Identifying the molecular mediators of VN and the IGF:VN complex-stimulated breast cancer cell survival

This project has identified a molecular signature involved in functions critical to breast cancer progression and metastasis mediated by vitronectin, an abundant protein in human plasma and victornectin:insulin-like growth factor complexes. This may have significant implications in designing future therapeutic targets for patient with tumours overexpressing vitronectin and/or the components of the insulin-like growth factor system:vitronectin axis. In particular, the findings from this project have identified Cyr61 and CTGF as key mediators involved in vitroncetin- and insulin-like growth factor I: Insulin-like growth factor-binding protein:vitronectin-induced breast cancer cell survival and migration.

Understanding the function and mechanisms of intestinal cell kinase in the growth and survival of prostate cancer cells

This project was a step forward in discovering the potential role of intestinal cell kinase in prostate cancer development. Intestinal cell kinase was shown to be upregulated in prostate cancer cells and altered expression led to changes in key cell survival proteins. This study used in vitro experiments to monitor changes in cell growth, protein and RNA expression.

The Piper Fatigue Scale-Revised: Translation and psychometric evaluation in Spanish-speaking breast cancer survivors

Background Cancer-related fatigue (CRF) is the most common and distressing symptom reported by breast cancer survivors. The primary aim of this study was to translate and evaluate psychometrically for the first time a Spanish version of the Piper Fatigue Scale-Revised (S-PFS-R). Methods One hundred and eleven women with stage I–IIIA breast cancer who had completed their primary cancer therapy in the previous 6 months with the exception of hormone therapy completed the S-PFS-R, the Profile of Mood States (POMS) Fatigue (POMS-F) and Vigor subscales (POMS-V), and bilateral force handgrip testing. Data analysis included test–retest reliability, construct validity, criterion-related validity, and exploratory factor analyses. Results Test–retest reliability was satisfactory (r > 0.86), and all subscales showed moderate to high construct validity estimates [corrected item-subscale correlations (Pearson r = ≥ 0.65)]. The exploratory factor analysis revealed four dimensions with 75.5 % of the common variance explained. The S-PFS-R total score positively correlated with the POMS-F subscale (r = 0.50–0.78) and negatively with the POMS-V subscale (r = −0.13 to −0.44) confirming criterion-related validity. Negative correlations among force handgrip testing, subscales, and total scores were weak (r = −0.26 to −0.29). Conclusions The Spanish version of PFS-R shows satisfactory psychometric properties in a sample of breast cancer survivors. This is the first study to translate the PFS-R into Spanish and further testing is warranted.

Predicting the need for adaptive radiotherapy in head and neck cancer

Background and purpose Adaptive radiotherapy (ART) can account for the dosimetric impact of anatomical change in head and neck cancer patients; however it can be resource intensive. Consequently, it is imperative that patients likely to require ART are identified. The purpose of this study was to find predictive factors that identify oropharyngeal squamous cell carcinoma (OPC) and nasopharyngeal carcinoma (NPC) patients more likely to need ART. Materials and methods One hundred and ten patients with OPC or NPC were analysed. Patient demographics and tumour characteristics were compared between patients who were replanned and those that were not. Factors found to be significant were included in logistic regression models. Risk profiles were developed from these models. A dosimetric analysis was performed. Results Nodal disease stage, pre-treatment largest involved node size, diagnosis and initial weight (categorised in 2 groups) were identified as significant for inclusion in the model. Two models were found to be significant (p = 0.001), correctly classifying 98.2% and 96.1% of patients respectively. Three ART risk profiles were developed. Conclusion Predictive factors identifying OPC or NPC patients more likely to require ART were reported. A risk profile approach could facilitate the effective implementation of ART into radiotherapy departments through forward planning and appropriate resource allocation.

Investigation of the relationship between BMI and prostate motion in radiation therapy treatment for prostate cancer

This thesis studied the influence of patient obesity on prostate motion during radiation therapy treatment delivery, an important consideration in the accurate treatment of prostate cancer. The study highlighted the importance of daily image guidance to correct for prostate motion, increasing radiation dose to the prostate while decreasing radiation dose to surrounding healthy tissues, thereby increasing patient quality of life.

Effects of compression on lymphoedema during resistance exercise in women with breast cancer-related lymphoedema: A randomised, cross-over trial

Background The use of compression garments during exercise is recommended for women with breast cancer-related lymphoedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomised, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphoedema status and its associated symptoms in women with breast cancer-related lymphoedema. Methods Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphoedema completed two resistance exercise sessions, one with compression and one without, in a randomised order separated by a 14 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphoedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphoedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. Results There was no difference in lymphoedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. Conclusions An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphoedema in women with breast cancer-related lymphoedema.

Latinos and political advocacy for cancer control in a United States-Mexico border community

Health policy interventions provide powerful tools for addressing health disparities. The Latino community is one of the fastest growing communities in the United States yet is largely underrepresented in government and advocacy efforts. This study includes 42 Latino adults (M age 5 45 years) who participated in focus group discussions and completed a brief questionnaire assessing their experiences with political health advocacy. Qualitative analyses revealed participants considered cancer a concern for the Latino community, but there was a lack of familiarity with political advocacy and its role in cancer control. Participants identified structural, practical, cultural, and contextual barriers to engaging in political health advocacy. This article presents a summary of the findings that suggest alternative ways to engage Latinos in cancer control advocacy.

Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

Adverse effects of androgen-deprivation therapy in prostate cancer and their management

Objective To provide an up-to-date summary of current literature on the management of adverse effects of androgen-deprivation therapy (ADT). Patients and Methods All relevant medical literature on men with prostate cancer treated with ADT from 2005 to 2014, and older relevant papers, were reviewed. Recent health advisory statements from the Australian government, societies and advocacy groups have been incorporated to the document. Results There are numerous adverse effects of ADT that require pro-active prevention and treatment. Ranging from cardiovascular disease, diabetes and osteoporosis, to depression, cognitive decline and sexual dysfunction, the range of adverse effects is wide. Baseline assessment, monitoring, prevention and consultation from a multidisciplinary team are important in minimising the harm from ADT. Conclusions This review provides a series of practical recommendations to assist with managing the adverse effects of ADT.

The effects of compression use during exercise in women with breast cancer-related lymphoedema

Compelling evidence demonstrates the importance of regular exercise following breast cancer, and this is particularly important for those who develop breast cancer-related lymphoedema. However, fear of lymphoedema exacerbation and the need to wear compression while exercising present as significant barriers for these women. This Master's research evaluated the need for wearing compression during exercise in women with breast cancer-related lymphoedema. Findings demonstrated that exercise performed without compression does not exacerbate lymphoedema or related symptoms. These findings are clinically relevant as they highlight that compression use during exercise should be prescribed on an individual basis, taking into consideration patient preferences and adherence issues.

Breast and prostate cancer survivor responses to group exercise and supportive group Psychotherapy

This study qualitatively examined an 8 week group exercise and counseling intervention for breast and prostate cancer survivors. Groups exercised 3 days per week, 50 minutes per session,performing moderate intensity aerobic and resistance training. Groups also underwent 90 minute supportive group psychotherapy sessions once per week. Survivors discussed their experiences in focus groups post intervention. Transcripts were analyzed using interpretative phenomenological analysis. Survivors described how exercise facilitated counseling by creating mutual aid and trust, and counseling helped participants with self-identity, sexuality, and returning to normalcy. When possible, counselors and fitness professionals should create partnerships to optimally support cancer survivors.

Exercise and cancer survivorship

Exercise has been identified as an integral component of comprehensive survivorship care and a promising adjuvant therapy to aid in the management of cancer. Leading organisations worldwide now advocate exercise for cancer survivors. Here we briefly review the existing evidence for exercise and survivorship, as well as current research endeavours in Australia. Discussion extends to identify the gaps between research and practice, as well as future research directions needed to drive the field forward. With continued efforts by scientists, clinicians and consumers, there is real potential to strengthen the nexus between scientific evidence and clinical practice and integrate exercise into standard cancer care.

Acute inflammatory response to low-, moderate- and high-load resistance exercise in women with breast cancer-related lymphoedema

Background Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer-related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose. To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low-, moderate- and high-loads. The impact on lymphoedema status and associated symptoms was also compared. Methods Twenty-one women aged 62 ± 10 years with mild to severe BCRL participated in the study. Participants completed a low-load (15-20 repetition maximum), moderate-load (10-12 repetition maximum) and high-load (6-8 repetition maximum) exercise sessions consisting of three sets of six upper-body resistance exercises. Sessions were completed in a randomized order separated by a seven to 10 day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation (creatine kinase [CK], C-reactive protein [CRP], interleukin-6 [IL-6] and tumour necrosis factor-alpha [TNF-α]). Lymphoedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using visual analogue scales (VAS) for pain, heaviness and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results No significant changes in CK, CRP, IL-6 and TNF-α were observed following the low-, moderate- or high-load resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the three resistance exercise conditions. Conclusions The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads. Given these observations, moderate- to high-load resistance training is recommended for this patient population as these loads prompt superior physiological and functional benefits.

Systematic review and meta-analysis of the effects of exercise for those with cancer-related lymphedema

Objective: To evaluate the effects of exercise on cancer-related lymphedema and related symptoms, and to determine the need for those with lymphedema to wear compression during exercise. Data Sources: CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus databases were searched for trials published prior to 1 January, 2015. Study Selection: Randomised and non-randomised, controlled trials, and single group pre-post studies published in English-language were included. Twenty-one (exercise) and four (compression and exercise) studies met inclusion criteria. Data Extraction: Data was extracted into tabular format using predefined data fields by one reviewer and assessed for accuracy by a second reviewer. Study quality was evaluated using the Effective Public Health Practice Project assessment tool. Data Synthesis: Data was pooled using a random effects model to assess the effects of acute and long-term exercise on lymphedema and lymphedema-associated symptoms, with subgroup analyses for exercise mode and intervention length. There was no effect of exercise (acute or intervention) on lymphedema or associated symptoms with standardised mean differences from all analyses ranging between −0.2 and 0.1 (p-values ≥0.22). Findings from subgroup analyses for exercise mode (aerobic, resistance, mixed, other) and intervention duration (>12 weeks or ≤12 weeks) were consistent with these findings; that is, no effect on lymphedema or associated symptoms. There were too few studies evaluating the effect of compression during regular exercise to conduct a meta-analysis. Conclusions: Individuals with secondary lymphedema can safely participate in progressive, regular exercise without experiencing a worsening of lymphedema or related-symptoms. However, the results also do not suggest any improvements will occur in lymphedema. At present, there is insufficient evidence to support or refute the current clinical recommendation to wear compression garments during regular exercise.

Predictors of physical activity in colorectal cancer survivors after participation in a telephone-delivered multiple health behavior change intervention

Purpose: Physical activity improves the health outcomes of colorectal cancer (CRC) survivors, yet few are exercising at levels known to yield health benefits. Baseline demographic, clinical, behavioral, and psychosocial predictors of physical activity at 12 months were investigated in CRC survivors. Methods: Participants were CRC survivors (n = 410) who completed a 12-month multiple health behavior change intervention trial (CanChange). The outcome variable was 12 month sufficient physical activity (≥150 min of moderate–vigorous physical activity/week). Baseline predictors included demographics and clinical variables, health behaviors, and psychosocial variables. Results: Multivariate linear regression revealed that baseline sufficient physical activity (p < 0.001), unemployment (p = 0.004), private health insurance (p = 0.040), higher cancer-specific quality of life (p = 0.031) and higher post-traumatic growth (p = 0.008) were independent predictors of sufficient physical activity at 12 months. The model explained 28.6 % of the variance. Conclusions: Assessment of demographics, health behaviors, and psychosocial functioning following a diagnosis of CRC may help to develop effective physical activity programs.