Imperial College London

ProfessorNagyHabib

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Hepatobiliary Surgery
 
 
 
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Contact

 

+44 (0)20 3313 8574nagy.habib

 
 
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Assistant

 

Mrs Benita White +44 (0)20 3313 2261

 
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Location

 

BN1/17 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

436 results found

Frampton AE, Prado MM, López-Jiménez E, Fajardo-Puerta AB, Jawad ZAR, Lawton P, Giovannetti E, Habib NA, Castellano L, Stebbing J, Krell J, Jiao LRet al., 2018, Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden., Oncotarget, Vol: 9, Pages: 19006-19013

Background: Glypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stromal fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able to detect early stages of PDAC. In this study, we investigated the usefulness of crExos GPC1 as a biomarker for PDAC. Methods: Plasma was obtained from patients with benign pancreatic disease (n = 16) and PDAC (n = 27) prior to pancreatectomy, and crExos were isolated by ultra-centrifugation. Protein was extracted from surgical specimens (adjacent normal pancreas, n = 13; and PDAC, n = 17). GPC1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: There was no significant difference in GPC1 levels between normal pancreas and PDAC tissues. This was also true when comparing matched pairs. However, GPC1 levels were enriched in PDAC crExos (n = 11), compared to the source tumors (n = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; P < 0.001). In addition, PDACs with high GPC1 expression tended to have crExos with higher GPC1 levels. Despite these findings, we were unable to distinguish PDAC from benign pancreatic disease using crExos GPC1 levels. Interestingly, we found that in matched pre and post-operative plasma samples there was a significant drop in crExos GPC1 levels after surgical resection for PDAC (n = 11 vs. 11; 97 ± 54 vs. 77.8 ± 32.4 pg/mL; P = 0.0428). Furthermore, we found that patients with high crExos GPC1 levels have significantly larger PDACs (>4 cm; P = 0.012). Conclusions: High GPC1 crExos may be able to determine PDAC tumor size and disease burden. However, further efforts are needed to elucidate its role as a diagnostic and/or prognostic biomarker using larger cohorts of PDAC patients.

JOURNAL ARTICLE

Kumar J, Reccia I, Sodergren MH, Kusano T, Zanellato A, Pai M, Spalding D, Zacharoulis D, Habib Net al., 2018, Radiofrequency assisted pancreaticoduodenectomy for palliative surgical resection of locally advanced pancreatic adenocarcinoma., Oncotarget, Vol: 9, Pages: 15732-15739

Background: Despite careful patient selection and preoperative investigations curative resection rate (R0) in pancreaticoduodenectomy ranges from 15% to 87%. Here we describe a new palliative approach for pancreaticoduodenectomy using a radiofrequency energy device to ablate tumor in situ in patients undergoing R1/R2 resections for locally advanced pancreatic ductal adenocarcinoma where vascular reconstruction was not feasible. Results: There was neither postoperative mortality nor significant morbidity. Each time the ablation lasted less than 15 minutes. Following radiofrequency ablation it was observed that the tumor remnant attached to the vessel had shrunk significantly. In four patients this allowed easier separation and dissection of the ablated tumor from the adherent vessel leading to R1 resection. In the other two patients, the ablated tumor did not separate from vessel due to true tumor invasion and patients had an R2 resection. The ablated remnant part of the tumor was left in situ. Conclusion: Whenever pancreaticoduodenectomy with R0 resection cannot be achieved, this new palliative procedure could be considered in order to facilitate resection and enable maximum destruction in remnant tumors. Method: Six patients with suspected tumor infiltration and where vascular reconstruction was not warranted underwent radiofrequency-assisted pancreaticoduodenectomy for locally advanced pancreatic ductal adenocarcinoma. Radiofrequency was applied across the tumor vertically 5-10 mm from the edge of the mesenteric and portal veins. Following ablation, the duodenum and the head of pancreas were removed after knife excision along the ablated line. The remaining ablated tissue was left in situ attached to the vessel.

JOURNAL ARTICLE

Mizandari M, Kumar J, Pai M, Chikovani T, Azrumelashvili T, Reccia I, Habib Net al., 2018, Interventional radiofrequency ablation: A promising therapeutic modality in the management of malignant biliary and pancreatic duct obstruction, JOURNAL OF CANCER, Vol: 9, Pages: 629-637, ISSN: 1837-9664

JOURNAL ARTICLE

Reccia I, Sodergren MH, Jayant K, Kurz E, Carneiro A, Spalding D, Pai M, Jiao L, Habib Net al., 2018, The journey of radiofrequency-assisted liver resection., Surg Oncol

JOURNAL ARTICLE

Reebye V, Huang K-W, Lin V, Jarvis S, Cutilas P, Dorman S, Ciriello S, Andrikakou P, Voutila J, Saetrom P, Mintz PJ, Reccia I, Rossi JJ, Huber H, Habib R, Kostomitsopoulos N, Blakey DC, Habib NAet al., 2018, Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer., Oncogene

Liver diseases are a growing epidemic worldwide. If unresolved, liver fibrosis develops and can lead to cirrhosis and clinical decompensation. Around 5% of cirrhotic liver diseased patients develop hepatocellular carcinoma (HCC), which in its advanced stages has limited therapeutic options and negative survival outcomes. CEPBA is a master regulator of hepatic function where its expression is known to be suppressed in many forms of liver disease including HCC. Injection of MTL-CEBPA, a small activating RNA oligonucleotide therapy (CEBPA-51) formulated in liposomal nanoparticles (NOV340- SMARTICLES) upregulates hepatic CEBPA expression. Here we show how MTL-CEBPA therapy promotes disease reversal in rodent models of cirrhosis, fibrosis, hepatosteatosis, and significantly reduces tumor burden in cirrhotic HCC. Restoration of liver function markers were observed in a carbon-tetrachloride-induced rat model of fibrosis following 2 weeks of MTL-CEBPA therapy. At 14 weeks, animals showed reduction in ascites and enhanced survival rates. MTL-CEBPA reversed changes associated with hepatosteatosis in non-alcoholic methionine and cholic-deficient diet-induced steaotic liver disease. In diethylnitrosamine induced cirrhotic HCC rats, MTL-CEBPA treatment led to a significant reduction in tumor burden. The data included here and the rapid adoption of MTL-CEBPA into a Phase 1 study may lead to new therapeutic oligonucleotides for undruggable diseases.

JOURNAL ARTICLE

Setten RL, Lightfoot HL, Habib NA, Rossi JJet al., 2018, Development of MTL-CEBPA: Small Activating RNA Drug for Hepatocellular Carcinoma., Curr Pharm Biotechnol

BACKGROUND: Oligonucleotide drug development has revolutionised the drug discovery field allowing the notoriously "undruggable" genome to potentially become "druggable". Within this field, 'small' or 'short' activating RNAs (saRNA) are a more recently discovered category of short double stranded RNA with clinical potential. SaRNAs promote endogenous transcription from target loci, a phenomenon widely observed in mammals known as RNA activation (RNAa). The ability to target a particular gene is dependent on the sequence of the saRNA. Hence, the potential clinical application of saRNA is to increase target gene expression in a sequence specific manner. SaRNA based oligonucleotide therapeutics present great promise in expanding the "druggable" genome with particular areas of interest including transcription factor activation and haploinsufficency. Review and Conclusion: In this mini-review, we describe the pre-clinical development of the first saRNA drug to enter the clinic. This saRNA, referred to as MTL-CEBPA, induces transcription of the transcription factor CCAAT/enhancer-binding protein alpha (CEBPα), a tumour suppressor and critical regulator of hepatocyte function. MTL-CEBPA is presently in Phase I clinical trials for hepatocellular carcinoma (HCC). The clinical development of MTL-CEBPA will demonstrate "proof of concept", showing that saRNAs can provide the basis for drugs which enhance targeted gene expression and consequently improve disease outcome in patients.

JOURNAL ARTICLE

Wong JK, Seifalian A, Mohseni R, Hamidieh AA, MacLaren RE, Habib N, Seifalian AMet al., 2018, Emerging In Vitro 3D Tumour Models in Nanoparticle-Based Gene and Drug Therapy, TRENDS IN BIOTECHNOLOGY, Vol: 36, Pages: 477-480, ISSN: 0167-7799

JOURNAL ARTICLE

Mizandari M, Azrumelashvili T, Kumar J, Habib Net al., 2017, Percutaneous Image-Guided Pancreatic Duct Drainage: Technique, Results and Expected Benefits, CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, Vol: 40, Pages: 1911-1920, ISSN: 0174-1551

JOURNAL ARTICLE

Mudan S, Kumar J, Mafalda NC, Kusano T, Reccia I, Zanallato A, Dalgleish A, Habib Net al., 2017, Case report on the role of radiofrequency-assisted spleen-preserving surgery for splenic metastasis in the era of check-point inhibitors, MEDICINE, Vol: 96, ISSN: 0025-7974

JOURNAL ARTICLE

Reccia I, Kumar J, Akladios C, Virdis F, Pai M, Habib N, Spalding Det al., 2017, Non-alcoholic fatty liver disease: A sign of systemic disease, METABOLISM-CLINICAL AND EXPERIMENTAL, Vol: 72, Pages: 94-108, ISSN: 0026-0495

JOURNAL ARTICLE

Reccia I, Kumar J, Kusano T, Zanellato A, Draz A, Spalding D, Habib N, Pai Met 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

JOURNAL ARTICLE

Vavra P, Roman J, Zonca P, Ihnat P, Nemec M, Kumar J, Habib N, El-Gendi Aet al., 2017, Recent Development of Augmented Reality in Surgery: A Review, JOURNAL OF HEALTHCARE ENGINEERING, ISSN: 2040-2295

JOURNAL ARTICLE

Voutila J, Reebye V, Roberts T, Blakey D, Habib R, Mallappa O, Anjaneyulu M, Jayaprakash A, Huber H, Saetrom P, Rossi J, Habib Net 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

CONFERENCE PAPER

Voutila J, Reebye V, Roberts TC, Protopapa P, Andrikakou P, Blakey DC, Habib R, Huber H, Saetrom P, Rossi JJ, Habib NAet al., 2017, Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer, MOLECULAR THERAPY, Vol: 25, Pages: 2705-2714, ISSN: 1525-0016

JOURNAL ARTICLE

Wong JKL, Mohseni R, Hamidieh AA, MacLaren RE, Habib N, Seifalian AMet al., 2017, Will Nanotechnology Bring New Hope for Gene Delivery?, TRENDS IN BIOTECHNOLOGY, Vol: 35, Pages: 434-451, ISSN: 0167-7799

JOURNAL ARTICLE

Wong JKL, Mohseni R, Hamidieh AA, MacLaren RE, Habib N, Seifalian AMet al., 2017, Limitations in Clinical Translation of Nanoparticle-Based Gene Therapy, TRENDS IN BIOTECHNOLOGY, Vol: 35, Pages: 1124-1125, ISSN: 0167-7799

JOURNAL ARTICLE

Yoon S, Armstrong B, Habib N, Rossi Jet 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

CONFERENCE PAPER

Yoon S, Armstrong B, Habib N, Rossi JJet 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

JOURNAL ARTICLE

Yoon S, Huang K-W, Reebye V, Spalding D, Przytycka TM, Wang Y, Swiderski P, Li L, Armstrong B, Reccia I, Zacharoulis D, Dimas K, Kusano T, Shively J, Habib N, Rossi JJet 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

JOURNAL ARTICLE

Zhao X, Voutila J, Ghobrial S, Habib NA, Reebye Vet al., 2017, Treatment of Liver Cancer by C/EBPA saRNA., Adv Exp Med Biol, Vol: 983, Pages: 189-194, ISSN: 0065-2598

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.

JOURNAL ARTICLE

Blakey D, Reebye V, Voutila J, Habib R, Saetrom P, Huber H, Huang KW, Rossi J, Habib Net 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

CONFERENCE PAPER

Clift A, Pai M, Habib N, Senturk H, Laktakia S, Reddy N, Cicinnati V, Kaba I, Beckebaum S, Drymousis P, Kahaleh M, Malczewska A, Zanellato A, Brugge W, Frilling Aet 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

CONFERENCE PAPER

Frampton AE, Krell J, Prado MM, Gall TMH, Abbassi-Ghadi N, Blanco GDV, Funel N, Giovannetti E, Castellano L, Basyouny M, Habib NA, Kaltsidis H, Vlavianos P, Stebbing J, Jiao LRet 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

JOURNAL ARTICLE

Giglio MC, Giakoustidis A, Draz A, Jawad ZAR, Pai M, Habib NA, Tait P, Frampton AE, Jiao LRet 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

JOURNAL ARTICLE

Giglio MC, Spalding DRC, Giakoustidis A, Le Bian AZ, Jiao LR, Habib NA, Pai Met 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

JOURNAL ARTICLE

Huan H, Wen X, Chen X, Wu L, Liu W, Habib NA, Bie P, Xia Fet 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

JOURNAL ARTICLE

Reebye V, Huang K-W, Czysz K, Ciriello S, Dorman S, Reccia I, Lai HS, Peng L, Kostomitsopoulos N, Nicholls J, Habib R, Tomalia D, Saetrom P, Wilkes E, Cutillas P, Rossi J, Habib Net 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

CONFERENCE PAPER

Reebye V, Voutila J, Blakey D, Habib R, Mallappa O, Muragundla A, Jayaprakash A, Huber HE, Saetrom P, Rossi J, Habib Net 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

CONFERENCE PAPER

Yoon S, Huang K-W, Habib N, Rossi Jet 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

CONFERENCE PAPER

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