Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN

The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P<0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P<0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.

Microarray expression profiling in melanoma reveals a BRAF mutation signature

We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase (MAPK) activation (either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.

Quality of life of women with lower-limb lymphedema following gynecological cancer

Secondary lower-limb lymphedema can develop following treatment for gynecological cancers, and has debilitating effects on quality of life (QoL). Lymphedema can limit mobility and ability to perform daily activities, and have adverse effects on psychological and social wellbeing. When assessing the effect of lymphedema treatment methods, the focus is on change in clinically measured lymphedema status, rather than QoL outcomes. Considering that treatment for lymphedema involves a significant and ongoing commitment from patients, it is essential to determine whether the benefits to patients outweigh the burden associated with treatment. This article summarizes the results of studies assessing the impact of lower-limb lymphedema on QoL in women with gynecological cancer, evaluates their methodologies and discusses limitations and priorities for future research.

Lymphedema after breast or gynecological cancer : use and effectiveness of mainstream and complementary therapies

Objectives: The purpose of this study was to describe the use, as well as perceived effectiveness, of mainstream and complementary and alternative medicine (CAM) therapies in the treatment of lymphedema following breast or gynecological cancer. Further, the study assessed the relationship between the characteristics of lymphedema (including type, severity, stability, and duration), and the use of CAM and/or mainstream treatment. Methods: This was a cross-sectional study using a convenience sample of women with lymphedema following breast and gynecological cancers. A self-administered questionnaire was sent to 247 potentially eligible women. Of those returned (50%), 23 were ineligible and 6 were excluded due to level of missing data. Results: In the previous 12 months, the majority of women (90%) had used mainstream treatments to treat their lymphedema, with massage being the most commonly used (86%). One (1) in 2 women had used CAM to treat their lymphedema, and 98% of those using CAM were also using mainstream treatments. Over 27 types of CAM were reported, with use of a chi machine, vitamin E supplements, yoga, and meditation being the most commonly reported forms. The perceived effectiveness ratings (1–7 with 7 = completely effective) of mainstream(mean – standard deviation (SD): 5.3 – 1.5) and CAM therapies (mean – SD: 5.2 + 1.6) were considered high. Conclusions: These results demonstrate that mainstream and CAM treatment use is common, varied, and considered to be effective among women with lymphedema following breast or gynecological cancer. Furthermore, it highlights the immediate need for larger prospective studies assessing the inter-relationship between the use of mainstream and CAM therapies for treatment success.

Impact of disability on families : Grandparents’ perspectives

Background Caring for a child with a disability can be a unique and challenging experience, with families often relying on informal networks for support. Often, grandparents are key support resources, yet little is known about their roles and experiences. Reporting on data collected in a larger Australian study, this article explores grandparents' experiences of caring for a child with a disability and the impact on their family relationships and quality of life. Method A qualitative purposive sampling design was utilised; semi-structured interviews were conducted with 22 grandparents (17 women, 5 men) of children with a disability. Grandparents ranged in age from 55 to 75 years old and lived within a 90-min drive of Brisbane, Australia. Interviews were transcribed and responses analysed using a thematic approach, identifying categories, themes and patterns. Findings Four key themes characterised grandparents' views about their role in the family: holding own emotions (decision to be positive), self-sacrifice (decision to put family needs first), maintaining family relationships (being the ‘go-between’) and quality of life for family in the future (concerns about the future). Conclusions Grandparents are central to family functioning and quality of life, but this contribution comes with a significant cost to their own personal well-being. Implications for policy, practice and research are discussed, particularly grandparents' fear that their family could not cope without their support.

Fitting in : a pervasive new graduate nurse need

Aim: This qualitative study aims to provide insight into how Australian New Graduate Nurses (NGNs) experienced their transition to acute care nursing practice. Method: Nine NGNs each participated in three in-depth interviews conducted across their first year of practice. Constant comparative analysis was used to identify the emergent themes. Findings: The desire to fit in (establishment of secure social bonds) with ward staff is an important element of NGN transition experiences. Fitting in was about feeling one's self to be part of a social group, and participants made it clear that their perceptions of their success in establishing secure and meaningful social bonds in each new ward was extremely important for their sense of being as NGNs. Current NGN Transition Programmes (NGNTPs) involve multiple ward rotations, increasing the demand for the NGN to fit in. Thus participants were engaged in a deeply personal transition experience that was not necessarily aligned with multiple ward rotations. Conclusions: Although NGNTPs have the word “transition” in their title, it may be that current programmes are more focussed on organisations’ desire to “orient” NGNs to working within the acute care setting than facilitating personal transitions to practice. Further investigation of the impact of NGNTPs on NGNs and the associated multiple ward rotations is required.

Weight management and its role in breast cancer rehabilitation

Overweight and obesity are risk factors for post-menopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery since obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent co-morbid conditions (e.g. cardiovascular disease and diabetes), poorer surgical outcomes (e.g., increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and co-morbidity, and improving lifestyle behaviors, functional status, and quality of life in this high-risk patient population.

More than just audiences

The creativity in audience engagement is not simply a delight for marketing or communications teams. New ways of engaging young audiences is now about everything from the actual art-making processes and outcomes to the hype surrounding your venue and your artists. In the process of reviewing and reporting on recent Australian and international research and practice this panel will comment upon the strengths and weakness of different ways of framing engagement: as learning, as social participation, as creative expression, and as co-creation.

'My grandchild has a disability' : impact on grandparenting identity, roles and relationships

Being a grandparent is an important and valued role for many older adults, who often have strong views about the type of grandparent they will be and what they will teach their grandchild. When their grandchild has a disability, grandparents may have to significantly adjust their expectations and interactions. This research explores if and how having a grandchild with a disability influences grandparents’ sense of identity and enactment of the grandparent role. Using qualitative purposive sampling, semi-structured interviews were conducted with 22 grandparents of children with an intellectual and/or physical disability residing in Brisbane, Australia. A thematic analysis identified three key themes characterising grandparent’s views: formation of grandparenting identity, styles of grandparenting, and role enactment. The results highlight the critical role of grandparents when a child has a disability, illustrating that the grandparenting experience and role enactment may be universal with only the context and delivery varying.