Publications by authors named "Matthias Moll"

11 Publications

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Comparison of EBRT and I-125 seed brachytherapy concerning outcome in intermediate-risk prostate cancer.

Strahlenther Onkol 2021 Aug 5. Epub 2021 Aug 5.

Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Purpose: This study's objective was the comparison of external beam radiotherapy (EBRT) and I‑125 seed brachytherapy regarding clinical outcome and development of side effects.

Patients And Methods: In all, 462 localized intermediate-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seed brachytherapy or EBRT with a dose of 74 or 78 Gy were included: 297 patients were treated with EBRT and 165 with seeds. Biochemical no evidence of disease (bNED) rates according to Phoenix definition as well as late gastrointestinal and urogenital side effects (EORTC/RTOG) were assessed.

Results: Patients were followed up yearly with a median follow-up of 54 (3-192) months. Observed bNED rates for 74 Gy, 78 Gy and seeds were 87, 92, and 88% after 5 years and 71, 85, and 76% after 9 years, respectively. No significant differences were found comparing seeds with 74 Gy (p = 0.81) and 78 Gy (p = 0.19), as well as between 74 and 78 Gy (p = 0.32). Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥ 2 toxicity compared to seeds, but at no point of the follow-up more than 10% of all patients. However, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 33% RTOG grade ≥ 2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time.

Conclusion: Favorable intermediate-risk prostate cancer patients can be treated either by external beam radiotherapy (74/78 Gy) or permanent interstitial seed brachytherapy.
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http://dx.doi.org/10.1007/s00066-021-01815-zDOI Listing
August 2021

Deep regional hyperthermia with preoperative radiochemotherapy in locally advanced rectal cancer, a prospective phase II trial.

Radiother Oncol 2021 06 17;159:155-160. Epub 2021 Mar 17.

University Hospital Tübingen, Department of Radiation Oncology, Germany; German Cancer Research Center (DKFZ) Heidelberg and German Consortium for Translational Cancer Research (DKTK), Partner Site Tübingen, Germany.

Purpose: The goal of the present study was to investigate the effect of deep regional hyperthermia on early and long-term oncological outcomes in the context of preoperative radiochemotherapy in rectal cancer.

Methods: In this prospective phase II trial, patients with locally advanced rectal cancer were treated with 5-fluorouracil based preoperative radiochemotherapy with 50.4 Gy in 28 fractions. Deep regional hyperthermia was scheduled twice weekly. Pathological tumor regression was scored according to the Dworak regression system. The primary endpoint was pathological complete response (pCR). Further endpoints were local control (LC), distant control (DC), disease-free survival (DFS) and overall survival (OS). Hyperthermia was defined as feasible if 70% of patients received at least eight treatments. Quality of life was assessed at follow-up by the EORTC-QLQ-C30 and QLQ-CR29 questionnaires. Time to event data was analyzed according to Kaplan-Meier based on first-events. The study was registered on clinicaltrials.gov (NCT02353858).

Results: From 2012 until 2017, 78 patients were recruited. Median follow-up was 54 months. Based on magnetic resonance imaging, the mesorectal fascia was involved or threatened in 60% of the patients. Compliance with radiotherapy was 99%, 91% received both cycles of chemotherapy and 77% had eight or more hyperthermia treatments. Median time from the end of radiotherapy to surgery was 6.7 weeks. A pathological complete response was reported in 14% of the patients, 50% had either Dworak 4 (complete regression) or Dworak 3 regression (scattered tumor cells only). Three year estimates for OS, DFS, LC and DC were 94%, 81%, 96% and 87%. Patients with higher hyperthermia related cumulative temperatures showed stronger tumor regression. Global health status based on EORTC-QLQ-C30 was comparable with data from the general population.

Conclusion: Deep regional hyperthermia was feasible, did not compromise standard treatments and resulted in promising long-term oncological outcomes and QoL.
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http://dx.doi.org/10.1016/j.radonc.2021.03.011DOI Listing
June 2021

Biochemical control after adjuvant radiation therapy for prostate cancer: a unicentric, retrospective analysis.

Strahlenther Onkol 2021 Jan 27. Epub 2021 Jan 27.

Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Purpose: To retrospectively evaluate the biochemical no evidence of disease (bNED) and late side effects after adjuvant radiotherapy in prostate cancer patients.

Methods: Patients (n = 85) treated with external beam radiotherapy between 1997 and 2013 following radical prostatectomy (RPE) with pathological tumour stage pT2c with positive surgical margins or pT3 and pT4 tumours with or without positive margins who presented with a postoperative and a preradiation prostate-specific antigen (PSA) level below 0.1 ng/ml. The mean dose applied was 66 Gy with conventional fractionation (4 field box-technique). No androgen deprivation therapy was administered, and patients with incomplete data (missing Gleason score, pT stage, or PSA values postoperatively and/or prior to radiation at the presentation at our department) have been excluded from the analysis. Biochemical recurrence was defined as reaching a PSA level > 0.2 ng/ml during follow-up and bNED rates were assessed. In addition, patients were divided into two groups according to the Roach formula for predicting the risk of pelvic node involvement at a cut-off value of 15%. Late urogenital and gastrointestinal side effects (EORTC/RTOG) were assessed.

Results: After a median follow-up of 60 months the bNED rate was 88% at 5 years and 72% at 10 years for all patients. Patients with low risk of lymph node involvement (group < 15%) had a 5 year and 10 year bNED of 97% and 85%, while patients with high risk of positive lymph node involvement (group > 15%) showed corresponding bNED rates of 77% and 52%, respectively. A significant difference according to the Roach stratification was detected (p ≤ 0.002). Late urogenital (UG) and gastrointestinal (GI) grade ≥ 2 side effects were detected in 10% and 15%, respectively.

Conclusion: Postoperative radiotherapy with an average dose of 66 Gy to the prostatic fossa following RPE provides excellent tumour control rates with acceptable side effects. Patients with a higher risk of positive lymph nodes (> 15%) according to the Roach formula show significant worse tumour control rates.
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http://dx.doi.org/10.1007/s00066-020-01742-5DOI Listing
January 2021

Treatment of low-risk prostate cancer: a retrospective study with 477 patients comparing external beam radiotherapy and I-125 seeds brachytherapy in terms of biochemical control and late side effects.

Strahlenther Onkol 2021 Feb 8;197(2):118-123. Epub 2020 Jul 8.

Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria.

Purpose: The goal of our study was comparison of external beam radiotherapy (EBRT) and I‑125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects.

Patients And Methods: 477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seeds brachytherapy or EBRT with a dose of 74 or 78 Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds.

Results: Patients were followed up yearly with a median follow-up of 70 (3-192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time.

Conclusion: Both EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.
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http://dx.doi.org/10.1007/s00066-020-01657-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840646PMC
February 2021

Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen.

Cell Rep 2015 Dec 25;13(10):2048-55. Epub 2015 Nov 25.

Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany; Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg and University of Regensburg, 93053 Regensburg, Germany. Electronic address:

Both hypoxic and inflammatory conditions activate transcription factors such as hypoxia-inducible factor (HIF)-1α and nuclear factor (NF)-κB, which play a crucial role in adaptive responses to these challenges. In dendritic cells (DC), lipopolysaccharide (LPS)-induced HIF1α accumulation requires NF-κB signaling and promotes inflammatory DC function. The mechanisms that drive LPS-induced HIF1α accumulation under normoxia are unclear. Here, we demonstrate that LPS inhibits prolyl hydroxylase domain enzyme (PHD) activity and thereby blocks HIF1α degradation. Of note, LPS-induced PHD inhibition was neither due to cosubstrate depletion (oxygen or α-ketoglutarate) nor due to increased levels of reactive oxygen species, fumarate, and succinate. Instead, LPS inhibited PHD activity through NF-κB-mediated induction of the iron storage protein ferritin and subsequent decrease of intracellular available iron, a critical cofactor of PHD. Thus, hypoxia and LPS both induce HIF1α accumulation via PHD inhibition but deploy distinct molecular mechanisms (lack of cosubstrate oxygen versus deprivation of co-factor iron).
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http://dx.doi.org/10.1016/j.celrep.2015.11.005DOI Listing
December 2015

3D Cultivation Techniques for Primary Human Hepatocytes.

Microarrays (Basel) 2015 Feb 16;4(1):64-83. Epub 2015 Feb 16.

BG Trauma Center, Siegfried Weller Institut, Eberhard Karls University Tübingen, Schnarrenbergstr. 95, 72076 Tü̈bingen, Germany.

One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in a loss of hepatocyte morphology and of liver-specific functions, such as drug-metabolizing enzymes and transporters. As it has been demonstrated that hepatocytes embedded between two sheets of collagen maintain their function, various hydrogels and scaffolds for the 3D cultivation of hepatocytes have been developed. To further improve or maintain hepatic functions, 3D cultivation has been combined with perfusion. In this manuscript, we discuss the benefits and drawbacks of different 3D microfluidic devices. For most systems that are currently available, the main issues are the requirement of large cell numbers, the low throughput, and expensive equipment, which render these devices unattractive for research and the drug-developing industry. A higher acceptance of these devices could be achieved by their simplification and their compatibility with high-throughput, as both aspects are of major importance for a user-friendly device.
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http://dx.doi.org/10.3390/microarrays4010064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996383PMC
February 2015

Enhanced water splitting activity of M-doped Ta3N5 (M = Na, K, Rb, Cs).

Chem Commun (Camb) 2012 Sep 23;48(69):8685-7. Epub 2012 Jul 23.

Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Martensstrasse 7, D-91058 Erlangen, Germany.

We use a highly aligned Ta(2)O(5) nanochannel structure to fabricate alkali metal ion (Na, K, Rb or Cs) doped Ta(3)N(5)via solution seeding and thermal conversion in NH(3). Under optimized conditions the resulting doped structures show a strongly enhanced visible light water splitting performance in comparison to undoped Ta(3)N(5).
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http://dx.doi.org/10.1039/c2cc33822jDOI Listing
September 2012

Oxide nanotubes on Ti-Ru alloys: strongly enhanced and stable photoelectrochemical activity for water splitting.

J Am Chem Soc 2011 Apr 29;133(15):5629-31. Epub 2011 Mar 29.

Department of Materials Science, WW4-LKO, University of Erlangen-Nuremberg, Martensstrasse 7, D-91058 Erlangen, Germany.

The present work shows a significant enhancement of the photoelectrochemical water-splitting performance of anodic TiO(2) nanotube layers grown on low concentration (0.01-0.2 at% Ru) Ti-Ru alloys. Under optimized preparation conditions (0.05 at% Ru, 450 °C annealing) the water splitting rate of the oxide tubes could be 6-fold increased. Moreover, the beneficial effect is very stable with illumination time; this is in contrast to other typical doping approaches of TiO(2).
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http://dx.doi.org/10.1021/ja110638yDOI Listing
April 2011

A trinuclear [NiFe] cluster exhibiting structural and functional key features of [NiFe] hydrogenases.

Angew Chem Int Ed Engl 2004 Jun;43(24):3141-4

Institut für Anorganische Chemie, Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany.

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http://dx.doi.org/10.1002/anie.200353440DOI Listing
June 2004

Heterolytic cleavage of H2 at a sulfur-bridged dinuclear ruthenium center.

Angew Chem Int Ed Engl 2004 Mar;43(14):1877-80

Institut für Anorganische Chemie, Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany.

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http://dx.doi.org/10.1002/anie.200453717DOI Listing
March 2004

ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiae.

Eur J Biochem 2002 Aug;269(16):4033-9

Lehrstuhl für Biochemie and the Lehrstuhl für Anorganische und Allgemeine Chemie, Universität Erlangen-Nürnberg, Erlangen, Germany.

In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation-extrusion ATPase gene, ENA1. Several well-studied signal transduction pathways are known correlating high salinity to the transcriptional activation of ENA1. Nevertheless, information on the actual sensing mechanism initiating these pathways is limited. Here, we report that the ISC1-encoded phosphosphingolipid-specific phospholipase C appears to be involved in stimulation of ENA1 expression and, consequently, in mediating Na+ and Li+ tolerance in yeast. Deletion of ISC1 distinctly decreased cellular Na+ and Li+ tolerance as growth of the Deltaisc1::HIS5 mutant, DZY1, was severely impaired by 0.5 m NaCl or 0.01 m LiCl. In contrast,K+ tolerance and general osmostress regulation wereunaffected. Isc1Delta mutant growth with 0.9 m KCl and glycerol accumulation in the presence of 0.9 m NaCl or 1.5 m sorbitol were comparable to that of the wild-type. ENA1-lacZ reporter studies suggested that the increased salt sensitivity of the isc1Delta mutant is related to a significant reduction of Na+/Li+-stimulated ENA1 expression. Correspondingly, Ena1p-dependent extrusion of Na+/Li+ ions was less efficient in the isc1Delta mutant than in wild-type cells. Itis suggested that ISC1-dependent hydrolysis of an unidentified yeast inositol phosphosphingolipid represents an early event in one of the salt-induced signalling pathways of ENA1 transcriptional activation.
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http://dx.doi.org/10.1046/j.1432-1033.2002.03096.xDOI Listing
August 2002
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