Aktuellste Publikationen

PLoS One 2022 Apr 22;17(4):e0266601.doi: 10.1371/journal.pone.0266601. eCollection 2022.

Targeting pancreatic cancer with combinatorial treatment of CPI-613 and inhibitors of lactate metabolism

Simone Kumstel  1 Tim Schreiber  1 Lea Goldstein  1 Jan Stenzel  2 Tobias Lindner  2 Markus Joksch  2 Xianbin Zhang  1 Edgar Heinz Uwe Wendt  1 Maria Schönrogge  1 Bernd Krause  3 Brigitte Vollmar  1 Dietmar Zechner  1

1 Rudolf-Zenker-Institute of Experimental Surgery, University Medical Center, Rostock, Germany.

2 Core Facility Multimodal Small Animal Imaging, University Medical Center, Rostock, Germany.

3 Department of Nuclear Medicine, University Medical Center, Rostock, Germany.

Abstract

Pancreatic cancer is the fourth leading cause of cancer death, with a 5-year survival rate of 10%. A stagnant high mortality rate over the last decades highlights the need for innovative therapeutic approaches. Pancreatic tumors pursue an altered metabolism in order to maintain energy generation under low nutrient influx and hypoxic conditions. Targeting these metabolic strategies might therefore be a reasonable therapeutic approach for pancreatic cancer. One promising agent is CPI- 613, a potent inhibitor of two enzymes of the tricarboxylic acid cycle. The present study evaluated the anti-cancerous efficacy of CPI-613 in combination with galloflavin, a lactate dehydrogenase inhibitor or with alpha-cyano-4-hydroxycinnamic acid, an inhibitor of monocarboxylate transporters. The efficacy of both combination therapies was tested in vitro on one human and two murine pancreatic cancer cell lines and in vivo in an orthotopic pancreatic cancer model. Tumor progression was evaluated by MRI and 18F-FDG PET-CT. Both combinatorial treatments demonstrated in vitro a significant inhibition of pancreatic cancer cell proliferation and induction of cell death. In contrast to the in vitro results, both combination therapies did not significantly reduce tumor growth in vivo. The in vitro results suggest that a combined inhibition of different metabolic pathways might be a promising approach for cancer therapy. However, the in vivo experiments indicate that applying a higher dosage or using other drugs targeting these metabolic pathways might be more promising.

 

 

Nutrients 2021 Aug 24;13(9):2916.doi: 10.3390/nu13092916.

Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice

Nicole Power Guerra  1   2 Alisha Parveen  1 Daniel Bühler  1 David Leon Brauer  3 Luisa Müller  1   4   5 Kristin Pilz  6 Martin Witt  2 Änne Glass  7 Rika Bajorat  8 Deborah Janowitz  6 Olaf Wolkenhauer  3   9 Brigitte Vollmar  1   5 Angela Kuhla  1   5

1 Rudolf-Zenker-Institute for Experimental Surgery, Rostock University Medical Centre, Schillingallee 69a, 18057 Rostock, Germany.

2 Department of Anatomy, Rostock University Medical Centre, Gertrudenstraße 9, 18057 Rostock, Germany.

3 Department of Systems Biology and Bioinformatics, University of Rostock, Ulmenstraße 69, 18057 Rostock, Germany.

4 Department of Psychosomatic Medicine and Psychotherapy, Rostock University Medical Centre, Gehlsheimerstraße 20, 18147 Rostock, Germany.

5 Centre for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Centre, Gehlsheimerstraße 20, 18147 Rostock, Germany.

6 Department of Psychiatry, University of Greifswald, Ellernholzstraße 1-2, 17489 Greifswald, Germany.

7 Institute for Biostatistics and Informatics, Rostock University Medical Centre, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.

8 Department of Anesthesiology and Intensive Care Medicine, Rostock University Medical Centre, Schillingallee 35, 18057 Rostock, Germany.

9 Leibniz-Institute for Food Systems Biology, Technical University of Munich, Lise-Meitner-Straße 34, 85354 Freising, Germany.

Abstract

Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.

 

 

Cancers (Basel) 2021 May 19;13(10):2483.doi: 10.3390/cancers13102483.

Multimodal Imaging Techniques to Evaluate the Anticancer Effect of Cold Atmospheric Pressure Plasma

Marcel Kordt  1 Isabell Trautmann  1 Christin Schlie  1 Tobias Lindner  2 Jan Stenzel  2 Anna Schildt  2 ,                 Lars Boeckmann  3 Sander Bekeschus  4 Jens Kurth  5 Bernd J Krause  2   5 Brigitte Vollmar  1 Eberhard Grambow  1   6

1 Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, 18057 Rostock, Germany.

2 Core Facility Multimodal Small Animal Imaging, Rostock University Medical Center, 18057 Rostock, Germany.

3 Clinic and Policlinic for Dermatology and Venereology, Rostock University Medical Center, 18057 Rostock, Germany.

4 Center for innovation competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489 Greifswald, Germany.

5 Department of Nuclear Medicine, Rostock University Medical Center, 18055 Rostock, Germany.

6 Department for General, Visceral-, Vascular- and Transplantation Surgery, Rostock University Medical Center, 18057 Rostock, Germany.

Abstract

Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM).

Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multimodal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three-weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non-invasive chemiluminescence imaging of L-012. Histological analysis and immunohistochemical staining for Ki-67, ApopTag®, F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase-3 and cleaved-caspase-3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP-treated tumours.

Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tumours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP.

Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer.