Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells.
نویسندگان
چکیده
Gemcitabine has been one of the most commonly used agents for pancreatic adenocarcinoma chemotherapy, but the determinants of the sensitivity of and resistance to this agent are not yet fully understood. In this study with pancreatic carcinoma and biliary tract carcinoma cell lines, we examined the gene expression levels of nucleotide transporters and others related to the metabolism of gemcitabine in the light of sensitivity to this agent. Quantitative RT-PCR demonstrated that one of the nucleotide transporter genes; human equilibrative nucleoside transporter 1 (hENT1) was associated with the sensitivity to gemcitabine as represented by IC50, while the other genes for nucleotide transporter and metabolism were not. We conclude that increased hENT1 expression is a most important determinant of gemcitabine sensitivity at least in an in vitro study.
منابع مشابه
Breaking Advances Highlights from Recent Cancer Literature
Pancreatic cancers are inherently refractory to conventional chemotherapies. Gemcitabine [20,20-difluoro-20deoxycytidine (dFdC)] is currently used as a first-line treatment against locally advanced and metastatic adenocarcinoma of the pancreas. Gemcitabine is phosphorylated intracellularly to its active diphosphate (dFdC-DP) and triphosphate (dFdC-TP) forms that inhibit DNA and RNA replication....
متن کاملThe absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma.
PURPOSE Gemcitabine monotherapy is the standard palliative chemotherapy for pancreatic adenocarcinoma. Gemcitabine requires plasma membrane nucleoside transporter proteins to efficiently enter cells and exert it cytotoxicity. In vitro studies have demonstrated that deficiency of human equilibrative nucleoside transporter 1 (hENT1), the most widely abundant and distributed nucleoside transporter...
متن کاملHuman Equilibrative Nucleoside Transporter 1 (hENT1) in Pancreatic Adenocarcinoma: Towards Individualized Treatment Decisions
Pancreatic cancer is one of the most lethal cancers, where curative surgical resections are rare and less than 5% of patients experience long-term survival. Despite numerous clinical trials, improvements in the systemic treatment of this disease have been limited. Gemcitabine, a nucleoside analogue, is still considered the standard of care chemotherapy for most patients in the advanced disease ...
متن کاملNucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2',2'-difluorodeoxycytidine- induced cytotoxicity.
PURPOSE Concentrative nucleoside transporter (CNT) 1, CNT3, equilibrative nucleoside transporter (ENT) 1, and, to a lesser extent, ENT2, appear to be the transporters responsible for 2',2'-difluorodeoxycytidine (gemcitabine; Gemzar) uptake into cells. Gemcitabine is used currently in the treatment of pancreatic cancer, but the role of specific nucleoside carrier proteins in gemcitabine cytotoxi...
متن کاملHuman equilibrative nucleoside transporter 1 (hENT1) protein is associated with short survival in resected ampullary cancer.
BACKGROUND Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples...
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ورودعنوان ژورنال:
- Oncology reports
دوره 17 5 شماره
صفحات -
تاریخ انتشار 2007