26 results on '"Koelble K"'
Search Results
2. Kopplung des Romano-Ward-Syndroms an HLA- und Komplement-Haplotypen
- Author
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Gumbrecht, H., Kölble, K., Kalies, I., Druschky, K.-F., Djonlagic, H., Neundörfer, B., Kalden, J. R., and Weinmann, Hans-Martin, editor
- Published
- 1989
- Full Text
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3. Verbesserte In-vitro-Diagnostik der Allergie gegen die Schimmelpilze Alternaria tenuis und Cladosporium herbarum bei Kindern
- Author
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Zimmermann, T., Nüsslein, H. G., Baum, M., Fuchs, C., Kölble, K., Schmidt-Redemann, Burkhard, editor, and Gonda, Sandor, editor
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- 1987
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4. Bedeutung des Klasse-III-Antigen-Polymorphismus für die Ausprägung der Myasthenia gravis
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Gleißner, B., Kalies, I., Kölble, K., Mohr, C., Druschky, K.-F., Kalden, J., Fischer, Peter-Alexander, editor, Baas, Horst, editor, and Enzensberger, Wolfgang, editor
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- 1989
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5. Identification and functional characterization of the tumor suppressor gene ST18 on human chromosome 8Q11 implicated in the development of breast cancer
- Author
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Jandrig, B, Rejman Lipinski, A, Hinzmann, B, Seitz, S, Arnold, W, Micheel, B, Koelble, K, Schlag, PM, Scherneck, S, and Rosenthal, A
- Subjects
ddc: 610 - Published
- 2006
6. Wertigkeit der bioptischen Diagnostik in der Neurologie
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Koelble, K., additional, Herring, A., additional, and Keyvani, K., additional
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- 2013
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7. Minimally Invasive Resection of a Right Atrial Mass in a Cardiac Transplant Recipient: A Case Report
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Conradi, L., primary, Deuse, T., additional, Treede, H., additional, Seiffert, M., additional, Adam, M., additional, Koelble, K., additional, Costard-Jaeckle, A., additional, Wagner, F.M., additional, and Reichenspurner, H., additional
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- 2011
- Full Text
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8. Length variation within intron 2 of the human IL-1 receptor antagonist protein gene (IL1RN)
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Steinkasserer, A., primary, Koelble, K., additional, and Sim, R.B., additional
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- 1991
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9. Antinuclear antibody profiles in rheumatic diseases
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Kohleisen, B., primary, Kalies, I., additional, Koelble, K., additional, and Kalden, J.R., additional
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- 1987
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10. Central Retinal Artery Occlusion in Sneddon's Disease Associated With Antiphospholipid Antibodies
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Jonas, J., Kölble, K., Völcker, H.E., and Kalden, J.R.
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- 1986
- Full Text
- View/download PDF
11. Regional mapping of short tandem repeats on human chromosome 10: Cytochrome P450 gene CYP2E, D10S196, D10S220, and D10S225
- Author
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Koelble, K [Univ. of Oxford (United Kingdom)]
- Published
- 1993
12. Dysmorphic neurons as cellular source for phase-amplitude coupling in Focal Cortical Dysplasia Type II.
- Author
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Rampp S, Rössler K, Hamer H, Illek M, Buchfelder M, Doerfler A, Pieper T, Hartlieb T, Kudernatsch M, Koelble K, Peixoto-Santos JE, Blümcke I, and Coras R
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- Adolescent, Adult, Child, Child, Preschool, Epilepsy diagnostic imaging, Female, Humans, Male, Malformations of Cortical Development, Group I diagnostic imaging, Neurons pathology, Pilot Projects, Proof of Concept Study, Retrospective Studies, Electrodes, Implanted, Electroencephalography methods, Epilepsy physiopathology, Epilepsy surgery, Malformations of Cortical Development, Group I physiopathology, Malformations of Cortical Development, Group I surgery, Neurons physiology
- Abstract
Objective: Reliable localization of the epileptogenic zone is necessary for successful epilepsy surgery. Neurophysiological biomarkers include ictal onsets and interictal spikes. Furthermore, the epileptic network shows oscillations with potential localization value and pathomechanistic implications. The cellular origin of such markers in invasive EEG in vivo remains to be clarified., Methods: In the presented pilot study, surgical brain samples and invasive EEG recordings of seven patients with surgically treated Focal Cortical Dysplasia (FCD) type II were coregistered using a novel protocol. Dysmorphic neurons and balloon cells were immunohistochemically quantified. Evaluated markers included seizure onset, spikes, and oscillatory activity in delta, theta, gamma and ripple frequency bands, as well as sample entropy and phase-amplitude coupling between delta, theta, alpha and beta phase and gamma amplitude., Results: Correlations between histopathology and neurophysiology provided evidence for a contribution of dysmorphic neurons to interictal spikes, fast gamma activity and ripples. Furthermore, seizure onset and phase-amplitude coupling in areas with dysmorphic neurons suggests preserved connectivity is related to seizure initiation. Balloon cells showed no association., Conclusions: Phase-amplitude coupling, spikes, fast gamma and ripples are related to the density of dysmorphic neurons and localize the seizure onset zone., Significance: The results of our pilot study provide a new powerful tool to address the cellular source of abnormal neurophysiology signals to leverage current and novel biomarkers for the localization of epileptic activity in the human brain., Competing Interests: Disclosure of Conflicts of Interest None of the authors has any conflict of interest to disclose., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)
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- 2021
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13. A comprehensive clinico-pathological and genetic evaluation of bottom-of-sulcus focal cortical dysplasia in patients with difficult-to-localize focal epilepsy.
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Ying Z, Wang I, Blümcke I, Bulacio J, Alexopoulos A, Jehi L, Bingaman W, Gonzalez-Martinez J, Kobow K, Niestroj LM, Lal D, Koelble K, and Najm I
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- Adolescent, Adult, Electrocorticography, Epilepsies, Partial genetics, Epilepsies, Partial pathology, Epilepsies, Partial physiopathology, Humans, Magnetic Resonance Imaging, Malformations of Cortical Development genetics, Malformations of Cortical Development pathology, Malformations of Cortical Development physiopathology, Middle Aged, Neurosurgical Procedures, Outcome Assessment, Health Care, Young Adult, Epilepsies, Partial diagnosis, Malformations of Cortical Development diagnosis
- Abstract
We comprehensively studied the clinical presentation, stereo-EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug-resistant patients with difficult-to-localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS-FCD). We identified 10 patients with BOS-FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video-EEG monitoring. Brain MRI, including voxel-based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next-generation sequencing. Postsurgical follow-up was available in nine patients. BOS-FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS-FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next-generation sequencing analysis of DNA extracted from lesion-enriched (micro-dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow-up were completely seizure-free (Engel Class IA) after a mean follow-up period of six years. Our results confirm previous studies classifying difficult-to-localize BOS-FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra-deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.
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- 2019
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14. The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.
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Barry P, Vatsiou A, Spiteri I, Nichol D, Cresswell GD, Acar A, Trahearn N, Hrebien S, Garcia-Murillas I, Chkhaidze K, Ermini L, Huntingford IS, Cottom H, Zabaglo L, Koelble K, Khalique S, Rusby JE, Muscara F, Dowsett M, Maley CC, Natrajan R, Yuan Y, Schiavon G, Turner N, and Sottoriva A
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- Adult, Aged, Aged, 80 and over, Axilla pathology, Breast Neoplasms blood, Breast Neoplasms pathology, Clonal Evolution genetics, Female, Gene Expression Regulation, Neoplastic genetics, Humans, Lymph Nodes pathology, Lymphatic Metastasis pathology, Middle Aged, Neoplasm Proteins blood, Neoplasm Staging, Breast Neoplasms genetics, Circulating Tumor DNA blood, Lymph Nodes metabolism, Lymphatic Metastasis genetics
- Abstract
Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors. Experimental Design: In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing ( n = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA. Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. Clin Cancer Res; 24(19); 4763-70. ©2018 AACR ., (©2018 American Association for Cancer Research.)
- Published
- 2018
- Full Text
- View/download PDF
15. An Unusual Case of YWHAE-NUTM2A/B Endometrial Stromal Sarcoma With Confinement to the Endometrium and Lack of High-Grade Morphology.
- Author
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Attygalle AD, Vroobel K, Wren D, Barton DP, Hazell SJ, Cin PD, Koelble K, and McCluggage WG
- Subjects
- Biomarkers, Tumor analysis, Female, Humans, In Situ Hybridization, Fluorescence, Middle Aged, Real-Time Polymerase Chain Reaction, 14-3-3 Proteins genetics, Endometrial Neoplasms genetics, Endometrial Neoplasms pathology, Oncogene Fusion genetics, Sarcoma, Endometrial Stromal genetics, Sarcoma, Endometrial Stromal pathology
- Abstract
Endometrial stromal sarcoma (ESS) characterized by YWHAE-NUTM2A/B genetic fusion is a recently recognized entity that is classified as a high-grade (HG) ESS in the 2014 World Health Organization Classification. These are myoinvasive neoplasms and typically contain a monomorphous HG round-cell cyclinD1-positive component with or without an accompanying low-grade (LG) component that is only focally positive/negative for cyclinD1. We report a case of YWHAE-NUTM2A/B ESS in a 46-yr-old woman that showed a number of unusual histologic features, including being entirely confined to the endometrium with no myoinvasion or lymphovascular space invasion. The initial hysteroscopic biopsy showed a cyclinD1-positive classic LG ESS-like component which merged with a smaller cyclinD1 negative/focally positive fibroblastic component with no HG areas. YWHAE-NUTM2A/B genetic fusion was shown by real-time quantitative polymerase chain reaction and Sanger sequencing. In the subsequent hysterectomy specimen, the tumor was entirely confined to the endometrium and was largely composed of cellular and classic LG ESS-like areas (80%) which were strongly and diffusely positive for cyclinD1 and a focal fibroblastic component (20%) which was largely cyclinD1 negative. Despite the cellular areas showing mild nuclear enlargement, the entire tumor had a very low mitotic and proliferation index and showed strong and diffuse positivity for estrogen and progesterone receptors. The patient remains alive and well with no evidence of disease 14 mo following diagnosis. To our knowledge, this is the first reported case of YWHAE-NUTM2A/B ESS that is confined to the endometrium and which exhibits entirely LG morphology.
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- 2017
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16. Similarity and diversity of the tumor microenvironment in multiple metastases: critical implications for overall and progression-free survival of high-grade serous ovarian cancer.
- Author
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Heindl A, Lan C, Rodrigues DN, Koelble K, and Yuan Y
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- Adult, Aged, Aged, 80 and over, Cystadenocarcinoma, Serous pathology, Disease-Free Survival, Female, Humans, Middle Aged, Neoplasm Metastasis, Ovarian Neoplasms pathology, Prognosis, Cystadenocarcinoma, Serous mortality, Ovarian Neoplasms mortality, Tumor Microenvironment
- Abstract
The tumor microenvironment is pivotal in influencing cancer progression and metastasis. Different cells co-exist with high spatial diversity within a patient, yet their combinatorial effects are poorly understood. We investigate the similarity of the tumor microenvironment of 192 local metastatic lesions in 61 ovarian cancer patients. An ecologically inspired measure of microenvironmental diversity derived from multiple metastasis sites is correlated with clinicopathological characteristics and prognostic outcome. We demonstrate a high accuracy of our automated analysis across multiple sites. A low level of similarity in microenvironmental composition is observed between ovary tumor and corresponding local metastases (stromal ratio r = 0.30, lymphocyte ratio r = 0.37). We identify a new measure of microenvironmental diversity derived from Shannon entropy that is highly predictive of poor overall (p = 0.002, HR = 3.18, 95% CI = 1.51-6.68) and progression-free survival (p = 0.0036, HR = 2.83, 95% CI = 1.41-5.7), independent of and stronger than clinical variables, subtype stratifications based on single cell types alone and number of sites. Although stromal influence in ovary tumors is known to have significant clinical implications, our findings reveal an even stronger impact orchestrated by diverse cell types. Quantitative histology-based measures can further enable objective selection of patients who are in urgent need of new therapeutic strategies such as combinatorial treatments targeting heterogeneous tumor microenvironment.
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- 2016
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17. Beyond immune density: critical role of spatial heterogeneity in estrogen receptor-negative breast cancer.
- Author
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Nawaz S, Heindl A, Koelble K, and Yuan Y
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- 2015
- Full Text
- View/download PDF
18. An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer.
- Author
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Maley CC, Koelble K, Natrajan R, Aktipis A, and Yuan Y
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- Adult, Aged, Aged, 80 and over, Breast Neoplasms mortality, Ecosystem, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Models, Biological, Multivariate Analysis, Prognosis, Proportional Hazards Models, Receptor, ErbB-2 metabolism, Young Adult, Breast Neoplasms immunology, Lymphocytes, Tumor-Infiltrating immunology
- Abstract
Introduction: Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. Beyond abundance, the spatial organization of immune cells in relation to cancer cells may also have significant functional and clinical implications. However there is a lack of systematic methods to quantify spatial associations between immune and cancer cells., Methods: We applied ecological measures of species interactions to digital pathology images for investigating the spatial associations of immune and cancer cells in breast cancer. We used the Morisita-Horn similarity index, an ecological measure of community structure and predator-prey interactions, to quantify the extent to which cancer cells and immune cells colocalize in whole-tumor histology sections. We related this index to disease-specific survival of 486 women with breast cancer and validated our findings in a set of 516 patients from different hospitals., Results: Colocalization of immune cells with cancer cells was significantly associated with a disease-specific survival benefit for all breast cancers combined. In HER2-positive subtypes, the prognostic value of immune-cancer cell colocalization was highly significant and exceeded those of known clinical variables. Furthermore, colocalization was a significant predictive factor for long-term outcome following chemotherapy and radiotherapy in HER2 and Luminal A subtypes, independent of and stronger than all known clinical variables., Conclusions: Our study demonstrates how ecological methods applied to the tumor microenvironment using routine histology can provide reproducible, quantitative biomarkers for identifying high-risk breast cancer patients. We found that the clinical value of immune-cancer interaction patterns is highly subtype-specific but substantial and independent to known clinicopathologic variables that mostly focused on cancer itself. Our approach can be developed into computer-assisted prediction based on histology samples that are already routinely collected.
- Published
- 2015
- Full Text
- View/download PDF
19. Radiation-induced liver damage: correlation of histopathology with hepatobiliary magnetic resonance imaging, a feasibility study.
- Author
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Seidensticker M, Burak M, Kalinski T, Garlipp B, Koelble K, Wust P, Antweiler K, Seidensticker R, Mohnike K, Pech M, and Ricke J
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- Aged, Contrast Media, Feasibility Studies, Female, Humans, Image Enhancement, Liver ultrastructure, Male, Meglumine analogs & derivatives, Middle Aged, Organometallic Compounds, Brachytherapy adverse effects, Liver pathology, Liver radiation effects, Liver Neoplasms radiotherapy, Magnetic Resonance Imaging methods, Radiation Injuries diagnosis
- Abstract
Purpose: Radiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA)., Methods: Patients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined., Results: Fourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition., Conclusions: Absence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.
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- 2015
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20. [Biopsy diagnosis in neurology].
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Koelble K, Herring A, and Keyvani K
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- Animals, Autoimmune Diseases diagnosis, Autoimmune Diseases pathology, Brain pathology, Brain Neoplasms diagnosis, Brain Neoplasms pathology, Central Nervous System Bacterial Infections diagnosis, Central Nervous System Bacterial Infections pathology, Dementia diagnosis, Dementia pathology, Humans, Immunohistochemistry, Inflammation diagnosis, Inflammation pathology, Intraoperative Period, Microscopy, Electron, Muscle, Skeletal pathology, Nervous System Diseases pathology, Neurology, Biopsy, Nervous System Diseases diagnosis
- Published
- 2013
- Full Text
- View/download PDF
21. Ileus due to severe aggravation of retroperitoneal fibrosis after sigmoidectomy.
- Author
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Martins PN, Glanemann M, Koelble K, Weidemann H, and Neuhaus P
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- Adenocarcinoma complications, Anti-Inflammatory Agents therapeutic use, Humans, Ileus therapy, Male, Middle Aged, Reoperation, Retroperitoneal Fibrosis complications, Retroperitoneal Fibrosis therapy, Severity of Illness Index, Sigmoid Neoplasms complications, Treatment Outcome, Adenocarcinoma surgery, Colectomy adverse effects, Ileus etiology, Retroperitoneal Fibrosis etiology, Sigmoid Neoplasms surgery
- Published
- 2008
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22. Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma.
- Author
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Schmitt-Graeff A, Ertelt-Heitzmann V, Allgaier HP, Olschewski M, Nitschke R, Haxelmans S, Koelble K, Behrens J, and Blum HE
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Cell Nucleus metabolism, Cell Nucleus pathology, Child, Cytoskeletal Proteins metabolism, Female, Fluorescent Antibody Technique, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Ki-67 Antigen metabolism, Liver Neoplasms mortality, Liver Neoplasms pathology, Lymphoid Enhancer-Binding Factor 1, Male, Microscopy, Confocal, Middle Aged, Survival Rate, Trans-Activators metabolism, beta Catenin, Carcinoma, Hepatocellular metabolism, Cyclin D1 metabolism, DNA-Binding Proteins metabolism, Liver Neoplasms metabolism, Transcription Factors metabolism
- Abstract
Background: While the Wnt pathway has been widely implicated in hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of beta-catenin-lymphoid enhancer factor-1 (LEF-1)/T-cell factor (TCF) signaling is controversely discussed., Methods: By immunohistochemical analyses we studied the subcellular localization of LEF-1/TCF and cyclin D1 in 162 hepatocellular carcinoma (HCC). Single- and double-label imaging by brightfield and confocal laser scanning microscopy was quantitated and correlated with beta-catenin, the Ki67(+) proliferation fraction (PF), tumor size, grade, the Okuda stage and patient survival., Results: The frequency of nuclear cyclin D1 expression was 28% and closely correlated with LEF-1/TCF (P<0.0001) and the Ki67(+) PF (P=0.03). Nuclear LEF-1/TCF expression was observed in 52% of all cases, but was also present in 42% of cyclin D1(-) cases. Nuclear beta-catenin was identified in 37% of all HCCs and correlated with LEF-1/TCF (P=0.04). The expression of cyclin D1, LEF-1/TCF or beta-catenin did not correlate with other clinico-pathological data., Conclusions: A large proportion of HCCs does not appear to be linked to a deregulation of cyclin D1. However, the coordinated expression of cyclin D1 and LEF-1/TCF in some cases suggests the role of cyclin D1 as a Wnt target gene in a subset of HCCs.
- Published
- 2005
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23. ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2.
- Author
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Jandrig B, Seitz S, Hinzmann B, Arnold W, Micheel B, Koelble K, Siebert R, Schwartz A, Ruecker K, Schlag PM, Scherneck S, and Rosenthal A
- Subjects
- Animals, Base Sequence, Breast Neoplasms pathology, Cell Line, Tumor, DNA Methylation, DNA Primers, Humans, In Situ Hybridization, Fluorescence, Loss of Heterozygosity, Mice, Promoter Regions, Genetic, RNA, Messenger genetics, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Subcellular Fractions metabolism, Breast Neoplasms genetics, Chromosomes, Human, Pair 8, DNA-Binding Proteins genetics, Genes, Tumor Suppressor
- Abstract
We have identified a gene, ST18 (suppression of tumorigenicity 18, breast carcinoma, zinc-finger protein), within a frequent imbalanced region of chromosome 8q11 as a breast cancer tumor suppressor gene. The ST18 gene encodes a zinc-finger DNA-binding protein with six fingers of the C2HC type (configuration Cys-X5-Cys-X12-His-X4-Cys) and an SMC domain. ST18 has the potential to act as transcriptional regulator. ST18 is expressed in a number of normal tissues including mammary epithelial cells although the level of expression is quite low. In breast cancer cell lines and the majority of primary breast tumors, ST18 mRNA is significantly downregulated. A 160 bp region within the promoter of the ST18 gene is hypermethylated in about 80% of the breast cancer samples and in the majority of breast cancer cell lines. The strong correlation between ST18 promoter hypermethylation and loss of ST18 expression in tumor cells suggests that this epigenetic mechanism is responsible for tumor-specific downregulation. We further show that ectopic ST18 expression in MCF-7 breast cancer cells strongly inhibits colony formation in soft agar and the formation of tumors in a xenograft mouse model.
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- 2004
- Full Text
- View/download PDF
24. Cellular retinol-binding protein-1 in hepatocellular carcinoma correlates with beta-catenin, Ki-67 index, and patient survival.
- Author
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Schmitt-Gräff A, Ertelt V, Allgaier HP, Koelble K, Olschewski M, Nitschke R, Bochaton-Piallat ML, Gabbiani G, and Blum HE
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- Carcinoma, Hepatocellular chemistry, Carcinoma, Hepatocellular mortality, Cytoplasm metabolism, Esterification, Gene Expression Regulation, Neoplastic, Humans, Liver chemistry, Liver physiology, Liver Cirrhosis physiopathology, Liver Neoplasms chemistry, Liver Neoplasms mortality, Proto-Oncogene Proteins physiology, Retinoids physiology, Retinol-Binding Proteins metabolism, Retinol-Binding Proteins, Cellular, Signal Transduction physiology, Survival Rate, Vitamin A metabolism, Wnt Proteins, beta Catenin, Carcinoma, Hepatocellular physiopathology, Cytoskeletal Proteins analysis, Ki-67 Antigen analysis, Liver Neoplasms physiopathology, Retinol-Binding Proteins genetics, Trans-Activators analysis, Zebrafish Proteins
- Abstract
The cellular retinol-binding protein-1 (CRBP-1) plays a key role in the esterification and intercellular transfer of retinol. By in situ hybridization, immunohistochemistry, and confocal laser scanning microscopy (CLSM), we show that, in normal liver, CRBP-1 is strongly expressed in the cytoplasm of hepatic stellate cells (HSCs) and myofibroblasts (MFs) with only low CRBP-1 levels in hepatocytes. By contrast, in 196 hepatocellular carcinoma (HCC) specimens CRBP-1 expression in MFs was down-regulated in 83%. Patients with high CRBP-1 expression in MFs had a significantly higher 2-year survival as compared with patients with low CRBP-1 expression (52% vs. 29%, respectively; P =.034). An aberrant nuclear CRBP-1 accumulation resulting from cytoplasmic invagination was found in 29% of HCCs. Nuclear CRBP-1 staining correlated positively with a favorable tumor stage (Okuda stage I; P =.01) and negatively with the Ki-67(+) proliferation fraction (PF). A Ki-67(+) PF of > or =10% was associated with a lower 2-year survival probability as compared with patients with a Ki-67(+) PF of <10% (12% vs. 40%, respectively; P =.015). Prognosis did not correlate with the nuclear beta-catenin expression. There was, however, a close correlation between nuclear CRBP-1 inclusions and nuclear beta-catenin staining in HCCs (P =.008), suggesting a cross talk between CRBP-1 and the Wnt/wingless signal transduction pathway. In conclusion, our findings demonstrate that CRBP-1 detection may be useful for the discrimination between nonneoplastic and neoplastic liver cells and suggest that modulation of CRBP-1 expression in HCCs contributes to tumor growth and progression via retinoid-mediated signaling and disruption of cellular vitamin A homeostasis.
- Published
- 2003
- Full Text
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25. Microsatellite Instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer.
- Author
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Salahshor S, Koelble K, Rubio C, and Lindblom A
- Subjects
- Adaptor Proteins, Signal Transducing, Carrier Proteins, Colorectal Neoplasms metabolism, Colorectal Neoplasms, Hereditary Nonpolyposis metabolism, DNA Methylation, DNA, Neoplasm chemistry, Gene Expression Regulation, Neoplastic, Germ-Line Mutation, Humans, Immunohistochemistry, MutL Protein Homolog 1, MutS Homolog 2 Protein, Neoplasm Proteins biosynthesis, Neoplasm Proteins immunology, Nuclear Proteins, Promoter Regions, Genetic, Proto-Oncogene Proteins biosynthesis, Proto-Oncogene Proteins immunology, Tumor Cells, Cultured, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, DNA-Binding Proteins, Microsatellite Repeats, Neoplasm Proteins genetics, Proto-Oncogene Proteins genetics
- Abstract
Immunohistochemical expression analysis of mismatch repair gene products has been suggested for the prediction of hereditary nonpolyposis colorectal cancer (HNPCC) carrier status in cancer families and the selection of microsatellite instability (MSI)-positive tumors in sporadic colorectal cancer. In this study, we aimed to evaluate hMSH2 and hMLH1 immunohistochemistry in familial and sporadic colorectal cancer. We found that immunohistochemistry allowed us to identify patients with germline mutations in hMSH2 and many cases with germline mutations in hMLH1. However, some missense and truncating mutations may be missed. In addition, hMLH1 promoter methylation, commonly occurring in familial and sporadic MSI-positive colorectal cancer, can complicate the interpretation of immunohistochemical expression analyses. Our results suggest that immunohistochemistry cannot replace testing for MSI to predict HNPCC carrier status or identify MSI-positive sporadic colorectal cancer.
- Published
- 2001
- Full Text
- View/download PDF
26. Microsatellite instability analysis: a multicenter study for reliability and quality control.
- Author
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Bocker T, Diermann J, Friedl W, Gebert J, Holinski-Feder E, Karner-Hanusch J, von Knebel-Doeberitz M, Koelble K, Moeslein G, Schackert HK, Wirtz HC, Fishel R, and Rüschoff J
- Subjects
- Chromosome Deletion, Clinical Laboratory Techniques standards, Colorectal Neoplasms classification, Genetic Techniques standards, Humans, Quality Control, Reproducibility of Results, Colorectal Neoplasms genetics, Microsatellite Repeats genetics
- Abstract
The molecular biology section of the Hereditary Non-Polyposis Colorectal Cancer study group-Germany, instituted a multicenter study to test the reliability and quality of microsatellite instability (MSI) analysis. Eight laboratories compared MSI analyses performed on 10 matched pairs of normal and tumor DNA from patients with colorectal carcinomas. A variety of techniques were applied to the detection of microsatellite changes: (a) silver and ethidium bromide staining of polyacrylamide gels; (b) radioactive labeling; and (c) automated fluorescence detection. The identification of highly unstable tumors and tumors without MSI was achieved in high concordance. However, the interpretation of the band patterns resulted in divergent classifications at several microsatellite marker loci for a large fraction of this tumor/normal panel. The data on more than 30 primers per case suggest that the enlargement of the microsatellite panel to more than 10 loci does not influence the results. In this study, cases with MSI in less than 10% of loci were classified as microsatellite stable, whereas MSI was diagnosed in cases with more than 40% of all markers unstable. We propose that a panel of five microsatellite loci consisting of repeats with different lengths should be analyzed in an initial analysis. When less than two marker loci display shifts in the microsatellite bands from tumor DNA, the panel should be enlarged to include an additional set of five marker loci. The number of marker loci analyzed as well as the number of unstable marker loci found should always be identified. These criteria should result in reports of MSI that are more comparable between studies.
- Published
- 1997
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