Title |
Down-regulation of argininosuccinate synthetase is associated with cisplatin resistance in hepatocellular carcinoma cell lines: implications for PEGylated arginine deiminase combination therapy
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Published in |
BMC Cancer, August 2014
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DOI | 10.1186/1471-2407-14-621 |
Pubmed ID | |
Authors |
Jennifer A McAlpine, Hsin-Tze Lu, Katherine C Wu, Susan K Knowles, James A Thomson |
Abstract |
Many advanced human tumors, including hepatocellular carcinomas (HCC) are auxotrophic for arginine due to down-regulation of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in arginine synthesis. The arginine-lowering agent PEGylated arginine deiminase (ADI-PEG 20) has shown efficacy as a monotherapy in clinical trials for treating arginine-auxotrophic tumors and is currently being evaluated in combination with cisplatin in other cancer types. Epigenetic silencing via methylation of the ASS1 promoter has been previously demonstrated in other cancer types, and a reciprocal relationship between ASS1 expression and cisplatin resistance has also been observed in ovarian cancer. However, the mechanism of ASS1 down-regulation, as well as the correlation with cisplatin resistance has not been explored in HCC. The present study investigates ADI-PEG 20 and cisplatin sensitivities in relation to ASS1 expression in HCC. In addition, we show how this biomarker is regulated by cisplatin alone and in combination with ADI-PEG 20. |
X Demographics
Geographical breakdown
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France | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 3% |
France | 1 | 3% |
Unknown | 34 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 9 | 25% |
Student > Bachelor | 8 | 22% |
Student > Master | 5 | 14% |
Student > Postgraduate | 3 | 8% |
Researcher | 3 | 8% |
Other | 3 | 8% |
Unknown | 5 | 14% |
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Agricultural and Biological Sciences | 12 | 33% |
Biochemistry, Genetics and Molecular Biology | 8 | 22% |
Medicine and Dentistry | 4 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
Immunology and Microbiology | 2 | 6% |
Other | 3 | 8% |
Unknown | 5 | 14% |