0000000000331385
AUTHOR
Günter Klöppel
StellaTUM: current consensus and discussion on pancreatic stellate cell research
The field of pancreatic stellate cell (PSC) biology is very young, as the essential in-vitro tools to study these cells (ie, methods to isolate and culture PSC) were only developed as recently as in 1998. Nonetheless, there has been an exponential increase in research output in this field over the past decade, with numerous research groups around the world focusing their energies into elucidating the biology and function of these cells. It is now well established that PSC are responsible for producing the stromal reaction (fibrosis) of two major diseases of the pancreas—chronic pancreatitis and pancreatic cancer. Despite exponentially increasing data, the methods for studying PSC remain var…
Wachstumsverhalten duktaler Pankreascarcinome. In vivo- und in vitro-Untersuchungen
Unter den exokrinen Pankreasneoplasmen ist das duktale Adenocarcinom mit einer relativen Haufigkeit von 80–90% der vorherrschende Tumor (1). Durch seine generell schlechte Prognose, nur etwa 2% der behandelten Patienten uberleben die Funfjahresgrenze (2) und seine langsam zunehmende Incidenz in den letzten 20 Jahren (3), ist das duktale Pankreascarcinom zu einer grosen Herausforderung in der Onkologie geworden. An einem geeigneten Tumormodell wie dem “Nacktmaussystem” konnten Tumorbiologie, Tumorwachstum und pratherapeutische Therapiestudien untersucht werden. In der vorliegenden Arbeit sollte zunachst uberpruft werden, inwieweit das Wachstumsverhalten duktaler Pankreascarcinome auf der Nac…
Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity
Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreatic NETs were reviewed for evidence of a somatostatinoma syndrome. Predominant or exclusive expression of somatostatin was found in 21 (26%) duodenal and 21 (4%) pancreatic NETs. They were classified as sporadic (n=31) or neurofibromatosis type 1 (NF1)-associated duodenal NETs (n=3), gangliocytic paragangliomas (GCPGs; n=6), or poorly differentiated neuroendocrine carcinomas (pd…
Histological and fine structural features of pancreatic ductal adenocarcinomas in relation to growth and prognosis: studies in xenografted tumours and clinico-histopathological correlation in a series of 75 cases
Histology and fine structure of pancreatic ductal adenocarcinomas were assessed with respect to their significance for tumour growth and prognosis. The histological parameters included glandular differentiation, nuclear anaplasia, nuclear size, and mitotic activity (number of mitoses per high power field). Using these criteria three grades of malignancy were distinguished. They correlated well with the growth kinetics of seven human pancreatic ductal adenocarcinomas transplanted into nude mice. The tumour doubling time of a G 3 carcinoma was about half that of a G 1 carcinoma. On electron microscopy the tumour grade was reflected in the degree of functional differentiation of the neoplastic…
In Vivo Molecular Imaging of Somatostatin Receptors in Pancreatic Islet Cells and Neuroendocrine Tumors by Miniaturized Confocal Laser-Scanning Fluorescence Microscopy
The aim of the study was to evaluate real time in vivo molecular imaging of somatostatin receptors (sstrs) using a handheld miniaturized confocal laser scan microscope (CLM) in conjunction with fluorescein-labeled octreotate (OcF) in healthy mice and murine models of neuroendocrine tumors. For CLM a small rigid probe (diameter 7 mm) with an integrated single line laser (488 nm) was used (optical slice thickness 7 μm; lateral resolution 0.7 μm). OcF was synthesized via Fmoc solid-phase peptide synthesis and purified by HPLC showing high-affinity binding to the sstr2 (IC50 6.2 nmol). For in vitro evaluation, rat and human pancreatic cancer cells were used and characterized with respect to its…
Pattern of secondary genomic changes in pancreatic tumors ofTgfα/Trp53+/−transgenic mice
Trp53+/− mice overexpressing Tgfα in a pancreas-specific manner represent a well-established animal model for pancreatic cancer. In this study we analyzed 38 pancreatic adenocarcinomas of these mice for secondary genomic changes by comparative genomic hybridization (CGH), loss of heterozygosity (LOH) analysis, real-time PCR, and methylation-specific analysis. CGH screening of the tumors revealed a recurrent pattern of genomic changes. In more than 50% of the tumors, chromosome 11 was affected. The gain of the proximal part spans about 16 cM, including the genes for Egfr, Rel, and Stk10. The distal part of chromosome 11, which contains the Trp53 locus, was deleted. LOH analysis proved that a…
6-18F-Fluoro-l-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to123I-Metaiodobenzyl-Guanidine Scintigraphy in the Detection of Extraadrenal and Hereditary Pheochromocytomas and Paragangliomas: Correlation with Vesicular Monoamine Transporter Expression
Context: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by 18F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than 123I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. Objective: The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. Design and Setting: Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. Patients: Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate de…
Einfluß von Steroidhormonen auf das Wachstum exokriner Pankreascarcinome. In vivo- und in vitro-Untersuchungen
In jungerer Zeit wurde in der Literatur uber eine mogliche Bedeutung von Steroidhormonen (SH) fur das Wachstum ductaler menschlicher Pankreascarcinome (PaCa) mehrfach berichtet (1, 2, 3). Auch die Steroidhormonkonzentration i.S. von Pankreascarcinomtragern scheint verandert zu sein (4). Um weitere Information uber den moglichen Einflus von Steroidhormonen auf das Wachstum von Pankreascarcinomen zu bekommen, wurden in dieser Arbeit folgende Fragen untersucht: 1. Lassen sich Steroidhormon-Receptoren in normalem Pankreas, in Gewebe von Pankreascarcinomen sowie in Gewebe transplantierter Pankreascarcinome auf der Nacktmaus nachweisen? 2. Lassen sich unterschiedliche Steroidhormon-Konzentratione…
Intraductal proliferation in the pancreas and its relationship to human and experimental carcinogenesis
In 21 patients who had undergone total pancreatectomy for pancreatic head carcinoma, the uninvolved pancreas was examined with regard to the type, incidence and regional distribution of duct epithelial proliferation. The results were compared with those in 37 operative specimens from patients with chronic pancreatitis, in 46 normal pancreases from autopsies and with findings in experimental pancreatic carcinogenesis. While the incidence of squamous metaplasia and non-papillary epithelial hypertrophy varied little in the different groups, papillary epithelial hyperplasia was found three times more often in cases of carcinoma, with associated mild duct obstruction. Atypical epithelial prolife…
In-vivo confocal real-time mini-microscopy in animal models of human inflammatory and neoplastic diseases
Background and study aims Although various improvements in tissue imaging modalities have recently been achieved, in-vivo molecular and subsurface imaging in the field of gastroenterology remains a technical challenge. In this study we evaluated a newly developed, handheld, miniaturized confocal laser microscopy probe for real-time in-vivo molecular and subsurface imaging in rodent models of human disease. Materials and methods The minimicroscope uses a 488-nm, single line laser for fluorophore excitation. The optical slice thickness is 7 microm, the lateral resolution 0.7 microm. The range of the z-axis is 0-250 microm below the tissue surface. Imaging was performed using different fluores…