Chapter title |
Rapid In-vitro Testing for Chemotherapy Sensitivity in Leukaemia Patients.
|
---|---|
Chapter number | 6 |
Book title |
Bioluminescence: Fundamentals and Applications in Biotechnology - Volume 2
|
Published in |
Advances in biochemical engineering biotechnology, January 2014
|
DOI | 10.1007/978-3-662-43619-6_6 |
Pubmed ID | |
Book ISBNs |
978-3-66-243618-9, 978-3-66-243619-6
|
Authors |
Elizabeth Anderson, Vyv Salisbury, Anderson E, Salisbury V, Anderson, Elizabeth, Salisbury, Vyv |
Abstract |
Bioluminescent bacterial biosensors can be used in a rapid in vitro assay to predict sensitivity to commonly used chemotherapy drugs in acute myeloid leukemia (AML). The nucleoside analog cytarabine (ara-C) is the key agent for treating AML; however, up to 30 % of patients fail to respond to treatment. Screening of patient blood samples to determine drug response before commencement of treatment is needed. To achieve this aim, a self-bioluminescent reporter strain of Escherichia coli has been constructed and evaluated for use as an ara-C biosensor and an in vitro assay has been designed to predict ara-C response in clinical samples. Transposition mutagenesis was used to create a cytidine deaminase (cdd)-deficient mutant of E. coli MG1655 that responded to ara-C. The strain was transformed with the luxCDABE operon and used as a whole-cell biosensor for development an 8-h assay to determine ara-C uptake and phosphorylation by leukemic cells. Intracellular concentrations of 0.025 μmol/L phosphorylated ara-C were detected by significantly increased light output (P < 0.05) from the bacterial biosensor. Results using AML cell lines with known response to ara-C showed close correlation between the 8-h assay and a 3-day cytotoxicity test for ara-C cell killing. In retrospective tests with 24 clinical samples of bone marrow or peripheral blood, the biosensor-based assay predicted leukemic cell response to ara-C within 8 h. The biosensor-based assay may offer a predictor for evaluating the sensitivity of leukemic cells to ara-C before patients undergo chemotherapy and allow customized treatment of drug-sensitive patients with reduced ara-C dose levels. The 8-h assay monitors intracellular ara-CTP (cytosine arabinoside triphosphate) levels and, if fully validated, may be suitable for use in clinical settings. |
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Unknown | 1 | 100% |
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Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 10 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 3 | 30% |
Researcher | 2 | 20% |
Lecturer | 1 | 10% |
Student > Postgraduate | 1 | 10% |
Unknown | 3 | 30% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 3 | 30% |
Medicine and Dentistry | 2 | 20% |
Biochemistry, Genetics and Molecular Biology | 1 | 10% |
Unknown | 4 | 40% |