Palus, Sandra

[["dc.bibliographiccitation.firstpage","3"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Cachexia, Sarcopenia and Muscle"],["dc.bibliographiccitation.lastpage","10"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Suzuki, Tsuyoshi"],["dc.contributor.author","Ebner, Nicole"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","Haehling, Stephan von"],["dc.contributor.author","Springer, Jochen"],["dc.date.accessioned","2019-07-08T12:29:23Z"],["dc.date.accessioned","2021-10-27T13:21:17Z"],["dc.date.available","2019-07-08T12:29:23Z"],["dc.date.available","2021-10-27T13:21:17Z"],["dc.date.issued","2019"],["dc.description.abstract","Background: Medroxyprogesterone (MPA) and megestrol acetate (MA) are synthetic progesterone derivates. Progestagen is an approved drug for cancer cachexia in the USA and some Europe. These agents have been described to increase appetite and to lead to weight gain. However, the effects on survival are still unknown. The aim of this study was to evaluate the effects of progesterone on survival, cardiac function as well as appetite and body weight in the Yoshida hepatoma AH‐130 rat cancer cachexia model. Methods: In this study the effects of progesterone were tested in cachectic tumor bearing rats. Rats were treated with 0.5, 5 or 50mg/kg/d, respectively or placebo daily, starting one day after tumor inoculation for a period of 16 days. Cardiac function was analyzed by echocardiography at baseline and at day 11. Food intake was assessed before tumor inoculation and at day 11. Body weight and body composition were evaluated at the beginning and the end of study or day of euthanasia. Results: Survival was significantly improved by 5 mg/kg/d (HR: 0.48, 95%CI: 0.24‐0.95, p=0.0356). However, there was no significant difference between the progesterone treatment groups compared to placebo in body weight change and body composition, as well as food intake on day 11. Cardiac function also showed no significant difference compared to placebo. Conclusion: Progesterone improves survival, but has no beneficial effects on cardiac function, body weight and food intake in this aggressive hepatoma cancer cachexia rat model. Further studies are needed to elucidate the mechanism of the survival benefit."],["dc.description.sponsorship","Open Access-Publikationsfonds 2019"],["dc.identifier.doi","10.1002/rco2.11"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92008"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Progesterone improves survival in hepatoma cachexia rat model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","193"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Cachexia Sarcopenia and Muscle"],["dc.bibliographiccitation.lastpage","198"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","von Haehling, Stephan"],["dc.contributor.author","Springer, Jochen"],["dc.date.accessioned","2018-11-07T09:35:56Z"],["dc.date.available","2018-11-07T09:35:56Z"],["dc.date.issued","2014"],["dc.description.abstract","The syndrome of cachexia, i.e., involuntary weight loss in patients with underlying diseases, sarcopenia, i.e., loss of muscle mass due to aging, and general muscle atrophy from disuse and/or prolonged bed rest have received more attention over the last decades. All lead to a higher morbidity and mortality in patients, and therefore, they represent a major socio-economic burden for the society today. This mini-review looks at recent developments in basic research that are relevant to the loss of skeletal muscle. It aims to cover the most significant publication of last 3 years on the causes and effects of muscle wasting, new targets for therapy development, and potential biomarkers for assessing skeletal muscle mass. The targets include the following: (1) E-3 ligases TRIM32, SOCS1, and SOCS3 by involving the elongin BC ubiquitin-ligase, Cbl-b, culling 7, Fbxo40, MG53 (TRIM72), and the mitochondrial Mul1; (2) the kinase MST1; and (3) the G-protein G alpha i(2). D(3)-creatine has the potential to be used as a novel biomarker that allows to monitor actual change in skeletal muscle mass over time. In conclusion, significant development efforts are being made by academic groups as well as numerous pharmaceutical companies to identify new target and biomarker muscles, as muscle wasting represents a great medical need, but no therapies have been approved in the last decades."],["dc.identifier.doi","10.1007/s13539-014-0157-7"],["dc.identifier.isi","000342061700005"],["dc.identifier.pmid","25163459"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12135"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32500"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","2190-6009"],["dc.relation.issn","2190-5991"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Muscle wasting: an overview of recent developments in basic research"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","594"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Cachexia, Sarcopenia and Muscle"],["dc.bibliographiccitation.lastpage","605"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Pötsch, Mareike S."],["dc.contributor.author","Ishida, Junichi"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","Tschirner, Anika"],["dc.contributor.author","Haehling, Stephan"],["dc.contributor.author","Doehner, Wolfram"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Springer, Jochen"],["dc.date.accessioned","2021-06-01T10:50:56Z"],["dc.date.available","2021-06-01T10:50:56Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1002/jcsm.12537"],["dc.identifier.eissn","2190-6009"],["dc.identifier.issn","2190-5991"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17186"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86832"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2190-6009"],["dc.relation.issn","2190-5991"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","MT‐102 prevents tissue wasting and improves survival in a rat model of severe cancer cachexia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","45"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of cachexia, sarcopenia and muscle"],["dc.bibliographiccitation.lastpage","52"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Cvan Trobec, Katja"],["dc.contributor.author","Kerec Kos, Mojca"],["dc.contributor.author","Trontelj, Jurij"],["dc.contributor.author","Grabnar, Iztok"],["dc.contributor.author","Tschirner, Anika"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Springer, Jochen"],["dc.contributor.author","Lainscak, Mitja"],["dc.date.accessioned","2019-07-09T11:42:33Z"],["dc.date.available","2019-07-09T11:42:33Z"],["dc.date.issued","2015-03-01"],["dc.description.abstract","BACKGROUND: Body wasting and cachexia change body composition and organ function, with effects on drug pharmacokinetics. The aim of this study was to investigate how cancer and cancer cachexia modify liver metabolism and renal drug elimination in rats. METHODS: Nine male Wistar-Han rats received a single oral dose of midazolam and propranolol (markers of hepatic metabolism), and 10 rats received single intravenous dose of iohexol, a marker of glomerular filtration rate. After drug delivery, multiple dried blood samples were obtained within 2 h post-dose to evaluate drug pharmacokinetic profiles. After baseline sampling (D0), rats were injected with tumour cells. Drug application and blood sampling were repeated when rats developed tumours (Day 5-D5), and when rats were severely cachectic (Day 10-D10). Clearance (CL) and volume of distribution (Vd) of drugs were assessed with non-linear mixed effects modelling. Weight and body composition were measured on D0 and D10 and were related to pharmacokinetic parameters. RESULTS: All three drugs showed non-significant trend towards increased CL and Vd on D5. On D10, midazolam and propranolol CL and midazolam Vd significantly decreased from baseline (-80.5%, -79.8%, and -72.0%, respectively, P < 0.05 for all). Iohexol CL decreased by 29.8% from baseline value on D10, which was related to body weight loss (Pearson's r = 0.837, P = 0.019). CONCLUSIONS: Hepatic metabolism and renal drug elimination are significantly reduced in cachexia, which could increase risk of dose-related adverse events."],["dc.identifier.doi","10.1002/jcsm.12012"],["dc.identifier.pmid","26136411"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13568"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58694"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2190-5991"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Influence of cancer cachexia on drug liver metabolism and renal elimination in rats."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","154"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","159"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Tschirner, Anika"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","Hetzer, Roland"],["dc.contributor.author","Meyer, Rudolf"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Springer, Jochen"],["dc.date.accessioned","2019-07-09T11:41:13Z"],["dc.date.available","2019-07-09T11:41:13Z"],["dc.date.issued","2015"],["dc.description.abstract","ackground Recently, it was shown that a knock-out (KO) of the polycomb histone methyltransferase Ezh2 leads to cardiac hypertrophy in mice, which was driven by the homeodom ain transcription factor Six1. Here, we analyzed the expression of Six1 and its regulating factor Ezh2 in cardiac tissue of pa- tients with end-stage dilative cardiomyopathy (DCM). Methods Tissue samples of patients with end-stage DCM (n = 35) were com- pared with control s (n = 12) for the protein expression of Ezh1, Ezh2, Six1, and a marker of protein expression p70S6K. Results Contrary to the Ezh2-KO mouse model, we found a down-regulation of Six1 (26%) and an up-regulation of Ezh2 (76%) in DCM hearts, (both P < 0.05). Expression of Ezh2 and Six1 did not correlate in human tissue (DCM: r 2 : 0.03, P = 0.31 and donor: r 2 : 0.05, P = 0.45). Expression of Six1 weakly correlated with left ventricula r end-systolic diameter and fractional shortening. In DCM, Six1 also showed a positive correlation to the expression of the ribosomal protein p70S6K (r: 0.39, P = 0.02 9), which is involved in pro- tein synthesis. This correlation was not seen in donor tissue, whic h showed a trend for a negative correlation (r: 0.49, P = 0.08 ). Conclusion Our data indicate that the Ezh2/Six1 axis might be involved in human DCM. However, Six1 expression may be regulated by factors other t han Ezh2, and more research is needed to determine the precise role of Ezh2/Six1 in human DCM."],["dc.identifier.doi","10.1002/ehf2.12017"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11849"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58375"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Six1 is down-regulated in end-stage human dilated cardiomyopathy independently of Ezh2"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","174"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Cachexia Sarcopenia and Muscle"],["dc.bibliographiccitation.lastpage","180"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Konishi, Masaaki"],["dc.contributor.author","Pelgrim, Loes"],["dc.contributor.author","Tschirner, Anika"],["dc.contributor.author","Baumgarten, Anna"],["dc.contributor.author","von Haehling, Stephan"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","Doehner, Wolfram"],["dc.contributor.author","Anker, Stefan-D."],["dc.contributor.author","Springer, Jochen"],["dc.date.accessioned","2018-11-07T09:56:41Z"],["dc.date.available","2018-11-07T09:56:41Z"],["dc.date.issued","2015"],["dc.description.abstract","Background Activity of xanthine oxidase is induced in cancer cachexia, and its inhibition by allopurinol or oxypurinol improves survival and reduces wasting in the Yoshida hepatoma cancer cachexia model. Here, we tested the effects of the second-generation xanthine oxidase inhibitor febuxostat compared with placebo in the same model as used previously by our group. Methods Wistar rats (similar to 200g) were treated daily with febuxostat at 5mg/kg/day or placebo via gavage for a maximum of 17days. Weight change, quality of life, and body composition were analysed. After sacrifice, proteasome activity in the gastrocnemius muscle was measured. Muscle-specific proteins involved in metabolism were analysed by western blotting. Results Treatment of the tumour-bearing rats with febuxostat led to a significantly improved survival compared with placebo (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93, P=0.03). Loss of body weight was reduced (-26.312.4g) compared with placebo (-50.2 +/- 2.1g, P<0.01). Wasting of lean mass was attenuated (-12.7 +/- 10.8g) vs. placebo (-31.9 +/- 2.1g, P<0.05). While we did not see an effect of febuxostat on proteasome activity at the end of the study, the pAkt/Akt ratio was improved by febuxostat (0.94 +/- 0.09) vs. placebo (0.41 +/- 0.05, P<0.01), suggesting an increase in protein synthesis. Conclusions Febuxostat attenuated cachexia progression and improved survival of tumour-bearing rats."],["dc.description.sponsorship","Sumitomo Life Welfare and Culture Foundation"],["dc.identifier.doi","10.1002/jcsm.12017"],["dc.identifier.isi","000355340500007"],["dc.identifier.pmid","26136193"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13567"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37010"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","2190-6009"],["dc.relation.issn","2190-5991"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Febuxostat improves outcome in a rat model of cancer cachexia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","555"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Cachexia, Sarcopenia and Muscle"],["dc.bibliographiccitation.lastpage","566"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Musolino, Vincenzo"],["dc.contributor.author","Palus, Sandra"],["dc.contributor.author","Tschirner, Anika"],["dc.contributor.author","Drescher, Cathleen"],["dc.contributor.author","Gliozzi, Micaela"],["dc.contributor.author","Carresi, Cristina"],["dc.contributor.author","Vitale, Cristiana"],["dc.contributor.author","Muscoli, Carolina"],["dc.contributor.author","Doehner, Wolfram"],["dc.contributor.author","von Haehling, Stephan"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Mollace, Vincenzo"],["dc.contributor.author","Springer, Jochen"],["dc.date.accessioned","2019-07-09T11:42:54Z"],["dc.date.available","2019-07-09T11:42:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Background Cachexia is a complex metabolic syndrome associated with cancer. One of the features of cachexia is the loss of muscle mass, characterized by an imbalance between protein synthesis and protein degradation. Muscle atrophy is caused by the hyperactivation of some of the main cellular catabolic pathways, including autophagy. Cachexia also affects the cardiac muscle. As a consequence of the atrophy of the heart, cardiac function is impaired and mortality is increased. Anticachectic therapy in patients with cancer cachexia is so far limited to nutritional support and anabolic steroids. The use of the appetite stimulant megestrol acetate (MA) has been discussed as a treatment for cachexia. Methods In this study the effects of MA were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Rats were treated daily with 100 mg/kg of MA or placebo starting one day after tumour inoculation, and for a period of 16 days. Body weight and body composition were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and at day 11. Locomotor activity and food intake were assessed before tumour inoculation and at day 11. Autophagic markers were assessed in gastrocnemius muscle and heart by western blot analysis. Results Treatment with 100 mg/kg/day MA significantly attenuated the loss of body weight ( 9 ± 12%, P<0.05) and the wasting of lean and fat mass ( 7.0 ± 6% and 22.4 ± 3 %, P<0.001 and P<0.05, respectively). Administration of 100 mg/kg/day MA significantly protected the heart from general atrophy (633.8 ± 30mg vs. placebo 474 ± 13 mg, P<0.001). Tumour-bearing rats displayed cardiac dysfunction, as indicated by the significant impairment of the left ventricular ejection fraction, the left ventricular fractional shortening, the stroke volume, the end dyastolic volume, and the end systolic volume. In contrast, MA significantly improved left ventricular ejection fraction, left ventricular fractional shortening, and left ventricular end systolic volume. Western blotting analysis showed an upregulation of the autophagic pathway in the gastrocnemius and hearts of the placebo-treated tumour-bearing rats. Treatment with MA, however, was able to modulate the autophagic markers (e.g. Beclin-1, p62, TRAF6, and LC3) in the gastrocnemius and in the hearts of tumourbearing rats. Most importantly, 100 mg/kg/day MA reduced mortality [hazard ratio (HR): 0.44; 95%CI: 0.20–1.00; P = 0.0486]. Conclusions Megestrol acetate improved survival and reduced wasting through a marked downregulation of autophagy, occurring in both skeletal and heart muscle, the latter effect leading to a significant improvement of cardiac function. Our data suggest thatMA might represent a valuable strategy to counteract the development of cancer cachexia-induced cardiomyopathy."],["dc.identifier.doi","10.1002/jcsm.12116"],["dc.identifier.pmid","27239419"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13987"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58781"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2190-6009"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Megestrol acetate improves cardiac function in a model of cancer cachexia-induced cardiomyopathy by autophagic modulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]