Enhanced RegIV Expression Predicts the Intrinsic 5-Fluorouracil (5-FU) Resistance in Advanced Gastric Cancer
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ORIGINAL ARTICLE
Enhanced RegIV Expression Predicts the Intrinsic 5-Fluorouracil (5-FU) Resistance in Advanced Gastric Cancer Li-Sha Ying • Jiang-Liu Yu • Xiao-Xiao Lu Zhi-Qiang Ling
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Received: 18 April 2012 / Accepted: 20 August 2012 / Published online: 26 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract Aim RegIV, a member of the Regenerating (REG) gene family, may be a marker for the prediction of resistance to 5-fluorouracil (5-FU)-based chemotherapy. However, the relationship between the intrinsic drug resistance of gastric cancer (GC) cells to 5-FU used alone (single FU) or in multidrug therapeutic regimens (5-FU combinations) and RegIV expression has not been investigated. Methods The patient cohort comprised 45 patients with primary GC. The chemoresistance of GC cells to therapeutic regimens consisting of single 5-FU or FU combinations was investigated using the ATP-tumor chemosensitivity assay. The level of RegIV mRNA transcripts was determined by realtime reverse transcriptase-PCR. RegIV expression was evaluated as a novel predictive biomarker for the intrinsic drug resistance of primary GC cells to single 5-FU or 5-FU combinations. Results Upregulation of RegIV mRNA transcripts was observed in 36 of the 45 tumor specimens and was positively correlated with the invasive depth of the tumor cells (p = 0.000), the clinical stages (p = 0.000) and the in vitro
L.-S. Ying J.-L. Yu X.-X. Lu Z.-Q. Ling (&) Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, People’s Republic of China e-mail: [email protected] L.-S. Ying e-mail: [email protected] J.-L. Yu e-mail: [email protected] X.-X. Lu e-mail: [email protected]
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intrinsic drug resistance of primary GC cells to 5-FU (p = 0.000) or 5-FU combinations. Conclusion RegIV mRNA transcript level was strongly associated with the intrinsic resistance of GC cells to single 5-FU or 5-FU combinations, suggesting that RegIV may play an important role in the intrinsic resistance of GC cells to 5-FU and that targeted therapy against the RegIV gene could be applied to overcome 5-FU resistance in the treatment of GC. Keywords Gastric cancer Regenerating islet-derived family, member 4 (RegIV) 5-Fluorouracil ATP-tumor chemosensitivity assay Real-time reverse transcriptasePCR
Introduction Gastric cancer (GC) is a significant cancer in Asian countries, including China, Japan, and South Korea, with high incidence rates and considerable mortality. In China, GC is the second most common cancer—nearly one in five of all cancer diagnoses—and represents the second leading cause of cancer-related mortality [1, 2]. In contrast, a much lower incidence is reported in areas of South Asia, such as India, Pakistan, and Thailand, North America, Australia, and Africa [3]. Surgery is still the most effective treatment for GC, where early radical resection of GC can yield a 5-year survival rate of [90 % [4]. However, the rate of early diagnosis is low, and th
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