56 resultados para survival of healthy and malignant cells

em Deakin Research Online - Australia


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Events happening in one season can affect life-history traits at (the) subsequent season(s) by carry-over effects. Wintering conditions are known to affect breeding success, but few studies have investigated carry-over effects on survival. The Eurasian oystercatcher Haematopus ostralegus is a coastal wader with sedentary populations at temperate sites and migratory populations in northern breeding grounds of Europe. We pooled continental European ringing-recovery datasets from 1975 to 2000 to estimate winter and summer survival rates of migrant and resident populations and to investigate long-term effects of winter habitat changes. During mild climatic periods, adults of both migratory and resident populations exhibited survival rates 2% lower in summer than in winter. Severe winters reduced survival rates (down to 25% reduction) and were often followed by a decline in survival during the following summer, via short-term carry-over effects. Habitat changes in the Dutch wintering grounds caused a reduction in food stocks, leading to reduced survival rates, particularly in young birds. Therefore, wintering habitat changes resulted in long-term (>10 years) 8.7 and 9.4% decrease in adult annual survival of migrant and resident populations respectively. Studying the impact of carry-over effects is crucial for understanding the life history of migratory birds and the development of conservation measures.

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Few studies use comprehensive ecological approaches considering multilevel factors to understand correlates of healthy (and unhealthy) dietary intake. The aim of this study was to examine the association between individual, social, and environmental factors on composite measures of healthy and unhealthy dietary intake in adults.

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 This study has investigated the patterns of colocalisation of the conventional K cell marker, glucagon-like insulinotropic peptide (GIP), and the L cell markers, glucagon like peptide-1 (GLP-1) and peptide YY (PYY), in enteroendocrine cells (EEC) of the small intestine and colon of mouse and pig. All combinations of the hormones, 3 in a cell, 2 in a cell and 1 at a time, were encountered. In both species, the three most common EEC types contained (1) both GLP-1 and PYY but not GIP, (2) GLP-1 alone or (3) GIP plus GLP-1 without PYY. Few GIP plus PYY cells and rare cells containing all 3 hormones were encountered. Gradients of cell types occurred along the intestine. For example, in mouse, there were no PYY cells in the duodenum and few in the jejunum, but >50 % of labelled EEC in the distal ileum and colon were PYY immunoreactive. By contrast, over 40 % of EEC in the pig duodenum contained PYY, and most also contained either GLP-1 or GIP. The gradient in pig was less pronounced. It is concluded that the traditional classification of K and L cells requires revision, and that there are major inter-species differences in the patterns of colocalisation of hormones that have been used to characterise K and L cells.

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Tumor intrinsic and extrinsic factors are thought to contribute to bone metastasis but little is known about how they cooperate to promote breast cancer spread to bone. We used the bone-metastatic 4T1BM2 mammary carcinoma model to investigate the cooperative interactions between tumor LM-511 and bone-derived soluble factors in vitro. We show that bone conditioned medium cooperates with LM-511 to enhance 4T1BM2 cell migration and invasion and is sufficient alone to promote survival in the absence of serum. These responses were associated with increased secretion of MMP-9 and activation of ERK and AKT signaling pathways and were partially blocked by pharmacological inhibitors of MMP-9, AKT-1/2 or MEK. Importantly, pre-treatment of 4T1BM2 cells with an AKT-1/2 inhibitor significantly reduced experimental metastasis to bone in vivo. Promotion of survival and invasive responses by bone-derived soluble factors and tumor-derived LM-511 are likely to contribute to the metastatic spread of breast tumors to bone.

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We developed a method for obtaining viable buccal cells from mouthwash samples for use as a source of mRNA and protein. Immunofluorescent analysis showed that most cells were derived from nonkeratinized parabasal epithelia, with a minor proportion of proliferative cells. Gene expression was detected in buccal cells using reverse transcription PCR, Western blot analysis, and immunofluorescence. Using a keratinocyte-specific medium, buccal cells could be cultured on Matrigel™-coated permeable filters for up to 2 weeks while maintaining the expression of some epithelial-specific markers, including cytokeratin 13, cytokeratin 10, transferrin receptor, and β-integrin. The basal marker cytokeratin 14 and Ki67, an indicator of cellular proliferation, were detected in a few cells. We show that buccal cells can be obtained from a noninvasive procedure for use as a source of material for biochemical analyses. A population of the buccal cells can be maintained in culture for up to 2 weeks using keratinocyte-specific medium in combination with extracellular matrix.

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While engaging in romantic relationships is regarded as a normative task during young adulthood, non-normative life events such as the emergence of chronic illness can mitigate against the successful negotiation of such tasks. Chronic illness brings with it a series of additional challenges and stressors to the realm of personal relationships that are thought to interrupt the development of normative interpersonal and intra-individual processes. However, few studies have examined how young adults faced with a chronic illness such as arthritis navigate romantic relationships and the consequences of illness and relationships on psychological adjustment. The aim of the study was to compare the relationship experiences of healthy young adults with those faced with arthritis. One hundred and nine young adults (M 23.01 years, SD 2.43) took part in the study. Of these participants 41 had been diagnosed with arthritis. A univariate MANOVA revealed arthritic young adults reported significantly more insecure attachment, lower levels of readiness for intimacy, and poorer relationship satisfaction compared to healthy young adults. Further correlational and regression analyses on the arthritic sample revealed psychological adjustment was related to arthritis severity, attachment and components of coping. Findings will be discussed in relation to attachment theory and coping processes.

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Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery. We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future.

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A simple and sensitive HPLC method was developed to simultaneously determine CPT-11 and its major metabolite SN-38 in culture media and cell lysates. Camptothecin (CPT) was used as internal standard (I.S.). Compounds were eluted with acetonitrile–50 mM disodium hydrogen phosphate buffer containing 10 mM sodium 1-heptane-sulfonate, with the pH adjusted to 3.0 using 85% (w/v) orthophosphoric acid (27/73, v/v) by a Hyperclon ODS (C18) column (200 mm × 4.6 mm i.d.), with detection at excitation and emission wavelengths of 380 and 540 nm, respectively. The average extraction efficiencies were 96.9–108.3% for CPT-11 in culture media and 94.3–107.2% for CPT-11 in cell lysates; and 87.7–106.8% for SN-38 in culture media and 90.1–105.6% for SN-38 in cell lysates. Within- and between-day precision and accuracy varied from 0.1 to 10.3%. The limit of quantitation (precision and accuracy <20%) was 5.0 and 2.0 ng/ml for CPT-11 and 1.0 and 0.5 ng/ml for SN-38 in culture media and cell lysates, respectively. This method was successfully applied to quantitate the cellular accumulation and metabolism of CPT-11 and SN-38 in H4-II-E, a rat hepatoma cell line.

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Preventative health strategies incorporating the views of target participants have improved the likelihood of success. This qualitative study aimed to elicit child and parent views regarding social and environmental barriers to healthy eating, physical activity and child obesity prevention programmes, acceptable foci, and appropriate modes of delivery. To obtain views across a range of social circumstances three demographically diverse primary schools in Victoria, Australia were selected. Children in Grades 2 (aged 7–8 years) and 5 (aged 10–11 years) participated in focus groups of three to six children. Groups were semi-structured using photo-based activities to initiate discussion. Focus groups with established parent groups were also conducted. Comments were recorded, collated, and themes extracted using grounded theory. 119 children and 17 parents participated. Nine themes emerged: information and awareness, contradiction between knowledge and behaviour, lifestyle balance, local environment, barriers to a healthy lifestyle, contradictory messages, myths, roles of the school and family, and timing and content of prevention strategies for childhood obesity. In conclusion, awareness of food ‘healthiness’ was high however perceptions of the ‘healthiness’ of some sedentary activities that are otherwise of benefit (e.g. reading) were uncertain. The contradictions in messages children receive were reported to be a barrier to a healthy lifestyle. Parent recommendations regarding the timing and content of childhood obesity prevention strategies were consistent with quantitative research. Contradictions in the explicit and implicit messages children receive around diet and physical activity need to be prevented. Consistent promotion of healthy food and activity choices across settings is core to population prevention programmes for childhood obesity.

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In the lactating breast, the development of secretory alveoli consisting of differentiated cells arranged around a central lumen is dependent on signals from the extracellular environment of the cells. There are few cell lines that model this process. We previously showed that the human breast carcinoma line PMC42-LA can be induced to form organoids, reminiscent of secretory alveoli found in the lactating human breast. In this report, we used high-resolution scanning electron microscopy to show that the formation of organoids is accompanied by development of cell surface microvilli. Extracellular matrix-induced formation of microvilli occurred on the internal and external surfaces of cells in the organoids and not on surfaces in contact with the extracellular matrix. Organoid formation of PMC42-LA cells induced a rearrangement of the extracellular matrix, seen in the form of radiating fibers from the organoids. In summary, there is an interaction between PMC42-LA cells and the underlying extracellular matrix, which leads to the formation of polarized cells with well-developed microvilli. This is accompanied by organization of the extracellular matrix. PMC42-LA is a relevant model of the human breast for investigations into cell-cell and cell-matrix interactions.

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In order to promote healthful nutrition, insight is needed into the determinants of nutrition behaviours. Behavioural determinant research and behavioural nutrition interventions have focused mostly on individual-level motivational factors. It has been argued that the individual's socio-cultural and physical environments may be the main determinants of nutrition behaviours. However, the theoretical basis and empirical evidence for environmental determinants of nutrition behaviours are not strong. The present paper is a narrative review informed by a series of systematic reviews and recent original studies on associations between environmental factors and nutrition behaviours to provide an overview and discussion of the evidence for environmental correlates and predictors of nutrition behaviour. Although the number of studies on potential environmental determinants of nutrition behaviours has increased steeply over the last decades, they include only a few well-designed studies with validated measures and guided by sound theoretical frameworks. The preliminary evidence from the available systematic reviews indicates that socio-cultural environmental factors defining what is socially acceptable, desirable and appropriate to eat may be more important for healthful eating than physical environments that define the availability and accessibility of foods. It is concluded that there is a lack of well-designed studies on environmental determinants of healthful eating behaviours. Preliminary evidence indicates that social environmental factors may be more important than physical environmental factors for healthful eating. Better-designed studies are needed to further build evidence-based theory on environmental determinants to guide the development of interventions to promote healthful eating.

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In this study, we aimed to detect morphological and biochemical changes in developing germ cells (Gc), testicular sperm (Tsp), and spawned sperm (Ssp) using capacitation-associated characteristics. Gradual changes in the profiles of two membrane proteins, namely NaCl- and detergent-extractable proteins, were observed as compared Gc with Tsp and Tsp with Ssp. These membrane modifications were accomplished mostly through the introduction of new protein sets, both peripheral and integral, into Tsp and Ssp membranes. Activation of serine proteases, particularly in Ssp detergent-extracted proteins with the molecular masses of 38–130 kDa was evident and marked a major difference between Ssp and Tsp. An increase in the level of tyrosine phosphorylation of the proteins ranging from 15 to 20 kDa was noted in Tsp and remained constant in Ssp. Specifically, these three capacitation-associated characteristics could be detected in Ssp, possessing full fertilizing capacity. The lack of an activated proteolytic activity in Tsp resulted in a delayed fertilization, but not affected fertilizing ability. We believe that these characteristics should be advantageous in predicting abalone sperm fertilizing capability, particularly in cases when isolated germ cells or purified Tsp are used in place of spawned sperm in abalone aquaculture.

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Purpose: Most women with early-stage breast cancer believe that psychosocial factors are an important influence over whether their cancer will recur. Studies of the issue have produced conflicting results.

Patients and Methods: A population-based sample of 708 Australian women diagnosed before age 60 years with nonmetastatic breast cancer was observed for a median of 8.2 years. Depression and anxiety, coping style, and social support were assessed at a median of 11 months after diagnosis. Hazard ratios for distant disease-free survival (DDFS) and overall survival (OS) associated with psychosocial factors were estimated separately using Cox proportional hazards survival models, with and without adjustment for known prognostic factors.

Results:
Distant recurrence occurred in 209 (33%) of 638 assessable patients, and 170 (24%) of 708 patients died during the follow-up period. There were no statistically significant associations between any of the measured psychosocial factors and DDFS or OS from the adjusted analyses. From unadjusted analyses, associations between greater anxious preoccupation and poorer DDFS and OS were observed (P = .02). These associations were no longer evident after adjustment for established prognostic factors; greater anxious preoccupation was associated with younger age at diagnosis (P = .03), higher tumor grade (P = .02), and greater number of involved axillary nodes (P = .008).

Conclusion:
The findings do not support the measured psychosocial factors being an important influence on breast cancer outcomes. Interventions for adverse psychosocial factors are warranted to improve quality of life but should not be expected to improve survival.