ProfessorBobBrown

Parenty ADC, Smith LV, Guthrie KM, Long DL, Plumb J, Brown R, Cronin Let al., 2005, Highly stable phenanthridinium frameworks as a new class of tunable DNA binding agents with cytotoxic properties, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 48, Pages: 4504-4506, ISSN: 0022-2623

• Author Web Link
• Cite
• Citations: 70

Strathdee G, Holyoake TL, Sim A, Melo JV, Soutar R, Parker A, Oscier DG, Brown Ret al., 2005, HoxA cluster genes are frequently targeted by DNA methylation in CML and other types of human leukaemia, 34th Annual Meeting of the International-Society-for-Experimental-Hematology, Publisher: ELSEVIER SCIENCE INC, Pages: 50-50, ISSN: 0301-472X

• Author Web Link
• Cite
• Citations: 2

Strathdee G, Vass JK, Oien KA, Siddiqui N, Curto-Garcia J, Brown Ret al., 2005, Demethylation of the <i>MCJ</i> gene in stage III/IV epithelial ovarian cancer and response to chemotherapy, GYNECOLOGIC ONCOLOGY, Vol: 97, Pages: 898-903, ISSN: 0090-8258

• Author Web Link
• Cite
• Citations: 58

Teodoridis JM, Hall J, Marsh S, Kannall HD, Smyth C, Curto J, Siddiqui N, Gabra H, McLeod HL, Strathdee G, Brown Ret al., 2005, CpG island methylation of DNA damage response genes in advanced ovarian cancer, Cancer Res, Vol: 65, Pages: 8961-8967

• Cite

Batch C, Huang THM, Brown R, Nephew KPet al., 2004, The epigenetics of ovarian cancer drug resistance and resensitization, AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol: 191, Pages: 1552-1572, ISSN: 0002-9378

• Author Web Link
• Cite
• Citations: 134

Lee C, Appleton K, Plumb J, Kaye S, Cruickshank C, Twelves C, Vasey P, Judson I, Brown R, Mackay Het al., 2004, A phase I trial of the DNA-hypomethylating agent 5-Aza-2'-Deoxycytidine in combination with carboplatin both given 4 weekly by intravenous injection in patients with advanced solid tumours., J Clin Oncol, Vol: 22

2005 Background: There is increasing evidence that DNA hypermethylation of CpG islands at key genes is associated with chemo resistance. For instance, methylation of a CpG-island at the hMLH1 promoter may be a major mechanism for loss of MLH1 expression associated with chemo resistance. Decitabine (5-Aza-2'-deoxycytidine) is a demethylating agent which has been shown in in vivo studies to reactivate MLH1 expression leading to sensitisation of chemo resistant tumours to a range of cytotoxic drugs. This Phase I study investigated the feasibility of delivering a dose of decitabine which would cause demethylation and hence potential sensitisation without causing prohibitive myelosuppression in combination with carboplatin. METHODS: Pts with a variety of malignancies were enrolled. The starting dose of decitabine (on Day 1) was 45mg/m2. This was escalated in steps of 45mg/m2. Carboplatin at a fixed dose of AUC5 was given on Day 8. The interval between decitabine and carboplatin was 8 days which was within the optimal time for demethylation from xenograft studies. Treatment was repeated every 4 weeks. RESULTS: 14 heavily-pretreated pts have been enrolled to date (6M/8F). Median age: 55; mean PS (ECOG): 1. Pts have been treated at 3 dose levels of decitabine: 45, 90 and 135mg/m2. Median number of cycles: 2 (range 0.5-6). 13/14 patients were evaluable for toxicity. MTD was identified as decitabine 135mg/m2 with grade 4 febrile neutropenia (1 pt), and grade 4 neutropenia necessitating delay of cycle 2 for >7 days (1 pt). Other possible treatment-related toxicities included: nausea, vomiting, diarrhoea, fatigue, anorexia, anaemia (all ≤grade 2 and easily manageable). PD studies showed reduction in 5-methylcytosine to total cytosine ratios in DNA isolated from peripheral mononuclear cells at all dose levels, and was maximal between Days 8 and 12 following decitabine infusion Conclusion: This study confirms that the combination of decitabine and carboplatin is feasible. F

• Abstract
• Author Web Link
• Cite

Gifford G, Paul J, Vasey PA, Kaye SB, Brown Ret al., 2004, The acquisition of <i>hMLH1</i> methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients, CLINICAL CANCER RESEARCH, Vol: 10, Pages: 4420-4426, ISSN: 1078-0432

• Author Web Link
• Cite
• Citations: 209

Morley S, MacDonald G, Kirn D, Kaye S, Brown R, Soutar Det al., 2004, The dl1520 virus is found preferentially in tumor tissue after direct intratumoral injection in oral carcinoma, CLINICAL CANCER RESEARCH, Vol: 10, Pages: 4357-4362, ISSN: 1078-0432

• Author Web Link
• Cite
• Citations: 33

Hall J, Paul J, Brown R, 2004, Critical evaluation of p53 as a prognostic marker in ovarian cancer., Expert Rev Mol Med, Vol: 6, Pages: 1-20

The tumour suppressor gene encoding p53 has been shown from experimental studies to have a crucial role in how cells respond to DNA damage. p53 has important functions in apoptosis, cell-cycle arrest and DNA repair, largely mediated by its activity on gene transcription. However, despite this wealth of in vitro data, its role in how tumours respond to DNA damage induced by chemotherapeutic drugs remains controversial. In this review, we highlight some of the problems surrounding design and analysis of studies of p53 as a prognostic marker of clinical outcome, using ovarian cancer as an example. We aim to build on the knowledge of the published literature in ovarian cancer to identify criteria for clinical studies that should give a more definitive estimate of the role of p53 in clinical drug resistance. A search of three public databases using keywords combined with Boolean operators identified 64 clinical publications investigating the relationship of p53 to clinical outcome following chemotherapy in ovarian cancer. Although 43% of 215 published analyses from the 64 papers reported a significant correlation between p53 status and a clinical endpoint relevant to chemoresistance, only six analyses fulfil minimum criteria and none of these finds a statistically significant correlation of p53 with chemotherapy-resistance endpoints. The results from published clinical studies suggest a more complex role of p53 mutation in the mechanism of resistance in ovarian cancer than is suggested by in vitro studies.

• Abstract
• Author Web Link
• Cite

Strathdee G, Davies BR, Vass JK, Siddiqui N, Brown Ret al., 2004, Cell type-specific methylation of an intronic CpG island controls expression of the <i>MCJ</i> gene, CARCINOGENESIS, Vol: 25, Pages: 693-701, ISSN: 0143-3334

• Author Web Link
• Cite
• Citations: 54

Barvaux VA, Ranson M, Brown R, McElhinney RS, McMurry TBH, Margison GPet al., 2004, Dual repair modulation reverses Temozolomide resistance <i>in vitro</i>, MOLECULAR CANCER THERAPEUTICS, Vol: 3, Pages: 123-127, ISSN: 1535-7163

• Author Web Link
• Cite
• Citations: 25

Teodoridis JM, Strathdee G, Brown R, 2004, Epigenetic silencing mediated by CpG island methylation: potential as a therapeutic target and as a biomarker, Drug Resist Updat, Vol: 7, Pages: 267-278

• Cite

Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown Ret al., 2003, Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101, MOLECULAR CANCER THERAPEUTICS, Vol: 2, Pages: 721-728, ISSN: 1535-7163

• Author Web Link
• Cite
• Citations: 310

Mac Partlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST, Matheson EC, Hall AG, Gillespie DAF, Brown Ret al., 2003, Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX, ONCOGENE, Vol: 22, Pages: 819-825, ISSN: 0950-9232

• Author Web Link
• Cite
• Citations: 17

Wei SH, Brown R, Huang THM, 2003, Aberrant DNA methylation in ovarian cancer is there an epigenetic predisposition to drug response?, EPIGENETICS IN CANCER PREVENTION: EARLY DETECTION AND RISK ASSESSMENT, Vol: 983, Pages: 243-250, ISSN: 0077-8923

• Author Web Link
• Cite
• Citations: 33

Brown R, Strathdee G, 2002, Epigenomics and epigenetic therapy of cancer, TRENDS IN MOLECULAR MEDICINE, Vol: 8, Pages: S43-S48, ISSN: 1471-4914

• Author Web Link
• Cite
• Citations: 113

Strathdee G, Sansom OJ, Sim A, Clarke AR, Brown Ret al., 2001, A role for mismatch repair in control of DNA ploidy following DNA damage, ONCOGENE, Vol: 20, Pages: 1923-1927, ISSN: 0950-9232

• Author Web Link
• Cite
• Citations: 29

Strathdee G, Appleton K, Illand M, Millan DWM, Sargent J, Paul J, Brown Ret al., 2001, Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes, AMERICAN JOURNAL OF PATHOLOGY, Vol: 158, Pages: 1121-1127, ISSN: 0002-9440

• Author Web Link
• Cite
• Citations: 165

Ganly I, Kim YT, Hann B, Balmain A, Brown Ret al., 2001, Replication and cytolysis of an E1B-attenuated adenovirus in drug-resistant ovarian tumour cells is associated with reduced apoptosis, GENE THERAPY, Vol: 8, Pages: 369-375, ISSN: 0969-7128

• Author Web Link
• Cite
• Citations: 22

Hirst GL, Brown R, 2001, Detection of the Replication Error Phenotype in Ovarian Cancer-PCR Analysis of Microsatellite Instability., Methods Mol Med, Vol: 39, Pages: 375-382, ISSN: 1543-1894

Microsatellites are simple, tandemly repeated DNA sequences that are abundantly distributed throughout the human genome, and because of their polymorphic nature have been widely utilized as genetic markers (1). They consist of a repeating unit of 1 to 5 basepairs, averaging 25 to 60 bases in length, and are commonly found in the form d(CA)n: d(GT)n (2). It has been estimated that there are approximately 100,000 CA/GT repeat sequences in the human genome (3). Studies in patients with HNPCC (hereditary nonpolyposis colorectal cancer) first reported the appearance of instability at microsatellites sequences involving either an expansion or contraction of the repeat sequence (4,5). The suggestion that this might reflect a defect in DNA repair was vindicated when subsequent work demonstrated defects in one of four mismatch repair genes [reviewed in (6)]. Such microsatellite instability (MI) has now been reported in a variety of different tumor types including lung, breast, ovary, stomach, endometrium, and bladder [reviewed in (7)].

• Abstract
• Author Web Link
• Cite

Plumb JA, Strathdee G, Sludden J, Kaye SB, Brown Ret al., 2000, Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the <i>hMLH1</i> gene promoter, CANCER RESEARCH, Vol: 60, Pages: 6039-6044, ISSN: 0008-5472

• Author Web Link
• Cite
• Citations: 423

Heise C, Ganly I, Kim YT, Sampson-Johannes A, Brown R, Kirn Det al., 2000, Efficacy of a replication-selective adenovirus against ovarian carcinomatosis is dependent on tumor burden, viral replication and p53 status, GENE THERAPY, Vol: 7, Pages: 1925-1929, ISSN: 0969-7128

• Author Web Link
• Cite
• Citations: 56

Mackay HJ, Cameron D, Rahilly M, Mackean MJ, Paul J, Kaye SB, Brown Ret al., 2000, Reduced MLH1 expression in breast tumors after primary chemotherapy predicts disease-free survival, JOURNAL OF CLINICAL ONCOLOGY, Vol: 18, Pages: 87-93, ISSN: 0732-183X

• Author Web Link
• Cite
• Citations: 88

Batra RS, Hatchwell E, Rider S, Brown R, Brown GK, Craig IWet al., 1997, Localization of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1) within a YAC contig in Xp11.21, GENOMICS, Vol: 40, Pages: 358-361, ISSN: 0888-7543

• Author Web Link
• Cite
• Citations: 4

Brown R, 1996, Cellular responses to DNA damage and cisplatin resistance, 1995 HHMT Forum on Ovarian Cancer, Publisher: CHAPMAN & HALL, Pages: 205-213

• Author Web Link
• Cite
• Citations: 2

THACKER J, BROWN R, CAWOOD AH, STRETCH Aet al., 1985, THE NATURE OF MUTATIONS INDUCED BY IONIZING-RADIATION IN CULTURED MAMMALIAN-CELLS, INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, Vol: 48, Pages: 453-453, ISSN: 0955-3002

• Author Web Link
• Cite
• Citations: 1

BROWN R, THACKER J, 1980, CHARACTERIZATION OF RADIATION-INDUCED MUTANTS OF CULTURED MAMMALIAN-CELLS, RADIATION AND ENVIRONMENTAL BIOPHYSICS, Vol: 17, Pages: 341-341, ISSN: 0301-634X

• Author Web Link
• Cite
• Citations: 4