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Pancreatic Neoplasms: HELP
Articles by Annika Blank
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, Annika Blank wrote the following 7 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Calcitonin-Producing Neuroendocrine Neoplasms of the Pancreas: Clinicopathological Study of 25 Cases and Review of the Literature. 2017

Uccella, Silvia / Blank, Annika / Maragliano, Roberta / Sessa, Fausto / Perren, Aurel / La Rosa, Stefano. ·Department of Medicine and Surgery, Unit of Pathology, University of Insubria, 21100, Varese, Italy. silvia.uccella@uninsubria.it. · Institute of Pathology, University of Bern, Bern, Switzerland. · Department of Medicine and Surgery, Unit of Pathology, University of Insubria, 21100, Varese, Italy. · Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland. ·Endocr Pathol · Pubmed #29063495.

ABSTRACT: Increased levels of circulating calcitonin are a clue in the diagnosis of medullary thyroid carcinoma. However, hypercalcitoninemia can also be related to other pathological conditions, including pancreatic neuroendocrine neoplasms (PanNENs). Ectopic hormonal production is not unusual in both functioning and non-functioning PanNENs; however, little is known about the frequency of calcitonin expression in these neoplasms. The aims of this study were to assess the frequency of calcitonin immunoreactivity in PanNENs, independently from serum calcitonin levels, and to evaluate the clinicopathological and prognostic features of calcitonin-immunoreactive (Cal-IR) PanNENs, including a comparison with cases already reported in the literature. We screened 229 PanNENs for the immunohistochemical expression of calcitonin, including both functioning and non-functioning neoplasms, as well as both well-differentiated and poorly differentiated PanNENs. Both the clinicopathological data and the follow-up information were available and were compared with the immunohistochemical results. In addition, we reviewed the features of the calcitonin-producing PanNENs previously reported in the literature. Calcitonin was expressed in 25 of our 229 PanNENs (10.9%). Examples of well- and poorly differentiated, as well as both functioning and non-functioning PanNENs, were found to be calcitonin immunoreactive. Cal-IR PanNENs did not show any significant difference with the whole series of neoplasms included in the study, when the clinicopathological parameters were considered, except for a younger age at diagnosis and for a larger size of the tumor in non-functioning Cal-IR PanNENs. Taken together, our results show that calcitonin immunoreactivity is not an exceptional event in PanNENs. Furthermore, calcitonin expression does not identify a separate clinical entity, in contrast to other PanNENs with ectopic hormone production, such as adrenocorticotropic hormone (ACTH)-producing PanNENs, which show a distinctively more aggressive behavior.

2 Review New Genetics and Genomic Data on Pancreatic Neuroendocrine Tumors: Implications for Diagnosis, Treatment, and Targeted Therapies. 2016

Schmitt, Anja M / Marinoni, Ilaria / Blank, Annika / Perren, Aurel. ·Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. anja.schmitt@pathology.unibe.ch. · Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. ·Endocr Pathol · Pubmed #27456058.

ABSTRACT: The recent findings on the roles of death-associated protein 6/α-thalassemia/mental retardation X-linked (DAXX/ATRX) in the development of pancreatic neuroendocrine tumors (PanNETs) have led to major advances in the molecular understanding of these rare tumors and open up completely new therapeutic windows. This overview aims at giving a simplified view on these findings and their possible therapeutic implications. The importance of epigenetic changes in PanNET is also underlined by recent findings of a cross-species study on microRNA (miRNA) and messenger RNA (mRNA) profiles in PanNETs.

3 Article Therapeutic targeting of tumor-associated macrophages in pancreatic neuroendocrine tumors. 2018

Krug, Sebastian / Abbassi, Rami / Griesmann, Heidi / Sipos, Bence / Wiese, Dominik / Rexin, Peter / Blank, Annika / Perren, Aurel / Haybaeck, Johannes / Hüttelmaier, Stefan / Rinke, Anja / Gress, Thomas M / Michl, Patrick. ·Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle, Saale, Germany. · Department of Gastroenterology and Endocrinology, Philipps-University, Marburg, Germany. · Institute of Pathology and Neuropathology, University Hospital of Tübingen, Tübingen, Germany. · Department of Visceral, Thoracic and Vascular Surgery, Philipps-University, Marburg, Germany. · Institute of Pathology, Philipps-University, Marburg, Germany. · Institute of Pathology, University of Bern, Bern, Switzerland. · Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany. · Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Halle, Saale, Germany. ·Int J Cancer · Pubmed #29696624.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) represent a heterogeneous group of neuroendocrine neoplasms with varying biological behavior and response to treatment. Although targeted therapies have been shown to improve the survival for patients at advanced stage, resistance to current therapies frequently occurs during the course of therapy. Previous reports indicate that the infiltration of tumor-associated macrophages (TAMs) in PNETs might correlate with tumor progression and metastasis formation. We aimed to evaluate the prognostic and functional impact of TAMs in human PNETs in vitro and in vivo and to investigate the effect of therapeutic targeting TAMs in a genetic PNET mouse model. TAM expression pattern was assessed immunohistochemically in human PNET tissue sections and a tissue-micro-array of PNET tumors with different functionality, stage, and grading. The effect of liposomal clodronate on TAM cell viability was analyzed in myeloid cell lines and isolated murine bone macrophages (mBMM). In vivo, RIP1Tag2 mice developing insulinomas were treated with liposomal clodronate or PBS-Liposomes. Tumor progression, angiogenesis and immune cell infiltration were assessed by immunohistochemistry. In human, insulinomas TAM density was correlated with invasiveness and malignant behavior. Moreover, TAM infiltration in liver metastases was significantly increased compared to primary tumors. In vitro, Liposomal clodronate selectively inhibited the viability of myeloid cells and murine bone macrophages, leaving PNET tumor cell lines largely unaffected. In vivo, repeated application of liposomal clodronate to RIP1Tag2 mice significantly diminished the malignant transformation of insulinomas, which was accompanied by a reduced infiltration of F4/80-positive TAM cells and simultaneously by a decreased microvessel density, suggesting a pronounced effect of clodronate-induced myeloid depletion on tumor angiogenesis. Concomitant treatment with the antiangiogenic TKI sunitinib, however, did not show any synergistic effects with liposomal clodronate. TAMs are crucial for malignant transformation in human PNET and correlate with metastatic behavior. Pharmacological targeting of TAMs via liposomal clodronate disrupts tumor progression in the RIP1Tag2 neuroendocrine tumor model and was associated with reduced tumor angiogenesis. Based on these results, using liposomal clodronate to target proangiogenic myeloid cells could be employed as novel therapeutic avenue in highly angiogenic tumors such as PNET.

4 Article Autophagy Inhibition Improves Sunitinib Efficacy in Pancreatic Neuroendocrine Tumors via a Lysosome-dependent Mechanism. 2017

Wiedmer, Tabea / Blank, Annika / Pantasis, Sophia / Normand, Lea / Bill, Ruben / Krebs, Philippe / Tschan, Mario P / Marinoni, Ilaria / Perren, Aurel. ·Institute of Pathology, University of Bern, Bern, Switzerland. · Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. · Department of Internal Medicine, Regional Hospital Emmental Burgdorf, Burgdorf, Switzerland. · Institute of Pathology, University of Bern, Bern, Switzerland. aurel.perren@pathology.unibe.ch ilaria.marinoni@pathology.unibe.ch. ·Mol Cancer Ther · Pubmed #28729403.

ABSTRACT: Increasing the efficacy of approved systemic treatments in metastasized pancreatic neuroendocrine tumors (PanNET) is an unmet medical need. The antiangiogenic tyrosine kinase inhibitor sunitinib is approved for PanNET treatment. In addition, sunitinib is a lysosomotropic drug and such drugs can induce lysosomal membrane permeabilization as well as autophagy. We investigated sunitinib-induced autophagy as a possible mechanism of PanNET therapy resistance. Sunitinib accumulated in lysosomes and induced autophagy in PanNET cell lines. Adding the autophagy inhibitor chloroquine reduced cell viability in cell lines and in primary cells isolated from PanNET patients. The same treatment combination reduced tumor burden in the Rip1Tag2 transgenic PanNET mouse model. The combination of sunitinib and chloroquine reduced recovery and induced apoptosis

5 Article Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors. 2015

Blank, Annika / Wehweck, Laura / Marinoni, Ilaria / Boos, Laura Amanda / Bergmann, Frank / Schmitt, Anja Maria / Perren, Aurel. ·University of Bern, Institute of Pathology, Murtenstr. 31, CH-3012, Bern, Switzerland. annika.blank@pathology.unibe.ch. · Department of Cardiology, Pneumology and Internal Intensive Care Medicine, Klinikum Neuperlach, Städtisches Klinikum München GmbH, Oskar-Maria-Graf-Ring 5, 83575, Munich, Germany. · University of Bern, Institute of Pathology, Murtenstr. 31, CH-3012, Bern, Switzerland. · University of Heidelberg, Institute of Pathology, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. ·Virchows Arch · Pubmed #26384025.

ABSTRACT: Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.

6 Article Glucagon-like-peptide-1 receptor expression in normal and diseased human thyroid and pancreas. 2015

Waser, Beatrice / Blank, Annika / Karamitopoulou, Eva / Perren, Aurel / Reubi, Jean C. ·Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland. ·Mod Pathol · Pubmed #25216224.

ABSTRACT: Glucagon-like-peptide-1 (GLP1) analogs may induce thyroid or pancreatic diseases in animals, raising questions about their use in diabetic patients. There is, however, controversy regarding expression of GLP1 receptors (GLP1R) in human normal and diseased thyroid and pancreas. Here, 221 human thyroid and pancreas samples were analyzed for GLP1R immunohistochemistry and compared with quantitative in vitro GLP1R autoradiography. Neither normal nor hyperplastic human thyroids containing parafollicular C cells express GLP1R with either method. Papillary thyroid cancer do not, and medullary thyroid carcinomas rarely express GLP1R. Insulin- and somatostatin-producing cells in the normal pancreas express a high density of GLP1R, whereas acinar cells express them in low amounts. Ductal epithelial cells do not express GLP1R. All benign insulinomas express high densities of GLP1R, whereas malignant insulinomas rarely express them. All ductal pancreatic carcinomas are GLP1R negative, whereas 6/20 PanIN 1/2 and 0/12 PanIN 3 express GLP1R. Therefore, normal thyroid, including normal and hyperplastic C cells, or papillary thyroid cancer are not targets for GLP1 analogs in humans. Conversely, all pancreatic insulin- and somatostatin-producing cells are physiological GLP1 targets, as well as most acini. As normal ductal epithelial cells or PanIN 3 or ductal pancreatic carcinomas do not express GLP1R, it seems unlikely that GLP1R is related to neoplastic transformation in pancreas. GLP1R-positive medullary thyroid carcinomas and all benign insulinomas are candidates for in vivo GLP1R targeting.

7 Article Prognostic and predictive roles of MGMT protein expression and promoter methylation in sporadic pancreatic neuroendocrine neoplasms. 2014

Schmitt, Anja Maria / Pavel, Marianne / Rudolph, Thomas / Dawson, Heather / Blank, Annika / Komminoth, Paul / Vassella, Erik / Perren, Aurel. ·Department of Pathology, Institute of Clinical Pathology, University of Bern, Bern, Switzerland. ·Neuroendocrinology · Pubmed #25012122.

ABSTRACT: BACKGROUND/AIMS: O(6)-methylguanine-methyltransferase (MGMT) is an important enzyme of DNA repair. MGMT promoter methylation is detectable in a subset of pancreatic neuroendocrine neoplasms (pNEN). A subset of pNEN responds to the alkylating agent temozolomide (TMZ). We wanted to correlate MGMT promoter methylation with MGMT protein loss in pNEN, correlate the findings with clinico-pathological data and determine the role of MGMT to predict response to TMZ chemotherapy. METHODS: We analysed a well-characterized collective of 141 resected pNEN with median follow-up of 83 months for MGMT protein expression and promoter methylation using methylation-specific PCR (MSP). A second collective of 10 metastasized, pretreated and progressive patients receiving TMZ was used to examine the predictive role of MGMT by determining protein expression and promoter methylation using primer extension-based quantitative PCR. RESULTS: In both collectives there was no correlation between MGMT protein expression and promoter methylation. Loss of MGMT protein was associated with an adverse outcome, this prognostic value, however, was not independent from grade and stage in multivariate analysis. Promoter hypermethylation was significantly associated with response to TMZ. CONCLUSION: Loss of MGMT protein expression is associated with adverse outcome in a surgical series of pNET. MGMT promoter methylation could be a predictive marker for TMZ chemotherapy in pNEN, but further, favourably prospective studies will be needed to confirm this result and before this observation can influence clinical routine.