Retrospective analysis of cancer survival across South-Western Victoria in Australia

OBJECTIVE: This paper aims to describe cancer survival and examine association between survival and socio-demographic characteristics across Barwon South-Western region (BSWR) in Victoria, Australia. DESIGN: This study is based on the retrospective cohort database of patients accessing oncology services across BSWR. SETTING: Six rural and three urban hospital settings across the BSWR. PARTICIPANTS: The participants were patients who were diagnosed with cancer in 2009. MAIN OUTCOME MEASURES: Overall survival (OS) of participants was the main outcome measure. RESULTS: Total of 1778 eligible patients had four-year OS for all cancers combined of 59.7% (95% CI, 57.4-62.0). Improved OS was observed for patients in the upper socio-economic tertile (64.2%; 95% CI, 60.9-67.5) compared to the middle (59.3%; 95% CI, 55.5-63.1) and lowest tertiles (49.6%; 95% CI, 44.2-54.9) (P < 0.01). On multivariate analyses, higher socio-economic status remained a significant predictor of OS adjusting for gender, remoteness and age (HR [hazard ratio] 0.81; 95% CI 0.74-0.89; P < 0.01). Remoteness was significantly associated with improved OS after adjusting for age, gender and socio-economic status (HR 0.86; 95% CI, 0.77-0.97; P = 0.01). Older age ≥70 years compared to <70 years conferred inferior OS (HR 3.08; 95% CI, 2.64-3.59; P < 0.01). CONCLUSIONS: Our study confirmed improved survival outcomes for patients of higher socio-economic status and younger age. Future research to explain the unexpected survival benefit in patients who lived in more remote areas should examine factors including the correlation between geographical residence and eventual treatment facility as well as compare the BSWR care model to other regions' approaches.

Fibroblast growth factor-2 over-rides insulin-like growth factor-I induced proliferation and cell survival in human neuroblastoma cells

The insulin-like growth factor (IGF) system is a key regulator of cell growth, survival and differentiation, and these functions are co-modulated by other growth factors including fibroblast growth factor-2 (FGF-2). To investigate IGF/FGF interactions in neuronal cells, we employed neuroblastoma cells (SK-N-MC). In serum free conditions proliferation of the SK-N-MC cells was promoted by IGF-I (25 ng/ml), but blunted by FGF-2 (50 ng/ml). IGF-I-induced proliferation was abolished in the presence of FGF-2 even when IGF-I was used at 100 ng/ml. In addition to our previously described FGF-2 induced proteolytic cleavage of IGFBP-2, we found that FGF-2 increased IGFBP-6 levels in conditioned medium (CM) without affecting IGFBP-6 mRNA abundance. Modulation of IGFBP-2 and -6 levels were not significant mechanisms involved in the blockade of IGF-I action since the potent IGF-I analogues [QAYL]IGF-I and des(1-3)IGF-I (minimal IGFBP affinity) were unable to overcome FGF-2 inhibition of cell proliferation. FGF-2 treated cells showed morphological differentiation expressing the TUJ1 neuronal marker while cells treated with IGF-I alone showed no morphological change. When IGF-I was combined with FGF-2, however, cell morphology was indistinguishable from that seen with FGF-2 alone. FGF-2 inhibited proliferation and enhanced differentiation was also associated with a 70% increase in cell death. Although IGF-I alone was potently anti-apoptotic (60% decreased), IGF-I was unable to prevent apoptosis when administrated in combination with FGF-2. Gene-array analysis confirmed FGF-2 activation of the intrinsic and extrinsic apoptotic pathways and blockade of IGF anti-apoptotic signaling. FGF-2, directly and indirectly, overcomes the proliferative and anti-apoptotic activity of IGF-I by complex mechanisms, including enhancement of differentiation and apoptotic pathways, and inhibition of IGF-I induced anti-apoptotic signalling. Modulation of IGF binding protein abundance by FGF-2 does not play a significant role in inhibition of IGF-I induced mitogenesis.

Dietary patterns, assessed from a weighed food record, and survival among elderly participants from the United Kingdom

Background/Objectives: There is variability in the association between dietary intake and health outcomes across different countries, especially among the elderly. We used the gold standard dietary assessment method, a weighed food record, to examine the association between dietary pattern and mortality in a representative sample of community dwelling participants from Great Britain aged 65 years and older.

Subjects/Methods: Dietary intake was recorded at baseline in 1017 elderly participants (520 men, 497 women, mean age 76.3±7.4 years). Exploratory factor analysis was performed to examine dietary patterns and participants were followed up over an average of 9.2 years for mortality.

Results: The factor analysis revealed four interpretable principal components accounting for approximately 9.8% of the total variance, with similar patterns across sex. A ‘Mediterranean-style’ dietary pattern explained the greatest proportion of the variance (3.7%), followed by ‘health-aware’ (2.2%), ‘traditional’ (2.0%) and ‘sweet and fat’ (1.9%) factors. There were a total of 683 deaths through follow-up. After adjustment for potential confounders, only the Mediterranean-style dietary pattern remained associated with mortality (highest vs lowest tertile; hazard ratio¼0.82, 95% CI, 0.68–1.00). The benefits of the Mediterranean-style diet were only observed among women (hazard ratio¼0.71, 95% CI 0.52–0.96) although in men the traditional diet was a risk factor for mortality (hazard ratio¼1.30, 95% CI 1.00–1.71).

Conclusions: Using a gold standard approach, our results confirm previous evidence that dietary patterns are important in longevity among the elderly.

Uncoupling the mechanisms that facilitate cell survival in hormone-deprived bovine mammary explants

Mammary explants can be hormonally stimulated to mimic the biochemical changes that occur during lactogenesis. Previous studies using mammary explants concluded that the addition of exogenous macromolecules were required for mammary epithelial cells to remain viable in culture. The present study examines the survival of mammary explants from the dairy cow using milk protein gene expression as a functional marker of lactation and cell viability. Mammary explants cultured from late pregnant cows mimicked lactogenesis and showed significantly elevated milk protein gene expression after 3 days of culture with lactogenic hormones. The subsequent removal of exogenous hormones from the media for 10 days resulted in the down-regulation of milk protein genes. During this time, the mammary explants remained hormone responsive, the alveolar architecture was maintained and the expression of milk protein genes was re-induced after a second challenge with lactogenic hormones. We report that a population of bovine mammary epithelial cells have an intrinsic capacity to remain viable and hormone responsive for extended periods in chemically defined media without any exogenous macromolecules. In addition, we found mammary explant viability was dependent on de novo protein and RNA synthesis. Global functional microarray analysis showed that differential expression of genes involved in energy production, immune responses, oxidative stress and apoptosis signalling might contribute to cell survival. As the decline in milk production in dairy cattle after peak lactation results in considerable economic loss, the identification of novel survival genes may be used as genetic markers for breeding programmes to improve lactational persistency in dairy cows.

Cancer survival in Australia 1992–1997 : geographic categories and socioeconomic status

Cancer Survival in Australia 1992-1997 is the first national analysis of how cancer survival varies by socioeconomic status and geographic region. It presents an analysis of five-year relative survival proportions by geographic category and socioeconomic status for persons diagnosed with cancer during the years 1992-1997.This analysis is presented by age and sex for all cancers (Excluding non-melanocytic skin cancers) combined and for the following National Health Priority Area cancers - colorectal cancer, cancer of the lung, melanoma, cancer of the breast (females only), cancer of the cervix, cancer of the prostate, and non-Hodgkin's lymphoma.This report is the third in a series of three reports on relative survival after being diagnosed with cancer. It is an important reference for all those interested in the health of Australians.

Introgression of domesticated alleles into a wild trout genotype and the impact on seasonal survival in natural lakes

We tested the fitness consequences of introgression of fast-growing domesticated fish into a wild population. Fry from wild and domesticated rainbow trout (Oncorhynchus mykiss) crosses, F1 hybrids, and first- and second-generation backcrosses were released into two natural lakes. Parentage analysis using microsatellite loci facilitated the identification of survivors, so fitness was estimated in nature from the first-feeding stage. Results indicated that under certain conditions, domesticated fish survived at least as well as wild fish within the same environment. Relative growth and survival of the crosses, however, were highly dependent on environment. During the first summer, fastest-growing crosses had the highest survival, but this trend was reversed after one winter and another summer. Although the F1 hybrids showed evidence of outbreeding depression because of the disruption of local adaptation, there was little evidence of outbreeding depression in the backcrosses, and the second-generation backcrosses exhibited a wild-type phenotype. This information is relevant for assessing the multigenerational risk of escaped or released domesticated fish should they successfully interbreed with wild populations and provides information on how to minimize detrimental impacts of a conservation breeding and/or management programme. These data also further understanding of the selection pressures in nature that maintain submaximal rates of growth.

Meta-analysis of movements in Atlantic leatherback turtles during the nesting season : conservation implications

Despite decades of conservation efforts on the nesting beaches, the critical status of leatherback turtles shows that their survival predominantly depends on our ability to reduce at-sea mortality. Although areas where leatherbacks meet fisheries have been identified during the long distance movements between 2 consecutive nesting seasons, hot-spots of lethal interactions are still poorly defined within the nesting season, when individuals concentrate close to land. Here we report movements of satellite-tracked gravid leatherback turtles during the nesting season in Western Central Africa, South America and the Caribbean Sea, which account for about 70% of the world population. We show that during and at the end of the nesting season, leatherback turtles have the propensity to remain over the continental shelf, yet sometimes perform extended movements and may even nest in neighbouring countries. Leatherbacks exploit coastal commercial fishing grounds and face substantial accidental capture by regional coastal fisheries (e.g. at least 10% in French Guiana). This emphasises the need for regional conservation strategies to be developed at the ocean scale—both at sea and on land—to ensure the survival of the last leatherback turtles.

Determining the sensitivity of the Antarctic amphipod Orchomenella pinguides to metals using a joint model of survival response to exposure concentration and duration

Developing water quality guidelines for Antarctic marine environments requires understanding the sensitivity of local biota to contaminant exposure. Antarctic invertebrates have shown slower contaminant responses in previous experiments compared to temperate and tropical species in standard toxicity tests. Consequently, test methods which take into account environmental conditions and biological characteristics of cold climate species need to be developed. This study investigated the effects of five metals on the survival of a common Antarctic amphipod, Orchomenella pinguides. Multiple observations assessing mortality to metal exposure were made over the 30 days exposure period. Traditional toxicity tests with quantal data sets are analysed using methods such as maximum likelihood regression (probit analysis) and Spearman–Kärber which treat individual time period endpoints independently. A new statistical model was developed to integrate the time-series concentration–response data obtained in this study. Grouped survival data were modelled using a generalized additive mixed model (GAMM) which incorporates all the data obtained from multiple observation times to derive time integrated point estimates. The sensitivity of the amphipod, O. pinguides, to metals increased with increasing exposure time. Response times varied for different metals with amphipods responding faster to copper than to cadmium, lead or zinc. As indicated by 30 days lethal concentration (LC50) estimates, copper was the most toxic metal (31 µg/L), followed by cadmium (168 µg/L), lead (256 µg/L) and zinc (822 µg/L). Nickel exposure (up to 1.12 mg/L) did not affect amphipod survival. Using longer exposure durations and utilising the GAMM model provides an improved methodology for assessing sensitivities of slow responding Antarctic marine invertebrates to contaminants.

Epidermal growth factor receptor-tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung: a meta-analysis.

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are well established in treating metastatic pulmonary adenocarcinoma, especially patients with activating EGFR mutations. EGFR mutations are rare in pulmonary squamous cell carcinomas (SCCs). There are conflicting data supporting the efficacy of EGFR-TKIs in advanced lung SCC. We analyzed the impact of EGFR-TKIs on progression-free survival (PFS) and overall survival (OS) in unselected patients with lung SCC.