Search results for "Equilibrative nucleoside transporter"
showing 10 items of 12 documents
Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer.
2010
Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patie…
Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to pre…
2014
Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. Methods mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients a…
Human equilibrative nucleoside transporter 1 as a predictor of efficacy to gemcitabine in angiosarcoma and leiomyosarcoma.
2016
11062Background: Human equilibrative nucleoside transporter 1 (hENT1) is the major gemcitabine transporter into cells. Gemcitabine is an active drug in different sarcoma subtypes including leiomyos...
Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC)
2009
Background and aim: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. Materials and Methods: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. Results: Positive hENT1 staining patients were…
A phase II study of elacytarabine in combination with idarubicin and of human equilibrative nucleoside transporter 1 expression in patients with acut…
2013
Unlike cytarabine, cellular entry of Elacytarabine, the elaidic acid ester derivative of cytarabine, is independent of the human equilibrative nucleoside transporter 1 (hENT1). This phase II study tested whether the hENT1 blast expression level can be used as a predictive marker for cytarabine response and if the efficacy of elacytarabine is independent of hENT1 expression. A total of 51 patients with acute myeloid leukemia (AML) induction failure were given elacytarabine-idarubicin as a second induction course. The hENT1 expression level was analyzed prior to first induction and/or prior to treatment with elacytarabine. The overall response rate (ORR) was 41% and the safety profile was man…
Transcription factors involved in the expression of SLC28 genes in human liver parenchymal cells.
2007
Human nucleoside transporters are encoded by SLC28 (hCNTs) and SLC29 (hENTs) genes. These proteins mediate the uptake of anticancer and some antiviral drugs and are also suitable candidates to facilitate nucleoside-derived drug uptake into hepatocytes for detoxification. Despite the putative relevance of these genes in liver physiology, the human SLC28 and SLC29 expression pattern is not known and suitable cell models are not available. These issues have been addressed by examining NT expression in human liver and primary cultures of human hepatocytes. Moreover, the effect of specific liver enriched transcription factors (LETFs) in hCNTs expression has been analyzed. Human hepatocytes expre…
Eight-Membered Rings With Two Heteroatoms 1,3
2022
Eight-membered rings with two heteroatoms in a 1,3-relationship, namely 1,3-diazocine, 2H-1,3-oxazocine, 2H-1,3-thiazocine, 4H-1,3-dioxocin, 4H-1,3-oxathiocin, and 4H-1,3-dithiocin, are discussed in this chapter, that covers the literature from 2007 to October 2020 (SciFindern search) and reports the chemistry of uncondensed derivatives, heterocines fused to carbocycles and heterocycles, as well as bridged heterocines. Among eight-membered 1,3-diheterocines, 1,3-diazocines and 1,3-oxazocines are the two largest classes, based on the number of publications, mostly due to the studies of the synthesis of these cyclic systems, their pharmacological properties and/or their important industrial a…
DESIGN OF SF3B1 SUBUNIT MODULATORS OF THE SF3B SPLICEOSOME COMPLEX
2022
The subject of this dissertation is the search for new therapeutic strategies for pancreatic cancer and aims to implement a Drug Discovery process for the rational design and synthesis of molecules active in the modulation of pathways related to the regulation of pre-mRNA splicing process. This research project is the result of a joint PhD between the University of Palermo, Italy, and the Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. It integrates complementary skills in pharmaceutical chemistry and translational cancer research with a special focus on the rational design of new anticancer compounds potentially active on SF3B1 (Splicing Factor 3B …
New Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives Inhibit FAK Phosphorylation and Potentiate the Antiproliferative Effects of Gemcitabine Through Modu…
2020
Background/aim A new class of imidazo[2,1-b][1,3,4]thiadiazole compounds have recently been evaluated as inhibitors of phosphorylation of focal adhesion kinase (FAK) in pancreatic cancer. FAK is overexpressed in mesothelioma and has recently emerged as an interesting target for the treatment of this disease. Materials and methods Ten imidazo[2,1-b][1,3,4]thiadiazole compounds characterized by indole bicycle and a thiophene ring, were evaluated for their cytotoxic activity in two primary cell cultures of peritoneal mesothelioma, MesoII and STO cells. Results Compounds 1a and 1b showed promising antitumor activity with IC50 values in the range of 0.59 to 2.81 μM in both cell lines growing as …
“Open Sesame?”: biomarker status of the human equilibrative nucleoside transporter-1 and molecular mechanisms influencing its expression and activity…
2020
Simple Summary Despite the enormous advance in biomarker discovery, many potential biomarkers of drug activity are unable to satisfy the clinical need due to inadequate sensitivity and specificity. The nucleoside transporter hENT-1 has been studied as a potential biomarker to predict the effect of the widely used anticancer drug gemcitabine in pancreatic cancer. However, several studies showed controversial results regarding the predictive value of hENT-1, prompting new analyses with larger cohorts of patients and standardized methodologies. Improved insights on molecular mechanisms underlying hENT-1 expression and activity should also help in the identification of subsets of patients who a…