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Pancreatic Neoplasms: HELP
Articles by Jan Sperveslage
Based on 6 articles published since 2010
(Why 6 articles?)

Between 2010 and 2020, J. Sperveslage wrote the following 6 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review [Will molecular diagnostics become established in pancreatic pathology?]. 2013

Sipos, B / Sperveslage, J. ·Allgemeine Pathologie und Pathologische Anatomie, Institut für Pathologie und Neuropathologie, Universitätsklinikum Tübingen, Liebermeisterstr. 8, 72076, Tübingen, Deutschland, bence.sipos@med.uni-tuebingen.de. ·Pathologe · Pubmed #24196616.

ABSTRACT: Genetic alterations of solid and cystic tumors of the pancreas have been increasingly more characterized over the last few years. Pancreatic ductal adenocarcinoma (PDAC) carries numerous point mutations and, to a lesser extent, deletions and amplifications of genes that are associated with at least 13 tumor relevant signalling pathways and processes. Besides the four common driver mutations in the KRAS, p53, CDKN2a and SMAD4 genes there are a number of low frequency driver mutations. The classification of PDAC subtypes has benefited from recent analyses of transcriptional profiles that revealed a classical KRAS driven and a KRAS independent quasi-mesenchymal subtype. The analyses of mRNA and miRNA expression profiles of fine needle aspirates serve as a basis for reliable preoperative diagnosis of pancreatic masses.The four most common cystic pancreatic tumors bear tumor-specific genetic alterations, such as GNAS mutations in intraductal papillary mucinous neoplasms, β-catenin mutations in solid pseudopapillary neoplasms and VHL mutations or loss of heterozygosity in serous cystadenoma. Recovery of DNA from aspirates of cyst fluids enables an improved preoperative management of cystic pancreatic tumors by mutational analysis. In addition to the analysis of DNA there are promising approaches in distinguishing benign and premalignant/malignant cystic tumors by evaluating miRNA profiles.In recent years much progress has been made in molecular genetic characterization and preoperative evaluation of pancreatic tumors. Hopefully these results will contribute to prognostic and therapeutic stratification of PDAC and to a reliable preoperative diagnostics of benign cystic pancreatic tumors in the future.

2 Article Neovascular Prostate-Specific Membrane Antigen Expression Is Associated with Improved Overall Survival under Palliative Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma. 2017

Stock, Katharina / Steinestel, Konrad / Wiesch, Rebekka / Mikesch, Jan-Henrik / Hansmeier, Anna / Trautmann, Marcel / Beller, Nora / Rehkämper, Jan / Wardelmann, Eva / Heitkötter, Birthe / Hartmann, Wolfgang / Sperveslage, Jan / Huss, Sebastian. ·Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany. · Institute of Pathology and Molecular Pathology, Bundeswehrkrankenhaus Ulm, Ulm, Germany. · Department of Medicine A, University Hospital Münster, Münster, Germany. ·Biomed Res Int · Pubmed #29209626.

ABSTRACT: Aims: Expression of PSMA (prostate-specific membrane antigen) has been demonstrated in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, PSMA expression in PDAC-associated neovasculature has so far not been systematically analyzed. Methods and Results: We analyzed PSMA expression in 81 PDAC tissue samples from 61 patients. Microvessel density (MVD) was assessed by software-based image analysis and showed a mean MVD of 63.7 microvessels/0.785 mm Conclusion: PSMA expression in tumor-associated neovasculature is a common feature and associated with improved overall survival under palliative chemotherapy in PDAC. Our results point towards a possible association between PSMA expression and response to therapy which might be based on enhanced intratumoral bioavailability of systemic chemotherapy.

3 Article RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. 2016

Lesina, Marina / Wörmann, Sonja Maria / Morton, Jennifer / Diakopoulos, Kalliope Nina / Korneeva, Olga / Wimmer, Margit / Einwächter, Henrik / Sperveslage, Jan / Demir, Ihsan Ekin / Kehl, Timo / Saur, Dieter / Sipos, Bence / Heikenwälder, Mathias / Steiner, Jörg Manfred / Wang, Timothy Cragin / Sansom, Owen J / Schmid, Roland Michael / Algül, Hana. · ·J Clin Invest · Pubmed #27454298.

ABSTRACT: Tumor suppression that is mediated by oncogene-induced senescence (OIS) is considered to function as a safeguard during development of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that regulate OIS in PDAC are poorly understood. Here, we have determined that nuclear RelA reinforces OIS to inhibit carcinogenesis in the Kras mouse model of PDAC. Inactivation of RelA accelerated pancreatic lesion formation in Kras mice by abrogating the senescence-associated secretory phenotype (SASP) gene transcription signature. Using genetic and pharmacological tools, we determined that RelA activation promotes OIS via elevation of the SASP factor CXCL1 (also known as KC), which activates CXCR2, during pancreatic carcinogenesis. In Kras mice, pancreas-specific inactivation of CXCR2 prevented OIS and was correlated with increased tumor proliferation and decreased survival. Moreover, reductions in CXCR2 levels were associated with advanced neoplastic lesions in tissue from human pancreatic specimens. Genetically disabling OIS in Kras mice caused RelA to promote tumor proliferation, suggesting a dual role for RelA signaling in pancreatic carcinogenesis. Taken together, our data suggest a pivotal role for RelA in regulating OIS in preneoplastic lesions and implicate the RelA/CXCL1/CXCR2 axis as an essential mechanism of tumor surveillance in PDAC.

4 Article Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations. 2015

Sipos, Bence / Sperveslage, Jan / Anlauf, Martin / Hoffmeister, Maike / Henopp, Tobias / Buch, Stephan / Hampe, Jochen / Weber, Achim / Hammel, Pascal / Couvelard, Anne / Höbling, Walter / Lieb, Wolfgang / Boehm, Bernhard O / Klöppel, Günter. ·Department of Pathology (B.S., J.S., M.H.), University of Tübingen, 72076 Germany · Institute of Pathology (M.A.), Limburg, 65549 Germany · Institute of Pathology (T.H.), Traunstein, 83278 Germany · POPGEN Biobank Project (S.B.), Christian-Albrechts-University, Kiel, 24105 Germany · First Department of Internal Medicine (J.H.), University Hospital, Dresden, 01304 Germany · Department of Clinical Pathology (A.W.), University Hospital Zürich, 8091 Switzerland · Service de Gastroentérologie-Pancréatologie (P.H.), Hôpital Beaujon, Clichy La Garenne, 92110 France · Department of Pathology (A.C.), Hôpital Bichat, Paris, 75018 France · Institute of Pathology (W.H.), Hospital Wels-Grieskirchen, Wels, 4600 Austria · Institute of Epidemiology and Biobank POPGEN (W.L.), Christian-Albrechts-University, 24105 Kiel, Germany · LKC Medicine (B.O.B.), Nanyang Technological University, 639798 Singapore and Imperial College London, London WC1E 6BT, UK and Department of Internal Medicine I, University of Ulm Medical Centre, Ulm, 89081 Germany · and Department of Pathology (G.K.), Technical University München, 80333 Germany. ·J Clin Endocrinol Metab · Pubmed #25695890.

ABSTRACT: CONTEXT: Glucagon cell adenomatosis (GCA) was recently recognized as a multifocal hyperplastic and neoplastic disease of the glucagon cells unrelated to multiple endocrine neoplasia type 1 and von-Hippel-Lindau disease. OBJECTIVE: The study focused on the molecular analysis of the glucagon receptor (GCGR) gene in GCA and a description of the clinicopathological features of GCA with and without GCGR mutations. DESIGN: Pancreatic tissues from patients showing multiple glucagon cell tumors were morphologically characterized and macro- or microdissected. All exons of the GCGR gene were analyzed for mutations by Sanger and next-generation sequencing. Genotyping for all detected GCGR variants was performed in 2560 healthy individuals. PATIENTS: Six patients with GCA, and the parents of one patient were included in the study. MAIN OUTCOME MEASURES: The main outcome measures were the correlations between the patients' GCGR mutation status and the respective clinicopathological data. RESULTS: GCGR germline mutations were found in three of six patients. Patient 1 harbored a homozygous stop mutation. This patient's parents showed an identical but heterozygous GCGR mutation. Patient 2 had two different heterozygous point mutations leading each to premature stop codons. Patient 3 exhibited two homozygous missense mutations. No GCGR mutations were identified in the three other patients and in a large cohort of healthy subjects. The patients harboring GCGR mutations exhibited a greater number of tumors and larger tumors than patients with wild-type GCGR. One of the patients with wild-type GCGR showed lymph node micrometastases. CONCLUSIONS: GCA with GCGR germline mutations seems to follow an autosomal-recessive trait. By interrupting the GCGR signaling pathways GCGR mutations probably cause GCA via glucagon cell hyperplasia. GCA also occurs in patients without GCGR mutations, but seems to be associated with fewer and smaller tumors.

5 Article Establishment of robust controls for the normalization of miRNA expression in neuroendocrine tumors of the ileum and pancreas. 2014

Sperveslage, J / Hoffmeister, M / Henopp, T / Klöppel, G / Sipos, B. ·Institute of Pathology, University of Tübingen, Liebermeisterstr.8, 72076, Tübingen, Germany, jan.sperveslage@med.uni-tuebingen.de. ·Endocrine · Pubmed #24535468.

ABSTRACT: There is need to determine tissue-specific robust controls for normalization of microRNA expression to avoid false results and misinterpretation. The aim of this study was to evaluate the expression of different small RNAs in neuroendocrine tumors (NETs) and their suitability as normalizers in miRNA real-time PCR experiments. We investigated the expression of the nine small RNAs miR-93, miR-191, SNORD48, SNORD61, SNORD68, SNORD72, SNORD95, SNORD96a, and RNU6-2 in formalin-fixed, paraffin-embedded tissue samples of 25 ileal NETs by real-time PCR determining the most stable controls for expression normalization using four different algorithms. This analysis was expended to ten pancreatic NETs. Finally, five small RNAs were further tested as normalizers for miRNA-133a expression, which is known to be downregulated in metastases of ileal NETs, in ten matched pairs of ileal NETs and their metastases. Ranking of the expression results revealed the following order of stability from high to low: SNORD61 < SNORD95 < SNORD72 < SNORD96a < SNORD68 < miR-191 < miR-93 < RNU6-2 < SNORD48 for ileal NETs and SNORD95 < miR-93 < SNORD96a < SNORD61 < SNORD68 < SNORD72 < RNU6-2 < miR-191 < SNORD48 for pancreatic NETs. The determination of SNORD61 and SNORD95 for ileal NETs and SNORD95 and miR-93 for pancreatic NETs as good normalizers presents a useful tool for experiments involving the analysis of miRNA expression.

6 Article Lack of CCR7 expression is rate limiting for lymphatic spread of pancreatic ductal adenocarcinoma. 2012

Sperveslage, Jan / Frank, Sunna / Heneweer, Carola / Egberts, Jan / Schniewind, Bodo / Buchholz, Malte / Bergmann, Frank / Giese, Nathalia / Munding, Johanna / Hahn, Stephan A / Kalthoff, Holger / Klöppel, Günter / Sipos, Bence. ·Institute of Pathology, University of Tübingen, Tübingen, Germany. ·Int J Cancer · Pubmed #22020953.

ABSTRACT: CCR7 expression on tumor cells promotes lymphatic spread in several malignant tumors. However, a comprehensive characterization of the CCL19/CCL21-CCR7 axis in pancreatic ductal adenocarcinoma (PDAC), which is known for its high rates of lymph-node metastases, is still lacking. CCR7 mRNA and CCR7 protein were found to be expressed in spheroid cultures of all six examined PDAC cell lines. In migration assays, CCR7 expressing PDAC cells showed enhanced migration toward CCL19 and CCL21, the two ligands of CCR7. In an orthotopic nude mouse model, CCR7-transfected PT45P1 cells gave rise to significantly larger tumors and showed a higher frequency of lymph vessel invasion and lymph-node metastases than mock-transfected cells. In an analysis using quantitative real-time PCR, CCR7 showed fourfold overexpression in microdissected PDAC cells compared to normal duct cells. Moderate-to-strong immunohistochemical CCR7 expression, found in 58 of 121 well-characterized human PDACs, correlated with high rates of lymph vessel invasion. Conversely, PDACs completely lacking CCR7 expression showed only low rates of lymph vessel invasion and lymph-node metastases. The evaluation of CCL21 expression by immunofluorescence staining revealed a significant upregulation of CCL21 in peritumoral and intratumoral lymph vessels compared to lymph vessels in disease-free pancreata. In conclusion, our study revealed strong evidence that lack of CCR7 impairs the metastatic potential of PDAC. Lymph vessel invasion by CCR7 expressing PDAC cells may be additionally enhanced by upregulation of CCL21 in tumor-associated lymph vessels, representing a previously unknown factor of lymphatic spread.