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Pancreatic Neoplasms: HELP
Articles by Oliver Schilling
Based on 5 articles published since 2010
(Why 5 articles?)
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Between 2010 and 2020, Oliver Schilling wrote the following 5 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer. 2019

Ligorio, Matteo / Sil, Srinjoy / Malagon-Lopez, Jose / Nieman, Linda T / Misale, Sandra / Di Pilato, Mauro / Ebright, Richard Y / Karabacak, Murat N / Kulkarni, Anupriya S / Liu, Ann / Vincent Jordan, Nicole / Franses, Joseph W / Philipp, Julia / Kreuzer, Johannes / Desai, Niyati / Arora, Kshitij S / Rajurkar, Mihir / Horwitz, Elad / Neyaz, Azfar / Tai, Eric / Magnus, Neelima K C / Vo, Kevin D / Yashaswini, Chittampalli N / Marangoni, Francesco / Boukhali, Myriam / Fatherree, Jackson P / Damon, Leah J / Xega, Kristina / Desai, Rushil / Choz, Melissa / Bersani, Francesca / Langenbucher, Adam / Thapar, Vishal / Morris, Robert / Wellner, Ulrich F / Schilling, Oliver / Lawrence, Michael S / Liss, Andrew S / Rivera, Miguel N / Deshpande, Vikram / Benes, Cyril H / Maheswaran, Shyamala / Haber, Daniel A / Fernandez-Del-Castillo, Carlos / Ferrone, Cristina R / Haas, Wilhelm / Aryee, Martin J / Ting, David T. ·Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. · Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. · Clinic of Surgery, UKSH Campus Lübeck, Germany. · Institute of Pathology, University Medical Center Freiburg, Germany. · Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: aryee.martin@mgh.harvard.edu. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: dting1@mgh.harvard.edu. ·Cell · Pubmed #31155233.

ABSTRACT: Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units." Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.

2 Article ADAM9 contributes to vascular invasion in pancreatic ductal adenocarcinoma. 2019

Oria, Victor O / Lopatta, Paul / Schmitz, Tatjana / Preca, Bogdan-Tiberius / Nyström, Alexander / Conrad, Catharina / Bartsch, Jörg W / Kulemann, Birte / Hoeppner, Jens / Maurer, Jochen / Bronsert, Peter / Schilling, Oliver. ·Institute of Molecular Medicine and Cell Research, University of Freiburg, Germany. · Spemann Graduate School of Biology and Medicine, University of Freiburg, Germany. · Faculty of Biology, University of Freiburg, Germany. · Department of Biomedicine, University of Basel, Switzerland. · Department of Dermatology, Medical Faculty, Medical Center - University of Freiburg, Germany. · Department of Neurosurgery, Philipps University Marburg, Germany. · Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, Germany. · Department of General and Visceral Surgery, Medical Center - University of Freiburg, Germany. · Faculty of Medicine, University of Freiburg, Germany. · Comprehensive Cancer Center Freiburg, Medical Center - University of Freiburg, Germany. · Department of Gynecology, University Clinic RWTH, Aachen, Germany. · Institute of Surgical Pathology, Medical Center - University of Freiburg, Germany. · German Cancer Consortium (DKTK) and Cancer Research Center (DKFZ), Heidelberg, Germany. · Tumorbank Comprehensive Cancer Center Freiburg, Medical Center - University of Freiburg, Germany. · Centre for Biological Signaling Studies BIOSS, University of Freiburg, Germany. ·Mol Oncol · Pubmed #30556643.

ABSTRACT: A disintegrin and a metalloprotease (ADAM)-9 is a metzincin cell-surface protease with strongly elevated expression in solid tumors, including pancreatic ductal adenocarcinoma (PDAC). In this study, we performed immunohistochemistry (IHC) of a tissue microarray (TMA) to examine the expression of ADAM9 in a cohort of >100 clinically annotated PDAC cases. We report that ADAM9 is prominently expressed by PDAC tumor cells, and increased ADAM9 expression levels correlate with poor tumor grading (P = 0.027) and the presence of vasculature invasion (P = 0.017). We employed gene expression silencing to generate a loss-of-function system for ADAM9 in two established PDAC cell lines. In vitro analysis showed that loss of ADAM9 does not impede cellular proliferation and invasiveness in basement membrane. However, ADAM9 plays a crucial role in mediating cell migration and adhesion to extracellular matrix substrates such as fibronectin, tenascin, and vitronectin. This effect appears to depend on its catalytic activity. In addition, ADAM9 facilitates anchorage-independent growth. In AsPC1 cells, but not in MiaPaCa-2 cells, we noted a pronounced yet heterogeneous impact of ADAM9 on the abundance of various integrins, a process that we characterized as post-translational regulation. Sprout formation of human umbilical vein endothelial cells (HUVECs) is promoted by ADAM9, as examined by transfer of cancer cell conditioned medium; this finding further supports a pro-angiogenic role of ADAM9 expressed by PDAC cancer cells. Immunoblotting analysis of cancer cell conditioned medium highlighted that ADAM9 regulates the levels of angiogenic factors, including shed heparin-binding EGF-like growth factor (HB-EGF). Finally, we carried out orthotopic seeding of either wild-type AsPC-1 cells or AsPC-1 cells with silenced ADAM9 expression into murine pancreas. In this in vivo setting, ADAM9 was also found to foster angiogenesis without an impact on tumor cell proliferation. In summary, our results characterize ADAM9 as an important regulator in PDAC tumor biology with a strong pro-angiogenic impact.

3 Article Mesopancreatic Stromal Clearance Defines Curative Resection of Pancreatic Head Cancer and Can Be Predicted Preoperatively by Radiologic Parameters: A Retrospective Study. 2016

Wellner, Ulrich F / Krauss, Tobias / Csanadi, Agnes / Lapshyn, Hryhoriy / Bolm, Louisa / Timme, Sylvia / Kulemann, Birte / Hoeppner, Jens / Kuesters, Simon / Seifert, Gabriel / Bausch, Dirk / Schilling, Oliver / Vashist, Yogesh K / Bruckner, Thomas / Langer, Mathias / Makowiec, Frank / Hopt, Ulrich T / Werner, Martin / Keck, Tobias / Bronsert, Peter. ·From the Clinic for Surgery, UKSH Campus Lübeck, Lübeck (UFW, HL, LB, DB, TK) · Clinic for Radiology (TK, ML) · Institute of Pathology (AC, ST, MW, PB) · Clinic for General and Visceral Surgery, University Medical Center Freiburg (BK, JH, SK, GS, FM, UTH) · Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg (OS) · Department of Surgery, University Hospital Hamburg-Eppendorf (UKE), Hamburg (YKV) · Institute of Medical Biometry and Informatics (IMBI), University of Heidelberg, Heidelberg (TB) · Comprehensive Cancer Center Freiburg, Freiburg (ML, FM, UTH, MW, PB) · and German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany (OS, MW, PB). ·Medicine (Baltimore) · Pubmed #26817896.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability.Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011.Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S-status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status.Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross-sectional imaging is possible, setting the basis for a new definition of borderline resectability.

4 Article Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma. 2015

Kohler, Ilona / Bronsert, Peter / Timme, Sylvia / Werner, Martin / Brabletz, Thomas / Hopt, Ulrich Theodor / Schilling, Oliver / Bausch, Dirk / Keck, Tobias / Wellner, Ulrich Friedrich. ·Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany. ·J Gastroenterol Hepatol · Pubmed #25827809.

ABSTRACT: BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. METHODS: Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis. RESULTS: Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis. CONCLUSIONS: Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor-host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.

5 Article Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer. 2014

Bronsert, Peter / Kohler, Ilona / Timme, Sylvia / Kiefer, Selina / Werner, Martin / Schilling, Oliver / Vashist, Yogesh / Makowiec, Frank / Brabletz, Thomas / Hopt, Ulrich T / Bausch, Dirk / Kulemann, Birte / Keck, Tobias / Wellner, Ulrich F. ·Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany; Comprehensive Cancer Center, Freiburg, Germany. Electronic address: peter.bronsert@uniklinik-freiburg.de. · Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany. · Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany; Comprehensive Cancer Center, Freiburg, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany. · Comprehensive Cancer Center, Freiburg, Germany; Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany. · Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany. · Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany; Clinic for Surgery, University Clinic Schleswig-Holstein Campus, Lübeck, Germany. ·Surgery · Pubmed #24929761.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an aggressive biology and poor prognosis. Experimental evidence has suggested a role for the transcriptional repressor Zinc finger E-box binding homeobox 1 (ZEB1) in epithelial-mesenchymal transition, invasion, and metastasis in PDAC. ZEB1 expression has been observed in cancer cells as well as stromal fibroblasts. Our study aimed to evaluate the prognostic value of ZEB1 expression in PDAC tissue. METHODS: Patient baseline and follow-up data were extracted from a prospectively maintained database. After clinicopathologic re-review, serial sliced tissue slides were immunostained for ZEB1, E-cadherin, vimentin, and pan-cytokeratin. ZEB1 expression in cancer cells and adjacent stromal fibroblasts was graded separately and correlated to routine histopathologic parameters and survival after resection. RESULTS: A total of 117 cases of PDAC were included in the study. High ZEB1 expression in cancer cells and in stromal cancer-associated fibroblasts was associated with poor prognosis. There was also a trend for poor prognosis with a lymph node ratio of greater than 0.10. In line with its role as an inducer of epithelial-mesenchymal transition, ZEB1 expression in cancer cells was positively correlated with Vimentin expression and negatively with E-Cadherin expression. In multivariate analysis, stromal ZEB1 expression grade was the only independent factor of survival after resection. CONCLUSION: Our data suggest that ZEB1 expression in cancer cells as well as in stromal fibroblasts are strong prognostic factors in PDAC. Stromal ZEB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC. This observation suggests that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts.