Authors: Sugimura Takashi , Wakabayashi Keiji , Nagao Minako 
Published: October 2007

Abstract
Tobacco smoking, diet, and infections/inflammation are three major factors for cancer causation in humans. There are many types of genotoxic compounds, such as mycotoxins, pyrrolidine alkaloids, mushroom hydrazines, nitrosamines, polycyclic aromatic hydrocarbons (PAHs), and heterocyclic amines (HCAs), in diet. They are derived from fungus metabolites, edible plant components, and produced during cooking, storage, and fermentation of food. Some are food additives, mainly of the preservative type. In addition to genotoxic agents present as microcomponents, macrocomponents, including fatty acids, salts, and fibres, are indicated to be associated with human cancer. At the same time, many anticarcinogenic compounds are also included in the diet. The significance of dietary factors for human cancer development is described.
RNAInterference
Authors: Moss Charlotte , Lemoine Nick 
Published: October 2007

AbstractRibonucleic acid interference (RNAi), a recently discovered novel mechanism of post‐transcriptional gene silencing (PTGS) has quickly found multiple applications in genetic research and is now established as the method of choice for achieving gene knockdown in functional genetic studies. The potential of this technique for therapeutic use has generated much excitement. This chapter aims to describe the mechanism underlying RNAi, to discuss some of the challenges anticipated in translating this powerful research tool into a clinical setting and how these are currently being addressed.
Collaborative Approach to Multidisciplinary Breast Cancer Care
Authors: Alvarado Michael D. , Ewing Cheryl , Esserman Laura J. 
Published: October 2007

Abstract
Care for the breast cancer patient is changing rapidly and a comprehensive breast care centre, utilizing a multidisciplinary approach, is becoming the standard of care. The mutidisciplinary approach brings together a highly coordinated setting composed of specialists from all the disciplines involved in breast cancer care. By designing systems that focus on the needs of the patient, a service delivery model can concentrate on the coordination of care, while improving the experience for the patient through innovation and translational research.