Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer

Santini, Daniele; Vincenzi, Bruno; Fratto, Maria Elisabetta; Perrone, Giuseppe; Lai, Raymond; Catalano, Vincenzo; Cass, Carol E.; Ruffini, Pier Adelchi; Spoto, Chiara; Muretto, Pietro; Rizzo, Sérgio; Muda, Andrea Onetti; Mackey, John R.; Russo, Antonio; Tonini, Giuseppe; Graziano, Francesco

doi:10.1002/jcp.22045

Cited by 39 publications

(32 citation statements)

References 25 publications

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“…Several investigators have examined intratumoral hENT1 expression in various malignant tumors. According to these reports, the proportion of patients with high intratumoral hENT1 expression was 72% for breast cancer, 34 71% for lung cancer, 23 50% for bladder cancer, 22 45% for gastric cancer, 31 and 37% to 43% for pancreatic cancer. [24][25][26][27] With regard to biliary carcinoma, an Italian group reported that high intratumoral hENT1 expression was found in 63% of patients with ampullary cancer 35 and 68% of patients with biliary tract cancer, 28 although these reports were based on a small number of patients.…”

Section: Discussionmentioning

confidence: 97%

“…Santini et al 31 reported that in a retrospective analysis of 111 patients with resected gastric cancer who did not receive chemotherapy including gemcitabine, patients with high hENT1 expression had a shorter overall or disease-free survival than those with low hENT1 expression. In addition, they also reported a similar result in an immunohistochemical analysis of 41 tumors from patients with ampullary cancer.…”

Section: Discussionmentioning

confidence: 98%

“…This cutoff value was determined on the basis of a previous report. 31 In cases of disagreement, consensus was reached by joint review.…”

Section: Immunohistochemistry For Hent1mentioning

confidence: 99%

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Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection

Kobayashi

Murakami²,

Uemura³

et al. 2012

Annals of Surgery

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

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Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection

Kobayashi

Murakami²,

Uemura³

et al. 2012

Annals of Surgery

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“…Immunohistochemistry of mCNT1-3 in mouse choroid plexus. IHC staining of formalin fixed paraffin embedded wild-type (FVB/N) mouse choroid plexus was undertaken using methods previously described [241]. The antibodies mCNT1 , mCNT2 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) and mCNT3 each reacted specifically on an immunoblot with a membrane isolate from yeast expressing the relevant nucleoside transporter (data not shown).…”

Section: Nucleoside Homeostasismentioning

confidence: 99%

Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain

Parkinson¹,

Damaraju²,

Graham³

et al. 2011

CTMC

167

149

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Pyrimidine and purine nucleosides and their derivatives have critical functions and pharmacological applications in the brain. Nucleosides and nucleobases are precursors of nucleotides, which serve as the energy-rich currency of intermediary metabolism and as precursors of nucleic acids. Nucleosides (e.g., adenosine) and nucleotides are key signaling molecules that modulate brain function through interaction with cell surface receptors. Brain pathologies involving nucleosides and their metabolites range from epilepsy to neurodegenerative disorders and psychiatric conditions to cerebrovascular ischemia. Nucleoside analogs are used clinically in the treatment of brain cancer and viral infections. Nucleosides are hydrophilic molecules, and transportability across cell membranes via specialized nucleoside transporter (NT) proteins is a critical determinant of their metabolism and, for nucleoside drugs, their pharmacologic actions. In mammals, there are two types of nucleoside transport process: bidirectional equilibrative processes driven by chemical gradients, and unidirectional concentrative processes driven by sodium (and proton) electrochemical gradients. In mammals, these processes, both of which are present in brain, are mediated by members of two structurally unrelated membrane protein families (ENT and CNT, respectively). In this Chapter, we review current knowledge of cellular, physiological, pathophysiological and therapeutic aspects of ENT and CNT distribution and function in the mammalian brain, including studies with NT inhibitors and new research involving NT knockout and transgenic mice. We also describe recent progress in functional and molecular studies of ENT and CNT proteins, and summarize emerging evidence of other transporter families with demonstrated or potential roles in the transport of nucleosides and their derivatives in the brain.

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“…At present, it has been considered that the occurrence of GC is closely related to Helicobacter pylori infection, gene mutation, diet, and other risk factors. [3][4][5] Despite much progress in the treatment of GC, the overall 5 year survival rate of patients with GC is still less than 30%. 6 Heterogeneity and a lack of effective therapeutic targets are the two major obstacles to the precise treatment of GC.…”

Section: 2mentioning

confidence: 99%

Tumor suppressor miR-449a inhibits the development of gastric cancerviadown-regulation of SGPL1

et al. 2018

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MicroRNAs (miRNAs) are small noncoding RNAs that are known to participate in the regulation of many physiological and pathological processes, which can indirectly influence the development of malignant behaviors. Numerous studies have demonstrated that miR-449a plays important roles in human carcinogenesis. However, its precise functional and regulatory roles remain unclear. In this study, we mainly explored the functional role of miR-449a in gastric cancer (GC). The expression levels of miR-449a in 98 cases of GC tissues and cell lines were determined by qRT-PCR. The possible mechanisms of miR-449a in GC cells were explored by fluorescence reporter assay. miR-449a expression was significantly lower in GC tissues compared to matched para-carcinoma tissues and was associated with tumor differentiation.Furthermore, in vitro knockdown of miR-449a by siRNA significantly inhibited MKN-28 cell proliferation, migration and invasion as well as tumorigenesis via inducing G0/G1 arrest of GC cells. In addition, we identified SGPL1 as a target of miR-449a and demonstrated that miR-449a regulated SGPL1 expression via binding its 3 0 -UTR region. The experiments indicated that miR-449a functions as a novel tumor suppressor in GC and its anti-oncogenic activity may involve its inhibition of the target gene SGPL1. These findings suggested that miR-449a may be a promising candidate for the development of antitumor drugs targeting GC.

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Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer

Cited by 39 publications

References 25 publications

Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection

Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Advanced Cholangiocarcinoma Patients Treated With Gemcitabine-Based Adjuvant Chemotherapy After Surgical Resection

Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain

Tumor suppressor miR-449a inhibits the development of gastric cancerviadown-regulation of SGPL1

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