Brain and behavior in health communication: The Canadian COVID-19 Experiences Project.

Background: Vaccine hesitancy and inconsistent mitigation behavior performance have been significant challenges throughout the COVID-19 pandemic. In Canada, despite relatively high vaccine availability and uptake, willingness to accept booster shots and maintain mitigation behaviors in the post-acute phase of COVID-19 remain uncertain. The aim of the Canadian COVID-19 Experiences Project (CCEP) is threefold: 1) to identify social-cognitive and neurocognitive predictors of mitigation behaviors, 2) to identify optimal communication strategies to promote vaccination and mitigation behaviors, and 3) to examine brain health outcomes of SARS-CoV-2 infection and examine their longevity. Methods: The CCEP is comprised of two components: a conventional population survey (Study 1) and a functionally interconnected laboratory study (Study 2). Study 1 will involve 6 waves of data collection. Wave 1, completed between 28 September and 21 October 2021, recruited 1,958 vaccine-hesitant (49.8%) and fully vaccinated (50.2%) adults using quota sampling to ensure maximum statistical power. Measures included a variety of social cognitive (e.g., beliefs, intentions) and neurocognitive (e.g., delay discounting) measures, followed by an opportunity to view and rate a set of professionally produced COVID-19 public service announcement (PSA) videos for perceived efficacy. Study 2 employs the same survey items and PSAs but coupled with lab-based eye tracking and functional near-infrared spectroscopy (fNIRS) to directly quantify neural indicators of attention capture and self-reflection in a smaller community sample. In the final phase of the project, subjective impressions and neural indicators of PSA efficacy will be compared and used to inform recommendations for construction of COVID-19 PSAs into the post-acute phase of the pandemic. Discussion: The CCEP provides a framework for evaluating effective COVID-19 communication strategies by levering conventional population surveys and the latest eye-tracking and brain imaging metrics. The CCEP will also yield important information about the brain health impacts of SARS-CoV-2 in the general population, in relation to current and future virus variants as they emerge.

The Predictive Utility of Valuing the Future for Smoking Cessation: Findings from the ITC 4 Country Surveys.

BACKGROUND: Delay discounting (DD) and time perspective (TP) are conceptually related constructs that are theorized as important determinants of the pursuit of future outcomes over present inclinations. This study explores their predictive relationships for smoking cessation. METHODS: 5006 daily smokers at a baseline wave provided 6710 paired observations of quitting activity between two waves. Data are from the International Tobacco Control (ITC) smoking and vaping surveys with samples from the USA, Canada, England, and Australia, across three waves conducted in 2016, 2018 and 2020. Smokers were assessed for TP and DD, plus smoking-specific predictors at one wave of cessation outcomes defined as either making a quit attempt and/or success among those who tried to quit which was ascertained at the subsequent survey wave. RESULTS: TP and DD were essentially uncorrelated. TP predicted making quit attempts, both on its own and controlling for other potential predictors but was negatively associated with quit success. By contrast, DD was not related to making quit attempts, but high DD predicted relapse. The presence of financial stress at baseline resulted in some moderation of effects. CONCLUSIONS: Understanding the mechanisms of action of TP and DD can advance our understanding of, and ability to enhance, goal-directed behavioural change. TP appears to contribute to future intention formation, but not necessarily practical thought of how to achieve goals. DD is more likely an index of capacity to effectively generate competing future possibilities in response to immediate gratification.

Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40-AS1 increases with disease progression. BHLHE40-AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40-AS1 modulates interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer-binding factor 3. These data suggest that BHLHE40-AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune-permissive microenvironment.

Time Perspective and All-Cause Mortality: Evidence From the English Longitudinal Study of Ageing.

BACKGROUND: Long-term future thinking has been associated with a range of favorable health behaviors. However, it is currently unclear whether this translates into an effect on morbidity and mortality. PURPOSE: The goal of this study was to study the relationship between time perspective and all-cause mortality and to examine the role of health behavior in explaining this association. METHODS: Participants (N = 9,949) aged 50 and over from the English Longitudinal Study of Ageing, a representative cohort of older English adults, estimated the length of their time horizon for financial planning (time perspective). Two thousand ninety-two deaths were recorded over a 9-year follow-up period (2002/2003-2012). Smoking, physical activity, and alcohol consumption were examined as factors that may underlie the time perspective-mortality link. RESULTS: Our prospective survival analyses showed that those who tend to plan for longer periods experienced a significantly reduced risk of all-cause mortality (HR = 0.83; 95% confidence interval [CI]: [0.80, 0.87], p < .001 per 1 SD increase in future time perspective). This association remained after adjusting for baseline socioeconomic status and health (HR = 0.92; 95% CI: [0.88, 0.97], p < .001). The link between time perspective and mortality was observed across the gradient of financial circumstances and did not appear to be due to reverse causality. Healthy behavior among the more future orientated explained 34% of the link between time perspective and mortality. CONCLUSIONS: Using a simply administered indicator of time perspective, this study suggests that a future-orientated time perspective may be an important predictor of reduced risk of death.

Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo.

Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans.

Prevention Neuroscience: A new frontier for preventive medicine.

Prevention neuroscience may be defined as follows: an interdisciplinary field concerned with the neurobiological factors that influence susceptibility to preventable disease, disability or mortality. It includes, but is not limited to: examination of brain health as an outcome, brain activity as a predictor of health outcomes, brain structures/systems as causal determinants of health outcomes (e.g., health behaviours), and the brain as a mediator of other causal influences (e.g., social conditions) on health outcomes. This commentary describes concepts, theory and research illustrating each of these scenarios using exercise, smoking cessation, dietary behaviour, and health disparities as examples. It is argued that neuroscience may provide both concepts and methods that may be possible (even fruitful) to incorporate into preventive medicine research and health promotion practise. Although public health practitioners and cognitive neuroscientists have not traditionally crossed paths outside of the context of neurodegenerative diseases such as Alzheimer's and other dementias, it is easy to envision a future where many common disease prevention activities involve collaboration between the two disciplines, and the cache of tools available to the preventive medicine expert includes neuroimaging and neuromodulation techniques.

Time perspective as a determinant of smoking cessation in four countries: Direct and mediated effects from the International Tobacco Control (ITC) 4-Country Surveys.

BACKGROUND: Future oriented time perspective predicts a number of important health behaviors and outcomes, including smoking cessation. However, it is not known how future orientation exerts its effects on such outcomes, and no large scale cross-national studies have examined the question prospectively. The aim of the current investigation was to examine the relationship between time perspective and success in smoking cessation, and social cognitive mediators of the association. METHODS: The ITC-4 is a multi-wave, four country survey (Australia, Canada, United States, United Kingdom) of current smokers (N=9772); the survey includes baseline measurements of time perspective, intentions, quit attempts, and self-reported quit status at follow-up over 8 years. We examined the predictive power of time perspective for smoking cessation, as mediated through strength of quit intentions and prior history of quit attempts. RESULTS: Findings indicated that those smokers with a stronger future orientation at baseline were more likely to have successfully quit at follow-up. This effect was partially explained by intention-mediated effects of future orientation on quit attempts. CONCLUSIONS: Future orientation predicts smoking cessation across four English-speaking countries; the cessation-facilitating effects of future orientation may be primarily due to future oriented individuals' motivated and sustained involvement in the quit cycle over time.

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats.

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/µCT imaging. GSK-3 inhibitors caused ß-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH1-34 or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/µCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption.

Inhibition of platelet-derived growth factor receptor α by MEDI-575 reduces tumor growth and stromal fibroblast content in a model of non-small cell lung cancer.

Platelet-derived growth factor receptor α (PDGFRα) is a receptor tyrosine kinase that promotes cell survival and is expressed in both the tumor and the stromal components of human cancers. We have developed a fully human monoclonal antibody, MEDI-575, that selectively binds to human PDGFRα with high affinity, with no observable affinity for murine PDGFRα. To more fully characterize the role of PDGFRα in the regulation of tumor stroma, we evaluated the in vivo antitumor effects of MEDI-575 in tumor-bearing severe combined immunodeficient (SCID) mice and in genetically altered SCID mice expressing human PDGFRα in place of murine PDGFRα. We used the Calu-6 non-small cell lung cancer model because it lacks an in vitro proliferative response to PDGFRα activation. Antitumor activity was observed when the study was performed in mice expressing the human receptor, but no activity was observed in the mice expressing the murine receptor. Immunohistologic analysis of the tumors from mice expressing human PDGFRα showed a highly significant reduction in stromal fibroblast content and only minor changes in tumor proliferative index in tumors exposed to MEDI-575 compared with the results seen in vehicle-treated tumors or in tumors from mice expressing murine PDGFRα. Additional in vitro studies indicated that exposure of primary cancer-associated fibroblasts to MEDI-575 can directly affect proliferation and key signaling pathways in these cells. These results highlight the potential for observing antitumor activity with MEDI-575 through modulation of the stromal component of tumors and confirm that the PDGFRα pathway can play a role in maintaining a tumor microenvironment conducive to tumor growth.

Time perspective as a predictor of smoking status: findings from the International Tobacco Control (ITC) Surveys in Scotland, France, Germany, China, and Malaysia.

BACKGROUND: Prior studies have demonstrated that time perspective-the propensity to consider short-versus long-term consequences of one's actions-is a potentially important predictor of health-related behaviors, including smoking. However, most prior studies have been conducted within single high-income countries. The aim of this study was to examine whether time perspective was associated with the likelihood of being a smoker or non-smoker across five countries that vary in smoking behavior and strength of tobacco control policies. METHODS: The data were from the International Tobacco Control (ITC) Surveys in five countries with large probability samples of both smokers (N=10,341) and non-smokers (N=4,955): Scotland, France, Germany, China, and Malaysia. The surveys were conducted between 2005-2008. Survey respondents indicated their smoking status (smoker vs. non-smoker) and time perspective (future oriented vs. not future-oriented) and provided demographic information. RESULTS: Across all five countries, non-smokers were significantly more likely to be future-oriented (66%) than were smokers (57%), χ(2)(1, N = 15,244) = 120.64, p < .001. This bivariate relationship between time perspective and smoking status held in a multivariate analysis. After controlling for country, age, sex, income, education, and ethnicity (language in France), those who were future-oriented had 36% greater odds of being a non-smoker than a smoker (95% CI: 1.22 to 1.51, p<.001). CONCLUSION: These findings establish time perspective as an important predictor of smoking status across multiple countries and suggest the potential value of incorporating material to enhance future orientation in smoking cessation interventions.

Do time perspective and sensation-seeking predict quitting activity among smokers? Findings from the International Tobacco Control (ITC) Four Country Survey.

Personality factors such as time perspective and sensation-seeking have been shown to predict smoking uptake. However, little is known about the influences of these variables on quitting behavior, and no prior studies have examined the association cross-nationally in a large probability sample. In the current study it was hypothesized that future time perspective would enhance - while sensation-seeking would inhibit - quitting activity among smokers. It was anticipated that the effects would be similar across English speaking countries. Using a prospective cohort design, this cross-national study of adult smokers (N=8845) examined the associations among time perspective, sensation-seeking and quitting activity using the first three waves of data gathered from the International Tobacco Control Four Country Survey (ITC-4), a random digit dialed telephone survey of adult smokers from the United Kingdom, United States, Canada and Australia. Findings revealed that future time perspective (but not sensation-seeking) was a significant predictor of quitting attempts over the 8-month follow-up after adjusting for socio-demographic variables, factors known to inhibit quitting (e.g., perceived addiction, enjoyment of smoking, and perceived value of smoking), and factors known to enhance quitting (e.g., quit intention strength, perceived benefit of quitting, concerns about health effects of smoking). The latter, particularly intention, were significant mediators of the effect of time perspective on quitting activity. The effects of time perspective on quitting activity were similar across all four English speaking countries sampled. If these associations are causal in nature, it may be the case that interventions and health communications that enhance future-orientation may foster more quit attempts among current smokers.

Expression of the SEPT9_i4 isoform confers resistance to microtubule-interacting drugs.

BACKGROUND: The evolutionarily conserved septin family of genes encode GTP binding proteins involved in a variety of cellular functions including cytokinesis, apoptosis, membrane dynamics and vesicle trafficking. Septin proteins can form hetero-oligomeric complexes and interact with other proteins including actin and tubulin. The human SEPT9 gene on chromosome 17q25.3 has a complex genomic architecture with 18 different transcripts that can encode 15 distinct polypeptides. Two distinct transcripts with unique 5' ends (SEPT9_v4 and SEPT9_v4*) encode the same protein. In tumours the ratio of these transcripts changes with elevated levels of SEPT9_v4* mRNA, a transcript that is translated with enhanced efficiency leading to increased SEPT9_i4 protein. METHODS: We have examined the effect of over-expression of SEPT9_i4 on the dynamics of microtubule polymer mass in cultured cells. RESULTS: We show that the microtubule network in SEPT9_i4 over-expressing cells resists disruption by paclitaxel or cold incubation but also repolymerises tubulin more slowly after microtubule depolymerisation. Finally we show that SEPT9_i4 over-expressing cells have enhanced survival in the presence of clinically relevant microtubule acting drugs but not after treatment with DNAinteracting agents. CONCLUSIONS: Given that SEPT9 over-expression is seen in diverse tumours and in particular ovarian and breast cancer, such data indicate that SEPT9_v4 expression may be clinically relevant and contribute to some forms of drug resistance.

Mammalian septins: dynamic heteromers with roles in cellular morphogenesis and compartmentalization.

The septins are a family of GTP-binding proteins, evolutionarily conserved from yeast through to mammals, with roles in multiple core cellular functions. Here we provide an overview of our current knowledge of septin structure and function and focus mainly on mammalian septins, but gain much insight by drawing on knowledge of septins in other organisms. We describe their genomic and transcriptional complexity: a complexity manifest also in the diversity of scaffold structures that septins can form. Septin complexes can act to localize interacting proteins at specific intracellular locales and can also define membrane compartments by defining diffusion barriers. By such activities, septins can contribute to the definition of spatial asymmetry and cell polarity and we suggest a potential role in stem cell biology. Finally, we review the evidence that septins contribute to various disease states and argue that it is a breakdown in the tight regulation of their expression (particularly of individual isoforms), and also their inherent ability to oligomerize, which is pathogenic. Study of the perturbation of septin complex formation in disease will provide valuable insights into septin biology and will be a fertile ground for study.

Time perspective and weight management behaviors in newly diagnosed Type 2 diabetes: a mediational analysis.

The primary objective of the current study was to examine the extent to which domain-specific time perspective predicts weight management behaviors (dietary behavior and physical activity) among those newly diagnosed with Type 2 diabetes. A secondary objective was to test potential mediators of the hypothesized effect (behavioral intention, self-efficacy and control beliefs). A total of 204 adults newly diagnosed (≤6 months) with Type 2 diabetes participated in the study, which included a baseline assessment of domain-general and domain-specific time perspective, as well as strength of intention to perform two weight-management behaviors (dietary choice and physical activity); both weight-management behaviors were assessed again at 6 month follow-up. Hierarchical multiple regression analyses revealed a prospective association between domain-specific time perspective and uptake of weight management behaviors. Individuals with newly diagnosed T2DM possessing a future-oriented time perspective reported making less frequent fatty food choices and greater increases in physical activity over the 6-month follow-up interval. These effects were selectively mediated by intention strength, and not competing social cognitive variables. For both behaviors, the total effects and meditational models were robust to adjustments for demographics, body composition and disease variables. A future-oriented time perspective is prospectively associated with superior uptake of weight management behaviors among those with newly diagnosed Type 2 diabetes. The facilitating effect of future-oriented thinking appears to occur via enhanced strength of intentions to perform weight management behaviors.

An introduction to genes, genomes and disease.

The human and other genome projects and subsequent resequencing programmes have provided new perspectives on the nature of the gene and how genes function. Understanding the complexity of the eukaryotic nucleus and the diversity of genetic regulatory mechanisms, including the role of non-coding RNAs, translational control mechanisms and the extraordinary prevalence of splicing, will be central to understanding how genes function, as will the recognition of gene dosage issues. This introduction to the 2010 Annual Review Issue, Genes, Genomes and Disease, provides overviews of these areas and then considers their relevance to a range of human diseases, including cardiovascular and renal disease, neural tube defects and cancer. The p53 gene is considered as an example of a massively regulated gene and the genetic perturbations in cancer are considered in a historical perspective. High-throughput genomic and transcriptomic methods have led to a paradigm shift in the way cancers are perceived and have changed the way translational research is performed. The progress in our understanding of chromosomal rearrangements in cancer, once believed to be incredibly rare events in epithelial malignancies, is discussed. The identification of low-penetrance cancer susceptibility genes through genome-wide association studies and their implications are reviewed. The contribution and limitations of expression profiling are discussed. In the last series of reviews, future challenges are addressed: the promise of synthetic lethality strategies in cancer therapy, a case for 'systems' approaches to genetic networks and the potential of single molecule genetic technologies. Finally, the question 'Does massively parallel DNA resequencing signify the end of histopathology as we know it?' is posed. Readers should find that the 2010 Annual Review Issue is an invaluable resource on contemporary genetics and its applications to understanding disease.

The Journal of Pathology 2008 Jeremy Jass Prize for Research Excellence in Pathology.

The first Jass Prize for Research Excellence has been awarded to a group from Hannover in Germany. These authors discovered the epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer and characterized its biological and clinical relevance. This frequent epigenetic silencing was found to occur early in the development of breast cancer, and illustrates another mechanism by which tumour development is influenced by genes that operate without expression as proteins.

Executive function moderates the intention-behavior link for physical activity and dietary behavior.

Dominant theories of health behavior posit that social-cognitive and conative variables are sufficient to explain health behavior tendencies. The current studies challenge this assumption in two ways: (1) by demonstrating that unique variance in health protective behavior is predictable by knowing about individual differences in executive functioning, and (2) by demonstrating that executive function moderates the association between intention and behavior. In Studies 1 and 2, participants completed a computer-based task of executive function (Go/NoGo task) and articulated 1-week behavioral intentions for physical activity (Study 1) and dietary behavior (Study 2). Hierarchical regression analyses revealed that executive function predicts unique variance in both behaviors, and strongly moderates the association between behavioral intention and behavioral performance. Together behavioral intention and executive function explain more variance in health protective behavior than 'rational actor' models that have been widely adopted and disseminated.

Translational control of SEPT9 isoforms is perturbed in disease.

A common feature of the mammalian septin gene family is complex genomic architecture with multiple alternate splice variants. Septin 9 has 18 distinct transcripts encoding 15 polypeptides, with two transcripts (SEPT9_v4 and v4*) encoding the same polypeptide. We have previously reported that the ratio of these distinct transcripts is altered in neoplasia, with the v4 transcript being the usual form in normal cells but v4* becoming predominant in tumours. This led us to ask what the functional differences between these two transcripts might be. The 5'-UTRs of v4 and v4* have distinct 5' ends encoded by exons 1beta (v4) and 1zeta and 2 (v4*) and a common 3' region and initiating ATG encoded within exon 3. Here we show that the two mRNAs are translated with different efficiencies and that cellular stress can alter this. A putative internal ribosome entry site can be identified in the common region of the v4 and v4* 5'-UTRs and translation is modulated by an upstream open-reading frame in the unique region of the v4 5'-UTR. Germline mutations in hereditary neuralgic amyotrophy (HNA) map to the region which is common to the two UTRs. These mutations dramatically enhance the translational efficiency of the v4 5'-UTR, leading to elevated SEPT9_v4 protein under hypoxic conditions. Our data provide a mechanistic insight into how the HNA mutations can alter the fine control of SEPT9_v4 protein and its regulation under physiologically relevant conditions and are consistent with the episodic and stress-induced nature of the clinical features of HNA.

Changed times at Hematological Oncology.

This editorial describes the changes to Hematological Oncology over the past 12 months and redefines the scope and the goals of the journal. As well as changes in format, an electronic manuscript submission system and a stringent peer-review policy (outlined here) have been implemented. The journal is a vehicle for high-quality articles in the broad field of experimental and clinical hematological oncology, and a medium for the publication of translational research. As well as submitted material, the journal solicits and publishes high-quality reviews from leading experts.

Altered patterns of transcription of the septin gene, SEPT9, in ovarian tumorigenesis.

Ovarian carcinoma represents the most lethal gynaecological malignancy. A variety of morphological subtypes are recognised (e.g. serous, mucinous, endometrioid), which may be benign, borderline or malignant. While their relationship is controversial, knowledge of the molecular mechanisms of ovarian tumorigenesis may help resolve this issue and perhaps identify early markers of disease. Perturbed patterns of expression of the SEPT9 gene on chromosome 17q25.3 have been implicated in a variety of tumour types including both breast and ovarian neoplasia. In preliminary studies, we showed that SEPT9 mRNA was upregulated in a bank of ovarian tumours, which included benign, borderline and malignant tumours, and reported increased levels of one splice variant, SEPT9_v4*. We now describe a comprehensive analysis of SEPT9 expression specifically in serous and mucinous ovarian tumours (benign, borderline and malignant), using cDNA microarray, semi- and quantitative RTPCR of microdissected archival tumour material. Our data show consistent and specific overexpression of both SEPT9_v1 and SEPT9_v4* transcripts in the epithelial component of ovarian tumours. These transcripts show highest levels of expression in serous and mucinous borderline tumours. SEPT9_v1 is also upregulated in both serous and mucinous carcinomas. Interestingly, highest levels of expression are observed in serous borderline and low-grade tumours rather than high-grade in keeping with a model of progression of benign, borderline and low-grade serous tumours.