Download or read book Target Identification to Selectively Eradicate Acute Myeloid Leukemia Stem Cells written by and published by . This book was released on 2018 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Download or read book Evaluating Nutraceuticals for Selective Toxicity Toward Leukemia Stem Cells written by Sarah-Grace Rota and published by . This book was released on 2015 with total page 86 pages. Available in PDF, EPUB and Kindle. Book excerpt: Targeting leukemia stem cells (LSCs) is critical to improving the poor outcome of acute myeloid leukemia (AML) patients. Nutraceuticals (i.e., food derived bioactive compounds) provide a wealthy resource for novel anti-cancer, and specifically anti-AML drug discovery. With the advent of novel LSC cell lines, preliminary screening of these compounds against LSC-like cells can be achieved rapidly. To identify potential novel anti-LSC therapeutics, we created and screened a unique library consisting of 288 nutraceuticals in an MTS assay against TEX leukemia cells, a surrogate LSC line and K562, a control cell line which does not possess LSC activity. Here, we identified diosmetin, a flavonoid found in citrus fruits and various green plants, as a novel anti- LSC agent (EC50: 6.0 ± 1.7[mu]M). To confirm its activity, diosmetin (10[mu]M) reduced clonogenic growth of primary AML cells (n = 4) with no effect on normal CD34 positive bone marrow derived stem cells (n = 3) observed in colony forming cell assays. A dose-response and time course analysis performed via the Annexin/PI assay and flow cytometry revealed that diosmetin induced apoptosis, as evidenced by the accumulation of ANN+/PI- cells. Apoptosis was further confirmed by a subG1 peak after performing cell cycle analysis. Utilizing the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool, we determined that the estrogen receptor (ER) was a potential molecular target for diosmetin's anti-leukemia activity. To assess the role of estrogen receptors, we measured ER[alpha] and ER[beta] protein levels in diosmetin sensitive and insensitive cell lines. Interestingly, diosmetin sensitive cell lines display significantly elevated ER[beta] protein levels compared to diosmetin insensitive cells. However, this pattern was not observed for ER[alpha]. Similar results were observed through quantitative PCR measures, as TEX cells displayed levels of ESR2 (ER[beta]) mRNA, with no observed levels of ESR1 (ER[alpha]) mRNA levels. The opposite results were observed in K562 cells. Through ER reporter assays, it was demonstrated that diosmetin acts as a partial agonist in ER[beta] reporter cells, increasing luciferase activity with increasing doses of diosmetin in ER[beta] reporter cells. Moreover, we find that caspase 8 but not caspase 9 is elevated following diosmetin treatment, consistent with the extrinsic pathway of apoptosis and our observed increased in TNF-[alpha], similar to previous reports highlighting the link between ER[beta] agonists and cancer cell death. In summary, these studies highlight that estrogen receptors, specifically ER[beta], is a novel LSC therapeutic target, and the potential role of nutraceuticals as promising compounds for future drug discovery endeavours.
Download or read book Mechanisms of Resistence of New Target Drugs in Acute Myeloid Leukemia written by Debora Capelli and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: New drugs targeting single mutations have been recently approved for Acute Myeloid Leukemia (AML) treatment, but allogeneic transplant still remains the only curative option in intermediate and unfavorable risk settings, because of the high incidence of relapse. Molecular analysis repertoire permits the identification of the target mutations and drives the choice of target drugs, but the etherogeneity of the disease reduces the curative potential of these agents. Primary and secondary AML resistance to new target agents is actually an intriguing issue and some of these mechanisms have already been explored and identified. Changes in mutations, release of microenvironment factors competing for the same therapeutic target or promoting the survival of blasts or of the leukemic stem cell, the upregulation of the target-downstream pathways and of proteins inhibiting the apoptosis, the inhibition of the cytochrome drug metabolism by other concomitant treatments are some of the recognized patterns of tumor escape. The knowledge of these topics might implement the model of the ,ÄòAML umbrella trial,Äô study through the combinations or sequences of new target drugs, preemptively targeting known mechanisms of resistance, with the aim to improve the potential curative rates, expecially in elderly patients not eligible to transplant.
Download or read book Identifying Optimal Corticosteroids to Target Acute Myeloid Leukemia Stem Cells written by LeRon Best and published by . This book was released on 2022 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Acute myeloid leukemia (AML) is a cancer of the blood characterized by an increase in the number of immature blood cells (blasts) in the bone marrow, which cause hematopoietic insufficiency. Chemotherapies used for AML have mostly stayed the same for the last 40 years and involve extremely intense toxic treatment, yet approximately 40% of AML is resistant to initial treatment or eventually relapse. The survival rate 5 years after diagnosis of pediatric AML patients is poor (approximately 60%) and accounts for almost half of the leukemic deaths in children. This is partially due to the chemoresistant nature of the leukemic stem cells (LSCs) that sustain the disease. Compounds that specifically target LSCs while sparing normal hematopoietic stem cells (HSCs) may significantly improve patient outcome and lower toxicity across a broad leukemia spectrum in adolescent and young adult (AYA) and pediatric patients. After conducting an initial drug screen, our lab was able to identify the glucocorticoids mometasone, halcinonide and budesonide as compounds that can target LSCs while sparing HSCs. Corticosteroids have been shown to trigger apoptosis in some AML. However, we observed that these glucocorticoids effectively eliminated LSCs by driving them to terminally differentiate. In an effort to find the optimal corticosteroids to target LSCs, I examined a broad set of 24 corticosteroids using an in vitro drug screen and high-throughput flow cytometry to identify those that can target LSCs more effectively than the three glucocorticoids from the initial drug screen. The results showed that the most effective compounds were from the same chemical structure groups as the three glucocorticoids from the initial screen. This demonstrated a correlation between the molecular structures of these corticosteroids and their anti-LSC activity. Further examination of their molecular structures showed that compounds with increased anti-LSC activity possessed the C1-C2 double bond, C6/C9 fluorine, C16 methyl group, C16-C17 acetonide group and C17 ester. These structures have been shown to increase binding affinity for the glucocorticoid receptor and corticosteroid potency. From the 24 corticosteroids examined, fluticasone propionate was identified as the ideal compound for targeting LSCs. It showed superior anti-LSC activity compared to the three corticosteroids from the initial screen and its molecular structure possesses all the necessary structures to increase anti-LSC activity. Altogether these findings suggest that the mechanism of action of corticosteroids in LSCs is through the glucocorticoid receptor and that corticosteroids can possibly be an effective therapy against AML LSCs"--
Download or read book Microarray Innovations written by Gary Hardiman and published by CRC Press. This book was released on 2009-04-02 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, high-density DNA microarrays have revolutionized biomedical research and drug discovery efforts by the pharmaceutical industry. Their efficacy in identifying and prioritizing drug targets based on their ability to confirm a large number of gene expression measurements in parallel has become a key element in drug discovery. Microarr
Download or read book Leukemia Stem Cells written by César Cobaleda and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Download or read book Allogeneic Stem Cell Transplantation written by Hillard M. Lazarus and published by Springer Science & Business Media. This book was released on 2010-03-02 with total page 885 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the original publication of Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Allogeneic hematopoietic stem cell transplantation (HSC) has undergone several fast-paced changes. In this second edition, the editors have focused on topics relevant to evolving knowledge in the field in order to better guide clinicians in decision-making and management of their patients, as well as help lead laboratory investigators in new directions emanating from clinical observations. Some of the most respected clinicians and scientists in this discipline have responded to the recent advances in the field by providing state-of-the-art discussions addressing these topics in the second edition. The text covers the scope of human genomic variation, the methods of HLA typing and interpretation of high-resolution HLA results. Comprehensive and up-to-date, Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Second Edition offers concise advice on today's best clinical practice and will be of significant benefit to all clinicians and researchers in allogeneic HSC transplantation.
Download or read book Human B Cell Populations written by Manlio Ferrarini and published by Karger Medical and Scientific Publishers. This book was released on 1997-01-01 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt: B cells used to be considered as a homogeneous population of cells destined to produce antibodies of increasing affinity and to maintain an immunological memory. In recent years, it has been determined that B cells can be subdivided into different subsets characterized by distinct morphologic, phenotypic, and functional features. Presenting results of research work on the definition of B cell subset populations, this book explains the basic mechanisms that control B cell activation, stimulation and regulation. Articles include studies on both normal and malignant B cells and describe the mechanisms underlying T-B cell interactions during the immune response. The most important advances in the field of immunodeficiency are also reported. This volume will be essential not only for basic and clinical immunologists, but also for hematologists, pathologists and rheumatologists with a special interest in the pathogenesis of lymphoproliferative or autoimmune disorders.
Download or read book Cell Surface Proteases written by and published by Elsevier. This book was released on 2003-05-03 with total page 475 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell Surface Proteases provides a comprehensive overview of these important enzymes that catalyze the hydrolysis of a protein as it degrades to a simpler substance. In the 1990s, an explosion of new discoveries shed light on the role of cell surface proteases and extended it beyond degradation of extracellular matrix components to include its influence on growth factors, cell signaling, and other cellular events. This volume unites the scientific literature from across disciplines and teases out unified themes of interactions between cell surface proteases and interconnecting cell surface-related systems -- including integrins and other adhesion molecules. Scientists and students involved in developmental biology, cell biology and disease processes will find this an indispensable resource. * Provides an overview of the entire field of cell surface proteases in a single volume* Presents major issues and astonishing discoveries at the forefront of modern developmental biology and developmental medicine * A thematic volume in the longest-running forum for contemporary issues in developmental biology with over 30 years of coverage
Download or read book Mitochondria as Targets for Phytochemicals in Cancer Prevention and Therapy written by Dhyan Chandra and published by Springer Science & Business Media. This book was released on 2013-12-11 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the importance of phytochemicals and mitochondria in cancer prevention and therapy. Recent scientific discoveries have identified that naturally occurring biologically active compounds (i.e. phytochemicals) target multiple steps of tumorigenesis leading to the inhibition or delay in cancer progression. Mitochondria, organelles within a cell, are a critical target for phytochemicals in regulating the initiation, promotion, and progression of cancer. The book is divided into three parts to better communicate the important findings related to phytochemicals and mitochondria in cancer research. The first part describes updates on environmental and genetic factors causing cancer initiation and progression, the role of mitochondria function in regulating the process of tumorigenesis, and the role of mitochondria in regulating cell death such as apoptosis, autophagy, and necroptosis. The second part focuses on the elucidation of key target proteins that could be exploited for cancer prevention, an the role of phytochemicals in cancer prevention, updates on basic research related to phytochemicals action critical for cancer prevention, and updates on translational knowledge on cancer prevention by phytochemicals. The third part provides updates on phytochemicals targeting mitochondria for cancer therapy, an overview of action of phytochemicals on cancer stem cells, updates on the role of microRNA in phytochemicals-based therapy of cancer, and updates on phytochemicals-based translation research on therapy for metastatic cancer.
Download or read book Small Molecule Microarrays Methods and Protocols written by Mahesh Uttamchandani and published by Methods in Molecular Biology. This book was released on 2018-12-05 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Myeloid Leukemia New Insights for the Healthcare Professional 2011 Edition written by and published by ScholarlyEditions. This book was released on 2012-01-09 with total page 104 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myeloid Leukemia: New Insights for the Healthcare Professional: 2011 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Myeloid Leukemia. The editors have built Myeloid Leukemia: New Insights for the Healthcare Professional: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Myeloid Leukemia in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Myeloid Leukemia: New Insights for the Healthcare Professional: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Download or read book Normal and Malignant Hematopoiesis written by Enrico Mihich and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt: ''An exciting glance at key issues in contemporary hematopoiesis.'' -The Quarterly Review of Biology
Download or read book Metabolism in Cancer written by Thorsten Cramer and published by Springer. This book was released on 2016-08-24 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.
Download or read book Intercellular Communication in Cancer written by Mustapha Kandouz and published by Springer. This book was released on 2015-11-20 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cells are by nature compelled to live in groups. They develop dependence over signaling cues received from their microenvironment, in particular from other cells, whether of their own “kind” or of a different type. Therefore, communicating with these cells is a critical aspect of their behavior and fate, as they live and die normally or as they undergo disease-related pathological changes, with dramatic repercussions. In this book, we have asked expert researchers in the field of Intercellular Communication in Cancer to provide chapters on different aspects of interaction between neighboring cells, in the context of cancer diseases. We have specifically focused our efforts on membrane-to-membrane contact-based rather than growth factors-mediated modes of intercellular communications. The contributing authors provide an extensive overview of their respective area of specialization, with an in-depth discussion of the molecular mechanisms of cell-cell interactions, the impact on tumor progression and response to therapies, as well as the cancer diagnostic value of this scientific information. This book aims to introduce essential aspects of the normal and pathological cellular fate and homeostasis to both scientists and clinicians, and also to provide established researchers with an update on the novelties and future directions this expanding field is witnessing.
