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Abstract: Objectives Gastric cancer (GC) is an aggressive disease due to late diagnosis resulting from the lack of easy diagnostic tools, resistances toward immunotherapy (due to low PD-L1 expression), or chemotherapies (due to p53 mutations), and comorbidity factors, notably muscle atrophy. To improve our understanding of this complex pathology, we established patient-derived xenograft (PDX) models and characterized the tumor ecosystem using a morpho-functional approach combining high-resolution imaging with molecular analyses, regarding the expression of relevant therapeutic biomarkers and the presence of muscle atrophy. Materials and methods GC tissues samples were implanted in nude mice. Established PDX, treated with cisplatin or not, were imaged by magnetic resonance imaging (MRI) and analyzed for the expression of relevant biomarkers (p53, PD-L1, PD-1, HER-2, CDX2, CAIX, CD31, a-SAM) and by transcriptomics. Results Three well-differentiated, one moderately and one poorly differentiated adenocarcinomas were established. All retained the architectural and histological features of their primary tumors. MRI allowed in-real-time evaluation of differences between PDX, in terms of substructure, post-therapeutic changes, and muscle atrophy. Immunohistochemistry showed differential expression of p53, HER-2, CDX2, a-SAM, PD-L1, PD-1, CAIX, and CD31 between models and upon cisplatin treatment. Transcriptomics revealed treatment-induced hypoxia and metabolic reprograming in the tumor microenvironment. Conclusion Our PDX models are representative for the heterogeneity and complexity of human tumors, with differences in structure, histology, muscle atrophy, and the different biomarkers making them valuable for the analyses of the impact of platinum drugs or new therapies on the tumor and its microenvironment
It is a great privilege to introduce this book devoted to the current and future roles in research and clinical practice of another exciting new development in MRI: Diffusi- weighted MR imaging. This new, quick and non-invasive technique, which requires no contrast media or i- izing radiation, offers great potential for the detection and characterization of disease in the body as well as for the assessment of tumour response to therapy. Indeed, whereas DW-MRI is already ? rmly established for the study of the brain, progress in MR techn- ogy has only recently enabled its successful application in the body. Although the main focus of this book is on the role of DW-MRI in patients with malignant tumours, n- oncological emerging applications in other conditions are also discussed. The editors of this volume, Dr. D. M. Koh and Prof. H. Thoeny, are internationally well known for their pioneering work in the ? eld and their original contributions to the l- erature on DW-MRI of the body. I am very much indebted to them for the enthusiasm and engagement with which they prepared and edited this splendid volume in a record short time for our series Medical Radiology – Diagnostic section.
The second, revised edition of this successful textbook provides an up-to-date description of the use of preoperative fMRI in patients with brain tumors and epilepsies. State of the art fMRI procedures are presented, with detailed consideration of practical aspects, imaging and data processing, normal and pathological findings, and diagnostic possibilities and limitations. Relevant information on brain physiology, functional neuroanatomy, imaging technique, and methodology is provided by recognized experts in these fields. Compared with the first edition, chapters have been updated to reflect the latest developments and in particular the current use of diffusion tensor imaging (DTI) and resting-state fMRI. Entirely new chapters are included on resting-state presurgical fMRI and the role of DTI and tractography in brain tumor surgery. Further chapters address multimodality functional neuroimaging, brain plasticity, and pitfalls, tips, and tricks.
Functional Neuroradiology: Principles and Clinical Applications, is a follow-up to Faro and Mohamed’s groundbreaking work, Functional (BOLD)MRI: Basic Principles and Clinical Applications. This new 49 chapter textbook is comprehensive and offers a complete introduction to the state-of-the-art functional imaging in Neuroradiology, including the physical principles and clinical applications of Diffusion, Perfusion, Permeability, MR spectroscopy, Positron Emission Tomography, BOLD fMRI and Diffusion Tensor Imaging. With chapters written by internationally distinguished neuroradiologists, neurologists, psychiatrists, cognitive neuroscientists, and physicists, Functional Neuroradiology is divided into 9 major sections, including: Physical principles of all key functional techniques, Lesion characterization using Diffusion, Perfusion, Permeability, MR spectroscopy, and Positron Emission Tomography, an overview of BOLD fMRI physical principles and key concepts, including scanning methodologies, experimental research design, data analysis, and functional connectivity, Eloquent Cortex and White matter localization using BOLD fMRI and Diffusion Tensor Imaging, Clinical applications of BOLD fMRI in Neurosurgery, Neurology, Psychiatry, Neuropsychology, and Neuropharmacology, Multi-modality functional Neuroradiology, Beyond Proton Imaging, Functional spine and CSF imaging, a full-color Neuroanatomical Brain atlas of eloquent cortex and key white matter tracts and BOLD fMRI paradigms. By offering readers a complete overview of functional imaging modalities and techniques currently used in patient diagnosis and management, as well as emerging technology, Functional Neuroradiology is a vital information source for physicians and cognitive neuroscientists involved in daily practice and research.
Over the past 20 years, technological advances in molecular biology have proven invaluable to the understanding of the pathogenesis of human cancer. The application of molecular technology to the study of cancer has not only led to advances in tumor diagnosis, but has also provided markers for the assessment of prognosis and disease progression. The aim of Molecular Ana- sis of Cancer is to provide a comprehensive collection of the most up-to-date techniques for the detection of molecular changes in human cancer. Leading researchers in the field have contributed chapters detailing practical pro- dures for a wide range of state-of-the-art techniques. Molecular Analysis of Cancer includes chapters describing techniques for the identification of chromosomal abnormalities and comprising: fluor- cent in situ hybridization (FISH), spectral karyotyping (SKY), comparative genomic hybridization (CGH), and microsatellite analysis. FISH has a pro- nent role in the molecular analysis of cancer and can be used for the detection of numerical and structural chromosomal abnormalities. The recently described SKY, in which all human metaphase chromosomes are visualized in specific colors, allows for the definition of all chromosomal rearrangements and marker chromosomes in a tumor cell. Protocols for the detection of chromosomal re- rangements by PCR and RT-PCR are described, as well as the technique of DNA fingerprinting, a powerful tool for studying somatic genetic alterations in tumorigenesis.
The reduction of greenhouse gas emissions—particularly from fossil fuel-powered vehicles and airplanes by means of weight savings and leaner fuel consumption, helps to restrain environmental impacts. In general, for a variety of industries, and specifically in the case of transport, where both weight savings and increased energy efficiency are pursued, the use of metal–polymer multi-material structures has been growing at an increasing and particularly fast pace in recent years. Several manufacturing techniques have been, or are being, developed, with the aim of being used for producing dissimilar materials in cost-efficient manners. This book presents recent developments in the state of the art of advanced additive manufacturing and the joining of metal–polymer multi-material structures in transportation. This publication mainly focuses on the correlations between microstructure, manufacturing process (i.e., AddJoining, adhesive bonding, friction riveting, friction-based staking and friction spot joining) properties, and the mechanical performance of metal–polymer multi-material structures.
This book offers a comprehensive overview of recent developments in the field of breast cancer biology. It is a complete and descriptive reference on motioning pathways and new treatment options for the future transnational scientists and clinicians working on cancer research and treatment. We greatly appreciate the work of all the contributors to this book. They have brought with them tremendous diversity of perspectives and fields, which is truly reflective of the complexity of the topic, and they have come together in this project to serve as the node of multidisciplinary collaboration in this field. Finally, we must acknowledge the thousands of cancer patients who have participated in the studies, and who have inspired us to gather information to significantly progress knowledge in the field in recent years.
Kinase drug discovery remains an area of significant interest across academia and in the pharmaceutical industry. There are now around 13 FDA approved small molecule drugs which target kinases and many more compounds in various stages of clinical development. Although there have been a number of reviews/publications on kinase research, this book fills a gap in the literature by considering the current and future opportunities and challenges in targeting this important family of enzymes. The book is forward-looking and identifies a number of hot topics and key areas for kinase drug discovery over the coming years. It includes contributions from highly respected authors with a combined experience in the industry of well over 200 years, which has resulted in a book of great interest to the kinase field and across drug discovery more generally. Readers will gain a real insight into the huge challenges and opportunities which this target class has presented drug discovery scientists. The many chapters cover a wide breadth of topics, are well written and include high quality colour and black and white images. Topics covered include an outline of how medicinal chemistry has been able to specifically exploit this unique target class, along with reflections on the mechanisms of kinases inhibitors. Also covered is resistance to kinase inhibitors caused by amino acid mutations, case studies of kinase programs and reviews areas beyond protein kinases and beyond the human kinome. Also described are modern approaches to finding kinase leads and the book finishes with a reflection of how kinase drug discovery may progress over the coming years.
This Special Issue is expected to advance our understanding of these emerging patterns, teleconnections, and extreme events in a changing world for more accurate prediction or projection of their changes especially on different spatial-time scales.
The development of computational methods that support human health and environmental risk assessment of engineered nanomaterials (ENMs) has attracted great interest because the application of these methods enables us to fill existing experimental data gaps. However, considering the high degree of complexity and multifunctionality of ENMs, computational methods originally developed for regular chemicals cannot always be applied explicitly in nanotoxicology. This book discusses the current state of the art and future needs in the development of computational modeling techniques for nanotoxicology. It focuses on (i) computational chemistry (quantum mechanics, semi-empirical methods, density functional theory, molecular mechanics, molecular dynamics), (ii) nanochemoinformatic methods (quantitative structure–activity relationship modeling, grouping, read-across), and (iii) nanobioinformatic methods (genomics, transcriptomics, proteomics, metabolomics). It reviews methods of calculating molecular descriptors sufficient to characterize the structure of nanoparticles, specifies recent trends in the validation of computational methods, and discusses ways to cope with the uncertainty of predictions. In addition, it highlights the status quo and further challenges in the application of computational methods in regulation (e.g., REACH, OECD) and in industry for product development and optimization and the future directions for increasing acceptance of computational modeling for nanotoxicology.