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.
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.
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.
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% (...
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...
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...
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.
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.
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
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-...
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, -...
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).
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%.
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.
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.
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.
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.
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% (...
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...
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...
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.
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.
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
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-...
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, -...
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).
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%.
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.
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Papers by Yuen Cheng