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Book ; Thesis: Retrospektive Analyse der klinischen Wertigkeit der PET-CT bei paraneoplastischen neurologischen Syndromen

Lambert, Jörg

2009

Author's details	vorgelegt von Jörg Lambert
Language	German
Size	III, 43 Bl., Ill.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Hamburg, Univ., FB Medizin, Diss., 2009
Note	Zsfassung in dt. Sprache
HBZ-ID	HT016299620
Database	Catalogue ZB MED Medicine, Health

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Article: Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis

Marchan, Rosemarie / Lambert, Joerg / Hengstler, Jan G.

Proceedings of the National Academy of Sciences of the United States of America, 109(21): 8155–8160

2012

Abstract: Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity ... ...

Institution	Leibniz-Institut für Analytische Wissenschaften Technische Universität Dortmund. Leibniz-Institut für Arbeitsforschung
Abstract	Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan–Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial (P < 0.001) and ovarian (P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.
Keywords	glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae) ; glycerophosphodiester phosphodiesterase domain containing 6 ; glycerophosphodiesterase 5 ; lysophosphatidic acid ; phosphatidic acid
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article: Automated metabolic assignment: Semi-supervised learning in metabolic analysis employing two dimensional Nuclear Magnetic Resonance (NMR).

Migdadi, Lubaba / Lambert, Jörg / Telfah, Ahmad / Hergenröder, Roland / Wöhler, Christian

Computational and structural biotechnology journal

2021 Volume 19, Page(s) 5047–5058

Abstract: Metabolomics is an expanding field of medical diagnostics since many diseases cause metabolic reprogramming alteration. Additionally, the metabolic point of view offers an insight into the molecular mechanisms of diseases. Due to the complexity of ... ...

Abstract	Metabolomics is an expanding field of medical diagnostics since many diseases cause metabolic reprogramming alteration. Additionally, the metabolic point of view offers an insight into the molecular mechanisms of diseases. Due to the complexity of metabolic assignment dependent on the 1D NMR spectral analysis, 2D NMR techniques are preferred because of spectral resolution issues. Thus, in this work, we introduce an automated metabolite identification and assignment from
Language	English
Publishing date	2021-08-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2021.08.048
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Automated metabolic assignment: Semi-supervised learning in metabolic analysis employing two dimensional Nuclear Magnetic Resonance (NMR)

Migdadi, Lubaba / Lambert, Jörg / Telfah, Ahmad / Hergenröder, Roland / Wöhler, Christian

Computational and Structural Biotechnology Journal. 2021, v. 19

2021

Abstract	Metabolomics is an expanding field of medical diagnostics since many diseases cause metabolic reprogramming alteration. Additionally, the metabolic point of view offers an insight into the molecular mechanisms of diseases. Due to the complexity of metabolic assignment dependent on the 1D NMR spectral analysis, 2D NMR techniques are preferred because of spectral resolution issues. Thus, in this work, we introduce an automated metabolite identification and assignment from ¹H-¹H TOCSY (total correlation spectroscopy) using real breast cancer tissue. The new approach is based on customized and extended semi-supervised classifiers: KNFST, SVM, third (PC3) and fourth (PC4) degree polynomial. In our approach, metabolic assignment is based only on the vertical and horizontal frequencies of the metabolites in the ¹H–¹H TOCSY. KNFST and SVM show high performance (high accuracy and low mislabeling rate) in relatively low size of initially labeled training data. PC3 and PC4 classifiers showed lower accuracy and high mislabeling rates, and both classifiers fail to provide an acceptable accuracy at extremely low size (≤9% of the entire dataset) of initial training data. Additionally, semi-supervised classifiers were implemented to obtain a fully automatic procedure for signal assignment and deconvolution of TOCSY, which is a big step forward in NMR metabolic profiling. A set of 27 metabolites were deduced from the TOCSY, and their assignments agreed with the metabolites deduced from a 1D NMR spectrum of the same sample analyzed by conventional human-based methodology.
Keywords	automation ; biotechnology ; breast neoplasms ; data collection ; diagnostic techniques ; metabolites ; metabolomics ; nuclear magnetic resonance spectroscopy ; spectral analysis
Language	English
Size	p. 5047-5058.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2021.08.048
Database	NAL-Catalogue (AGRICOLA)

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Article: In Vitro Spatio-Temporal NMR Metabolomics of Living 3D Cell Models

Knitsch, Robert / AlWahsh, Mohammad / Raschke, Hannes / Lambert, Jörg / Hergenröder, Roland

Analytical chemistry. 2021 Sept. 03, v. 93, no. 40

2021

Abstract: Three-dimensional cell cultures are of growing importance in biochemical research as they represent tissue features more accurately than standard two-dimensional systems, but to investigate these challenging new models an adaptation of established ... ...

Abstract	Three-dimensional cell cultures are of growing importance in biochemical research as they represent tissue features more accurately than standard two-dimensional systems, but to investigate these challenging new models an adaptation of established analytical techniques is required. Spatially resolved data for living organoids are needed to gain insight into transport processes and biochemical characteristics of domains with different nutrient supply and waste product removal. Within this work, we present an NMR-based approach to obtain dynamically radial metabolite profiles for cell spheroids, one of the most frequently used 3D models. Our approach combines an easy to reproduce custom-made measurement design, maintaining physiological conditions without inhibition of the NMR experiment, with spatially selective NMR pulse sequences. To overcome the inherently low sensitivity of NMR spectroscopy we excited slices instead of smaller cube-like voxels in combination with an efficient interleaved measurement approach and employed a commercially available cryogenic NMR probe. Finally, radial metabolite profiles could be obtained via double Abel inversion of the measured one-dimensional intensity profiles. Applying this method to Ty82 cancer cell spheroids demonstrates the achieved spatial resolution, for instance confirming exceedingly high lactic acid and strongly decreased glucose concentrations in the oxygen-depleted core of the spheroid. Furthermore, our approach can be employed to investigate fast and slow metabolic changes in single spheroids simultaneously, which is shown as an example of a spheroid degrading over several days after stopping the nutrient supply.
Keywords	analytical chemistry ; glucose ; lactic acid ; metabolites ; metabolomics ; neoplasm cells ; nuclear magnetic resonance spectroscopy ; organoids
Language	English
Dates of publication	2021-0903
Size	p. 13485-13494.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.1c02221
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: In Vitro Spatio-Temporal NMR Metabolomics of Living 3D Cell Models.

Knitsch, Robert / AlWahsh, Mohammad / Raschke, Hannes / Lambert, Jörg / Hergenröder, Roland

Analytical chemistry

2021 Volume 93, Issue 40, Page(s) 13485–13494

Abstract	Three-dimensional cell cultures are of growing importance in biochemical research as they represent tissue features more accurately than standard two-dimensional systems, but to investigate these challenging new models an adaptation of established analytical techniques is required. Spatially resolved data for living organoids are needed to gain insight into transport processes and biochemical characteristics of domains with different nutrient supply and waste product removal. Within this work, we present an NMR-based approach to obtain dynamically radial metabolite profiles for cell spheroids, one of the most frequently used 3D models. Our approach combines an easy to reproduce custom-made measurement design, maintaining physiological conditions without inhibition of the NMR experiment, with spatially selective NMR pulse sequences. To overcome the inherently low sensitivity of NMR spectroscopy we excited slices instead of smaller cube-like voxels in combination with an efficient interleaved measurement approach and employed a commercially available cryogenic NMR probe. Finally, radial metabolite profiles could be obtained via double Abel inversion of the measured one-dimensional intensity profiles. Applying this method to Ty82 cancer cell spheroids demonstrates the achieved spatial resolution, for instance confirming exceedingly high lactic acid and strongly decreased glucose concentrations in the oxygen-depleted core of the spheroid. Furthermore, our approach can be employed to investigate fast and slow metabolic changes in single spheroids simultaneously, which is shown as an example of a spheroid degrading over several days after stopping the nutrient supply.
MeSH term(s)	Cell Culture Techniques ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Metabolomics ; Spheroids, Cellular
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.1c02221
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Article ; Online: A flow microslot NMR probe coupled with a capillary isotachophoresis system exhibits improved properties compared to solenoid designs.

Gogiashvili, Mikheil / Telfah, Ahmad / Lambert, Jörg / Hergenröder, Roland

Analytical and bioanalytical chemistry

2017 Volume 409, Issue 9, Page(s) 2471–2475

Abstract: We report on the hyphenation of capillary isotachophoresis (cITP) separations with online nuclear magnetic resonance (NMR) detection using a planar microslot waveguide probe design. While cITP is commonly coupled with a solenoidal microcoil NMR probe, ... ...

Abstract	We report on the hyphenation of capillary isotachophoresis (cITP) separations with online nuclear magnetic resonance (NMR) detection using a planar microslot waveguide probe design. While cITP is commonly coupled with a solenoidal microcoil NMR probe, the structural information provided is limited by broad resonances and poor spectral resolution due to the magnetic field created by the separation current. The microslot probe design described herein allows the separation capillary to be oriented parallel to the static magnetic field, B
Language	English
Publishing date	2017-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-017-0196-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: HR-MAS NMR Based Quantitative Metabolomics in Breast Cancer.

Gogiashvili, Mikheil / Nowacki, Jessica / Hergenröder, Roland / Hengstler, Jan G / Lambert, Jörg / Edlund, Karolina

Metabolites

2019 Volume 9, Issue 2

Abstract: High resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy is increasingly used for profiling of breast cancer tissue, delivering quantitative information for approximately 40 metabolites. One unique advantage of the ... ...

Abstract	High resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy is increasingly used for profiling of breast cancer tissue, delivering quantitative information for approximately 40 metabolites. One unique advantage of the method is that it can be used to analyse intact tissue, thereby requiring only minimal sample preparation. Importantly, since the method is non-destructive, it allows further investigations of the same specimen using for instance transcriptomics. Here, we discuss technical aspects critical for a successful analysis - including sample handling, measurement conditions, pulse sequences for one- and two dimensional analysis, and quantification methods - and summarize available studies, with a focus on significant associations of metabolite levels with clinically relevant parameters.
Language	English
Publishing date	2019-01-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo9020019
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Article ; Online: Looking into Living Cell Systems: Planar Waveguide Microfluidic NMR Detector for in Vitro Metabolomics of Tumor Spheroids.

Kalfe, Ayten / Telfah, Ahmad / Lambert, Jörg / Hergenröder, Roland

Analytical chemistry

2015 Volume 87, Issue 14, Page(s) 7402–7410

Abstract: The complex cell metabolism and its link to oncogenic signaling pathways have received huge interest within the last few years. But the lack of advanced analytical tools for the investigation of living cell metabolism is still a challenge to be faced. ... ...

Abstract	The complex cell metabolism and its link to oncogenic signaling pathways have received huge interest within the last few years. But the lack of advanced analytical tools for the investigation of living cell metabolism is still a challenge to be faced. Therefore, we designed and fabricated a novel miniaturized microslot NMR detector with on-board heater integrated with a microfluidic device as NMR sample holder. For the first time, a tumor spheroid of 500 μm diameter and consisting of 9000 cells has been studied noninvasively and online for 24 h. The dynamic processes of production and degradation of 23 intra- and extracellular metabolites were monitored. Remarkably high concentrations of lactate and alanine were observed, being an indicator for a shift from oxidative to glycolytic metabolism. In summary, this methodical development has proven to be a successful analytical tool for the elucidation of cellular functions and their corresponding biochemical pathways. Additionally, the planar geometry of the microslot NMR detector allows the hyphenation with versatile lab-on-a chip (LOC) technology. This opens a new window for metabolomics studies on living cells and can be implemented into new application fields in biotechnology and life sciences.
MeSH term(s)	HT29 Cells ; Humans ; Metabolomics ; Microfluidic Analytical Techniques/instrumentation ; Neoplasms/pathology ; Nuclear Magnetic Resonance, Biomolecular/instrumentation ; Particle Size ; Spheroids, Cellular/pathology ; Tumor Cells, Cultured
Language	English
Publishing date	2015-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.5b01603
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Optimized multiple-quantum filter for robust selective excitation of metabolite signals.

Holbach, Mirjam / Lambert, Jörg / Suter, Dieter

Journal of magnetic resonance (San Diego, Calif. : 1997)

2014 Volume 243, Page(s) 8–16

Abstract: The selective excitation of metabolite signals in vivo requires the use of specially adapted pulse techniques, in particular when the signals are weak and the resonances overlap with those of unwanted molecules. Several pulse sequences have been proposed ...

Abstract	The selective excitation of metabolite signals in vivo requires the use of specially adapted pulse techniques, in particular when the signals are weak and the resonances overlap with those of unwanted molecules. Several pulse sequences have been proposed for this spectral editing task. However, their performance is strongly degraded by unavoidable experimental imperfections. Here, we show that optimal control theory can be used to generate pulses and sequences that perform almost ideally over a range of rf field strengths and frequency offsets that can be chosen according to the specifics of the spectrometer or scanner being used. We demonstrate this scheme by applying it to lactate editing. In addition to the robust excitation, we also have designed the pulses to minimize the signal of unwanted molecular species.
MeSH term(s)	Alanine/analysis ; Algorithms ; Lactic Acid/analysis ; Lipids/analysis ; Magnetic Resonance Spectroscopy/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Signal Processing, Computer-Assisted
Chemical Substances	Lipids ; Lactic Acid (33X04XA5AT) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2014-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1469665-4
ISSN	1096-0856 ; 1557-8968 ; 1090-7807 ; 0022-2364
ISSN (online)	1096-0856 ; 1557-8968
ISSN	1090-7807 ; 0022-2364
DOI	10.1016/j.jmr.2014.03.007
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