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Book ; Thesis: Aktivierungsabhängige translationelle Regulation der Orai1-Expression in Thrombozyten

Tolios, Alexander

2013

Author's details	vorgelegt von Alexander Tolios
Language	German
Size	75 S. : Ill., graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Tübingen, Univ., Diss., 2013
HBZ-ID	HT017730008
Database	Catalogue ZB MED Medicine, Health

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Article: Systematic Analysis of the Transcriptome Profiles and Co-Expression Networks of Tumour Endothelial Cells Identifies Several Tumour-Associated Modules and Potential Therapeutic Targets in Hepatocellular Carcinoma.

Mohr, Thomas / Katz, Sonja / Paulitschke, Verena / Aizarani, Nadim / Tolios, Alexander

Cancers

2021 Volume 13, Issue 8

Abstract: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related death, with tumour associated liver endothelial cells being thought to be major drivers in HCC progression. This study aims to compare the ... ...

Abstract	Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related death, with tumour associated liver endothelial cells being thought to be major drivers in HCC progression. This study aims to compare the gene expression profiles of tumour endothelial cells from the liver with endothelial cells from non-tumour liver tissue, to identify perturbed biologic functions, co-expression modules, and potentially drugable hub genes that could give rise to novel therapeutic targets and strategies. Gene Set Variation Analysis (GSVA) showed that cell growth-related pathways were upregulated, whereas apoptosis induction, immune and inflammatory-related pathways were downregulated in tumour endothelial cells. Weighted Gene Co-expression Network Analysis (WGCNA) identified several modules strongly associated to tumour endothelial cells or angiogenic activated endothelial cells with high endoglin (
Language	English
Publishing date	2021-04-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13081768
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Article ; Online: The necessity of repeat testing for von Willebrand disease in adult patients with mild to moderate bleeding disorders.

Mehic, Dino / Kraemmer, Daniel / Tolios, Alexander / Bücheler, Julia / Quehenberger, Peter / Haslacher, Helmuth / Ay, Cihan / Pabinger, Ingrid / Gebhart, Johanna

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 1, Page(s) 101–111

Abstract: Background: In patients with mild-to-moderate bleeding disorders (MBD), von Willebrand disease (VWD) is diagnosed at von Willebrand factor (VWF) levels ≤50 IU/dL. Although VWF levels are unstable, repeated testing for VWD diagnosis is not necessarily ... ...

Abstract	Background: In patients with mild-to-moderate bleeding disorders (MBD), von Willebrand disease (VWD) is diagnosed at von Willebrand factor (VWF) levels ≤50 IU/dL. Although VWF levels are unstable, repeated testing for VWD diagnosis is not necessarily advised in recent guidelines. Objectives: To analyze the relevance of repeated VWF testing to diagnose VWD in patients with MBD. Methods: Data of 277 patients with MBD from the Vienna Bleeding Biobank with at least 2 separate assessments of VWF antigen (VWF:Ag) and activity (VWF:Act) were analyzed. Results: In repeated VWF measurements, 36 patients (13.0%) had "changing" VWF levels (≤/>50 IU/dL), 27 (9.7%) had persistent levels ≤50 IU/dL ("pathologic"), and 214 (77.3%) had levels >50 IU/dL ("normal"). Of the 36 changing patients, 22 (61%) were diagnosed with VWD at baseline, whereas the others only met VWD diagnostic criteria at repeated measurements. Using logistic regression, we estimated a probability of change of 26.4% (95% CI, 12.5-47.4) at baseline VWF levels of 30 IU/dL, 50.8% (95% CI, 35.6-65.8) at 50 IU/dL, 18.8% (95% CI, 12.3-27.6) at 60 IU/dL, and 1.2% (95% CI, 0.3-4.9) at 80 IU/dL. Baseline VWF was a strong predictor for changing status (Χ Conclusion: Our data emphasize an overlap between patients with VWD and MBD with bleeding disorder of unknown cause and underline the need for repeated VWF testing, especially in patients with VWF levels <80 IU/dL.
MeSH term(s)	Adult ; Humans ; von Willebrand Diseases ; von Willebrand Factor ; Hemorrhage ; Blood Coagulation Tests ; Risk Factors
Chemical Substances	von Willebrand Factor
Language	English
Publishing date	2023-09-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.09.010
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 295: Show issues

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Article ; Online: Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples.

Lacom, Conrad / Tolios, Alexander / Löffler, Markus W / Eichelberger, Beate / Quehenberger, Peter / Schaden, Eva / Wiegele, Marion

Biochemia medica

2022 Volume 32, Issue 2, Page(s) 20713

Abstract: Introduction: Point-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet ...

Abstract	Introduction: Point-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet count required to obtain valid test results were defined and a testing method to facilitate comparability between different tests was established. Materials and methods: We assessed platelet function in whole blood samples of healthy volunteers at decreasing platelet counts (> 100, 80-100, 50-80, 30-50 and < 30 x10 Results: The minimal platelet count required for reliable test results was 100 x10 Conclusion: Calculating the ED
MeSH term(s)	Blood Platelets ; Flow Cytometry ; Humans ; Platelet Aggregation ; Platelet Count ; Platelet Function Tests/methods ; Point-of-Care Systems ; Thrombocytopenia
Language	English
Publishing date	2022-07-05
Publishing country	Croatia
Document type	Journal Article
ZDB-ID	1208725-7
ISSN	1846-7482 ; 1330-0962
ISSN (online)	1846-7482
ISSN	1330-0962
DOI	10.11613/BM.2022.020713
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Zs.A 4273: Show issues

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Article ; Online: The assessment of platelet function by thromboelastometry as a point-of-care test to guide Intercept-treated platelet support in hemato-oncological patients and hematopoietic stem cell transplantation recipients.

Leitner, Gerda C / Ho, Markus / Tolios, Alexander / Hopfinger, Georg / Rabitsch, Werner / Wohlfarth, Philipp

Transfusion

2020 Volume 60, Issue 7, Page(s) 1391–1399

Abstract: Background: Pathogen inactivation (PI) techniques for platelet concentrates (PCs) are one of the latest innovations to improve blood safety and reduce the risk of transfusion-transmitted infections (TTIs). An impaired function and in vivo recovery of ... ...

Abstract	Background: Pathogen inactivation (PI) techniques for platelet concentrates (PCs) are one of the latest innovations to improve blood safety and reduce the risk of transfusion-transmitted infections (TTIs). An impaired function and in vivo recovery of platelets as well as an increased PC demand are concerns regarding these techniques. The intent of this study was to evaluate the hemostatic effect of PCs treated with the Intercept™ System by thromboelastometry (TEM) and to assess the clinical validity of its results in comparison to post-transfusion increase (PTI) and corrected count increment (CCI). Study-design and methods: This prospective-observational study included 47 patients (m:f = 25:22; median age: 54 years [21-70]) of our Bone Marrow Transplantation unit with hemato-oncological malignancies transfused with Intercept™-treated PCs. Serial TEM measurements were performed just before and 1 hour after PC transfusion and were analyzed for their correlation with PTI and CCI as well as for clinical variables. Results: The majority of our patients had received a hematopoietic stem cell transplantation (HSCT) (n = 41; 87%). In median 9 (1-50) PCs were transfused. Serial TEM, PTI, and CCI measurements were available for 150 transfusion episodes. The median platelet dose transfused was 2.65 × 10 Conclusion: Serial TEM measurements indicate the hemostatic effect of Intercept™-treated PCs. The 1-hour PTI and CCI may not appropriately reflect the in vivo function of platelets after PI PC transfusion.
MeSH term(s)	Adult ; Aged ; Allografts ; Blood Platelets/metabolism ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Neoplasms/blood ; Neoplasms/therapy ; Platelet Transfusion ; Point-of-Care Testing ; Prospective Studies ; Thrombelastography
Language	English
Publishing date	2020-04-22
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Observational Study
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.15783
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Zs.A 284: Show issues

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Article ; Online: Potentials and pitfalls of ChatGPT and natural-language artificial intelligence models for the understanding of laboratory medicine test results. An assessment by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Artificial Intelligence (WG-AI).

Cadamuro, Janne / Cabitza, Federico / Debeljak, Zeljko / De Bruyne, Sander / Frans, Glynis / Perez, Salomon Martin / Ozdemir, Habib / Tolios, Alexander / Carobene, Anna / Padoan, Andrea

Clinical chemistry and laboratory medicine

2023 Volume 61, Issue 7, Page(s) 1158–1166

Abstract: Objectives: ChatGPT, a tool based on natural language processing (NLP), is on everyone's mind, and several potential applications in healthcare have been already proposed. However, since the ability of this tool to interpret laboratory test results has ... ...

Abstract	Objectives: ChatGPT, a tool based on natural language processing (NLP), is on everyone's mind, and several potential applications in healthcare have been already proposed. However, since the ability of this tool to interpret laboratory test results has not yet been tested, the EFLM Working group on Artificial Intelligence (WG-AI) has set itself the task of closing this gap with a systematic approach. Methods: WG-AI members generated 10 simulated laboratory reports of common parameters, which were then passed to ChatGPT for interpretation, according to reference intervals (RI) and units, using an optimized prompt. The results were subsequently evaluated independently by all WG-AI members with respect to relevance, correctness, helpfulness and safety. Results: ChatGPT recognized all laboratory tests, it could detect if they deviated from the RI and gave a test-by-test as well as an overall interpretation. The interpretations were rather superficial, not always correct, and, only in some cases, judged coherently. The magnitude of the deviation from the RI seldom plays a role in the interpretation of laboratory tests, and artificial intelligence (AI) did not make any meaningful suggestion regarding follow-up diagnostics or further procedures in general. Conclusions: ChatGPT in its current form, being not specifically trained on medical data or laboratory data in particular, may only be considered a tool capable of interpreting a laboratory report on a test-by-test basis at best, but not on the interpretation of an overall diagnostic picture. Future generations of similar AIs with medical ground truth training data might surely revolutionize current processes in healthcare, despite this implementation is not ready yet.
MeSH term(s)	Humans ; Artificial Intelligence ; Chemistry, Clinical ; Laboratories
Language	English
Publishing date	2023-04-24
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2023-0355
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Zs.A 121: Show issues

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Article ; Online: High Rate of Passenger Lymphocyte Syndrome after ABO Minor Incompatible Lung Transplantation.

Kohl, Mirjam M / Schwarz, Stefan / Jaksch, Peter / Muraközy, Gabriella / Kurz, Martin / Schönbacher, Marlies / Tolios, Alexander / Frommlet, Florian / Hoetzenecker, Konrad / Körmöczi, Günther F

American journal of respiratory and critical care medicine

2023 Volume 209, Issue 8, Page(s) 995–1000

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Humans ; Hemolysis ; Blood Group Incompatibility/complications ; Retrospective Studies ; Cohort Studies ; Prospective Studies ; Lymphocytes ; Lung Transplantation/adverse effects
Language	English
Publishing date	2023-12-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202306-1107OC
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Article ; Online: A novel EGFR inhibitor acts as potent tool for hypoxia-activated prodrug systems and exerts strong synergistic activity with VEGFR inhibition in vitro and in vivo.

Caban, Monika / Koblmueller, Bettina / Groza, Diana / Schueffl, Hemma H / Terenzi, Alessio / Tolios, Alexander / Mohr, Thomas / Mathuber, Marlene / Kryeziu, Kushtrim / Jaunecker, Carola / Pirker, Christine / Keppler, Bernhard K / Berger, Walter / Kowol, Christian R / Heffeter, Petra

Cancer letters

2023 Volume 565, Page(s) 216237

Abstract: Small-molecule EGFR inhibitors have distinctly improved the overall survival especially in EGFR-mutated lung cancer. However, their use is often limited by severe adverse effects and rapid resistance development. To overcome these limitations, a hypoxia- ... ...

Abstract	Small-molecule EGFR inhibitors have distinctly improved the overall survival especially in EGFR-mutated lung cancer. However, their use is often limited by severe adverse effects and rapid resistance development. To overcome these limitations, a hypoxia-activatable Co(III)-based prodrug (KP2334) was recently synthesized releasing the new EGFR inhibitor KP2187 in a highly tumor-specific manner only in hypoxic areas of the tumor. However, the chemical modifications in KP2187 necessary for cobalt chelation could potentially interfere with its EGFR-binding ability. Consequently, in this study, the biological activity and EGFR inhibition potential of KP2187 was compared to clinically approved EGFR inhibitors. In general, the activity as well as EGFR binding (shown in docking studies) was very similar to erlotinib and gefitinib (while other EGFR-inhibitory drugs behaved different) indicating no interference of the chelating moiety with the EGFR binding. Moreover, KP2187 significantly inhibited cancer cell proliferation as well as EGFR pathway activation in vitro and in vivo. Finally, KP2187 proved to be highly synergistic with VEGFR inhibitors such as sunitinib. This indicates that KP2187-releasing hypoxia-activated prodrug systems are promising candidates to overcome the clinically observed enhanced toxicity of EGFR-VEGFR inhibitor combination therapies.
MeSH term(s)	Humans ; Prodrugs/pharmacology ; Prodrugs/therapeutic use ; ErbB Receptors/metabolism ; Protein Kinase Inhibitors/therapeutic use ; Erlotinib Hydrochloride/pharmacology ; Lung Neoplasms/metabolism ; Cell Proliferation ; Hypoxia/metabolism ; Cell Line, Tumor ; Antineoplastic Agents/therapeutic use
Chemical Substances	Prodrugs ; ErbB Receptors (EC 2.7.10.1) ; Protein Kinase Inhibitors ; Erlotinib Hydrochloride (DA87705X9K) ; Antineoplastic Agents ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-05-19
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2023.216237
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Zs.A 1177: Show issues

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Article ; Online: Thrombomodulin in patients with mild to moderate bleeding tendency.

Mehic, Dino / Tolios, Alexander / Hofer, Stefanie / Ay, Cihan / Haslacher, Helmuth / Downes, Kate / Haimel, Matthias / Pabinger, Ingrid / Gebhart, Johanna

Haemophilia : the official journal of the World Federation of Hemophilia

2021 Volume 27, Issue 6, Page(s) 1028–1036

Abstract: Introduction: A massive increase of soluble thrombomodulin (sTM) due to variants in the thrombomodulin gene (THBD) has recently been identified as a novel bleeding disorder.: Aim: To investigate sTM levels and underlying genetic variants as a cause ... ...

Abstract	Introduction: A massive increase of soluble thrombomodulin (sTM) due to variants in the thrombomodulin gene (THBD) has recently been identified as a novel bleeding disorder. Aim: To investigate sTM levels and underlying genetic variants as a cause for haemostatic impairment and bleeding in a large number of patients with a mild to moderate bleeding disorder (MBD), including patients with bleeding of unknown cause (BUC). Patients and methods: In 507 MBD patients, sTM levels, thrombin generation and plasma clot formation were measured and compared to 90 age- and sex-matched healthy controls. In patients, genetic analysis of the THBD gene was performed. Results: No difference in sTM levels between patients and controls was found overall (median ([IQR] 5.0 [3.8-6.3] vs. 5.1 [3.7-6.4] ng/ml, p = .762), and according to specific diagnoses of MBD or BUC, and high sTM levels (≥95th percentile of healthy controls) were not overrepresented in patients. Soluble TM levels had no impact on bleeding severity or global tests of haemostasis, including thrombin generation or plasma clot formation. In the THBD gene, no known pathogenic or novel disease-causing variants affecting sTM plasma levels were identified in our patient cohort. Conclusion: TM-associated coagulopathy appears to be rare, as it was not identified in our large cohort of patients with MBD. Soluble TM did not arise as a risk factor for bleeding or altered haemostasis in these patients.
MeSH term(s)	Blood Coagulation Disorders ; Blood Coagulation Tests ; Hemorrhagic Disorders ; Humans ; Thrombin ; Thrombomodulin/genetics
Chemical Substances	Thrombomodulin ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2021-10-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14433
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Zs.A 4249: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Preanalytical Conditions and DNA Isolation Methods Affect Telomere Length Quantification in Whole Blood.

Tolios, Alexander / Teupser, Daniel / Holdt, Lesca M

PloS one

2015 Volume 10, Issue 12, Page(s) e0143889

Abstract: Telomeres are located at chromosome ends and their length (TL) has been associated with aging and human diseases such as cancer. Whole blood DNA is frequently used for TL measurements but the influence of preanalytical conditions and DNA isolation ... ...

Abstract	Telomeres are located at chromosome ends and their length (TL) has been associated with aging and human diseases such as cancer. Whole blood DNA is frequently used for TL measurements but the influence of preanalytical conditions and DNA isolation methods on TL quantification has not been thoroughly investigated. To evaluate potential preanalytical as well as methodological bias on TL, anonymized leftover EDTA-whole blood samples were pooled according to leukocyte counts and were incubated with and without actinomycin D to induce apoptosis as a prototype of sample degradation. DNA was isolated from fresh blood pools and after freezing at -80°C. Commercially available kits using beads (Invitrogen), spin columns (Qiagen, Macherey-Nagel and 5prime) or precipitation (Stratec/Invisorb) and a published isopropanol precipitation protocol (IPP) were used for DNA isolation. TL was assessed by qPCR, and normalized to the single copy reference gene 36B4 using two established single-plex and a new multiplex protocol. We show that the method of DNA isolation significantly affected TL (e.g. 1.86-fold longer TL when comparing IPP vs. Invitrogen). Sample degradation led to an average TL decrease of 22% when using all except for one DNA isolation method (5prime). Preanalytical storage conditions did not affect TL with exception of samples that were isolated with the 5prime kit, where a 27% increase in TL was observed after freezing. Finally, performance of the multiplex qPCR protocol was comparable to the single-plex assays, but showed superior time- and cost-effectiveness and required > 80% less DNA. Findings of the current study highlight the need for standardization of whole blood processing and DNA isolation in clinical study settings to avoid preanalytical bias of TL quantification and show that multiplex assays may improve TL/SCG measurements.
MeSH term(s)	DNA, Neoplasm/chemistry ; DNA, Neoplasm/genetics ; DNA, Neoplasm/isolation & purification ; Female ; Humans ; Male ; Neoplasms/chemistry ; Neoplasms/genetics ; Telomere/chemistry ; Telomere/genetics ; Telomere Homeostasis
Chemical Substances	DNA, Neoplasm
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0143889
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