Publications
74 results found
Openshaw MR, Fotopoulou C, Blagden S, et al., 2015, The next steps in improving the outcomes of advanced ovarian cancer, Women's Health, Vol: 11, Pages: 355-367, ISSN: 1745-5057
Worldwide ovarian cancer affects over 200,000 women per year. Overall survival rates are poor due to two predominate reasons. First, the majority of patients present with advanced disease creating significant difficulty with effecting disease eradication. Second, acquisition of chemotherapy resistance results in untreatable progressive disease. Advances in treatment of advanced ovarian cancer involve a spectrum of interventions including improvements in frontline debulking surgery and combination chemotherapy. Anti-angiogenic factors have been shown to have activity in frontline and recurrent disease while novel chemotherapeutic agents and targeted treatments are in development particularly for disease that is resistant to platinum-based chemotherapy. These developments aim to improve the progression-free and overall survival of women with advanced ovarian cancer.
Rizzuto I, Stavraka C, Chatterjee J, et 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.
Hopkins TG, Stavraka C, Gabra H, et al., 2015, Sexual activity and functioning in ovarian cancer survivors: an internet-based evaluation, CLIMACTERIC, Vol: 18, Pages: 94-98, ISSN: 1369-7137
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- Citations: 23
Blagden S, Omlin A, Josephs D, et al., 2015, First-in-Human Study of CH5132799, an Oral Class I PI3K Inhibitor, Studying Toxicity, Pharmacokinetics, and Pharmacodynamics, in Patients with Metastatic Cancer (vol 20, pg 5908, 2014), CLINICAL CANCER RESEARCH, Vol: 21, Pages: 660-660, ISSN: 1078-0432
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- Citations: 3
Mura M, Hopkins TG, Michael T, et 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.
Blagden S, Olmin A, Josephs D, et al., 2014, First-in-Human Study of CH5132799, an Oral Class I PI3K Inhibitor, Studying Toxicity, Pharmacokinetics, and Pharmacodynamics, in Patients with Metastatic Cancer, CLINICAL CANCER RESEARCH, Vol: 20, Pages: 5908-5917, ISSN: 1078-0432
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- Citations: 28
Blagden S, Hamilton A, Mileshkin L, et al., 2014, Afuresertib (GSK2110183), an oral AKT kinase inhibitor, in combination with carboplatin and paclitaxel in recurrent ovarian cancer, 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 7-7, ISSN: 0959-8049
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- Citations: 5
Ghazaly EA, Slusarczyk M, Mason M, et al., 2014, NUC-1031: A novel ProTide that overcomes the key cancer resistance mechanisms associated with poor survival, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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- Citations: 2
Borley J, Wilhelm-Benartzi C, Farthing A, et al., 2014, Radiological predictors of cytoreductive outcomes in patients with advanced ovarian cancer, BJOG: An International Journal of Obstetrics and Gynaecology, ISSN: 1470-0328
Objective: To assess site of disease on preoperative computed tomography (CT) to predict surgical debulking in patients with ovarian cancer. Design: Two-phase retrospective cohort study. Setting: West London Gynaecological Cancer Centre, UK. Population: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal cancer undergoing cytoreductive surgery. Methods: Preoperative CT images were reviewed by experienced radiologists to assess the presence or absence of disease at predetermined sites. Multivariable stepwise logistic regression models determined sites of disease which were significantly associated with surgical outcomes in the test (n = 111) and validation (n = 70) sets. Main outcome measures: Sensitivity and specificity of CT in predicting surgical outcome. Results: Stepwise logistic regression identified that the presence of lung metastasis, pleural effusion, deposits on the large-bowel mesentery and small-bowel mesentery, and infrarenal para-aortic nodes were associated with debulking status. Logistic regression determined a surgical predictive score which was able to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846) and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of 75.0% and negative predictive value of 65.2%. These results remained significant in a recent validation set. There was a significant difference in residual disease volume in the test and validation sets (P < 0.001) in keeping with improved optimal debulking rates. Conclusions: The presence of disease at some sites on preoperative CT scan is significantly associated with suboptimal debulking and may be an indication for a change in surgical planning. © 2014 Royal College of Obstetricians and Gynaecologists.
Hopkins TG, Weir J, Mura M, et al., 2014, The mRNA-binding protein LARP1 is a pro-survival factor that promotes tumourigenicity and chemotherapy resistance in ovarian cancer, EUROPEAN JOURNAL OF CANCER, Vol: 50, Pages: S26-S26, ISSN: 0959-8049
Slusarczyk M, Lopez MH, Balzarini J, et al., 2014, Application of ProTide Technology to Gemcitabine: A Successful Approach to Overcome the Key Cancer Resistance Mechanisms Leads to a New Agent (NUC-1031) in Clinical Development, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 57, Pages: 1531-1542, ISSN: 0022-2623
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- Citations: 117
Blagden SP, 2014, The Perfect Arrangement, JOURNAL OF CLINICAL ONCOLOGY, Vol: 32, Pages: 601-602, ISSN: 0732-183X
Stavraka C, Pinato DJ, Turnbull SJ, et al., 2014, Developing an Objective Marker to Optimize Patient Selection and Predict Survival Benefit in Early-Phase Cancer Trials, CANCER, Vol: 120, Pages: 262-270, ISSN: 0008-543X
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- Citations: 12
Fotopoulou C, Vergote I, Mainwaring P, et al., 2014, Weekly AUC2 carboplatin in acquired platinum resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase Ill OVATURE multicenter randomized study, ANNALS OF ONCOLOGY, Vol: 25, Pages: 160-165, ISSN: 0923-7534
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- Citations: 23
Camarata M, Davies R, Copley S, et al., 2013, Tumour lysis syndrome in a patient with intravascular spread from a recurrent epithelial ovarian cancer., BMJ case reports, Vol: 2013
Tumour lysis syndrome is a potentially life-threatening oncological emergency most commonly encountered in patients with rapidly proliferating, treatment-responsive haematological malignancies. It is rarely observed in solid tumours and, to our knowledge, this is the first time that it has been reported in a cancer with an intravascular tumour extension. In this report, we describe a case of a woman who presented with recurrent ovarian cancer and was found to have tumour invading into her vasculature. The patient subsequently developed tumour lysis syndrome after receiving chemotherapy. The case highlights the importance of considering tumour lysis syndrome prophylaxis when treating patients with intravascular involvement from a solid malignancy even if, as in this case, it is a recurrent tumour. Included is a brief review of the literature. We propose that 'intravascular tumour invasion is recognised as an important risk factor for the development of tumour lysis syndrome.
Fotopoulou C, Spiers L, Pickford E, et al., 2013, CONTINUOUS LOW-FLOW ASCITES-DRAINAGE AND SEQUENTIAL NON-INVASIVE TUMOR-CELL SAMPLING THROUGH THE URINARY BLADDER VIA THE ALFA-PUMP CLOSED SYSTEM IN PLATINUM-RESISTANT-OVARIAN-CANCER (PROC), INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 23, ISSN: 1048-891X
Hopkins TG, Jayantha C, Gabra H, et al., 2013, OUTCOMES IN MUCINOUS OVARIAN CARCINOMAS: 10 YEARS OF EXPERIENCE IN A TERTIARY CENTRE, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 23, ISSN: 1048-891X
Hopkins TG, Stavraka C, Hood C, et al., 2013, THE IMPACT OF OVARIAN CANCER TREATMENT ON WOMEN'S SEXUAL WELLBEING, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 23, ISSN: 1048-891X
O'Cathail SM, Shaboodien R, Mahmoud S, et al., 2013, Intravenous Versus Oral Dexamethasone Premedication in Preventing Paclitaxel Infusion Hypersensitivity Reactions in Gynecological Malignancies, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 23, Pages: 1318-1325, ISSN: 1048-891X
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- Citations: 8
Chatterjee J, Hopkins T, Wahba J, et al., 2013, Early stage mucinous ovarian carcinomas: 10 years of experience in a tertiary centre, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 120, Pages: 282-283, ISSN: 1470-0328
Fotopoulou C, Spiers L, Pickford E, et al., 2013, Continuous low-flow ascites drainage and sequential non-invasive tumor-cell sampling through the urinary bladder via the alfa-pump closed system in platinum-resistant ovarian cancer (PROC): First clinical experience in a cancer patient., 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Camarata M, Davies R, Copley S, et al., 2013, Tumour lysis syndrome in a patient with intravascular spread from a recurrent epithelial ovarian cancer., BMJ Case Rep, Vol: 2013
Tumour lysis syndrome is a potentially life-threatening oncological emergency most commonly encountered in patients with rapidly proliferating, treatment-responsive haematological malignancies. It is rarely observed in solid tumours and, to our knowledge, this is the first time that it has been reported in a cancer with an intravascular tumour extension. In this report, we describe a case of a woman who presented with recurrent ovarian cancer and was found to have tumour invading into her vasculature. The patient subsequently developed tumour lysis syndrome after receiving chemotherapy. The case highlights the importance of considering tumour lysis syndrome prophylaxis when treating patients with intravascular involvement from a solid malignancy even if, as in this case, it is a recurrent tumour. Included is a brief review of the literature. We propose that 'intravascular tumour invasion is recognised as an important risk factor for the development of tumour lysis syndrome.
Shaboodien R, Diamantis N, Blagden S, et al., 2013, Feasibility of Trials in Ovarian Cancer by Line of Therapy and Platinum Sensitivity, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 23, Pages: 481-487, ISSN: 1048-891X
Ghazali E, Joel S, Gribben J, et al., 2013, ProGem1: Phase I first-in- human study of the novel nucleotide NUC-1031 in adult patients with advanced solid tumors., 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), AMER SOC CLINICAL ONCOLOGY
Mura M, He Y, Colley C, et al., 2012, MNK 1 and 2 Inhibitors Are Active in Platinum-resistant Ovarian Cancer Cells, 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 26-26, ISSN: 0959-8049
Gan H, Nebot N, Soria JC, et al., 2012, Pharmacokinetics/pharmacodynamics (PK/PD) of GSK2256098, a Focal Adhesion Kinase (FAK) Inhibitor, in Patients with Advanced Solid Tumors, 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 189-189, ISSN: 0959-8049
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- Citations: 2
Soria JC, Plummer R, Ranson M, et al., 2012, Loss of the Tumor Suppressor Merlin as a Potential Predictive Biomarker of Clinical Activity for the Oral, Focal Adhesion Kinase (FAK) Inhibitor GSK2256098 in Pts with Recurrent Mesothelioma, 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Publisher: ELSEVIER SCI LTD, Pages: 188-188, ISSN: 0959-8049
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- Citations: 7
Harding V, Fenu E, Medani H, et al., 2012, Safety, cost-effectiveness and feasibility of daycase paracentesis in the management of malignant ascites with a focus on ovarian cancer, British Journal of Cancer, Vol: 107, Pages: 925-930, ISSN: 0007-0920
Background:Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3–5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis.Method:Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010–January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May–December 2011).Results:Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage.Conclusions:Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.
Mura M, Abd Latip N, Michael T, et al., 2012, LARP1 Regulates the Site-specific Synthesis of Proteins Required for Cancer Cell Invasion and Migration, 22nd Biennial Congress of the European-Association-for-Cancer-Research, Publisher: ELSEVIER SCI LTD, Pages: S77-S77, ISSN: 0959-8049
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