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Aktuellste Publikationen

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.


ALTEX. 2019 Dec 9. doi: 10.14573/altex.1909111. [Epub ahead of print]

A rational approach of early humane endpoint determination in a murine model for cholestasis.

Zhang X1, Kumstel S1, Tang G1, Talbot SR2, Seume N1, Abshagen K1, Vollmar B1, Zechner D1.

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

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

Abstract

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of score sheets and do not attempt to reduce the suffering of animals by determining earlier and therefore more humane endpoints. The present study uses data assessed from BALB/cANCrl mice after bile duct ligation to retrospectively analyze which score sheet criteria are informative to determine humane endpoints. The performance of each single as well as combinations of multiple animal welfare parameters was analyzed by a Cox proportional-hazards model followed by Harrell's concordance index. The addition of behavioral parameters, such as burrowing activity, helped to define a more humane early endpoint for euthanizing these animals. Using this approach, we determined that a body weight loss of 10-20 % combined with a reduction of burrowing activity by more than 79.4 % was able to predict that these animals died within two days. Thus, this approach successfully determined an earlier humane endpoint and will therefore reduce the suffering of animals in future experiments. A consequent application of such an approach or similar methods will contribute to the refinement of various animal experiments.