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      Detection approaches for multidrug resistance genes of leukemia

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      Drug Design, Development and Therapy

      Dove Medical Press

      leukemia, multidrug resistance, MDR, detection approaches

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          Abstract

          Leukemia is a clonal malignant hematopoietic stem cell disease. It is the sixth most lethal cancer and accounts for 4% of all cancers. The main form of treatment for leukemia is chemotherapy. While some cancer types with a higher incidence than leukemia, such as lung and gastric cancer, have shown a sharp decline in mortality rates in recent years, leukemia has not followed this trend. Drug resistance is often regarded as the main clinical obstacle to effective chemotherapy in patients diagnosed with leukemia. Many resistance mechanisms have now been identified, and multidrug resistance (MDR) is considered the most important and prevalent mechanism involved in the failure of chemotherapy in leukemia. In order to reverse MDR and improve leukemia prognosis, effective detection methods are needed to identify drug resistance genes at initial diagnosis. This article provides a comprehensive overview of published approaches for the detection of MDR in leukemia. Identification of relevant MDR genes and methods for early detection of these genes will be needed in order to treat leukemia more effectively.

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          Most cited references 80

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          Digital PCR.

          The identification of predefined mutations expected to be present in a minor fraction of a cell population is important for a variety of basic research and clinical applications. Here, we describe an approach for transforming the exponential, analog nature of the PCR into a linear, digital signal suitable for this purpose. Single molecules are isolated by dilution and individually amplified by PCR; each product is then analyzed separately for the presence of mutations by using fluorescent probes. The feasibility of the approach is demonstrated through the detection of a mutant ras oncogene in the stool of patients with colorectal cancer. The process provides a reliable and quantitative measure of the proportion of variant sequences within a DNA sample.
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            Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches.

            Multi-drug resistance (MDR) has become the largest obstacle to the success of cancer chemotherapies. The mechanisms of MDR and the approaches to test MDR have been discovered, yet not fully understood. This review covers the in vivo and in vitro approaches for the detection of MDR in the laboratory and the mechanisms of MDR in cancers. This study also envisages the future developments toward the clinical and therapeutic applications of MDR in cancer treatment. Future therapeutics for cancer treatment will likely combine the existing therapies with drugs originated from MDR mechanisms such as anti-cancer stem cell drugs, anti-miRNA drugs or anti-epigenetic drugs. The challenges for the clinical detection of MDR will be to find new biomarkers and to determine new evaluation systems before the drug resistance emerges. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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              Fluorescence in situ hybridization: past, present and future.

              Fluorescence in situ hybridization (FISH), the assay of choice for localization of specific nucleic acids sequences in native context, is a 20-year-old technology that has developed continuously. Over its maturation, various methodologies and modifications have been introduced to optimize the detection of DNA and RNA. The pervasiveness of this technique is largely because of its wide variety of applications and the relative ease of implementation and performance of in situ studies. Although the basic principles of FISH have remained unchanged, high-sensitivity detection, simultaneous assay of multiple species, and automated data collection and analysis have advanced the field significantly. The introduction of FISH surpassed previously available technology to become a foremost biological assay. Key methodological advances have allowed facile preparation of low-noise hybridization probes, and technological breakthroughs now permit multi-target visualization and quantitative analysis - both factors that have made FISH accessible to all and applicable to any investigation of nucleic acids. In the future, this technique is likely to have significant further impact on live-cell imaging and on medical diagnostics.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                18 April 2017
                : 11
                : 1255-1261
                Affiliations
                Department of Hematology and Oncology (Key Department of Jiangsu Medicine), School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China
                Author notes
                Correspondence: Baoan Chen, Department of Hematology and Oncology, School of Medicine, Zhongda Hospital, Southeast University, Dingjiaqiao 87, Gulou District, Nanjing 210009, Jiangsu Province, People’s Republic of China, Tel +86 25 8327 2006, Fax +86 25 8327 2011, Email cba8888@ 123456hotmail.com
                Article
                dddt-11-1255
                10.2147/DDDT.S134529
                5402920
                © 2017 Du and Chen. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Pharmacology & Pharmaceutical medicine

                detection approaches, mdr, multidrug resistance, leukemia

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