Publications
331 results found
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
Bobrie A, Krumeich S, Reyal F, et al., 2012, Rab27a Supports Exosome-Dependent and -Independent Mechanisms That Modify the Tumor Microenvironment and Can Promote Tumor Progression, CANCER RESEARCH, Vol: 72, Pages: 4920-4930, ISSN: 0008-5472
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- Citations: 442
Chapman-Rothe N, Curry E, Zeller C, et al., 2012, Chromatin H3K27me3/H3K4me3 histone marks define gene sets in high grade serous ovarian cancer that distinguish malignant, tumour sustaining and chemo-resistant ovarian tumour cells, Oncogene
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.
Stavraka C, MacLaran K, Gabra H, et al., 2012, A study to evaluate the cause of bone demineralisation in gynaecological cancer survivors.
Jayasena CN, Comninos AN, Januszewski A, et al., 2012, Plasma Kisspeptin: A Potential Biomarker of Tumor Metastasis in Patients with Ovarian Carcinoma, CLINICAL CHEMISTRY, Vol: 58, Pages: 1061-1063, ISSN: 0009-9147
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- Citations: 12
Menghi F, Woo X, Gong M, et al., 2012, Unravelling the complexity of individual cancer genomes, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Nawathe SR, Zanini E, Hayward G, et al., 2012, The OPCML tumor suppressor binds and negatively regulates the Axl receptor tyrosine kinase, sensitizing cells to foretinib in epithelial ovarian cancer (EOC), CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Singh RK, Liao W, Tracey-White D, et al., 2012, Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 1652-1656, ISSN: 0021-9533
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- Citations: 16
Stavraka C, Ford A, Ghaem-Maghami S, et al., 2012, A study of symptoms described by ovarian cancer survivors, GYNECOLOGIC ONCOLOGY, Vol: 125, Pages: 59-64, ISSN: 0090-8258
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- Citations: 54
Jayasena CN, Comninos AN, Januszewski A, et al., 2012, Plasma Kisspeptin: A Potential Biomarker of Tumor Metastasis in Patients with Ovarian Carcinoma., Clinical Chemistry (Washington, DC): international journal of molecular diagnostics and laboratory medicine
Mckie AB, Vaughan S, Zanini E, et al., 2012, The OPCML Tumor Suppressor Functions as a Cell Surface Repressor–Adaptor, Negatively Regulating Receptor Tyrosine Kinases in Epithelial Ovarian Cancer, Cancer Discovery
Li HK, Harding V, Williamson R, et al., 2012, Cerebral Sinus Thrombosis and Leptomeningeal Carcinomatosis in a Patient With Ovarian Cancer, JOURNAL OF CLINICAL ONCOLOGY, Vol: 30, Pages: E19-E20, ISSN: 0732-183X
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- Citations: 8
Gabra H, Blagden S, 2012, Epithelial Ovarian Cancer, Pages: 760-775
Although relatively uncommon, epithelial ovarian cancer is the most lethal gynaecological malignancy, partly due to its insidious presentation but also because of its intrinsic histological and molecular heterogeneity. The 5-year survival rate has recently improved to almost 50%, predominantly through optimal specialist surgical intervention and the use of platinum-based chemotherapy. However, for the majority of patients, the disease will relapse following initial treatment and become increasingly chemotherapy resistant with each episode of recurrence. Future treatment strategies, as well as improving response to front-line therapy, are focusing on ways to overcome chemotherapy resistance in the relapsed setting, with the judicious use of novel cytotoxic and/or targeted therapies. These options become more feasible with improvements in our understanding of the molecular behaviour of the disease and of its various histological subtypes. We summarize the current status quo in the surgical and medical management of ovarian cancer and present results of a number of key studies that have explored genetically, molecularly and histologically targeted strategies in the treatment of this disease. © 2012 John Wiley and Sons, Ltd..
Gabra H, 2012, OPCML, a novel systems regulator of tyrosine kinase signaling in ovarian and other cancers, Hereditary Cancer in Clinical Practice, Vol: 10, Pages: A34-A34, ISSN: 1897-4287
Blagden SB, Gabra H, 2011, Dewhurst's Textbook of Obstetrics and Gynaecology, Dewhurst's Textbook of Obstetrics and Gynaecology, Editors: Edmonds, Publisher: Wiley, ISBN: 9781119979418
This 8th edition has been comprehensively updated to reflect modern clinical needs. Summary boxes throughout enable rapid assimilation of key information for effective clinical practice.
Stronach EA, Chen M, Maginn EN, et al., 2011, DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance, NEOPLASIA, Vol: 13, Pages: 1069-U114, ISSN: 1476-5586
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- Citations: 112
Gabra H, 2011, Cancer methods., WO/2011/128701
A method of treating a patient having a cancer in which HER2, HER4, FGFR1, EPHA2 and/or FGFR3 is upregulated and/or in which HER2, HER4, FGFR1, EPHA2 and/or FGFR3 mediated-signaling is upregulated, the method comprising administering to the patient a compound comprising or consisting of an OPCML polypeptide (SEQ ID NO: 1), or a fragment thereof which comprises at least one Ig domain of OPCML, or a variant thereof having at least 90% sequence identity with the OPCML polypeptide or the fragment thereof, or a nucleic acid molecule which encodes the OPCML polypeptide or fragment or variant thereof.
Ledermann JA, Hackshaw A, Kaye S, et al., 2011, Randomized Phase II Placebo-Controlled Trial of Maintenance Therapy Using the Oral Triple Angiokinase Inhibitor BIBF 1120 After Chemotherapy for Relapsed Ovarian Cancer, JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, Pages: 3798-3804, ISSN: 0732-183X
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- Citations: 168
Vaughan S, Coward JI, Bast RC, et al., 2011, Rethinking ovarian cancer: recommendations for improving outcomes, NATURE REVIEWS CANCER, Vol: 11, Pages: 719-725, ISSN: 1474-175X
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- Citations: 942
Gungor H, Stronach E, Curry E, et al., 2011, Mutation and Protein Expression Biomarkers Correlate with Response to AKT Inhibition in a Phase I Trial of the Oral Pan AKT Inhibitor GSK2141795 (GSK795) in Patients (pts) with Platinum Resistant Ovarian Cancer, EUROPEAN JOURNAL OF CANCER, Vol: 47, Pages: 12-13, ISSN: 0959-8049
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- Citations: 1
Sharma R, Graham J, Blagden S, et al., 2011, Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer, BMC Cancer, Vol: 11, ISSN: 1471-2407
BackgroundPlatinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored.MethodsWe treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel.ResultsWe were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity.ConclusionsWe conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.
Stronach EA, Alfraidi A, Rama N, et al., 2011, HDAC4-Regulated STAT1 Activation Mediates Platinum Resistance in Ovarian Cancer, CANCER RESEARCH, Vol: 71, Pages: 4412-4422, ISSN: 0008-5472
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- Citations: 135
Bell D, Berchuck A, Birrer M, et al., 2011, Integrated genomic analyses of ovarian carcinoma, Nature, Vol: 474, Pages: 609-615, ISSN: 0028-0836
A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and theDNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNAcopy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptionalsignature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
Gungor H, Saleem A, Agarwal R, et al., 2011, Pharmacokinetic (PK)/pharmacodynamic (PD) analysis of escalating repeat doses of the AKT inhibitor GSK2141795 (GSK795) in patients (pts) with ovarian cancer., JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, ISSN: 0732-183X
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- Citations: 7
McGuigan C, Habib NA, Wasan HS, et al., 2011, A phosphoramidate ProTide (NUC-1031) and acquired and intrinsic resistance to gemcitabine, JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, ISSN: 0732-183X
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- Citations: 7
McGuigan C, Habib NA, Wasan HS, et al., 2011, A phosphoramidate ProTide (NUC-1031) and acquired and intrinsic resistance to gemcitabine., J Clin Oncol, Vol: 29
e13540 Background: Resistance to gemcitabine is a major problem in the treatment of cancer. The key resistance mechanisms associated with gemcitabine are: lack of nucleoside transporters; lack of kinases for phosphorylation; and/or, rapid metabolism by deaminases. Resistance results in complete response rates of less than 10% in pancreatic cancer. The addition of a phosphoramidate ProTide moiety to gemcitabine enables: passive entry into the cell, by-passing the reliance on transporters; reduced reliance on kinases for phosphorylation; and, less susceptibility to deamination. METHODS: The ProTide (NUC-1031) was compared to the parent molecule (gemcitabine) in two pancreatic tumor xenograft models: Mia-Pa-Ca-2 (n=40), which is partially responsive to gemcitabine; and BxPC-3 (n=40), which is resistant. Two dose regimens for each tumor type were used, with NUC-1031 administered IP at doses of 0.076 or 0.19 mMol/kg when tumors had reached 150 - 200mm(3). The objective was to determine the ability of a novel agent (NUC-1031) to overcome gemcitabine resistance by measuring tumor growth in partially responsive and resistant pancreatic cell lines. RESULTS: The anti-tumor effect of NUC-1031 was greater and longer lasting than that of gemcitabine and control in both cell lines. NUC-1031 inhibition of tumor growth was significantly different from control in Mia-Pa-Ca-2 on days 4, 11, 14, 18, 21 and 25, and in BxPC-3 cells on days 25, 29, 33 and 37. In Mia-Pa-Ca-2 the tumor volume decreased immediately after first dosing and held at low levels until the end of the experiment. NUC-1031 was well tolerated and animals lost <2% body weight on treatment and this was regained rapidly after cessation of treatment. CONCLUSIONS: NUC-1031 showed statistically significant reduction in pancreatic tumor volume compared with gemcitabine and control. A phase I/II study of NUC-1031 in resistant/refractory pancreatic cancer is scheduled.
Gungor H, Saleem A, Agarwal R, et al., 2011, Pharmacokinetic (PK)/pharmacodynamic (PD) analysis of escalating repeat doses of the AKT inhibitor GSK2141795 (GSK795) in patients (pts) with ovarian cancer, ASCO 2011
Background: GSK795 is a potent, ATP-competitive, pan AKT inhibitor. The purpose of this study was to characterize the relationship between AKT inhibition by GSK795 and downstream effects in platinum resistant ovarian cancer pts. Methods: Pts with recurrent platinum-resistant ovarian cancer received 25, 50 or 75mg of oral GSK795 daily. Dynamic FDG-PET scans and paired tumor biopsies (PTB) were performed prior to first dose and at 2 and/or 4 weeks post treatment. Semi-quantitative (SUV) and quantitative (Ki, MRglu) PET PD parameters were derived. PTB were analyzed by immunohistochemistry (IHC) for PD marker expression. PK samples were obtained in parallel. Response was monitored by RECIST and CA125 criteria. Results: 12 pts have been treated on study: 4 at 25mg, 4 at 50mg and 4 at 75mg. After completion of the 2 or 4 week post-treatment PD assessment, all eligible pts underwent intra-subject dose escalation to 75mg. The most common drug-related adverse events ( 10%) were decreased appetite (18%) and vomiting (18%), all G1/2. Mean Cmax and AUC24 increased with increasing doses and increased 1.2-fold from Week 2 to Week 4 where 2 and 4 week doses were the same. Median Tmax was 4 h. Overall tumor FDG metabolism decreased in 71% of tumors with treatment, although inter- and intra-patient variability in tumor uptake measurements following therapy was seen. There was no clear temporal or dose-response effect in FDG uptake. IHC analysis of PTB from 5 pts dosed at either 50 or75mg indicated that pAKT levels increased in 2/2 pts dosed at 75mg, pPRAS40 levels decreased in 4/5 pts, and Ki67 levels decreased in 4/5 pts after treatment with GSK795. 8/12 pts had stable disease and 4/12 had progressive disease by RECIST criteria at week 4. Currently 4 pts are still on the study, 2 > 24 weeks, with tumor regressions of 26% and 11% and CA125 decreases of 70% and 58% respectively. Conclusions: A dose response relationship between changes in FDG-PET and GSK795 was not observed in pts
McKie AB, Vaughan S, Okon I, et al., 2011, The OPCML tumor suppressor negatively regulates a specific repertoire of 5 receptor tyrosine kinases via a novel proteasomal mechanism, and its recombinant derivative is a potent in-vivo anticancer protein therapy, CANCER RESEARCH, Vol: 71, ISSN: 0008-5472
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