Gliomas are fatal diseases, but also represent good models for tumor research with the aim to eventually discover new and appropriate therapeutics against this disease. Glioma experimental research models are of help to investigate tumorigenesis (tumor stem cell theory versus "classical" opinions), tumor angiogenesis (since they are highly vascularized) and tumor invasion (since they grow without limits). In addition, they have a very special microenvironment (the brain) and limited tumor stroma cells (mainly microglia and endothelial cells). This book addresses the molecular mechanisms of the various tumor stages, describes the interaction with the tumor microenvironment and furthermore depicts experimental models for Glioma research and future therapeutic concepts. The book is composed and written for Scientists and Medical Doctors in Oncology, Neurosciences and Molecular Biology. "

The World Health Organization has identified chronic alcohol consumption as one of the top ten risk factors for worldwide burden of disease. The International Agency for Research on Cancer has identified alcohol as carcinogenic to humans, including cancers of the upper aerodigestive tract, colon, liver and breast. Alcohol's actions may be direct e.g. effects on retinoic acid and one-carbon metabolism, or indirect, through metabolites such as acetaldehyde and reactive oxygen species or through various signaling pathways that influence cell cycle and apoptosis that may contribute to carcinogenesis. This report reviews the state of the art in alcohol-related cancer research in ten chapters.

"HPV and Cancer" is a concise read that covers all aspects of the Human Papilloma Virus as it relates to human cancers. While written by professionals, it design to be understandable by those that are not in the field, yet it has the technical details that professionals want to stay abreast of this changing field. The book starts out the history of HPV and progresses into the molecular biology of the virus and our current understand of the structure and functions of the proteins and genes it encodes. We then look at the dynamic trends of this infectious agent in the human population, how it interacts with human cells, and the role it plays with other organisms to produce both benign and malignant tumors. Lastly, there is a discussion about a new vaccine for HPV and the hopes that are held by many to change the trends with this virus and the associated cancers it produces.

In addition to surgery and radiotherapy, local treatment modalities for the management of brain tumours are increasingly being developed and clinically tested. This book describes for the first time basic tumour biology as well as all current procedures in progress at the most recent level of knowledge, presented by leading experts in the respective fields. Image guided resection procedures, fluorescence guided surgery, developments in interstitial radiosurgery are addressed, just as intracavitary chemotherapy and all current concepts and studies of interstitial targeted therapy. Owing to its topicality this book will remain for long the standard for this comprehensively treated subject.

The success rate for treatment of primary neoplasms has improved sig nificantly due to improved surgical, radiotherapy, and chemotherapy methods, and by supportive patient care. In contrast, the treatment of cancer metastases, the cause of most cancer deaths, has not been very successful. Approximately 50% or more of patients with primary malignant neoplasms already have established metastases. Consequently, the most important problem in cancer treatment is the destruction or prevention of metastases. Metastases research has obvious clinical importance. Yet it has only been recently that investigators have attempted to study the mechanisms in volved in this process. This is in part due to the complexity of metastases formation. A metastatic colony is the result of a complicated series of steps involving mUltiple tumor host interactions. It is expected that multiple biochemical factors and gene products derived both from the host and the tumor cell may be required for the metastasizing tumor cell to invade, survive host defenses, travel in the circulation, arrest and adhere in the target organ, invade out, and grow as a metastatic colony. Some of these factors have recently been identified by investigators who have focused on individual steps in the metastatic process and have employed new technologies in immunology, biochemistry and molecular biology. The purpose of this volume is to capture some of the excitement in the field of metastases based on such new discoveries."

This volume provides a comprehensive review of resistance induced by photodynamic therapy (PDT) in tumor cells. Understanding the underlying mechanisms in this process leads to the improvement of therapeutic modality, in combination with chemotherapy, immunotherapy, and radiotherapy. Photodynamic therapy is a minimally invasive therapeutic procedure that can exert a selective or preferential cytotoxic activity toward malignant cells. The procedure involves administration of an intrinsically non-toxic photosensitizing agent (PS) followed by irradiation at a wavelength corresponding to a visible absorption band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Studies reveal that PDT can be curative, particularly in early stage tumors and this volume explores the potential of PDT, but also reveals strategic approaches to overcome resistance in tumor cells.

Experimental chemotherapy continues to be at the forefront of cancer thera- peutics. Topics covered in the preceding volume on cancer chemotherapy in this series such as study of drugs by alkaline elution, the development of the antimetabolite tiazofurin, and the treatment of germ cell tumors have become informative references to current experimentalists and practitioners. In even earlier volumes, reviews of the platinum compounds, anthracyclines, and osteosarcoma represent topics associated with such rapid progress requiring a look back to provide the appropriate perspective. Similarly, we venture to predict that the topics in this volume will become useful landmarks for future drug development and disease strategies. In the area of drug development, what is being learned about old, estab- lished antineoplastics is raising renewed expectations that it will be translated into improved applications and patient benefit. For example, we now have the ability to modulate the action of alkylating agents and fluorinated pyri- midines to achieve greater sensitivity. A new compound for an old target, trimetrexate, an antifolate that does not polyglutaminate, will have a role not only in treatment of neoplastic diseases, but also protozoal infection.

Homeostasis. The health of an organism is influenced by external and internal changes that may lead to the loss of homeostasis. Under healthy conditions organisms compensate these changes. If compensation fails disease ensues. Attention will be paid to lifestyle, environmental changes, genetic makeup and health system. It willbe answered how lifestyle, environment, genetic makeup and social conditions help to maintain or upset the biological balance and lead to cancer.
Tumor formation. To understand this process the transfer of intracellular and the pathways of extracellular information (signal transduction) will be reviewed briefly. Loss of cellular balance may lead to cell death (.e.g. apoptosis) or to rapid cell growth of cells leading to tumor formation.
Metastasis. Animal tumor models serve to understand the spread of the primary tumor cells to distant locations of the organism. Different types of tumors and metastases will be reviewed. "

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbiihl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publi cation of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.

Great advances were made in the pharmacologic-based treatment of cancer in prior decades. However, despite a marked increase in our understanding ofcell and molecular mechanisms underlying the neoplastic process, therapy for advanced disease remains limited. While the reasons for this are many, it is generally accepted that advanced neoplasms contain a relatively large number of genetic and molecularalterations contributingto the maintenanceofthe neoplastic process. Such a situation precludes easy pharmacologic intervention. However, our ability to detect cancer at an earlier stage, coupled with our increased understandingofcarcinogenesis, are propellingboth basic and clinical scientiststo pursue early intervention/chemopreventive approaches. This is based upon the notion that fewer molecularaberrations are presentearlyon inthedisease process. It also takes advantage ofthe fact that advances in both technology, and in the field ofcancer biology, coupled with a heightened vigilance, have increased our ability to detect early disease more readily. The chemopreventive approach is highly attractive for a number ofreasons. First, treatment ofpre-neoplastic, or early neoplastic, lesions would prevent the significant mobility and mortality associated with advanced neoplastic disorders.

Chemokines and Cancer synthesizes a state-of-the-art understanding of the role that chemokines and their receptors play in the pathophysiology of malignancy. It examines the influence of chemokines on a broad array of malignant cells, including their effects on such intrinsic properties as growth and movement, as well as exploring their influence on the host's response to a growing tumor. The authors also demonstrate the physiological consequences of chemokine expression and suggest how chemokines can be used to regulate tumor growth in vivo, including their direct effects on tumor growth, on tumor destruction by host inflammatory cells, and on tumor angiogenesis. The only book available that relates chemokines to cancer, Chemokines and Cancer holds out the promise of novel therapeutic approaches to malignancy through the manipulation of chemokines and/or their receptors.

Volume 12 in this series explores the latest experimental and clinical uses of stem cells in the treatment of disease and of injuries and reviews methods for isolating multipotent endothelial-like cells from human adipose tissue and discusses clinical applications in cell therapy and regenerative medicine.

The book is organized in five parts: Cancer Stem Cells, Pluripotent Stem Cells, Dendritic Stem Cells, Regenerative Medicine and General Applications. The first section includes chapters on histamine in the neural and cancer stem cell niches and emerging concepts of stem cell organization in the normal lung and in lung cancer. The section on Pluripotent Stem Cells includes discussion of the differentiation of dendritic cells from human induced pluripotent stem cell and the molecular mechanisms involved in reprogramming human somatic cells to generate induced pluripotent stem cells. Additional chapters cover the differentiation of induced pluripotent stem cells into functional cardiomyocytes, characteristics of satellite cells and multipotent adult stem cells in the skeletal muscle. The section on Dendritic Stem Cells explores the critical role of notch signaling in the differentiation and function of dendrite. Other chapters cover hypertensive emergencies in children after stem cell transplantation and overcoming the radio resistance of lung cancer stem cells. The section on Regenerative Medicine reports on experiments on improved renal revascularization in pigs using stem cells and phenotypic correction of murine Hemophilia A using cell-based therapy. The concluding section, General Applications, discusses such topics as methods in mathematical modeling for stem cells, as well as molecular and functional characterization of human adipocytes.

Like its eleven predecessors in the series," " this volume stands out for its comprehensive approach, its roster of some 51 expert contributors representing a dozen different countries and its up-to-date review of leading-edge technology and methods.

It is now widely accepted that multidisciplinary collaboration and multimodality treatment approaches are important in improving the survival of patients with hepatocellular carcinoma. In this comprehensive textbook, internationally renowned experts in the field present and discuss the various strategies employed in the treatment of the disease. Up-to-date information is provided on the indications for and outcome of a range of treatment options, including surgical resection, liver transplantation, radiofrequency ablation, transarterial chemoembolization, yttrium-90 transarterial radioembolization, and systemic therapy. In addition, important background information is included on biology, pathology, staging, and imaging. This book will be particularly helpful to all professionals and trainees worldwide who have an interest in the diagnosis and treatment of hepatocellular carcinoma.

Leading cancer researchers update and review the mechanisms of action and the therapeutic selectivity and efficacy of 5-FU with and without leucovorin and its prodrugs in the treatment of colorectal cancer. Among the combination agents considered are UFT/LV, 5-FU/EU, capecitabine (Xeloda), S-1, and a variety of thymidylate synthase inhibitors. The authors discuss the potential advantages and disadvantages of these varied drugs and their mode of administration. Based on historical results with these agents when used alone, they also present a rationale for their results when used in combination with other agents.

Thesocietalburdenofcancerisoneofthemajorpublichealthchallengesofour time. Yetthatburdenisnotequallysharedbyall. Troublingdisparitieshave been documented not only by racial/ethnic group but also by social class, insurancestatus,geography,andahostofotherdimensions. Furthermore, suchdisparitiesrepresenttheendresultofaconstellationofforcesstemming frominsideandoutsidethehealthcaresystem. Manycancerdisparitiesshould bepreventable. Fewhaveattemptedtocapturethebreadthanddepthofthedimensionsof cancerdisparitiesfrombothclinicalaswellaspublichealthperspectives. To addressthisneed,wepresentthisvolumeto: broaden concepts of disparities beyond traditional discussions of race/ ethnicitytoexplorehow,where,andwhytheyoccur; focusoncancerdisparitiesintheUS,whilecitingsomemajorexamplesfrom abroad; analyzecertainmajorcancerswithrespecttodisparities,withemphasison socioeconomicposition; examinethesourcesofdisparitiesfrombothinsideandoutsidethehealth caresystem; identifyinitialinterventionsthatattempttoreduceandeliminatethesed- parities;and identifyissuesthatdeserveattentionwithrespecttofutureresearch. Ourmonographaddressescancerdisparitiesacrossthecontinuum(fromp- vention to mortality and by the domains of social inequality). We begin by exploringbroaddimensionsuchasdefinitionsofdisparities,datasystems,the roleofgenesandenvironment,andtheroleofworkandoccupationincancer disparities. Thenwemoveintospecificchallengesincancerdisparitiessuchas tobaccouseandlungcancer,breastcancer,colorectalcancer,prostatecancer, cervicalcancer,melanoma,andhepatocellularcarcinoma. Wethenconcludewith someavenuestoaddresscancerdisparities,includingpolicyandadvocacy,health v vi Preface communication, overcoming barriers to cancer care, and community-based approaches. Oureffortsarefarfromexhaustive,buttheyrepresentoneofthe firstattemptstoaddresscancerdisparitiesfromsuchacomprehensiveperspective. Thisvolumereflectstheworkofanumberofnationalexpertsincancer disparities. Many are members of the Executive Committee of the Cancer Disparities Program-in-Development of the Dana-Farber/Harvard Cancer Center. Still others are also investigators in the National Cancer Institute Community Network Program MassCONECT (Massachusetts Community NetworkstoEliminateCancerDisparitiesthroughEducation,Researchand Training). Also,thisvolumeupdatesandexpandsaearlier2005monographon thetopicpublishedinthejournalCancerCausesandControl. Allauthorsare dedicatedtothegoalofeliminatingcancerdisparitiesandIamindebtedto them. IamparticularlygratefultoRachelWarren,TerraZipoyrnSnider,andDr. ClaudiaArriggfortheirunendingencouragementandsupport. Itismyhope thatthismonographrepresentsanothercontributiontowardhelpingallpeople enjoytheirhighestattainablestandardofhealth. Boston,MA HowardK. Koh,MD,MPH Contents PartI DimensionsofCancerDisparities 1 Defining,Investigating,andAddressingCancerInequities: CriticalIssues...3 NancyKrieger,KarenM. Emmons,andDavidWilliams 2 CancerDisparities:DataSystems,Sources,andInterpretation...29 BarbaraD. Powe,AhmedinJemal,DexterCooper, andLokieHarmond 3 Genes,Environment,andCancerDisparities...49 AlexandraE. Shields,StephanieM. Fullerton,andKennethOlden 4 WorkandOccupation:ImportantIndicatorsofSocioeconomic PositionandLifeExperiencesInfluencingCancerDisparities...83 GlorianSorensen,GraceSembajwe,AmyHarley, andLisaQuintiliani PartII SpecificChallengesinCancerDisparities 5 DisparitiesinTobaccoUseandLungCancer...109 HowardK. Koh,LorisElqura,andSarahMassinShort 6 SocioeconomicStatusandBreastCancerDisparities...137 SherrieFlyntWallington,OtisW. Brawley, andMichelleD. Holmes 7 DisparitiesandColorectalCancer...161 EricC. Schneider 8 DisparitiesinProstateCancer...179 OtisW. BrawleyandSherrieFlyntWallington vii viii Contents 9 DisparitiesandCervicalCancer...203 MarceladelCarmenandTeresaDiaz-Montez 10 MelanomaandPrimaryHepatocellularCarcinoma...227 ChristopherA. Aoki,AlanGeller,andMoonS. Chen PartIII SomeAvenuestoAddressCancerDisparities 11 Interventions,Policy,andAdvocacy...259 DeborahKleinWalkerandChristineM. Judge 12 HealthCommunicationandCommunicationInequalities inAddressingCancerDisparities...277 K. ViswanathandKarenM. Emmons 13 OvercomingBarrierstoCancerCare:PatientandPublic Perspectives...299 KarenDonelan 14 Community-BasedApproachestoCancerDisparities...317 BarbaraGottlieb Index...359 Contributors ChristopherA. Aoki DivisionofGastroenterologyandHepatology, DepartmentofInternalMedicine,SchoolofMedicine,Universityof California,Davis,CA OtisW. Brawley AmericanCancerSocietyandEmoryUniversity,Atlanta,GA MarceladelCarmen DivisionofGynecologicOncology,Massachusetts GeneralHospital,HarvardMedicalSchool,Boston,MA MoonS.

This volume is intended to present an eclectic selection of informative reviews on aspects of the malignant lymphomas, including Hodgkin's disease. The choice of suitable review topics in this field is made hazardous by several facts. First, the growth of insight into basic mechanisms of lymphomagenesis is explosive, as is the expansion of our understanding of the need for precise morphologic classification of these diseases. Second, new therapeutic agents, cytotoxic and biologic, as well as new drug delivery strategies, are appearing with remarkable frequency. Finally, old "standard" approaches, such as the staging laparotomy for Hodgkin's disease, are being reconsidered and deserve attention in an up-to-date collection of papers. The 10 reviews presented here fall generally into three categories. First, the optimal diagnostic and therapeutic approaches to Hodgkin's disease are considered by Mark Leibenhaut, who reviews the status of the diagnostic staging laparotomy, and by Philip Bierman, who discusses his thoughts on the timing of high-dose treatment with bone marrow transplantation for this disease. There follow four reviews of current management of specific histologic subtypes of malignant lymphoma. First, Velasquez reviews prognostic factors in both intermediate and high grade lymphomas. Miller and Dahlberg review and update the Southwest Oncology Group experience in developing curative cytotoxic combination therapies for diffuse large-cell lymphomas. Lastly, optimal therapy for two kinds of high grade lymphoma are presented. Butler and Hainsworth describe the Vanderbilt experience with diffuse small noncleaved cell lymphoma and Picozzi reviews lymphoblastic lymphoma.

This volume brings together the key research issues in clinical and laboratory science relating to metastasis in prostate cancer. It is especially suitable for those in the field, whether physicians and/or scientists, and whether in active research or in training, who wish to broaden their understanding, with regard to their own discipline, and also to another. It is also a resource for those whose research is in metastasis, but in diseases other than prostate cancer. The intention of this volume is to help to empower those who seek to further exploit the potential for translational research in this field.Written by a team of internationally recognised experts, coverage ranges from the most fundamental aspects of the molecular biology of metastasis, to the patient in the clinic. The therapeutic approaches range from conventional drug design to immunogene therapy.

Transferring hematopoietic stem cells and immune cells has continued to be a promising therapeutic alternative and a fascinating area of cell biology as well as a field of persistent procedural problems. This explains why substantial parts of basic research on cell growth and differentiation, immune tolerance and antitumor effects, gene transfer, minimal residual disease and supportive care have settled around clinical transplantation in hematology and oncology. This second volume updates the current role of allogeneic and autologous transplantation in leukemias, lymphomas and solid cancers, including controversial strategies and novel experimental approaches. Outstanding representatives of leading groups guarantee first-hand information and indicate how we can work and cooperate more effectively to the benefit of our patients.

Over the past two decades, there has been a tremendous increase in our understa- ing of ubiquitination and proteasome degradation. As the editors, we thank Springer Publishing for allowing us to organize this collection of reviews on the ubiquit- proteasome system, oncogenesis, and cancer therapy. We asked our colleagues, who are experts in the field, to provide an overview of their research and recent progress. Each chapter covers a broad range of topics that include defects in ubiquitination identified in specific tumors to new directions to treat cancer. In the Introduction, Rati Verma gives the background of our current understanding of the proteasome. A general overview of ubiquitin ligases and cancer is provided by Angelika Burger and Arun Seth. Patricia McChesney and Gary Kupfer discuss the role of the Fanconi anemia/BRCA1 pathways in breast cancer and potential targets for therapy. Defects in the tumor suppressor, von Hippel-Lindau E3 ligase, and the role of this protein complex are discussed by William Kim and William Kaelin. Kyung-bo Kim and colleagues describe the development of novel proteasome inhibitors to treat cancer patients. Progress in our understanding of deubiquitinating enzymes is summarized by Massimo Loda and his colleagues. Finally, Agustin Rodriguez-Gonzalez and Kathleen Sakamoto discuss an approach to recruit cancer-causing proteins to ub- uitin ligases through a chimeric molecule known as protacs.

How hype, money, and bias can mislead the public into thinking that many worthless or unproven treatments are effective. Each week, people read about new and exciting cancer drugs. Some of these drugs are truly transformative, offering major improvements in how long patients live or how they feel-but what is often missing from the popular narrative is that, far too often, these new drugs have marginal or minimal benefits. Some are even harmful. In Malignant, hematologist-oncologist Dr. Vinayak K. Prasad writes about the many sobering examples of how patients are too often failed by cancer policy and by how oncology is practiced. Throughout this work, Prasad illuminates deceptive practices which * promote novel cancer therapies long before credible data are available to support such treatment; and * exaggerate the potential benefits of new therapies, many of which cost thousands and in some cases hundreds of thousands of dollars. Prasad then critiques the financial conflicts of interest that pervade the oncology field, the pharmaceutical industry, and the US Food and Drug administration. This is a book about how the actions of human beings-our policies, our standards of evidence, and our drug regulation-incentivize the pursuit of marginal or unproven therapies at lofty and unsustainable prices. Prasad takes us through how cancer trials are conducted, how drugs come to market, and how pricing decisions are made, asking how we can ensure that more cancer drugs deliver both greater benefit and a lower price. Ultimately, Prasad says, * more cancer clinical trials should measure outcomes that actually matter to people with cancer; * patients on those trials should look more like actual global citizens; * we need drug regulators to raise, not perpetually lower, the bar for approval; and * we need unbiased patient advocates and experts. This well-written, opinionated, and engaging book explains what we can do differently to make serious and sustained progress against cancer-and how we can avoid repeating the policy and practice mistakes of the past.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung cancer, geni tourinary cancer, pediatric oncology, etc. Second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

In the approach to the analysis of disease, including, of course, cancer, two major thrusts may be distinguished. These may be referred to, in shorthand, as agents and processes: the causative agents (chemical, microbial, physical, environmental, and psychosocial) and the organismic processes, initiated and furthered by the agents, culminating in observable pathology (at the macromolecular, cytological, histological, organ function, locomotor, and behavioral levels). The past 25 years, since the appearance of the first volume of the predecessor series (1) authored by the Editors of this present volume, have seen an impressive number of studies on chemicals (and other agents) as etiologic factors in the induction of cancer. The major emphasis has been on the discovery of many chemical carcinogens of widely different structures, their metabolism by various tissues and cells, and, in turn, their molecular-biochemical effects on the cells. This rapidly expanded body of information, as effectively covered in the predecessor volumes, is an excellent entree to the second half of the overall problem of chemical carcinogenesis, the processes. The active agents trigger a large array of molecular-biochemical alterations to which the target cells, target tissues, and target organisms respond in many select and common ways. This second major aspect of the induction of cancer by chemicals (and by other agents)- the sequence of cellular and tissue changes clearly relevant to cancer-remains the challenge for the future.