Flinders Centre for Innovation in Cancer Collected Works

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    Non-Coding RNA Journal Club: Highlights on Recent Papers—7
    (MDPI, 2019-06-11) Xiao, Hua; Shiu, Patrick K T; Gabryleska, Marta; Conn, Simon; Dey, Abhishek; Chakrabarti, Kausik; Regouc, Manuel; Pichler, Martin; Orom, Ulf Andersson Vang; Santulli, Gaetano; Nishiwada, Satoshi; Goel, Ajay; Nagarajan, Vaishnavi; Timmons, Lisa; Alahari, Suresh K; Laprovitera, Noemi; Ferracin, Manuela; Hu, Po; Jin, Hailing
    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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    miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking
    (EMBO Press/Wiley, 2018-06-05) Pillman, Katherine A; Phillips, Caroline A; Roslan, Suraya; Toubia, John; Dredge, B Kate; Bert, Andrew G; Lumb, Rachael; Neumann, Daniel P; Li, Xiaochun; Conn, Simon; Liu, Dawei; Bracken, Cameron P; Lawrence, David M; Stylianou, Nataly; Schreiber, Andreas W; Tilley, Wayne D; Hollier, Brett G; Khew-Goodall, Yeesim; Selth, Luke A; Goodall, Gregory J; Gregory, Philip A
    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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    Demand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal Immunochemical Test and Age-Sex-Specific Thresholds for Test Positivity
    (Elsevier, 2018-06) Chen, Sam Li-Sheng; Hsu, Chen-Yang; Yen, Amy Ming-Fang; Young, Graeme Paul; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Lee, Yi-Chia; Chiu, Han-Mo; Chiou, Shu-Ti; Chen, Hsiu-Hsi
    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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    Health-Related Quality of Life among Women Breast Cancer Patients in Eastern China
    (Hindawi, 2018-07-03) Chen, Qing; Li, Shunping; Wang, Min; Liu, Liu; Chen, Gang
    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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    Prevalence, perceptions and predictors of alcohol consumption and abstinence among South Australian school students: a cross-sectional analysis
    (BioMed Central, 2017-06-07) Bowden, Jacqueline A; Delfabbro, Paul; Miller, Caroline; Wilson, Carlene J
    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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    Exploring the Potential of Anticipated Regret as an Emotional Cue to Improve Bowel Cancer Screening Uptake
    (Hindawi Publishing Corporation, 2017-02-02) Zajac, Ian; Duncan, Amy; Freegard, Suzana; Wilson, Carlene J; Flight, Ingrid; Turnbull, Deborah
    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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    In vitro inhibitory activities of selected Australian medicinal plant extracts against protein glycation, angiotensin converting enzyme (ACE) and digestive enzymes linked to type II diabetes
    (BioMed Central, 2016-11-04) Deo, P; Hewawasam, E; Karakoulakis, A; Claudie, D J; Nelson, R; Simpson, Bradley S; Smith, N M; Semple, S J
    Background There is a need to develop potential new therapies for the management of diabetes and hypertension. Australian medicinal plants collected from the Kuuku I’yu (Northern Kaanju) homelands, Cape York Peninsula, Queensland, Australia were investigated to determine their therapeutic potential. Extracts were tested for inhibition of protein glycation and key enzymes relevant to the management of hyperglycaemia and hypertension. The inhibitory activities were further correlated with the antioxidant activities. Methods Extracts of five selected plant species were investigated: Petalostigma pubescens, Petalostigma banksii, Memecylon pauciflorum, Millettia pinnata and Grewia mesomischa. Enzyme inhibitory activity of the plant extracts was assessed against α-amylase, α-glucosidase and angiotensin converting enzyme (ACE). Antiglycation activity was determined using glucose-induced protein glycation models and formation of protein-bound fluorescent advanced glycation endproducts (AGEs). Antioxidant activity was determined by measuring the scavenging effect of plant extracts against 1, 1-diphenyl-2-picryl hydrazyl (DPPH) and using the ferric reducing anti-oxidant potential assay (FRAP). Total phenolic and flavonoid contents were also determined. Results Extracts of the leaves of Petalostigma banksii and P. pubescens showed the strongest inhibition of α-amylase with IC50 values of 166.50 ± 5.50 μg/mL and 160.20 ± 27.92 μg/mL, respectively. The P. pubescens leaf extract was also the strongest inhibitor of α-glucosidase with an IC50 of 167.83 ± 23.82 μg/mL. Testing for the antiglycation potential of the extracts, measured as inhibition of formation of protein-bound fluorescent AGEs, showed that P. banksii root and fruit extracts had IC50 values of 34.49 ± 4.31 μg/mL and 47.72 ± 1.65 μg/mL, respectively, which were significantly lower (p < 0.05) than other extracts. The inhibitory effect on α-amylase, α-glucosidase and the antiglycation potential of the extracts did not correlate with the total phenolic, total flavonoid, FRAP or DPPH. For ACE inhibition, IC50 values ranged between 266.27 ± 6.91 to 695.17 ± 15.38 μg/mL. Conclusions The tested Australian medicinal plant extracts inhibit glucose-induced fluorescent AGEs, α-amylase, α-glucosidase and ACE with extracts of Petalostigma species showing the most promising activity. These medicinal plants could potentially be further developed as therapeutic agents in the treatment of hyperglycaemia and hypertension.
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    What causes breast cancer? A systematic review of causal attributions among breast cancer survivors and how these compare to expert endorsed risks.
    (Springer Verlag, 2014-07) Dumalaon-Canaria, Jo Anne; Hutchinson, Amanda; Prichard, Ivanka Joyce; Wilson, Carlene J
    Purpose. The aim of this paper was to review published research that analyzed causal attributions for breast cancer among women previously diagnosed with breast cancer. These attributions were compared with risk factors identified by published scientific evidence in order to determine the level of agreement between cancer survivors’ attributions and expert opinion. Methods. A comprehensive search for articles, published between 1982 and 2012, reporting studies on causal attributions for breast cancer among patients and survivors was undertaken. Of 5,135 potentially relevant articles, 22 studies met the inclusion criteria. Two additional articles were sourced from reference lists of included studies. Results. Results indicated a consistent belief among survivors that their own breast cancer could be attributed to family history, environmental factors, stress, fate or chance. Lifestyle factors were less frequently identified, despite expert health information highlighting the importance of these factors in controlling and modifying cancer risk. This review demonstrated that misperceptions about the contribution of modifiable lifestyle factors to the risk of breast cancer have remained largely unchanged over the past 30 years. Conclusions. The findings of this review indicate that beliefs about the causes of breast cancer among affected women are not always consistent with the judgment of experts. Breast cancer survivors did not regularly identify causal factors supported by expert consensus such as age, physical inactivity, breast density, alcohol consumption and reproductive history. Further research examining psychological predictors of attributions and the impact of cancer prevention messages on adjustment and well-being of cancer survivors is warranted.
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    Modeling the cost-effectiveness of strategies for treating esophageal adenocarcinoma and high-grade dysplasia
    (Springer-Verlag, 2012-08) Gordon, Louisa G; Hirst, Nicholas G; Mayne, George C; Watson, David Ian; Bright, Tim Flaxman; Cai, Wang; Barbour, Andrew P; Smithers, B Mark; Whiteman, David C; Eckermann, Simon Douglas; Australian Cancer Study Clinical Follow-Up Study Group
    Objective: To synthesize cost and health outcomes for current treatment pathways for esophageal adenocarcinoma and high grade dysplasia, and model comparative net clinical and economic benefits of alternative management scenarios. Methods: A decision-analytic model of real-world practices for esophageal adenocarcinoma treatment by tumor stage was constructed and validated. The model synthesized treatment probabilities, survival, quality-of-life and resource use extracted from epidemiological datasets, published literature and expert opinion. Comparative analyses between current practice and five hypothetical scenarios for modified treatment were undertaken. Results: Over five years, outcomes across T stage ranged from 4.06 quality-adjusted life-years and costs of $3,179 for high grade dysplasia, to 1.62 and $50,226 for stage T4. Greater use of endoscopic mucosal resection for stage T1 and measures to reduce esophagectomy mortality to 0-3% produced modest gains whereas a 20% reduction in the proportion of patients presenting at stage T3 produced large incremental net benefits of $4,971 (95% interval: $1,560, $8,368). Conclusion: These findings support measures that promote earlier diagnosis, such as developing risk assessment processes or endoscopic surveillance of Barrett’s esophagus. Incremental net monetary benefits for other strategies are relatively small in comparison to predicted gains from early detection strategies.
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    Self-reported bowel screening rates in older Australians and the implications for public health screening programs.
    (Australasian Medical Journal, 2013-08-31) Zajac, Ian; Flight, Ingrid; Turnbull, Deborah; Young, Graeme Paul; Cole, Stephen Russell; Wilson, Carlene J
    BACKGROUND: This paper sought to determine the status of older Australians with regard to Bowel Cancer screening practices occurring outside of the National Bowel Cancer Screening Program. METHOD: A random sample of N=25,511 urban Australians aged 50 to 74 years received a questionnaire via mail asking questions relating to bowel screening. N=8,762 (34.3%) returned a completed questionnaire. RESULTS: Approximately 33% (N=2863) of respondents indicated they had undergone colonoscopy in the preceding five years and 21% (N=1840) had used a Faecal Occult Blood Test (FOBT) in the preceding 12 months. Furthermore, 27% (N=497) of those who had completed an FOBT had also undergone colonoscopy. CONCLUSION: A significant proportion of older Australians might be participating in bowel screening practices outside of the national program (NBCSP). Moreover, the proportion of individuals reporting use of both FOBT and endoscopic services is much higher than the positivity rate of FOBT. Large population FOBT screening programs, such as the NBCSP, that do not consider participation in screening external to the program may underestimate true population screening rates.
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    Exploring the Validity of the Continuum of Resistance Model for Discriminating Early from Late and Non-uptake of Colorectal Cancer Screening: Implications for the Design of Invitation and Reminder Letters.
    (Springer., 2013-12) Gregory, Tess Anne; Cole, Stephen Russell; Wilson, Carlene J; Flight, Ingrid; Zajac, Ian; Turnbull, Deborah; Young, Graeme Paul
    Background The continuum of resistance model contends that respondents lie at one end of a continuum and non-respondents at the other with respect to factors demonstrated to impact on screening participation. Purpose The aim of this study was to explore the validity of this model for the prediction of participation in colorectal cancer screening. Method People aged 50 to 74 years were asked to complete a survey (n = 1,250). Eligible respondents (n = 376, 30 %) were invited to complete a faecal occult blood test (FOBT). The cutoff period for the determination of participation rates was 12 weeks, with a reminder sent at 6 weeks. Results FOBTs were returned by n = 196 people (132 within 6 weeks, 64 following a reminder). Participation was generally influenced by the same variables in both the first 6 weeks and the second 6 weeks, consistent with the continuum of resistance model. These variables were having known someone with bowel cancer and the social cognitive factor, perceptions of barriers to screening. There is a suggestion, however, that other factors may be differentially associated with early, late and non-participants. Conclusion Participation in screening appears somewhat consistent with the continuum of resistance model in that early and late participants respond to some of the same factors. This suggests that the same messages are relevant to early, late and non-screeners, but further consideration of what other factors may be influencing discrete stages of readiness to participate is necessary.
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    Ambivalence and its influence on participation and non-participation in screening for colorectal cancer
    (SAGE, 2013-09) Oster, Candice; Zajac, Ian; Flight, Ingrid; Hart, Elizabeth; Turnbull, Deborah; Wilson, Carlene J; Young, Graeme Paul
    Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and an ideal target for early detection and prevention through cancer screening. Unfortunately, rates of participation in screening are less than adequate. In this article we explore why people who were offered a fecal immunochemical test for CRC decided to participate or not, and for those who did participate, what influenced them to take action and complete the test. We conducted four focus groups and 30 telephone interviews with 63 people. The main reason people decided to screen was “wanting to know” their CRC status, which operated on a continuum ranging from wanting to know, through varying degrees of ambivalence, to not wanting to know. The majority of participants expressed ambivalence about CRC screening, and the main cue to action was the opportunity to screen without being too inconvenienced.
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    Using the Transtheoretical Model of Behaviour Change to describe readiness to rescreen for colorectal cancer with Faecal Occult Blood Testing
    (CSIRO Publishing, 2012) Duncan, Amy; Turnbull, Deborah; Gregory, Tess Anne; Cole, Stephen Russell; Young, Graeme Paul; Flight, Ingrid; Wilson, Carlene J
    Issue addressed: This study used the Transtheoretical Model of Behaviour Change (TTM) to describe reparticipation in colorectal cancer (CRC) screening according to social cognitive and background variables. Methods: A random sample of men and women aged 50-74 years living in South Australia completed a questionnaire measuring TTM stage and attitudes toward screening using a faecal occult blood test (FOBT). Participants were categorised according to four stages of readiness to rescreen: action, maintenance, relapse and inconsistent. Multivariate techniques were used to determine predictors of lower readiness stages compared with maintenance. Results: Of the 849 study participants, 29.9% were either non-adherent or had no intentions to maintain adherence (inconsistent and relapse). Compared with maintenance rescreeners, relapse participants reported less: social influences to screen (RR=0.86, p<0.001); satisfaction with prior screening (RR=0.87, p=0.03), self-efficacy (RR=0.96, p=0.01); and screening benefits (RR=0.84, p<0.001). Relapse participants were also more likely to not have private health insurance (RR=1.33, p=0.04) and be unaware of the need to repeat screening (RR=1.41, p=0.02). Inconsistent screeners were less likely to have planned when they will next rescreen (RR= 0.84, p=0.04) and reported greater barriers to rescreening (RR=1.05, p=0.05). Action participants were younger (RR= 0.98, p=<0.001), reported less social influences to screen (RR=0.94, p<0.001) and were less likely to have known someone who has had CRC (RR=0.82, p=0.01). Conclusions: Social cognitive, demographic and background variables significantly differentiated screening maintenance from lower readiness stages
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    Dietary red meat aggravates dextran sulfate sodium-induced colitis in mice whereas resistant starch attenuates inflammation
    (Springer-Verlag, 2013-08-29) Le Leu, Richard Kevin; Young, Graeme Paul; Hu, Ying; Winter, Jean; Conlon, Michael A
    Although a genetic component has been identified as a risk factor for developing inflammatory bowel disease, there is evidence that dietary factors also play a role in the development of this disease. Aims The aim of this study was to determine the effects of feeding a red meat diet with and without resistant starch (RS) to mice with dextran sulfate sodium (DSS)-induced colitis. Methods Colonic experimental colitis was induced in Balb/c mice using DSS. The severity of colitis was evaluated based on a disease activity index (based on bodyweight loss, stool consistency, rectal bleeding, and overall condition of the animal) and a histological score. Estimations were made of numbers of a range of different bacteria in the treatment pools of cecal digesta using quantitative real-time PCR. Results Consumption of a diet high in red meat increased DSS-induced colitis as evidenced by higher disease activity and histopathological scores. Addition of RS to the red meat diet exerted a beneficial effect in acute DSS-induced colitis. Subjective analysis of numbers of a range of bacterial targets suggest changes in the gut microbiota abundance were induced by red meat and RS treatments and these changes could contribute to the reported outcomes. Conclusions A dietary intake of red meat aggravates DSS-induced colitis whereas co-consumption of resistant starch reduces the severity of colitis.
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    Comparing the effects of COX and non-COX-inhibiting NSAIDs on enhancement of apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal cancer model
    (International Institute of Anticancer Research, 2013) Martin, Jonathan Edward; Young, Graeme Paul; Le Leu, Richard Kevin; Hu, Ying
    The protection against colorectal cancer (CRC) by non-steroidal anti-inflammatory drugs (NSAIDs) is in part dependent on inhibition of cyclooxygenase (COX). We compared the efficacy of the non-COX-inhibiting R flurbiprofen (R-FB) with COX-inhibiting sulindac and racemic flurbiprofen (Rac-FB), and determined their effects on apoptosis, in an azoxymethane (AOM)-induced rat CRC model. In experiment 1, groups of rats were given daily drug gavage (R-FB 30 mg/kg, Rac-FB 10 mg/kg and Sulindac 20 mg/kg) for one week, followed by AOM treatment and were killed eight hours later, colons were examined for apoptosis and cell proliferation. In experiment 2, groups of rats were given two AOM treatments, followed by daily drug gavage until they were killed ten weeks later, colons were examined for aberrant crypt foci (ACF) and prostaglandin E 2 production. All drugs significantly enhanced apoptosis and inhibited ACF, irrespective of their COX-inhibiting potency (p<0.01), but sulindac was more potent in inhibition of large ACF, p<0.05. COX-inhibiting sulindac achieved the greatest protective effect. The greater safety profile of Rac-FB should provide an advantage for chemoprevention.
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    Sample preference for colorectal cancer screening tests: blood or stool?
    (Scientific Research Publishing, 2012-08) Osborne, Joanne M; Wilson, Carlene J; Moore, Vivienne M; Gregory, Tess Anne; Flight, Ingrid; Young, Graeme Paul
    Objective: Despite the high prevalence of CRC and the proven benefits of faecal sampling tests, participation rates in CRC screening are suboptimal. Literature has identified a number of barriers to participation, including faecal aversion. Emerging test technologies suggest blood-based molecular markers might provide an alternative, more acceptable option, for CRC screening tests. We aim to determine preference for blood compared to faeces as the sample for the screening test. Methods: A survey was mailed to 956 South Australians aged 50 to 74 years. Data were collected on sample preference, demographic variables, and ratings of screening test convenience and comfort. Results: The survey yielded a 43% response rate. The majority of participants preferred to provide a blood sample (78% v 22%, p < 0.001). Women were more likely to prefer blood than men (82% vs 74%, p = 0.05). Sample experience influenced preferences, with a significantly higher preference for faeces among participants with experience in faecal sampling (27% vs 17% with no experience, p < 0.05). Participants who preferred to provide a faecal sample rated it significantly more convenient (p < 0.001), more comfortable (p < 0.001), and more acceptable (p < 0.001) than those who preferred blood sampling. Conclusions: Survey participants overwhelmingly indicate a preference for the idea of a blood sample over a faecal sample for CRC screening. Preference was influenced by gender, experience with sampling method and the individual’s perception of sampling convenience, sampling comfort and sample acceptability. Our results suggest population participation rates are likely to improve with blood-based screening tests.
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    Discovery and validation of molecular biomarkers for colorectal adenomas and cancer with application to blood testing
    (Public Library of Science, 2012-01-19) LaPointe, Lawrence C; Pedersen, Susanne K; Dunne, Robert; Brown, Glenn S; Pimlott, Letitia; Gaur, Snigdha; McEvoy, Aidan; Thomas, Melissa; Wattchow, David Anthony; Molloy, Peter L; Young, Graeme Paul
    Results: Genome-wide analysis uncovered reproducible gene expression signatures for both adenomas and cancers compared to controls. 386/489 (79%) of the adenoma and 439/529 (83%) of the adenocarcinoma biomarkers were validated in independent tissues. We also identified genes differentially expressed in adenomas compared to cancer. KIAA1199 was selected for further analysis based on consistent up-regulation in neoplasia, previous studies and its interest as an uncharacterized gene. Plasma KIAA1199 RNA levels were significantly higher in patients with either cancer or adenoma (31/ 40) compared to neoplasia-free controls (6/20).
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    Predictors of re-participation in faecal occult blood test-based screening for colorectal cancer
    (National Cancer Center, Korea, 2012) Cole, Stephen Russell; Gregory, Tess Anne; Whibley, Alex; Ward, Paul Russell; Turnbull, Deborah; Wilson, Carlene J; Flight, Ingrid; Esterman, Adrian Jeffrey; Young, Graeme Paul
    Background: There is little information on longitudinal patterns of participation in faecal occult blood test (FOBT) based colorectal cancer (CRC) screening or on demographic or behavioural factors associated with participation in re-screening. The lack of an agreed system for describing participatory behaviour over multiple rounds also hampers our ability to report, understand and make use of observed associations. Our aims were to develop a system for describing patterns of participatory behaviour in FOBT-based CRC screening programs and to identify factors associated with particular behavioural patterns. Methods: A descriptive framework was developed and applied to a data extract of screening invitation outcomes over two rounds of the NBCSP. The proportion of invitees in each behaviour category was determined and associations between behaviour patterns and demographic and program factors were identified using multivariate analyses. Results: We considered Re- Participants, Dropouts, Late Entrants and Never Participants to be the most appropriate labels for the four possible observed participatory categories after two invitation rounds. The screening participation rate of the South Australian cohort of the NBCSP remained stable over two rounds at 51%, with second round Dropouts (10.3%) being balanced by Late Entrants (10.5%). Non-Participants comprised 38.7% of invitees. Relative to Re-Participants, Dropouts were older, more likely to be female, of lower SES, had changed their place of residence between offers had a positive test result in the first round. Late Entrants tended to be in the youngest age band. Conclusions: Specific demographic characteristics are associated with behavioural sub-groups defined by responses to 2 offers of CRC screening. Targeted group-specific strategies could reduce dropout behaviour or encourage those who declined the first invitation to participate in the second round. It will be important to keep first round participants engaged in order to maximise the benefit of a CRC screening program.
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    Combination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkers
    (Public Library of Science, 2013-05-23) Hu, Ying; McIntosh, Graeme H; Le Leu, Richard Kevin; Nyskohus, Laura S; Woodman, Richard John; Young, Graeme Paul
    Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1ppm selenium as selenium-enriched milk protein, or combination of 1ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ß-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P,0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P,0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ß-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.
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    Equity of colorectal cancer screening: which groups have inequitable participation and what can we do about it?
    (CSIRO Publishing, 2011) Ward, Paul Russell; Javanparast, Sara; Wilson, Carlene J
    The National Bowel Cancer Screening Program (NBCSP) offers population-based screening for colorectal cancer (CRC) across Australia. The aims of this paper were to highlight the inequities in CRC screening in South Australia (SA) and the system-related barriers and enablers to CRC screening from the perspective of participants identified as having inequitable participation. First, de-identified data for the SA population of the NBCSP were statistically analysed and then mapped. Second, 117 in-depth interviews were conducted with culturally and linguistically diverse (CALD) groups, Indigenous and Anglo-Saxon Australians. Participation rates in the NBCSP were geographically and statistically significantly different (P < 0.0001) on the basis of gender (higher for women), age (higher for older people) and socioeconomic status (higher for more affluent people). The main system-related barriers were the lack of awareness of CRC or CRC screening within these groups, the problems with language due to most of the information being in English and the lack of recommendation by a doctor. This study revealed that inequity exists in the NBCSP participation in SA, and we identified both barriers and facilitators to CRC screening that require action at the level of both policy and practice. There is a large role in primary health care of both recommending CRC screening and facilitating equitable participation.