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Pancreatic Neoplasms: HELP
Articles by Oliver H. Krämer
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, O. H. Krämer wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Concepts to Target MYC in Pancreatic Cancer. 2016

Wirth, Matthias / Mahboobi, Siavosh / Krämer, Oliver H / Schneider, Günter. ·II. Medizinische Klinik, Technische Universität München, München, Germany. · Institute of Pharmacy, Department of Pharmaceutical Chemistry I, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany. · Department of Toxicology, University of Mainz Medical Center, Mainz, Germany. · II. Medizinische Klinik, Technische Universität München, München, Germany. guenter.schneider@tum.de. ·Mol Cancer Ther · Pubmed #27406986.

ABSTRACT: Current data suggest that MYC is an important signaling hub and driver in pancreatic ductal adenocarcinoma (PDAC), a tumor entity with a strikingly poor prognosis. No targeted therapies with a meaningful clinical impact were successfully developed against PDAC so far. This points to the need to establish novel concepts targeting the relevant drivers of PDAC, like KRAS or MYC. Here, we discuss recent developments of direct or indirect MYC inhibitors and their potential mode of action in PDAC. Mol Cancer Ther; 15(8); 1792-8. ©2016 AACR.

2 Review Acetylation as a transcriptional control mechanism-HDACs and HATs in pancreatic ductal adenocarcinoma. 2011

Schneider, Günter / Krämer, Oliver H / Schmid, Roland M / Saur, Dieter. ·Klinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, Ismaninger Strasse 22, Munich, Germany. guenter.schneider@lrz.tum.de ·J Gastrointest Cancer · Pubmed #21271301.

ABSTRACT: INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a dismal prognosis. Although our understanding of the carcinogenesis of the disease increases continuously, no effective conservative therapeutic strategies exist. Therefore, novel targets have to be defined at the experimental level. Histone deacetylases (HDACs), especially the class I isoenzymes HDAC1, 2, and 3, are highly expressed in PDAC. CONCLUSION: This article summarizes the expression and functions of HDAC isoenzymes in PDAC, with a special focus on their promoter-specific mode of action. Although we have gained some molecular insight into the HDAC function in PDAC, less is known about the relevance of histone acetyltransferases (HATs) in PDAC. As an example, we will summarize function of the HAT p300, for which promoter-specific functions were described recently. Increasing the molecular insights into the functions of the acetylating and deacetylating machineries in PDAC are important, since this will lead to novel rationally based therapeutic strategies in the future.

3 Article MTOR inhibitor-based combination therapies for pancreatic cancer. 2018

Hassan, Zonera / Schneeweis, Christian / Wirth, Matthias / Veltkamp, Christian / Dantes, Zahra / Feuerecker, Benedikt / Ceyhan, Güralp O / Knauer, Shirley K / Weichert, Wilko / Schmid, Roland M / Stauber, Roland / Arlt, Alexander / Krämer, Oliver H / Rad, Roland / Reichert, Maximilian / Saur, Dieter / Schneider, Günter. ·Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University Munich, 81675 München, Germany. · Institute of Pathology, Heinrich-Heine University and University Hospital Düsseldorf, 40225 Düsseldorf, Germany. · Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, 81675 München, Germany. · German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. · Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 München, Germany. · Molecular Biology, Centre for Medical Biotechnology (ZMB), University Duisburg-Essen, 45141 Essen, Germany. · Institute of Pathology, Technische Universität München, 81675 München, Germany. · Molecular and Cellular Oncology/ENT, University Medical Center Mainz, Langenbeckstrasse 1, Mainz 55131, Germany. · Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany. · Department of Toxicology, University of Mainz Medical Center, Mainz 55131, Germany. · Division of Gastroenterology and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ·Br J Cancer · Pubmed #29384525.

ABSTRACT: BACKGROUND: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. METHODS: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pharmacological intervention studies were used to recapitulate genetic data in human models, including primary human 3D PDAC cultures. RESULTS: Genetic deletion of the Mtor gene in the pancreas results in exocrine and endocrine insufficiency. In established murine PDAC cells, MTOR is linked to metabolic pathways and maintains the glucose uptake and growth. Importantly, blocking MTOR genetically as well as pharmacologically results in adaptive rewiring of oncogenic signalling with activation of canonical extracellular signal-regulated kinase and phosphoinositide 3-kinase-AKT pathways. We provide evidence that interfering with such adaptive signalling in murine and human PDAC models is important in a subgroup. CONCLUSIONS: Our data suggest developing dual MTORC1/TORC2 inhibitor-based therapies for subtype-specific intervention.

4 Article HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer. 2017

Stojanovic, N / Hassan, Z / Wirth, M / Wenzel, P / Beyer, M / Schäfer, C / Brand, P / Kroemer, A / Stauber, R H / Schmid, R M / Arlt, A / Sellmer, A / Mahboobi, S / Rad, R / Reichert, M / Saur, D / Krämer, O H / Schneider, G. ·II. Medizinische Klinik, Technische Universität München, München, Germany. · Department of Toxicology, University of Mainz Medical Center, Mainz, Germany. · Institute of Biochemistry and Biophysics/Center for Molecular Biomedicine (CMB), Friedrich-Schiller-University Jena, Jena, Germany. · Molecular and Cellular Oncology/ENT, University Medical Center Mainz, Mainz, Germany. · Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. · Institute of Pharmacy, Department of Pharmaceutical Chemistry I, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany. · German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. · Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ·Oncogene · Pubmed #27721407.

ABSTRACT: Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.

5 Article Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death. 2013

Conradt, Laura / Henrich, Annika / Wirth, Matthias / Reichert, Maximilian / Lesina, Marina / Algül, Hana / Schmid, Roland M / Krämer, Oliver H / Saur, Dieter / Schneider, Günter. ·II. Medizinische Klinik, Technische Universität München, München, Germany. ·Int J Cancer · Pubmed #23115126.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth leading cause of cancer death in the western world, with a 5-year survival rate below 5%. Murine double minute 2 (Mdm2) is an important negative regulator of the tumor suppressor p53. Reactivation of wild-type p53 is a promising treatment strategy, and inhibitors of Mdm2 have already entered clinical trials. To investigate the effects of Mdm2 inhibitors in PDAC, we used a murine cell line platform with a genetically defined status of p53. Here, we describe that Mdm2 inhibitors can act on a subset of murine PDAC cell lines p53 independently. Furthermore, we observed that Mdm2 inhibitors increase the sensitivity of murine PDAC cell lines toward topoisomerase II inhibitors by inducing effector caspase-independent cell death. The combination of Mdm2 inhibitors with topoisomerase II inhibitors acts independent of the survival factor NFκB/RelA. Mechanistically, Mdm2 inhibitors increase topoisomerase II inhibitor-induced DNA double-strand breaks. We show that Mdm2 binds to Nbs1 of the Mre11-Rad50-Nijmegen breakage syndrome (Nbs) 1 DNA repair complex. In addition, we provide evidence that Mdm2 inhibitors delay DNA repair. These findings may help to design novel therapeutic strategies to overcome therapeutic resistance of PDAC.

6 Article A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer. 2012

Schneider, Günter / Krämer, Oliver H / Saur, Dieter. ·II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, München, Germany. guenter.schneider@lrz.tum.de ·Gut · Pubmed #22147511.

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