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  • Conference paper
    Fotopoulou C, Cunnea P, Rama NR, Wulandari R, Gorgy T, Gabra H, Stronach EAet al., 2015,

    Characterising phenotypically relevant intratumoural heterogeneity in high grade serous ovarian cancer.

    , 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
  • Journal article
    Sayasneh A, Kaijser J, Preisler J, Smith AA, Raslan F, Johnson S, Husicka R, Ferrara L, Stalder C, Ghaem-Maghami S, Timmerman D, Bourne Tet al., 2015,

    Accuracy of ultrasonography performed by examiners with varied training and experience in predicting specific pathology of adnexal masses

    , ULTRASOUND IN OBSTETRICS & GYNECOLOGY, Vol: 45, Pages: 605-612, ISSN: 0960-7692
  • Journal article
    Stronach EA, Cunnea P, Turner C, Guney T, Aiyappa R, Jeyapalan S, de Sousa CH, Browne A, Magdy N, Studd JB, Sriraksa R, Gabra H, El-Bahrawy Met al., 2015,

    The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma

    , Oncotarget, Vol: 6, Pages: 31593-31603, ISSN: 1949-2553

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

  • Journal article
    Rizzuto I, Stavraka C, Chatterjee J, Borley J, Hopkins TG, Gabra H, Ghaem-Maghami S, Huson L, Blagden SPet al., 2015,

    Risk of Ovarian Cancer Relapse Score A Prognostic Algorithm to Predict Relapse Following Treatment for Advanced Ovarian Cancer

    , International Journal of Gynecological Cancer, Vol: 25, Pages: 416-422, ISSN: 1525-1438

    Objective: The aim of this study was to construct a prognostic index that predicts risk ofrelapse in women who have completed first-line treatment for ovarian cancer (OC).Methods: A database of OC cases from 2000 to 2010 was interrogated for InternationalFederation of Gynecology and Obstetrics stage, grade and histological subtype of cancer,preoperative and posttreatment CA-125 level, presence or absence of residual disease aftercytoreductive surgery and on postchemotherapy computed tomography scan, and time toprogression and death. The strongest predictors of relapse were included into an algorithm,the Risk of Ovarian Cancer Relapse (ROVAR) score.Results: Three hundred fifty-four cases of OC were analyzed to generate the ROVARscore. Factors selected were preoperative serum CA-125, International Federation ofGynecology and Obstetrics stage and grade of cancer, and presence of residual disease atposttreatment computed tomography scan. In the validation data set, the ROVAR score had asensitivity and specificity of 94% and 61%, respectively. The concordance index for thevalidation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patientstratification into low (G0.33), intermediate (0.34Y0.67), and high (90.67) probability ofrelapse.Conclusions: The ROVAR score stratifies patients according to their risk of relapsefollowing first-line treatment for OC. This can broadly facilitate the appropriate tailoring ofposttreatment care and support.

  • Conference paper
    Wu W, Vitharana K, Gorgy T, Paterson A, Cunnea P, Gabra H, Fotopoulou C, Boutelle MG, Drakakis EMet al., 2015,

    A Method for Voltage Measurements of Cancerous vs Non-cancerous Omentum

    , 37th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC), Publisher: IEEE, Pages: 7514-7517, ISSN: 1557-170X
  • Journal article
    Flanagan JM, Brook MN, Orr N, Tomczyk K, Coulson P, Fletcher O, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow A, Brown R, Garcia-Closas Met al., 2015,

    Temporal Stability and Determinants of White Blood Cell DNA Methylation in the Breakthrough Generations Study

    , CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 24, Pages: 221-229, ISSN: 1055-9965
  • Journal article
    Borley J, Brown R, 2015,

    Epigenetic mechanisms and therapeutic targets of chemotherapy resistance in epithelial ovarian cancer

    , ANNALS OF MEDICINE, Vol: 47, Pages: 359-369, ISSN: 0785-3890
  • Journal article
    Flanagan JM, 2015,

    Epigenome-wide association studies (EWAS): past, present, and future.

    , Methods Mol Biol, Vol: 1238, Pages: 51-63

    Just as genome-wide association studies (GWAS) grew from the field of genetic epidemiology, so too do epigenome-wide association studies (EWAS) derive from the burgeoning field of epigenetic epidemiology, with both aiming to understand the molecular basis for disease risk. While genetic risk of disease is currently unmodifiable, there is hope that epigenetic risk may be reversible and or modifiable. This review will take a look back at the origins of this field and revisit the past early efforts to conduct EWAS using the 27k Illumina methylation beadarrays, to the present where most investigators are using the 450k Illumina beadarrays and finally to the future where next generation sequencing based methods beckon. There have been numerous diseases, exposures and lifestyle factors investigated with EWAS, with several significant associations now identified. However, much like the GWAS studies, EWAS are likely to require large international consortium-based approaches to reach the numbers of subjects, and statistical and scientific rigor, required for robust findings.

  • Journal article
    Mura M, Hopkins TG, Michael T, Abd-Latip N, Weir J, Aboagye E, Mauri F, Jameson C, Sturge J, Gabra H, Bushell M, Willis AE, Curry E, Blagden SPet al., 2014,

    LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

    , Oncogene, Vol: 34, Pages: 5025-5036, ISSN: 1476-5594

    RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5′-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.

  • Journal article
    Parente-Pereira AC, Shmeeda H, Whilding LM, Zambirinis CP, Foster J, van der Stegen SJC, Beatson R, Zabinski T, Brewig N, Sosabowski JK, Mather S, Ghaem-Maghami S, Gabizon A, Maher Jet al., 2014,

    Adoptive Immunotherapy of Epithelial Ovarian Cancer with V gamma 9V delta 2 T Cells, Potentiated by Liposomal Alendronic Acid

    , JOURNAL OF IMMUNOLOGY, Vol: 193, Pages: 5557-5566, ISSN: 0022-1767

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