Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma
- Sharma, Revati, Kadife, Elif, Myers, Mark, Kannourakis, George, Prithviraj, Prashanth, Ahmed, Nuzhat
- Authors: Sharma, Revati , Kadife, Elif , Myers, Mark , Kannourakis, George , Prithviraj, Prashanth , Ahmed, Nuzhat
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Journal of Experimental and Clinical Cancer Research Vol. 40, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies. © 2021, The Author(s).
- Authors: Sharma, Revati , Kadife, Elif , Myers, Mark , Kannourakis, George , Prithviraj, Prashanth , Ahmed, Nuzhat
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Journal of Experimental and Clinical Cancer Research Vol. 40, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies. © 2021, The Author(s).
Using agricultural metadata : a novel investigation of trends in sowing date in on-farm research trials using the online farm trials database
- Walters, Judi, Light, Kate, Robinson, Nathan
- Authors: Walters, Judi , Light, Kate , Robinson, Nathan
- Date: 2021
- Type: Text , Journal article
- Relation: F1000Research Vol. 9, no. (2021), p.1305-1305
- Full Text:
- Reviewed:
- Description: Background: A growing ability to collect data, together with the development and adoption of the FAIR guiding principles, has increased the amount of data available in many disciplines. This has given rise to an urgent need for robust metadata. Within the Australian grains industry, data from thousands of on-farm research trials (Trial Projects) have been made available via the Online Farm Trials (OFT) website. OFT Trial Project metadata were developed as filters to refine front-end database searches, but could also be used as a dataset to investigate trends in metadata elements. Australian grains crops are being sown earlier, but whether on-farm research trials reflect this change is currently unknown. Methods: We investigated whether OFT Trial Project metadata could be used to detect trends in sowing dates of on-farm crop research trials across Australia, testing the hypothesis that research trials are being sown earlier in line with local farming practices. The investigation included 15 autumn-sown, winter crop species listed in the database, with trial records from 1993 to 2019. Results: Our analyses showed that (i) OFT Trial Project metadata can be used as a dataset to detect trends in sowing date; and (ii) cropping research trials are being sown earlier in Victoria and Western Australia, but no trend exists within the other states. Discussion/Conclusion: Our findings show that OFT Trial Project metadata can be used to detect trends in crop sowing date, suggesting that metadata could also be used to detect trends in other elements such as harvest date. Because OFT is a national database of research trials, further assessment of metadata may uncover important agronomic, cultural or economic trends within or across the Australian cropping regions. New information could then be used to lead practice change and increase productivity within the Australian grains industry. © 2021 Walters J et al.
- Authors: Walters, Judi , Light, Kate , Robinson, Nathan
- Date: 2021
- Type: Text , Journal article
- Relation: F1000Research Vol. 9, no. (2021), p.1305-1305
- Full Text:
- Reviewed:
- Description: Background: A growing ability to collect data, together with the development and adoption of the FAIR guiding principles, has increased the amount of data available in many disciplines. This has given rise to an urgent need for robust metadata. Within the Australian grains industry, data from thousands of on-farm research trials (Trial Projects) have been made available via the Online Farm Trials (OFT) website. OFT Trial Project metadata were developed as filters to refine front-end database searches, but could also be used as a dataset to investigate trends in metadata elements. Australian grains crops are being sown earlier, but whether on-farm research trials reflect this change is currently unknown. Methods: We investigated whether OFT Trial Project metadata could be used to detect trends in sowing dates of on-farm crop research trials across Australia, testing the hypothesis that research trials are being sown earlier in line with local farming practices. The investigation included 15 autumn-sown, winter crop species listed in the database, with trial records from 1993 to 2019. Results: Our analyses showed that (i) OFT Trial Project metadata can be used as a dataset to detect trends in sowing date; and (ii) cropping research trials are being sown earlier in Victoria and Western Australia, but no trend exists within the other states. Discussion/Conclusion: Our findings show that OFT Trial Project metadata can be used to detect trends in crop sowing date, suggesting that metadata could also be used to detect trends in other elements such as harvest date. Because OFT is a national database of research trials, further assessment of metadata may uncover important agronomic, cultural or economic trends within or across the Australian cropping regions. New information could then be used to lead practice change and increase productivity within the Australian grains industry. © 2021 Walters J et al.
Aerobic, resistance, and mind-body exercise are equivalent to mitigate symptoms of depression in older adults: A systematic review and network meta-analysis of randomised controlled trials
- Miller, Kyle, Areerob, Pinyadapat, Hennessy, Declan, Gonçalves-Bradley, Daniela, Mesagno, Christopher, Grace, Fergal
- Authors: Miller, Kyle , Areerob, Pinyadapat , Hennessy, Declan , Gonçalves-Bradley, Daniela , Mesagno, Christopher , Grace, Fergal
- Date: 2020
- Type: Text , Journal article
- Relation: F1000Research Vol. 9, no. (2020), p. 1-51
- Full Text:
- Reviewed:
- Description: Background: Exercise has been identified as an allied health strategy that can support the management of depression in older adults, yet the relative effectiveness for different exercise modalities is unknown. To meet this gap in knowledge, we present a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the head-to-head effectiveness of aerobic, resistance, and mind-body exercise to mitigate depressive symptoms in adults aged ≥ 65 years. Methods: A PRISMA-NMA compliant review was undertaken on RCTs from inception to September 12 th, 2019. PubMed, Web of Science, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, PsycINFO, and SPORTDiscus were systematically searched for eligible RCTs enrolling adults with a mean age ≥ 65 years, comparing one or more exercise intervention arms, and which used valid measures of depressive symptomology. Comparative effectiveness was evaluated using network meta-analysis to combine direct and indirect evidence, controlling for inherent variation in trial control groups. Results: The systematic review included 81 RCTs, with 69 meeting eligibility for the network meta-analysis ( n = 5,379 participants). Pooled analysis found each exercise type to be effective compared with controls (Hedges' g = -0.27 to -0.51). Relative head-to-head comparisons were statistically comparable between exercise types: resistance versus aerobic (Hedges' g = -0.06, PrI = -0.91, 0.79), mind-body versus aerobic (Hedges' g = -0.12, PrI = -0.95, 0.72), mind-body versus resistance (Hedges' g = -0.06, PrI = -0.90, 0.79). High levels of compliance were demonstrated for each exercise treatment. Conclusions: Aerobic, resistance, and mind-body exercise demonstrate equivalence to mitigate symptoms of depression in older adults aged ≥ 65 years, with comparably encouraging levels of compliance to exercise treatment. These findings coalesce with previous findings in clinically depressed older adults to encourage personal preference when prescribing exercise for depressive symptoms in older adults, irrespective of severity. Registration: PROSPERO CRD42018115866 (23/11/2018). © 2020 Miller KJ et al.
- Authors: Miller, Kyle , Areerob, Pinyadapat , Hennessy, Declan , Gonçalves-Bradley, Daniela , Mesagno, Christopher , Grace, Fergal
- Date: 2020
- Type: Text , Journal article
- Relation: F1000Research Vol. 9, no. (2020), p. 1-51
- Full Text:
- Reviewed:
- Description: Background: Exercise has been identified as an allied health strategy that can support the management of depression in older adults, yet the relative effectiveness for different exercise modalities is unknown. To meet this gap in knowledge, we present a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the head-to-head effectiveness of aerobic, resistance, and mind-body exercise to mitigate depressive symptoms in adults aged ≥ 65 years. Methods: A PRISMA-NMA compliant review was undertaken on RCTs from inception to September 12 th, 2019. PubMed, Web of Science, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, PsycINFO, and SPORTDiscus were systematically searched for eligible RCTs enrolling adults with a mean age ≥ 65 years, comparing one or more exercise intervention arms, and which used valid measures of depressive symptomology. Comparative effectiveness was evaluated using network meta-analysis to combine direct and indirect evidence, controlling for inherent variation in trial control groups. Results: The systematic review included 81 RCTs, with 69 meeting eligibility for the network meta-analysis ( n = 5,379 participants). Pooled analysis found each exercise type to be effective compared with controls (Hedges' g = -0.27 to -0.51). Relative head-to-head comparisons were statistically comparable between exercise types: resistance versus aerobic (Hedges' g = -0.06, PrI = -0.91, 0.79), mind-body versus aerobic (Hedges' g = -0.12, PrI = -0.95, 0.72), mind-body versus resistance (Hedges' g = -0.06, PrI = -0.90, 0.79). High levels of compliance were demonstrated for each exercise treatment. Conclusions: Aerobic, resistance, and mind-body exercise demonstrate equivalence to mitigate symptoms of depression in older adults aged ≥ 65 years, with comparably encouraging levels of compliance to exercise treatment. These findings coalesce with previous findings in clinically depressed older adults to encourage personal preference when prescribing exercise for depressive symptoms in older adults, irrespective of severity. Registration: PROSPERO CRD42018115866 (23/11/2018). © 2020 Miller KJ et al.
- Wallen, Matthew, Hennessy, Declan, Brown, Stephen, Evans, Luke, Rawstorn, Jonathan, Wong Shee, Anna, Hall, Adrian
- Authors: Wallen, Matthew , Hennessy, Declan , Brown, Stephen , Evans, Luke , Rawstorn, Jonathan , Wong Shee, Anna , Hall, Adrian
- Date: 2020
- Type: Text , Journal article , Review
- Relation: European Journal of Cancer Care Vol. 29, no. 4 (2020), p.
- Full Text: false
- Reviewed:
- Description: Objective: The primary objective of this systematic review and meta-analysis was to compare the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) and usual care (UC) on cardiorespiratory fitness (peak V̇O2) in cancer patients and survivors. Secondary objectives were to compare the effects of HIIT versus MICT and UC on other cardiopulmonary exercise testing (CPET) indices. Safety and adherence to HIIT were also evaluated. Methods: A systematic review and meta-analysis of controlled trials were undertaken using eligible studies from electronic database searching (inception—December 2019). Mean differences (MD) with 95% confidence intervals (CI) were compared and heterogeneity assessed using Cochran's Q and I2 statistic. Results: Twelve eligible studies included 516 participants with post-intervention CPET data. No serious adverse events occurred. Adherence to HIIT ranged between 71.2% and 95.6%. HIIT had significantly higher peak V̇O2 compared with UC (MD = 2.11 ml kg−1 min−1, 95% CI 0.75–3.47, p =.002). No significant difference was found between HIIT and MICT (MD = 2.03 ml kg−1 min−1, 95%CI −0.75–4.83, p =.15). HIIT was more effective than UC to improve peak oxygen pulse (MD = 1.59 ml/beat, 95%CI 0.06–3.12, p =.04). Conclusions: Quantitative assessment of HIIT studies indicates good compliance, with a significant effect on peak V̇O2 and peak oxygen pulse compared with UC in cancer patients and survivors. HIIT demonstrates a comparable effect with MICT to improve peak V̇O2. © 2020 John Wiley & Sons Ltd
- Description: Western Alliance Academic Health Science Centre , WA-739501
Work-related factors affecting exclusive breastfeeding among employed women in ethiopia : managers’ perspective using a qualitative approach
- Gebrekidan, Kahsu, Plummer, Virginia, Fooladi, Ensieh, Hall, Helen
- Authors: Gebrekidan, Kahsu , Plummer, Virginia , Fooladi, Ensieh , Hall, Helen
- Date: 2020
- Type: Text , Journal article
- Relation: International Journal of Women's Health Vol. 12, no. (2020), p. 473-480
- Full Text:
- Reviewed:
- Description: Background: Only 21% of employed mothers in Ethiopia breastfeed exclusively until six months. Evidence from other countries has shown that support from managers encourages mothers to continue breastfeeding. Whereas lack of physical resources, time for breastfeed-ing and supportive policies adversely impact the continuation of breastfeeding. The aim of this study was to explore the perspective of managers regarding breastfeeding in the Ethiopian context. Methods: Managers of district level, government institutions were interviewed in the Tigray region of North Ethiopia. Semi-structured, face to face interviews were used to explore managers’ perspectives and views about breastfeeding, the level of support they provide to breastfeeding mothers, and the challenges they faced. The data were transcribed verbatim and thematically analysed. Results: Fifteen managers were interviewed from 12 organizations. The data were categor-ized into three themes. The first theme related to the attitudes and preference of managers and revealed that overall participants had positive views towards breastfeeding. The second theme highlighted managers’ concern about the impact of breastfeeding on staffing and workplace productivity. The third theme focused on managers’ assertions that, despite improvements, there were still inadequate policies and government strategies to support employed breastfeeding women in North Ethiopia. Conclusion: It is promising that managers in North Ethiopia expressed a positive attitude towards supporting breastfeeding mothers. Managers raised concern about the impact of breastfeeding on work performance, as well as the lack of physical facilities and government resources that affects the level of support they can provide. © 2020 Gebrekidan et al.
- Authors: Gebrekidan, Kahsu , Plummer, Virginia , Fooladi, Ensieh , Hall, Helen
- Date: 2020
- Type: Text , Journal article
- Relation: International Journal of Women's Health Vol. 12, no. (2020), p. 473-480
- Full Text:
- Reviewed:
- Description: Background: Only 21% of employed mothers in Ethiopia breastfeed exclusively until six months. Evidence from other countries has shown that support from managers encourages mothers to continue breastfeeding. Whereas lack of physical resources, time for breastfeed-ing and supportive policies adversely impact the continuation of breastfeeding. The aim of this study was to explore the perspective of managers regarding breastfeeding in the Ethiopian context. Methods: Managers of district level, government institutions were interviewed in the Tigray region of North Ethiopia. Semi-structured, face to face interviews were used to explore managers’ perspectives and views about breastfeeding, the level of support they provide to breastfeeding mothers, and the challenges they faced. The data were transcribed verbatim and thematically analysed. Results: Fifteen managers were interviewed from 12 organizations. The data were categor-ized into three themes. The first theme related to the attitudes and preference of managers and revealed that overall participants had positive views towards breastfeeding. The second theme highlighted managers’ concern about the impact of breastfeeding on staffing and workplace productivity. The third theme focused on managers’ assertions that, despite improvements, there were still inadequate policies and government strategies to support employed breastfeeding women in North Ethiopia. Conclusion: It is promising that managers in North Ethiopia expressed a positive attitude towards supporting breastfeeding mothers. Managers raised concern about the impact of breastfeeding on work performance, as well as the lack of physical facilities and government resources that affects the level of support they can provide. © 2020 Gebrekidan et al.
- Smith, Allan., Bamgboje-Ayodele, Adeola, Butow, Phyllis, Klein, Britt, Turner, Jane, Sharpe, Louise, Fardell, Joanna, Beatty, Lisa, Pearce, Alison, Thewes, Belinda, Beith, Jane, Girgis, Afaf, iConquerFear Community Advisory, Group
- Authors: Smith, Allan. , Bamgboje-Ayodele, Adeola , Butow, Phyllis , Klein, Britt , Turner, Jane , Sharpe, Louise , Fardell, Joanna , Beatty, Lisa , Pearce, Alison , Thewes, Belinda , Beith, Jane , Girgis, Afaf , iConquerFear Community Advisory, Group
- Date: 2019
- Type: Text , Journal article
- Relation: Psycho-Oncology Vol. , no. (2019), p.
- Full Text: false
- Reviewed:
- Description: Objective: To develop and evaluate the usability of iConquerFear, an online self-management adaptation of an efficacious face-to-face therapist-delivered treatment for fear of cancer recurrence (FCR). Methods: iConquerFear development was theory based and person based. Development was guided by Ritterband et al's behaviour change model for internet interventions. iConquerFear end users (cancer survivors) provided iterative feedback in accordance with Yardley et al's person-based approach to maximise engagement and usability. Online focus groups and cognitive interviews were conducted to evaluate the usability of iConquerFear. Discussions were recorded, transcribed verbatim, and thematically analysed. Results: Five online FCR modules were developed. Twenty-three cancer survivors (47% of those eligible) participated; 11/23 (58%) were breast cancer survivors, and average age was 53 years (SD = 10.8). Thematic saturation was reached after six focus groups (n = 16) and seven individual think-aloud interviews. Thematic analysis produced five overarching themes: easy navigation essential; satisfaction and engagement with content; flexible access is key; normalising and empowering; and a useful first step. Conclusions: Online self-management interventions like iConquerFear have the potential to address the unmet supportive care needs reported by burgeoning numbers of cancer survivors. However, that potential may not be realised unless interventions are rigorously developed and user tested, as benefits are constrained by limited engagement. Themes from the usability testing of iConquerFear highlight the importance of developing flexible, tailored, interactive, and contextual online self-management interventions for people with cancer. © 2019 John Wiley & Sons, Ltd.
Paclitaxel-induced Src activation is inhibited by dasatinib treatment, independently of cancer stem cell properties, in a mouse model of ovarian cancer
- Kadife, Elif, Chan, Emily, Luwor, Rodney, Kannourakis, George, Findlay, Jock, Ahmed, Nuzhat
- Authors: Kadife, Elif , Chan, Emily , Luwor, Rodney , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2019
- Type: Text , Journal article
- Relation: Cancers Vol. 11, no. 2 (2019), p. 1-24
- Full Text:
- Reviewed:
- Description: Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.
- Authors: Kadife, Elif , Chan, Emily , Luwor, Rodney , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2019
- Type: Text , Journal article
- Relation: Cancers Vol. 11, no. 2 (2019), p. 1-24
- Full Text:
- Reviewed:
- Description: Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.
- Lau, Patricia, Lee, Christina, Ho, ChyeKok
- Authors: Lau, Patricia , Lee, Christina , Ho, ChyeKok
- Date: 2019
- Type: Text , Journal article
- Relation: Education and Training Vol. 61, no. 3 (2019), p. 342-358
- Full Text: false
- Reviewed:
- Description: Purpose: The purpose of this paper is to explore how university fieldtrips progressively deepen student engagement, and explain that stage-by-stage using the organismic integration theory. Design/methodology/approach: Using reflective logs, follow-up focus groups after two years and facilitator observations, this Malaysian qualitative study followed 12 business students across two three-day rainforest fieldtrips. Findings: Students progressed toward greater – and enduring – engagement, and transferable socio-cognitive skills, via three thematic stages. Voice and self-reflection – motivated by protecting group harmony – were key, enabled by facilitator and peer encouragement. Research limitations/implications: This exploratory study invites research in specified education cultures. Further, a longitudinal, quantitative study could be designed to examine the conceptual framework developed in Figure 1. Practical implications: University curricula, especially in collectivist high power distance cultures, should include fieldtrips as a particularly powerful form of experiential learning. Benefits of deeper engagement extend beyond present to future courses and the workplace. Higher student attraction/retention and employability may follow. Intrinsic motivation grows through the student–instructor interaction, watching theoretical principles in action, and having eureka moments through reflection, expression and exchange of ideas. Originality/value: The research fills a gap by mapping student engagement progressively from extrinsic to intrinsic motivation along with socio-cognitive competencies. The authors reveal the centrality of voice and reflection to promote group harmony, explain the roles of facilitators and peers and show long-lasting transferable benefits to learning. Novelly, the authors provide empirical support for existing conceptual frameworks but also extend these.
Best practice data life cycle approaches for the life sciences
- Griffin, Philippa, Khadake, Jyoti, LeMay, Kate, Lewis, Suzanna, Orchard, Sandra, Pask, Andrew, Pope, Bernard, Roessner, Ute, Russell, Keith, Seemann, Torsten, Treloar, Andrew, Tyagi, Sonika, Christiansen, Jeffrey, Dayalan, Saravanan, Gladman, Simon, Hangartner, Sandra, Hayden, Helen, Ho, William, Keeble-Gagnère, Gabriel, Korhonen, Pasi, Neish, Peter, Prestes, Priscilla, Richardson, Mark, Watson-Haigh, Nathan, Wyres, Kelly, Young, Neil, Schneider, Maria
- Authors: Griffin, Philippa , Khadake, Jyoti , LeMay, Kate , Lewis, Suzanna , Orchard, Sandra , Pask, Andrew , Pope, Bernard , Roessner, Ute , Russell, Keith , Seemann, Torsten , Treloar, Andrew , Tyagi, Sonika , Christiansen, Jeffrey , Dayalan, Saravanan , Gladman, Simon , Hangartner, Sandra , Hayden, Helen , Ho, William , Keeble-Gagnère, Gabriel , Korhonen, Pasi , Neish, Peter , Prestes, Priscilla , Richardson, Mark , Watson-Haigh, Nathan , Wyres, Kelly , Young, Neil , Schneider, Maria
- Date: 2018
- Type: Text , Journal article
- Relation: F1000 Research Vol. 6, no. (2018), p. 1-28
- Full Text:
- Reviewed:
- Description: Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. © 2018 Griffin PC et al.
- Authors: Griffin, Philippa , Khadake, Jyoti , LeMay, Kate , Lewis, Suzanna , Orchard, Sandra , Pask, Andrew , Pope, Bernard , Roessner, Ute , Russell, Keith , Seemann, Torsten , Treloar, Andrew , Tyagi, Sonika , Christiansen, Jeffrey , Dayalan, Saravanan , Gladman, Simon , Hangartner, Sandra , Hayden, Helen , Ho, William , Keeble-Gagnère, Gabriel , Korhonen, Pasi , Neish, Peter , Prestes, Priscilla , Richardson, Mark , Watson-Haigh, Nathan , Wyres, Kelly , Young, Neil , Schneider, Maria
- Date: 2018
- Type: Text , Journal article
- Relation: F1000 Research Vol. 6, no. (2018), p. 1-28
- Full Text:
- Reviewed:
- Description: Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. © 2018 Griffin PC et al.
Caucasian and south Asian men show equivalent improvements in surrogate biomarkers of cardiovascular and metabolic health following 6-weeks of supervised resistance training
- Knox, Allan, Sculthorpe, Nicholas, Grace, Fergal
- Authors: Knox, Allan , Sculthorpe, Nicholas , Grace, Fergal
- Date: 2018
- Type: Text , Journal article
- Relation: F1000Research Vol. 7, no. (2018), p. 1-16
- Full Text:
- Reviewed:
- Description: Background: The South Asian population have greater cardiovascular risk than their age-matched Caucasian counterparts, characterized by unfavorable biomarkers. South Asians may also be partially resistant to the pleiotropic benefits of physical activity on cardiovascular health. There is a current absence of studies that compare markers of cardio-metabolic health between Caucasians and South Asians employing resistance exercise. This study set out to compare the response in biomarkers of cardio-metabolic health in Caucasians and South Asians in response to resistance exercise. Methods: Caucasian (n=15, 25.5 ± 4.8 yrs) and South Asian (n=13, 25.4 ± 7.0 yrs) males completed a 6-week progressive resistance exercise protocol. Fasting blood glucose, insulin, and their product insulin resistance (HOMA-IR), triglycerides (TRIGS), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), vascular endothelial growth factor (VEGF), asymmetric dimythylarginine (ADMA), L-arginine (L-ARG) and C-reactive protein (CRP) were established at baseline and following resistance exercise. Results: There were significant improvements in fasting glucose, TC, LDL, HDL and VEGF in both groups following resistance exercise ( p<0.05, for all). No change was observed in insulin, HOMA-IR, TRIGS, ADMA, L-ARG following resistance exercise ( p>0.05, in both groups). CRP increased in the South Asian group ( p<0.05) but not the Caucasian group ( p>0.05) Conclusions: The cardio-metabolic response to resistance exercise is comparable in young Caucasian and South Asian males though inflammatory response to exercise may be prolonged in South Asians.
- Authors: Knox, Allan , Sculthorpe, Nicholas , Grace, Fergal
- Date: 2018
- Type: Text , Journal article
- Relation: F1000Research Vol. 7, no. (2018), p. 1-16
- Full Text:
- Reviewed:
- Description: Background: The South Asian population have greater cardiovascular risk than their age-matched Caucasian counterparts, characterized by unfavorable biomarkers. South Asians may also be partially resistant to the pleiotropic benefits of physical activity on cardiovascular health. There is a current absence of studies that compare markers of cardio-metabolic health between Caucasians and South Asians employing resistance exercise. This study set out to compare the response in biomarkers of cardio-metabolic health in Caucasians and South Asians in response to resistance exercise. Methods: Caucasian (n=15, 25.5 ± 4.8 yrs) and South Asian (n=13, 25.4 ± 7.0 yrs) males completed a 6-week progressive resistance exercise protocol. Fasting blood glucose, insulin, and their product insulin resistance (HOMA-IR), triglycerides (TRIGS), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), vascular endothelial growth factor (VEGF), asymmetric dimythylarginine (ADMA), L-arginine (L-ARG) and C-reactive protein (CRP) were established at baseline and following resistance exercise. Results: There were significant improvements in fasting glucose, TC, LDL, HDL and VEGF in both groups following resistance exercise ( p<0.05, for all). No change was observed in insulin, HOMA-IR, TRIGS, ADMA, L-ARG following resistance exercise ( p>0.05, in both groups). CRP increased in the South Asian group ( p<0.05) but not the Caucasian group ( p>0.05) Conclusions: The cardio-metabolic response to resistance exercise is comparable in young Caucasian and South Asian males though inflammatory response to exercise may be prolonged in South Asians.
Momelotinib decreased cancer stem cell associated tumor burden and prolonged disease-free remission period in a mouse model of human ovarian cancer
- Chan, Emily, Luwor, Rodney, Burns, Christopher, Kannourakis, George, Findlay, Jock, Ahmed, Nuzhat
- Authors: Chan, Emily , Luwor, Rodney , Burns, Christopher , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2018
- Type: Text , Journal article
- Relation: Oncotarget Vol. 9, no. 24 (2018), p. 16599-16618
- Full Text:
- Reviewed:
- Description: Despite a good initial response to front-line chemotherapy, majority of the ovarian cancer patients relapse with consecutive phases of recurrences; and nearly 60% die within 5 years due to the development of a chemoresistant disease. This study investigated whether inhibition of the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway by momelotinib is sufficient in suppressing tumor burden and prolonging the disease-free survival period in a mouse model of ovarian cancer. We demonstrate that paclitaxel treatment enhanced JAK2/STAT3 activation which resulted in the enrichment of cancer stem cell (CSC)- like phenotype in the surviving ovarian cancer cells in vitro and in in vivo mouse xenografts. Combined treatment with paclitaxel and momelotinib inhibited paclitaxelinduced JAK2/STAT3 activation and CSC-like development in mice xenografts, and consequently reduced the tumor burden significantly greater than that achieved by paclitaxel-treatment alone. However, robust recurrent tumor growth with enhanced JAK2/STAT3 activation and CSC-like phenotype was observed in all mice groups after termination of treatments, but was delayed significantly in the paclitaxel and momelotinib treated group compared to other treatment groups. Daily oral gavage of momelotinib after termination of paclitaxel treatment showed sustained inhibition of tumor growth and a prolonged disease-free survival period in 50% of the mice. The other 50% of mice that developed tumors with ongoing momelotinib treatment also showed significantly increased survival benefit and a smaller tumor burden. These preliminary findings may have a profound clinical impact in developing an effective momelotinib-based 'maintenance-therapy' in ovarian cancer patients' postchemotherapy treatment. © Chan et al.
- Authors: Chan, Emily , Luwor, Rodney , Burns, Christopher , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2018
- Type: Text , Journal article
- Relation: Oncotarget Vol. 9, no. 24 (2018), p. 16599-16618
- Full Text:
- Reviewed:
- Description: Despite a good initial response to front-line chemotherapy, majority of the ovarian cancer patients relapse with consecutive phases of recurrences; and nearly 60% die within 5 years due to the development of a chemoresistant disease. This study investigated whether inhibition of the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway by momelotinib is sufficient in suppressing tumor burden and prolonging the disease-free survival period in a mouse model of ovarian cancer. We demonstrate that paclitaxel treatment enhanced JAK2/STAT3 activation which resulted in the enrichment of cancer stem cell (CSC)- like phenotype in the surviving ovarian cancer cells in vitro and in in vivo mouse xenografts. Combined treatment with paclitaxel and momelotinib inhibited paclitaxelinduced JAK2/STAT3 activation and CSC-like development in mice xenografts, and consequently reduced the tumor burden significantly greater than that achieved by paclitaxel-treatment alone. However, robust recurrent tumor growth with enhanced JAK2/STAT3 activation and CSC-like phenotype was observed in all mice groups after termination of treatments, but was delayed significantly in the paclitaxel and momelotinib treated group compared to other treatment groups. Daily oral gavage of momelotinib after termination of paclitaxel treatment showed sustained inhibition of tumor growth and a prolonged disease-free survival period in 50% of the mice. The other 50% of mice that developed tumors with ongoing momelotinib treatment also showed significantly increased survival benefit and a smaller tumor burden. These preliminary findings may have a profound clinical impact in developing an effective momelotinib-based 'maintenance-therapy' in ovarian cancer patients' postchemotherapy treatment. © Chan et al.
Tumour microenvironment and metabolic plasticity in cancer and cancer stem cells : Perspectives on metabolic and immune regulatory signatures in chemoresistant ovarian cancer stem cells
- Ahmed, Nuzhat, Escalona, Ruth, Leung, Dilys, Chan, Emily, Kannourakis, George
- Authors: Ahmed, Nuzhat , Escalona, Ruth , Leung, Dilys , Chan, Emily , Kannourakis, George
- Date: 2018
- Type: Text , Journal article , Review
- Relation: Seminars in Cancer Biology Vol. 53, no. (2018), p. 265-281
- Full Text:
- Reviewed:
- Description: Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
- Authors: Ahmed, Nuzhat , Escalona, Ruth , Leung, Dilys , Chan, Emily , Kannourakis, George
- Date: 2018
- Type: Text , Journal article , Review
- Relation: Seminars in Cancer Biology Vol. 53, no. (2018), p. 265-281
- Full Text:
- Reviewed:
- Description: Cancer stem cells (CSCs) are a sub-population of tumour cells, which are responsible to drive tumour growth, metastasis and therapy resistance. It has recently been proposed that enhanced glucose metabolism and immune evasion by tumour cells are linked, and are modulated by the changing tumour microenvironment (TME) that creates a competition for nutrient consumption between tumour and different sub-types of cells attracted to the TME. To facilitate efficient nutrient distribution, oncogene-induced inflammatory milieu in the tumours facilitate adaptive metabolic changes in the surrounding non-malignant cells to secrete metabolites that are used as alternative nutrient sources by the tumours to sustain its increasing energy needs for growth and anabolic functions. This scenario also affects CSCs residing at the primary or metastatic niches. This review summarises recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the TME. We also discuss how the evolving TME modulates tumour cells and CSCs in cancer progression. Using previously described proteomic and genomic platforms, ovarian cancer cell lines and a mouse xenograft model we highlight the existence of metabolic and immune regulatory signatures in chemoresistant ovarian CSCs, and discuss how these processes may affect recurrence in ovarian tumours. We propose that progress in cancer control and eradication may depend not only on the elimination of highly chemoresistant CSCs, but also in designing novel strategies which would intervene with the tumour-promoting TME factors.
- Heiniger, Louise, Smith, Allan, Olver, Ian, Grimison, Peter, Klein, Britt, Wootten, Addie, Abbott, Jo-Anne, Price, Melanie, McJannett, Margaret, Tran, Ben, Stockler, Martin, Gurney, Howard, Butow, Phyllis
- Authors: Heiniger, Louise , Smith, Allan , Olver, Ian , Grimison, Peter , Klein, Britt , Wootten, Addie , Abbott, Jo-Anne , Price, Melanie , McJannett, Margaret , Tran, Ben , Stockler, Martin , Gurney, Howard , Butow, Phyllis
- Date: 2017
- Type: Text , Journal article
- Relation: European Journal of Cancer Care Vol. 26, no. 6 (2017), p. 1-10
- Full Text: false
- Reviewed:
- Description: e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme. Six men also completed a qualitative interview to provide detailed feedback on their experiences using e-TC. Fourteen men (56%) completed at least 80% of the programme. Participants reported a high level of satisfaction with the programme. Men's limited time was a barrier to programme use and completion, and participants suggested that men with a more recent diagnosis and a higher level of distress may be more likely to engage with the programme. e-TC appears to be a feasible and acceptable online intervention for survivors of testicular cancer. Findings from this study are currently being used to refine e-TC and guide the design of a larger efficacy study. © 2017 John Wiley & Sons Ltd
- Wootten, Addie C, Meyer, Denny, Abbott, Jo-Anne, Chisholm, Katherine, Austin, David, Klein, Britt, McCabe, Marita, Murphy, Declan G, Costello, Anthony
- Authors: Wootten, Addie C , Meyer, Denny , Abbott, Jo-Anne , Chisholm, Katherine , Austin, David , Klein, Britt , McCabe, Marita , Murphy, Declan G , Costello, Anthony
- Date: 2016
- Type: Text , Journal article
- Relation: Psycho-Oncology Vol. 26, no. 7 (2016), p. 975-981
- Full Text: false
- Reviewed:
- Description: BACKGROUND: Prostate cancer treatment often results in significant psycho-sexual challenges for men following treatment; however, many men report difficulty in accessing appropriate care. METHODS: A randomized controlled trial was undertaken to assess the efficacy of a 10-week self-guided online psychological intervention called My Road Ahead (MRA) for men with localized prostate cancer in improving sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone or MRA plus online forum, or forum access alone. Pre, post, and follow-up assessments of overall sexual satisfaction were conducted. Mixed models and structural equation modeling were used to analyze the data. RESULTS: One hundred forty-two men (mean age 61 y; SD = 7) participated. The majority of participants had undergone radical prostatectomy (88%) and all men had received treatment for localized prostate cancer. Significant differences were obtained for the 3 groups (P = .026) and a significant improvement in total sexual satisfaction was observed only for participants who were allocated to MRA + forum with a large effect size (P = .004, partial eta2 = 0.256). Structural equation modeling indicated that increases in sexual function, masculine self-esteem, and sexual confidence contributed significantly to overall sexual satisfaction for the MRA + forum plus forum condition. CONCLUSIONS: This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men with prostate cancer. The findings indicate the potential for MRA to deliver support that men may not otherwise receive and also highlight the importance of psychological intervention to facilitate improved sexual outcomes.
Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer
- Samardzija, Chantel, Luwor, Rodney, Quinn, Michael, Kannourakis, George, Findlay, Jock, Ahmed, Nuzhat
- Authors: Samardzija, Chantel , Luwor, Rodney , Quinn, Michael , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2016
- Type: Text , Journal article
- Relation: BMC Cancer Vol. 16, no. 1 (2016), p. 1-16
- Full Text:
- Reviewed:
- Description: Background: Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis. Methods: The expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice. Results: We report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin β1 expression and associated α5 and α2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34 and CD31 compared to vector control cell-derived xenografts. Conclusion: The expression of Oct4A may be crucial to promote and sustain integrin-mediated extracellular matrix (ECM) remodeling requisite for tumor metastasis in ovarian cancer patients. © 2016 The Author(s).
- Authors: Samardzija, Chantel , Luwor, Rodney , Quinn, Michael , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2016
- Type: Text , Journal article
- Relation: BMC Cancer Vol. 16, no. 1 (2016), p. 1-16
- Full Text:
- Reviewed:
- Description: Background: Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis. Methods: The expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice. Results: We report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin β1 expression and associated α5 and α2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34 and CD31 compared to vector control cell-derived xenografts. Conclusion: The expression of Oct4A may be crucial to promote and sustain integrin-mediated extracellular matrix (ECM) remodeling requisite for tumor metastasis in ovarian cancer patients. © 2016 The Author(s).
- Davis, Ian, Long, A., Yip, Sonia, Espinoza, David, Thompson, John F., Kichenadasse, G., Harrison, M., Lowenthal, R. M., Pavlakis, N., Azad, Arman, Kannourakis, George, Steer, C., Goldstein, D., Shapiro, J., Harvie, R., Jovanovic, L., Hudson, Amanda, Nelson, Chris, Stockler, Martin, Martin, Andrew
- Authors: Davis, Ian , Long, A. , Yip, Sonia , Espinoza, David , Thompson, John F. , Kichenadasse, G. , Harrison, M. , Lowenthal, R. M. , Pavlakis, N. , Azad, Arman , Kannourakis, George , Steer, C. , Goldstein, D. , Shapiro, J. , Harvie, R. , Jovanovic, L. , Hudson, Amanda , Nelson, Chris , Stockler, Martin , Martin, Andrew
- Date: 2015
- Type: Text , Journal article
- Relation: Annals of Oncology Vol. 26, no. 6 (2015), p. 1118-1123
- Full Text: false
- Reviewed:
- Description: Background: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results: We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received >= 22 weeks of alternating therapy; 78% received >= 22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.
- Alqahtani, Mohammed, Jones, Linda
- Authors: Alqahtani, Mohammed , Jones, Linda
- Date: 2015
- Type: Text , Journal article
- Relation: European Journal of Oncology Nursing Vol. 19, no. 1 (2015), p. 44-49
- Full Text: false
- Reviewed:
- Description: Pain is an unpleasant human experience, often associated with underlying medical conditions, and a key reason for individuals experiencing pain to seek medical advice. However, the pain experience is unique and subjective, and affects people's quality of life, as well as impacting on their concerned family members. Optimal pain management requires adequate knowledge, a positive attitude, and competent pain assessment measures. It has been reported that oncology nurses in the Kingdom of Saudi Arabia (KSA) have inadequate knowledge, assessment skills and management of pain. Objective: This paper aims to examine nurses' knowledge and attitudes regarding pain management in Saudi Arabian hospitals (SA). Method: A cross-sectional survey was administered to 320 nurses exhibiting considerable racial, cultural, religious and professional diversity, working in oncology units at five hospitals in the KSA. Self-completed survey questionnaires were distributed using the 'Knowledge and Attitudes Survey Regarding Pain' (KASRP) tool. Results: The nurses exhibited a relatively poor overall knowledge of pain management (mean score=45.1%; 95% CI=43.9%, 46.2%). The mean KASRP scores varied significantly at α=0.05 with respect to the nurses' nationality, whether they had attended pain-related courses, and whether they had participated in research. Conclusion: The results indicate the urgency needed to reform pain management education for oncology nurses in the KSA. © 2014 Elsevier Ltd.
Measurement of absolute copy number variation reveals association with essential hypertension
- Marques, Francine, Prestes, Priscilla, Pinheiro, Leonardo, Scurrah, Katrina, Emslie, Kerry, Tomaszewski, Maciej, Harrap, Stephen, Charchar, Fadi
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
- Authors: Marques, Francine , Prestes, Priscilla , Pinheiro, Leonardo , Scurrah, Katrina , Emslie, Kerry , Tomaszewski, Maciej , Harrap, Stephen , Charchar, Fadi
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Medical Genomics Vol. 7, no. (2014), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: The role of copy number variation (CNV) has been poorly explored in essential hypertension in part due to technical difficulties in accurately assessing absolute numbers of DNA copies. Droplet digital PCR (ddPCR) provides a powerful new approach to CNV quantitation. The aim of our study was to investigate whether CNVs located in regions previously associated with blood pressure (BP) variation in genome-wide association studies (GWAS) were associated with essential hypertension by the use of ddPCR. Methods: Using a "power of extreme" approach, we quantified nucleic acids using ddPCR in white subjects from the Victorian Family Heart Study with extremely high (n = 96) and low (n = 92) SBP, providing power equivalent to 1714 subjects selected at random. Results: A deletion of the CNVs esv27061 and esv2757747 on chromosome 1p13.2 was significantly more prevalent in extreme high BP subjects after adjustment for age, body mass index and sex (12.6% vs. 2.2%; P = 0.013). Conclusions: Our data suggests that CNVs within regions identified in previous GWAS may play a role in human essential hypertension.
My Road Ahead study protocol: A randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer
- Wootten, Addie, Abbott, Jo-Anne, Chisholm, Katherine, Austin, David, Klein, Britt, McCabe, Marita, Meyer, Denny, Costello, Anthony, Murphy, Declan
- Authors: Wootten, Addie , Abbott, Jo-Anne , Chisholm, Katherine , Austin, David , Klein, Britt , McCabe, Marita , Meyer, Denny , Costello, Anthony , Murphy, Declan
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Cancer Vol. 14, no. 1 (2014), p.83
- Full Text:
- Reviewed:
- Description: Background: There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone. Methods/design: This study utilises a RCT design with three groups receiving: 1) the 6-module My Road Ahead intervention alone; 2) the My Road Ahead intervention plus a moderated online forum; and 3) the moderated online forum alone. It is expected that 150 men with localised prostate cancer will be recruited into the RCT. Online measures will assess men's psychological distress as well as sexual and relationship adjustment at baseline, post-intervention, 3 month follow-up and 6 month follow-up. The study is being conducted in Australia and participants will be recruited from April 2012 to Feb 2014. The primary aim of this study is to evaluate the efficacy of My Road Ahead in reducing psychological distress. Discussion: To our knowledge, My Road Ahead is the first self-directed online psychological intervention developed for men who have been treated for localised prostate cancer. The RCT will assess the efficacy of this intervention in improving psychological well-being, sexual satisfaction, relationship satisfaction and overall quality of life. If successful, this intervention could provide much needed support to men receiving treatment for localised prostate cancer in a highly accessible manner. Trial registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12611000278932. © 2014 Wootten et al.; licensee BioMed Central Ltd.
- Authors: Wootten, Addie , Abbott, Jo-Anne , Chisholm, Katherine , Austin, David , Klein, Britt , McCabe, Marita , Meyer, Denny , Costello, Anthony , Murphy, Declan
- Date: 2014
- Type: Text , Journal article
- Relation: BMC Cancer Vol. 14, no. 1 (2014), p.83
- Full Text:
- Reviewed:
- Description: Background: There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone. Methods/design: This study utilises a RCT design with three groups receiving: 1) the 6-module My Road Ahead intervention alone; 2) the My Road Ahead intervention plus a moderated online forum; and 3) the moderated online forum alone. It is expected that 150 men with localised prostate cancer will be recruited into the RCT. Online measures will assess men's psychological distress as well as sexual and relationship adjustment at baseline, post-intervention, 3 month follow-up and 6 month follow-up. The study is being conducted in Australia and participants will be recruited from April 2012 to Feb 2014. The primary aim of this study is to evaluate the efficacy of My Road Ahead in reducing psychological distress. Discussion: To our knowledge, My Road Ahead is the first self-directed online psychological intervention developed for men who have been treated for localised prostate cancer. The RCT will assess the efficacy of this intervention in improving psychological well-being, sexual satisfaction, relationship satisfaction and overall quality of life. If successful, this intervention could provide much needed support to men receiving treatment for localised prostate cancer in a highly accessible manner. Trial registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12611000278932. © 2014 Wootten et al.; licensee BioMed Central Ltd.
The impact of prostate cancer on partners: A qualitative exploration
- Wootten, Addie, Abbott, Jo-Anne, Osborne, Dawn, Austin, David, Klein, Britt, Costello, Anthony, Murphy, Declan
- Authors: Wootten, Addie , Abbott, Jo-Anne , Osborne, Dawn , Austin, David , Klein, Britt , Costello, Anthony , Murphy, Declan
- Date: 2014
- Type: Text , Journal article
- Relation: Psycho-Oncology Vol. 23, no. 11 (2014), p. 1252-1258
- Full Text: false
- Reviewed:
- Description: Objective: Prostate cancer and its treatment can result in numerous physical and psychological morbidities for the patient as well as his partner. This qualitative study aimed to explore the experiences of intimate spouses or partners of men diagnosed and/or treated for prostate cancer to better understand the personal impact of prostate cancer on the partner. Methods: Twenty-seven partners participated in this study. Six focus groups were convened, and one in-depth interview was undertaken to explore the practical impact of prostate cancer on the intimate spouse/partner. All discussions were audio-recorded and transcribed and then coded using a thematic approach. Results: Six themes emerged: (a) The influence of the man's response to prostate cancer on the partner, (b) The need to be involved in treatment and medical decision making, (c) Supporting a man who is experiencing a loss of masculinity, (d) Degree of congruence between each partner's coping responses, (e) Constrained communication, and (f) Changed roles and increased practical management. Conclusions: It is clear that prostate cancer impacts substantially on many areas of partner well-being. An effective intervention provided to this population seems warranted and may lead to improvements in partner well-being, assist the couple in lessening the impact of prostate cancer and its treatment on their relationship, and assist in the man's recovery. © 2014 John Wiley & Sons, Ltd.