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Pierre-Antoine Bissey, Jacqueline H Law, Jeff P Bruce, Wei Shi, Aline Renoult, Melvin L K Chua, Kenneth W Yip, Fei-Fei Liu
Despite the improvement in locoregional control of nasopharyngeal carcinoma (NPC), distant metastasis (DM), and chemoresistance persist as major causes of mortality. This study identified a novel role for miR-449b, an overexpressed gene in a validated four-miRNA signature for NPC DM, leading to chemoresistance via the direct targeting of transforming growth factor beta-induced (TGFBI). In vitro shRNA-mediated downregulation of TGFBI induced phosphorylation of PTEN and AKT, increasing cisplatin resistance. Conversely, the overexpression of TGFBI sensitized the NPC cells to cisplatin...
May 22, 2018: Oncogenesis
Qi-Bing Wu, Xin Sheng, Ning Zhang, Ming-Wei Yang, Fan Wang
Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1...
April 2018: Molecular and Clinical Oncology
Anne Haahr Mellergaard Eriksen, Flemming Brandt Sørensen, Rikke Fredslund Andersen, Anders Jakobsen, Torben Frøstrup Hansen
Preoperative chemoradiotherapy (CRT) followed by mesorectal excision is the standard treatment for patients with locally advanced rectal cancer (LARC). The balance between treatment efficacy and toxicity is a major issue in the clinical management of these patients. There is a requirement for the identification of predictive molecular biomarkers for the response of patients to CRT. The present study aimed to analyze the association between microRNA (miRNA/miR) expression and treatment efficacy in patients with LARC who were treated with preoperative CRT...
July 2017: Oncology Letters
So-Hee Ahn, Jung-Hyuck Ahn, Dong-Ryeol Ryu, Jisoo Lee, Min-Sun Cho, Youn-Hee Choi
PURPOSE: Glioblastoma multiforme (GBM) is the most common adult primary intracranial tumor. The remarkable features of GBM include central necrosis. MicroRNAs (miRNAs) have been considered as diagnostic/prognostic biomarkers for many cancers, including glioblastoma. However, the effect of necrosis on the miRNA expression profile and predicted miRNA-mRNA regulatory information remain unclear. The purpose of this study is to examine the effect of necrotic cells on the modulation of miRNA and mRNA expression profiles and miRNA-mRNA network in CRT-MG cells...
April 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Rocío Retamales-Ortega, Lorena Oróstica, Carolina Vera, Paula Cuevas, Andrea Hernández, Iván Hurtado, Margarita Vega, Carmen Romero
Ovarian cancer is the eighth most common cancer in women worldwide, and epithelial ovarian cancer (EOC) represents 90% of cases. Nerve growth factor (NGF) and its high affinity receptor tyrosine kinase A receptor (TRKA) have been associated with the development of several types of cancer, including EOC; both NGF and TRKA levels are elevated in this pathology. EOC presents high angiogenesis and several molecules have been reported to induce this process. NGF increases angiogenesis through its TRKA receptor on endothelial cells, and by indirectly inducing vascular endothelial growth factor expression...
February 26, 2017: International Journal of Molecular Sciences
Jing Yu, Ning Li, Xin Wang, Hua Ren, Weihu Wang, Shulian Wang, Yongwen Song, Yueping Liu, Yexiong Li, Xuantong Zhou, Aiping Luo, Zhihua Liu, Jing Jin
Preoperative chemoradiotherapy (pre-CRT) has been represented as the standard treatment for locally advanced rectal cancer (LARC), but large variations of tumor radiation response to CRT have been reported in the clinic. To explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC, we analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment. MiR-345 was significantly elevated in the CRT-resistant group. Therefore, miR-345 was selected as a candidate for further analysis...
September 27, 2016: Oncotarget
Azadeh Azizian, Jens Gruber, B Michael Ghadimi, Jochen Gaedcke
In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits...
May 15, 2016: World Journal of Gastrointestinal Oncology
Jing Wen, Kongjia Luo, Hui Liu, Shiliang Liu, Guangrong Lin, Yi Hu, Xu Zhang, Geng Wang, Yuping Chen, Zhijian Chen, Yi Li, Ting Lin, Xiuying Xie, Mengzhong Liu, Huiyun Wang, Hong Yang, Jianhua Fu
OBJECTIVE: To identify miRNA markers useful for esophageal squamous cell carcinoma (ESCC) neoadjuvant chemoradiotherapy (neo-CRT) response prediction. SUMMARY: Neo-CRT followed by surgery improves ESCC patients' survival compared with surgery alone. However, CRT outcomes are heterogeneous, and no current methods can predict CRT responses. METHODS: Differentially expressed miRNAs between ESCC pathological responders and nonresponders after neo-CRT were identified by miRNA profiling and verified by real-time quantitative polymerase chain reaction (qPCR) of 27 ESCCs in the training set...
May 2016: Annals of Surgery
Jianhua Xu, Qin Ai, Hanhai Cao, Quan Liu
BACKGROUND MiR-185-3p and miR-324-3p are 2 miRNAs that regulate nasopharyngeal carcinoma (NPC) radioresistance. This study tried to assess the clinical values of low miR-185-3p and low miR-324-3p expression in predicting response to radiotherapy (RT) and prognosis of NPC and to explore their new downstream targets. MATERIAL AND METHODS We recruited 80 patients with primary NPC. MiR-185-3p and miR-324-3p expression in the tumor tissues before and after RT or chemoradiotherapy (CRT) were determined. Overall survival and recurrence-free survival curves were estimated to assess the prognostic values of these 2 miRNAs...
2015: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Toshihiro Nakao, Takashi Iwata, Masanori Hotchi, Kozo Yoshikawa, Jun Higashijima, Masaaki Nishi, Chie Takasu, Shohei Eto, Hiroki Teraoku, Mitsuo Shimada
Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29)...
October 2015: Oncology Reports
Becky A S Bibby, John V Reynolds, Stephen G Maher
Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment...
2015: PloS One
Yonathan F Melman, Ravi Shah, Kirsty Danielson, Junjie Xiao, Bridget Simonson, Andreas Barth, Khalid Chakir, Gregory D Lewis, Zachary Lavender, Quynh A Truong, Andre Kleber, Ranendra Das, Anthony Rosenzweig, Yaoyu Wang, David Kass, Jagmeet P Singh, Saumya Das
BACKGROUND: Biomarkers that predict response to cardiac resynchronization therapy (CRT) in heart failure patients with dyssynchrony (HFDYS) would be clinically important. Circulating extracellular microRNAs (miRNAs) have emerged as novel biomarkers that may also play important functional roles, but their relevance as markers for CRT response has not been examined. METHODS AND RESULTS: Comprehensive miRNA polymerase chain reaction arrays were used to assess baseline levels of 766 plasma miRNAs in patients undergoing clinically indicated CRT in an initial discovery set (n=12) with and without subsequent echocardiographic improvement at 6 months after CRT...
June 23, 2015: Circulation
Azadeh Azizian, Frank Kramer, Peter Jo, Hendrik A Wolff, Tim Beißbarth, Robert Skarupke, Markus Bernhardt, Marian Grade, B Michael Ghadimi, Jochen Gaedcke
BACKGROUND: In locally advanced rectal cancer, therapeutic success of preoperative chemoradiotherapy (CRT) ranges from resistance to complete regression. For those patients that respond well to CRT, local resection (LR) procedures are currently under investigation to minimize surgical morbidity and to improve functional outcome. To maintain the oncologic benefit appropriate staging procedures are essential. However, current clinical assessment and imaging techniques need further improvement...
September 2015: World Journal of Surgery
Ting Xu, Zhongxing Liao, Michael S O'Reilly, Lawrence B Levy, James W Welsh, Li-E Wang, Steven H Lin, Ritsuko Komaki, Zhensheng Liu, Qingyi Wei, Daniel R Gomez
BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological processes. We sought to investigate whether three serum miRNAs related to immunity or inflammation were associated with esophagitis induced by chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: We measured serum miR-155, miR-221 and miR-21, before and during week 1-2 of CRT for 101 NSCLC patients by real-time PCR...
December 2014: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Masanori Hotchi, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Hirohiko Sato, Shinya Morimoto, Kozo Yoshikawa, Jun Higashijima, Tomohiko Miyatani
Although global microRNA (miRNA) expression patterns of several embryologic, physiological and oncogenic processes have been thoroughly studied, no studies are available on the role of miRNAs in pre-operative chemoradiotherapy (CRT) in rectal cancer. This study aimed to delineate the expression pattern of miRNAs for the prediction of response to CRT in rectal cancer. Rectal cancer patients (n=43), who underwent pre-operative CRT (40 Gy radiotherapy combined with S-1), were studied. RNA harvested from rectal cancer biopsy specimens prior to pre-operative CRT was hybridized to miRNA microarrays (821 genes)...
January 2013: Molecular and Clinical Oncology
Carrie Luu, Eileen L Heinrich, Marjun Duldulao, Amanda K Arrington, Marwan Fakih, Julio Garcia-Aguilar, Joseph Kim
Recent reports have indicated that KRAS and TP53 mutations predict response to therapy in colorectal cancer. However, little is known about the relationship between these two common genetic alterations. Micro-RNAs (miRNAs), a class of noncoding RNA implicated in cellular processes, have been increasingly linked to KRAS and TP53. We hypothesized that lethal-7a (let-7a) miRNA regulates KRAS through TP53. To investigate the relationship between KRAS, TP53, and let-7a, we used HCT116 KRAS(mut) human colorectal cancer cells with four different genotypic modifications in TP53 (TP53(-/-), TP53(+/-), TP53(mut/+), and TP53(mut/-) )...
2013: PloS One
Junius Salendo, Melanie Spitzner, Frank Kramer, Xin Zhang, Peter Jo, Hendrik A Wolff, Julia Kitz, Silke Kaulfuß, Tim Beißbarth, Matthias Dobbelstein, Michael Ghadimi, Marian Grade, Jochen Gaedcke
BACKGROUND AND PURPOSE: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. MATERIAL AND METHODS: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established...
September 2013: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Raffaele Marfella, Clara Di Filippo, Nicoletta Potenza, Celestino Sardu, Maria Rosaria Rizzo, Mario Siniscalchi, Emilio Musacchio, Michelangela Barbieri, Ciro Mauro, Nicola Mosca, Francesco Solimene, Maria Teresa Mottola, Aniello Russo, Francesco Rossi, Giuseppe Paolisso, Michele D'Amico
AIMS: MicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of the failing heart through their ability to regulate negatively the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodelling. We studied whether LV reverse remodelling after CRT was associated with changes of circulating miRNAs in patients with heart failure (HF) and dyssynchrony. METHODS AND RESULTS: A prospective, non-randomized self-control trial was performed in 81 patients with HF eligible for CRT...
November 2013: European Journal of Heart Failure
Elrasheid A H Kheirelseid, Nicola Miller, Kah Hoong Chang, Catherine Curran, Emer Hennessey, Margaret Sheehan, John Newell, Christophe Lemetre, Graham Balls, Michael J Kerin
INTRODUCTION: Neoadjuvant chemoradiation therapy has been shown to improve the outcome in patients with rectal cancer and is generally accepted as standard care; however, only selected patients would benefit from this treatment. We aimed to identify predictors of response to neoadjuvant chemoradiation therapy in colorectal cancer using formalin-fixed paraffin-embedded (FFPE) tissues as source of genetic materials and microarray analysis as investigation tool. METHODS: After optimization of RNA extraction methods from FFPE, microarray analysis was carried out on total RNA extracted from 12 pre-treatment FFPE rectal tissues using Megaplex pool A...
February 2013: International Journal of Colorectal Disease
Niamh Lynam-Lennon, John V Reynolds, Laure Marignol, Orla M Sheils, Graham P Pidgeon, Stephen G Maher
Chemoradiation therapy (CRT) prior to surgery is increasingly the standard of care for locally advanced oesophageal cancer. Radiation therapy is important for local tumour control; however, tumour resistance to radiation is a substantial clinical problem. The mechanism(s) of radioresistance are still poorly understood, however, mounting evidence supports a role for microRNA (miRNA) in modulating key cellular pathways mediating response to radiation. Global miRNA profiling of an established isogenic model of radioresistance in oesophageal adenocarcinoma demonstrated a significant downregulation of miR-31 in radioresistant cells, both basally and in response to radiation...
December 2012: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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