429 results found
Mizandari M, Azrumelashvili T, Kumar J, et al., 2017, Percutaneous Image-Guided Pancreatic Duct Drainage: Technique, Results and Expected Benefits., Cardiovasc Intervent Radiol
PURPOSE: The aim of this study is to provide a technical detail and feasibility of percutaneous image-guided pancreatic duct (PD) drainage and to discuss its subtleties in a series of patients with obstructed PD. MATERIALS AND METHODS: Thirty patients presenting with PD obstruction from pancreatic head tumour or pancreatitis were subjected to percutaneous image-guided PD drainage under a guidance of ultrasound or computed tomography. Following the successful puncture of PD, a locking loop drainage catheter was placed using conventional guidewire techniques under real-time fluoroscopy guidance. RESULTS: The percutaneous drainage of obstructed PD was completed in 29 (96.7%) patients as an independent therapeutic intent or as a bridge to further percutaneous procedures. Clinical improvement following drainage was documented by the gradual reduction in clinical symptoms, including pain, nausea and fever and improved blood test results, showing the significant decrease of amylase concentration. The amount of pancreatic fluid drained post procedure was between 300 and 900 mL/day. No major procedure-related complications were observed. Subsequently, 14 of 29 patients underwent further procedures, including endoluminal placement of metal stent with or without radiofrequency ablation, balloon assisted percutaneous descending litholapaxy (BAPDL), endoluminal biopsy and balloon dilatation using the same drainage tract. CONCLUSION: The percutaneous PD drainage appears to be a safe and effective procedure. It should be considered in patients with obstructed PD secondary to malignancy, pancreatitis etc., where endoscopic retrograde cannulation has been failed or impracticable. The procedure can also be contemplated either as an independent treatment option or as an initial step for the subsequent therapeutic endoluminal procedures.
Reccia I, Kumar J, Akladios C, et al., 2017, Non-alcoholic fatty liver disease: A sign of systemic disease, METABOLISM-CLINICAL AND EXPERIMENTAL, Vol: 72, Pages: 94-108, ISSN: 0026-0495
Reccia I, Kumar J, Kusano T, et al., 2017, A systematic review on radiofrequency assisted laparoscopic liver resection: Challenges and window to excel, SURGICAL ONCOLOGY-OXFORD, Vol: 26, Pages: 296-304, ISSN: 0960-7404
Vavra P, Roman J, Zonca P, et al., 2017, Recent Development of Augmented Reality in Surgery: A Review, JOURNAL OF HEALTHCARE ENGINEERING, ISSN: 2040-2295
Voutila J, Reebye V, Roberts T, et al., 2017, Mechanism and In Vivo Activity of a Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Disease, 20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Publisher: CELL PRESS, Pages: 34-34, ISSN: 1525-0016
Voutila J, Reebye V, Roberts TC, et al., 2017, Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer., Mol Ther
Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells. A nuclear run-on assay confirmed that this upregulation is a transcriptionally driven process. Mechanistic experiments demonstrate that Argonaute-2 (Ago2) is required for saRNA activity, with the guide strand of the saRNA shown to be associated with Ago2 and localized at the CEBPA genomic locus using RNA chromatin immunoprecipitation (ChIP) assays. The data support a sequence-specific on-target saRNA activity that leads to enhanced CEBPA mRNA transcription. Chemical modifications were introduced in the saRNA duplex to prevent activation of the innate immunity. This modified saRNA retains activation of CEBPA mRNA and downstream targets and inhibits growth of liver cancer cell lines in vitro. This novel drug has been encapsulated in a liposomal formulation for liver delivery, is currently in a phase I clinical trial for patients with liver cancer, and represents the first human study of an saRNA therapeutic.
Wong JKL, Mohseni R, Hamidieh AA, et al., 2017, Will Nanotechnology Bring New Hope for Gene Delivery?, TRENDS IN BIOTECHNOLOGY, Vol: 35, Pages: 434-451, ISSN: 0167-7799
Wong JKL, Mohseni R, Hamidieh AA, et al., 2017, Limitations in Clinical Translation of Nanoparticle-Based Gene Therapy., Trends Biotechnol
Organic nanoparticle-based (ONP) gene therapy is a potential strategy to cure human cancer. However, there are still many practical barriers before the promising results from in vitro and preclinical studies can be translated to clinical success. We discuss the reasons behind the hesitant uptake by the clinic.
Yoon S, Armstrong B, Habib N, et al., 2017, RNA Aptamers Selected Through Blind-SELEX Inhibit Pancreatic Cancer Cell Metastasis and Invasion by Regulating Epithelial Mesenchymal Transition(EMT), 20th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Publisher: CELL PRESS, Pages: 43-43, ISSN: 1525-0016
Yoon S, Armstrong B, Habib N, et al., 2017, Blind SELEX Approach Identifies RNA Aptamers That Regulate EMT and Inhibit Metastasis, MOLECULAR CANCER RESEARCH, Vol: 15, Pages: 811-820, ISSN: 1541-7786
Yoon S, Huang K-W, Reebye V, et al., 2017, Aptamer-Drug Conjugates of Active Metabolites of Nucleoside Analogs and Cytotoxic Agents Inhibit Pancreatic Tumor Cell Growth, MOLECULAR THERAPY-NUCLEIC ACIDS, Vol: 6, Pages: 80-88, ISSN: 2162-2531
The prognosis for hepatocellular carcinoma (HCC) remains poor and has not improved in over two decades. Most patients with advanced HCC who are not eligible for surgery have limited treatment options due to poor liver function or large, unresectable tumors. Although sorafenib is the standard-of-care treatment for these patients, only a small number respond. For the remaining, the outlook remains bleak. A better approach to target "undruggable" molecular pathways that reverse HCC is therefore urgently needed. Small activating RNAs (saRNAs) may provide a novel strategy to activate expression of genes that become dysregulated in chronic disease. The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα), a critical regulator of hepatocyte function, is suppressed in many advanced liver diseases. By using an saRNA to activate C/EBPα, we can exploit the cell's own transcription machinery to enhance gene expression without relying on exogenous vectors that have been the backbone of gene therapy. saRNAs do not integrate into the host genome and can be modified to avoid immune stimulation. In preclinical models of liver disease, treatment with C/EBPα saRNA has shown reduction in tumor volume and improvement in serum markers of essential liver function such as albumin, bilirubin, aspartate aminotransferase (AST), and alanine transaminase (ALT). This saRNA that activates C/EBPα for advanced HCC is the first saRNA therapy to have entered a human clinical trial. The hope is that this new tool will help break the dismal 20-year trend and provide a more positive prognosis for patients with severe liver disease.
Blakey D, Reebye V, Voutila J, et al., 2016, Small activating RNA to CEBPA as a novel therapeutic approach to treat patients with liver cancer, 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: S149-S149, ISSN: 0959-8049
Clift A, Pai M, Habib N, et al., 2016, Endoscopic Ultrasound-Guided Radiofrequency Ablation for Pancreatic Neoplasms, 13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 91-91, ISSN: 0028-3835
Frampton AE, Krell J, Prado MM, et al., 2016, Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies, ONCOTARGET, Vol: 7, Pages: 28556-28569, ISSN: 1949-2553
Giglio MC, Giakoustidis A, Draz A, et al., 2016, Oncological Outcomes of Major Liver Resection Following Portal Vein Embolization: A Systematic Review and Meta-analysis, ANNALS OF SURGICAL ONCOLOGY, Vol: 23, Pages: 3709-3717, ISSN: 1068-9265
Giglio MC, Spalding DRC, Giakoustidis A, et al., 2016, Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection, BRITISH JOURNAL OF SURGERY, Vol: 103, Pages: 328-336, ISSN: 0007-1323
Huan H, Wen X, Chen X, et al., 2016, C/EBP alpha Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma through Inhibiting EGFR/beta-Catenin Signaling Mediated EMT, PLOS ONE, Vol: 11, ISSN: 1932-6203
Reebye V, Huang K-W, Czysz K, et al., 2016, Hepatocellular Nuclear Factor 4 alpha (HNF-4 alpha) activation by saRNA rescues dyslipidemia and promotes favorable metabolic profile in a high fat diet (HFD) fed rat model., 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD), Publisher: WILEY, Pages: 794A-794A, ISSN: 0270-9139
Reebye V, Voutila J, Blakey D, et al., 2016, The clinical candidate MTL-CEBPA leads to significant reduction in ascites and improvement in overall survival in a CCl4-induced acute liver failure model., 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD), Publisher: WILEY, Pages: 1045A-1046A, ISSN: 0270-9139
Yoon S, Huang K-W, Habib N, et al., 2016, Potent Anti-Tumor Effects of ApDCs (Aptamer Drug Conjugates) for Targeted Therapeutics in Pancreatic Cancer, 19th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Publisher: NATURE PUBLISHING GROUP, Pages: S265-S265, ISSN: 1525-0016
Yoon S, Huang K-W, Reebye V, et al., 2016, Targeted Delivery of C/EBP alpha -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo, MOLECULAR THERAPY, Vol: 24, Pages: 1106-1116, ISSN: 1525-0016
Blagden SP, Rizzuto I, Stavraka C, et al., 2015, A first in human Phase I/II study of NUC-1031 in patients with advanced gynecological cancers., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) / Clinical Science Symposium on Predicting and Improving Adverse Outcomes in Older Adults with Cancer, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Blagden SP, Rizzuto I, Stavraka C, et al., 2015, Final results of ProGem1, the first in-human phase I/II study of NUC-1031 in patients with solid malignancies., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) / Clinical Science Symposium on Predicting and Improving Adverse Outcomes in Older Adults with Cancer, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Cheng Z, Lv Y, Pang S, et al., 2015, Kallistatin, a new and reliable biomarker for the diagnosis of liver cirrhosis, ACTA PHARMACEUTICA SINICA B, Vol: 5, Pages: 194-200, ISSN: 2211-3835
Frampton AE, Castellano L, Colombo T, et al., 2015, Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression, LANCET, Vol: 385, Pages: 37-37, ISSN: 0140-6736
Frampton AE, Krell J, Jamieson NB, et al., 2015, microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis, EUROPEAN JOURNAL OF CANCER, Vol: 51, Pages: 1389-1404, ISSN: 0959-8049
Gall TMH, Sodergren MH, Frampton AE, et al., 2015, Radio-frequency-assisted Liver Partition With Portal Vein Ligation (RALPP) for Liver Regeneration, ANNALS OF SURGERY, Vol: 261, Pages: E45-E46, ISSN: 0003-4932
Kallis Y, Phillips N, Steel A, et al., 2015, Analysis of Endoscopic Radiofrequency Ablation of Biliary Malignant Strictures in Pancreatic Cancer Suggests Potential Survival Benefit, DIGESTIVE DISEASES AND SCIENCES, Vol: 60, Pages: 3449-3455, ISSN: 0163-2116
Pai M, Habib N, Senturk H, et al., 2015, Endoscopic ultrasound guided radiofrequency ablation, for pancreatic cystic neoplasms and neuroendocrine tumors, WORLD JOURNAL OF GASTROINTESTINAL SURGERY, Vol: 7, Pages: 52-59, ISSN: 1948-9366
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