DrAdamFrampton

Gall TMH, Frampton AE, Krell J, Castellano L, Stebbing J, Jiao LRet al., 2013, Blood-based miRNAs as noninvasive diagnostic and surrogative biomarkers in colorectal cancer, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 13, Pages: 141-145, ISSN: 1473-7159

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• Citations: 12

Gall TMH, Frampton AE, Krell J, Castellano L, Jiao LRet al., 2013, Circulating molecular markers in pancreatic cancer: ready for clinical use?, FUTURE ONCOLOGY, Vol: 9, Pages: 141-144, ISSN: 1479-6694

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• Citations: 3

Krell J, Frampton AE, Stebbing J, 2013, MicroRNAs in the cancer clinic., Front Biosci (Elite Ed), Vol: 5, Pages: 204-213

Over recent years there have been major advances in our understanding of tumour biology which have led to improved diagnostic and prognostic techniques and the development of novel targeted therapies. However the reliability of such biomarkers is questionable and the efficacy of new treatments remains predominantly limited by a combination of drug resistance, toxicity and persisting insufficiencies in our comprehension of tumour-signalling pathways. Following their recent discovery, microRNAs (miRNAs) have been established as key regulators of gene-expression, and their putative roles as oncogenes and tumour suppressor genes has provided a potentially new dimension to our clinical approach to cancer diagnosis and treatment. Their role as biomarkers and therapeutic targets is appealing but several obstacles have as yet limited our ability to translate this potential into a clinical reality. This review focuses on currently accepted roles of miRNAs in cancer pathogenesis, and highlights the challenges and breakthroughs in this field to date with relevance to the cancer clinic.

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Avan A, Quint K, Nicolini F, Funel N, Frampton AE, Maftouh M, Pelliccioni S, Schuurhuis GJ, Peters GJ, Giovannetti Eet al., 2013, Enhancement of the antiproliferative activity of gemcitabine by modulation of c-Met pathway in pancreatic cancer, Current Pharmaceutical Design, Vol: 19, Pages: 940-950, ISSN: 1381-6128

Pancreatic-ductal-adenocarcinoma (PDAC) is amongst the most lethal malignancies, mainly because of its metastatic spread and multifactorial chemoresistance. Since c-Met is a marker of pancreatic-cancer-stem-cells (CSC), playing a key role in metastasis and chemoresistance, this study evaluated the therapeutic potential of the novel c-Met/ALK inhibitor crizotinib against PDAC cells, including the Capan-1-gemcitabine-resistant cells (Capan-1-R). Crizotinib inhibited PDAC cell-growth with IC50 of 1.5 μM in Capan-1-R, and synergistically enhanced the antiproliferative and proapoptotic activity of gemcitabine, as detected by sulforhodamine-B-assay, flow cytometry and combination-index method. Capan-1-R had higher expression of the CSC markers CD44+/CD133+/CD326+, but their combined expression was significantly reduced by crizotinib, as detected by quantitative-RT-PCR and FACS-analysis. Similarly, Capan-1-R cells had significantly higher protein-expression of c-Met (=2-fold), and increased migratory activity, which was reduced by crizotinib (e.g., >50% reduction of cell-migration in Capan-1-R after 8-hour exposure, compared to untreated-cells), in association with reduced vimentin expression. Capan-1-R had also significantly higher mRNA expression of the gemcitabine catabolism-enzyme CDA, potentially explaining the higher CDA activity and statistically significant lower levels of gemcitabine-nucleotides in Capan-1-R compared to Capan-1, as detected by Liquid-chromatography-massspectrometry. Conversely, crizotinib significantly reduced CDA expression in both Capan-1 and Capan-1-R cells. In aggregate, these data show the ability of crizotinib to specifically target CSC-like-subpopulations, interfere with cell-proliferation, induce apoptosis, reduce migration and synergistically interact with gemcitabine, supporting further studies on this novel therapeutic approach for PDAC. © 2013 Bentham Science Publishers.

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• Citations: 61

Frampton AE, Gall TMH, Krell J, Ahmad R, Jiao LRet al., 2013, Is there a 'margin' for error in pancreatic cancer surgery?, FUTURE ONCOLOGY, Vol: 9, Pages: 31-34, ISSN: 1479-6694

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• Citations: 7

Frampton AE, Gall TMH, Castellano L, Stebbing J, Jiao LR, Krell Jet al., 2013, Towards a clinical use of miRNAs in pancreatic cancer biopsies, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 13, Pages: 31-34, ISSN: 1473-7159

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• Citations: 16

Hossain MA, Chung R, Frampton AE, Chemla ESet al., 2013, Is there an optimal interventional device for the salvage of thrombosed native angioaccess for hemodialysis?, EXPERT REVIEW OF MEDICAL DEVICES, Vol: 10, Pages: 27-31, ISSN: 1743-4440

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• Citations: 2

Pellegrino L, Jacob J, Roca-Alonso L, Krell J, Castellano L, Frampton AEet al., 2013, Altered expression of the miRNA processing endoribonuclease Dicer has prognostic significance in human cancers, EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 13, Pages: 21-27, ISSN: 1473-7140

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• Citations: 13

Frampton AL, Krell J, Giovannetti E, Jiao LR, Stebbing Jet al., 2012, Role of miRNAs in the response to anticancer therapy, PHARMACOGENOMICS, Vol: 13, Pages: 1663-1666, ISSN: 1462-2416

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• Citations: 2

Silver B, Krell J, Frampton AE, 2012, Do miRNAs hold the key to controlling EBV-driven tumorigenesis?, FUTURE VIROLOGY, Vol: 7, Pages: 1045-1049, ISSN: 1746-0794

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• Citations: 1

Frampton AE, Krell J, Zhang Y, Stebbing J, Castellano L, Jiao LRet al., 2012, The role of miR-10b in metastatic pancreatic ductal adenocarcinoma, SURGERY, Vol: 152, Pages: 936-938, ISSN: 0039-6060

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• Citations: 6

Keeler BD, Krell J, Acheson AG, Brookes MJ, Stebbing J, Frampton AEet al., 2012, Is there a role for intravenous iron therapy in patients undergoing colorectal cancer resection?, EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 12, Pages: 1407-1412, ISSN: 1473-7140

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Zhang Y, Frampton AE, Cohen P, Kyriakides C, Bong JJ, Habib NA, Spalding DRC, Ahmad R, Jiao LRet al., 2012, Tumor Infiltration in the Medial Resection Margin Predicts Survival After Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma, JOURNAL OF GASTROINTESTINAL SURGERY, Vol: 16, Pages: 1875-1882, ISSN: 1091-255X

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• Citations: 47

Frampton AE, Pai M, Krell J, Vlavianos P, Jiao LR, Spalding DRet al., 2012, The "malignant truth" about the recurrence of pancreatic intraductal papillary mucinous neoplasms., Archives of Surgery, Vol: 147, Pages: 977-979

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Zhang Y, Frampton AE, Martin JL, Kyriakides C, Bong JJ, Habib NA, Vlavianos P, Jiao LRet al., 2012, 18F-fluorodeoxyglucose positron emission tomography in management of pancreatic cystic tumors, NUCLEAR MEDICINE AND BIOLOGY, Vol: 39, Pages: 982-985, ISSN: 0969-8051

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• Citations: 8

Frampton AE, Krell J, Giovannetti E, Krell D, Stebbing J, Castellano L, Jiao LRet al., 2012, Defining a prognostic molecular profile for ductal adenocarcinoma of the pancreas highlights known key signaling pathways, EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 12, Pages: 1275-1278, ISSN: 1473-7140

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• Citations: 3

Zabron AA, Frampton AE, Krell J, Castellano L, Stebbing J, Khan SA, Taylor-Robinson SD, Jiao LRet al., 2012, MicroRNAs in malignant bile as diagnostic biomarkers for pancreatic ductal adenocarcinoma., UEGW, Pages: A119-A119

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Frampton AE, Krell J, 2012, Cancer vaccines: is prevention better than cure?, FUTURE ONCOLOGY, Vol: 8, Pages: 899-901, ISSN: 1479-6694

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• Citations: 1

Frampton AE, Krell J, Jacob J, Stebbing J, Castellano L, Jiao LRet al., 2012, Loss of miR-126 is crucial to pancreatic cancer progression, EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 12, Pages: 881-884, ISSN: 1473-7140

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• Citations: 37

Frampton AE, Stebbing J, 2012, Raising a glass of red wine against cancer, or not?, LANCET ONCOLOGY, Vol: 13, Pages: 669-670, ISSN: 1470-2045

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• Citations: 1

Krell J, Frampton AE, Jiao LR, Stebbing Jet al., 2012, Can pharmacogenomics guide effective anticancer therapy in pancreatic ductal adenocarcinoma?, PHARMACOGENOMICS, Vol: 13, Pages: 977-979, ISSN: 1462-2416

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• Citations: 1

Zhang Y, Frampton AE, Kyriakides C, Bong JJ, Habib N, Ahmad R, Jiao LRet al., 2012, Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol: 138, Pages: 1063-1071, ISSN: 0171-5216

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• Citations: 48

Jacob J, Frampton AE, Castellano L, Stebbing J, Krell Jet al., 2012, Retinoblastoma protein determines aggressiveness in triple-negative breast cancer, EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 12, Pages: 581-584, ISSN: 1473-7140

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• Citations: 3

Krell J, Frampton AE, Stebbing J, 2012, The clinical significance of tumor infiltrating lymphoctyes in breast cancer: does subtype matter?, BMC CANCER, Vol: 12, ISSN: 1471-2407

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• Citations: 4

Krell J, Frampton AE, Cascorbi I, Werk A, Stebbing Jet al., 2012, miRNAs modulating endocrine resistance in breast cancer, PHARMACOGENOMICS, Vol: 13, Pages: 645-646, ISSN: 1462-2416

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Krell J, Frampton AE, Jacob J, Castellano L, Stebbing Jet al., 2012, miRNAs in breast cancer: ready for real time?, PHARMACOGENOMICS, Vol: 13, Pages: 709-719, ISSN: 1462-2416

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• Citations: 13

Frampton AE, Krell J, Pellegrino L, Roca-Alonso L, Jiao LR, Stebbing J, Castellano L, Jacob Jet al., 2012, Integrated analysis of miRNA and mRNA profiles enables target acquisition in human cancers, EXPERT REVIEW OF ANTICANCER THERAPY, Vol: 12, Pages: 323-330, ISSN: 1473-7140

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• Citations: 2

Pai M, Frampton AE, Mikhail S, Resende V, Kornasiewicz O, Spalding DR, Jiao LR, Habib NAet al., 2012, Radiofrequency assisted liver resection: Analysis of 604 consecutive cases., Eur J Surg Oncol., Vol: 38, Pages: 274-280

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Jiao LR, Frampton AE, Jacob J, Pellegrino L, Krell J, Giamas G, Tsim N, Vlavianos P, Cohen P, Ahmad R, Keller A, Habib NA, Stebbing J, Castellano Let al., 2012, MicroRNAs Targeting Oncogenes Are Down-Regulated in Pancreatic Malignant Transformation from Benign Tumors, PLOS ONE, Vol: 7, ISSN: 1932-6203

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• Citations: 109

Fletcher AM, Andrews JC, Frampton AE, 2012, Individualizing hemodynamic optimization during the management of circulatory collapse, Expert Review of Cardiovascular Therapy, Vol: 10, Pages: 1217-1220, ISSN: 1477-9072

The best method of hemodynamic monitoring to guide the resuscitation and management of the critically ill patient is unclear. The evaluated article presents data from a prospective randomized controlled trial that recruited 120 shocked patients (n = 60 in each arm) to compare volume-limited versus pressure-limited hemodynamic management. Patients were randomized into two protocolized fluid therapy algorithms using either the upper limits of hemodynamic indices of arterial pulse contour cardiac output and transpulmonary thermodilution (TPTD) analysis (extra vascular lung water <10 ml/kg and global end-diastolic volume index 850 ml/m2) or pulmonary artery catheter pressures (<18–20 mmHg). Primary outcomes were ventilator-free days, duration of mechanical ventilation, intensive care unit and hospital stay. Secondary outcomes included sequential organ failure assessment scores and mortality. No benefit was found between pulmonary artery catheter and TPTD in the primary outcomes; interestingly, the nonseptic patients who were monitored with TPTD spent longer on mechanical ventilation and in the intensive care unit. © 2012, Expert Reviews Ltd.

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• Citations: 1