Maréchal Raphaël, Van Laethem Jean-Luc
Department of Gastroenterology and Pancreatology, Gastrointestinal Cancer Unit Erasme University Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Expert Rev Anticancer Ther. 2009 Oct;9(10):1439-41. doi: 10.1586/era.09.119.
Costantino CL, Witkiewicz AK, Kuwano Y et al. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res. 69, 4567-4572 (2009). Gemcitabine has been the standard of care for pancreatic cancer for a decade but is only effective in some patients. As a prodrug, gemcitabine is activated by different protein kinases. The deoxycytidine kinase (dCK) is the first step of intracellular activation. We review the study by Costantino and colleagues, evaluating the consequence of modulating Hu antigen R (HuR), a stress response protein, on dCK expression and the correlation between HuR expression levels and pancreatic cancer outcome. This study demonstrates that dCK protein concentration levels were regulated by HuR and that a high cytoplasmic HuR level was associated with a sevenfold decreased risk of mortality after resection of pancreatic adenocarcinoma and gemcitabine therapy.
科斯坦蒂诺·C·L、维特凯维茨·A·K、久保野·Y等。HuR在胰腺癌吉西他滨疗效中的作用：HuR上调吉西他滨代谢酶脱氧胞苷激酶的表达。《癌症研究》69卷，4567 - 4572页（2009年）。十年来，吉西他滨一直是胰腺癌的标准治疗药物，但仅对部分患者有效。作为一种前体药物，吉西他滨由不同的蛋白激酶激活。脱氧胞苷激酶（dCK）是细胞内激活的第一步。我们回顾了科斯坦蒂诺及其同事的研究，评估调节应激反应蛋白Hu抗原R（HuR）对dCK表达的影响以及HuR表达水平与胰腺癌预后的相关性。这项研究表明，dCK蛋白浓度水平受HuR调节，并且高细胞质HuR水平与胰腺腺癌切除术后及吉西他滨治疗后死亡风险降低7倍相关。
