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Book ; Online: Diffuses großzelliges B-Zell-Lymphom

Lenz, Georg / Chapuy, Björn / Glaß, Bertram / Keil, Felix / Klapper, Wolfram / Nickelsen, Maike / Urban, Novak / Schmidberger, Heinz

Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen

(Onkopedia Leitlinien)

2021

Abstract: Das diffuse großzellige B-Zell-Lymphom ist die häufigste Neoplasie des lymphatischen Systems ... Es geht von reifen B-Zellen aus und führt unbehandelt rasch zum Tode. Charakteristisch sind rasch ... progrediente Lymphknotenvergrößerungen und/oder extranodale Manifestationen sowie Allgemeinsymptome (B ...

Institution	Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie Schweizerische Gesellschaft für Medizinische Onkologie Schweizerische Gesellschaft für Hämatologie
Author's details	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V., OeGHO - Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie, SSMO/SSOM/SGMO - Schweizerische Gesellschaft für Medizinische Onkologie, SGH-SSH - Schweizerische Gesellschaft für Hämatologie/Société Suisse d'Hématologie ; Autoren: Georg Lenz, Björn Chapuy, Bertram Glaß, Felix Keil, Wolfram Klapper, Maike Nickelsen, Novak Urban, Heinz Schmidberger ; Vorherige Autoren: Ulrich Dührsen, Michael A. Fridrik, Norbert Schmitz
Series title	Onkopedia Leitlinien
Abstract	Das diffuse großzellige B-Zell-Lymphom ist die häufigste Neoplasie des lymphatischen Systems. Es geht von reifen B-Zellen aus und führt unbehandelt rasch zum Tode. Charakteristisch sind rasch progrediente Lymphknotenvergrößerungen und/oder extranodale Manifestationen sowie Allgemeinsymptome (B-Symptomatik). Die individuelle Prognose kann mit Hilfe des Internationalen Prognostischen Index (IPI) abgeschätzt werden. Der Therapieanspruch ist kurativ. Die Erstlinientherapie erfolgt mit 6 - 8 Zyklen des R-CHOPProtokolls. In frühen Stadien ist eine Reduktion der Therapiezyklen möglich. Der Stellenwert der Bestrahlung ist nicht endgültig geklärt. Weitere ungeklärte Fragen wie Prognose- oder Response-gesteuerte Therapie, der Wert intensiverer Therapieprotokolle oder die Wirksamkeit neuer Substanzen sind Gegenstand prospektiver klinischer Studien. Die Heilungsrate von Patienten mit diffusem großzelligen B-Zell-Lymphom liegt bei etwa 60 - 70%.
Subject code	610
Language	German
Size	1 Online-Ressource (23 Seiten), Illustrationen
Edition	Stand: April 2021
Publisher	DGHO - Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V
Publishing place	Berlin
Publishing country	Germany
Document type	Book ; Online
Note	Open Access
HBZ-ID	HT021146732
DOI	10.4126/FRL01-006430346
Database	Repository for Life Sciences

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Article ; Online: Amyloid Formation of Stefin B Protein Studied by Infrared Spectroscopy.

Novak, Urban / Žerovnik, Eva / Taler-Verčič, Ajda / Žnidarič, MagdaTušek / Zupančič, Barbara / Grdadolnik, Jože

Frontiers in bioscience (Landmark edition)

2023 Volume 28, Issue 3, Page(s) 46

Abstract: Background: Stefin B, an established model protein for studying the stability and mechanism ... but not pH dependence of stefin B structure.: Results: We show that pH value has significant role ... in the monomer stability of stefin B. Protein is less stable in acidic environment and becomes more stable ...

Abstract	Background: Stefin B, an established model protein for studying the stability and mechanism of protein folding, was used for monitoring protein aggregation and formation of amyloid structure by infrared spectroscopy. Methods: The analyses of the integral intensities of the low frequency part of the Amide I band, which is directly connected to the appearance of the cross-β structure reveals the temperature but not pH dependence of stefin B structure. Results: We show that pH value has significant role in the monomer stability of stefin B. Protein is less stable in acidic environment and becomes more stable in neutral or basic conditions. While in the case of the Amide I band area analysis we apply only spectral regions characteristic for only part of the protein in cross-β structure, the temperature study using multivariate curve resolution (MCR) analysis contains also information about the protein conformation states which do not correspond to native protein nor protein in cross-β structure. Conclusions: These facts results in the slightly different shapes of fitted sigmoid functions fitted to the weighted amount of the second basic spectrum (sc2), which is the closed approximation of the protein spectra with cross-β structure. Nevertheless, the applied method detects the initial change of the protein structure. Upon the analysis of infrared data a model for stefin B aggregation is proposed.
MeSH term(s)	Cystatin B ; Cystatins/chemistry ; Cystatins/metabolism ; Amyloid/chemistry ; Amyloid/metabolism ; Protein Conformation ; Spectrum Analysis
Chemical Substances	Cystatin B (88844-95-5) ; Cystatins ; Amyloid
Language	English
Publishing date	2023-04-01
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2704569-9
ISSN	2768-6698 ; 2768-6698
ISSN (online)	2768-6698
ISSN	2768-6698
DOI	10.31083/j.fbl2803046
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Article ; Online: Efficacy of Cochleated Amphotericin B in Mouse and Human Mucocutaneous Candidiasis.

Desai, Jigar V / Urban, Amanda / Swaim, Doris Z / Colton, Benjamin / Kibathi, Lilian W / Ferrè, Elise M N / Stratton, Pamela / Merideth, Melissa A / Hunsberger, Sally / Matkovits, Theresa / Mannino, Raphael / Holland, Steven M / Tramont, Edmund / Lionakis, Michail S / Freeman, Alexandra F

Antimicrobial agents and chemotherapy

2022 Volume 66, Issue 7, Page(s) e0030822

Abstract: ... with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral ...

Abstract	Candida albicans causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity. In this study, we evaluated cochleated AMB (CAMB), a new oral AMB formulation, in mouse models of oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC) and in patients with azole-resistant CMC. OPC and VVC were modeled in
MeSH term(s)	Amphotericin B/adverse effects ; Animals ; Antifungal Agents/adverse effects ; Azoles ; Candida albicans ; Candidiasis/drug therapy ; Candidiasis, Chronic Mucocutaneous/drug therapy ; Candidiasis, Oral/drug therapy ; Candidiasis, Vulvovaginal/drug therapy ; Female ; Humans ; Mice
Chemical Substances	Antifungal Agents ; Azoles ; Amphotericin B (7XU7A7DROE)
Language	English
Publishing date	2022-06-14
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.00308-22
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Article: Uvaol Prevents Group B

Silva, Ana Lucia Mendes / Silva, Elaine Cristina Oliveira / Botelho, Rayane Martins / Tenorio, Liliane Patricia Gonçalves / Marques, Aldilane Lays Xavier / Rodrigues, Ingredy Brunele Albuquerque Costa / Almeida, Larissa Iolanda Moreira / Sousa, Ashelley Kettyllem Alves / Pires, Keyla Silva Nobre / Tanabe, Ithallo Sathio Bessoni / Allard, Marie-Julie / Sébire, Guillaume / Souza, Samuel Teixeira / Fonseca, Eduardo Jorge Silva / Borbely, Karen Steponavicius Cruz / Borbely, Alexandre Urban

Frontiers in physiology

2021 Volume 12, Page(s) 766382

Abstract: Group B ...

Abstract	Group B
Language	English
Publishing date	2021-12-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.766382
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Article ; Online: Potent broadly neutralizing antibody VIR-3434 controls hepatitis B and D virus infection and reduces HBsAg in humanized mice.

Lempp, Florian A / Volz, Tassilo / Cameroni, Elisabetta / Benigni, Fabio / Zhou, Jiayi / Rosen, Laura E / Noack, Julia / Zatta, Fabrizia / Kaiser, Hannah / Bianchi, Siro / Lombardo, Gloria / Jaconi, Stefano / Vincenzetti, Lucia / Imam, Hasan / Soriaga, Leah B / Passini, Nadia / Belnap, David M / Schulze, Andreas / Lütgehetmann, Marc /

Telenti, Amalio / Cathcart, Andrea L / Snell, Gyorgy / Purcell, Lisa A / Hebner, Christy M / Urban, Stephan / Dandri, Maura / Corti, Davide / Schmid, Michael A

Journal of hepatology

2023 Volume 79, Issue 5, Page(s) 1129–1138

Abstract: Background & aims: Chronic hepatitis B is a global public health problem, and coinfection ... with hepatitis delta virus (HDV) worsens disease outcome. Here, we describe a hepatitis B virus (HBV) surface antigen (HBsAg ... targeting monoclonal antibody (mAb) with the potential to treat chronic hepatitis B and chronic hepatitis D ...

Abstract	Background & aims: Chronic hepatitis B is a global public health problem, and coinfection with hepatitis delta virus (HDV) worsens disease outcome. Here, we describe a hepatitis B virus (HBV) surface antigen (HBsAg)-targeting monoclonal antibody (mAb) with the potential to treat chronic hepatitis B and chronic hepatitis D. Methods: HBsAg-specific mAbs were isolated from memory B cells of HBV vaccinated individuals. In vitro neutralization was determined against HBV and HDV enveloped with HBsAg representing eight HBV genotypes. Human liver-chimeric mice were treated twice weekly with a candidate mAb starting 3 weeks post HBV inoculation (spreading phase) or during stable HBV or HBV/HDV coinfection (chronic phase). Results: From a panel of human anti-HBs mAbs, VIR-3434 was selected and engineered for pre-clinical development. VIR-3434 targets a conserved, conformational epitope within the antigenic loop of HBsAg and neutralized HBV and HDV infection with higher potency than hepatitis B immunoglobulins in vitro. Neutralization was pan-genotypic against strains representative of HBV genotypes A-H. In the spreading phase of HBV infection in human liver-chimeric mice, a parental mAb of VIR-3434 (HBC34) prevented HBV dissemination and the increase in intrahepatic HBV RNA and covalently closed circular DNA. In the chronic phase of HBV infection or co-infection with HDV, HBC34 treatment decreased circulating HBsAg by >1 log and HDV RNA by >2 logs. Conclusions: The potently neutralizing anti-HBs mAb VIR-3434 reduces circulating HBsAg and HBV/HDV viremia in human liver-chimeric mice. VIR-3434 is currently in clinical development for treatment of patients with chronic hepatitis B or D. Impact and implications: Chronic infection with hepatitis B virus and co-infection with hepatitis D virus place approximately 290 million individuals worldwide at risk of severe liver disease and cancer. Available treatments result in low rates of functional cure or require lifelong therapy that does not eliminate the risk of liver disease. We isolated and characterized a potent human antibody that neutralizes hepatitis B and D viruses and reduces infection in a mouse model. This antibody could provide a new treatment for patients with chronic hepatitis B and D.
Language	English
Publishing date	2023-07-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2023.07.003
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Article ; Online: Repurposing of 8-Hydroxyquinoline-Based Butyrylcholinesterase and Cathepsin B Ligands as Potent Nonpeptidic Deoxyribonuclease I Inhibitors.

Gajic, Mihajlo / Knez, Damijan / Sosič, Izidor / Mravljak, Janez / Meden, Anže / Košak, Urban / Leitzbach, Luisa / George, Sven / Hofmann, Bettina / Zivkovic, Aleksandra / Steinhilber, Dieter / Stark, Holger / Gobec, Stanislav / Smelcerovic, Andrija / Anderluh, Marko

ChemMedChem

2022 Volume 17, Issue 5, Page(s) e202100694

Abstract: A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors was screened ...

Abstract	A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors was screened in vitro for inhibition of deoxyribonuclease I (DNase I). Compounds 22, 8 and 7 are among the most potent synthetic non-peptide DNase I inhibitors reported to date. Three 8-hydroxyquinoline analogues inhibited both DNase I and BChE with IC
MeSH term(s)	Acetylcholinesterase/metabolism ; Butyrylcholinesterase/metabolism ; Cathepsin B ; Cholinesterase Inhibitors/chemistry ; Cholinesterase Inhibitors/pharmacology ; Deoxyribonuclease I/chemistry ; Deoxyribonuclease I/pharmacology ; Ligands ; Molecular Docking Simulation ; Oxyquinoline ; Structure-Activity Relationship
Chemical Substances	Cholinesterase Inhibitors ; Ligands ; Oxyquinoline (5UTX5635HP) ; Acetylcholinesterase (EC 3.1.1.7) ; Butyrylcholinesterase (EC 3.1.1.8) ; Deoxyribonuclease I (EC 3.1.21.1) ; Cathepsin B (EC 3.4.22.1)
Language	English
Publishing date	2022-02-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202100694
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Article ; Online: Mitosis of hepatitis B virus-infected cells

Tu, Thomas / Zehnder, Benno / Wettengel, Jochen M / Zhang, Henrik / Coulter, Sally / Ho, Vikki / Douglas, Mark W / Protzer, Ulrike / George, Jacob / Urban, Stephan

JHEP reports : innovation in hepatology

2022 Volume 4, Issue 9, Page(s) 100514

Abstract: ... turnover (: Lay summary: Chronic hepatitis B affects 300 million people (killing 884,000 per year) and ... uninfected cells. Our work informs new approaches to develop cures for chronic hepatitis B infections. ...

Abstract	Background & aims: The chronicity of HBV (and resultant liver disease) is determined by intrahepatic persistence of the HBV covalently closed circular DNA (cccDNA), an episomal form that encodes all viral transcripts. Therefore, cccDNA is a key target for new treatments, with the ultimate therapeutic aim being its complete elimination. Although established cccDNA molecules are known to be stable in resting hepatocytes, we aimed to understand their fate in dividing cells using Methods: We infected HepG2-NTCP and HepaRG-NTCP cells with HBV and induced mitosis by passaging cells. We measured cccDNA copy number (by precise PCR assays) and HBV-expressing cells (by immunofluorescence) with wild-type HBV. We used reporter viruses expressing luciferase or RFP to track number of HBV-expressing cells over time after mitosis induction using luciferase assays and live imaging, respectively. Results: In all cases, we observed dramatic reductions in cccDNA levels, HBV-positive cell numbers, and cccDNA-dependent protein expression after each round of cell mitosis. The rates of reduction were highly consistent with mathematical models of a complete cccDNA loss in (as opposed to dilution into) daughter cells. Conclusions: Our results are concordant with previous animal models of HBV infection and show that HBV persistence can be efficiently overcome by inducing cell mitosis. These results support therapeutic approaches that induce liver turnover ( Lay summary: Chronic hepatitis B affects 300 million people (killing 884,000 per year) and is incurable. To cure it, we need to clear the HBV genome from the liver. In this study, we looked at how the virus behaves after a cell divides. We found that it completely clears the virus, making 2 new uninfected cells. Our work informs new approaches to develop cures for chronic hepatitis B infections.
Language	English
Publishing date	2022-06-15
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-5559
ISSN (online)	2589-5559
DOI	10.1016/j.jhepr.2022.100514
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Article ; Online: Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators.

Detta, Elena / Corcuera, Angelica / Urban, Andreas / Goldner, Thomas / Bonsmann, Susanne / Engel, Florian / May, Marina M / Buschmann, Helmut / Fianchini, Mauro / Alza, Esther / Pericàs, Miquel A / Pushkarev, Pavel A / Varenyk, Anatolii O / Yakovyuk, Taras Y / Homon, Anton A / Sokoliuk, Pavlo A / Smaliy, Radomyr / Donald, Alastair

Bioorganic & medicinal chemistry letters

2023 Volume 93, Page(s) 129412

Abstract: ... antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is ...

Abstract	Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis. Lead compound 42 and close analogues 56 and 57 exhibited in vitro potency in the sub- and micromolar range along with good physico-chemical properties and were further evaluated in molecular docking and mechanism of action studies.
MeSH term(s)	Humans ; Hepatitis B virus ; Capsid ; Hepatitis B, Chronic ; Virus Assembly ; Molecular Docking Simulation ; Capsid Proteins ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; Virus Replication ; Hepatitis B
Chemical Substances	Capsid Proteins ; Antiviral Agents
Language	English
Publishing date	2023-07-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2023.129412
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Article ; Online: Structure of antiviral drug bulevirtide bound to hepatitis B and D virus receptor protein NTCP.

Liu, Hongtao / Zakrzewicz, Dariusz / Nosol, Kamil / Irobalieva, Rossitza N / Mukherjee, Somnath / Bang-Sørensen, Rose / Goldmann, Nora / Kunz, Sebastian / Rossi, Lorenzo / Kossiakoff, Anthony A / Urban, Stephan / Glebe, Dieter / Geyer, Joachim / Locher, Kaspar P

Nature communications

2024 Volume 15, Issue 1, Page(s) 2476

Abstract: Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface ...

Abstract	Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface polypeptide preS1 to the hepatobiliary transporter Na
MeSH term(s)	Humans ; Hepatitis B virus/physiology ; Antiviral Agents/therapeutic use ; Hepatitis B ; Receptors, Virus/metabolism ; Bile Acids and Salts/metabolism ; Hepatitis Delta Virus/physiology ; Symporters/metabolism ; Virus Internalization ; Hepatocytes/metabolism ; Lipopeptides
Chemical Substances	bulevirtide ; Antiviral Agents ; Receptors, Virus ; Bile Acids and Salts ; Symporters ; Lipopeptides
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46706-w
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Article ; Online: Organ complications after CD19 CAR T-cell therapy for large B cell lymphoma: a retrospective study from the EBMT transplant complications and lymphoma working party.

Penack, Olaf / Peczynski, Christophe / Koenecke, Christian / Polge, Emmanuelle / Sanderson, Robin / Yakoub-Agha, Ibrahim / Fegueux, Nathalie / Daskalakis, Michael / Collin, Matthew / Dreger, Peter / Kröger, Nicolaus / Schanz, Urs / Bloor, Adrian / Ganser, Arnold / Besley, Caroline / Wulf, Gerald G / Novak, Urban / Moiseev, Ivan / Schoemans, Hélène /

Basak, Grzegorz W / Chabannon, Christian / Sureda, Anna / Glass, Bertram / Peric, Zinaida

Frontiers in immunology

2023 Volume 14, Page(s) 1252811

Abstract: ... cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell ...

Abstract	We investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.3%), gastro-intestinal (2.3%) and hepatic (1.8%). The majority occurred within three weeks after CAR-T cell therapy. Overall survival was 83.1% [79.8-86.5; 95% CI] at 3 months and 53.5% [49-58.4; 95% CI] at one year after CAR-T. The most frequent cause of death was tumour progression (85.1%). Non-relapse mortality was 3.1% [2.3-4.1; 95% CI] at 3 months and 5.2% [4.1-6.5; 95% CI] at one year after CAR-T. The most frequent causes of non-relapse mortality were cell-therapy-related toxicities including organ toxicities (6.4% of total deaths) and infections (4.4% of total deaths). Our data demonstrates good safety in the European real-world setting.
MeSH term(s)	Humans ; Immunotherapy, Adoptive/adverse effects ; Retrospective Studies ; Receptors, Chimeric Antigen ; Lymphoma, Large B-Cell, Diffuse/etiology ; Lymphoma, Large B-Cell, Diffuse/therapy ; Adaptor Proteins, Signal Transducing ; Antigens, CD19
Chemical Substances	Receptors, Chimeric Antigen ; Adaptor Proteins, Signal Transducing ; Antigens, CD19
Language	English
Publishing date	2023-09-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1252811
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