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  • 1
    Language: English
    In: Surgery Today, 2010, Vol.40(2), pp.132-136
    Description: Byline: Ralf J. Rieker (1,2), Peter Schirmacher (1), Philipp A. Schnabel (1), Katharina Moser (2), Hans Hoffmann (3), Hendrik Dienemann (3), Joachim Pfannschmidt (3) Keywords: Thymolipoma; Myasthenia gravis; Surgery; Oncology Abstract: Purpose Thymolipomas are rare tumors of the anterior mediastinum accounting for up to 9% of all thymic tumors. These tumors are associated with autoimmune diseases in up to 50% of the patients, including myasthenia gravis, aplastic anemia, hypogammaglobulinemia, lichen planus, and Graves' disease. These tumors with a fatty appearance also can arise in older patients with autoimmune disease. Methods This retrospective study evaluated the thymolipomas from nine patients at a single institution, which were resected between 2002 and 2007. The clinical data as well as radiologic findings were evaluated, together with the follow-up. Results Seven patients initially presented with myasthenia gravis, and therefore they underwent a resection of the thymus, even though imaging techniques did not reveal a tumor in any of the cases. Another patient showed no symptoms of autoimmune disease for 20 years, and though cardiomegaly was suspected, further investigation revealed a thymolipoma. The symptoms of myasthenia gravis improved following the surgery in one patient. During follow-up, one patient died due to esophageal cancer, and the remaining patients are alive without recurrence. Conclusions Thymolipomas are benign tumors that show an excellent outcome. Patients with autoimmune disease symptoms occasionally show an improvement of the symptoms after a resection of the tumors. Author Affiliation: (1) Department of Pathology, University Hospital, Heidelberg, Germany (2) Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria (3) Department of Thoracic Surgery, Thoraxklinik, University of Heidelberg, Amalienstrasse 5, D-69126, Heidelberg, Germany Article History: Registration Date: 26/01/2009 Received Date: 26/02/2009 Accepted Date: 16/06/2009 Online Date: 28/01/2010
    Keywords: Thymolipoma ; Myasthenia gravis ; Surgery ; Oncology
    ISSN: 0941-1291
    E-ISSN: 1436-2813
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  • 2
    Language: English
    In: Gastroenterology, April 2016, Vol.150(4), pp.S958-S958
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0016-5085(16)33236-X Byline: Lothar Veits, Andreas Poetzl, Johannes Schumacher, Nils Kosiol, Jessica Becker, Ines Gockel, Ralf J. Rieker, Michael Vieth
    Keywords: Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
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  • 3
    Language: English
    In: Gastroenterology, May 2013, Vol.144(5), pp.S-499-S-499
    Keywords: Medicine
    ISSN: 0016-5085
    E-ISSN: 1528-0012
    Source: ScienceDirect Journals (Elsevier)
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  • 4
    Language: English
    In: Cancer research, 01 November 2017, Vol.77(21), pp.5963-5976
    Description: The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC). RNAi-mediated attenuation of in human NSCLC cells rendered them resistant to serum starvation-induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell-mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell-intrinsic and -extrinsic mechanisms to suppress tumor cell growth, most notably by enabling an effective antitumor immune response by the host. .
    Keywords: Immune Evasion ; Carcinoma, Non-Small-Cell Lung -- Metabolism ; Lung Neoplasms -- Metabolism ; Sphingomyelin Phosphodiesterase -- Metabolism
    ISSN: 00085472
    E-ISSN: 1538-7445
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  • 5
    Language: English
    In: Virchows Archiv, May, 2013, Vol.462(5), p.507(7)
    Description: Byline: Arne Warth (1), Ludger Fink (2), Annette Fisseler-Eckhoff (3), Danny Jonigk (4), Marius Keller (1), German Ott (5), Ralf J. Rieker (6), Peter Sinn (1), Stephan Soder (6), Alex Soltermann (7), Klaus Willenbrock (3), Wilko Weichert (1) Keywords: Pulmonary carcinoids; Proliferation; Prognosis; Mitosis; Interobserver agreement; Ki-67 Abstract: Evaluation of proliferative activity is a cornerstone in the classification of endocrine tumors in pulmonary carcinoids, the mitotic count delineates typical carcinoid (TC) from atypical carcinoid (AC). Data on the reproducibility of manual mitotic counting and other methods of proliferation index evaluation in this tumor entity are sparse. Nine experienced pulmonary pathologists evaluated 20 carcinoid tumors for mitotic count (hematoxylin and eosin) and Ki-67 index. In addition, Ki-67 index was automatically evaluated with a software-based algorithm. Results were compared with respect to correlation coefficients (CC) and kappa values for clinically relevant grouping algorithms. Evaluation of mitotic activity resulted in a low interobserver agreement with a median CC of 0.196 and a median kappa of 0.213 for the delineation of TC from AC. The median CC for hotspot (0.658) and overall (0.746) Ki-67 evaluation was considerably higher. However, kappa values for grouped comparisons of overall Ki-67 were only fair (median 0.323). The agreement of manual and automated Ki-67 evaluation was good (median CC 0.851, median kappa 0.805) and was further increased when more than one participant evaluated a given case. Ki-67 staining clearly outperforms mitotic count with respect to interobserver agreement in pulmonary carcinoids, with the latter having an unacceptable low performance status. Manual evaluation of Ki-67 is reliable, and consistency further increases with more than one evaluator per case. Although the prognostic value needs further validation, Ki-67 might perspectively be considered a helpful diagnostic parameter to optimize the separation of TC from AC. Author Affiliation: (1) Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany (2) Institute of Pathology and Cytology, Wetzlar, Germany (3) Institute of Pathology and Cytology, Horst-Schmidt Hospital, Wiesbaden, Germany (4) Institute for Pathology, University Hospital Hannover, Hannover, Germany (5) Department of Clinical Pathology, Robert-Bosch Hospital and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany (6) Institute for Pathology, University Hospital Erlangen-Nurnberg, Erlangen, Germany (7) Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland Article History: Registration Date: 27/03/2013 Received Date: 04/02/2013 Accepted Date: 26/03/2013 Online Date: 05/04/2013 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00428-013-1408-2) contains supplementary material, which is available to authorized users.
    Keywords: Tumors ; Algorithms
    ISSN: 0945-6317
    Source: Cengage Learning, Inc.
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  • 6
    Language: English
    In: Virchows Archiv, 2011, Vol.459(2), pp.221-226
    Description: Carcinoma showing thymus-like elements (CASTLE) is a rare neoplasm of the thyroid gland resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus and is thought to arise from ectopic thymic tissue within the thyroid gland or rudimentary branchial pouches along the thymic line. Using comparative genomic hybridization (CGH), chromosomal imbalances have been detected in several types of thymomas and thymic carcinomas. To evaluate whether there are hints of an underlying sequence in the pathogenesis of CASTLE analogue to those found in thymomas and thymic carcinomas, we evaluated four of these rare neoplasms for chromosomal imbalances using CGH. The most frequent gains were seen on chromosomal arm 1q (3/4), and losses were most frequently detected on 6p (4/4), 6q (3/4) and 16q (3/4). These CGH data show that CASTLE is characterized by chromosomal imbalances similar to those found in thymomas and thymic carcinomas and indicate a similar sequence in tumour development.
    Keywords: CASTLE ; Carcinoma showing thymus-like elements ; Chromosomal imbalances ; CGH
    ISSN: 0945-6317
    E-ISSN: 1432-2307
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  • 7
    Language: English
    In: Virchows Archiv, 2010, Vol.456(3), pp.277-285
    Description: With the aim to provide more insight into their biology, a series of 79 liposarcomas (LS) representative of all main subtypes was analysed for chromosomal imbalances using comparative genomic hybridization. Based on the genetic data, unsupervised hierarchical clustering unveiled two main LS clusters, each with two subclusters, one comprising three subsets. The first main cluster consisted of one larger subcluster, being characterised by gains/high-level amplifications of chromosomal subregions 12q13–q15, and exclusively included well-differentiated and dedifferentiated LS. A smaller subcluster was set apart on the basis of recurrent gains of 20q13 and 8q24, and mainly comprised pleomorphic and myxoid/round cell LS. The larger subcluster was subdivided into three subsets, one with nearly exclusive overrepresentations of 12q13–q15, the second with additional frequent gains of 1q21–q24, and the third with further recurrent overrepresentations of 6q22–q24, 20q13, and 12q24 and frequent losses of 13q14–q21 and 11q22–q23. While the first subset comprised both well-differentiated and dedifferentiated LS, the second and third subsets entirely included dedifferentiated LS. The second main cluster was characterised by recurrent overrepresentations of 5p13–p15, 1q21–q24, 1p12–p21, and 17p11.2–p12 and essentially comprised pleomorphic and myxoid/round cell LS. A separation of this second main cluster into two subclusters was based on additional gains on 22q13 and losses on 1q42–q43. Genomic profiling reveals genetically distinct subsets of dedifferentiated LS, which are clearly different from pleomorphic, myxoid/round cell, and, for some subsets, from well-differentiated LS. These data indicate that dedifferentiated LS follow separate tumourigenic pathways and that genetic analysis is important to unravel these differences.
    Keywords: Liposarcoma ; Comparative genomic hybridization ; Genomic profiling ; Cluster analysis
    ISSN: 0945-6317
    E-ISSN: 1432-2307
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  • 8
    Language: English
    In: Cancer research, 01 July 2018, Vol.78(13), pp.3619-3633
    Description: Nuclear factor of activated T cells 1 (NFATc1) is a transcription factor activated by T-cell receptor (TCR) and Ca signaling that affects T-cell activation and effector function. Upon tumor antigen challenge, TCR and calcium-release-activated channels are induced, promoting NFAT dephosphorylation and translocation into the nucleus. In this study, we report a progressive decrease of NFATc1 in lung tumor tissue and in tumor-infiltrating lymphocytes (TIL) of patients suffering from advanced-stage non-small cell lung cancer (NSCLC). Mice harboring conditionally inactivated NFATc1 in T cells (NFATc1) showed increased lung tumor growth associated with impaired T-cell activation and function. Furthermore, in the absence of NFATc1, reduced IL2 influenced the development of memory CD8 T cells. We found a reduction of effector memory and CD103 tissue-resident memory (TRM) T cells in the lung of tumor-bearing NFATc1 mice, underlining an impaired cytotoxic T-cell response and a reduced TRM tissue-homing capacity. In CD4ICOS T cells, programmed cell death 1 (PD-1) was induced in the draining lymph nodes of these mice and associated with lung tumor cell growth. Targeting PD-1 resulted in NFATc1 induction in CD4 and CD8 T cells in tumor-bearing mice and was associated with increased antitumor cytotoxic functions. This study reveals a role of NFATc1 in the activation and cytotoxic functions of T cells, in the development of memory CD8 T-cell subsets, and in the regulation of T-cell exhaustion. These data underline the indispensability of NFATc1 for successful antitumor immune responses in patients with NSCLC. The multifaceted role of NFATc1 in the activation and function of T cells during lung cancer development makes it a critical participant in antitumor immune responses in patients with NSCLC. .
    Keywords: Cytotoxicity ; Activation ; Mice ; Calcium Signalling ; Cancer ; Cytotoxicity ; Mice ; Exhaustion ; Patients ; Antitumor Activity ; Cell Migration ; Differentiation (Biology) ; Calcium Channels ; Lymph Nodes ; Cd4 Antigen ; Nf-At Protein ; Homing ; Cell Activation ; Immunological Memory ; Interleukin 2 ; Lymphocytes ; T Cell Receptors ; Calcium ; Lymphocytes ; Cell Death ; Drainage ; Cd103 Antigen ; Tumors ; Cell Differentiation ; Lung Cancer ; Apoptosis ; T-Cell Receptor ; Cancer ; Memory Cells ; Tumor-Infiltrating Lymphocytes ; Lymphocytes ; Dephosphorylation ; Transcription Factors ; PD-1 Protein ; Lymph Nodes ; Cell Death ; Cd8 Antigen ; Translocation ; Icos Protein ; Lung Cancer ; Calcium Ions ; Immune Response ; Lymphocytes T ; Lungs ; Non-Small Cell Lung Carcinoma;
    ISSN: 00085472
    E-ISSN: 1538-7445
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  • 9
    In: Pathology, 2013, Vol.45(4), pp.388-392
    Description: AIMS:: The pathogenesis and classification of multicentric smooth muscle tumours with benign appearance and concurrent/metachronous uterine and peritoneal involvement is controversial and may on occasion be diagnostically challenging. Leiomyomatosis peritonealis disseminata (LPD) is a rare condition affecting women of reproductive age, characterised by the occurrence of multiple small peritoneal smooth muscle nodules with bland histology. METHODS:: We investigated a total of 12 uterine and seven concurrent/metachronous peritoneal smooth muscle nodules with benign appearance from two females for mutations in the mediator complex subunit 12 (MED12), which has recently been identified as the most frequent genetic aberration in uterine leiomyomas. RESULTS:: The first case harboured different MED12 mutations in the peritoneal nodules. Mutational status of peritoneal nodules was discordant with that of the uterine leiomyomas. The second case displayed the same MED12 mutation in all five peritoneal nodules, but this mutation was not detected in her current uterine leiomyomas. CONCLUSIONS:: Our results suggest that smooth muscle neoplasms with benign appearance of the primary and secondary müllerian system share a similar genetic background of MED12 mutation in combination with oestrogen dependency. Analysis of MED12 mutation status might be a valuable adjunct tool for the future classification of these sometimes diagnostically challenging multicentric tumours.
    Keywords: Leiomyomatosis Peritonealis Disseminata ; Med12 ; Uterine Leiomyoma;
    ISSN: 1465-3931
    ISSN: 00313025
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  • 10
    Language: English
    In: Nutrition Journal, Sept 17, 2014, Vol.13(1)
    Description: Gastrointestinal bleeding and iron deficiency anaemia may cause severe symptoms and may require extensive diagnostics and substantial amounts of health resources. This case report focuses on the clinical presentation of a 22 year old patient with recurrent gastrointestinal bleeding from multilocular non-healing ulcers of the stomach, duodenum and jejunum over a period of four years. Extensive gastroenterological and allergological standard diagnostic procedures showed benign ulcerative lesions with tissue eosinophilia, but no conclusive diagnosis. Multiple diagnostic procedures were performed, until finally, endoscopically guided segmental gut lavage identified locally produced, intestinal IgE antibodies by fluoro-enzyme-immunoassay. IgE antibody concentrations at the intestinal level were found to be more-fold increased for total IgE and food-specific IgE against nuts, rye flour, wheat flour, pork, beef and egg yolk compared with healthy controls. Thus, a diet eliminating these allergens was introduced along with antihistamines and administration of a hypoallergenic formula, which resulted in complete healing of the multilocular ulcers with resolution of gastrointestinal bleeding. All gastrointestinal lesions disappeared and total serum IgE levels dropped to normal within 9 months. The patient has been in remission now for more than two years. Eosinophilic gastroenteritis (EG) is well known to induce refractory ulcer disease. In this case, the mechanisms for intestinal damage and gastrointestinal bleeding were identified as local gastrointestinal type I allergy. Therefore, future diagnostics in EG should also be focused on the intestinal level as identification of causative food-specific IgE antibodies proved to be effective to induce remission in this patient. Keywords: Eosinophilic gastroenteritis (EG), Gastrointestinally mediated allergy (GMA), Refractory ulcer disease, Gastrointestinal bleeding, Seronegative food allergy
    Keywords: Antiulcer Agents ; Anemia
    ISSN: 1475-2891
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