Flinders Centre for Innovation in Cancer Collected Works
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ItemNon-Coding RNA Journal Club: Highlights on Recent Papers—7(MDPI, 2019-06-11)We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently. We hope to keep you up-to-date with non-coding RNA research works that are outside your study area. The Non-Coding RNA Scientific Board wishes you an exciting and fruitful read.
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ItemmiR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking(EMBO Press/Wiley, 2018-06-05)Members of the miR‐200 family are critical gatekeepers of the epithelial state, restraining expression of pro‐mesenchymal genes that drive epithelial–mesenchymal transition (EMT) and contribute to metastatic cancer progression. Here, we show that miR‐200c and another epithelial‐enriched miRNA, miR‐375, exert widespread control of alternative splicing in cancer cells by suppressing the RNA‐binding protein Quaking (QKI). During EMT, QKI‐5 directly binds to and regulates hundreds of alternative splicing targets and exerts pleiotropic effects, such as increasing cell migration and invasion and restraining tumour growth, without appreciably affecting mRNA levels. QKI‐5 is both necessary and sufficient to direct EMT‐associated alternative splicing changes, and this splicing signature is broadly conserved across many epithelial‐derived cancer types. Importantly, several actin cytoskeleton‐associated genes are directly targeted by both QKI and miR‐200c, revealing coordinated control of alternative splicing and mRNA abundance during EMT. These findings demonstrate the existence of a miR‐200/miR‐375/QKI axis that impacts cancer‐associated epithelial cell plasticity through widespread control of alternative splicing.
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ItemDemand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal Immunochemical Test and Age-Sex-Specific Thresholds for Test Positivity(Elsevier, 2018-06)Background: Despite age and sex differences in fecal hemoglobin (f-Hb) concentrations, most fecal immunochemical test (FIT) screening programs use population-average cut-points for test positivity. The impact of age/sex-specific threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening are unknown. Methods: Using data from 723,113 participants enrolled in a Taiwanese population-based colorectal cancer screening with single FIT between 2004 and 2009, sensitivity and specificity were estimated for various f-Hb thresholds for test positivity. This included estimates based on a “universal” threshold, receiver-operating-characteristic curve–derived threshold, targeted sensitivity, targeted false-positive rate, and a colonoscopy-capacity-adjusted method integrating colonoscopy workload with and without age/sex adjustments. Results: Optimal age/sex-specific thresholds were found to be equal to or lower than the universal 20 μg Hb/g threshold. For older males, a higher threshold (24 μg Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear relationship was observed between sensitivity and colonoscopy workload with workload rising disproportionately to sensitivity at 16 μg Hb/g. At this “colonoscopy-capacity-adjusted” threshold, the test positivity (colonoscopy workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0% workload and a lower 78.7% sensitivity using 20 μg Hb/g. When constrained on capacity, age/sex-adjusted estimates were generally lower. However, optimizing age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or greater compared with a universal threshold. Conclusions: Age/sex-specific thresholds improve FIT accuracy with modest increases in colonoscopy demand. Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds may be useful in optimizing individual screening programs based on detection accuracy, population characteristics, and clinical capacity
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ItemHealth-Related Quality of Life among Women Breast Cancer Patients in Eastern China(Hindawi, 2018-07-03)Objectives. Breast cancer is one of the major cancers in Chinese women. European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-BR23) are now the most common and well developed instruments assessing the health-related quality of life (HRQOL) of breast cancer patients internationally, whereas there are relatively few Chinese studies. This study has two aims: to investigate the HRQOL and explore which dimensions of HRQOL play more important roles in breast cancer patients’ overall quality of life in China and to explore the latent factor structure and the potential complementary relationship between these two EORTC questionnaires. Methods. This cross-sectional and descriptive study was performed from October 2014 to February 2015 in Qingdao Municipal Hospital, China. A total of 621 women breast cancer patients were enrolled. EOTRC QLQ-C30 and QLQ-BR23 were used to evaluate the HRQOL of the participants. The nonparametric test, multiple linear regression, and exploratory factor analysis (EFA) were the main statistical methods we used. Results. 608 participants completed the questionnaires with a response rate of 97.9%. The mean age of the participants was 48.0 years (SD=9.6). About 33% were illiterate or only finished primary school education. Almost half participants (47.4%) only adopted chemotherapy. HRQOL was significantly different with regard to patients’ social-demographic and clinical characteristics. Age, residence, educational level, employment status, and TNM stage were five significant predictors for global health status. Pain, dyspnea, sexual enjoyment, and systemic therapy side-effect were main subscales which had a significant impact on the global health status for patients in different TNM stage. The EFA result suggested that QLQ-C30 and QLQ-BR23 were complementary questionnaires. Conclusions. The EORTC QLQ-C30 and QLQ-BR23 questionnaires provide complementary information regarding breast cancer patients’ HRQOL, and depending on the different cancer staging functional/symptom scales which significantly contributed to the overall HRQOL differed.
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ItemPrevalence, perceptions and predictors of alcohol consumption and abstinence among South Australian school students: a cross-sectional analysis(BioMed Central, 2017-06-07)Background Alcohol consumption by young people (particularly early initiation) is a predictor for poorer health in later life. In addition, evidence now clearly shows a causal link between alcohol and cancer. This study investigated prevalence, predictors of alcohol consumption among adolescents including perceptions of the link between alcohol and cancer, and the role of parents and peers. Methods A sample of Australian school students aged 12–17 years participated in a survey (n = 2885). Logistic regression analysis was undertaken to determine predictors. Results Alcohol use increased with age and by 16, most had tried alcohol with 33.1% of students aged 12–17 reporting that they drank at least occasionally (95% CI = 31.0–35.2). Awareness of the link between alcohol and cancer was low (28.5%). Smoking status and friends’ approval were predictive of drinking, whereas parental disapproval was protective. Those aged 14–17 who did not think the link between alcohol and cancer was important were more likely to drink, as were those living in areas of least disadvantage. The only factors that predicted recent drinking were smoking and the perception that alcohol was easy to purchase. Conclusions An education campaign highlighting the link between alcohol and cancer may have positive flow-on effects for young people, and schools should incorporate this messaging into any alcohol education programs. Consideration should be given to factors that serve to regulate under-aged accessibility of alcohol.
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ItemExploring the Potential of Anticipated Regret as an Emotional Cue to Improve Bowel Cancer Screening Uptake(Hindawi Publishing Corporation, 2017-02-02)Objective. Bowel cancer is currently the second leading cause of cancer-related death in Australia and screening participation is suboptimal. This study examined the role of emotion in the form of anticipated regret (AR) and its relationship to screening intentions. Methods. N=173 persons aged 45 to 80 years completed a survey measuring demographic variables, readiness to screen, relative importance of health by comparison to other life priorities, satisfaction with current health, and AR if not participating in future bowel cancer screening. Results. AR was a significant predictor of future screening intentions. Those with higher levels of AR were seven times more likely (OR = 7.18) to intend to screen in the future compared to those with lower AR. This relationship was not compromised when controlling for other variables including gender and satisfaction with one’s health. AR levels were significantly lower in people who had been screened previously and in those with full health insurance. Conclusions. These results demonstrate that AR is uniquely related to future bowel cancer screening intentions. Future studies should continue to consider this as a useful target for behavioural interventions and identify new ways of delivering these interventions to improve their reach.
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