A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread

Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevance of the 3D microenvironment and integrin engagement. In a spheroid-based animal model, KLK4-7-overexpression induced tumor growth after 4 weeks and intraperitoneal spread after 8 weeks. Upon paclitaxel administration, KLK4-7-expressing tumors declined in size by 91% (controls: 87%) and showed 90% less metastatic outgrowth (controls: 33%, P<0.001). KLK4-7-expressing spheroids showed 53% survival upon paclitaxel treatment (controls: 51%), accompanied by enhanced chemoresistance-related factors, and their survival was further reduced by combination treatment of paclitaxel with KLK4/5/7 (22%, P=0.007) or MAPK (6%, P=0.006) inhibition. The concomitant presence of KLK4-7 in ovarian cancer cells together with integrin activation drives spheroid formation and proliferation. Combinatorial approaches of paclitaxel and KLK/MAPK inhibition may be more efficient for late-stage disease than chemotherapeutics alone as these inhibitory regimens reduced cancer spheroid growth to a greater extent than paclitaxel alone.

Assessment of gene expression of intracellular calcium channels, pumps and exchangers with epidermal growth factor-induced epithelial-mesenchymal transition in a breast cancer cell line

Background Epithelial-mesenchymal transition (EMT) is a process implicated in cancer metastasis that involves the conversion of epithelial cells to a more mesenchymal and invasive cell phenotype. In breast cancer cells EMT is associated with altered store-operated calcium influx and changes in calcium signalling mediated by activation of cell surface purinergic receptors. In this study, we investigated whether MDA-MB-468 breast cancer cells induced to undergo EMT exhibit changes in mRNA levels of calcium channels, pumps and exchangers located on intracellular calcium storing organelles, including the Golgi, mitochondria and endoplasmic reticulum (ER). Methods Epidermal growth factor (EGF) was used to induce EMT in MDA-MB-468 breast cancer cells. Serum-deprived cells were treated with EGF (50 ng/mL) for 12 h and gene expression was assessed using quantitative RT-PCR. Results and conclusions These data reveal no significant alterations in mRNA levels of the Golgi calcium pump secretory pathway calcium ATPases (SPCA1 and SPCA2), or the mitochondrial calcium uniporter (MCU) or Na+/Ca2+ exchanger (NCLX). However, EGF-induced EMT was associated with significant alterations in mRNA levels of specific ER calcium channels and pumps, including (sarco)-endoplasmic reticulum calcium ATPases (SERCAs), and inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RYR) calcium channel isoforms. The most prominent change in gene expression between the epithelial and mesenchymal-like states was RYR2, which was enriched 45-fold in EGF-treated MDA-MB-468 cells. These findings indicate that EGF-induced EMT in breast cancer cells may be associated with major alterations in ER calcium homeostasis.

Experimental assessment of the effects of sublethal salinities on growth performance and stress in cultured tra catfish (Pangasianodon hypophthalmus)

The effects of a range of different sublethal salinities were assessed on physiological processes and growth performance in the freshwater ‘tra’ catfish (Pangasianodon hypophthalmus) juveniles over an 8-week experiment. Fish were distributed randomly among 6 salinity treatments [2, 6, 10, 14 and 18 g/L of salinity and a control (0 g/L)] with a subsequent 13-day period of acclimation. Low salinity conditions from 2 to 10 g/L provided optimal conditions with high survival and good growth performance, while 0 g/L and salinities[14 g/L gave poorer survival rates (p\0.05). Salinity levels from freshwater to 10 g/L did not have any negative effects on fish weight gain, daily weight gain, or specific growth rate. Food conversion ratio, however, was lowest in the control treatment (p\0.05) and highest at the maximum salinities tested (18 g/L treatment). Cortisol levels were elevated in the 14 and 18 g/L treatments after 6 h and reached a peak after 24-h exposure, and this also led to increases in plasma glucose concentration. After 14 days, surviving fish in all treatments appeared to have acclimated to their respective conditions with cortisol levels remaining under 5 ng/ mL with glucose concentrations stable. Tra catfish do not appear to be efficient osmoregulators when salinity levels exceed 10 g/L, and at raised salinity levels, growth performance is compromised. In general, results of this study confirm that providing culture environments in the Mekong River Basin do not exceed 10 g/L salinity and that cultured tra catfish can continue to perform well.

Rapid assessment of genotype-by-environment interactions and heritability for growth rate in aquaculture species using in vitro fertilisation and DNA tagging

Commercial environments may receive only a fraction of expected genetic gains for growth rate as predicted from the selection environment This fraction is the result of undesirable genotype-by-environment interactions (G x E) and measured by the genetic correlation (r(g)) of growth between environments. Rapid estimates of genetic correlation achieved in one generation are notoriously difficult to estimate with precision. A new design is proposed where genetic correlations can be estimated by utilising artificial mating from cryopreserved semen and unfertilised eggs stripped from a single female. We compare a traditional phenotype analysis of growth to a threshold model where only the largest fish are genotyped for sire identification. The threshold model was robust to differences in family mortality differing up to 30%. The design is unique as it negates potential re-ranking of families caused by an interaction between common maternal environmental effects and growing environment. The design is suitable for rapid assessment of G x E over one generation with a true 0.70 genetic correlation yielding standard errors as low as 0.07. Different design scenarios were tested for bias and accuracy with a range of heritability values, number of half-sib families created, number of progeny within each full-sib family, number of fish genotyped, number of fish stocked, differing family survival rates and at various simulated genetic correlation levels

An assessment of construction labour productivity in Malaysia

The construction industry is one of major strategic importance. Its level of productivity has a significant effect on national economic growth. The analysis of published census/biannual surveys of construction by the Department of Statistics of Malaysia shows that Malaysia managed to achieve construction labour productivity growth between 1996 and 2005 despite increases in cost per employee. The decrease in unit labour costs is attributed to the value added improvement per worker through the increase in capital intensity. The marginal decline in capital productivity is due to the gestation period and the overcapacity of the industry. The civil engineering sub-sector recorded the highest labour productivity and is the most labour competitive in terms of unit labour cost and added value per labour cost. The residential sub-sectors recorded greatest change in the productivity indicators between 1996 and 2005.

An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal [mu]-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. [mu]-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Assessment of commercial network RTK user positioning performance over long inter-station distances

The paper provides an assessment of the performance of commercial Real Time Kinematic (RTK) systems over longer than recommended inter-station distances. The experiments were set up to test and analyse solutions from the i-MAX, MAX and VRS systems being operated with three triangle shaped network cells, each having an average inter-station distance of 69km, 118km and 166km. The performance characteristics appraised included initialization success rate, initialization time, RTK position accuracy and availability, ambiguity resolution risk and RTK integrity risk in order to provide a wider perspective of the performance of the testing systems. ----- ----- The results showed that the performances of all network RTK solutions assessed were affected by the increase in the inter-station distances to similar degrees. The MAX solution achieved the highest initialization success rate of 96.6% on average, albeit with a longer initialisation time. Two VRS approaches achieved lower initialization success rate of 80% over the large triangle. In terms of RTK positioning accuracy after successful initialisation, the results indicated a good agreement between the actual error growth in both horizontal and vertical components and the accuracy specified in the RMS and part per million (ppm) values by the manufacturers. ----- ----- Additionally, the VRS approaches performed better than the MAX and i-MAX when being tested under the standard triangle network with a mean inter-station distance of 69km. However as the inter-station distance increases, the network RTK software may fail to generate VRS correction and then may turn to operate in the nearest single-base RTK (or RAW) mode. The position uncertainty reached beyond 2 meters occasionally, showing that the RTK rover software was using an incorrect ambiguity fixed solution to estimate the rover position rather than automatically dropping back to using an ambiguity float solution. Results identified that the risk of incorrectly resolving ambiguities reached 18%, 20%, 13% and 25% for i-MAX, MAX, Leica VRS and Trimble VRS respectively when operating over the large triangle network. Additionally, the Coordinate Quality indicator values given by the Leica GX1230 GG rover receiver tended to be over-optimistic and not functioning well with the identification of incorrectly fixed integer ambiguity solutions. In summary, this independent assessment has identified some problems and failures that can occur in all of the systems tested, especially when being pushed beyond the recommended limits. While such failures are expected, they can offer useful insights into where users should be wary and how manufacturers might improve their products. The results also demonstrate that integrity monitoring of RTK solutions is indeed necessary for precision applications, thus deserving serious attention from researchers and system providers.

Preliminary development of a sewerage infrastructure buffer assessment tool for engineering risk and strategic land use planning

Urban expansion continues to encroach on once isolated sewerage infrastructure. In this context,legislation and guidelines provide limited direction to the amenity allocation of appropriate buffer distances for land use planners and infrastructure providers. Topography, wind speed and direction,temperature, humidity, existing land uses and vegetation profiles are some of the factors that require investigation in analytically determining a basis for buffer separations. This paper discusses the compilation and analysis of six years of Logan sewerage odour complaint data. Graphically,relationships between the complaints, topographical features and meteorological data are presented. Application of a buffer sizing process could assist planners and infrastructure designers alike, whilst automatically providing extra green spaces. Establishing a justifiable criterion for buffer zone allocations can only assist in promoting manageable growth for healthier and more sustainable communities.

Analysis of acoustic emission data for accurate damage assessment for structural health monitoring applications

Structural health monitoring (SHM) refers to the procedure used to assess the condition of structures so that their performance can be monitored and any damage can be detected early. Early detection of damage and appropriate retrofitting will aid in preventing failure of the structure and save money spent on maintenance or replacement and ensure the structure operates safely and efficiently during its whole intended life. Though visual inspection and other techniques such as vibration based ones are available for SHM of structures such as bridges, the use of acoustic emission (AE) technique is an attractive option and is increasing in use. AE waves are high frequency stress waves generated by rapid release of energy from localised sources within a material, such as crack initiation and growth. AE technique involves recording these waves by means of sensors attached on the surface and then analysing the signals to extract information about the nature of the source. High sensitivity to crack growth, ability to locate source, passive nature (no need to supply energy from outside, but energy from damage source itself is utilised) and possibility to perform real time monitoring (detecting crack as it occurs or grows) are some of the attractive features of AE technique. In spite of these advantages, challenges still exist in using AE technique for monitoring applications, especially in the area of analysis of recorded AE data, as large volumes of data are usually generated during monitoring. The need for effective data analysis can be linked with three main aims of monitoring: (a) accurately locating the source of damage; (b) identifying and discriminating signals from different sources of acoustic emission and (c) quantifying the level of damage of AE source for severity assessment. In AE technique, the location of the emission source is usually calculated using the times of arrival and velocities of the AE signals recorded by a number of sensors. But complications arise as AE waves can travel in a structure in a number of different modes that have different velocities and frequencies. Hence, to accurately locate a source it is necessary to identify the modes recorded by the sensors. This study has proposed and tested the use of time-frequency analysis tools such as short time Fourier transform to identify the modes and the use of the velocities of these modes to achieve very accurate results. Further, this study has explored the possibility of reducing the number of sensors needed for data capture by using the velocities of modes captured by a single sensor for source localization. A major problem in practical use of AE technique is the presence of sources of AE other than crack related, such as rubbing and impacts between different components of a structure. These spurious AE signals often mask the signals from the crack activity; hence discrimination of signals to identify the sources is very important. This work developed a model that uses different signal processing tools such as cross-correlation, magnitude squared coherence and energy distribution in different frequency bands as well as modal analysis (comparing amplitudes of identified modes) for accurately differentiating signals from different simulated AE sources. Quantification tools to assess the severity of the damage sources are highly desirable in practical applications. Though different damage quantification methods have been proposed in AE technique, not all have achieved universal approval or have been approved as suitable for all situations. The b-value analysis, which involves the study of distribution of amplitudes of AE signals, and its modified form (known as improved b-value analysis), was investigated for suitability for damage quantification purposes in ductile materials such as steel. This was found to give encouraging results for analysis of data from laboratory, thereby extending the possibility of its use for real life structures. By addressing these primary issues, it is believed that this thesis has helped improve the effectiveness of AE technique for structural health monitoring of civil infrastructures such as bridges.

GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.

Platelet-derived endothelial cell growth factor (thymidine phosphorylase) expression in lung cancer

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is an enzyme with angiogenic and cell motility properties. Moreover, it is involved in the transformation of fluoropyrimidines into active cytotoxic metabolites, In the present study, the expression of PD-ECGF in normal lung and lung cancer was immunohistochemically evaluated using the P-GF.44C monoclonal antibody. Alveolar and tumoural macrophages mere invariably stained and mere used as an internal control for assessment of the staining. Alveolar epithelium was always negative, whilst bronchiolar epithelium showed occasional positive reactivity. Normal lung and tumour endothelium was occasionally positive, Positive staining in more than 50 per cent of cells was observed in 23/71 squamous carcinomas (32 per cent), 16/38 (42 per cent) adenocarcinomas, and 2/6 (33 per cent) adenosquamous carcinomas. Differentiated areas and areas of squamous metaplasia mere more strongly positive than other tumour areas. All 22 small cell carcinomas and one carcinoid tumour were negative. The present study provides a baseline for future studies in non-small cell lung cancer to correlate PD-ECGF expression with tumour vascularization, prognosis, and response to chemotherapy.

Assessment of freestanding membranes prepared from Antheraea pernyi silk fibroin as a potential vehicle for corneal epithelial cell transplantation

Freestanding membranes created from Bombyx mori silk fibroin (BMSF) offer a potential vehicle for corneal cell transplantation since they are transparent and support the growth of human corneal epithelial cells (HCE). Fibroin derived from the wild silkworm Antheraea pernyi (APSF) might provide a superior material by virtue of containing putative cell- attachment sites that are absent from BMSF. Thus we have investigated the feasibility of producing transparent, freestanding membranes from APSF and have analysed the behaviour of HCE cells on this material. No significant differences in cell numbers or phenotype were observed in short term HCE cell cultures established on either fibroin. Production of transparent freestanding APSF membranes, however, proved to be problematic as cast solutions of APSF were more prone to becoming opaque, displayed significantly lower permeability and were more brittle than BMSF-membranes. Cultures of HCE cells established on either membrane developed a normal stratified morphology with cytokeratin pair 3/12 being immuno-localized to the superficial layers. We conclude that while it is feasible to produce transparent freestanding membranes from APSF, the technical difficulties associated with this biomaterial, along with an absence of enhanced cell growth, currently favours the continued development of BMSF as a preferred vehicle for corneal cell transplantation. Nevertheless, it remains possible that refinement of techniques for processing APSF might yet lead to improvements in the handling properties and performance of this material.

Characteristics of spatial variation, size distribution, formation and growth of particles in urban environments

This thesis is the first comprehensive study of important parameters relating to aerosols' impact on climate and human health, namely spatial variation, particle size distribution and new particle formation. We determined the importance of spatial variation of particle number concentration in microscale environments, developed a method for particle size parameterisation and provided knowledge about the chemistry of new particle formation. This is a significant contribution to our understanding of processes behind the transformation and dynamics of urban aerosols. This PhD project included extensive measurements of air quality parameters using state of the art instrumentation at each of the 25 sites within the Brisbane metropolitan area and advanced statistical analysis.

Assessment of angiogenic potential--the use of AIDS-KS cell supernatants as an in vitro model

Metastasis, the passage of primary tumour cells throughout the body via the vascular system and their subsequent proliferation into secondary lesions in distant organs, represents a poor prognosis and therefore an understandably feared event for cancer patients. Despite considerable advances in cancer diagnosis and treatment, most deaths are the result of metastases resistant to conventional treatment [1]. Rather than being a random process, metastasis involves a series of organised steps leading to the growth of a secondary tumour. Malignant tumours stimulate the production of new vessels by the host, and this process is a prerequisite for the increase in size of a new tumour [2]. Angiogenesis, not only permits tumour expansion but also allows the entry of tumour cells into the circulation and is probably the most vital event for the metastatic process [3]. Metastasis and angiogenesis [4] have received much attention in recent years. A biological understanding of both phenomena seems to be an urgent priority towards the search for an effective prevention and treatment of tumour progression. Studies in vitro and in vivo have shown that one of the most important barriers to the passage of malignant cells is the basement membrane. The crossing of such barriers is a vital step in the formation of a metastasis [5].