Yuen Cheng | The University of Sydney (original) (raw)

Papers by Yuen Cheng

Research paper thumbnail of Singlet Oxygen Mediated Photochemical Upconversion of NIR Light

We report photochemical upconversion (UC) of near-infrared (NIR) light to the visible spectrum me... more We report photochemical upconversion (UC) of near-infrared (NIR) light to the visible spectrum mediated by molecular oxygen. Thereby, we address two of the main challenges in the field of photochemical UC, (i) UC of photons above 800 nm and (ii) utilization of molecular oxygen, which is necessarily excluded in conventional photochemical UC systems. In the employed system, singlet oxygen is generated upon photoexcitation of the sensitizer molecules and then acts as an energy transmitter for the UC process. The excitation energy of two singlet oxygen molecules is subsequently harvested by emitter molecules, which in turn gives rise to delayed fluorescence of the emitter species. We discuss strategies for improvement of the currently achieved efficiencies of ≤0.01% to produce excited singlet states in the emitter molecules.

Research paper thumbnail of Highly efficient photochemical upconversion in a quasi-solid organogel

J. Mater. Chem. C, 2014

ABSTRACT Despite the promise of photochemical upconversion as a means to extend the light-harvest... more ABSTRACT Despite the promise of photochemical upconversion as a means to extend the light-harvesting capabilities of a range of photovoltaic solar energy conversion devices, it remains a challenge to create efficient, solid state upconverting materials. Until now, a material has yet to be found which is as efficient as a liquid composition. Here, a gelated photochemical upconversion material is reported with a performance indistinguishable from an otherwise identical liquid composition. The sensitizer phosphorescence lifetime, Stern-Volmer quenching constants and upconversion performance (6% under one-sun illumination) were all found to be unchanged in a quasi-solid gelated sample when compared to the liquid sample. The result paves the way to a new family of efficient photochemical upconversion materials comprised of macroscopically solid, but microscopically liquid gel, for application in photovoltaics and photocatalytic water-splitting.

Research paper thumbnail of Deuteration of Perylene Enhances Photochemical Upconversion Efficiency

The Journal of Physical Chemistry Letters, 2015

Photochemical upconversion via triplet-triplet annihilation is a promising technology for improvi... more Photochemical upconversion via triplet-triplet annihilation is a promising technology for improving the efficiency of photovoltaic devices. Previous studies have shown that the efficiency of upconversion depends largely on two rate constants intrinsic to the emitting species. Here, we report that one of these rate constants can be altered by deuteration, leading to enhanced upconversion efficiency. For perylene, deuteration decreases the first order decay rate constant by 16 ± 9% at 298 K, which increases the linear upconversion response by 45 ± 21% in the low excitation regime.

Research paper thumbnail of Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis

British journal of cancer, Jan 11, 2015

Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mes... more Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively. FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (...

Research paper thumbnail of miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

Oncotarget, Jan 22, 2015

Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displ... more Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated...

Research paper thumbnail of An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma

British journal of cancer, Jan 21, 2014

Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothel... more Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed. Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour sam...

Research paper thumbnail of Blockade of Aquaporin 1 Inhibits Proliferation, Motility, and Metastatic Potential of Mesothelioma In Vitro but not in an In Vivo Model

Disease Markers, 2015

Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly t... more Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM. Methods. Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies. Results. Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours. Conclusions. Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo.

Research paper thumbnail of Two-photon triplet-triplet annihilation upconversion for photovoltaics

2011 37th IEEE Photovoltaic Specialists Conference, 2011

ABSTRACT Upconversion is a promising technique for significantly enhancing the efficiency of phot... more ABSTRACT Upconversion is a promising technique for significantly enhancing the efficiency of photovoltaic cells. Molecular systems provide an environment in which long lived triplet states can be exploited to achieve high upconversion efficiencies under solar illumination. We report on the investigation of bi-molecular triplet-triplet annihilation upconversion (TTA-UC) in a Palladium (II) tetrakisquinoxalino porphyrin (PQ4Pd)/rubrene solution. These molecules were studied in solution using UV/VIS spectroscopy to determine their stability in air over a period of weeks. Transient absorption spectroscopy (TAS) was used to directly measure the lifetime of triplet states within these mixtures and hence determine the photoinduced kinetics of the system. The lifetime of porphyrin triplets was reduced from 92.4 μs in pristine PQ4Pd to 2.4 μs in the presence of rubrene. From this change, the rate constant associated with triplet energy transfer (kTET) was calculated as 3.38 × 108M−1s−1. Additionally, a reduction in the absorption of 530 nm light (the ground state rubrene absorption peak) was observed, while the mixture was pumped at the absorption peak of the porphyrin (670 nm). This change became apparent nearly 6 μs after the laser pulse, showing energy transfer from the porphyrin to the rubrene, and allowing further insight into the kinetics of the mechanism.

Research paper thumbnail of Molecular approaches to third generation photovoltaics: Photochemical up-conversion

Next Generation (Nano) Photonic and Cell Technologies for Solar Energy Conversion, 2010

We have investigated a photochemical up-conversion system comprising a molecular mixture of a pal... more We have investigated a photochemical up-conversion system comprising a molecular mixture of a palladium porphyrin to harvest light, and a polycyclic aromatic hydrocarbon to emit light. The energy of harvested photons is stored as molecular triplet states which then annihilate to bring about up-converted fluorescence. The limiting efficiency of such triplet-triplet annihilation up-conversion has been believed to be 11% for some time. However, by rigorously investigating the kinetics of delayed fluorescence following pulsed excitation, we demonstrate instantaneous annihilation efficiencies exceeding 40%, and limiting efficiencies for the current system of ~60%. We attribute the high efficiencies obtained to the electronic structure of the emitting molecule, which exhibits an exceptionally high T2 molecular state. We utilize the kinetic data obtained to model an up-converting layer irradiated with broadband sunlight, finding that ~3% efficiencies can be obtained with the current system, with this improving dramatically upon optimization of various parameters.

Research paper thumbnail of The virtual product-process design laboratory for design and analysis of formulations

Computer Aided Chemical Engineering, 2009

The objective of this paper is to present a virtual laboratory for chemical product-process desig... more The objective of this paper is to present a virtual laboratory for chemical product-process design (virtual PPD-lab) as a tool for the design and analysis of formulations. With the virtual PPD-lab, users can test their design ideas on model-based computer-aided tools before performing experiments to validate the designed product; also, manifold product and process alternatives matching a priori defined targets

Research paper thumbnail of Towards an aligned luminophore solar concentrator

Optics Express, 2010

Luminescent solar concentrators promise to reduce the cost of solar energy, but are hindered by a... more Luminescent solar concentrators promise to reduce the cost of solar energy, but are hindered by a number of losses. Escape of luminescence through the large waveguide-air interfaces can be attenuated through alignment of the optical transition dipole of the luminophore along the waveguide surface normal, directing the maximum possible proportion of luminescence into waveguide modes. We demonstrate such alignment using a guest-host dye-doped liquid crystal sandwiched between conductive glass slides. Application of a potential while illuminating through a narrow edge caused a drop in the intensity of luminescence escaping the large surfaces, and an increase in the intensity of light escaping the narrow edges of the system. This is explained in terms of alignment of the transition dipoles of the dye. We discuss implementation in a luminescent solar concentrator.

Research paper thumbnail of Integrating a triplet-triplet annihilation up-conversion system to enhance dye-sensitized solar cell response to sub-bandgap light

Journal of visualized experiments : JoVE, 2014

The poor response of dye-sensitized solar cells (DSCs) to red and infrared light is a significant... more The poor response of dye-sensitized solar cells (DSCs) to red and infrared light is a significant impediment to the realization of higher photocurrents and hence higher efficiencies. Photon up-conversion by way of triplet-triplet annihilation (TTA-UC) is an attractive technique for using these otherwise wasted low energy photons to produce photocurrent, while not interfering with the photoanodic performance in a deleterious manner. Further to this, TTA-UC has a number of features, distinct from other reported photon up-conversion technologies, which renders it particularly suitable for coupling with DSC technology. In this work, a proven high performance TTA-UC system, comprising a palladium porphyrin sensitizer and rubrene emitter, is combined with a high performance DSC (utilizing the organic dye D149) in an integrated device. The device shows an enhanced response to sub-bandgap light over the absorption range of the TTA-UC sub-unit resulting in the highest figure of merit for up-...

Research paper thumbnail of MiR-Score: A novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma

Molecular oncology, Jan 2, 2014

Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatme... more Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients. Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors following extrapleural pneumonectomy (EPP) were validated by RT-qPCR in 48 additional EPP samples. Kaplan-Meier log ranking was used to further explore the association between microRNA expression and overall survival (OS). Binary logistic regression was used to construct a microRNA signature (miR-Score) that was able to predict an OS of ≥20 months. Performance of the miR-Score was evaluated by receiver operating characteristic (ROC) curve analysis and validated in a series of 43 tumor samples from patients who underwent palliative surgery [pleurectomy/decortication (P/D)]. The miR-Score, using expression data of six microRNAs (miR-21-5p, -...

Research paper thumbnail of Promoter Hypermethylation Mediates Downregulation of Thiamine Receptor SLC19A3 in Gastric Cancer

Tumor Biology, 2009

As an important way to inactivate tumor suppressor genes (TSGs) during cancer development, promot... more As an important way to inactivate tumor suppressor genes (TSGs) during cancer development, promoter hypermethylation can be used to define novel TSGs and identify biomarkers for cancer diagnosis. SLC19A3 (solute carrier family 19, member 3) was found to be such a biomarker. SLC19A3 expression was downregulated in gastric cancer cell lines (71%, 5/7) and restored after pharmacological demethylation. Notably, hypermethylation of SLC19A3 promoter was detected in gastric cancer cell lines (57%, 4/7), primary gastric carcinoma tissues (51%, 52/101) and precancerous lesion (intestinal metaplasia) tissues (32%, 8/25). Exogenous SLC19A3 expression caused growth inhibition of gastric cancer cells. In summary, SLC19A3 was epigenetically downregulated in gastric cancer. Methylation of SLC19A3 promoter could be a novel biomarker for early gastric cancer development.

Research paper thumbnail of Entropically Driven Photochemical Upconversion

The Journal of Physical Chemistry A, 2011

Conventional photochemical upconversion (UC) through homo-geneous triplet-triplet annihilation (T... more Conventional photochemical upconversion (UC) through homo-geneous triplet-triplet annihilation (TTA) is subject to several enthalpic losses that limit the UC margin. Here, we address one of these losses: the triplet energy transfer (TET) from the sensitizer to the emitter molecules. Usually, the triplet energy level of the emitter is set below that of the sensitizer. In our system, the triplet energy level of the emitter exceeds that of the sensitizer by ∼600 cm(-1). Choosing suitable concentrations for the sensitizer and emitter molecules, we can exploit entropy as a driving force for the migration of triplet excitation from the sensitizer to the emitter manifolds. Thereby we obtain a new record for the peak-to-peak TTA-UC energy margin of 0.94 eV. A modified Stern-Volmer analysis yields a TET rate constant of 2.0 × 10(7) M(-1) s(-1). Despite being relatively inefficient, the upconverted fluorescence is easily visible to the naked eye with irradiation intensities as low as 2 W cm(-2).

Research paper thumbnail of Long Non Coding RNAs (lncRNAs) Are Dysregulated in Malignant Pleural Mesothelioma (MPM)

PLoS ONE, 2013

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanc... more Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs .200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P,0.05) and biological significance (.3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Research paper thumbnail of On the efficiency limit of triplet–triplet annihilation for photochemical upconversion

Physical Chemistry Chemical Physics, 2010

Photochemical upconversion is performed, whereby emitter triplet states are produced through trip... more Photochemical upconversion is performed, whereby emitter triplet states are produced through triplet energy transfer from sensitizer molecules excited with low energy photons. The triplet emitter molecules undergo triplet-triplet annihilation to yield excited singlet states which emit upconverted fluorescence. Experiments comparing the 560 nm prompt fluorescence when rubrene emitter molecules are excited directly, using 525 nm laser pulses, to the delayed, upconverted fluorescence when the porphyrin sensitizer molecules are excited with 670 nm laser pulses reveal annihilation efficiencies to produce excited singlet emitters in excess of 20%. Conservative measurements reveal a 25% annihilation efficiency, while a direct comparison between the prompt and delayed fluorescence yield suggests a value as high as 33%. Due to fluorescence quenching, the photon upconversion efficiencies are lower, at 16%.

Research paper thumbnail of Synthesis and Luminescence Properties of Iridium(III) Azide- and Triazole-Bisterpyridine Complexes

Molecules, 2013

We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the "ch... more We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the "chemistry on the complex" strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition "click chemistry" reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III) bisterpyridines, but this effect can be reversed by the addition of copper(II) sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III) bisterpyridines can be functionalized for use in "click chemistry" facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications.

Research paper thumbnail of 147 ALTERED SIGNIFICANCE OF D'AMICO RISK ASSESSMENT IN BRCA2 POSITIVE VS NEGATIVE PATIENTS FROM HIGH RISK BREAST CANCER FAMILIES

The Journal of Urology, 2011

Research paper thumbnail of Increased Circulating miR-625-3p

Journal of Thoracic Oncology, 2012

We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a bio... more We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM). Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples. We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy. Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.

Research paper thumbnail of Singlet Oxygen Mediated Photochemical Upconversion of NIR Light

We report photochemical upconversion (UC) of near-infrared (NIR) light to the visible spectrum me... more We report photochemical upconversion (UC) of near-infrared (NIR) light to the visible spectrum mediated by molecular oxygen. Thereby, we address two of the main challenges in the field of photochemical UC, (i) UC of photons above 800 nm and (ii) utilization of molecular oxygen, which is necessarily excluded in conventional photochemical UC systems. In the employed system, singlet oxygen is generated upon photoexcitation of the sensitizer molecules and then acts as an energy transmitter for the UC process. The excitation energy of two singlet oxygen molecules is subsequently harvested by emitter molecules, which in turn gives rise to delayed fluorescence of the emitter species. We discuss strategies for improvement of the currently achieved efficiencies of ≤0.01% to produce excited singlet states in the emitter molecules.

Research paper thumbnail of Highly efficient photochemical upconversion in a quasi-solid organogel

J. Mater. Chem. C, 2014

ABSTRACT Despite the promise of photochemical upconversion as a means to extend the light-harvest... more ABSTRACT Despite the promise of photochemical upconversion as a means to extend the light-harvesting capabilities of a range of photovoltaic solar energy conversion devices, it remains a challenge to create efficient, solid state upconverting materials. Until now, a material has yet to be found which is as efficient as a liquid composition. Here, a gelated photochemical upconversion material is reported with a performance indistinguishable from an otherwise identical liquid composition. The sensitizer phosphorescence lifetime, Stern-Volmer quenching constants and upconversion performance (6% under one-sun illumination) were all found to be unchanged in a quasi-solid gelated sample when compared to the liquid sample. The result paves the way to a new family of efficient photochemical upconversion materials comprised of macroscopically solid, but microscopically liquid gel, for application in photovoltaics and photocatalytic water-splitting.

Research paper thumbnail of Deuteration of Perylene Enhances Photochemical Upconversion Efficiency

The Journal of Physical Chemistry Letters, 2015

Photochemical upconversion via triplet-triplet annihilation is a promising technology for improvi... more Photochemical upconversion via triplet-triplet annihilation is a promising technology for improving the efficiency of photovoltaic devices. Previous studies have shown that the efficiency of upconversion depends largely on two rate constants intrinsic to the emitting species. Here, we report that one of these rate constants can be altered by deuteration, leading to enhanced upconversion efficiency. For perylene, deuteration decreases the first order decay rate constant by 16 ± 9% at 298 K, which increases the linear upconversion response by 45 ± 21% in the low excitation regime.

Research paper thumbnail of Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis

British journal of cancer, Jan 11, 2015

Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mes... more Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively. FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (...

Research paper thumbnail of miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

Oncotarget, Jan 22, 2015

Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displ... more Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated...

Research paper thumbnail of An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma

British journal of cancer, Jan 21, 2014

Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothel... more Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed. Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour sam...

Research paper thumbnail of Blockade of Aquaporin 1 Inhibits Proliferation, Motility, and Metastatic Potential of Mesothelioma In Vitro but not in an In Vivo Model

Disease Markers, 2015

Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly t... more Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM. Methods. Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies. Results. Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours. Conclusions. Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo.

Research paper thumbnail of Two-photon triplet-triplet annihilation upconversion for photovoltaics

2011 37th IEEE Photovoltaic Specialists Conference, 2011

ABSTRACT Upconversion is a promising technique for significantly enhancing the efficiency of phot... more ABSTRACT Upconversion is a promising technique for significantly enhancing the efficiency of photovoltaic cells. Molecular systems provide an environment in which long lived triplet states can be exploited to achieve high upconversion efficiencies under solar illumination. We report on the investigation of bi-molecular triplet-triplet annihilation upconversion (TTA-UC) in a Palladium (II) tetrakisquinoxalino porphyrin (PQ4Pd)/rubrene solution. These molecules were studied in solution using UV/VIS spectroscopy to determine their stability in air over a period of weeks. Transient absorption spectroscopy (TAS) was used to directly measure the lifetime of triplet states within these mixtures and hence determine the photoinduced kinetics of the system. The lifetime of porphyrin triplets was reduced from 92.4 μs in pristine PQ4Pd to 2.4 μs in the presence of rubrene. From this change, the rate constant associated with triplet energy transfer (kTET) was calculated as 3.38 × 108M−1s−1. Additionally, a reduction in the absorption of 530 nm light (the ground state rubrene absorption peak) was observed, while the mixture was pumped at the absorption peak of the porphyrin (670 nm). This change became apparent nearly 6 μs after the laser pulse, showing energy transfer from the porphyrin to the rubrene, and allowing further insight into the kinetics of the mechanism.

Research paper thumbnail of Molecular approaches to third generation photovoltaics: Photochemical up-conversion

Next Generation (Nano) Photonic and Cell Technologies for Solar Energy Conversion, 2010

We have investigated a photochemical up-conversion system comprising a molecular mixture of a pal... more We have investigated a photochemical up-conversion system comprising a molecular mixture of a palladium porphyrin to harvest light, and a polycyclic aromatic hydrocarbon to emit light. The energy of harvested photons is stored as molecular triplet states which then annihilate to bring about up-converted fluorescence. The limiting efficiency of such triplet-triplet annihilation up-conversion has been believed to be 11% for some time. However, by rigorously investigating the kinetics of delayed fluorescence following pulsed excitation, we demonstrate instantaneous annihilation efficiencies exceeding 40%, and limiting efficiencies for the current system of ~60%. We attribute the high efficiencies obtained to the electronic structure of the emitting molecule, which exhibits an exceptionally high T2 molecular state. We utilize the kinetic data obtained to model an up-converting layer irradiated with broadband sunlight, finding that ~3% efficiencies can be obtained with the current system, with this improving dramatically upon optimization of various parameters.

Research paper thumbnail of The virtual product-process design laboratory for design and analysis of formulations

Computer Aided Chemical Engineering, 2009

The objective of this paper is to present a virtual laboratory for chemical product-process desig... more The objective of this paper is to present a virtual laboratory for chemical product-process design (virtual PPD-lab) as a tool for the design and analysis of formulations. With the virtual PPD-lab, users can test their design ideas on model-based computer-aided tools before performing experiments to validate the designed product; also, manifold product and process alternatives matching a priori defined targets

Research paper thumbnail of Towards an aligned luminophore solar concentrator

Optics Express, 2010

Luminescent solar concentrators promise to reduce the cost of solar energy, but are hindered by a... more Luminescent solar concentrators promise to reduce the cost of solar energy, but are hindered by a number of losses. Escape of luminescence through the large waveguide-air interfaces can be attenuated through alignment of the optical transition dipole of the luminophore along the waveguide surface normal, directing the maximum possible proportion of luminescence into waveguide modes. We demonstrate such alignment using a guest-host dye-doped liquid crystal sandwiched between conductive glass slides. Application of a potential while illuminating through a narrow edge caused a drop in the intensity of luminescence escaping the large surfaces, and an increase in the intensity of light escaping the narrow edges of the system. This is explained in terms of alignment of the transition dipoles of the dye. We discuss implementation in a luminescent solar concentrator.

Research paper thumbnail of Integrating a triplet-triplet annihilation up-conversion system to enhance dye-sensitized solar cell response to sub-bandgap light

Journal of visualized experiments : JoVE, 2014

The poor response of dye-sensitized solar cells (DSCs) to red and infrared light is a significant... more The poor response of dye-sensitized solar cells (DSCs) to red and infrared light is a significant impediment to the realization of higher photocurrents and hence higher efficiencies. Photon up-conversion by way of triplet-triplet annihilation (TTA-UC) is an attractive technique for using these otherwise wasted low energy photons to produce photocurrent, while not interfering with the photoanodic performance in a deleterious manner. Further to this, TTA-UC has a number of features, distinct from other reported photon up-conversion technologies, which renders it particularly suitable for coupling with DSC technology. In this work, a proven high performance TTA-UC system, comprising a palladium porphyrin sensitizer and rubrene emitter, is combined with a high performance DSC (utilizing the organic dye D149) in an integrated device. The device shows an enhanced response to sub-bandgap light over the absorption range of the TTA-UC sub-unit resulting in the highest figure of merit for up-...

Research paper thumbnail of MiR-Score: A novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma

Molecular oncology, Jan 2, 2014

Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatme... more Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients. Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors following extrapleural pneumonectomy (EPP) were validated by RT-qPCR in 48 additional EPP samples. Kaplan-Meier log ranking was used to further explore the association between microRNA expression and overall survival (OS). Binary logistic regression was used to construct a microRNA signature (miR-Score) that was able to predict an OS of ≥20 months. Performance of the miR-Score was evaluated by receiver operating characteristic (ROC) curve analysis and validated in a series of 43 tumor samples from patients who underwent palliative surgery [pleurectomy/decortication (P/D)]. The miR-Score, using expression data of six microRNAs (miR-21-5p, -...

Research paper thumbnail of Promoter Hypermethylation Mediates Downregulation of Thiamine Receptor SLC19A3 in Gastric Cancer

Tumor Biology, 2009

As an important way to inactivate tumor suppressor genes (TSGs) during cancer development, promot... more As an important way to inactivate tumor suppressor genes (TSGs) during cancer development, promoter hypermethylation can be used to define novel TSGs and identify biomarkers for cancer diagnosis. SLC19A3 (solute carrier family 19, member 3) was found to be such a biomarker. SLC19A3 expression was downregulated in gastric cancer cell lines (71%, 5/7) and restored after pharmacological demethylation. Notably, hypermethylation of SLC19A3 promoter was detected in gastric cancer cell lines (57%, 4/7), primary gastric carcinoma tissues (51%, 52/101) and precancerous lesion (intestinal metaplasia) tissues (32%, 8/25). Exogenous SLC19A3 expression caused growth inhibition of gastric cancer cells. In summary, SLC19A3 was epigenetically downregulated in gastric cancer. Methylation of SLC19A3 promoter could be a novel biomarker for early gastric cancer development.

Research paper thumbnail of Entropically Driven Photochemical Upconversion

The Journal of Physical Chemistry A, 2011

Conventional photochemical upconversion (UC) through homo-geneous triplet-triplet annihilation (T... more Conventional photochemical upconversion (UC) through homo-geneous triplet-triplet annihilation (TTA) is subject to several enthalpic losses that limit the UC margin. Here, we address one of these losses: the triplet energy transfer (TET) from the sensitizer to the emitter molecules. Usually, the triplet energy level of the emitter is set below that of the sensitizer. In our system, the triplet energy level of the emitter exceeds that of the sensitizer by ∼600 cm(-1). Choosing suitable concentrations for the sensitizer and emitter molecules, we can exploit entropy as a driving force for the migration of triplet excitation from the sensitizer to the emitter manifolds. Thereby we obtain a new record for the peak-to-peak TTA-UC energy margin of 0.94 eV. A modified Stern-Volmer analysis yields a TET rate constant of 2.0 × 10(7) M(-1) s(-1). Despite being relatively inefficient, the upconverted fluorescence is easily visible to the naked eye with irradiation intensities as low as 2 W cm(-2).

Research paper thumbnail of Long Non Coding RNAs (lncRNAs) Are Dysregulated in Malignant Pleural Mesothelioma (MPM)

PLoS ONE, 2013

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanc... more Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs .200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P,0.05) and biological significance (.3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Research paper thumbnail of On the efficiency limit of triplet–triplet annihilation for photochemical upconversion

Physical Chemistry Chemical Physics, 2010

Photochemical upconversion is performed, whereby emitter triplet states are produced through trip... more Photochemical upconversion is performed, whereby emitter triplet states are produced through triplet energy transfer from sensitizer molecules excited with low energy photons. The triplet emitter molecules undergo triplet-triplet annihilation to yield excited singlet states which emit upconverted fluorescence. Experiments comparing the 560 nm prompt fluorescence when rubrene emitter molecules are excited directly, using 525 nm laser pulses, to the delayed, upconverted fluorescence when the porphyrin sensitizer molecules are excited with 670 nm laser pulses reveal annihilation efficiencies to produce excited singlet emitters in excess of 20%. Conservative measurements reveal a 25% annihilation efficiency, while a direct comparison between the prompt and delayed fluorescence yield suggests a value as high as 33%. Due to fluorescence quenching, the photon upconversion efficiencies are lower, at 16%.

Research paper thumbnail of Synthesis and Luminescence Properties of Iridium(III) Azide- and Triazole-Bisterpyridine Complexes

Molecules, 2013

We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the "ch... more We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the "chemistry on the complex" strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition "click chemistry" reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III) bisterpyridines, but this effect can be reversed by the addition of copper(II) sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III) bisterpyridines can be functionalized for use in "click chemistry" facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications.

Research paper thumbnail of 147 ALTERED SIGNIFICANCE OF D'AMICO RISK ASSESSMENT IN BRCA2 POSITIVE VS NEGATIVE PATIENTS FROM HIGH RISK BREAST CANCER FAMILIES

The Journal of Urology, 2011

Research paper thumbnail of Increased Circulating miR-625-3p

Journal of Thoracic Oncology, 2012

We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a bio... more We investigated the ability of cell-free microRNAs (miRNAs) in plasma and serum to serve as a biomarker for malignant mesothelioma (MM). Using miRNA microarrays, we profiled plasma samples from MM patients and healthy controls. miRNAs with significantly different abundance between cases and controls were validated in a larger series of MM patients and in an independent series of MM patients using quantitative real-time polymerase chain reaction. Levels of candidate miRNAs were also quantified in MM tumor samples. We compared cell-free miRNA profiles in plasma from MM patients with healthy controls. Reviewing 90 miRNAs previously reported to be associated with MM, we found that the levels of two miRNAs, miR-29c* and miR-92a, were elevated in plasma samples from MM patients. In addition, we identified 15 novel miRNAs present at significantly higher levels in the plasma of MM patients. Further analysis of candidate miRNAs by real time-quantitative polymerase chain reaction confirmed that one of them, miR-625-3p, was present in significantly higher concentration in plasma/serum from MM patients and was able to discriminate between cases and controls, in both the original and the independent series of patients. MiR-625-3p was also found to be up-regulated in tumor specimens from a group of 18 MM patients, who underwent extrapleural pneumonectomy. Our data confirm the potential of miR-29c* and miR-92a as candidate tumor markers and reveal that miR-625-3p is a promising novel diagnostic marker for MM.