scholarly journals L-Carnitine–Mediated Tumor Cell Protection and Poor Patient Survival Associated with OCTN2 Overexpression in Glioblastoma Multiforme

2019 ◽  
Vol 25 (9) ◽  
pp. 2874-2886 ◽  
Author(s):  
Matthias A. Fink ◽  
Heiko Paland ◽  
Susann Herzog ◽  
Markus Grube ◽  
Silke Vogelgesang ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Cell ◽  
Patient Survival ◽  
Cell Protection ◽  
Poor Patient ◽  
Poor Patient Survival

scholarly journals PD-1 expression on uveal melanoma induces tumor proliferation and predicts poor patient survival

2020 ◽  
Vol 35 (3) ◽  
pp. 50-58
Author(s):  
Zhongming Jiang ◽  
Yuexiang Yan ◽  
Juan Dong ◽  
Lingling Duan
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Uveal Melanoma ◽  
Patient Survival ◽  
Malignant Tumors ◽  
Tumor Diameter ◽  
Tumor Cell Proliferation ◽  
Poor Patient ◽  
Poor Patient Survival

Introduction: Uveal melanoma is one of the most common primary intraocular malignant tumors with poor prognosis and limited treatments. Programmed cell death receptor-1 (PD-1) blockade represents the primary treatment strategy of immune checkpoint inhibition; however, there is a lack of studies on whether PD-1 expression in primary (ocular) uveal melanoma affects tumor progression. Methods: PD-1 expression in 82 cases of primary (ocular) uveal melanoma was detected by immunohistochemistry. The clinical significance of PD-1 expression was evaluated using univariate and multivariate analysis. PD-1 overexpression and knockdown studies were conducted in C918 and Mum-2B cell lines to analyze the effect of PD-1 expression on tumor cell proliferation and intracellular cell signaling transduction. real-time qPCR (RT-qPCR) and western blot analysis were performed to investigate the gene expression level. CCK8 assays were performed to examine the cell proliferation ability. Results: High expression of primary (ocular) intratumor PD-1 was associated with poor patient survival. Moreover, PD-1 expression was correlated with the largest tumor diameter. PD-1 expression and optic nerve invasion were independent prognostic risk factors. PD-1 overexpression in uveal melanoma cell lines promoted tumor cell proliferation, while knockdown of PD-1 inhibited cell proliferation capacity. Conclusion: Our study established the role of PD-1 in the progression of uveal melanoma and provided a new potential treatment selection for uveal melanoma.

scholarly journals Tumor microRNA-126 controls cell viability and associates with poor survival in patients with esophageal adenocarcinoma

2019 ◽  
Vol 244 (14) ◽  
pp. 1210-1219
Author(s):  
ELA Toxopeus ◽  
N Lynam-Lennon ◽  
K Biermann ◽  
G Dickens ◽  
PE de Ruiter ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cell Viability ◽  
Tumor Cells ◽  
Esophageal Adenocarcinoma ◽  
Patient Survival ◽  
Poor Survival ◽  
Poor Patient ◽  
Pre Treatment ◽  
Poor Patient Survival

Esophageal adenocarcinoma displays a poor prognosis and current treatments are often not curative. Pathological TNM-stage is a prognostic parameter, but a better understanding of the pathophysiology of esophageal adenocarcinoma is needed to better predict survival. Recent work in other malignancies indicated an important role for the regulator microRNA-126 (miR-126) in tumors. The aim of this study was to investigate the function of miR-126 in esophageal adenocarcinoma and to correlate expression of miR-126 with tumor cell behavior and patient survival. Functional assays were performed in esophageal adenocarcinoma cell lines (OE33) in vitro by overexpressing or antagonizing miR-126 and assessing cellular processes linked to the hallmarks of cancer. In vivo pre-treatment biopsies of 58 patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiotherapy and surgery were analyzed for miR-126 expression in tumor cells by qRT-PCR and patient survival was analyzed by Kaplan–Meier and Cox regression. In OE33 cancer cells, stable overexpression of miR-126 modest though significantly altered expression of genes related to cell death (MEK1) and DNA repair (POLB and TERF1) was observed. Also the secretion of the angiogenic and pro-inflammatory factors, VEGF, IL-1β, and IL-6 were regulated by miR-126 ( P < 0.029). Importantly, miR-126 was found to be a regulator of cell viability in OE33 cells. Overexpressing ( P = 0.043) and antagonizing ( P = 0.035) miR-126 showed reciprocal effects on tumor cell viability and significantly regulated expression of pro- and anti-apoptotic genes, TP53, and GATA6 ( P < 0.031). In patients, high levels of miR-126 expression in pre-treatment tumors were significantly associated with poor survival ( P = 0.031). In multivariable analysis, high miR-126 ( P = 0.038) together with ypN-stage ( P = 0.048) were shown to be independent risk factors for poor survival. In conclusion, high expression of miR-126 in esophageal adenocarcinoma prevents tumor-cell death and is associated with poor patient survival. This study warrants further analysis of miR-126 as biomarker or potential therapeutic target for OAC. Impact statement Esophageal adenocarcinoma is a common form of cancer of the esophagus. It has an increasing health impact as it is associated with very poor patient survival. A better understanding of the pathophysiology of this cancer is needed to identify better treatment strategies and to provide a better prognosis for these patients. MicroRNAs have emerged as important molecular regulators of cancer cell viability and proliferation. The aim of our study was to investigate the role of one very well established microRNA, miR-126, in esophageal adenocarcinoma. Our research shows clear experimental evidence that miR-126 controls cell viability of esophageal adenocarcinoma cells. High (over)expression of miR-126 increased the viability of these cells. Our preclinical data were shown to be clinically relevant for this field of oncology. In an independent validation study of esophageal adenocarcinoma biopsies, we confirmed that high miR-126 expression in tumor cells was an independent risk factor for poor patient survival.

scholarly journals Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Fei Sun ◽  
Wen Ding ◽  
Jie-Hua He ◽  
Xiao-Jing Wang ◽  
Ze-Biao Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Patient Survival ◽  
Poor Patient ◽  
Poor Patient Survival

scholarly journals Elevated expression of SATB1 is involved in pancreatic tumorigenesis and is associated with poor patient survival

2017 ◽  
Vol 16 (6) ◽  
pp. 8842-8848 ◽  
Author(s):  
Lei Guo ◽  
Jianjiang Zheng ◽  
Tao Yu ◽  
Yuequan Liu ◽  
Lukun Duo
Keyword(s):  
Patient Survival ◽  
Poor Patient ◽  
Elevated Expression ◽  
Poor Patient Survival

Lamins as cancer biomarkers

2010 ◽  
Vol 38 (1) ◽  
pp. 297-300 ◽  
Author(s):  
Clare R. Foster ◽  
Stefan A. Przyborski ◽  
Robert G. Wilson ◽  
Christopher J. Hutchison
Keyword(s):  
Cancer Cells ◽  
Patient Survival ◽  
Cancer Biomarkers ◽  
Tumour Cells ◽  
Diagnostic Biomarkers ◽  
Cancer Subtypes ◽  
Multifunctional Proteins ◽  
Poor Patient ◽  
Poor Patient Survival

Lamins are multifunctional proteins that are often aberrantly expressed or localized in tumours. Here, we endeavour to assess their uses as cancer biomarkers: to diagnose tumours, analyse cancer characteristics and predict patient survival. It appears that the nature of lamin function in cancer is very complex. Lamin expression can be variable between and even within cancer subtypes, which limits their uses as diagnostic biomarkers. Expression of A-type lamins is a marker of differentiated tumour cells and has been shown to be a marker of good or poor patient survival depending on tumour subtype. Further research into the functions of lamins in cancer cells and the mechanisms that determine its patterns of expression may provide more potential uses of lamins as cancer biomarkers.

scholarly journals The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Yang Jiang ◽  
Jinpeng Zhou ◽  
Junshuang Zhao ◽  
Haiying Zhang ◽  
Long Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Development ◽  
Feedback Loop ◽  
Rna Binding ◽  
Patient Survival ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Glioma Stem Cells ◽  
Poor Patient ◽  
Poor Patient Survival

Abstract Background Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma. Methods Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342–3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules. Results We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342–3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival. Conclusions Our study identified a novel feedback loop among U2AF2, cARF1, miR-342–3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

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