Family coping: issues and challenges for cancer nursing

A large body of research now exists suggesting that families are dramatically affected by a diagnosis of cancer, and that they have a wide range of support needs. In particular, evidence suggests that the emotional strains of living with a family member who has cancer are an especially difficult coping challenge, and that such strains have a significant impact on the day-to-day lives of family members. Despite this evidence, there has been little analysis to date on the nature of the families' experience with cancer and what implications the unique features of family relationships and interactions in the context of cancer have for nursing practice. Some of these specific features of the families' experience with cancer are examined in this article. It is suggested that enormous scope exists for improving nurses' contribution to care for families of people with cancer. Specific recommendations for achieving such improvements include a critical review of the constraints that exist on efforts to care for families, and the development of approaches to care that appreciate the interconnectedness of family responses and the considerable needs of family members for emotional and practical support.

A study of post diagnosis breast cancer concerns for women living in rural and remote Queensland. Part I : Personal concerns

The findings presented in this paper are part of a research project designed to provide a preliminary indication of the support needs of postdiagnosis women with breast cancer in remote and isolated areas in Queensland. This discussion will present data that focuses on the women’s expressed personal concerns. For participants in this research a diagnosis of breast cancer involves a confrontation with their own mortality and the possibility of a reduced life span. This is a definite life crisis, creating shock and needing considerable adjustment. Along with these generic issues the participants also articulated significant issues in relation to their experience as women in a rural setting. These concerns centred around worries about how their partner and families cope during their absences for treatment, the additional burden on the family of having to cope with running the property or farm during the participant’s absence or illness, added financial strain brought about by the cost of travel for treatment, maintenance of properties during absences, and problems created by time off from properties or self-employment. These findings accord with other reports of health and welfare services for rural Australian and the generic literature on psycho-oncology studies of breast cancer.

A study of postdiagnosis breast cancer concerns for women living in rural and remote Queensland. Part II : support issues

This paper presents the recent findings from a study on the postdiagnosis support needs of women with breast cancer living in rural and remote Queensland. The findings presented in this discussion focus on support needs from the perspective of the women experiencing breast cancer as well as health service providers. The tyranny of distance imposes unique hardships, such as separation from family and friends, during a time of great vulnerability for treatment, the need to travel long distances for support and follow-up services, and extra financial burdens, which can combine to cause strains on the marital relationship and family cohesion. Positive indications are, however, that the rural communities operate on strong, informal networks of support. This network of family, friends and community can, and does, play an active role in the provision of emotional and practical support.

Towards a reconceptualization of hope for patients with a diagnosis of cancer

Recent years have seen increased attention given to examining the phenomenon of hope in patients with metastatic cancer One of the results of this activity has been a greater appreciation of the significance of hope for the dying patient However, there are many questions about the experience of hope and its impact on the lives of patients with cancer which remain to be answered This paper discusses how hope is currently conceptualized in the nursing literature, and considers the implications that this conceptualization has for how we care for cancer patients Some alternative ways of looking at the experience and the impact of hope are also discussed

Patients with terminal cancer who use alternative therapies: their beliefs and practices

This paper examines the extent to which patients who have been diagnosed as having terminal cancer choose to use non-medical therapies. In particular it is concerned with the illness behaviour of patients who are receiving conventional cytotoxic drug and radiation treatments, who also decide to use a wide range of ‘alternative’ medications and therapies. The paper discusses the findings of a study of 152 patients with metastatic cancer that examined the extent to which they used alternative cancer therapies, as well as the beliefs and attitudes they have about their cancer, its treatment, and the practitioners providing that treatment. Four groups of users of alternative therapies, who differ according to their commitment to and the type of therapies they use, were identified. Results of logistic regression analyses indicate that those using alternative therapies were different in range of social attitudes. These differences were primarily their greater reported ‘will to live’ and desire for control over treatment decisions, and the differing beliefs they hold about their disease.

In vitro functional characterisation of IGF-I : VN-induced breast cancer progression

Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.

Developing an adaptive radiotherapy technique for virally mediated head and neck cancer

Purpose Virally mediated head and neck cancers (VMHNC) often present with nodal involvement and are highly radioresponsive, meaning that treatment plan adaptation during radiotherapy (RT) in a subset of patients is required. We sought to determine potential risk profiles and a corresponding adaptive treatment strategy for these patients. Methodology 121 patients with virally mediated, node positive nasopharyngeal (Epstein Barr Virus positive) or oropharyngeal (Human Papillomavirus positive) cancers, receiving curative intent RT were reviewed. The type, frequency and timing of adaptive interventions, including source-to-skin distance (SSD) corrections, re-scanning and re-planning, were evaluated. Patients were reviewed based on the maximum size of the dominant node to assess the need for plan adaptation. Results Forty-six patients (38%) required plan adaptation during treatment. The median fraction at which the adaptive intervention occurred was 26 for SSD corrections and 22 for re-planning CTs. A trend toward 3 risk profile groupings was discovered: 1) Low risk with minimal need (< 10%) for adaptive intervention (dominant pre-treatment nodal size of ≤ 35 mm), 2) Intermediate risk with possible need (< 20%) for adaptive intervention (dominant pre-treatment nodal size of 36 mm – 45 mm) and 3) High-risk with increased likelihood (> 50%) for adaptive intervention (dominant pre-treatment nodal size of ≥ 46 mm). Conclusion In this study, patients with VMHNC and a maximum dominant nodal size of > 46 mm were identified at a higher risk of requiring re-planning during a course of definitive RT. Findings will be tested in a future prospective adaptive RT study.

Evolution and innovation in guardianship laws: Assisted decision-making

Guardianship laws in most Western societies provide decision-making mechanisms for adults with impaired capacity. Since the inception of these laws, the principle of autonomy and recognition of human rights for those coming within guardianship regimes has gained prominence. A new legal model has emerged, which seeks to incorporate ‘assisted decision-making’ models into guardianship laws. Such models legally recognise that an adult’s capacity may be maintained through assistance or support provided by another person, and provide formal recognition of the person in that ‘assisting’ role. This article situates this latest legal innovation within a historical context, examining the social and legal evolution of guardianship laws and determining whether modern assisted decision-making models remain consistent with guardianship reform thus far. It identifies and critically analyses the different assisted decision-making models which exist internationally. Finally, it discusses a number of conceptual, legal and practical concerns that remain unresolved. These issues require serious consideration before assisted decisionmaking models are adopted in guardianship regimes in Australia.

Do nursing interventions targeting concurrent symptoms hold promise for managing fatigue in patients with advanced cancer?

TO THE EDITOR: It was with great interest that I read two recent articles by de Raaf et al1, and Bruera et al2. These authors are to be congratulated for completing two of the very few high quality randomized trials that evaluate complex interventions for managing fatigue in patients with advanced cancer. de Raaf et al conducted a non-blinded RCT with 152 patients with advanced cancer and reported significant reduction of fatigue in patients who received a nurse-led monitoring and protocol-guided treatment of physical symptoms compared with those who received usual care1. Patients who received this intervention experienced a significant improvement over time in general fatigue, at one-month follow-up and two-month follow-up. Another recent RCT conducted with 141 patients with advanced cancer by Bruera et al2 did not find any benefits of a nursing telephone intervention that involved systematic symptom assessment/management, medication review, psychosocial support and patient education in fatigue reduction, compared to those who received a control telephone intervention conducted by a non-professional...

Genomic evidence for the parallel evolution of coastal forms in the Senecio lautus complex

Instances of parallel ecotypic divergence where adaptation to similar conditions repeatedly cause similar phenotypic changes in closely related organisms are useful for studying the role of ecological selection in speciation. Here we used a combination of traditional and next generation genotyping techniques to test for the parallel divergence of plants from the Senecio lautus complex, a phenotypically variable groundsel that has adapted to disparate environments in the South Pacific. Phylogenetic analysis of a broad selection of Senecio species showed that members of the S. lautus complex form a distinct lineage that has diversified recently in Australasia. An inspection of thousands of polymorphisms in the genome of 27 natural populations from the S. lautus complex in Australia revealed a signal of strong genetic structure independent of habitat and phenotype. Additionally, genetic differentiation between populations was correlated with the geographical distance separating them, and the genetic diversity of populations strongly depended on geographical location. Importantly, coastal forms appeared in several independent phylogenetic clades, a pattern that is consistent with the parallel evolution of these forms. Analyses of the patterns of genomic differentiation between populations further revealed that adjacent populations displayed greater genomic heterogeneity than allopatric populations and are differentiated according to variation in soil composition. These results are consistent with a process of parallel ecotypic divergence in face of gene flow.

Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells

An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.

The evolution and biogeography of the austral horse fly tribe Scionini (Diptera: Tabanidae: Pangoniinae) inferred from multiple mitochondrial and nuclear genes

Phylogenetic relationships within the Tabanidae are largely unknown, despite their considerable medical and ecological importance. The first robust phylogenetic hypothesis for the horse fly tribe Scionini is provided, completing the systematic placement of all tribes in the subfamily Pangoniinae. The Scionini consists of seven mostly southern hemisphere genera distributed in Australia, New Guinea, New Zealand and South America. A 5757. bp alignment of 6 genes, including mitochondrial (COI and COII), ribosomal (28S) and nuclear (AATS and CAD regions 1, 3 and 4) genes, was analysed for 176 taxa using both Bayesian and maximum likelihood approaches. Results indicate the Scionini are strongly monophyletic, with the exclusion of the only northern hemisphere genus Goniops. The South American genera Fidena, Pityocera and Scione were strongly monophyletic, corresponding to current morphology-based classification schemes. The most widespread genus Scaptia was paraphyletic and formed nine strongly supported monophyletic clades, each corresponding to either the current subgenera or several previously synonymised genera that should be formally resurrected. Molecular results also reveal a newly recognised genus endemic to New Zealand, formerly placed within Scaptia. Divergence time estimation was employed to assess the global biogeographical patterns in the Pangoniinae. These analyses demonstrated that the Scionini are a typical Gondwanan group whose diversification was influenced by the fragmentation of that ancient land mass. Furthermore, results indicate that the Scionini most likely originated in Australia and subsequently radiated to New Zealand and South American by both long distance dispersal and vicariance. The phylogenetic framework of the Scionini provided herein will be valuable for taxonomic revisions of the Tabanidae.

Timing, origin and emplacement dynamics of mass flows offshore of SE Montserrat in the last 110 ka : implications for landslide and tsunami hazards, eruption history, and volcanic island evolution

Mass flows on volcanic islands generated by volcanic lava dome collapse and by larger-volume flank collapse can be highly dangerous locally and may generate tsunamis that threaten a wider area. It is therefore important to understand their frequency, emplacement dynamics, and relationship to volcanic eruption cycles. The best record of mass flow on volcanic islands may be found offshore, where most material is deposited and where intervening hemipelagic sediment aids dating. Here we analyze what is arguably the most comprehensive sediment core data set collected offshore from a volcanic island. The cores are located southeast of Montserrat, on which the Soufriere Hills volcano has been erupting since 1995. The cores provide a record of mass flow events during the last 110 thousand years. Older mass flow deposits differ significantly from those generated by the repeated lava dome collapses observed since 1995. The oldest mass flow deposit originated through collapse of the basaltic South Soufriere Hills at 103-110 ka, some 20-30 ka after eruptions formed this volcanic center. A ∼1.8 km3 blocky debris avalanche deposit that extends from a chute in the island shelf records a particularly deep-seated failure. It likely formed from a collapse of almost equal amounts of volcanic edifice and coeval carbonate shelf, emplacing a mixed bioclastic-andesitic turbidite in a complex series of stages. This study illustrates how volcanic island growth and collapse involved extensive, large-volume submarine mass flows with highly variable composition. Runout turbidites indicate that mass flows are emplaced either in multiple stages or as single events.

Investigation of the 1758G>C and 2880A>G variants within the NCOA3 gene in a breast cancer affected Australian population

NCOA3 is a known low to moderate-risk breast cancer susceptibility gene, amplified in 5–10% and over expressed in about 60% of breast tumours. Additionally, this over expression is associated with Tamoxifen resistance and poor prognosis. Previously, two variants of NCOA3, 1758G > C and 2880A > G have been associated with breast cancer in two independent populations. Here we assessed the influence of the two NCOA3 variants on breast cancer risk by genotyping an Australian case–control study population. 172 cases and 178 controls were successfully genotyped for the 1758G > C variant and 186 cases and 182 controls were successfully genotyped for the 2880A > G variant using high-resolution melt analysis (HRM). The genotypes of the 1758G > C variant were validated by sequencing. χ2 tests were performed to determine if significant differences exist in the genotype and allele frequencies between the cases and controls. χ2 analysis returned no statistically significant difference (p > 0.05) for genotype frequencies between cases and controls for 1758G > C (χ2 = 0.97, p = 0.6158) or 2880A > G (χ2 = 2.09, p = 0.3516). Similarly, no statistical difference was observed for allele frequencies for 1758G > C (χ2 = 0.07, p = 0.7867) or 2880A > G (χ2 = 0.04, p = 0.8365). Haplotype analysis of the two SNPs also showed no difference between the cases and the controls (p = 0.9585). Our findings in an Australian Caucasian population composed of breast cancer sufferers and an age matched control population did not support the findings of previous studies demonstrating that these markers play a significant role in breast cancer susceptibility. Here, no significant difference was detected between breast cancer patients and healthy matched controls by either the genotype or allele frequencies for the investigated variants (all p ≥ 0.05). While an association of the two variants and breast cancer was not detected in our case–control study population, exploring these variants in a larger population of the same kind may obtain results in concordance with previous studies. Given the importance of NCOA3 and its involvement in biological processes involved in breast cancer and the possible implications variants of the gene could have on the response to Tamoxifen therapy, NCOA3 remains a candidate for further investigations.

Investigation of two Wnt signalling pathway single nucleotide polymorphisms in a breast cancer-affected Australian population

In the mammary gland, Wnt signals are strongly implicated in initial development of the mammary rudiments and in the ductal branching and alveolar morphogenesis that occurs during pregnancy. Previously, we identified two Wnt signaling pathway-implicated genes, PPP3CA and MARK4, as having a role in more aggressive and potentially metastatic breast tumors. In this study, we examined two SNPs within PPP3CA and MARK4 in an Australian case-control study population for a potential role in human breast cancers. 182 cases and 180 controls were successfully genotyped for the PPP3CA SNP (rs2850328) and 182 cases and 177 controls were successfully genotyped for the MARK4 SNP (rs2395) using High Resolution Melt (HRM) analysis. Genotypes of randomly selected samples for both SNPs were validated by dye terminator sequencing. Chi-square tests were performed to determine any significant differences in the genotype and allele frequencies between the cases and controls. Chi-square analysis showed no statistically significant difference (p > .05) for genotype frequencies between cases and controls for rs2850328 (χ2 = 1.2, p = .5476) or rs2395 (χ2 = .3, p = .8608). Similarly, no statistical difference was observed for allele frequencies for rs2850328 (χ2 = .68, p = .4108) or rs2395 (χ2 = .02, p = .893). Even though an association of the polymorphisms rs2850328 and rs2395 and breast cancer was not detected in our case-control study population, other variants within the PPP3CA and MARK4 genes may still be associated with breast cancer, as both genes are implicated with processes involved in the disease as well as their mutual partaking in the Wnt signaling pathway.