Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen- activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

MTI-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of antiangiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists. - Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

Promoting posttraumatic growth in police recruits : preliminary results of a randomised controlled resilience intervention trial

Recent research has demonstrated that the same experiences that may elicit symptoms of post-traumatic stress disorder (PTSD) in emergency service personnel can also provide a catalyst for positive personal changes such as posttraumatic growth (PTG). In this research newly recruited police officers (N = 412) participated in a randomised control trial of a program specifically designed to promote mental health. On entry to the academy, new recruits were randomly allocated, by classrooms, to either a treatment as usual condition (i.e., existing psychoeducation program) or to the intervention group. The Promoting Resilient Officers (PRO) program is a resilience building intervention adapted from an earlier resilience building program in collaboration with the police service. The PRO program also includes additional components on trauma and PTG. The current research included the participants who had experienced trauma prior to or during the research period (N = 246). It was hypothesised that participation in the PRO program would increase levels of PTG and lower levels of PTSD when compared to recruits in the control condition. Using multilevel modelling and post-hoc analyses, results indicated there were significantly higher levels of PTG across multiple dimensions when compared to the control group. There was no effect on PTSD symptoms with both conditions showing a floor effect. The research indicated the potential value of developing interventions that elicit reflections on the potential for positive as well as negative outcomes of experiencing traumatic and other highly challenging events.

Elevated level of inhibin-α subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer

The biological function of inhibin-a subunit (INHa) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHa in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHa. We conducted a cross-sectional study to determine a link between INHa expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHa in advanced cancer. Elevated expression of INHa in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Overexpressing INHa in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INHa-positive LNCaP demonstrated reduced tumour growth whereas INHa-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INHa associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INHa expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa.

Association between single-nucleotide polymorphisms in growth factor genes and quality of life in men with prostate cancer and the general population

Purpose Improved survival for men with prostate cancer has led to increased attention to factors influencing quality of life (QOL). As protein levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) have been reported to be associated with QOL in people with cancer, we sought to identify whether single-nucleotide polymorphisms (SNPs) of these genes were associated with QOL in men with prostate cancer. Methods Multiple linear regression of two data sets (including approximately 750 men newly diagnosed with prostate cancer and 550 men from the general population) was used to investigate SNPs of VEGF and IGF-1 (10 SNPs in total) for associations with QOL (measured by the SF-36v2 health survey). Results Men with prostate cancer who carried the minor ‘T’ allele for IGF-1 SNP rs35767 had higher mean Role-Physical scale scores (≥0.3 SD) compared to non-carriers (p < 0.05). While this association was not identified in men from the general population, one IGF-1 SNP rs7965399 was associated with higher mean Bodily Pain scale scores in men from the general population that was not found in men with prostate cancer. Men from the general population who carried the rare ‘C’ allele had higher mean Bodily Pain scale scores (≥0.3 SD) than non-carriers (p < 0.05). Conclusions Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes. Future research may identify biomarkers associated with increased risk of poor QOL that could assist in the provision of pre-emptive support for those identified at risk.

Molecular characterisation and carotenoid quantification of pro-vitamin A biofortified genetically modified bananas in Uganda

In Uganda, a significant proportion of the population depends on the micronutrient poor East African highland banana as a food staple. Consequently, micronutrient deficiencies such as vitamin A deficiency are an important health concern in the country. To reach most vulnerable rural poor populations, staple crops can be biofortified with essential micronutrients though conventional breeding or genetic engineering. This thesis provided proof of concept that genetically modified East African highland bananas with enhanced provitamin A levels can be generated and fully characterised in Uganda. In addition, provitamin A levels present in popular banana varieties was documented.

Pro-angiogenic and anti-angiogenic factors in the degradation of osteoarthritic cartilage

This project has determined angiogenic and anti-angiogenic factors in osteoarthritis cartilage. The work has expanded our knowledge and understanding of the importance of anti-angiogenic factors in maintaining cartilage homeostasis. This study also tested the concept of topical application of anti-angiogenic treatment strategy for osteoarthritis.

Urban growth and development of contemporary neighbourhood public space in Kathmandu Valley, Nepal

Rapid and unplanned growth of Kathmandu Valley towns over the past decades has resulted in the haphazard development of new neighbourhoods with significant consequences on their public space. This paper examines the development of public space in the valley’s new neighbourhoods in the context of the current urban growth. A case study approach of three new neighbourhoods was developed to examine the provision of public space with data collected from site observations, interviews with neighbourhood residents and other secondary sources. The cases studies consist of both planned and unplanned new neighbourhoods. Findings reveal a severe loss of public space in the unplanned new neighbourhoods. In planned new neighbourhoods, the provision of public space remains poor in terms of physical features, and thus, does not support community activities and needs. Several factors, which are an outcome of the lack of proper urban growth initiatives and control measures, such as an overall drawback in the formation of new neighbourhoods, the poor capacity of local community-based organisations and the encroachment of public land are responsible for the present development of neighbourhood public space. The problems with ongoing management of public spaces are a significant issue in both unplanned and planned new neighbourhoods.

Intake, growth and carcass characteristics of lambs consuming low digestible hay and cereal grain

The influence of barley and oat grain supplements on hay dry matter intake (DMI), carcass components gain and meat quality in lambs fed a low quality basal diet was examined. Thirty five crossbred wether lambs (9 months of age) were divided into four groups. After adaptation to a basal diet of 85% oat hay and 15% lucerne hay for one week, an initial group of 11 was slaughtered. The weights of carcass components and digesta-free empty body weight (EBW) of this group was used to estimate the weight of carcass components of the other three experimental groups at the start of the experiment. The remaining three groups were randomly assigned to pens and fed ad libitum the basal diet alone (basal), basal with 300 g air dry barley grain (barley), basal with 300 g air dry oat grain (oat). Supplements were fed twice weekly (i.e., 900 g on Tuesday and 1200 g on Friday). After 13 weeks of feeding, animals were slaughtered and, at 24 h post-mortem meat quality and subcutaneous fat colour were measured. Samples of longissimus muscle were collected for determination of sarcomere length and meat tenderness. Hay DMI was reduced (P<0.01) by both barley and oat supplements. Lambs fed barley or oat had a higher and moderate digestibility of DM, and a higher intake of CP (P<0.05) and ME (P<0.01) than basal lambs. Final live weight of barley and oat lambs was higher (P<0.05) than basal, but this was not reflected in EBW or hot carcass weight. Lambs fed barley or oat had increases in protein (P<0.01) and water (P<0.001) in the carcass, but fat gain was not changed (P>0.05). There were no differences in eye muscle area or fat depth (total muscle and adipose tissue depth at 12th rib, 110 mm from midline; GR) among groups. The increased levels of protein and water components in the carcass of barley and oat fed lambs, associated with improved muscle production, were small and did not alter (P>0.05) any of the carcass/meat quality attributes compared to lambs fed a low quality forage diet. Feeding barley or oat grain at 0.9–1% of live weight daily to lambs consuming poor quality hay may not substantially improve carcass quality, but may be useful in maintaining body condition of lambs through the dry season for slaughter out of season

Field evaluation of 64 rootstocks for growth and yield of 'Kensington Pride' mango

Despite an abundance of polyembryonic genotypes and the need for rootstocks that improve scion yield and productivity, simultaneous field testing of a wide range of mango (Mangifera indica L.) genotypes as rootstocks has not previously been reported. In this experiment, we examined the growth and yield of 'Kensington Pride' on 64 mango genotypes of diverse origin during the first four seasons of fruit production to identify those worth longer-term assessment. We also recorded morphological characteristics of seedlings of 46 of these genotypes in an attempt to relate these measures to subsequent field performance. Tree canopy development on the most vigorous rootstocks was almost double that on the least vigorous. Growth rates differed by more than 160%. Cumulative marketable yield ranged from 36 kg/tree for the lowest yielding rootstock to 181 kg/tree for the most productive. Yield efficiency also differed markedly among the 64 rootstocks with the best treatment being 3.5 times more efficient than the poorest treatment. No relationship was found between yield efficiency and tree size, suggesting it is possible to select highly efficient rootstocks of differing vigor. Two genotypes ('Brodie' and 'MYP') stood out as providing high yield efficiency with small tree size. A further two genotypes ('B' and 'Watertank') were identified as offering high yield efficiency and large tree size and should provide high early yields at traditional tree spacing. Efforts to relate the morphology of different genotype seedlings to subsequent performance as a rootstock showed that nursery performance of mango seedlings is no indication of their likely behavior as a rootstock. The economic cost of poor yields and low yield efficiencies during the early years of commercial orchard production provide a rationale for culling many of the rootstock treatments in this experiment and concentrating future assessment on the top ~20% of the 64 treatments. Of these, 'MYP', 'B', 'Watertank', 'Manzano', and 'Pancho' currently show the most promise.

Heritability of reproductive traits and genetic correlations with growth in the black tiger prawn Penaeus monodon reared in tanks

Captive-reared broodstock of the black tiger prawn (Penaeus monodon) have exhibited poor reproductive performance limiting attempts to domesticate this species. The potential for improved reproductive performance was assessed by determining heritabilities of four measures of reproductive performance, their genetic correlations with each other and with growth rate and weight at age. Heritability estimates (h2 ± S.E.) obtained from √ (days to spawn), √ (egg number), √ (nauplii number) and arcsin √ (proportion hatched) were 0.47 ± 0.15, 0.41 ± 0.18, 0.27 ± 0.16, and 0.18 ± 0.16, respectively. Estimates of genetic correlations between reproductive traits and weight at age, or growth rate were less than 0.5 except for √ (egg number) and weight at 54 weeks (0.93 ± 0.19) and √ (egg number) and 16-54-week growth (0.63 ± 0.29).

Row spacing and planting density effects on the growth and yield of sugarcane. 3. Responses with different cultivars.

The promotion of controlled traffic (matching wheel and row spacing) in the Australian sugar industry is necessitating a widening of row spacing beyond the standard 1.5 m. As all cultivars grown in the Australian industry have been selected under the standard row spacing there are concerns that at least some cultivars may not be suitable for wider rows. To address this issue, experiments were established in northern and southern Queensland in which cultivars, with different growth characteristics, recommended for each region, were grown under a range of different row configurations. In the northern Queensland experiment at Gordonvale, cultivars Q187((sic)), Q200((sic)), Q201((sic)), and Q218((sic)) were grown in 1.5-m single rows, 1.8-m single rows, 1.8-m dual rows (50 cm between duals), and 2.3-m dual rows (80 cm between duals). In the southern Queensland experiment at Farnsfield, cvv. Q138, Q205((sic)), Q222((sic)) and Q188((sic)) were also grown in 1.5-m single rows, 1.8-m single rows, 1.8-m dual rows (50 cm between duals), while 1.8-m-wide throat planted single row and 2.0-m dual row (80 cm between duals) configurations were also included. There was no difference in yield between the different row configurations at Farnsfield but there was a significant row configuration x cultivar interaction at Gordonvale due to good yields in 1.8-m single and dual rows with Q201((sic)) and poor yields with Q200((sic)) at the same row spacings. There was no significant difference between the two cultivars in 1.5-m single and 2.3-m dual rows. The experiments once again demonstrated the compensatory capacity that exists in sugarcane to manipulate stalk number and individual stalk weight as a means of producing similar yields across a range of row configurations and planting densities. There was evidence of different growth patterns between cultivars in response to different row configurations (viz. propensity to tiller, susceptibility to lodging, ability to compensate between stalk number and stalk weight), suggesting that there may be genetic differences in response to row configuration. It is argued that there is a need to evaluate potential cultivars under a wider range of row configurations than the standard 1.5-m single rows. Cultivars that perform well in row configurations ranging from 1.8 to 2.0 m are essential if the adverse effects of soil compaction are to be managed through the adoption of controlled traffic.

Effects of stage of defoliation on seed production and growth of Stylosanthes humilis.

Stylosanthes humilis swards grown at Brisbane in irrigated boxes were defoliated (about 60 per cent removal of tops) at floral initiation, first flower appearance, or advanced flowering stages ; seed yield was 45, 16, and 14 per cent respectively of seed yield in undefoliated swards. Decreased yields were primarily due to poor seed set of florets, were also associated with reduced inflorescence density and floret number per inflorescence, and occurred despite increases (in some defoliation treatments) in seed size, leaf growth rate, and differentiation of leaves and branches. Total seasonal plant growth was independent of defoliation treatment.

TlBr raw material purification, crystal growth, annealing, detector fabrication and characterisation for gamma-ray detector applications

The research reported in this thesis dealt with single crystals of thallium bromide grown for gamma-ray detector applications. The crystals were used to fabricate room temperature gamma-ray detectors. Routinely produced TlBr detectors often are poor quality. Therefore, this study concentrated on developing the manufacturing processes for TlBr detectors and methods of characterisation that can be used for optimisation of TlBr purity and crystal quality. The processes under concern were TlBr raw material purification, crystal growth, annealing and detector fabrication. The study focused on single crystals of TlBr grown from material purified by a hydrothermal recrystallisation method. In addition, hydrothermal conditions for synthesis, recrystallisation, crystal growth and annealing of TlBr crystals were examined. The final manufacturing process presented in this thesis deals with TlBr material purified by the Bridgman method. Then, material is hydrothermally recrystallised in pure water. A travelling molten zone (TMZ) method is used for additional purification of the recrystallised product and then for the final crystal growth. Subsequent processing is similar to that described in the literature. In this thesis, literature on improving quality of TlBr material/crystal and detector performance is reviewed. Aging aspects as well as the influence of different factors (temperature, time, electrode material and so on) on detector stability are considered and examined. The results of the process development are summarised and discussed. This thesis shows the considerable improvement in the charge carrier properties of a detector due to additional purification by hydrothermal recrystallisation. As an example, a thick (4 mm) TlBr detector produced by the process was fabricated and found to operate successfully in gamma-ray detection, confirming the validity of the proposed purification and technological steps. However, for the complete improvement of detector performance, further developments in crystal growth are required. The detector manufacturing process was optimized by characterisation of material and crystals using methods such as X-ray diffraction (XRD), polarisation microscopy, high-resolution inductively coupled plasma mass (HR-ICPM), Fourier transform infrared (FTIR), ultraviolet and visual (UV-Vis) spectroscopy, field emission scanning electron microscope (FESEM) and energy-dispersive X-ray spectroscopy (EDS), current-voltage (I-V) and capacity voltage (CV) characterisation, and photoconductivity, as well direct detector examination.