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Patient Derived Tumor Xenograft Models

Patient Derived Tumor Xenograft Models
Promise, Potential and Practice

by Rajesh Uthamanthil,Peggy Tinkey,Elisa de Stanchina

  • Publisher : Academic Press
  • Release : 2016-10-13
  • Pages : 486
  • ISBN : 0128040610
  • Language : En, Es, Fr & De
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Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains. In addition, proper methodologies suitable for growing different type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory. Offers guidance on data interpretation and regulatory aspects Provides useful techniques and strategies for working with PDX models Includes practical tools and potential pitfalls for best practices Compiles all knowledge of PDX models research in one resource Presents the results of first ever global survey on standards of PDX development and usage in academia and industry

Patient-Derived Xenograft Models of Human Cancer

Patient-Derived Xenograft Models of Human Cancer
A Book

by Yuzhuo Wang,Dong Lin,Peter W. Gout

  • Publisher : Springer
  • Release : 2017-06-27
  • Pages : 204
  • ISBN : 3319558250
  • Language : En, Es, Fr & De
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This book provides a comprehensive, state-of-the-art review of PDX cancer models. In separately produced chapters, the history and evolution of PDX models is reviewed, methods of PDX model development are compared in detail, characteristics of available established models are presented, current applications are summarized and new perspectives about use of PDX models are proposed. Each chapter is written by a world-renowned expert who is conducting cutting-edge research in the field. Each of the subsections provide a comprehensive review of existing literature addressing the particular topic followed by a conclusive paragraph detailing future directions. Extensive illustrations make this an interactive text. Patient-Derived Xenograft Models of Human Cancer will serve as a highly useful resource for researchers and clinicians dealing with, or interested in, this important topic. It will provide a concise yet comprehensive summary of the current status of the field that will help guide preclinical and clinical applications as well as stimulate investigative efforts. This book will propagate innovative concepts and prompt the development of ground-breaking technological solutions in this field.

Patient-Derived Mouse Models of Cancer

Patient-Derived Mouse Models of Cancer
Patient-Derived Orthotopic Xenografts (PDOX)

by Robert M. Hoffman

  • Publisher : Springer
  • Release : 2017-08-01
  • Pages : 296
  • ISBN : 3319574248
  • Language : En, Es, Fr & De
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This text highlights seminal discoveries and also provides comprehensive and state-of the-art approach to mouse models of human patient tumors. These areas include training, basic techniques, as well as general troubleshooting. Subsequent chapters focus on the different mouse models of patient tumors including the various strains of immunodeficient mice currently available and the transplantation techniques that can be used as well as state-of-the-art imaging techniques. Practical applications of the models from drug discovery, genome analysis to personalized treatment are also covered. Written by experts in that field, each of these sections address these critical issues. A brief review of the existing literature addressing the particular topic follows in each section. Presently, there is no single source to provide information on technique and uses of mouse models of human patient tumors. Patient-Derived Mouse Models of Cancer will satisfy this need for cancer researchers, oncologists, pharmaceutical and biotechnology industry scientists as well as molecular biologists studying in vivo systems

Patient-derived Organoid Systems for the Study of Castrate-resistant Metastatic Prostate Cancer

Patient-derived Organoid Systems for the Study of Castrate-resistant Metastatic Prostate Cancer
A Book

by William Zhu

  • Publisher : Unknown Publisher
  • Release : 2019
  • Pages : 15
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Bone metastases of prostate cancer continue to elude effective clinical management world-wide. A newly developed xenograft model, PCSD1, is a pre-clinical therapeutic development and testing platform to understand the mechanisms of resistance to androgen deprivation therapy of bone metastatic prostate cancer. Prostate cancer is a heterogeneous disease for which it is especially important to study models that represent the range of different patients. However, of the patient samples investigated by Christina Jamieson's lab at UCSD, only 5 out of 20 (25%) were able to successfully create xenografts. The hypothesis I tested is that metastatic cells that have failed to xenograft into a patient-derived tumor xenograft mouse model will be able to successfully survive in vitro in an organoid culture system. The goals of my research were twofold: to successfully develop organoid cultures for both cells that have successfully and unsuccessfully xenografted into the mouse model and to perform imaging and genetic analysis on these organoids

Development of a Patient-derived Xenograft Model of Ovarian Cancer to Characterize the Chemotherapy Resistant Population

Development of a Patient-derived Xenograft Model of Ovarian Cancer to Characterize the Chemotherapy Resistant Population
A Book

by Zachary Christopher Dobbin

  • Publisher : Unknown Publisher
  • Release : 2014
  • Pages : 131
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Ovarian cancer while the second most common gynecologic malignancy is the most commons cause of death due to a gynecologic malignancy and the fifth most common cause of death to cancer in women. In 2014, there will be an expected 21,980 cases and 14,270 deaths. Unfortunately, the five-year survival for ovarian cancer is only 40% and this has barely increased over the past 30 years. New approaches need to be developed in order to study ovarian cancer and identify methods of overcoming chemotherapy resistance. This dissertation presents the work conducted in the development of a patient-derived xenograft model of ovarian cancer to characterize the chemotherapy resistant population and identify novel methods of targeting ovarian cancer. The ovarian cancer patient-derived xenograft model recapitulates the heterogeneity of the patients’ tumor and has demonstrated clinical relevance in response to primary therapy. Using RNA-seq, it was identified that ribosomal synthesis was upregulated and targeting RNA Polymerase I is a potential method of overcoming chemotherapy resistance. Using a patient-derived xenograft model provides a novel platform for understanding chemotherapy resistance and recurrence in ovarian cancer.

Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy, and Origins

Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy, and Origins

by Viive Maarika Howell,Ben Davidson,TIAN-Li WANG,Christina Annunziata

  • Publisher : Frontiers Media SA
  • Release : 2016-02-03
  • Pages : 129
  • ISBN : 2889197697
  • Language : En, Es, Fr & De
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This eBook provides a compendium of the current state-of-the-art in research tools for, and understanding of, the critical research areas in epithelial ovarian cancer (EOC) with a strong emphasis on (HG-SOC). Research areas covered include therapy response and development, microenvironmental influences and the etiology and progression of EOC. Ten articles detail established and novel in vivo and in vitro model systems. These include primary and immortalized cell culture in 2D and 3D as well as genetically engineered, transgenic, spontaneous, syngeneic, classical xenograft and patient derived xenograft mouse models. The generation of genetically engineered mouse models of HG-SOC has been a major dilemma as models with the oncogenic aberrations common in the human malignancy do not accurately recapitulate HG-SOC. Conversely, commonly used HG-SOC cell lines have been found to not harbor the expected genetic changes. These issues as well as the rapid acceptance of patient derived xenograft models are reviewed. Five articles discuss different aspects of the tumor microenvironment including its role in therapy resistance, disease progression and metastasis. Mutation of BRCA1/2 continues to be the best defined risk factor for HG-SOC. Three articles discuss BRCA-loss in the context of disease development, targeted therapies and changes in preventative measures proposed for mutation carriers in light of the recent advances in knowledge regarding the origins of this malignancy. An image of HG-SOC with reduced BRCA1 expression is featured on the cover (image by VM Howell). A major clinical issue for patients with HG-SOC is the development of therapy resistance. Five articles focus on therapy resistance and different ways to overcome resistance. Overall, this eBook is an outstanding resource to aid researchers design their programs of research and determine the most appropriate and up-to-date EOC model systems to address their research questions.

Differential Antitumor Activity of Aflibercept and Bevacizumab in Patient-derived Xenograft Models of Colorectal Cancer

Differential Antitumor Activity of Aflibercept and Bevacizumab in Patient-derived Xenograft Models of Colorectal Cancer
A Book

by Marielle Chiron

  • Publisher : Unknown Publisher
  • Release : 2014
  • Pages : 9
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Animal Models in Cancer Drug Discovery

Animal Models in Cancer Drug Discovery
A Book

by Asfar Azmi,Ramzi M. Mohammad

  • Publisher : Academic Press
  • Release : 2019-04-16
  • Pages : 470
  • ISBN : 0128147059
  • Language : En, Es, Fr & De
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Animal Models in Cancer Drug Discovery brings forward the most cutting-edge developments in tumor model systems for translational cancer research. The reader can find under this one volume virtually all types of existing and emerging tumor models in use by the research community. This book provides a deeper insight on how these newer models could de-risk modern drug discovery. Areas covered include up to date information on latest organoid derived models and newer genetic models. Additionally, the book discusses humanized animal tumor models for cancer immunotherapy and how they leverage personalized therapies. The chapter on larger animal, canine models and their use in and their use in pre-investigational new drug (pre-IND) development makes the volume unique. Unlike before, the incorporation of several simplified protocols, breeding methodologies, handling and assessment procedures to study drug intervention makes this book a must read. Animal Models in Cancer Drug Discovery is a valuable resource for basic and translational cancer researchers, drug discovery researchers, contract research organizations, and knowledge seekers at all levels in the biomedical field. Encompasses discussions on innovative animal models, xenograft, genetic models, primary models, organoid systems, humanized and other models in modern biology paradigms that are enhancing research in the field of drug discover Covers the use of these models in personalized medicine, immunotherapy, toxicology, pre-IND assessments and related drug development arenas Presents protocols, procedures, and a comprehensive glossary to help new readers understand technical terms and specialized nomenclature

Leveraging Protein Evolution to Elucidate Oncogenic Cytokine Signaling Axes and Develop Novel Therapeutics for Highly Lethal Cancers

Leveraging Protein Evolution to Elucidate Oncogenic Cytokine Signaling Axes and Develop Novel Therapeutics for Highly Lethal Cancers
A Book

by César Márquez

  • Publisher : Unknown Publisher
  • Release : 2020
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Pro-inflammatory cytokines in the tumor microenvironment (TME) can promote tumor growth, yet their value as therapeutic targets remains underexploited. Monoclonal antibodies have been the most widely used strategy to block ligand-receptor interactions and neutralize biological activity. An alternative approach involves engineering an extracellular fragment of a soluble receptor as a 'decoy' that binds to and sequesters the cognate ligand from activating cell surface receptors. Lung cancer is the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common subtype. While approximately 30% of patients with LUAD harbor a mutation in KRAS, there are currently few targeted therapeutic options. Our group previously described a cytokine, cardiotrophin-like cytokine factor 1 (CLCF1), in a LUAD genetically-engineered mouse model (GEMM). CLCF1 is secreted by cancer-associated fibroblasts, binds to a receptor, ciliary neurotrophic factor receptor (CNTFR), on neoplastic cells, and promotes tumor growth. We first validated the functional significance of the CLCF1-CNTFR signaling axis in human LUAD. In collaboration with Dr. Jennifer Cochran, using directed evolution via yeast surface display technology, we generated a high affinity soluble receptor, eCNTFR-Fc, that neutralizes the ligand, CLCF1, thereby inhibiting its oncogenic effects. eCNTFR-Fc inhibits tumor growth in multiple cell line and patient-derived tumor xenograft (PDTX) models and an autochthonous, highly aggressive GEMM of LUAD driven by activation of oncogenic Kras and loss of the tumor suppressor, Trp53. We also engineered an antagonistic ligand, ss6AA, which functions as a competitive antagonist of wild-type CLCF1 in tumor cell signaling and murine xenograft models. Mechanistic studies revealed that CLCF1 modulates ERK and STAT3 activity through SHP2, which in turn functions as an upstream regulator of both oncogenic and wild-type KRAS. As expected, abrogation of CLCF1 through eCNTFR-Fc is particularly effective in tumors driven by specific genotypes of mutant KRAS. This finding is significant given the recent observations highlighting the importance of upstream signaling molecules for both wild-type and oncogenic KRAS when the capacity to cycle between a GTP- and GDP-bound state is maintained. Indeed, we found that KRAS mutants most amenable to treatment also cycled more frequently between the two states. Our work, therefore, links novel cytokine signaling pathways with pro-tumorigenic downstream effectors. It also identifies a potential biomarker for further clinical development and provides an innovative therapeutic approach for a subset of tumors with limited available therapies. Overall, we nominate blockade of CLCF1-CNTFR signaling as a novel therapeutic opportunity for LUAD and potentially other tumor types, such as pancreatic ductal adenocarcinoma, in which CLCF1 is present in the TME. We decipher the mechanistic underpinnings of this pro-tumorigenic cytokine signaling axis and establish a link to oncogenic KRAS. We describe the development and preclinical testing of two first-in-class therapeutic candidates, an inhibitor (ss6AA) and a receptor decoy (eCNTFR-Fc), in multiple PDTXs and GEMMs. We demonstrate significant antitumor activity across a wide range of genetic subtypes, including KRAS-driven LUAD subsets, previously termed undruggable. Furthermore, we identified specific biomarkers that may portend increased sensitivity. These biomarkers could be used to stratify patients with tumors most likely to be inhibited by these agents in clinical trials.

Colorectal Cancer Patient-derived Xenograft (PDX) Models as Platform for Drug Screening, Molecular and Response Analysis

Colorectal Cancer Patient-derived Xenograft (PDX) Models as Platform for Drug Screening, Molecular and Response Analysis
A Book

by Maria Rivera

  • Publisher : Unknown Publisher
  • Release : 2016
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Tumor Models in Cancer Research

Tumor Models in Cancer Research
A Book

by Beverly A. Teicher

  • Publisher : Springer Science & Business Media
  • Release : 2010-12-01
  • Pages : 693
  • ISBN : 1607619687
  • Language : En, Es, Fr & De
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The past 6 years since the first edition of this book have seen great progress in the development of genetically engineered mouse (GEM) models of cancer. These models are finding an important role in furthering our understanding of the biology of malignant disease. A comfortable position for GEM models in the routine conduct of screening for potential new therapeutics is coming more slowly but is coming. Increasing numbers of genetically engineered mice are available, some with conditional activation of oncogenes, some with multiple genetic changes providing mouse models that are moving closer to the human disease.

Translational Research in Breast Cancer

Translational Research in Breast Cancer
A Book

by Dong-Young Noh,Wonshik Han,Masakazu Toi

  • Publisher : Springer Nature
  • Release : 2021-05-13
  • Pages : 630
  • ISBN : 9813296208
  • Language : En, Es, Fr & De
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This book describes recent advances in translational research in breast cancer and presents emerging applications of this research that promise to have meaningful impacts on diagnosis and treatment. It introduces ideas and materials derived from the clinic that have been brought to "the bench" for basic research, as well as findings that have been applied back to "the bedside". Detailed attention is devoted to breast cancer biology and cell signaling pathways and to cancer stem cell and tumor heterogeneity in breast cancer. Various patient-derived research models are discussed, and a further focus is the role of biomarkers in precision medicine for breast cancer patients. Next-generation clinical research receives detailed attention, addressing the increasingly important role of big data in breast cancer research and a wide range of other emerging developments. An entire section is also devoted to the management of women with high-risk breast cancer. Translational Research in Breast Cancer will help clinicians and scientists to optimize their collaboration in order to achieve the common goal of conquering breast cancer.

Molecular Diagnosis and Targeting for Gynecologic Malignancy

Molecular Diagnosis and Targeting for Gynecologic Malignancy
A Book

by Seiji Isonishi,Yoshihiro Kikuchi

  • Publisher : Springer Nature
  • Release : 2021-03-05
  • Pages : 165
  • ISBN : 9813360135
  • Language : En, Es, Fr & De
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This book summarizes the important developments in the field of cancer research, specifically uterine cervical/endometrial cancer and ovarian cancer. It highlights the recent advances in gynecologic cancer, such as next generation models of genetically engineered animal models or cancer cell lines, focusing on their significance for advancing our understanding of gynecologic cancer biology, prevention and treatment, and drug response and resistance. Cancer research in the area of gynecologic tumors has undergone an enormous transformation over the past decade, with a greater understanding of tumor biology, elucidation of novel targets for therapeutic intervention, and better recognition of genetic predisposition syndromes. At the same time, the recent advances in basic cancer research have provided key insights into all aspects of gynecologic cancer biology, including developmental pathways and the impact of lineage plasticity, understanding metastatic progression, uncovering the roles of the tumor microenvironment , exploring tumor evolution, and discovering new therapeutic approaches and mechanisms of drug sensitivity and adaptive response. Molecular Diagnosis and Targeting for Gynecologic Malignancy appeals to investigators, clinicians, residents and postdocs who are curious about new research on gynecologic malignancies. It not only presents basic and translational research, but also explores the generalizability of the evidence covering the interface between basic and clinical science. Furthermore, a number of the topics offer the basis for new ideas that have the potential to advance into the gynecologic malignancies. This book provides readers with state-of-the-art information that will help improve the lives of patients with these challenging diseases.

Nanotechnology Applications for Cancer Chemotherapy

Nanotechnology Applications for Cancer Chemotherapy
A Book

by Sanyog Jain,Kaisar Raza,Ashish Kumar Agrawal,Ankur Vaidya

  • Publisher : Elsevier
  • Release : 2020-09-30
  • Pages : 702
  • ISBN : 0128178477
  • Language : En, Es, Fr & De
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Applications of Nanotechnology in Cancer Chemotherapy offers a complete and concise summary of nanotechnological interventions for cancer management. It highlights the basics of oncology, the cancer microenvironment, targets for active drug delivery, the underlying mechanisms and molecular pathways to enhance the drug delivery to the cancer site. The book discusses the principles of basic and innovative nanocarrier-based therapeutic approaches to modulate the progression of the disease. In addition, this book also explores the evolving targeting approaches specific to the cancer site and type. The scope of the book is not limited to targeted drug delivery for various cancers, but also explores the advancements in cancer imaging and diagnostics employing the nanotechnological tools. Emphasis has been given on the important evaluation techniques like in-vitro cell culture and in-vivo animal models to assess the performance of cancer nanomedicines. The book includes clinical study reports of various drug moieties explored using variety of nanoconstructs in myriad cancer conditions with the input of global market and pharmacoeconomics. Discusses how organic and inorganic nanoplatforms are being used in cancer treatment Shows how nanotechnology is being used to create new and more accurate diagnostic tools Surveys the current generation of cancer nanomedicines, assessing their advantages and challenges

Patient-Derived Models of IDH1-Mutant, Hypermutated Glioma

Patient-Derived Models of IDH1-Mutant, Hypermutated Glioma
A Book

by Lindsey Elise Jones

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 73
  • ISBN : 9780438778245
  • Language : En, Es, Fr & De
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Gliomas are a group of central nervous system tumors that are classified based upon histopathological and molecular features. IDH-mutant low-grade gliomas (LGG) are prognostically favorable tumors and are often treated with temozolomide, but can undergo malignant progression via TMZ-induced hypermutation. Cell cultures that faithfully model this genetically distinct and clinically relevant hypermutated (HM) tumor subgroup are lacking, and are necessary to advance our understanding of HM tumors. We established patient-derived cell culture and xenograft models of HM oligodendroglioma and astrocytoma that faithfully recapitulate the molecular and functional features observed in their tumor of origin. We thoroughly characterized these cell lines and established that they are suitable for studying HM glioma, IDH-driven phenotypes, TERT promoter- and alternative lengthening of telomeres-driven cellular immortality, therapy-driven evolution, and intratumoral heterogeneity. These models have been widely shared with the neuro-oncology community and accelerated research at institutions across the United States.

Topics in Anti-Cancer Research: Volume 10

Topics in Anti-Cancer Research: Volume 10
A Book

by Atta-ur-Rahman

  • Publisher : Bentham Science Publishers
  • Release : 2021-12-13
  • Pages : 170
  • ISBN : 981503930X
  • Language : En, Es, Fr & De
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Topics in Anti-Cancer Research covers new developments in the field of cancer diagnosis and drug therapy. Novel drugs as anticancer agents include natural and synthetic phenazirines and other anti-cancer compounds. The series also covers information on the current understanding of the pathology and molecular biology of specific neoplasms. The diversity of research topics published in this book series give broad and valuable perspectives for cancer researchers, clinicians, cancer professionals aiming to develop novel anti-cancer targets and patents for the treatment of various cancers. The topics covered in this volume are: - Peptides can play a major role in combating cancer diseases - Studying of the CLL after treatment using fractal parameter of neoplastic lymphocytes detection (ΛNLD) - Mechanistic insight of rhenium-based compounds as anti- cancer agents - Targeting cancer-specific inflammatory components in cancer therapeutics - Marine natural products as a source of novel anticancer agents: a treasure from the ocean - PDX clinical trial design in anti-cancer research

Advances in Radiation Therapy

Advances in Radiation Therapy
A Book

by M. Guckenberger,S.E. Combs,D. Zips

  • Publisher : Karger Medical and Scientific Publishers
  • Release : 2018-04-12
  • Pages : 134
  • ISBN : 3318063622
  • Language : En, Es, Fr & De
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Developments in radiation oncology have been key to the tremendous progress made in the field in recent years. The combination of optimal systemic treatment and local therapy has resulted in continuing improved outcomes of cancer therapy. This progress forms the basis for current pre-clinical and clinical research which will strengthen the position of radiation oncology as an essential component of oncological care. This book summarizes recent advances in radiotherapy research and clinical patient care. Topics include radiobiology, radiotherapy technology, and particle therapy. Chapters cover a summary and analysis of recent developments in the search for biomarkers for precision radiotherapy, novel imaging possibilities and treatment planning, and advances in understanding the differences between photon and particle radiotherapy. Advances in Radiation Therapy is an invaluable source of information for scientists and clinicians working in the field of radiation oncology. It is also a relevant resource for those interested in the broad topic of radiotherapy in general.

Bioinformatics Analysis of Single Cell Sequencing Data and Applications in Precision Medicine

Bioinformatics Analysis of Single Cell Sequencing Data and Applications in Precision Medicine
A Book

by Jialiang Yang,Liao Bo,Tuo Zhang,Yifei Xu

  • Publisher : Frontiers Media SA
  • Release : 2020-02-27
  • Pages : 129
  • ISBN : 2889635287
  • Language : En, Es, Fr & De
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Chick Chorioallantoic Membrane Model and Precision Cancer Therapy

Chick Chorioallantoic Membrane Model and Precision Cancer Therapy
A Book

by Fuyuhiko Tamanoi

  • Publisher : Academic Press
  • Release : 2019-11-12
  • Pages : 178
  • ISBN : 0128173998
  • Language : En, Es, Fr & De
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Chick Chorioallantoic Membrane Model and Precision Cancer Therapy, Volume 46 in The Enzymes series, highlights new advances in the field, with this new volume presenting interesting chapters on the history of CAM model development, an overview of various CAM-based cancer models, the chick embryo chorioallantoic membrane as an in vivo experimental model to study multiple myelomak, bioluminescent CAM models for screening drugs against pancreatic cancer, X-ray sensitizer screen, patient derived tumor model for esophageal cancer, renal cancer and metastasis, nanoparticle characterization and tumor targeting, and patient derived tumor model for human nasopharyngeal carcinoma. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in The Enzymes series

Ex Vivo Engineering of the Tumor Microenvironment

Ex Vivo Engineering of the Tumor Microenvironment
A Book

by Amir R. Aref,David Barbie

  • Publisher : Springer
  • Release : 2016-12-09
  • Pages : 135
  • ISBN : 3319453971
  • Language : En, Es, Fr & De
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This volume will outline how to recreate the tumor microenvironment, to culture primary tumors without the need for developmental priming factors, and to deliver targeted therapeutics in a manner that recapitulates pharmacokinetics in vivo. Much of what may be learned from this volume will aid in understanding many aspects of the enhanced study of tumor cell biology in a physiologic context, open new avenues for drug screening and biomarker development, and accelerate the preclinical evaluation of novel personalized medicine strategies for patients in real time.