With the publication of these proceedings from the Second Drug Discovery and Development Symposium, this forum has become the main mechanism for bringing together the principal groups involved in both discovering and developing new approaches to the treatment of cancer. This Second Symposium emphasized the types of materials being discovered and their therapeutic activity. This is especially evident in the natural product discovery programs, where unique and active structures are being identified. The major contributors to the meeting were the investigators participating in the National Cooperative (Natural Products) Drug Discovery Groups [NC(NP)DDG]. These groups reflect an association among researchers at universities or cancer centers, pharmaceutical companies and the National Cancer Institute. Their sources of materials are varied, reflecting chemical inventories of pharmaceutical companies, organic synthetic compounds from the laboratory, cytotoxics as well as biologics and their hybrids, and natural products obtained from plants, marine organisms and microorganisms. The models employed in the discovery systems vary from broadly cellular based to specific enzymes to defined cellular functions. Each of them is believed important to the malignant state and will allow for the discovery of compounds which will have efficacy in cancer therapy. The goal of the participants is both to discover new anticancer agents and to develop them as efficiently as possible into clinically useful additions to treatment. Of importance is the fact that there are a number of promising leads which will soon be moving into the clinic thereby testing the effectiveness of this NC (NP) DDG approach.

Concepts, Mechanisms, and New Targets for Chemotherapy describes new interconnections between rationally designed and empirically discovered compounds. One route that has not been travelled previously is that of protein kinase C inhibition. This pathway may be exploited to give potent inhibitors, such as the bryostatins, now in clinical trial. A summary is given of the current status of topoisomerase, focusing on recent clinical advances with camptothecin analogs based on connecting empiricism with concepts of drug selectivity. Modification of existing therapies based on the pursuit of leads arising from mechanistic studies is also being applied clinically on a wide scale. Greater understanding should follow from the studies of reversal of the multidrug resistant phenotype, on the use of hydroxyurea to reverse resistance mediated by extrachromosomal DNA, and on various aspects of the fluoropyrimidine pathways. Successful applications of chemotherapy to the treatment of specific diseases include the growing applications of systemic therapy using various skin malignancies. In prostate cancer, estramustine phosphate will likely play an expanding role. Taxanes are restructuring treatment regimens in breast cancer, and high-dose strategies are described with peripheral blood progenitor autografting in the treatment of ovarian and breast cancers.

Resistance to treatment represents the final common outcome for far too many patients with cancer. Even our most promising new drugs fall victim to drug resistance. Hormones and newer biological therapies, though safe and active, also lose their activity over time. In this volume of Drug Resistance, leading investigators in the field have reviewed the most basic mechanisms of drug resistance, and have proposed ways to modulate resistance. This comprehensive volume should be of value for basic and clinical scientists who wish to delve more deeply into this intriguing problem in the laboratory and devastating problem in the clinic.

Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.

Malignant pleural mesothelioma, a malignancy due largely to asbestos exposure, represents an increasingly common challenge to clinical and medical oncologists, respiratory physicians, and cardiothoracic surgeons, as well as researchers in the field. The disease has yet to reach its peak and is expected to kill over 100,000 people worldwide. As malignant pleural mesothelioma gains in profile, Kenneth O'Byrne and Valerie Rusch present a comprehensive overview of the subject, aimed at all health care professionals who come into contact with patients with the disease. The book includes chapters on epidemiology, diagnosis, histopathology, radiology, surgery, chemotherapy, immune therapy, radiotherapy, and palliative medicine, written by an international team of contributors. A molecular biology section focuses on the carcinogenic effects of asbestos fibres and simian virus 40, angiogenesis and angiogenic growth factors, the immune response, and genetic abnormalities detected in the disease. Future therapies are also covered, as is a perspective on the distinct legal issues related to the disease. This highly-illustrated, full colour book provides the ultimate, timely resource on this devastating disease.

Principles of Clinical Cancer Research provides comprehensive coverage of the fundamentals of clinical cancer research, including the full spectrum of methodologies used in the field. For those involved in research or considering research careers, this book offers a mix of practical advice and analytical tools for effective training in theoretical principles as well as specific, usable teaching examples. The clinical oncologist or trainee will find a high-yield, practical guide to the interpretation of the oncology literature and the application of data to real-world settings. Valuable for both researchers and clinicians who wish to sharpen their skills, this book contains all the cornerstones and explanation needed to produce and recognize quality clinical science in oncology.Written from the physician-scientist's perspective, it lays a strong foundation in pre-clinical sciences that is highly relevant to careers in translational oncology research along with coverage of population and outcomes research and clinical trials. It brings together fundamental principles in oncology with the statistical concepts one needs to know to design and interpret studies successfully. With each chapter including perspectives of both clinicians and scientists, Principles of Clinical Cancer Research provides balanced, instructive, and high-quality topic overviews and applications that are accessible and thorough for anyone in the field. Key Features: Gives real-world examples and rationales behind which research methods to use when and why Includes numerous tables featuring key statistical methods and programming commands used in everyday clinical research Contains illustrative practical examples and figures in each chapter to help the reader master the main concepts Provides tips and pointers for structuring a career, avoiding pitfalls, and achieving success in the field of clinical cancer research Access to fully downloadable ebook

Updated and expanded, this Second Edition of Essentials of Clinical Radiation Oncology continues to provide a succinct and effective review of the most important studies in the field. Organized by disease topic and grouped by body part, each chapter employs structured sections for targeted information retrieval and retention. Chapters begin with a "Quick Hit" overview of each disease summarizing the most significant paradigms before moving into dedicated summaries on epidemiology, risk factors, anatomy, pathology, genetics, screening, clinical presentation, workup, prognostic factors, staging, treatment paradigm, and medical management. An evidence-based question and answer section concludes each chapter, which pairs commonly encountered clinical questions with answers connecting historical context and pertinent clinical studies to better inform decision making and treatment planning.Providing the latest treatment paradigms and guidelines, this comprehensive second edition now outlines the evidence and must-know considerations for using radiation therapy with immunotherapy, the strategies for metastasis-directed therapy for oligometastatic disease, and much more. Written for the practicing radiation oncologist, related practitioner, and radiation oncology resident entering the field, this "one-stop" resource is the go-to reference for everyday practice. Key Features: Structured sections offer high-yield information for targeted review Cites need-to-know clinical studies and treatment guidelines in evidence-based question and answer format Each chapter has been reviewed and updated to include the most recent and relevant studies New chapters on spine tumors, thyroid cancer, sinonasal tumors, cholangiocarcinoma, renal cell carcinoma, multiple myeloma and plasmacytoma, miscellaneous pediatric tumors, and treatment of oligometastatic disease from underlying cancers Designed for quick reference with comprehensive tables on treatment options and patient selection, workup, and prognostic factors by disease site Purchase includes digital access for use on most mobile devices or computers

There is now a range of cytotoxic drugs that have considerable clinical usefulness in producing responses in tumors and even, in a small proportion of cases, cure. However, the acquisition of drug resistance is a major clinical problem and is perhaps the main limiting factor in successful treatment of cancer. Thus, a tumor initially sensitive to chemotherapy will, in the majority of cases, eventually recur as a resistant tumor, which will then progress. Much of our understanding of drug resistance mechanisms comes from the study of tumor cell lines grown in tissue culture. We now understand many of the - lecular mechanisms that can lead to a cell acquiring resistance to antic- cer drugs; however, we still do not know which mechanism(s) are those most relevant to the problem of clinical drug resistance. Indeed, given that many of the cytotoxic anticancer drugs were discovered by random screening, it is - clear what features give a clinically useful anticancer drug a sufficient the- peutic index to be of value. The aim of Cytotoxic Drug Resistance Mechanisms is to provide pro- cols that are appropriate for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumor samples. Tumor cell lines have been enormously useful as experimental models of drug resistance mechanisms, however they have limitations and we need to address the relevance of such mechanisms in patients' tumors. Examining drug resistance in tumors is much more problematic than in cell lines.

This book presents an overview of the development of targeted therapies for the treatment of cancer with an emphasis on clinical application. The volume covers the complexity of the rapidly developing area of targeted therapies for the treatment of patients with cancer. It is structured in a way so readers may begin with chapters that most interest them and work through the rest of the chapters in the order of their choice.

Tyrosine Kinase Inhibitors as Sensitizing Agents for Chemotherapy, the fourth volume in the Cancer Sensitizing Agents for Chemotherapy Series, focuses on strategic combination therapies that involve a variety of tyrosine kinase inhibitors working together to overcome multi-drug resistance in cancer cells. The book discusses several tyrosine kinase inhibitors that have been used as sensitizing agents, such as EGFR, BCR-ABL, ALK and BRAF. In each chapter, readers will find comprehensive knowledge on the inhibitor and its action, including its biochemical, genetic, and molecular mechanisms' emphases. This book is a valuable source for oncologists, cancer researchers and those interested in applying new sensitizing agents to their research in clinical practice and in trials.

The introduction of new anticancer drugs and drug combinations, as well as the use of high-dose chemotherapy with growth factor and hemopoietic stem cell support, has greatly increased clinical remission rates. Unfortunately palliation, rather than cure, remains the most realistic goal of chemotherapy for many patients. The failure to cure metastatic cancer is commonly attributed to drug "resistance." Resistance can be broadly viewed as the survival of malignant cells because of a failure to deliver an effective drug dose to the (cellular) target, resulting from any one of or combination of individual factors. For example, inter-individual genetic differences in drug metabolism, as well as differences in tumor kinetics and vascularization, may be important for treatment outcome. In addition, numerous molecular mechanisms of resistance have been elucidated at the level of the individual tumor cell.
The present volume reviews clinically relevant aspects of the pharmacokinetics of commonly used anticancer agents as well as mechanisms of cellular/experimental resistance to such agents. This extends to technological advances that enable high-throughput studies of genetic polymorphisms, which has opened up new avenues to the study of drug resistance and to the individualization of chemotherapy in order to decrease clinical toxicity and optimize treatment results.
"This text provides a comprehensive review of the mechanisms of resistance to cancer chemotherapuetic agents. Leading experts discuss molecular and biochemical pathways that influence cytotoxicity. Knowledge of these potential obstacles to therapy will allow for the development of more effective strategies to treat malignantdiseases."
Steven T. Rosen, M.D., Series Editor

App included with purchase! See inside front cover for access instructions. Radiation Oncology Board Review with Flashcard App efficiently tests and reinforces your knowledge of key concepts, critical studies, and major clinical guidelines, with the most important radiation oncology citations included. Organized by treatment site, detailed questions cover natural history, epidemiology, diagnosis, staging, treatment options, and treatment-related side effects all in a newly configured format. Each question tests your recall and sharpens your skills so that you can practice and feel confident in your ability to manage all disease site areas according to the standard guidelines and key literature in the field. This updated second edition to Radiation Oncology Self-Assessment Guide also includes a companion flashcard app, so you can easily access and navigate over 950 questions on a smartphone, tablet or desktop computer. Written by residents and expert radiation oncologists from the Cleveland Clinic Taussig Cancer Institute, this review is a comprehensive study guide for anyone preparing for the board exam, for practicing physicians reviewing a topic, or preparing for MOC. Whether you are a few minutes between patients or are having a dedicated study session, this book and app bundle is an invaluable resource that will strengthen your knowledge of the field. Key Features: Updated and revised to reflect the new AJCC 8th Edition criteria, data guidelines for SBRT, hypofractionation for breast and prostate cancers, new advanced treatment planning and delivery techniques, and a dedicated Sarcomas section Covers all clinical topics and disease site areas that are in the ABR clinical radiation oncology exam and MOC Updated flashcard layout and organization of questions and answers Includes free access to mobile and online app-track and sync your progress on up to three devices!

We are in an exciting era in the war against cancer, with real prospects for novel anticancer drugs that are cancer cell-specific without the toxicities that have been the hallmark of conventional cytotoxic cancer chemotherapy. Advances in cancer cell biology fueled by the molecular biology revolution have resulted in the uncovering of many novel potential molecular targets for cancer therapy. New anticancer drug discovery and development is now largely focused on exploiting these new molecular targets, which encompass oncogenes, tumor s- pressor genes, and their gene products, as well as targets involved in tumor angiogenesis, metastasis, survival, and longevity mechanisms. Exploitation of some of these targets has already yielded fruits and introduced new paradigms of molecularly targeted cancer therapy into the clinic, namely, protein kinase in- bition by antibodies or small molecules, exemplified by Herceptin (R) (trastuzumab), a humanized antibody targeted against the HER-2 growth factor receptor tyrosine kinase for the treatment of metastatic breast cancer; and Gleevec, a small molecule bcr-abl kinase inhibitor for the treatment of chronic myel- enous leukemia.

Handbook of Geriatric Oncology is a practical resource for oncologists and related clinicians who want to provide comprehensive, patient-centered care to the elderly cancer patient. Divided into nine succinct sections, it includes topics spanning an Overview of Geriatric Oncology and Aging, Geriatric Syndromes, Geriatric Assessment, Select Cancers Commonly Diagnosed in the Elderly, Communication with the Older Cancer Patient, the Nursing Home Patient with Cancer, Models of Care and Survivorship, Palliative Care, and Integrative Medicine. Complex issues such as the physiologic changes of aging and their effect on cancer, corresponding social and psychological aspects that accompany aging and a cancer diagnosis, assessment of frailty, managing comorbid conditions and diseases, effective communication among healthcare providers, the patient and caregivers, as well as the risks and benefits of cancer screening, are made simpler with helpful clinical guidance and clinical pearls. Spearheaded by world experts in geriatric oncology from Memorial Sloan Kettering Cancer Center in New York, this book is the definitive resource for oncologists and related clinicians to meet the demands of clinical management along the continuum of geriatric cancer care. Key Features: Provides best practices for evaluating geriatric syndromes such as functional dependency, falls, cognitive impairment and dementia, delirium, depression and anxiety, social isolation as well as syndromes related to nutrition, comorbid conditions, and polypharmacy. Includes practical guidance on when to treat and when not to treat cancer in older patients Discusses unique factors associated with breast cancer, prostate cancer, colorectal cancer, lung cancer, ovarian cancer, bladder cancer, pancreatic cancer, head and neck cancers, and myelodysplastic syndromes in the elderly that impact care plans and treatment.

Leading international experts comprehensively review all aspects of platinum anticancer drugs and their current use in treatment, as well as examining their future therapeutic prospects. Writing from a variety of disciplines, these authorities discuss the chemistry of cisplatin in aqueous solution, the molecular interaction of platinum drugs with DNA, and such exciting new areas as DNA mismatch repair and replicative bypass, apoptosis, and the transport of platinum drugs into tumor cells. The emergent platinum drugs of the future-orally active agents, the sterically hindered ZD0473, and the polynuclear charged platinum BBR3464-are also fully considered. Timely and interdisciplinary, Platinum-Based Drugs in Cancer Therapy offers cancer therapeutics specialists an illuminating survey of every aspect of platinum drugs from mechanisms of action to toxicology, tumor resistance, and new analogs.

Named after Selene, Greek goddess of the moon, selenium (Se) has moved has moved from being thought of as a toxicant to being considered an essential nutrient with the potential to reduce cancer risk in the span of seven decades. Diversity of Selenium Functions in Health and Disease focuses on current knowledge of aspects of Se research relevant to its medical use, and particularly to chemoprevention of cancer. It covers how Se is integrated into selenoproteins, selenium compounds with individual functions and dual functions, and unexpected links to Se such as with diabetes. The text ends with a discussion of polymorphisms and mutations in genes of selenoproteins. The chapters elucidate why studies undertaken to prevent diseases with selenium ended with disappointing outcomes and often with the opposite result, i.e. disease promotion. They show that benefit, failure, or side effects depend on: The chemical form and dose of selenium The selenium status of the individual ingesting selenium The capacity of selenium form to serve as a source for selenoprotein biosynthesis The function of selenoproteins reacting to a change in the selenium status The stage of the disease (mainly cancer) at the time point of intervention The genetic background of individuals to be treated Bringing together the accumulated evidence regarding selenium biochemistry, the book covers aspects not found in available general monographs. The narrow focus on medical uses of Se helps resolve the present confusion about potential benefits and hazards of selenium in human health. The book gives you a solid scientific basis for optimum use of selenium in preventing or treating human diseases and answering the questions: Why is selenium essential? How much is required? What are the health consequences of low selenium and can selenium reduce cancer risk?

The discovery of the anti-tumour activity of cisplatin in 1965, and its subsequent introduction into clinical trials in 1971, was the catalyst for a major research effort into the potential of metal compounds in cancer therapy. This book provides a discussion of metal compounds in cancer therapy. This book should be of interest to research workers in the pharmaceutical industry, particularly tumour pharmacologists, tumour biologists, medicinal chemists and oncologists.

There have been tremendous recent advances in the pharmacotherapy, dose regimens, and combinations used to treat cancer and for the treatment or prevention of the spread of disease. As a direct result of these advances, there are an increasing number of cancer survivors, although research dealing with chemotherapy-induced pain is still in its early years.

Written for pain management specialists, oncologists, pharmacologists, students, and primary care practitioners, Chemotherapy-Induced Neuropathic Pain provides insight into the important area of chemotherapy-induced neuropathic pain. It reviews the basic and clinical research into the normal physiology of pain transmission pathways, neuropathic pain pathology, the chemotherapeutic drug mechanisms of action and adverse effects, chemotherapy-induced neuropathy, and drug discovery efforts for treatment.

The contributors comprise an impressive list of clinical and basic science experts in the fields of pain mechanisms and pain management. Included are clinical directors of pain clinics and clinical research facilities, directors of large academic pain research laboratories, analgesic drug developers, and presidents of the International Association for the Study of Pain (IASP), Association of Chronic Pain Patients (ACPP), and the British Pain Society (BPS). Through them, the book provides the reader with an exceptional opportunity to acquire a fundamental understanding of the basic concepts related to this topic.

The approach to drug discovery from natural sources has yielded many important new pharmaceuticals inaccessible by other routes. In many cases the isolated natural product may not be an effective drug for any of several reasons, but it nevertheless may become a drug through chemical modification or have a novel pharmacophore for future drug design. In summarizing the status of natural products as cancer chemotherapeutics, Anticancer Agents from Natural Products, Second Edition covers the: History of each covered drug-a discussion of its mechanism on action, medicinal chemistry, synthesis, and clinical applications Potential for novel drug discovery through the use of genome mining as well as future developments in anticancer drug discovery Important biosynthetic approaches to "unnatural" natural products Anticancer Agents from Natural Products, Second Edition discusses how complex target-oriented synthesis-enabled by historic advances in methodology-has enormously expanded the scope of the possible. This book covers the current clinically used anticancer agents that are either natural products or are clearly derived from natural product leads. It also reviews drug candidates currently in clinical development since many of these will be clinically used drugs in the future. Examples include the drugs etoposide and teniposide derived from the lead compound podophyllotoxin; numerous analogs derived from taxol; topotecan, derived from camptothecin; and the synthetic clinical candidates, E7389 and HTI-286, developed from the marine leads, halichondrin B and hemiasterlin.

One third of human cancers have a hormonal basis. Breast cancer, the most common cancer of women, is increasing in incidence in many countries, as, in epidemic proportions, is prostate cancer, the second most common cancer of men. Concurrently, the development of molecular biology has led to a refinement of the definition of hormones to include the complex interaction between tumour cells and both locally and distantly secreted factors. This volume in the series Cancer: Clinical Science in Practice considers the many aspects of hormonally dependent cancer, including the molecular basis for the autocrine and paracrine regulation of cancer, molecular strategies for cancer detection, preventive strategies in limiting the epidemic of hormonally related cancers, and new treatment approaches. Concise and authoritative, volumes in this series are intended for a wide audience of clinicians and researchers with an interest in the application of biomedical science to the understanding and management of cancer.

Intraperitoneal Cancer Therapy: Principles and Practice is one of the first books to combine the latest clinical developments in the treatment of patients with peritoneal surface disease and the scientific principles that underlie the concept of intraperitoneal cancer therapy. The book covers basic concepts such as anatomy, physiology, pharmacology, and mathematical models of drug transport as well as practical clinical applications, highlighted with results from clinical trials and promising novel preclinical developments. The book is a state-of-the-art reference for surgical and medical oncologists interested in the treatment of carcinomatosis. It also establishes and promotes basic and translational research interest in the field of intraperitoneal drug delivery, which has the potential to improve the outcome for this dreaded condition. Edited by two renowned surgical oncologists, it represents the definitive reference in the field of intraperitoneal cancer therapy.

Microspheres and Regional Cancer Therapy takes an interdisciplinary approach to the subject of microspheres and regional cancer therapy. It synthesizes laboratory and clinical data to demonstrate the utility of microsphere-based strategies in the treatment of localized solid tumors (particularly in the liver) not amenable to surgery and as a component of strategies for treatment of disseminated disease. Using the same techniques that show the deficiencies of delivery strategies involving antibodies, liposomes, and synthetic polymers, clear evidence is presented describing how microspheres of appropriate size can be localized in solid tumor deposits in the liver with little exposure to other organs. To exploit this phenomenon, the extent and nature of the incorporation of active agents within microspheres is discussed in relation to release, pharmacokinetics, and tumor response achieved by intensification of therapy in the manner described. This book will benefit laboratory-based scientists and clinicians in pharmaceutics, pharmacology, physiology, surgical oncology, and nuclear medicine. In addition, cancer clinicians interested in the value of regional therapy will be able to evaluate the underlying theory and learn the necessary methodology.

Covering all aspects of photodynamic therapy, 70 expert contributors from the fields of photochemistry, photobiology, photophysics, pharmacology, oncology and surgery, provide multidisciplinary discussions on photodynamic therapy - a rapidly-developing approach to the treatment of solid tumours.;Photodynamic Therapy: Basic Principles and Clinical Applications describes the molecular and cellular effects of photodynamic treatment; elucidates the complex events leading to photodynamics tissue destruction, particularly vascular and inflammatory responses; discusses the principles of light penetration through tissues and optical dosimetry; examines photosensitizer pharmacology and delivery systems; reviews in detail photosensitizer structure-activity relationships; illustrates novel devices that aid light dosimetry and fluorescence detection; and extensively delineates clinical applications, including early diagnosis and treatment.;A comprehensive and up-to-date reference, this book should be useful for oncologists, pharmacologists, surgeons, photobiologists, optical engineers, laser technicians, biologists, physicists, chemists and biochemists involved in cancer research, as well as graduate-level students in these disciplines.

Peritoneal dissemination is a common route of cancer metastasis. The benefit of administering chemotherapy directly into the peritoneal cavity is supported by preclinical and pharmacokinetic data. In comparison to intravenous (IV) treatment, intraperitoneal (IP) administration results in a several-fold increase in drug concentration within the abdominal cavity. There is now growing evidence from clinical studies showing a survival advantage for IP chemotherapy in various tumor typies, including ovarian, gastric and colorectal cancer. However, while the use of IP chemotherapy is slowly gaining acceptance, it is not universal, largely due to the greater toxicity associated with this approach. Moreover, efficacy of IP chemotherapy is limited by poor distribution within the abdominal cavity and by poor tissue penetration. A new way of IP chemotherapy is the application of cytotoxics in form of a pressurized aerosol into the abdominal of thoracic cavity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is applied through laparoscopic access using two balloon trocars in an operating room equipped with laminar air-flow. In a first step,a normothermic capnoperitoneum is established with a pressure of 12 mmHg. A cytotoxic solution (about 10% of a normal systemic dose) is nebulized with a micropump into the abdominal cavity, and maintained for 30 min. The aerosol is then removed through a closed suction system. Applying an aerosol in the peritoneal cavity allows a homogeneous distribution of the chemotherapeutic agent within the abdomen. Furthermore, an artificial pressure gradient is generated that overcomes tumoral interstitial fluid pressure, an obstacle in cancer therapy. This results in a higher local drug concentration compared to conventional IP or IV chemotherapy. At the same time the plasma concentration of the chemotherapeutic agent remains low. In first clinical studies with limited number of patients in ovarian, gastric and colorectal cancer, as well as peritoneal mesothelioma, PIPAC has obtained encouraging tumor response rates and survival, with a low-side effects profile. Larger clinical trials are currently ongoing to examine if these data can be reproduced and extrapolated to other situations.