2024 |
Lincz LF, Theron DZ, Barry DL, Scorgie FE, Sillar J, Sefhore O, et al., 'High Expression of ENO1 and Low Levels of Circulating Anti-ENO1 Autoantibodies in Patients with Myelodysplastic Neoplasms and Acute Myeloid Leukaemia.', Cancers, 16 884 (2024)
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2024 |
Lincz LF, Makhija K, Attalla K, Scorgie FE, Enjeti AK, Prasad R, 'A comparative evaluation of three consecutive artificial intelligence algorithms released by Techcyte for identification of blasts and white blood cells in abnormal peripheral blood films.', Int J Lab Hematol, 46 92-98 (2024) [C1]
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Nova |
2022 |
Skelding KA, Barry DL, Theron DZ, Lincz LF, 'Targeting the two-pore channel 2 in cancer progression and metastasis', Exploration of Targeted Anti-tumor Therapy, 3 62-89 (2022)
The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently... [more]
The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions of TPC2 and a discussion of its potential as a target for therapeutic intervention, including a summary of clinical trials examining the TPC2 inhibitors, naringenin, tetrandrine, and verapamil for the treatment of various cancers is provided.
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2022 |
Skelding KA, Barry DL, Theron DZ, Lincz LF, 'Targeting the two-pore channel 2 in cancer progression and metastasis', Exploration of Targeted Anti-tumor Therapy, 62-89 [C1]
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Nova |
2022 |
Silva A, Scorgie FE, Lincz LF, Maduwage K, Siribaddana S, Isbister GK, 'Indian Polyvalent Antivenom Accelerates Recovery From Venom-Induced Consumption Coagulopathy (VICC) in Sri Lankan Russell's Viper (Daboia russelii) Envenoming', FRONTIERS IN MEDICINE, 9 (2022) [C1]
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Nova |
2022 |
Skelding KA, Barry DL, Theron DZ, Lincz LF, 'Bone Marrow Microenvironment as a Source of New Drug Targets for the Treatment of Acute Myeloid Leukaemia.', Int J Mol Sci, 24 (2022) [C1]
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Nova |
2021 |
Makhija K, Lincz LF, Attalla K, Scorgie FE, Enjeti AK, Prasad R, 'White blood cell evaluation in haematological malignancies using a web-based digital microscopy platform', INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, 43 1379-1387 (2021) [C1]
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Nova |
2021 |
Birgersson M, Chi M, Miller C, Brzozowski JS, Brown J, Schofield L, et al., 'A Novel Role for Brain and Acute Leukemia Cytoplasmic (BAALC) in Human Breast Cancer Metastasis', FRONTIERS IN ONCOLOGY, 11 (2021) [C1]
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2021 |
Skelding KA, Lincz LF, 'Parp inhibitors and haematological malignancies friend or foe?', Cancers, 13 (2021) [C1]
Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibi-tors (PARPi) have become the standard of care for breast and gynaecological cancers with BRC... [more]
Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibi-tors (PARPi) have become the standard of care for breast and gynaecological cancers with BRCA gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tu-mour cells, they should be ideally suited to combatting haematological malignancies where these pathways are notoriously defective, even though BRCA mutations are rare. To date, despite prom-ising results in vitro, few clinical trials in humans for haematological malignancies have been per-formed, and additional investigation is required. Paradoxically, secondary haematological malignancies have arisen in patients after treatment with PARPi, raising concerns about their potential use as therapies for any blood or bone marrow-related disorders. Here, we provide a comprehensive review of the biological, pre-clinical, and clinical evidence for and against treating individual haematological malignancies with approved and experimental PARPi. We conclude that the prom-ise of effective treatment still exists, but remains limited by the lack of investigation into useful biomarkers unique to these malignancies.
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2020 |
Holliday E, Lillicrap T, Kleinig T, Choi PMC, Maguire J, Bivard A, et al., 'Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study', BMJ OPEN, 10 (2020)
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2020 |
Batt TJ, Lincz LF, Prasad R, Patel RP, Shastri M, Lioufas N, et al., 'Plasma levels of enoxaparin oligosaccharides, antifactor-Xa and thrombin generation in patients undergoing haemodialysis.', Blood Coagul Fibrinolysis, 31 152-159 (2020) [C1]
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2020 |
Scorgie FE, Garg MB, Gilbert J, Sakoff JA, Lincz LF, 'A simplified method to calculate telomere length from Southern blot images of terminal restriction fragment lengths', BioTechniques, 68 28-34 (2020) [C1]
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Nova |
2020 |
Lillicrap T, Keragala CB, Draxler DF, Chan J, Ho H, Harman S, et al., 'Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples', FRONTIERS IN NEUROLOGY, 11 (2020)
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2020 |
Schofield L, Lincz LF, Skelding KA, 'Unlikely role of glycolytic enzyme -enolase in cancer metastasis and its potential as a prognostic biomarker', Journal of Cancer Metastasis and Treatment, 6 1-12 (2020) [C1]
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Nova |
2019 |
Enjeti AK, Lincz LF, Seldon M, Isbister GK, 'Circulating microvesicles in snakebite patients with microangiopathy', RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, 3 121-125 (2019) [C1]
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Nova |
2019 |
Liu D, Baqar S, Lincz LL, Ekinci E, 'Sodium Intake, Circulating Microvesicles and Cardiovascular Outcomes in Type 2 Diabetes', CURRENT DIABETES REVIEWS, 15 435-445 (2019)
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2019 |
Chapman K, Scorgie FE, Ariyarajah A, Stephens E, Enjeti AK, Lincz LF, 'The effects of tetrahydrocurcumin compared to curcuminoids on human platelet aggregation and blood coagulation in vitro', Thrombosis Research, 179 28-30 (2019) [C1]
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Nova |
2019 |
Enjeti AK, Lincz LF, Seldon M, Isbister GK, 'Microangiopathy in snake bitesbubble trouble: Response to commentary', RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, 3 298-299 (2019)
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2019 |
Enjeti AK, Ariyarajah A, D'Crus A, Riveros C, Seldon M, Lincz LF, 'Circulating microvesicles are less procoagulant and carry different miRNA cargo in myelodysplasia', BLOOD CELLS MOLECULES AND DISEASES, 74 37-43 (2019) [C1]
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Nova |
2019 |
Ahmed AF, de Bock CE, Sontag E, Hondermarck H, Lincz LF, Thorne RF, 'FAT1 cadherin controls neuritogenesis during NTera2 cell differentiation', Biochemical and Biophysical Research Communications, 514 625-631 (2019) [C1]
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Nova |
2018 |
Pearsall EA, Lincz LF, Skelding KA, 'The role of DNA repair pathways in AML chemosensitivity', Current Drug Targets, 19 (2018) [C1]
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Nova |
2018 |
Alkhatatbeh MJ, Enjeti AK, Baqar S, Ekinci EI, Liu D, Thorne RF, Lincz LF, 'Strategies for enumeration of circulating microvesicles on a conventional flow cytometer: Counting beads and scatter parameters.', Journal of Circulating Biomarkers, 7 1-10 (2018) [C1]
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Nova |
2018 |
Baqar S, Liu D, Lincz LF, Kong YW, Jerums G, Ekinci EI, 'The relationship between habitual dietary sodium intake and RAAS blockade on circulating microparticle levels in type two diabetes', CLINICAL SCIENCE, 132 2207-2220 (2018)
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2017 |
Pagram H, Bivard A, Lincz LF, Levi C, 'Immunity and stroke, the hurdles of stroke research translation', International Journal of Stroke, 12 123-131 (2017) [C1]
Immunomodulatory therapies after stroke have the potential to provide clinical benefit to a subset of patients, but risk subverting the protective, healing aspects of the innate i... [more]
Immunomodulatory therapies after stroke have the potential to provide clinical benefit to a subset of patients, but risk subverting the protective, healing aspects of the innate immune response. Neutrophils clear necrotic cerebral tissue and are important in immunomodulation, but can also contribute to tissue injury. Human trials for immunomodulatory stroke treatments in the sub-acute time frame have attempted to prevent peripheral neutrophil infiltration, but none have been successful and one trial demonstrated harm. These unselected trials had broad inclusion criteria and appear to not have had a specific treatment target. Unfortunately, due to the heterogeneous nature of brain ischemia in humans resulting in variation in clinical severity, the negative effect of thrombolytic drugs on the blood¿brain barrier, and the heterogeneity of immune response, it may only be a subset of stroke patients who can realistically benefit from immunomodulation therapies. Translational research strategies require both an understanding of lab practices which create highly controlled environments in contrast to clinical practice where the diagnosis of stroke does not require the identification of a vessel occlusion. These differences between lab and clinical practices can be resolved through the integration of appropriate patient selection criteria and use of advanced imaging and ridged patient selection practices in clinical trials which will be an important part to the success of any future trials of translational research such as immunomodulation.
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Nova |
2017 |
Malik R, Dau T, Gonik M, Sivakumar A, Deredge DJ, Edeleva EV, et al., 'Common coding variant in SERPINA1 increases the risk for large artery stroke', Proceedings of the National Academy of Sciences of the United States of America, 114 3613-3618 (2017) [C1]
Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation i... [more]
Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis.
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Nova |
2017 |
Isbister GK, Jayamanne S, Mohamed F, Dawson AH, Maduwage K, Gawarammana I, et al., 'A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming', Journal of Thrombosis and Haemostasis, 15 645-654 (2017) [C1]
Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on c... [more]
Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. Summary: Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient.
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Nova |
2017 |
Alkhatatbeh MJ, Lincz LF, Thorne RF, 'Bio-maleimide-stained plasma microparticles can be purified in a native state and target human proximal tubular HK2 cells', BIOMEDICAL REPORTS, 6 63-68 (2017) [C1]
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Nova |
2017 |
Enjeti AK, Ariyarajah A, D'Crus A, Seldon M, Lincz LF, 'Circulating microvesicle number, function and small RNA content vary with age, gender, smoking status, lipid and hormone profiles', Thrombosis Research, 156 65-72 (2017) [C1]
Background Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied. Objectives We evaluated the influe... [more]
Background Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied. Objectives We evaluated the influence of age, gender, smoking status, lipid and hormone profiles on circulating MV in healthy subjects. Methods Platelet free plasma from 143 volunteer blood donors (males¿=¿80, females¿=¿63) was evaluated by standardized flow cytometry for MV expressing CD41 (platelet-derived), CD105 (endothelial-derived), CD235 (red cell-derived), TF (tissue factor) and phosphatidylserine (PS) MV. Procoagulant function was measured by the Xa based assay (XaCT) and endogenous thrombin potential (ETP) using thrombin generation assay. Results Those =¿29¿years and =¿60¿years had higher levels of MV subsets (CD41, CD235, TF and PS) compared to those aged 30¿59¿years. The median CD41, CD105, CD235, TF and PS expressing MV by flow cytometry were similar or lower in females, whilst procoagulant activity by the XaCT assay was higher (p¿=¿0.002). In smokers (n¿=¿21), certain MV subsets (CD41, TF and PS) and functional activity (ETP) was lower (p¿<¿0.05). Regression analysis showed that MV parameters of CD41, CD105, TF and ETP could be predicted independently by age, whilst smoking predicted for CD105, CD235, TF, PS and ETP. Certain MV parameters also correlated with BMI, lipid and hormone levels. The small RNA and miRNA levels did not differ by age group, smoking status or gender. Conclusions It is important to recognize that differences may arise depending on age, gender, BMI, lipid, hormone levels and smoking status in apparently healthy subjects when evaluating MV for pathogenic potential.
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Nova |
2017 |
Bivard A, Lincz LF, Maquire J, Parsons M, Levi C, 'Platelet microparticles: a biomarker for recanalization in rtPA-treated ischemic stroke patients', ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 4 175-179 (2017) [C1]
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Nova |
2016 |
Alkhatatbeh MJ, Lincz LF, Thorne RF, 'Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG
Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition caused by hepatic lipid accumulation that is associated with insulin resistance, diabetes and metabolic synd... [more]
Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition caused by hepatic lipid accumulation that is associated with insulin resistance, diabetes and metabolic syndrome. Although statins should be used with caution in liver diseases, they are increasingly investigated as a possible treatment for NAFLD. The present study recreated an in vitro model of NAFLD using HepG2 cells exposed to oleic acid (OA), which was used to quantify OA-induced lipid accumulation in HepG2 cells treated with various concentrations of simvastatin. In addition, the effect of simvastatin on HepG2 cell morphology and microparticle generation as a marker of cell apoptosis was assessed. OA-induced lipid accumulation was quantified by Oil Red O staining and extraction for optical density determination. Stained lipid droplets were visualized using phase contrast microscopy. Furthermore, HepG2 cell-derived microparticles were counted by flow cytometry subsequent to staining for Annexin V. HepG2 cells treated with 0-1 mM OA showed dose-dependent lipid accumulation. Treatment of HepG2 cells with increasing concentrations of simvastatin followed by treatment with 1 mM OA showed that low simvastatin concen- trations (4-10 µM) were able to reduce lipid accumulation by ~40%, whereas high simvastatin concentrations (20 and 30 µM) induced apoptotic changes in cell morphology and increased the production of Annexin V+ microparticles. This suggests that low simvastatin doses may have a role in preventing NAFLD. However, further investigations are required to confirm this action in vivo and to determine the underlying mechanism by which simvastatin reduces hepatic steatosis.
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Nova |
2016 |
Maduwage KP, Scorgie FE, Lincz LF, O'Leary MA, Isbister GK, 'Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models', Thrombosis Research, 137 174-177 (2016) [C1]
Background Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagul... [more]
Background Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Methods Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, Guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Results Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while Guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 µg/ml), D. russelli (0.4 and 0.1 µg/ml), E. carinatus (0.6 and 0.1 µg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 µg/ml) venom. Cow, rat, pig and Guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Conclusions Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose.
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Nova |
2016 |
Phang M, Thorne RF, Alkhatatbeh MJ, Garg ML, Lincz LF, 'Circulating CD36+microparticles are not altered by docosahexaenoic or eicosapentaenoic acid supplementation', NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, 26 254-260 (2016) [C1]
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Nova |
2016 |
Alkhatatbeh MJ, Ayoub NM, Mhaidat NM, Saadeh NA, Lincz LF, 'Soluble cluster of differentiation 36 concentrations are not associated with cardiovascular risk factors in middle-aged subjects', BIOMEDICAL REPORTS, 4 642-648 (2016) [C1]
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Nova |
2016 |
Enjeti AK, Ariyarajah A, D'Crus A, Seldon M, Lincz LF, 'Correlative analysis of nanoparticle tracking, flow cytometric and functional measurements for circulating microvesicles in normal subjects', Thrombosis Research, 145 18-23 (2016) [C1]
Introduction Circulating microvesicles (MV) can be analysed using a number of different techniques. The aim of this study was to evaluate the correlation between functional procoa... [more]
Introduction Circulating microvesicles (MV) can be analysed using a number of different techniques. The aim of this study was to evaluate the correlation between functional procoagulant based assays including thrombin generation, factor Xa activation test (XaCT), and phosphatidylserine factor Xa-activity by ELISA with optical MV enumeration by flow cytometry and nanoparticle tracking analysis. Methods Citrated blood samples were collected from 60 healthy volunteer blood donors after informed consent. Platelet free plasma was prepared using a standardized published protocol. MV subsets were enumerated by flow cytometry (BDFACS Canto) after staining with specific antibodies for platelets (CD41), endothelial cells (CD105), red cells (CD235) monocytes (CD14), tissue factor (CD142) and for phosphatidylserine expression by binding to annexin V. A standardized protocol using counting beads was employed. Nanotracking analysis was performed on both scatter and fluorescent settings after MV staining with quantum dot stain, Qdot 655. Procoagulant function was assessed by the XaCT assay on an automated coagulation analyser and by thrombin generation assay measuring endogenous thrombin potential (ETP), lagtime, peak (PEAK) and time to peak (ttPEAK) using a Calibrated Automated Thrombogram (CAT). The statistical analysis was carried out with Statistica 12 software using non-parametric tests (Spearman rank order correlations, with significance set at p¿<¿0.05). Results In normal healthy subjects, thrombin generation parameters correlated with levels of MV measured by flow cytometry. ETP, lagtime, ttPEAK and PEAK correlated with MV expressing phosphatidylserine (rs, Spearman rank order correlation was 0.29, 0.40, 0.31 and 0.34 respectively, p¿<¿0.05), and MV expressing tissue factor (rs was 0.29, 0.40, 0.31 and 0.34 respectively, p¿<¿0.05), whilst red cell derived MV correlated with lagtime, ttPEAK and PEAK (rs, was 0.35,0.30 and 0.3, respectively, p¿<¿0.05). Lagtime and ttPEAK negatively correlated with the clot based XaCT test (rs, was -¿0.34 and -¿0.30 respectively, p¿<¿0.05) and positively correlated with the ELISA MP-activity assay (rs¿=¿0.42 for both, p¿<¿0.05). In addition, endothelial MV levels weakly correlated with white cell counts (rs = 0.27, p¿<¿0.05). Conclusions Thrombin generation and flow cytometry for phosphatidylserine or tissue factor expressing MV correlate well as markers for procoagulant activity. A combination of optical or non-optical enumeration as well as functional methods may be required for a complete profiling of circulating MV.
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Nova |
2016 |
Pagram H, Bivard A, Lincz LF, Levi C, 'Peripheral Immune Cell Counts and Advanced Imaging as Biomarkers of Stroke Outcome.', Cerebrovasc Dis Extra, 6 120-128 (2016) [C1]
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Nova |
2015 |
Isbister GK, Maduwage K, Scorgie FE, Shahmy S, Mohamed F, Abeysinghe C, et al., 'Venom concentrations and clotting factor levels in a prospective cohort of russell s viper bites with coagulopathy', PLoS Neglected Tropical Diseases, 9 (2015) [C1]
Background Russell¿s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics... [more]
Background Russell¿s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell¿s viper envenoming. Methodology/Principal Findings In a prospective cohort of 146 patients with Russell¿s viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39y (16¿82y) and 111 were male. The median peak INR was 6.8 (interquartile range[IQR]:3.7 to >13), associated with low fibrinogen [median,<0.01g/L;IQR:<0.01¿0.9g/L), low factor V levels [median,<5%;IQR:<5¿4%], low factor VIII levels [median,40%;IQR:12¿79%] and low factor X levels [median,48%; IQR:29¿67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48h post-antivenom. The median INR remained >3 at 6h post-antivenom but had reduced to <2, by 24h. The aPTT had also returned to close to normal (<50sec) at 24h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis). Conclusions Russell¿s viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48h. Severity of clotting abnormalities was associated with venom concentrations.
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Nova |
2015 |
Cheng YC, Anderson CD, Bione S, Keene K, Maguire JM, Nalls M, et al., 'Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke? (vol 43, pg 980, 2012)', STROKE, 46 E204-E204 (2015) [C3]
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2015 |
Ahmed AF, De Bock CE, Lincz LF, Pundavela J, Zouikr I, Sontag E, et al., 'FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation', Cellular and Molecular Life Sciences, 72 4653-4669 (2015) [C1]
The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are ... [more]
The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.
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Nova |
2015 |
Holliday EG, Traylor M, Malik R, Bevan S, Falcone G, Hopewell JC, et al., 'Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke', STROKE, 46 615-+ (2015) [C1]
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Nova |
2014 |
Maduwage K, O'Leary MA, Scorgie FE, Shahmy S, Mohamed F, Abeysinghe C, et al., 'Detection of venom after antivenom is not associated with persistent coagulopathy in a prospective cohort of Russell's viper (Daboia russelii) envenomings.', PLoS Negl Trop Dis, 8 e3304 (2014) [C1]
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Nova |
2014 |
Lincz LF, Scorgie FE, Johnston CI, O'Leary M, Prasad R, Seldon M, et al., 'Comparative sensitivity of commercially available aPTT reagents to mulga snake (Pseudechis australis) venom.', Pathology, 46 444-449 (2014) [C1]
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Nova |
2014 |
Pundavela J, Demont Y, Jobling P, Lincz LF, Roselli S, Thorne RF, et al., 'ProNGF correlates with Gleason score and is a potential driver of nerve infiltration in prostate cancer', American Journal of Pathology, 184 3156-3162 (2014) [C1]
Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of... [more]
Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of nerve growth factor (proNGF) is overexpressed in prostate cancer and involved in the ability of prostate cancer cells to induce axonogenesis. A series of 120 prostate cancer and benign prostate hyperplasia (BPH) samples were analyzed by IHC for proNGF. ProNGF was mainly localized in the cytoplasm of epithelial cells, with marked expression in cancer compared with BPH. Importantly, the proNGF level positively correlated with the Gleason score (n = 104, tB = 0.51). A higher level of proNGF was observed in tumors with a Gleason score of =8 compared with a Gleason score of 7 and 6 (P < 0.001). In vitro, proNGF was detected in LNCaP, DU145, and PC-3 prostate cancer cells and BPH-1 cells but not in RWPE-1 immortalized nontumorigenic prostate epithelial cells or primary normal prostate epithelial cells. Co-culture of PC12 neuronal-like cells or 50B11 neurons with PC-3 cells resulted in neurite outgrowth in neuronal cells that was inhibited by blocking antibodies against proNGF, indicating that prostate cancer cells can induce axonogenesis via secretion of proNGF. These data reveal that ProNGF is a biomarker associated with high-risk prostate cancers and a potential driver of infiltration by nerves.
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Nova |
2014 |
Golledge J, Clancy P, Maguire J, Lincz L, Koblar S, Mcevoy M, et al., 'Plasma angiopoietin-1 is lower after ischemic stroke and associated with major disability but not stroke incidence', Stroke, 45 1064-1068 (2014) [C1]
BACKGROUND AND PURPOSE - : Studies in rodent models suggest that upregulating angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to assess the associati... [more]
BACKGROUND AND PURPOSE - : Studies in rodent models suggest that upregulating angiopoietin-1 (Angpt1) improves stroke outcomes. The aims of this study were to assess the association of plasma Angpt1 with stroke occurrence and outcome. METHODS - : Plasma Angpt1 was measured in 336 patients who had experienced a recent stroke and 321 healthy controls with no stroke history. Patients with stroke (n=285) were reassessed at 3 months and plasma Angpt1 concentration on admission compared between those with severe and minor disability as assessed by the modified Rankin scale. In a separate cohort of 4032 community-acquired older men prospectively followed for a minimum of 6 years, the association of plasma Angpt1 with stroke incidence was examined. RESULTS - : Median plasma Angpt1 was 3-fold lower in patients who had experienced a recent stroke (6.42, interquartile range, 4.26-9.53 compared with 17.36; interquartile range, 14.01-22.46 ng/mL; P<0.001) and remained associated with stroke after adjustment for other risk factors. Plasma Angpt1 concentrations on admission were lower in patients who had severe disability or died at 3 months (median, 5.52; interquartile range, 3.81-8.75 ng/mL for modified Rankin scale 3-6; n=91) compared with those with minor disability (median, 7.04; interquartile range, 4.75-9.92 ng/mL for modified Rankin scale 0-2; n=194), P=0.012, and remained negatively associated with severe disability or death after adjusting for other risk factors. Plasma Angpt1 was not predictive of stroke incidence in community-dwelling older men. CONCLUSIONS - : Plasma Angpt1 concentrations are low after ischemic stroke particularly in patients with poor stroke outcomes at 3 months. Interventions effective at upregulating Angpt1 could potentially improve stroke outcomes. © 2014 American Heart Association, Inc.
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Nova |
2014 |
Phang M, Scorgie FE, Seldon M, Garg ML, Lincz LF, 'Reduction of prothrombin and Factor V levels following supplementation with omega-3 fatty acids is sex dependent: A randomised controlled study', Journal of Nutritional Biochemistry, 25 997-1002 (2014) [C1]
Background: LCn-3PUFA comprised of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer cardioprotection involving a decrease in coagulant activity; however, the evide... [more]
Background: LCn-3PUFA comprised of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer cardioprotection involving a decrease in coagulant activity; however, the evidence is equivocal. We have previously demonstrated that the acute (24. h) effects and chronic (4. weeks) effects of LCn-3PUFA supplementation on platelet aggregation in human subjects are sex specific. This study investigated the mechanisms of the sex-dependent effects of LCn-3PUFA with 4. weeks supplementation of EPA-rich vs. DHA-rich oils on procoagulant and platelet activity in healthy subjects. Design: A double-blinded, placebo-controlled randomised trial was conducted in 94 healthy adults: male (. n=41) and female (. n=53). Platelet coagulation parameters including factors I, II, V, VII, VIII, IX, X, vWF:Ag and endogenous thrombin potential were measured at baseline and 4. weeks postsupplementation with EPA-rich or DHA-rich oil capsules. Results: We have previously reported that platelet aggregation is specifically reduced by supplementation with EPA in males and DHA in females. This sex-specific effect was also observed for decreases in plasma levels of Factor II (-7.9±3.8%, P=.026), Factor V (-6.5±4.5%, P=.022) and vWF:Ag (-7.3±2.1%, P=.034) and was most pronounced in males supplemented with EPA. In contrast, DHA-mediated reduction in platelet aggregation in females was not accompanied by any significant changes in the coagulation parameters tested. Conclusion: Significant interactions between sex and specific LCn-3PUFA exist to reduce procoagulant activity differentially in males vs. females and could have profound effects on managing risk of thrombotic disease.
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Nova |
2014 |
Clancy P, Lincz LF, Maguire J, McEvoy M, Koblar SA, Golledge J, 'Tenascin-C is increased in atherothrombotic stroke patients and has an anti-inflammatory effect in the human carotid artery.', BioFactors (Oxford, England), 40 448-457 (2014) [C1]
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Nova |
2013 |
Phang M, Lincz LF, Garg ML, 'Eicosapentaenoic and Docosahexaenoic Acid Supplementations Reduce Platelet Aggregation and Hemostatic Markers Differentially in Men and Women', JOURNAL OF NUTRITION, 143 457-463 (2013) [C1]
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Nova |
2013 |
Ardjmand A, de Bock CE, Shahrokhi S, Lincz LF, Boyd AW, Burns GF, Thorne RF, 'Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia', HEMATOLOGY, 18 315-321 (2013) [C1]
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Nova |
2013 |
Isbister GK, Buckley NA, Page CB, Scorgie FE, Lincz LF, Seldon M, Brown SGA, 'A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18)', Journal of Thrombosis and Haemostasis, 11 1310-1318 (2013) [C1]
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Nova |
2013 |
Maduwage K, Scorgie FE, Silva A, Shahmy S, Mohamed F, Abeysinghe C, et al., 'Hump-nosed pit viper (Hypnale hypnale) envenoming causes mild coagulopathy with incomplete clotting factor consumption', CLINICAL TOXICOLOGY, 51 527-531 (2013) [C1]
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Nova |
2013 |
Alkhatatbeh MJ, Enjeti AK, Acharya S, Thorne RF, Lincz LF, 'The origin of circulating CD36 in type 2 diabetes', NUTRITION & DIABETES, 3 (2013) [C1]
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Nova |
2012 |
Cheng YC, Anderson CD, Bione S, Keene K, Maguire JM, Nalls M, et al., 'Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?', Stroke, 43 980-U143 (2012) [C1]
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Nova |
2012 |
Lincz L, Scorgie FE, Enjeti A, Seldon M, 'Variable plasma levels of Factor V Leiden correlate with circulating platelet microparticles in carriers of Factor V Leiden', Thrombosis Research, 129 192-196 (2012) [C1]
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Nova |
2012 |
De Bock CE, Ardjmand Ghahestani A, Molloy TJ, Bone SM, Johnstone DM, Campbell DM, et al., 'The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia', Leukemia, 26 918-926 (2012) [C1]
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Nova |
2012 |
Phang M, Sinclair AJ, Lincz L, Garg ML, 'Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation', Nutrition Metabolism and Cardiovascular Diseases, 22 109-114 (2012) [C1]
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Nova |
2012 |
Phang M, Lincz L, Seldon M, Garg ML, 'Acute supplementation with eicosapentaenoic acid reduces platelet microparticle activity in healthy subjects', Journal of Nutritional Biochemistry, 23 1128-1133 (2012) [C1]
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Nova |
2012 |
Holliday EG, Maguire JM, Evans T-J, Koblar SA, Jannes J, Sturm J, et al., 'Common variants at 6p21.1 are associated with large artery atherosclerotic stroke', Nature Genetics, 44 1147-1153 (2012) [C1]
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Nova |
2012 |
Garg MB, Lincz L, Adler K, Scorgie FE, Ackland S, Sakoff JA, 'Predicting 5-Fluorouracil toxicity in colorectal cancer patients from peripheral blood cell telomere length - A multivariate analysis', British Journal of Cancer, 107 1525-1533 (2012) [C1]
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Nova |
2011 |
Alkhatatbeh MJ, Mhaidat NM, Enjeti AK, Lincz L, Thorne RF, 'The putative diabetic plasma marker, soluble CD36, is non-cleaved, non-soluble and entirely associated with microparticles', Journal of Thrombosis and Haemostasis, 9 844-851 (2011) [C1]
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2011 |
Golledge J, Clancy P, Maguire JM, Lincz L, Koblar S, 'The role of tenascin C in cardiovascular disease', Cardiovascular Research, 92 19-28 (2011) [C1]
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Nova |
2011 |
Maguire JM, Thakkinstian A, Levi CR, Lincz L, Bisset L, Sturm J, et al., 'Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 polymorphisms on 90-day ischemic stroke functional outcome: A novel finding', Journal of Stroke and Cerebrovascular Diseases, 20 134-144 (2011) [C1]
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Nova |
2011 |
McGettigan P, Lincz L, Attia JR, McElduff P, Bissett L, Peel R, et al., 'The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene', British Journal of Clinical Pharmacology, 72 707-714 (2011) [C1]
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Nova |
2010 |
Lacroix R, Robert S, Poncelet P, Kasthuri RS, Key NS, Dignat-George F, 'Standardization of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop', JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 8 2571-2574 (2010)
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2010 |
Isbister GK, Scorgie FE, O'Leary MA, Seldon M, Brown SGA, Lincz L, 'Factor deficiencies in venom-induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP-10)', Journal of Thrombosis and Haemostasis, 8 2504-2513 (2010) [C1]
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Nova |
2010 |
Isbister GK, Woods D, Alley S, O'Leary MA, Seldon M, Lincz L, 'Endogenous thrombin potential as a novel method for the characterization of procoagulant snake venoms and the efficacy of antivenom', Toxicon, 56 75-85 (2010) [C1]
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Nova |
2010 |
Enjeti A, Lincz L, Scorgie FE, Seldon MR, 'Circulating microparticles are elevated in carriers of Factor V Leiden', Thrombosis Research, 126 250-253 (2010) [C1]
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Nova |
2010 |
De Bock CE, Garg ML, Scott NM, Sakoff JA, Scorgie FE, Ackland S, Lincz L, 'Association of thymidylate synthase enhancer region polymorphisms with thymidylate synthase activity in vivo', Pharmacogenomics Journal, 1-8 (2010) [C1]
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Nova |
2009 |
Isbister GK, Scorgie FE, Seldon MR, Lincz L, 'Clinical relevance of brown snake (Pseudonaja spp) factor V escaping hemostatic regulation', Blood, 114 2563 (2009) [C3]
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Nova |
2009 |
Lincz L, Gupta SA, Wratten C, Kilmurray J, Nash S, Seldon M, et al., 'Thrombin generation as a predictor of radiotherapy induced skin erythema', Radiotherapy and Oncology, 90 136-140 (2009) [C1]
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Nova |
2008 |
Lincz L, Mudge L-M, Scorgie FE, Sakoff JA, Hamilton C, Seldon MR, 'Quantification of hTERT splice variants in melanoma by SYBR green real-time polymerase chain reaction indicates a negative regulatory role for the [beta symbol] deletion variant', Neoplasia, 10 1131-1137 (2008) [C1]
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Nova |
2008 |
Enjeti AK, Lincz L, Seldon MR, 'Bio-maleimide as a generic stain for detection and quantitation of microparticles', International Journal of Laboratory Hematology, 30 196-199 (2008) [C1]
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Nova |
2008 |
Maguire JM, Thakkinstian A, Sturm J, Levi CR, Lincz L, Parsons MW, et al., 'Polymorphisms in platelet glycoprotein 1b [alpha] and factor VII and risk of ischemic stroke', Stroke, 39 1710-1716 (2008) [C1]
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Nova |
2008 |
Enjeti AK, Lincz L, Seldon MR, 'Microparticles in health and disease', Seminars in Thrombosis and Haemostasis, 34 683-692 (2008) [C1]
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Nova |
2007 |
Lincz L, Adams MJ, Scorgie FE, Thom J, Baker RI, Seldon M, 'Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden', Blood Coagulation & Fibrinolysis, 18 559-564 (2007) [C1]
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2007 |
Attia JR, Thakkinstian A, Wang Y, Lincz L, Parsons MW, Sturm J, et al., 'The PAI-1 4G/5G gene polymorphism and ischemic stroke: An association study and meta-analysis', Journal of Stroke and Cerebrovascular Diseases, 16 173-179 (2007) [C1]
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2007 |
Au GG, Lincz L, Enno A, Shafren DR, 'Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma', British Journal of Haematology, 137 133-141 (2007) [C1]
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2007 |
Lincz L, Scorgie FE, Garg MB, Ackland S, 'Identification of a novel single nucleotide polymorphism in the second tandem repeat sequence of the thymidylate synthase 2R allele', International Journal of Cancer, 120 1930-1934 (2007) [C1]
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2007 |
Lincz L, Scorgie FE, Garg ML, Ackland S, 'Reply to the letter to the editor 'Classification of thymidylate synthase gene enhancer region polymorphisms'', International Journal of Cancer, 121 2581-2582 (2007) [C3]
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2007 |
Enjeti AK, Lincz L, Seldon M, 'Detection and measurement of microparticles: An evolving research tool for vascular biology', Seminars in Thrombosis and Hemostasis, 33 771-779 (2007) [C1]
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2007 |
Lincz L, Scorgie FE, Robertson R, Enno A, 'Genetic variations in benzene metabolism and susceptibility to multiple myeloma', Leukemia Research, 31 759-763 (2007) [C1]
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2006 |
Lincz L, Lonergan A, Scorgie FE, Rowlings PA, Gibson R, Lawrie A, Seldon MR, 'Endogenous thrombin potential for predicting risk of venous thromboembolism in carriers of Factor V Leiden', Pathophysiology of Haemostatis and Thrombosis, 35 435-439 (2006) [C1]
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2004 |
Lincz L, Scorgie F, Sakoff J, Fagan K, Ackland S, Enno A, 'Telomere length predicts neutrophil recovery in absence of G-CSF after autologous peripheral blood stem cell transplantation', Bone Marrow Transplant, 34 439-445 (2004) [C1]
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2004 |
Lincz L, Kerridge I, Scorgie FE, Bailey M, Enno A, Spencer A, 'Xenobiotic gene polymorphisms and susceptibility to multiple myeloma', Haematologica, 89 628-629 (2004) [C3]
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2003 |
Lincz L, Scorgie FE, Kerridge I, Potts R, Spencer A, Enno A, 'Methionine synthase genetic polymorphism MS A2756G alters susceptibility to follicular but not diffuse large B-cell non-Hodgkin's lymphoma or multiple myeloma', British Journal of Haematology, 120 1051-1054 (2003) [C1]
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Nova |
2002 |
Sakoff J, De Waal E, Garg M, Denham J, Scorgie F, Enno A, et al., 'Telomere Length in Haemopoietic Stem Cells can be Determined from that of Mononuclear Blood Cells or Whole Blood', Leukemia and Lymphoma, 43(10) 2017-2020 (2002) [C1]
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2002 |
Kerridge I, Lincz L, Scorgie F, Hickey D, Granter N, Spencer A, 'Association between xenobiotic gene polymorphisms and non-Hodgkin's lymphoma risk', BRITISH JOURNAL OF HAEMATOLOGY, 118 477-481 (2002)
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2002 |
Kerridge I, Lincz LF, Scorgie FE, Granter N, Hickey D, Enno A, Spencer A, 'Xenobiotic enzyme polymorphisms and lymphoma susceptibility', Br. J. Haemtol, 118 477-481 (2002) [C1] |
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2001 |
Lincz L, Yeh T-X, Spencer A, 'TRAIL-induced eradication of primary tumour cells from multiple myeloma patient bone marrows is not related to TRAIL receptor expression or prior chemotherapy', Leukemia, 15 1650-1657 (2001) [C1]
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Nova |
2001 |
Lincz L, Crooks RL, Way SL, Granter N, Spencer A, 'Tumour Kinetics in Multiple Myeloma Before, During, and After Treatment', Leukemia & Lymphoma, 40 373-384 (2001) [C1]
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2000 |
Lincz LF, Yeh TH, Enno A, Spencer A, 'Variations in TRAIL-induced apoptosis of freshly obtained myeloma cells are not related to TRAIL receptor expression or prior chemotherapy.', BLOOD, 96 162A-162A (2000) |
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2000 |
Lincz LF, Yeh TH, Enno A, Spencer A, 'Variations in trail-induced apoptosis of freshly obtained myeloma cells are not related to trail receptor expression or prior chemotherapy', Blood, 96 (2000)
TNF-related apoptosis-inducing ligand (TRAIL) is a potent and selective inducer of apoptosis in malignant cells. Using the combined methods of Annexin V labelling, cell cycle anal... [more]
TNF-related apoptosis-inducing ligand (TRAIL) is a potent and selective inducer of apoptosis in malignant cells. Using the combined methods of Annexin V labelling, cell cycle analysis and DNA electrophoresis, we have demonstrated susceptibility to TRAILinduced apoptosis in the human multiple myeloma (MM) cell lines NCI H929, RPMI 8226, OPM-2 and LP-1, while the lymphoblastoid cell lines (LCL) U266 and MC/CAR were resistant. Two different forms of TRAIL were tested: purified human recombinant soluble TRAIL (s-TRAIL; residues 114-281; Biomol, Plymouth Meeting, PA) demonstrated maximal apoptosis induction at 1 u,g/ml in sensitive cell lines, while a leucine zipper construct (LZ-TRAIL; Immunex Corp., Seattle, WA) was equally effective when used at a concentration of 500 ng/ml. BM samples obtained from 16 MM patients at various stages of disease were incubated for 24 hours with or without either 2u,g/tnl sTRAIL (n = 8) or lug/ml LZ-TRAIL (n = 8). The percentage of viable MM cells was then determined by flow cytometric quantification of anti-CD138 stained cells and the relative TRAIL-induced reduction in MM cells calculated using the formula: [(Untreated)-(TRAlLTreated)]/Untreated x 100%. BM samples from 6 of 16 (38%) patients demonstrated a significant ( 10%) relative reduction in the number of MM cells following TRAIL incubation (range: 11% to 59%). This did not correlate with prior therapy, as a reduction was seen in 2/5 samples obtained from patients at diagnosis, 2/5 samples following standard-dose chemotherapy and 2/6 samples following high-dose chemotherapy. The relationship between TRAIL-receptor expression (TRAIL-R1, R2, R3, R4 and OPG) and TRAILinduced apoptosis was examined in 2 sensitive (NCI H929, RPMI 8226) and the 2 resistant cell lines and 5 MM BM samples (2 sensitive, 3 resistant) utilising RT-PCR and surface immunostaining of purified MM cells. Concordance between TRAIL-receptor mRNA detection and cell surface expression was shown in all cell lines. Furthermore, all cell lines and patient samples demonstrated mRNA expression for the intracellular deathdomain containing TRAIL-R1. Variable expression of the 2 decoy (TRAIL-R3 and R4) and soluble (OPG) receptors was seen and this did not correlate with TRAIL sensitivity. We conclude that MM cell expression of death effector receptors for TRAIL is insufficient to confer sensitivity to TRAIL-induced apoptosis but that in a significant minority of patients, irrespective of prior therapy, MM cells are sensitive to TRAIL-induced apoptosis.
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1998 |
Lincz L, 'Deciphering the apoptotic pathway: All roads lead to death', Immunology & Cell Biology, 76 1-19 (1998) [C1]
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1997 |
Lincz L, Buret A, Burns GF, 'Formation of spheroid structures in a human colon carcinoma cell line involves a complex series of intercellular rearrangements', Differentiation, 61 261-274 (1997) [C1]
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1996 |
Dorahy DJ, Lincz LF, Meldrum CJ, Burns GF, 'Biochemical isolation of a membrane microdomain from resting platelets highly enriched in the plasma membrane glycoprotein CD36', BIOCHEMICAL JOURNAL, 319 67-72 (1996)
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1995 |
BATES RC, LINCZ LF, BURNS GF, 'INVOLVEMENT OF INTEGRINS IN CELL-SURVIVAL', CANCER AND METASTASIS REVIEWS, 14 191-203 (1995)
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