Download or read book Utilizing Primary Derived Cancer Organoids and Mouse Models to Validate the Translational Potential of Enhancing Mtorc1 2 Inhibition in Pik3ca Mutant Colorectal Cancer written by Rebecca Anna DeStefanis and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer-derived organoids are a preclinical tool that better recapitulates the diseases from which they are derived better than conventional models. The refinement of organoid cultures has occurred rapidly, but there is still an attempt to apply well-level response assessment assays used in 2-dimentional (2D) cultures to these unique 3-dimentional (3D) organoid cultures. However, it is becoming more apparent that these well-level assays, which evaluate the population as a whole, might not be as appropriate for organoid cultures. While culture conditions unique to 2D cell lines have been well characterized, such as culture confluency, no group has sought to identify if the unique properties of organoid cultures influence how treatment response assays are conducted and interpreted. It is important to identify if potential confounding factors exist in these models. Here we demonstrate the utility of establishing and validating organoids as a prospective clinical response tool. We then examine if unique organoid culture conditions influence the heterogeneity of individual organoid responses and the overall response of the entire organoid population.PIK3CA mutations are found in ~18% of all colorectal cancers (CRC). Mutations in this gene lead to constitutive activation of the PI3K signaling pathway. No targeted therapies are used in standard of care strategies for this population, though there is interest in identifying potential therapeutic strategies for CRC patients having these mutations. With established methods of identifying therapeutic response and accounting for the unique properties of this model, these cultures can be used to identify novel therapeutic strategies. Furthermore, cancer organoids derived from unique molecular profiles have the potential to identify and further refine personalized medicine strategies. Here we demonstrate the use of cancer-derived organoids as a tool to identify and evaluate novel therapeutic strategies for PIK3CA mutant CRC. Two identified combination therapies, copanlisib (MTORC1/2 inhibition) and navitoclax (BCL-2 family inhibition), and copanlisib and romidepsin (HDAC1/2 inhibition), are validated in multiple in vitro and in vivo models of PIK3CA mutant CRC. Altogether, these studies advance our understanding of cancer-derived organoids as tools for the identification and development of therapeutic strategies using clinically relevant in vitro and in vivo cancer model systems.
Download or read book Utilizing Primary Derived Cancer Organoids and Mouse Models to Validate the Translational Potential of Enhancing Mtorc1 2 Inhibition in Pik3ca Mutant Colorectal Cancer written by Rebecca Anna DeStefanis and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer-derived organoids are a preclinical tool that better recapitulates the diseases from which they are derived better than conventional models. The refinement of organoid cultures has occurred rapidly, but there is still an attempt to apply well-level response assessment assays used in 2-dimentional (2D) cultures to these unique 3-dimentional (3D) organoid cultures. However, it is becoming more apparent that these well-level assays, which evaluate the population as a whole, might not be as appropriate for organoid cultures. While culture conditions unique to 2D cell lines have been well characterized, such as culture confluency, no group has sought to identify if the unique properties of organoid cultures influence how treatment response assays are conducted and interpreted. It is important to identify if potential confounding factors exist in these models. Here we demonstrate the utility of establishing and validating organoids as a prospective clinical response tool. We then examine if unique organoid culture conditions influence the heterogeneity of individual organoid responses and the overall response of the entire organoid population.PIK3CA mutations are found in ~18% of all colorectal cancers (CRC). Mutations in this gene lead to constitutive activation of the PI3K signaling pathway. No targeted therapies are used in standard of care strategies for this population, though there is interest in identifying potential therapeutic strategies for CRC patients having these mutations. With established methods of identifying therapeutic response and accounting for the unique properties of this model, these cultures can be used to identify novel therapeutic strategies. Furthermore, cancer organoids derived from unique molecular profiles have the potential to identify and further refine personalized medicine strategies. Here we demonstrate the use of cancer-derived organoids as a tool to identify and evaluate novel therapeutic strategies for PIK3CA mutant CRC. Two identified combination therapies, copanlisib (MTORC1/2 inhibition) and navitoclax (BCL-2 family inhibition), and copanlisib and romidepsin (HDAC1/2 inhibition), are validated in multiple in vitro and in vivo models of PIK3CA mutant CRC. Altogether, these studies advance our understanding of cancer-derived organoids as tools for the identification and development of therapeutic strategies using clinically relevant in vitro and in vivo cancer model systems.
Download or read book Colon Cancer Cells written by Mary Pat Moyer and published by . This book was released on 1990 with total page 586 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book New Prognostic and Predictive Markers in Cancer Progression written by Susan Costantini Alfredo Budillon and published by MDPI. This book was released on 2021-02-12 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomarkers are of critical medical importance for oncologists, allowing them to predict and detect disease and to determine the best course of action for cancer patient care. Prognostic markers are used to evaluate a patient’s outcome and cancer recurrence probability after initial interventions such as surgery or drug treatments and, hence, to select follow-up and further treatment strategies. On the other hand, predictive markers are increasingly being used to evaluate the probability of benefit from clinical intervention(s), driving personalized medicine. Evolving technologies and the increasing availability of “multiomics” data are leading to the selection of numerous potential biomarkers, based on DNA, RNA, miRNA, protein, and metabolic alterations within cancer cells or tumor microenvironment, that may be combined with clinical and pathological data to greatly improve the prediction of both cancer progression and therapeutic treatment responses. However, in recent years, few biomarkers have progressed from discovery to become validated tools to be used in clinical practice. This Special Issue comprises eight review articles and five original studies on novel potential prognostic and predictive markers for different cancer types.
Download or read book Killing Cancer written by Tuula Kallunki and published by MDPI. This book was released on 2020-11-17 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite the efficiency of current cancer treatments, cancer is still a deadly disease for too many. In 2008, 7.6 million people died of cancer; with the current development, it is estimated that the annual cancer death number will grow to 13 million by 2030. There is clearly a need for not only more research but also more innovative and out of the mainstream scientific ideas to discover and develop even better cancer treatments. This book presents the collective works published in the recent Special Issue entitled “Killing Cancer: Discovery and Selection of New Target Molecules”. These articles comprise a selection of studies, ideas, and opinions that aim to facilitate knowledge, thoughts, and discussion about which biological and molecular mechanisms in cancer we should target and how we should target them.
Download or read book mTOR in Human Diseases written by Olivier Dormond and published by MDPI. This book was released on 2019-06-18 with total page 480 pages. Available in PDF, EPUB and Kindle. Book excerpt: The mechanistic target of rapamycin (mTOR) is a major signaling intermediary that coordinates favorable environmental conditions with cell growth. Indeed, as part of two functionally distinct protein complexes, named mTORC1 and mTORC2, mTOR regulates a variety of cellular processes, including protein, lipid, and nucleotide synthesis, as well as autophagy. Over the last two decades, major molecular advances have been made in mTOR signaling and have revealed the complexity of the events implicated in mTOR function and regulation. In parallel, the role of mTOR in diverse pathological conditions has also been identified, including in cancer, hamartoma, neurological, and metabolic diseases. Through a series of articles, this book focuses on the role played by mTOR in cellular processes, metabolism in particular, and highlights a panel of human diseases for which mTOR inhibition provides or might provide benefits. It also addresses future studies needed to further characterize the role of mTOR in selected disorders, which will help design novel therapeutic approaches. It is therefore intended for everyone who has an interest in mTOR biology and its application in human pathologies.
Download or read book Tumor Microenvironments in Organs written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-06 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the tumor microenvironment in over thirty human organs, including the parathyroid gland, heart, intestine, testicles, and more. Taken alongside its companion volumes, these books update us on what we know about the different aspects of the tumor microenvironments in distinct organs as well as future directions. Tumor Microenvironments in Organs: From the Brain to the Skin – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.
Download or read book Drug Resistance in Colorectal Cancer Molecular Mechanisms and Therapeutic Strategies written by Chi Hin Cho and published by Academic Press. This book was released on 2020-06-10 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies, Volume Eight, summarizes the molecular mechanisms of drug resistance in colorectal cancer, along with the most up-to-date therapeutic strategies available. The book discusses reasons why colorectal tumors become refractory during the progression of the disease, but also explains how drug resistance occurs during chemotherapy. In addition, users will find the current therapeutic strategies used by clinicians in their practice in treating colorectal cancer. The combination of conventional anticancer drugs with chemotherapy-sensitizing agents plays a pivotal role in improving the outcome of colorectal cancer patients, in particular those with drug-resistant cancer cells. From a clinical point-of-view, the content of this book provides clinicians with updated therapeutic strategies for a better choice of drugs for drug-resistant colorectal cancer patients. It will be a valuable source for cancer researchers, oncologists and several members of biomedical field who are dedicated to better treat patients with colorectal cancer. Presents a systemic summary of molecular mechanisms for a quick and in-depth understanding Updates current trends in the field with pioneering information on drug resistance Encompasses both basic and clinical approaches for a better understanding of unsolved problems from a holistic point-of-view
Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Download or read book Cancer Signaling written by Christoph Wagener and published by John Wiley & Sons. This book was released on 2016-08-12 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer, which has become the second-most prevalent health issue globally, is essentially a malfunction of cell signaling. Understanding how the intricate signaling networks of cells and tissues allow cancer to thrive - and how they can be turned into potent weapons against it - is the key to managing cancer in the clinic and improving the outcome of cancer therapies. In their ground-breaking textbook, the authors provide a compelling story of how cancer works on the molecular level, and how targeted therapies using kinase inhibitors and other modulators of signaling pathways can contain and eventually cure it. The first part of the book gives an introduction into the cell and molecular biology of cancer, focusing on the key mechanisms of cancer formation. The second part of the book introduces the main signaling transduction mechanisms responsible for carcinogenesis and compares their function in healthy versus cancer cells. In contrast to the complexity of its topic, the text is easy to read. 32 specially prepared teaching videos on key concepts and pathways in cancer signaling are available online for users of the print edition and have been integrated into the text in the enhanced e-book edition.
Download or read book Gene Regulation and Therapeutics for Cancer written by Surinder K. Batra and published by CRC Press. This book was released on 2021-03-22 with total page 315 pages. Available in PDF, EPUB and Kindle. Book excerpt: Differential gene regulation and targeted therapy are the critical aspects of several cancers. This book covers specific gene regulation and targeted therapies in different malignancies. It offers a comprehensive assessment of the transcriptional dysregulation in cancer, and considers some examples of transcriptional regulators as definitive oncogenic drivers in solid tumors, followed by a brief discussion of transcriptional effectors of the programs they drive, and discusses its specific targets. Most targeted therapeutics developed to date have been directed against a limited set of oncogenic drivers, exemplified by those encoding cell surface or cytoplasmic kinases that function in intracellular signaling cascades.
Download or read book Toxicoepigenetics written by Shaun D. McCullough and published by Academic Press. This book was released on 2018-11-02 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: Toxicoepigenetics: Core Principles and Applications examines the core aspects of epigenetics, including chromatin biology, DNA methylation, and non-coding RNA, as well as fundamental techniques and considerations for studying each of these mechanisms of epigenetic regulation. Although its integration into the field of toxicology is in its infancy, epigenetics have taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration. Increasing the presence of epigenetics in toxicological research allows for a more in-depth understanding of important aspects of toxicology such as the role of the environment and lifestyle influencing the individual susceptibility to these effects and the trans-generational transmission of these health effects and susceptibilities. Methods chapters are included to help improve efficacy and efficiency of protocols in both the laboratory and the classroom. Toxicoepigenetics: Core Principles and Applications is an essential book for researchers and academics using epigenetics in toxicology research and study. Introduces the fundamental principles and practices for understanding the role of the epigenome in toxicology Presents the foundation of epigenetics for toxicologists with a broad range of backgrounds Discusses the incorporation of epigenetics and epigenomics into current toxicological studies and interpretation of epigenetic data in toxicological applications
Download or read book Phytochemicals Targeting Tumor Microenvironment in Gastrointestinal Cancers written by Ganji Purnachandra Nagaraju and published by Springer Nature. This book was released on 2020-10-07 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gastrointestinal (GI) malignancies account for a large portion of cancers worldwide. Although incidence of esophageal, gastric, and colorectal cancers has decreased in recent years, pancreatic and liver cancer have increased. The mainstay of GI cancer therapy is chemoradiation and surgery. Despite significant medical advancements, diagnosis and therapy for GI cancers remain challenging due to tumor cell resistance to chemoradiotherapy. The tumor’s increased cell signalling due to excessive transcription factor activation and increased stellate cell activity leads to collagen deposition formation of a dense stroma around the tumor, which prevents drugs from reaching the malignant cells. This leads to tumor chemoresistance. To circumvent these difficulties, drug therapy targeting the tumor’s specific microenvironment and the additive anticancer effect of phytochemicals can allow for more effective treatment. This volume will be the first on the market on the topic of phytochemicals and their effect on the tumor microenvironment (TME). TME is an emerging area of research and the book will be a welcome introductory addition to the field.
Download or read book Intestinal Stem Cells written by Paloma Ordóñez-Morán and published by Humana. This book was released on 2021-08-07 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed book encapsulates the most up-to-date methods of the intestinal stem cell field and provides guidance on a variety of techniques for studying intestinal stem cells properties. Beginning with a section on in vitro techniques to study different aspects of the intestinal stem cell functions by innovative imaging and functional assays, the volume continues with chapters detailing the single-cell transcriptional profiling method, the isolation of intestinal crypts to generate and establish 3D organoids, as well as different animal models of gastrointestinal cancer and examples of the use of in vivo methods for studying intestinal tumor-initiating cells or cancer stem cells. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and state-of-the-art, Intestinal Stem Cells: Methods and Protocols aims to provide comprehensive and easy to follow protocols designed to be helpful to both seasoned researchers and newcomers to this dynamic field.
Download or read book Intestinal Stem Cell Niche written by and published by Academic Press. This book was released on 2018-04-24 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Stem Cells and Their Niches addresses stem cells during development, homeostasis, and disease/injury of the respective organs, presenting new developments in the field, including new data on disease and clinical applications. Video content illustrates such areas as protocols, transplantation techniques, and work with mice. Explores not only reviews of research, but also shares methods, protocols, and transplantation techniques Contains video content to illustrate such areas as protocols, transplantation techniques, and work with mice Each volume concentrates on one organ, making this a unique publication
Download or read book Mechanisms of Molecular Carcinogenesis Volume 1 written by Johannes Haybaeck and published by Springer. This book was released on 2017-05-23 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: Divided into two volumes the work offers a so far unmatched broad and at the same time deep knowledge on molecular and cellular mechanisms of carcinogenesis and offers comprehensive insight into clinical, therapeutic and technological aspects. This 1st Volume presents tumor entities of the ocular system, the thyroid organ, the oesophagus, gliomas, non-glial brain tumors, head and neck as well as lung cancer. In addition it also discusses in-depth potential novel molecular players and the role of stem cells as well as the endocannabinoid system in carcinogenesis, it furthermore explains tumor metabolism components and signaling pathways. Each of the chapters discusses potential therapeutic strategies and novel drug targets. The book addresses basic scientists and medical researchers interested in translational cancer research.
Download or read book Molecular Pathogenesis and Signal Transduction by Helicobacter pylori written by Nicole Tegtmeyer and published by Springer. This book was released on 2017-01-23 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume reviews the current state of research concerning bacterial virulence factors and the infection biology of Helicobacter pylori, which is the leading cause of peptic ulcers and gastric cancer worldwide. The chapters include cutting-edge findings on this fascinating microbe and discuss the general strategies of H. pylori infection and persistence, news on important H. pylori virulence factors, crosstalk with the microbiota, hot novel models and signaling mechanisms, risk factors of gastric disease and stomach cancer, and the impact of H. pylori infection on non-gastric diseases. Written by internationally respected scientists, this book will appeal to clinicians, researchers and advanced students alike.
