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BackgroundAdenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. The oncogenic potential of this type of cancer is mainly characterized by its extreme growth rate triggered by the activation of signaling cascades. Modern oncological treatment strategies aim at efficiently modulating specific signaling and transcriptional pathways. Recently, anti-tumoral potential has been proven for several substances that are not primarily used in cancer treatment. In some tumor entities, for example, administration of glutamate antagonists inhibits cell proliferation, cell cycle arrest, and finally cell death.To attain endogenic proof of NMDA receptor type expression in the pancreatic cancer cell lines PaTu8988t and Panc-1 and to investigate the impact of ketamine, s-ketamine, and the NMDA receptor antagonist MK 801 on proliferation, apoptosis, and necrosis in pancreatic carcinoma.MethodsCell proliferation was measured by means of the ELISA BrdU assay, and the apoptosis rate was analyzed by annexin V staining. Immunoblotting were also used.ResultsThe NMDA receptor type R2a was expressed in both pancreatic carcinoma cell lines. Furthermore, ketamine, s-ketamine, and MK 801 significantly inhibited proliferation and apoptosis.ConclusionsIn this study, we showed the expression of the NMDA receptor type R2a in pancreatic cancer cells. The NMDA antagonists ketamine, s-ketamine, and MK 801 inhibited cell proliferation and cell death. Further clinical studies are warranted to identify the impact of these agents on the treatment of cancer patients.

Purpose: Colorectal cancer patients receiving neoadjuvant treatment with bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor (VEGF), may suffer from wound healing complications after surgery as the antibody persists in patient blood. We characterized the systemic angiogenic balance in the perioperative period to evaluate its effect on physiologic angiogenesis. Experimental Design: Nineteen patients receiving combination chemotherapy and bevacizumab for six neoadjuvant cycles were compared with 14 patients receiving chemotherapy without bevacizumab. Plasma from perioperative days −1, +1, +7, and +21 was analyzed for VEGF, thrombospondin-1 (TSP-1), and PD-ECGF concentrations. The angiogenic capacity was further tested in an in vitro assay of endothelial cell proliferation and migration. Results: On day +1, the onset of wound healing was reflected in a change of balance, i.e., an increase of proangiogenic factors VEGF and platelet-derived endothelial cell growth factor compared with low TSP-1 inhibitor levels in both treatment groups. Patients with bevacizumab therapy showed significantly higher blood levels of total VEGF throughout the evaluation period. However, most VEGF molecules were inactive, i.e., complexed with antibody. Nevertheless, the capacity to stimulate endothelial growth was higher for these plasma samples and was reflected in low TSP-1 levels and an altered TSP-1 sensitivity. When purified TSP-1 protein was added, plasma samples of the bevacizumab but not the chemotherapy group showed reduced endothelial growth. Conclusions: Feedback mechanisms of bevacizumab therapy are not restricted to VEGF expression but seem to involve additional factors, such as TSP-1, which influences the systemic angiogenic balance and permits endothelial growth.

The aim of the study was to analyze the effect of personal restrictions on physical activity, mental health, stress experience, resilience, and sleep quality in patients with pulmonary hypertension (PH) during the “lockdown” period of the COVID-19 pandemic. In total, 112 PH patients and 52 age-matched healthy control subjects completed a questionnaire on the topics of physical activity, mental health, resilience, and sleep quality. PH patients had significantly lower physical activity, mental health, and sleep quality compared to age-matched healthy controls. Physical activity positively correlated with mental health and sleep quality in the PH group. Mental wellbeing and life satisfaction could be predicted by total physical activity, sleep, stress level, and resilience. PH patients appeared as an especially vulnerable group, demanding interventions to promote an active lifestyle and protect mental health in these patients. This could be helpful in counseling on how to carry out physical activity while maintaining infection control.