Publications by authors named "Brian Naylor"

Context: The biologic potential of prostate cancer (pCA) is variable, and the ability to identify tumours that might cause morbidity and mortality is limited.

Objective: This systematic review sought to establish whether measurement of tumour extent in biopsies provides additional prognostic information on the risk of disease progression.

Evidence Acquisition: A comprehensive 31-step search strategy was run in MEDLINE, EMBASE, and the Web of Knowledge (January 1990-July 2007) and supplemented by the hand-searching of references in retrieved articles and relevant journals to identify publications related to the measurement of the length of cancer in biopsies and biochemical or clinical recurrence or pCA death.

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Clinically localized prostate cancer is associated with a wide variation in biologic behavior, and men with the less aggressive form of the disease may never develop symptoms. There has been a rise in prostate cancer incidence in countries in which the blood test for prostatic-specific antigen (PSA) is common, and concerns have been expressed that this may be because of the increased detection of indolent disease, subjecting these men to unnecessary treatment and associated side effects. For the current review, the authors conducted a systematic evaluation of the literature regarding the outcomes of men who were diagnosed on the basis of a small volume of cancer in prostatic biopsies.

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Men with clinically localized prostate cancer are faced with a wide range of treatment options, and only Gleason grading is universally used as a histopathological prognostic factor for this disease. The significance of perineural invasion in diagnostic biopsies is controversial. Opinion about whether or not it should influence treatment decisions is currently almost equally divided.

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Objectives: To analyze matrix metalloproteinase-10 (MMP-10) expression in transitional cell carcinoma (TCC) of the bladder, evaluate the correlations between MMP-10 protein expression and clinicopathologic parameters, and address the viability of MMP-10 as a therapeutic target for TCC. MMP-mediated degradation of the extracellular matrix is an important factor in the pathogenesis of tumorigenesis and metastasis.

Methods: Using immunohistochemistry, the expression of MMP-10 was assessed using both tissue microarrays and whole sections of archival tissue specimens representative of all grades and stages of human bladder TCC (n = 60).

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NAD(P)H:Quinone oxidoreductase-1 (NQO1) has been implicated in the bioreductive activation of the clinically active anticancer drug Mitomycin C (MMC) and a polymorphic variant of NQO1 which lacks functional enzyme activity (NQO1*2) has been linked with poor survival in patients treated with MMC. The relationship between NQO1 activity and cellular response to MMC is however controversial and the aim of this study was to determine whether the response of bladder cancer patients to MMC can be forecast on the basis of NQO1*2 genotype status. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue from 148 patients with low to intermediate grade (G1/G2) superficial (Ta/T1) bladder cancers and NQO1*2 genotype status determined by PCR-RFLP.

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NQO1 is a cytosolic flavoprotein that plays a dual role in the detoxification of potentially carcinogenic compounds and the bioreductive activation of quinone based anticancer drugs. Two polymorphic variants of NQO1 exist (NQO1*2 and NQO1*3) which cause significant phenotypic reductions in NQO1 protein content and activity. Current methods for detecting NQO1 polymorphisms commonly use PCR-RFLP techniques and have exclusively used DNA isolated from fresh tissues.

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A central theme within the concept of enzyme-directed bioreductive drug development is the potential to predict tumour response based on the profiling of enzymes involved in the bioreductive activation process. Mitomycin C (MMC) is the prototypical bioreductive drug that is reduced to active intermediates by several reductases including NAD(P)H:quinone oxidoreductase (NQO1) and NADPH cytochrome P450 reductase (P450R). The purpose of our study was to determine whether NQO1 and P450R protein expression in a panel of low-grade, human superficial bladder tumours correlates with clinical response to MMC.

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