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Your search keyword '"hERG1 Channels"' showing total 2 results
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2 results on '"hERG1 Channels"'

1. hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy

Author

Muratori L, Petroni G, Antonuzzo L, Boni L, Iorio J, Lastraioli E, Bartoli G, Messerini L, Di Costanzo F, and Arcangeli A

Subjects
potassium channels, hERG1 channels, Glut-1 glucose transporter, colorectal cancer, biomolecular markers., Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Leonardo Muratori,1,* Giulia Petroni,1,* Lorenzo Antonuzzo,2,3 Luca Boni,4 Jessica Iorio,1,3 Elena Lastraioli,1 Gianluca Bartoli,1 Luca Messerini,1 Francesco Di Costanzo,2 Annarosa Arcangeli1 1Department of Experimental and Clinical Medicine, University of Florence, 2Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, 3Department of Medical Biotechnologies, University of Siena, Siena, 4Clinical Trials Coordinating Center, Istituto Toscano Tumori, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy *These authors contributed equally to this work Background: The identification of early-stage colorectal cancer (CRC) with high risk of progression is one major clinical challenge, mainly due to lack of validated biomarkers. The aims of the present study were to analyze the prognostic impact of three molecular markers belonging to the ion channels and transporters family: the ether-à-go-go-related gene 1 (hERG1) and the calcium-activated KCa3.1 potassium channels, as well as the glucose transporter 1 (Glut-1); and to define the impact of adjuvant chemotherapy in conjunction with the abovementioned biomarkers, in a cohort of radically resected stage I–III CRC patients. Patients and methods: The expressions of hERG1, KCa3.1, and Glut-1 were tested by immunohistochemistry on 162 surgical samples of nonmetastatic, stage I–III CRC patients. The median follow-up was 32 months. The association between biological markers, clinicopathological features, and survival outcomes was investigated by evaluating both disease-free survival and overall survival. Results: Although no prognostic valence emerged for KCa3.1, evidence of a negative impact of hERG1 expression on survival outcomes was provided. On the contrary, Glut-1 expression had a positive impact. According to the results of the multivariate analysis, patients were stratified in four risk groups, based on TNM stage and hERG1/Glut-1 expression. After adjusting for adjuvant therapy, stage I and II, Glut-1-negative, and hERG1-positive patients showed the worst survival experience. Conclusion: This study strongly indicates that the combination of hERG1 positivity and Glut-1 negativity behaves as a prognostic biomarker in radically resected CRC patients. This combination identifies a group of stage I and II CRC patients with a bad prognosis, even worse than that of stage III patients, regardless of adjuvant therapy accomplishment. Keywords: potassium channels, glucose transporter, biomolecular markers, ion channels, prognostic markers

Published
2016

2. hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathological correlations and therapeutical implications

Author

Olivia, Crociani, Elena, Lastraioli, Luca, Boni, Serena, Pillozzi, Maria Raffaella, Romoli, Massimo, D'Amico, Matteo, Stefanini, Silvia, Crescioli, Alessio, Masi, Antonio, Taddei, Lapo, Bencini, Marco, Bernini, Marco, Farsi, Stefania, Beghelli, Aldo, Scarpa, Luca, Messerini, Anna, Tomezzoli, Carla, Vindigni, Paolo, Morgagni, Luca, Saragoni, Elisa, Giommoni, Silvia, Gasperoni, Francesco, Di Costanzo, Franco, Roviello, Giovanni, De Manzoni, Paolo, Bechi, and Annarosa, Arcangeli

Subjects
hERG1 Channels, VEGF-A Secretion, GASTRIC CANCER, Vascular Endothelial Growth Factor A, ERG1 Potassium Channel, Pathology, medicine.medical_specialty, Cancer Research, Nude, Mice, Nude, Enzyme-Linked Immunosorbent Assay, Biology, Adenocarcinoma, bevacizumab, Real-Time Polymerase Chain Reaction, Transfection, Cell Line, 1 [2 (6 methyl 2 pyridyl)ethyl] 4 (4 methylsulfonylaminobenzoyl)piperidine, Mice, In vivo, Stomach Neoplasms, Cell Line, Tumor, medicine, Animals, Humans, Secretion, Grading (tumors), Ether-A-Go-Go Potassium Channels, Heterografts, Immunohistochemistry, Reverse Transcriptase Polymerase Chain Reaction, Oncology, Medicine (all), Tumor, bevacizumab, potassium channel HERG, potassium channel HERG1, unclassified drug, vasculotropin A, medicine.disease, potassium channel HERG1, potassium channel HERG, unclassified drug, Vascular endothelial growth factor A, Real-time polymerase chain reaction, vasculotropin A, Cancer cell, Cancer research
Abstract

Purpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. Results: hERG1 was positive in 69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1–G2 grading, I and II tumor—node—metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. Clin Cancer Res; 20(6); 1502–12. ©2014 AACR.

Published
2014

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