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Article ; Online: Susceptibility of multiple myeloma to B-cell lymphoma 2 family inhibitors.

Lernoux, Manon / Schnekenburger, Michael / Dicato, Mario / Diederich, Marc

2021 Volume 188, Page(s) 114526

Abstract: Multiple myeloma (MM) is a biologically complex hematological disorder defined by the clonal proliferation of malignant plasma cells producing excessive monoclonal immunoglobulin that interacts with components of the bone marrow microenvironment, ... ...

Abstract	Multiple myeloma (MM) is a biologically complex hematological disorder defined by the clonal proliferation of malignant plasma cells producing excessive monoclonal immunoglobulin that interacts with components of the bone marrow microenvironment, resulting in the major clinical features of MM. Despite the development of numerous protocols to treat MM patients, this cancer remains currently incurable; due in part to the emergence of resistant clones, highlighting the unmet need for innovative therapeutic approaches. Accumulating evidence suggests that the survival of MM molecular subgroups depends on the expression profiles of specific subsets of anti-apoptotic B-cell lymphoma (BCL)-2 family members. This review summarizes the mechanisms underlying the anti-myeloma activities of the potent BCL-2 family protein inhibitors, individually or in combination with conventional therapeutic options, and provides an overview of the strong rationale to clinically investigate such interventions for MM therapy.
MeSH term(s)	Animals ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/physiology ; Humans ; Immunotherapy/methods ; Lymphoma, B-Cell/drug therapy ; Lymphoma, B-Cell/immunology ; Lymphoma, B-Cell/metabolism ; Multiple Myeloma/drug therapy ; Multiple Myeloma/immunology ; Multiple Myeloma/metabolism ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2/immunology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/physiology
Chemical Substances	Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2021-03-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2021.114526
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Zs.A 19: Show issues

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Book ; Thesis: Das Verhalten des Kallikrein-Kinn-Systems nach großen orthopädischen Eingriffen

Schnekenburger, Michael

1987

Size	105 S. : Ill., graph. Darst.
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Tübingen, Univ., Diss., 1987
HBZ-ID	HT002989579
Database	Catalogue ZB MED Medicine, Health

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87 D 5585	order for loan	Magazin

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Article: HDAC6-an Emerging Target Against Chronic Myeloid Leukemia?

Losson, Hélène / Schnekenburger, Michael / Dicato, Mario / Diederich, Marc

Cancers

2020 Volume 12, Issue 2

Abstract: Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and ... ...

Abstract	Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the molecular characteristics of the HDAC6 protein, as well as its overexpression in CML leukemic stem cells, which make it a promising therapeutic target for the treatment of CML.
Language	English
Publishing date	2020-01-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12020318
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Article ; Online: Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

Schnekenburger, Michael / Dicato, Mario / Diederich, Marc F

Cancer

2019 Volume 125, Issue 10, Page(s) 1612–1628

Abstract: The immune system represents the major primary defense line against carcinogenesis and acts by identifying and eradicating nascent transformed cells. A growing body of evidence is indicating that aberrant epigenetic reprogramming plays a key role in ... ...

Abstract	The immune system represents the major primary defense line against carcinogenesis and acts by identifying and eradicating nascent transformed cells. A growing body of evidence is indicating that aberrant epigenetic reprogramming plays a key role in tumor immune escape through: 1) impaired efficient recognition of neoplastic cells by the immune system, resulting from a downregulation or loss of the expression of tumor-associated antigens, human leukocyte antigens, antigen processing and presenting machinery, and costimulatory molecule genes; 2) aberrant expression of immune checkpoint proteins and their ligands; and 3) modification of cytokine profiles and tumor-associated immune cell populations toward an immunosuppressive state in the tumor microenvironment. Consistent with the inherent reversibility of epigenetic alterations, epigenetic drugs, including DNA methyltransferase and histone deacetylase inhibitors, have the unique potential to favorably modify the tumor microenvironment, restore tumor recognition and stimulate an antitumor immune response. The objective of this review is to highlight selected, naturally occurring epigenetic modulators, namely, butyrate, curcumin, (-)-epigallocatechin-3-gallate, resveratrol, romidepsin, and trichostatin A, with a special focus on their antitumor immune properties.
MeSH term(s)	Antineoplastic Agents/pharmacology ; DNA Modification Methylases/antagonists & inhibitors ; Epigenesis, Genetic/drug effects ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/pathology ; Tumor Escape/genetics ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	Antineoplastic Agents ; Histone Deacetylase Inhibitors ; DNA Modification Methylases (EC 2.1.1.-)
Language	English
Publishing date	2019-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.32041
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Uh III Zs.146: Show issues

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Article ; Online: Epigenetic mechanisms underlying the therapeutic effects of HDAC inhibitors in chronic myeloid leukemia.

Lernoux, Manon / Schnekenburger, Michael / Dicato, Mario / Diederich, Marc

Biochemical pharmacology

2019 Volume 173, Page(s) 113698

Abstract: Chronic myeloid leukemia (CML) is a hematological disorder caused by the oncogenic BCR-ABL fusion protein in more than 90% of patients. Despite the striking improvements in the management of CML patients since the introduction of tyrosine kinase ... ...

Abstract	Chronic myeloid leukemia (CML) is a hematological disorder caused by the oncogenic BCR-ABL fusion protein in more than 90% of patients. Despite the striking improvements in the management of CML patients since the introduction of tyrosine kinase inhibitors (TKis), the appearance of TKi resistance and side effects lead to treatment failure, justifying the need of novel therapeutic approaches. Histone deacetylase inhibitors (HDACis), able to modulate gene expression patterns and important cellular signaling pathways through the regulation of the acetylation status of both histone and non-histone protein targets, have been reported to display promising anti-leukemic properties alone or in combination with TKis. This review summarizes pre-clinical and clinical studies that investigated the mechanisms underlying the anticancer potential of HDACis and discusses the rationale for a combination of HDACis with TKis as a therapeutic option in CML.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Epigenesis, Genetic ; Fusion Proteins, bcr-abl/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic/drug effects ; Histone Deacetylase Inhibitors/administration & dosage ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Histone Deacetylase Inhibitors ; Protein Kinase Inhibitors ; Fusion Proteins, bcr-abl (EC 2.7.10.2)
Language	English
Publishing date	2019-11-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2019.113698
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Zs.A 19: Show issues

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Article ; Online: Perspectives in Medicinal Chemistry: DNA Methylation and Demethylation Mechanisms as Therapeutic Targets?

Schnekenburger, Michael / Diederich, Marc

Current topics in medicinal chemistry

2015 Volume 16, Issue 8, Page(s) 807–808

MeSH term(s)	Azacitidine/analogs & derivatives ; Azacitidine/pharmacology ; Chemistry, Pharmaceutical/methods ; Chemistry, Pharmaceutical/trends ; DNA Glycosylases/metabolism ; DNA Methylation ; Decitabine ; Endodeoxyribonucleases/metabolism ; Epigenesis, Genetic ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics
Chemical Substances	Decitabine (776B62CQ27) ; Endodeoxyribonucleases (EC 3.1.-) ; MBD4 protein, human (EC 3.1.-) ; DNA Glycosylases (EC 3.2.2.-) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2015-09-28
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2064823-6
ISSN	1873-4294 ; 1568-0266
ISSN (online)	1873-4294
ISSN	1568-0266
DOI	10.2174/1568026616999151013124703
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Zs.A 5572: Show issues

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Article ; Online: Anti-cancer effects of naturally derived compounds targeting histone deacetylase 6-related pathways.

Lernoux, Manon / Schnekenburger, Michael / Dicato, Mario / Diederich, Marc

Pharmacological research

2017 Volume 129, Page(s) 337–356

Abstract: Alterations of the epigenetic machinery, affecting multiple biological functions, represent a major hallmark enabling the development of tumors. Among epigenetic regulatory proteins, histone deacetylase (HDAC)6 has emerged as an interesting potential ... ...

Abstract	Alterations of the epigenetic machinery, affecting multiple biological functions, represent a major hallmark enabling the development of tumors. Among epigenetic regulatory proteins, histone deacetylase (HDAC)6 has emerged as an interesting potential therapeutic target towards a variety of diseases including cancer. Accordingly, this isoenzyme regulates many vital cellular regulatory processes and pathways essential to physiological homeostasis, as well as tumor multistep transformation involving initiation, promotion, progression and metastasis. In this review, we will consequently discuss the critical implications of HDAC6 in distinct mechanisms relevant to physiological and cancerous conditions, as well as the anticancer properties of synthetic, natural and natural-derived compounds through the modulation of HDAC6-related pathways.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Histone Deacetylase 6/metabolism ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Signal Transduction
Chemical Substances	Antineoplastic Agents ; Histone Deacetylase 6 (EC 3.5.1.98)
Language	English
Publishing date	2017-11-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2017.11.004
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Zs.A 721: Show issues

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Article: Discovery of Sulforaphane as an Inducer of Ferroptosis in U-937 Leukemia Cells: Expanding Its Anticancer Potential.

Greco, Giulia / Schnekenburger, Michael / Catanzaro, Elena / Turrini, Eleonora / Ferrini, Fabio / Sestili, Piero / Diederich, Marc / Fimognari, Carmela

Cancers

2021 Volume 14, Issue 1

Abstract: In recent years, natural compounds have emerged as inducers of non-canonical cell death. The isothiocyanate sulforaphane (SFN) is a well-known natural anticancer compound with remarkable pro-apoptotic activity. Its ability to promote non-apoptotic cell- ... ...

Abstract	In recent years, natural compounds have emerged as inducers of non-canonical cell death. The isothiocyanate sulforaphane (SFN) is a well-known natural anticancer compound with remarkable pro-apoptotic activity. Its ability to promote non-apoptotic cell-death mechanisms remains poorly investigated. This work aimed to explore the capacity of SFN to induce non-apoptotic cell death modalities. SFN was tested on different acute myeloid leukemia cell lines. The mechanism of cell death was investigated using a multi-parametric approach including fluorescence microscopy, western blotting, and flow cytometry. SFN triggered different cell-death modalities in a dose-dependent manner. At 25 μM, SFN induced caspase-dependent apoptosis and at 50 μM ferroptosis was induced through depletion of glutathione (GSH), decreased GSH peroxidase 4 protein expression, and lipid peroxidation. In contrast, necroptosis was not involved in SFN-induced cell death, as demonstrated by the non-significant increase in phosphorylation of receptor-interacting protein kinase 3 and phosphorylation of the necroptotic effector mixed lineage kinase domain-like pseudokinase. Taken together, our results suggest that the antileukemic activity of SFN can be mediated via both ferroptotic and apoptotic cell death modalities.
Language	English
Publishing date	2021-12-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14010076
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Article ; Online: Natural Compound Histone Deacetylase Inhibitors (HDACi): Synergy with Inflammatory Signaling Pathway Modulators and Clinical Applications in Cancer.

Losson, Hélène / Schnekenburger, Michael / Dicato, Mario / Diederich, Marc

Molecules (Basel, Switzerland)

2016 Volume 21, Issue 11

Abstract: The remarkable complexity of cancer involving multiple mechanisms of action and specific organs led researchers Hanahan and Weinberg to distinguish biological capabilities acquired by cancer cells during the multistep development of human tumors to ... ...

Abstract	The remarkable complexity of cancer involving multiple mechanisms of action and specific organs led researchers Hanahan and Weinberg to distinguish biological capabilities acquired by cancer cells during the multistep development of human tumors to simplify its understanding. These characteristic hallmarks include the abilities to sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, avoid immune destruction, and deregulate cellular energetics. Furthermore, two important characteristics of tumor cells that facilitate the acquisition of emerging hallmarks are tumor-promoting inflammation and genome instability. To treat a multifactorial disease such as cancer, a combination treatment strategy seems to be the best approach. Here we focus on natural histone deacetylase inhibitors (HDACi), their clinical uses as well as synergies with modulators of the pro-inflammatory transcription factor signaling pathways.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Drug Synergism ; Genomic Instability/drug effects ; Histone Deacetylase Inhibitors/chemistry ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/immunology ; Signal Transduction/drug effects ; Transcription Factors/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Histone Deacetylase Inhibitors ; Transcription Factors
Language	English
Publishing date	2016-11-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules21111608
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Zs.MO 81: Show issues

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Article ; Online: Quantitative phase imaging for cell culture quality control.

Kastl, Lena / Isbach, Michael / Dirksen, Dieter / Schnekenburger, Jürgen / Kemper, Björn

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2017 Volume 91, Issue 5, Page(s) 470–481

Abstract: The potential of quantitative phase imaging (QPI) with digital holographic microscopy (DHM) for quantification of cell culture quality was explored. Label-free QPI of detached single cells in suspension was performed by Michelson interferometer-based ... ...

Abstract	The potential of quantitative phase imaging (QPI) with digital holographic microscopy (DHM) for quantification of cell culture quality was explored. Label-free QPI of detached single cells in suspension was performed by Michelson interferometer-based self-interference DHM. Two pancreatic tumor cell lines were chosen as cellular model and analyzed for refractive index, volume, and dry mass under varying culture conditions. Firstly, adequate cell numbers for reliable statistics were identified. Then, to characterize the performance and reproducibility of the method, we compared results from independently repeated measurements and quantified the cellular response to osmolality changes of the cell culture medium. Finally, it was demonstrated that the evaluation of QPI images allows the extraction of absolute cell parameters which are related to cell layer confluence states. In summary, the results show that QPI enables label-free imaging cytometry, which provides novel complementary integral biophysical data sets for sophisticated quantification of cell culture quality with minimized sample preparation. © 2017 International Society for Advancement of Cytometry.
Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.23082
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Zs.A 1688: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 68: Show issues

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