'I Can Step outside My Comfort Zone.'

On embarking upon such a multifactorial, professional degree as Pharmacy, students often find it difficult to meld the scientific- and practice-based components of the course. In final year of the undergraduate Masters of Pharmacy degree (MPharm) within the School of Pharmacy and Life Sciences at Robert Gordon University (RGU), students undertake a research project within a specific area. The aims of this study were to explore the effectiveness of a novel practice based approach to a biomedical science project, to identify elements of difficulty in the process, and to explore students' perceptions and reflections. Final year students were assigned to perform a systematic literature review working within a defined area of pharmacovigilance. Students were given individual ownership of the research question and were able to choose a topic of interest. Following the successful completion of the assignment, students were invited to explore their attitudes and views of the project and reflect on the process through a focus group using a talking wall method. The findings clearly identified a shift in mindset from predominantly negative opinions initially to an overwhelming positive viewpoint.

Profiling cytochrome P450 expression in ovarian cancer: identification of prognostic markers.

PURPOSE: The cytochromes P450 are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs and biologically active endogenous compounds. The purpose of this study was to define the cytochrome P450 profile of ovarian cancer and identify novel therapeutic targets and establish the prognostic significance of expression of individual cytochrome P450s in this type of cancer. EXPERIMENTAL DESIGN: Immunohistochemistry for a panel of 23 cytochrome P450s and cytochrome P450 reductase was done on an ovarian cancer tissue microarray consisting of 99 primary epithelial ovarian cancers, 22 peritoneal metastasis, and 13 normal ovarian samples. The intensity of immunoreactivity in each sample was established by light microscopy. RESULTS: In primary ovarian cancer, several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP2R1, CYP2U1, CYP3A5, CYP3A7, CYP3A43, CYP4Z1, CYP26A1, and CYP51) were present at a significantly higher level of intensity compared with normal ovary. P450 expression was also detected in ovarian cancer metastasis and CYP2S1 and P450 reductase both showed significantly increased expression in metastasis compared with primary ovarian cancer. The presence of low/negative CYP2A/2B (log rank = 7.06, P = 0.008) or positive CYP4Z1 (log rank = 6.19, P = 0.01) immunoreactivity in primary ovarian cancer were each associated with poor prognosis. Both CYP2A/2B and CYP4Z1 were also independent markers of prognosis. CONCLUSIONS: The expression profile of individual P450s has been established in ovarian cancer. Several P450s show increased expression in ovarian cancer and this provides the basis for developing P450-based therapeutics in ovarian cancer. Expression of CYP2A/2B or CYP4Z1 in primary ovarian cancer were independent markers of prognosis.

Cytochrome P450 enzymes: novel options for cancer therapeutics.

The concept of overexpression of individual forms of cytochrome P450 enzymes in tumor cells is now becoming well recognized. Indeed, a growing body of research highlights the overexpression of P450s, particularly CYP1B1, in tumor cells as representing novel targets for anticancer therapy. The purpose of this review is to outline the novel therapeutic options and opportunities arising from both enhanced endogenous expression of cytochrome P450 in tumors and cytochrome P450-mediated gene therapy.

Quantitative analysis of the Ah receptor/cytochrome P450 CYP1B1/CYP1A1 signalling pathway.

Cytochrome P450 (CYP) drug metabolising enzymes CYP1A1 and CYP1B1 are regulated through the ligand-activated aryl hydrocarbon (Ah) receptor. Differential expression of CYP1A1 and CYP1B1 mRNA and protein has previously been reported in human tissues with the presence of the message often extrapolated to indicate the presence of protein. The aim of this study was to clarify these potentially misleading findings, by analysing components of the Ah receptor pathway (CYP1B1, CYP1A1, Ah receptor and ARNT) using a combination of quantitative real-time RT-PCR and immunoblotting. Three human cell lines (MOG-G-CCM, MCF7 and HEPG2) known to differentially express CYP1A1 and CYP1B1 mRNA and protein were exposed to the Ah receptor agonist 3-MC, and basal and inducible levels of CYP1A1, CYP1B1, Ah receptor and ARNT were determined. The key finding of this study was the demonstration of equivalent levels of CYP1B1 mRNA in both the treated and untreated MOG-G-CCM cell lines, with expression of the corresponding CYP1B1 protein only after exposure to an Ah receptor agonist. This finding suggests that a post-transcriptional mechanism is involved in the regulation of CYP1B1. In addition, the expression pattern of CYP1B1 mRNA and protein in the MOG-G-CCM cells highlights this cell line as a potential model for studying CYP1B1 expression in human tissue.

Cytochrome P450 1B1: a novel anticancer therapeutic target.

Cytochrome P450 (CYP)1B1 is overexpressed in tumor cells and is also recognized as a biomarker of the tumor phenotype. This review highlights the tremendous potential of this enzyme as a novel cancer therapeutic target. The range of therapeutic strategies including immunotherapeutics, CYP1B1-activated prodrugs and CYP1B1 inhibitors, that are currently being developed to exploit the presence and activity of CYP1B1 in tumor cells is outlined. The therapeutic strategy, which is at the most advanced stage of development, is a CYP1B1-based vaccine which has already successfully completed a Phase I clinical trial.

The candidate oncogene ZNF217 is frequently amplified in colon cancer.

In this study we have defined the changes in gene copy number of the candidate oncogene ZNF217 during colon cancer development and progression. This gene is mapped to chromosome 20q and lies within 20q13.2, a region which we have previously shown to be highly amplified in colorectal cancer by comparative genomic hybridization. The gene copy number of ZNF217 was assessed in 100 colon carcinomas (19 Dukes' A, 42 Dukes' B and 39 Dukes' C), 13 colonic adenomas and 10 normal colon samples. DNA extracted from laser microdissected cells was amplified by multiplex real-time PCR at two distinct gene loci--ZNF217 and beta-globin (control gene)--on an ABI7700 sequence detection system. Of the 100 colon cancers studied, 61 showed some level of amplification of ZNF217, 15 had loss of ZNF217, while 24 were diploid. All the adenomas except one were diploid. In this study we have found that ZNF217 amplification is a frequent event in colon cancer and that the extent of its amplification varies markedly between tumours (range 3-13 copies). There was a trend toward poorer survival in patients whose cancers had either gain or loss of ZNF217.