The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

The beliefs which influence young males to speed and strategies to slow them down : informing the content of anti-speeding messages

Young male drivers are over-represented in road-related fatalities. Speeding represents a pervasive and significant contributor to road trauma. Anti-speeding messages represent a long-standing strategy aimed at discouraging drivers from speeding. These messages, however, have not always achieved their persuasive objectives which may be due, in part, to them not always targeting the most salient beliefs underpinning the speeding behavior of particular driver groups. The current study elicited key beliefs underpinning speeding behavior as well as strategies used to avoid speeding, using a well-validated belief-based model, the Theory of Planned Behavior and in-depth qualitative methods. To obtain the most comprehensive understanding about the salient beliefs and strategies of young male drivers, how such beliefs and strategies compared with those of drivers of varying ages and gender, was also explored. Overall, 75 males and females (aged 17-25 or 30-55 years) participated in group discussions. The findings revealed beliefs that were particularly relevant to young males and that would likely represent key foci for developing message content. For instance, the need to feel in control and the desire to experience positive affect when driving were salient advantages; while infringements were a salient disadvantage and, in particular, the loss of points and the implications associated with potential licence loss as opposed to the monetary (fine) loss (behavioral beliefs). For normative influences, young males appeared to hold notable misperceptions (compared with other drivers, such as young females); for instance, young males believed that females/girlfriends were impressed by their speeding. In the case of control beliefs, the findings revealed low perceptions of control with respect to being able to not speed and a belief that something “extraordinary” would need to happen for a young male driver to lose control of their vehicle while speeding. The practical implications of the findings, in terms of providing suggestions for devising the content of anti-speeding messages, are discussed.

Inclusion, schools and anti-discrimination law : parents' experiences and inclusion

With the increasing enrolment of students with disabilities in primary schools and the enactment of legislative protections for students with disabilities in Disability Discrimination legislation and the Disability Standards for Education, this study examines the experiences of parents of students with disabilities in Queensland State schools. This study is concerned with the experiences that parents of children with disabilities have in relation to the concept and processes of inclusive classroom practice within the primary school. The experiences of parents in large metropolitan schools in Queensland, Australia are analysed in light of current anti-discrimination legislation operating within Australia. Data were collected using a mixed methodology in which 50 parents from nine large metropolitan Queensland State schools responded to a Parent Questionnaire about their experiences in their child’s school. This was followed by two focus groups with a total of six parents who described their experiences in their child’s school. Together the qualitative and quantitative information complemented the other to provide a unique perspective on the impact of anti-discrimination legislation. The findings from the study suggest that parents and their children continue to be discriminated against and that the legislation and associated standards have not eliminated this discrimination. Recommendations are made in the final chapter that propose an inclusive schooling framework for students with disabilities. This intends to ensure not only compliance with the ‘spirit’ of Anti-Discrimination legislation and the Disability Standards, but also a means by which schools may evolve to become inclusive and embracing of difference as part of overall richness of schools as opposed to deficiency.

Analysis of the design-construction supply chain in the thermal performance of sub-tropical and tropical housing

Background: In sub-tropical and tropical Queensland, a legacy of poor housing design,minimal building regulations with few compliance measures, an absence of post-construction performance evaluation and various social and market factors has led to a high and growing penetration of, and reliance on, air conditioners to provide thermal comfort for occupants. The pervasive reliance on air conditioners has arguably impacted on building forms, changed cultural expectations of comfort and social practices for achieving comfort, and may have resulted in a loss of skills in designing and constructing high performance building envelopes. Aim: The aim of this paper is to report on initial outcomes of a project that sought to determine how the predicted building thermal performance of twenty-five houses in subtropical and tropical Queensland compared with objective performance measures and comfort performance as perceived by occupants. The purpose of the project was to shed light on the role of various supply chain agents in the realisation of thermal performance outcomes. Methodology: The case study methodology embraced a socio-technical approach incorporating building science and sociology. Building simulation was used to model thermal performance under controlled comfort assumptions and adaptive comfort conditions. Actual indoor climate conditions were measured by temperature and relative humidity sensors placed throughout each house, whilst occupants’ expectations of thermal comfort and their self-reported behaviours were gathered through semi-structured interviews and periodic comfort surveys. Thermal imaging and air infiltration tests, along with building design documents, were analysed to evaluate the influence of various supply chain agents on the actual performance outcomes. Results: The results clearly show that in the housing supply chain – from designer to constructor to occupant – there is limited understanding from each agent of their role in contributing to, or inhibiting, occupants’ comfort.

Isolation of bioactive compounds that relate to the anti-platelet activity of Cymbopogon ambiguus

Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, Eugenol methylether and trans-isoelemicin. While both Eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC(50) value of 46.6 microM, in comparison to aspirin, with an IC(50) value of 46.1 microM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of Headache and Inflammatory conditions.

Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer

We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance

Pten and Ndufb8 aberrations in cervical cancer tissue

Cervical cancer is one of the world's major health issues. Despite many studies in this field, the carcinogenetic events of malignant conversion in cervical tumours have not been significantly characterised. The first aim of this project was to investigate the mutation status of the tumour suppressor gene- Phosphatase and Tension Homolog (PTEN)- in cervical cancer tissue. The second aim of this study was the analysis in the same cervical cancer tissue for aberrations in the mitochondrial electron transport chain subunit gene NDUFB8, which is localised to the same chromosomal contig as PTEN. The third aim was the evaluation of the potential therapeutic anti-cancer drug 2,4-Thiazolidinediones (TZDs) and its affect in regulating the PTEN protein in a cervical cancer cell line (HeLa). To approach the aims, paraffin-embedded cancerous cervical tissue and non-cancerous cervical tissue were obtained. DNA recovered from those tissues was then used to investigate the putative genomic changes regarding the NDUFB8 gene utilising SYBR Green I Real-Time PCR. The PTEN gene was studied via Dual-Labelled probe Real-Time PCR. To investigate the protein expression change of the PTEN protein, HeLa cells were firstly treated with different concentrations of 2,4-Thiazolidinediones and the level of PTEN protein expression was then observed utilising standard protein assays. Results indicated that there were putative copy-number changes between the cancerous cervical tissue and non-cancerous cervical tissue, with regard to the PTEN locus. This implies a potential gain of the PTEN gene in cancerous cervical tissue. With regards to normal cervical tissue versus cancerous cervical tissue no significant melting temperature differences were observed with the SYBR Green I Real-Time PCR in respect to the NDUFB8 gene. A putative up-regulation of PTEN protein was observed in TZD treated HeLa cells. © 2008 Springer Science+Business Media, LLC.

A fuzzy TOPSIS based multi criteria performance measurement model for lean supply chain

Increasing global competition, rapid technological changes, advances in manufacturing and information technology and discerning customers are forcing supply chains to adopt improvement practices that enable them to deliver high quality products at a lower cost and in a shorter period of time. A lean initiative is one of the most effective approaches toward achieving this goal. In the lean improvement process, it is critical to measure current and desired performance level in order to clearly evaluate the lean implementation efforts. Many attempts have tried to measure supply chain performance incorporating both quantitative and qualitative measures but failed to provide an effective method of measuring improvements in performances for dynamic lean supply chain situations. Therefore, the necessity of appropriate measurement of lean supply chain performance has become imperative. There are many lean tools available for supply chains; however, effectiveness of a lean tool depends on the type of the product and supply chain. One tool may be highly effective for a supply chain involved in high volume products but may not be effective for low volume products. There is currently no systematic methodology available for selecting appropriate lean strategies based on the type of supply chain and market strategy This thesis develops an effective method to measure the performance of supply chain consisting of both quantitative and qualitative metrics and investigates the effects of product types and lean tool selection on the supply chain performance Supply chain performance matrices and the effects of various lean tools over performance metrics mentioned in the SCOR framework have been investigated. A lean supply chain model based on the SCOR metric framework is then developed where non- lean and lean as well as quantitative and qualitative metrics are incorporated in appropriate metrics. The values of appropriate metrics are converted into triangular fuzzy numbers using similarity rules and heuristic methods. Data have been collected from an apparel manufacturing company for multiple supply chain products and then a fuzzy based method is applied to measure the performance improvements in supply chains. Using the fuzzy TOPSIS method, which chooses an optimum alternative to maximise similarities with positive ideal solutions and to minimise similarities with negative ideal solutions, the performances of lean and non- lean supply chain situations for three different apparel products have been evaluated. To address the research questions related to effective performance evaluation method and the effects of lean tools over different types of supply chains; a conceptual framework and two hypotheses are investigated. Empirical results show that implementation of lean tools have significant effects over performance improvements in terms of time, quality and flexibility. Fuzzy TOPSIS based method developed is able to integrate multiple supply chain matrices onto a single performance measure while lean supply chain model incorporates qualitative and quantitative metrics. It can therefore effectively measure the improvements for supply chain after implementing lean tools. It is demonstrated that product types involved in the supply chain and ability to select right lean tools have significant effect on lean supply chain performance. Future study can conduct multiple case studies in different contexts.

Examining gender differences in drivers' thoughts and feelings about different outcomes of speeding: Implications for future anti-speeding messages

Speeding remains a pervasive road safety problem, increasing both crash frequency and severity. Advertising countermeasures which aim to change individuals’ attitudes and behaviours are a key component in the array of countermeasures aimed at reducing this risky behaviour. Enhancing individuals’ perceptions of the personal relevance of such messages is important for increasing persuasiveness. This study examined what males and females reported as the most concerning aspects associated with (i) receiving a speeding fine, (ii) losing one’s license, and (iii) being involved in a crash. For each of these outcomes, a range of specific and appropriate aspects were assessed. For instance, in relation to receiving a fine, individuals reported the extent to which they would, for example, feel concerned about losing demerit points and paying more in insurance premiums. An online survey of 751 drivers (579 males; 16-79 years) was administered. When controlling for age, overall significant gender differences were found in relation to two of the three outcomes; receiving a fine and being in a crash. Follow-up tests of univariate effects revealed that females consistently reported being significantly more concerned than males on all aspects. Thus, for being fined, females were significantly more concerned with, for example, being caught and receiving a ticket in the mail; while, for being in a crash, specific aspects included, for example, injuring/killing oneself and seeing oneself as not a good/safe driver. The findings are discussed in terms of their implications for developing well-targeted messages aimed at discouraging drivers from speeding.

IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF

Background IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. Methods The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. Results The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p < 0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p < 0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. Conclusions This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment. © 2011 Elsevier Ltd. All rights reserved.

Gemcitabine reactivates epigenetically silenced genes and functions as a DNA methyltransferase inhibitor

Gemcitabine is indicated in combination with cisplatin as first-line therapy for solid tumours including non-small cell lung cancer (NSCLC), bladder cancer and mesothelioma. Gemcitabine is an analogue of pyrimidine cytosine and functions as an anti-metabolite. Structurally, however, gemcitabine has similarities to 5-aza-2-deoxycytidine (decitabine/Dacogen®), a DNA methyltransferase inhibitor (DNMTi). NSCLC, mesothelioma and prostate cancer cell lines were treated with decitabine and gemcitabine. Reactivation of epigenetically silenced genes was examined by RT-PCR/qPCR. DNA methyltransferase activity in nuclear extracts and recombinant proteins was measured using a DNA methyltransferase assay, and alterations in DNA methylation status were examined using methylation-specific PCR (MS-PCR) and pyrosequencing. We observe a reactivation of several epigenetically silenced genes including GSTP1, IGFBP3 and RASSF1A. Gemcitabine functionally inhibited DNA methyltransferase activity in both nuclear extracts and recombinant proteins. Gemcitabine dramatically destabilised DNMT1 protein. However, DNA CpG methylation was for the most part unaffected by gemcitabine. In conclusion, gemcitabine both inhibits and destabilises DNA methyltransferases and reactivates epigenetically silenced genes having activity equivalent to decitabine at concentrations significantly lower than those achieved in the treatment of patients with solid tumours. This property may contribute to the anticancer activity of gemcitabine.

Molecular approaches to diagnosis and management of ovarian cancer

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.