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Aktuellste Publikationen

Ann N Y Acad Sci. 2020 Mar 24. doi: 10.1111/nyas.14338. [Epub ahead of print]

Grading animal distress and side effects of therapies.

Kumstel S1, Wendt EHU1, Eichberg J1, Talbot SR2, Häger C2, Zhang X1, Abdelrahman A1, Schönrogge M1, Palme R3, Bleich A2, Vollmar B1, Zechner D1.

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

2 Institute for Laboratory Animal Science, Hannover Medical School, Hanover, Germany.

3 Unit of Physiology, Pathophysiology and Experimental Endocrinology, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.

Abstract

In order to combine high-quality research with minimal harm to animals, a prospective severity assessment for animal experiments is legally required in many countries. In addition, an assessment of the evidence-based severity level might allow realistic harm-benefit analysis and the appraisal of refinement methods. However, only a few examples describe the distress of animals by simple, cost-efficient, and noninvasive methods. We, therefore, evaluated the severity of an orthotopic mouse model for pancreatic cancer using C57BL/6J mice when pursuing two different chemotherapies. We assessed fecal corticosterone metabolites, body weight, distress score, and burrowing, as well as nesting activity. Moreover, we established a multifactorial model using multivariate logistic regression to describe animal distress. This multifactorial analysis revealed that metformin + galloflavin treatment caused higher distress than metformin + α-cyano-4-hydroxycinnamate therapy. Similar results were obtained by using the best cutoff calculated by Youden's J index when using only single parameters, such as burrowing activity or fecal corticosterone metabolite concentration. Thus, the present study revealed that single readout parameters, as well as multivariate analysis, can help to assess the severity of animal experiments and detect side effects of therapies.

 

J Cancer. 2020 Jan 1;11(2):479-487. doi: 10.7150/jca.33029. eCollection 2020.

Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1.

Zhang X1,2, Liu P3, Shang Y2,4, Kerndl H1, Kumstel S1, Gong P3, Vollmar B1, Zechner D1.

1 Institute for Experimental Surgery, Rostock University Medical Center, Schillingallee 69a, 18059, Rostock, Germany.

2 Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, 250117, Jinan, China.

3 Department of General Surgery, Shenzhen University General Hospital, Xueyuan Road 1098, 518055, Shenzhen, China.

4 Molecular Oncology and Immunotherapy, Department of General Surgery, Rostock University Medical Center, Schillingallee 69, 18059, Rostock, Germany.

Abstract

The poor survival rate of pancreatic cancer is still a major challenge for the clinicians and their patients. In this study, we evaluated the efficacy of metformin, an inhibitor of oxidative phosphorylation, in combination with LW6, which impairs malate dehydrogenase 2 activities, in treating pancreatic cancer cells. We observed that this combinational therapy significantly reduced cell proliferation, migration, and significantly induced cell death when compared to cells treated by each monotherapy or Sham. In addition, we found that the combination of metformin and LW6 increased the phosphorylation of yes-associated protein 1 at serine 127 and attenuated the nuclear localization of this transcription factor. This combinatorial treatment also decreased the level of cellular yes-associated protein 1. This suggests that metformin in combination with LW6 impairs pancreatic cancer cells and reduces nuclear localization of yes-associated protein 1.