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Melanoma: HELP
Articles by Peter W. Szlosarek
Based on 8 articles published since 2008

Between 2008 and 2019, P. Szlosarek wrote the following 8 articles about Melanoma.
+ Citations + Abstracts
1 Guideline Uveal Melanoma UK National Guidelines. 2015

Nathan, P / Cohen, V / Coupland, S / Curtis, K / Damato, B / Evans, J / Fenwick, S / Kirkpatrick, L / Li, O / Marshall, E / McGuirk, K / Ottensmeier, C / Pearce, N / Salvi, S / Stedman, B / Szlosarek, P / Turnbull, N / Anonymous4090839. ·Mount Vernon Cancer Centre, Northwood, Middlesex, UK. Electronic address: nathan.pd@gmail.com. · Ocular Oncology Service, St Bartholomew's and Moorfields Eye Hospital, London, UK. · Department Molecular and Clinical Cancer Medicine, University of Liverpool, UK. · OcuMel UK, UK. · Royal Liverpool University Hospital, Liverpool, UK. · University Hospital Aintree, Liverpool, UK. · Patient Representative, UK. · Moorfields Eye Hospital, London, UK. · The Clatterbridge Cancer Centre, NHS Foundation Trust, Liverpool, UK. · Southampton University Hospitals and University of Southampton, UK. · University Hospital Southampton, Southampton, UK. · Royal Hallamshire Hospital, Sheffield, UK. · Southampton University Hospitals, NHS Trust, Southampton, UK. · St Bartholomew's Hospital, UK; Barts Cancer Institute, Queen Mary University of London, London, UK. · Project Manager, London, UK. ·Eur J Cancer · Pubmed #26278648.

ABSTRACT: The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.

2 Article The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention. 2019

Renziehausen, Alexander / Wang, Hexiao / Rao, Bhavya / Weir, Lynda / Nigro, Cristiana Lo / Lattanzio, Laura / Merlano, Marco / Vega-Rioja, Antonio / Del Carmen Fernandez-Carranco, Maria / Hajji, Nabil / Matin, Rubeta / Harwood, Catherine / Li, Su / Sim, Van Ren / O'Neill, Kevin / Evans, Alan / Thompson, Alastair / Szlosarek, Peter / Fleming, Colin / Stebbing, Justin / Proby, Charlotte / Tzakos, Andreas G / Syed, Nelofer / Crook, Tim. ·John Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK. · Department of Dermatology, The First Hospital of China Medical University, Shenyang, China. · Medical Research Institute, Ninewells Hospital & Medical School, Dundee, UK. · Department of Oncology, Ospedale San Croce e Carle, Cuneo, Italy. · Hospital Universitario Virgen Macarena, Sevilla, Spain. · Barts and the London School of Medicine and Dentistry, London, UK. · Royal Marsden Hospital, Fulham Road, London, UK. · Kent Oncology Centre, Maidstone Hospital, Maidstone, ME16 9QQ, UK. · Department of Neurosurgery, Charing Cross Hospital, London, UK. · Department of Pathology, Ninewells Hospital, Dundee, UK. · Breast Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA. · Department of Medical Oncology, Bart's Cancer Centre, London, UK. · Department of Dermatology, Ninewells Hospital, Dundee, UK. · Imperial College, London, UK. · Department of Chemistry, University of Ioannina, Ioannina, Greece. · John Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK. N.syed@imperial.ac.uk. · St Lukes Cancer Centre, Guildford, UK. timothycrook@nhs.net. ·Oncogene · Pubmed #30478450.

ABSTRACT: Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin-angiotensin system (RAS) is a major physiological regulatory pathway controlling salt-water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma.

3 Article Staging Uveal Melanoma with Whole-Body Positron-Emission Tomography/Computed Tomography and Abdominal Ultrasound: Low Incidence of Metastatic Disease, High Incidence of Second Primary Cancers. 2018

Cohen, Victoria M L / Pavlidou, Efthymia / DaCosta, Joanna / Arora, Amit K / Szyszko, Teressa / Sagoo, Mandeep S / Szlosarek, Peter. ·Ocular Oncology Service, Moorfields Eye Hospital and St Bartholomew's Hospital, London, UK. · NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK. · Department of Nuclear Medicine, Barts health NHS Trust, London, UK. · Department of Medical Oncology, Barts health NHS Trust, London, UK. ·Middle East Afr J Ophthalmol · Pubmed #30122854.

ABSTRACT: PURPOSE: The purpose of this study was to report the results of staging primary uveal melanoma with whole-body (18) fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) and abdominal ultrasound. MATERIALS AND METHODS: From January 2012, patients with uveal melanoma over 4 mm in thickness were staged with FDG PET/CT and abdominal ultrasound. RESULTS: Over 2 years, 108 patients with medium-to-large melanoma underwent dual imaging. According to the tumor, node, and metastasis classification, there were 75% T3, 11% T2, and 14% T1 uveal melanomas. Only, three of 108 patients (2.8%) were found to have metastatic uveal melanoma. All three had liver metastases confirmed following biopsy; one of three had additional extrahepatic widespread metastases. In these three patients, liver findings using both imaging techniques were consistent in one patient. In the second case, abdominal ultrasound missed the diagnosis of metastatic disease; however, FDG PET/CT revealed intense metabolic activity of the liver. In the third case, PET/CT missed the liver metastases; however, this was identified on abdominal ultrasound. PET/CT identified incidental second primary malignancies in 10 patients (9%). Second malignancies were found in the lung, breast, colon, thyroid, and adrenal gland. Abdominal ultrasound detected benign hepatic abnormalities in 20 patients (18%). CONCLUSIONS: Whole-body PET/CT and abdominal ultrasound complement each other in the staging of uveal melanoma. Benign hepatic abnormalities found using ultrasound is common. Of importance, a second asymptomatic primary malignancy associated with uveal melanoma was detected almost one in 10 patients.

4 Article A major responder to ipilimumab and nivolumab in metastatic uveal melanoma with concomitant autoimmunity. 2017

Chan, Pui Ying / Hall, Peter / Hay, Gordon / Cohen, Victoria M L / Szlosarek, Peter W. ·Department of Medical Oncology, St Bartholomew's Hospital, London, UK. · Department of Ocular Oncology, Moorfields Eye Hospital, London, UK. · UCL Institute of Ophthalmology, London, UK. · Department of Ocular Oncology, St Bartholomew's Hospital, London, UK. · Centre for Molecular Oncology, Barts Cancer Institute, London, UK. ·Pigment Cell Melanoma Res · Pubmed #28640512.

ABSTRACT: The use of immune checkpoint inhibition has led to major improvements in outcome for patients with metastatic cutaneous melanoma. The combination of ipilimumab and nivolumab has demonstrated greater activity over single-agent immunotherapy in phase III trials. Clinical trials of combination CTLA-4 and PD-1 inhibition are underway in uveal melanoma, for which there are currently no data. Here, we present the case of a 74-year-old male patient with metastatic uveal melanoma, who was treated with a combination of ipilimumab and nivolumab. He developed sequential autoimmune transaminitis, diabetes and uveitis, which necessitated discontinuation of maintenance nivolumab 3 months after commencement of treatment. The patient continues to demonstrate an ongoing partial response 10 months from the initial combination immunotherapy, with the evidence of depigmentation of the primary ocular tumour.

5 Article Synchronous melanoma and renal carcinoma: a clinicopathological study of five cases. 2013

Matin, R N / Szlosarek, P / McGregor, J M / Cerio, R / Harwood, C A. ·Dermatology Department, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, UK. rnhmatin@doctors.org.uk ·Clin Exp Dermatol · Pubmed #22681124.

ABSTRACT: An increased frequency of renal carcinoma in men with melanoma has been reported in population based-studies. We report the clinicopathological findings of five cases of synchronous renal cell carcinoma (RCC), identified after routine radiological staging for cutaneous malignant melanoma (MM) between October 2006 and October 2008. The five patients (three men and two women, with a mean age of 62.4 years), presented with six melanomas of varying subtypes. The mean Breslow thickness was 1.87 mm. There was no family history of cancer in any of the cases. Routine radiological staging identified a mass arising from the left kidney in three cases and the right kidney in two cases. All patients underwent radical nephrectomy, and histology in each case confirmed RCC of the clear-cell subtype. Mean follow-up was 3 years. Although the simultaneous occurrence of RCC and MM may be coincidental, there are several plausible aetiological links. Further analysis of the synchronous occurrence of MM and renal cancer may provide therapeutic insights into these two important tumours.

6 Article NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. 2012

Wang, H / Lee, S / Nigro, C Lo / Lattanzio, L / Merlano, M / Monteverde, M / Matin, R / Purdie, K / Mladkova, N / Bergamaschi, D / Harwood, C / Syed, N / Szlosarek, P / Briasoulis, E / McHugh, A / Thompson, A / Evans, A / Leigh, I / Fleming, C / Inman, G J / Hatzimichael, E / Proby, C / Crook, T. ·Wellcome Trust Centre for Molecular Medicine, Division of Medical Sciences, Clinical Research Centre, Dundee, UK. ·Br J Cancer · Pubmed #22454080.

ABSTRACT: BACKGROUND: Novel prognostic biomarkers and therapeutic strategies are urgently required for malignant melanoma. Ecto-5-prime-nucleotidase (NT5E; CD73) overexpression has been reported in several human cancers. The mechanism(s) underlying deregulated expression and the clinical consequences of changes in expression are not known. METHODS: We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse expression and regulation of NT5E in malignant melanoma cell lines and primary and metastatic melanomas. RESULTS: NT5E is subject to epigenetic regulation in melanoma. NT5E mRNA is downregulated by methylation-dependent transcriptional silencing in the melanoma cell lines SKMel2, SKMel23, WM35, Mel501, Mel505 and C81-61 and expression is reactivated by azacytidine. In contrast, the CpG island is unmethylated and the gene expressed in cultured normal melanocytes. In clinical cases of melanoma, methylation in the NT5E CpG island occurs in both primary and metastatic melanomas and correlates with transcriptional downregulation of NT5E mRNA. Relapse with metastatic disease, particularly to the visceral sites and brain, is more common in primary melanomas lacking NT5E methylation. Primary melanomas with methylation in NT5E show limited metastatic potential or more commonly metastasise predominantly to nodal sites rather than viscera and brain (P=0.01). CONCLUSION: Deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island. Confirmation of our results in larger clinical series would support the candidacy of NT5E as a clinical biomarker in melanoma, which could be applied in both primary and relapsed disease. Inhibition of NT5E may have therapeutic potential in melanoma, particularly in patients with more aggressive disease metastatic to viscera or the brain.

7 Article KIT and BRAF mutational status in a patient with a synchronous lentigo maligna melanoma and a gastrointestinal stromal tumor. 2012

Matin, Rubeta N / Gonzalez, David / Thompson, Lisa / Lambert, Sally R / Bakr, Farrah / Dhomen, Nathalie / Marais, Richard / McGregor, Jane M / Szlosarek, Peter / Cerio, Rino / Harwood, Catherine A. · ·Am J Clin Dermatol · Pubmed #22175303.

ABSTRACT: -- No abstract --

8 Minor Rituximab in the treatment of pembrolizumab-induced myasthenia gravis. 2018

Crusz, S M / Radunovic, A / Shepherd, S / Shah, S / Newey, V / Phillips, M / Lim, L / Powles, T / Szlosarek, P W / Shamash, J / Rashid, S. ·Department of Medical Oncology, Barts Health NHS Trust, Basement Level, KGV Building, London, EC1A 7BE, UK. Electronic address: shanthini.crusz@bartshealth.nhs.uk. · Department of Neurology, Barts Health NHS Trust, 4th Floor Front Block, Whitechapel, London, EH1 1BB, UK. · Department Perioperative Medicine, Barts Health NHS Trust, 6th Floor, KGV Building, London, EC1A 7BE, UK. · Department of Medical Oncology, Barts Health NHS Trust, Basement Level, KGV Building, London, EC1A 7BE, UK. ·Eur J Cancer · Pubmed #30138772.

ABSTRACT: -- No abstract --