100 results on '"Prall, Friedrich"'
Search Results
2. High mutational burden in colorectal carcinomas with monoallelic POLE mutations: absence of allelic loss and gene promoter methylation
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Hühns, Maja, Nürnberg, Sylvia, Kandashwamy, Krishna Kumar, Maletzki, Claudia, Bauer, Peter, and Prall, Friedrich
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- 2020
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3. NSG mice as hosts for oncological precision medicine
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Maletzki, Claudia, Bock, Stephanie, Fruh, Philipp, Macius, Karolis, Witt, Anika, Prall, Friedrich, and Linnebacher, Michael
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- 2020
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4. Engraftment Efficiency after Intra–Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model
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Lange, Sandra, Steder, Anne, Killian, Doreen, Knuebel, Gudrun, Sekora, Anett, Vogel, Heike, Lindner, Iris, Dunkelmann, Simone, Prall, Friedrich, Murua Escobar, Hugo, Freund, Mathias, and Junghanss, Christian
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- 2017
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5. Bronchoalveolar lavage for the diagnosis of Pulmonary Langerhans cell histiocytosis
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Lommatzsch, Marek, Bratke, Kai, Stoll, Paul, Mülleneisen, Norbert, Prall, Friedrich, Bier, Andrea, and Virchow, J. Christian
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- 2016
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6. Establishment, characterization, and drug screening of low-passage patient individual non-small cell lung cancer in vitro models including the rare pleomorphic subentity.
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Andus, Ingo, Prall, Friedrich, Linnebacher, Michael, and Linnebacher, Christina S.
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NON-small-cell lung carcinoma ,LINCRNA ,GENETICS ,MEDICAL screening ,IMMUNOMODULATORS - Abstract
Introduction: For pre-clinical drug development and precision oncology research, robust cancer cell models are essential. Patient-derived models in low passages retain more genetic and phenotypic characteristics of their original tumors than conventional cancer cell lines. Subentity, individual genetics, and heterogeneity greatly influence drug sensitivity and clinical outcome. Materials and methods: Here, we report on the establishment and characterization of three patient-derived cell lines (PDCs) of different subentities of non-small cell lung cancer (NSCLC): adeno-, squamous cell, and pleomorphic carcinoma. The in-depth characterization of our PDCs included phenotype, proliferation, surface protein expression, invasion, and migration behavior as well as whole-exome and RNA sequencing. Additionally, in vitro drug sensitivity towards standard-of-care chemotherapeutic regimens was evaluated. Results: The pathological and molecular properties of the patients' tumors were preserved in the PDC models HROLu22, HROLu55, and HROBML01. All cell lines expressed HLA I, while none were positive for HLA II. The epithelial cell marker CD326 and the lung tumor markers CCDC59, LYPD3, and DSG3 were also detected. The most frequently mutated genes included TP53, MXRA5, MUC16, and MUC19. Among the most overexpressed genes in tumor cells compared to normal tissue were the transcription factors HOXB9, SIM2, ZIC5, SP8, TFAP2A, FOXE1, HOXB13, and SALL4; the cancer testis antigen CT83; and the cytokine IL23A. The most downregulated genes on the RNA level encode the long noncoding RNA LANCL1-AS1, LINC00670, BANCR, and LOC100652999; the regulator of angiogenesis ANGPT4; the signaling molecules PLA2G1B and RS1; and the immune modulator SFTPD. Furthermore, neither pre-existing therapy resistances nor drug antagonistic effects could be observed. Conclusion: In summary, we successfully established three novel NSCLC PDC models from an adeno-, a squamous cell, and a pleomorphic carcinoma. Of note, NSCLC cell models of the pleomorphic subentity are very rare. The detailed characterization including molecular, morphological, and drug-sensitivity profiling makes these models valuable pre-clinical tools for drug development applications and research on precision cancer therapy. The pleomorphic model additionally enables research on a functional and cell-based level of this rare NCSLC subentity. [ABSTRACT FROM AUTHOR]
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- 2023
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7. The PD‐1 expressing immune phenotype of T cell exhaustion is prominent in the ‘immunoreactive’ microenvironment of colorectal carcinoma
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Prall, Friedrich and Hühns, Maja
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- 2017
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8. IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom
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Stockhammer, Florian, Misch, Martin, Helms, Hans-Joachim, Lengler, Ulrike, Prall, Friedrich, von Deimling, Andreas, and Hartmann, Christian
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- 2012
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9. HROP68: A rare case of medullary pancreatic cancer-characterization and chemosensitivity of the first patient-derived cell line.
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von den Driesc, Jens, Flöttmann, Jana, Prall, Friedrich, Mullins, Christina S., Linnebacher, Michael, and Bürtin, Florian
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Introduction: Medullary pancreatic carcinoma (MPC) is a rare subtype of pancreatic ductal adenocarcinoma. MPCs represent less than 1% of all pancreatic cancers, and, with only 26 cases in the literature, knowledge regarding drug response and treatment outcome is very limited. Material and methods: We present the case of a 64-year-old male patient with MPC who was treated by left pancreatic resection and adjuvant chemotherapy. Due to local recurrence, the patient underwent intended curative reoperation. From both surgical specimens, patient-derived xenografts (PDXs) and, from the recurrence, a patient-derived cell line (PDCL) were established. We subsequently performed an in-depth characterization of this cell line including phenotypic characterization, surface protein expression, growth, and migratory performance as well as mutational analysis using whole-exome sequencing (WES). Additionally, in vitro drug sensitivity toward the standard-of-care chemotherapeutic regimen and selected targeted therapies was evaluated. Results: The pathological and molecular properties of this rare MPC case observed in the patient's tumors are preserved in the corresponding PDX and the PDCL of HROP68Tu2. Despite displaying an "immunogenic phenotype" with marked T-cell infiltration and a high-level expression of HLA II and Programmed death-ligand 1 (PD-L1), molecular analysis revealed microsatellite stability but a multitude of mutations affecting KRAS, TP53, KAT6B, FOXG1, RUNX1, and GRIK2 among others. Furthermore, HROP68Tu2 cells were susceptible toward 5-FU, irinotecan, oxaliplatin, gemcitabine, paclitaxel, and erlotinib as single agents, but only a moderate synergistic response was seen to the drugs of the FOLFIRINOX regimen. Even worse, the drugs of the two combinations gemcitabine plus paclitaxel and gemcitabine plus erlotinib showed antagonistic effects. Moreover, lapatinib, PRIMA-Met1, and olaparib selected as targeted therapeutics according to the mutational profiles and protein expression inhibited HROP68Tu2 cells' growth. Conclusion: This study illustrates the establishment of the first preclinical MPC models as well as the first in-depth characterization of an MPC PDCL. Since the scientific and clinical knowledge of this rare pancreatic cancer type is very limited, the presented models contribute to a better understanding of MPC and might be a valuable tool for the development of future treatment options. [ABSTRACT FROM AUTHOR]
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- 2023
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10. The “North German Tumor Bank of Colorectal Cancer”: status report after the first 2 years of support by the German Cancer Aid Foundation
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Oberländer, Martina, Linnebacher, Michael, König, Alexandra, Bogoevska, Valentina, Brodersen, Christiane, Kaatz, Regina, Krohn, Mathias, Hackmann, Michael, Ingenerf, Josef, Christoph, Jan, Mate, Sebastian, Prokosch, Hans-Ulrich, Yekebas, Emre F., Thorns, Christoph, Büning, Jürgen, Prall, Friedrich, Uhlig, Ria, Roblick, Uwe J., Izbicki, Jakob R., Klar, Ernst, Bruch, Hans-Peter, Vollmar, Brigitte, Habermann, Jens K., and On behalf of the ColoNet consortium
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- 2013
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11. Postoperative Chemotherapy May Not Be Necessary for Patients With ypN0-Category After Neoadjuvant Chemoradiotherapy of Rectal Cancer
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Fietkau, Rainer, Barten, Malte, Klautke, Gunther, Klar, Ernst, Ludwig, Kaja, Thomas, Hartmut, Brinckmann, Wolfgang, Friedrich, Andreas, Prall, Friedrich, Hartung, Gernot, Küchenmeister, Ute, and Kundt, Gunther
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- 2006
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12. Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’
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Prall, Friedrich, Maletzki, Claudia, and Linnebacher, Michael
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- 2012
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13. R1 resection in pancreatic cancer has significant impact on long-term outcome in standardized pathology modified for routine use
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Rau, Bettina M., Moritz, Katharina, Schuschan, Sarah, Alsfasser, Guido, Prall, Friedrich, and Klar, Ernst
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- 2012
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14. Aggressive colorectal carcinoma phenotypes of invasion can be assessed reproducibly and effectively predict poor survival: interobserver study and multivariate survival analysis of a prospectively collected series of 299 patients after potentially curative resections with long-term follow-up
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Wöhlke, Michael, Schiffmann, Leif, and Prall, Friedrich
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- 2011
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15. Rigid confocal endoscopy for in vivo imaging of experimental oral squamous intra-epithelial lesions
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Farahati, Behnaz, Stachs, Oliver, Prall, Friedrich, Stave, Joachim, Guthoff, Rudolf, Pau, Hans Wilhelm, and Just, Tino
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- 2010
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16. Hemophagocytic Lymphohistiocytosis And Kawasaki Disease: Combined Manifestation And Differential Diagnosis
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Titze, Ulf, Janka, Gritta, Schneider, Marion E., Prall, Friedrich, Haffner, Dieter, and Classen, Carl Friedrich
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- 2009
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17. Tumour regression and mesorectal lymph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum
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PRALL, FRIEDRICH, WÖHLKE, MICHAEL, KLAUTKE, GUNTHER, SCHIFFMANN, LEIF, FIETKAU, RAINER, and BARTEN, MALTE
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- 2006
18. Seltene Ursache für unspezifische Beschwerden im Bereich des rechten Kniegelenks.
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Jiménez, Alba Antón, Prall, Friedrich, Saß, Marko, and Weber, Marc-André
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- 2021
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19. A novel sialyl LeX expression score as a potential prognostic tool in colorectal cancer
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Schiffmann Leif, Schwarz Fabian, Linnebacher Michael, Prall Friedrich, Pahnke Jens, Krentz Helga, Vollmar Brigitte, and Klar Ernst
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Colorectal cancer ,prognosis ,sialyl Le X ,tumor staging ,Surgery ,RD1-811 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Treatment decisions in colorectal cancer subsequent to surgery are based mainly on the TNM system. There is a need to establish novel prognostic markers based on the molecular characterization of tumor cells. Evidence exists that sialyl LeX expression is correlated with an unfavorable outcome in colorectal cancer. The aim of this study was to establish a simple sialyl LeX staining score and to determine a potential correlation with the prognosis in a series of advanced colorectal carcinoma patients. Methods In order to implement routine use of sialyl LeX immunohistology, we established a new, easily reproducible score and defined a cutoff which discriminated groups with better or worse outcome, respectively. We then correlated sialyl LeX expression of 215 UICC stage III and IV patients with disease-free and cancer-related survival. Results A five-stage score could be established based on automated immunohistochemical stainings. Using a statistical model, we calculated a cutoff to discriminate between weak and strong staining positivity of sialyl LeX. Patients with strong positive specimens had a worse cancer-related survival (P = 0.004) but no difference was observed for disease-free survival (P = 0.352). Conclusions These results demonstrate a strong correlation between high sialyl LeX-expression in colorectal carcinomas and cancer-related survival. Our highly standardized and easy-to-use staining score is suitable for routine use and hence it could be recommended to evaluate sialyl LeX-expression as part of the standard histopathological analysis of colorectal carcinomas and to validate the score prospectively based on a larger population.
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- 2012
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20. Cryopreservation of human colorectal carcinomas prior to xenografting
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Krohn Mathias, Klier Ulrike, Ostwald Christiane, Maletzki Claudia, Linnebacher Michael, Klar Ernst, and Prall Friedrich
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Methods Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Results Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Conclusions Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research.
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- 2010
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21. Cancer in a bang: panel next‐generation gene sequencing and OncoScan array analysis of a minute colorectal adenocarcinoma and its precursor adenoma.
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Hühns, Maja, Holzmann, Carsten, and Prall, Friedrich
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ADENOMATOUS polyps ,ADENOCARCINOMA ,CANCER ,GENES - Abstract
We found five gene mutations in the adenoma, all of which were also present in the carcinoma (KIT, FBXW7, APC, PTPN11, KRAS), and there was also a PDGFRA and a second KIT gene mutation in the carcinoma. List of gene mutations detected in the adenoma and in the carcinoma samples Regarding intratumoral heterogeneity, the PDGFRA mutation was found only in two of the three carcinoma samples, and at low variant allele frequency (the mutations were confirmed by Sanger resequencing). [Extracted from the article]
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- 2019
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22. Suspected Hereditary Cancer Syndromes in Young Patients: Heterogeneous Clinical and Genetic Presentation of Colorectal Cancers.
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Maletzki, Claudia, Hühns, Maja, Bauer, Ingrid, Prall, Friedrich, Junghanss, Christian, and Henze, Larissa
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AGE factors in disease ,COLON tumors ,GENETIC disorders ,METASTASIS ,GENETIC mutation ,RECTUM tumors ,TUMOR classification ,GENETIC testing ,DISEASE prevalence ,HEALTH literacy ,FAMILY history (Medicine) ,HEREDITARY cancer syndromes ,DISEASE risk factors ,ADULTS ,TUMOR risk factors ,CANCER risk factors - Abstract
Colorectal cancer (CRC) is rare in young patients without a confirmed family history of cancer. Reports of an increased prevalence of POLD1/POLE mutations in young patients with colorectal cancer have raised awareness and support routine genetic testing for patients with early‐onset tumors. In cases of CRC without proven MMR‐germline mutation, molecular analyses are warranted to confirm or rule out other familial CRC syndromes. This article describes the cases of two young male patients, who presented with locally advanced and metastatic CRC, and reports the results of the germline mutational analyses done for both patients. These cases demonstrate the importance of special care and molecular diagnostic procedures for young patients with CRC. Key Points: Patients with colorectal cancer who are younger than 50 years at initial diagnosis (early onset) should routinely undergo genetic testing.Early‐ and very‐early‐onset patients (younger than 40 years) with absence of microsatellite instability should be considered for tumor mutation burden testing and/or DNA polymerase proofreading mutation.The mutational signature of HSP110 within mismatch repair deficiency‐related tumors may help to identify patients likely to benefit from 5‐fluorouracil‐based chemotherapy.Intensified, maintained, and specific surveillance may help to reduce secondary tumor progression. This article describes the clinic‐pathological and molecular features of two young male patients, who presented with locally advanced and metastatic colorectal cancer. These cases show the importance of the special care and molecular diagnostic procedures needed for young patients. [ABSTRACT FROM AUTHOR]
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- 2019
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23. 'Null-pattern' mismatch repair enzyme immunostaining in a sporadic microsatellite-unstable colorectal carcinoma with biallelic somatic MSH6 gene aberrations.
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Hühns, Maja and Prall, Friedrich
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COLORECTAL cancer , *GENES , *IMMUNOSTAINING , *CELL adhesion molecules , *SOFT tissue tumors , *DNA mismatch repair - Abstract
Sanger sequencing electropherograms showing codons 1086, 1087 and 1088 ofMSH6with non-tumour DNA obtained from mucosa (top), tumour DNA obtained from whole tissue sections (middle), and tumour DNA enriched by laser-capture microdissection (bottom). "Null-pattern" mismatch repair enzyme immunostaining in a sporadic microsatellite-unstable colorectal carcinoma with biallelic somatic MSH6 gene aberrations. Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. "Null-pattern" mismatch repair enzyme immunostaining in a sporadic microsatellite-unstable colorectal carcinoma with biallelic somatic MSH6 gene aberrations DOI: 10.1111/his.14255 © 2020 John Wiley & Sons Ltd Sir: Sporadic microsatellite-unstable colorectal carcinomas are readily recognised as a unique type of colorectal carcinoma by surgical pathologists. [Extracted from the article]
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- 2021
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24. Colorectal carcinoma tumour budding and podia formation in the xenograft microenvironment.
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Prall, Friedrich, Maletzki, Claudia, Hühns, Maja, Krohn, Mathias, and Linnebacher, Michael
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COLON cancer , *TUMOR budding , *XENOGRAFTS , *CANCER cells , *SURGICAL pathology , *IMMUNOHISTOCHEMISTRY - Abstract
Tumour budding and podia formation are well-appreciated in surgical pathology as an aggressive invasion phenotype of colorectal carcinoma cells that is attained in the microenvironment of the invasive margin. In this study, we addressed how tumour budding and podia formation feature in xenografts. Primary colorectal carcinomas (N = 44) of various molecular types (sporadic standard type, high-degree microsatellite-unstable, CpG island methylator phenotype) were transplanted subcutaneously into T and B cell-deficient NSG mice, making possible immunohistochemistry with routine surgical pathology antibodies. Tumor budding and podia formation were both appreciably present in the xenografts. Quantitative evaluations of cytokeratin immunostains of primaries and their corresponding xenografts showed a reduction of tumour buds in the xenografts. Furthermore, in xenografts tumour cells were completely negative by pSTAT3 immunohistochemistry, indicating absence of cytokine/chemokine signalling, but nuclear β-catenin and SMAD4 immunostainings as read-out of wnt and BMP pathway activation, respectively, were maintained. Carcinoma cells in most xenografts retained immunostaining of at least some nuclei by immunohistochemistry with antibodies against pERK1/2. K-ras/B-raf mutational status did not correlate with tumour budding or podia formation in the xenografts. Our results indicate that tumour budding and podia formation can be modelled by xenografting, and in NSG mice it can be studied with the same immunohistochemical methods as used for primaries in surgical pathology. Dysregulation of wnt and BMP signalling appears to be transferred into the xenograft microenvironment, but not cytokine/chemokine signalling. [ABSTRACT FROM AUTHOR]
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- 2017
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25. Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair-deficiency and Lynch syndrome.
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Maletzki, Claudia, Huehns, Maja, Bauer, Ingrid, Ripperger, Tim, Mork, Maureen M., Vilar, Eduardo, Klöcking, Sabine, Zettl, Heike, Prall, Friedrich, and Linnebacher, Michael
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- 2017
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26. Tumor Take Rate Optimization for Colorectal Carcinoma Patient-Derived Xenograft Models.
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Gock, Michael, Kühn, Florian, Mullins, Christina Susanne, Krohn, Mathias, Prall, Friedrich, Klar, Ernst, and Linnebacher, Michael
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ADENOCARCINOMA ,CANCER treatment ,RECTUM tumors ,ANIMAL experimentation ,COLON tumors ,BIOLOGICAL models ,CELL culture ,CELL physiology ,CHI-squared test ,CRYOPRESERVATION of organs, tissues, etc. ,RESEARCH methodology ,MICE ,POLYMERASE chain reaction ,PROBABILITY theory ,STAINS & staining (Microscopy) ,TISSUE culture ,XENOGRAFTS ,DATA analysis software ,DESCRIPTIVE statistics ,CANCER cell culture ,GENETICS ,TUMOR treatment - Abstract
Background. For development of individualized treatment on a routine basis, transfer of patients’ tumor tissue in a xenograft model (i.e., generation of patient-derived xenografts (PDX)) is desirable for molecular, biochemical, or functional analyses. Drawbacks are dissatisfactory tumor take rates, the necessity of fast tumor tissue processing, and extensive logistics demanding teamwork of surgeons, pathologists, and laboratory researchers. Methods. The take rates of ten colorectal cancer (CRC) tissue samples in immunodeficient mice were compared after direct cryopreservation and after a 24 h cooling period at 4°C prior to cryopreservation. Additionally, the effect of simultaneous Matrigel application on the take rates was investigated. Beside take rates, tumor growth characteristics and cell culture success were analyzed. Results. Tumor takes of CRC tissue samples were significantly improved after Matrigel application (8 versus 15 takes, p=0.04). As expected, they diminished furthermore after 24 h cooling. Application of Matrigel could counteract this decrease significantly (2 versus 7 takes, p=0.03). Cumulative take rate after cryopreservation was satisfactory (70%). Conclusion. Matrigel application after 24 h delay in tissue processing facilitates CRC PDX model development. These data help developing strategies for individualized tumor therapies in the context of multicenter clinical studies and for basic research on primary patient tumors. [ABSTRACT FROM AUTHOR]
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- 2016
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27. Functional Characterization and Drug Response of Freshly Established Patient-Derived Tumor Models with CpG Island Methylator Phenotype.
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Maletzki, Claudia, Huehns, Maja, Knapp, Patrick, Waukosin, Nancy, Klar, Ernst, Prall, Friedrich, and Linnebacher, Michael
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CPG nucleotides ,PHENOTYPES ,GENETIC translation ,COLON cancer ,DNA fingerprinting - Abstract
Patient-individual tumor models constitute a powerful platform for basic and translational analyses both in vitro and in vivo. However, due to the labor-intensive and highly time-consuming process, only few well-characterized patient-derived cell lines and/or corresponding xenografts exist. In this study, we describe successful generation and functional analysis of novel tumor models from patients with sporadic primary colorectal carcinomas (CRC) showing CpG island methylator phenotype (CIMP). Initial DNA fingerprint analysis confirmed identity with the patient in all four cases. These freshly established cells showed characteristic features associated with the CIMP-phenotype (HROC40: APC
wt , TP53mut , KRASmut ; 3/8 marker methylated; HROC43: APCmut , TP53mut , KRASmut ; 4/8 marker methylated; HROC60: APCwt , TP53mut , KRASwt ; 4/8 marker methylated; HROC183: APCmut , TP53mut , KRASmut ; 6/8 marker methylated). Cell lines were of epithelial origin (EpCAM+ ) with distinct morphology and growth kinetics. Response to chemotherapeutics was quite individual between cells, with stage I-derived cell line HROC60 being most susceptible towards standard clinically approved chemotherapeutics (e.g. 5-FU, Irinotecan). Of note, most cell lines were sensitive towards “non-classical” CRC standard drugs (sensitivity: Gemcitabin > Rapamycin > Nilotinib). This comprehensive analysis of tumor biology, genetic alterations and assessment of chemosensitivity towards a broad range of (chemo-) therapeutics helps bringing forward the concept of personalized tumor therapy. [ABSTRACT FROM AUTHOR]- Published
- 2015
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28. Tumor regression in rectal cancer after intensified neoadjuvant chemoradiation: a morphometric and clinicopathological study.
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Prall, Friedrich, Schmitt, Oliver, and Schiffmann, Leif
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RECTAL cancer , *ABDOMINOPERINEAL resection , *SPONTANEOUS cancer regression , *LYMPH node diseases , *CARCINOGENS - Abstract
Background: High interobserver variation is a well known drawback of conventional tumor regression grading, and reaching consensus among pathologists may require a considerable effort. Therefore, in this study, morphometry was tried to assess tumor regression, and its prognostic role was explored. Methods: Tumor regression was quantified by a point counting method to yield tumor area fraction (TAF) as an index of remaining vital tumor. Results: In a series of 104 patients with clinically advanced rectal cancer treated with neoadjuvant radiochemotherapy, TAFs were distributed continuously towards complete regression which was observed in 8.7% of the cases. Plotting TAFs grouped by a conventional regression grading (Dworak's) revealed considerable overlap between groups. In a control series of untreated cancers, only TAFs of cancers with an expansive invasive border were setoff clearly from TAFs obtained for the study cases, but TAFs of control cases with an infiltrative invasive border and mucinous carcinomas extended well into the range of TAFs recorded for regressing tumors. Locoregional recurrence (N = 10) was significantly associated with perineural tumor infiltration and capsule transgressing lymph node metastasis/tumor deposits but not with the degree of tumor regression. Overall survival was better for patients with major regressions (≤20th percentile by morphometry, or Dworak regression grade (DRG) 4/5), although statistical significance was not reached. Conclusions: Morphometry of tumor regression is feasible and explains why conventional regression grading is so difficult to perform. Assessment of tumor regression, by subjective grading or morphometry, does not appear to convey major prognostic information, at least not substantially beyond histopathological tumor staging. This observation discourages expending too much effort on developing this aspect of the pathomorphological workup of the resection specimens. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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29. Intensified neoadjuvant radiochemotherapy for rectal cancer enhances surgical complications.
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Schiffmann, Leif, Wedermann, Nicole, Gock, Michael, Prall, Friedrich, Klautke, Gunther, Fietkau, Rainer, Rau, Bettina, and Klar, Ernst
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RECTAL cancer treatment ,SURGICAL complications ,CANCER relapse ,RETROSPECTIVE studies ,HEALTH outcome assessment ,CANCER chemotherapy - Abstract
Background: Neoadjuvant radiochemotherapy has proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases. The present study aimed at addressing the effects of an intensified protocol of neoadjuvant treatment on the development of postoperative complications. Methods: A total of 387 patients underwent oncological resection for rectal cancer in our institution between January 2000 and December 2009. 106 patients received an intensified radiochemotherapy. Perioperative morbidity and mortality were analyzed retrospectively with special attention on complication rates after intensified radiochemotherapy. Therefore, for each patient subjected to neoadjuvant treatment a patient without neoadjuvant treatment was matched in the following order for tumor height, discontinuous resection/exstirpation, T-category of the TNM-system, dividing stoma and UICC stage. Results: Of all patients operated for rectal cancer, 27.4% received an intensified neoadjuvant treatment. Tumor location in the matched patients were in the lower third (55.2%), middle third (41.0%) and upper third (3.8%) of the rectum. Postoperatively, surgical morbidity was higher after intensified neoadjuvant treatment. In the subgroup with low anterior resection (LAR) the anastomosis leakage rate was higher (26.6% vs. 9.7%) and in the subgroup of patients with rectal exstirpations the perineal wound infection rate was increased (42.2% vs. 18.8%) after intensified radiochemotherapy. Conclusions: In rectal cancer the decision for an intensified neoadjuvant treatment comes along with an increase of anastomotic leakage and perineal wound infection. Quality of life is often reduced considerably and has to be balanced against the potential benefit of intensifying neoadjuvant radiochemotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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30. Prognosis of rectal cancer patients improves with downstaging by intensified neoadjuvant radiochemotherapy - a matched pair analysis.
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Schiffmann, Leif, Klautke, Gunther, Wedermann, Nicole, Gock, Michael, Prall, Friedrich, Fietkau, Rainer, Rau, Bettina, and Klar, Ernst
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RECTAL cancer treatment ,RADIOTHERAPY ,CANCER chemotherapy ,HISTOPATHOLOGY ,CANCER patients - Abstract
Background: Neoadjuvant radiochemotherapy has been proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases in standard protocols of neoadjuvant radiochemotherapy. The present study aimed at addressing the effects of an intensified neoadjuvant radiochemotherapy on long term cancer related and disease free survival. Methods: A total of 387 patients underwent oncologic resection for rectal cancer in our institution between January 2000 and December 2009. There were 106 patients (27.4%) who received an intensified radiochemotherapy protocol completely and without excluding criteria (study group). A matched pair analysis was performed by comparing the study group with patients undergoing primary surgery and postoperative radiochemotherapy, if necessary and possible (control group). Matching was carried out in descending order for UICC stage, R-status, tumor height, T-, N-, V-, L-, M- and G-category of the TNM-system according to the histopathological staging. Follow-up data included local recurrence rate, cancer related and disease free survival. Results: In the study group histopathological work-up of the specimen revealed a treatment response in terms of tumor regression in 92.5% (98/106) of these patients. Undergoing intensified neoadjuvant RCT the actuarial cancer related and disease free survival was 67.9% and 70.4%, local recurrence was 5.7% after an observation period of 4.3 ± 2.55 years. In the control group cancer related and disease free survival was 71.7% and 82.7%, local recurrence was 4.7% after an observation period of 3.8 ± 3.05 years revealing no statistical significant difference between the two groups. Moreover, estimated 5-year results of cancer related survival (66.7% vs 67.9% (controls)), the disease free survival (66.7% vs 79.9% (controls)) as well as subgroup analysis of UICC 0-III and UICC IV patients showed no difference between the study and control group as well. Conclusion: In our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor regression. The resulting inferior histopathological tumor stage shows the same long term local control and systemic tumor control as the control group with a primary more favorable tumor stage. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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31. Establishment, Characterization and Chemosensitivity of Three Mismatch Repair Deficient Cell Lines from Sporadic and Inherited Colorectal Carcinomas.
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Maletzki, Claudia, Stier, Saskia, Gruenert, Ulrike, Gock, Michael, Ostwald, Christiane, Prall, Friedrich, and Linnebacher, Michael
- Subjects
COLON cancer ,DRUG efficacy ,TUMORS ,XENOGRAFTS ,FLOW cytometry ,CELL lines - Abstract
Background: Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113) along with their corresponding xenografts. Methodology: MMR-D cell lines (HROC24, HROC87, and HROC113) were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total). Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. Principal Findings: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras
wt , B-rafmut , HROC87: Kraswt , B-rafmut ), whereas the HROC113 cell line (K-rasmut , B-rafwt ) was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM+ ) tumor cells, showing surface tumor marker expression (CEACAM+ ). MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. Conclusions: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the biological characteristics of MMR-D CRCs, both of sporadic and hereditary origin. Additionally, matched patient-derived immune cells allow for comparative genetic studies. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
32. Ex-vivo Clonally Expanded B Lymphocytes Infiltrating Colorectal Carcinoma Are of Mature Immunophenotype and Produce Functional IgG.
- Author
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Maletzki, Claudia, Jahnke, Annika, Ostwald, Christiane, Klar, Ernst, Prall, Friedrich, and Linnebacher, Michael
- Subjects
EPSTEIN-Barr virus ,TUMORS ,B cells ,IMMUNOGLOBULIN G ,FLOW cytometry ,IMMUNOPHENOTYPING - Abstract
Background: Tumor infiltrating B cells (TiBc) have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC). Methods/Results: TiBc cultures were generated by Epstein-Barr virus (EBV) immortalization. With this method, monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow cytometry and ELISA, TiBc showed an activated immunophenotype (CD23
+ , CD80+ ) and produced immunoglobulin (Ig; IgG secretion in 55% of the cultures). In functional in vitro analysis, most of the IgGs specifically bound to allogeneic CRC target cells. These data suggest that TiBc are antigenexperienced and thus may exhibit functionality in situ. Additionally, mini-cultures generated from 12 further CRCs revealed TiBc outgrowth exclusively in the presence of EBV. Conclusion: In summary, this simple method provides a cellular tool and our data set the stage for analysing the bivalent role of TiBc; being antigen-presenting cells on the one hand and tumor-specific antibody producers on the other. Additionally, the generation of long-term TiBc cultures and their monoclonal Ig may serve to identify novel tumor-specific antigens. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
33. Optical coherence tomography allows for the reliable identification of laryngeal epithelial dysplasia and for precise biopsy: A clinicopathological study of 61 patients undergoing microlaryngoscopy.
- Author
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Just, Tino, Lankenau, Eva, Prall, Friedrich, Hüttmann, Gereon, Pau, Hans Wilhelm, and Sommer, Konrad
- Abstract
Objectives/Hypothesis: A newly developed microscope-based spectral-domain optical coherence tomography (SD-OCT) device and an endoscope-based time-domain OCT (TD-OCT) were used to assess the inter-rater reliability, sensitivity, specificity, and accuracy of benign and dysplastic laryngeal epithelial lesions. Study Design: Prospective study. Methods: OCT during microlaryngoscopy was done on 35 patients with an endoscope-based TD-OCT, and on 26 patients by an SD-OCT system integrated into an operating microscope. Biopsies were taken from microscopically suspicious lesions allowing comparative study of OCT images and histology. Results: Thickness of the epithelium was seen to be the main criterion for degree of dysplasia. The inter-rater reliability for two observers was found to be kappa = 0.74 (P <.001) for OCT. OCT provided test outcomes for differentiation between benign laryngeal lesions and dysplasia/CIS with sensitivity of 88%, specificity of 89%, PPV of 85%, NPV of 91%, and predictive accuracy of 88%. However, because of the limited penetration depth of the laser light primarily in hyperkeratotic lesions (thickness above 1.5 mm), the basal cell layer was no longer visible, precluding reliable assessment of such lesions. Conclusions: OCT allows for a fairly accurate assessment of benign and dysplastic laryngeal epithelial lesion and greatly facilitates the taking of precise biopsies. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
34. Endolymphatic Non-Langerhans Cell Histiocytosis of the Larynx.
- Author
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Classen, Carl Friedrich, Haffner, Dieter, Nizze, Horst, Möller, Peter, and Prall, Friedrich
- Published
- 2010
- Full Text
- View/download PDF
35. Cryopreservation of human colorectal carcinomasprior to xenografting.
- Author
-
Linnebacher, Michael, Maletzki, Claudia, Ostwald, Christiane, Klier, Ulrike, Krohn, Mathias, Klar, Ernst, and Prall, Friedrich
- Subjects
COLON cancer ,CANCER patients ,PATHOLOGY ,SURGERY ,CRYOPRESERVATION of organs, tissues, etc. - Abstract
Background: Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Methods: Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Results: Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Conclusions: Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
36. Poly(3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects - an animal study with minipigs.
- Author
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Bernd, Hans Edgar, Kunze, Carmen, Freier, Thomas, Sternberg, Katrin, Kramer, Sven, Behrend, Detlef, Prall, Friedrich, Donat, Martina, and Kramp, Burkhard
- Subjects
SKULL ,SKELETON ,MICROBIOLOGY ,POLYHYDROXYBUTYRATE ,ELECTRON microscopy - Abstract
Conclusion: We conclude that PHB patch material may fulfil the specific requirements that are necessary for a dural substitute, including defect closure, stability and biocompatibility. Our results support the assumed positive influence of PHB on bone regeneration. Objectives: Although many experimental and clinical studies have been performed to identify a suitable material to repair defects of the dura mater, no ideal dural substitute is currently available. PHB is a biodegradable and biocompatible polymer that might serve as dural substitute and osteosynthesis material in cranial bone defects. Materials and methods: Different standardized PHB patches were used in six minipigs for covering defined bone defects in the anterior skull base including a dura mater lesion as well as in the frontal sinus front wall. After a defined time of implantation of 3, 6, and 9 months PHB patches were explanted and examined for clinical findings, biodegradation, presence of microorganisms, histological findings, and electron microscopy. Results: The examinations revealed an increasing closure of bone defect corresponding with time. The anterior skull base bone defect was completely closed after 9 months. The histological findings revealed a connective tissue and callus formation around the PHB patches with fibroblasts and foreign body/giant cell reaction growing through PHB membrane pores. There were no reactions or adhesions between brain and PHB or dura mater and PHB, respectively. Investigations of biodegradation and electron microscopy revealed a continuous breakdown of PHB in the course of time with variations due to different PHB structures. Microbiological investigations could not detect any florid intracranial infection. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
37. Urinary Retention Due to Severe Pseudocystic Mucoid Degeneration of the Prostatic Matrix: A Rare Urologic Manifestation of Cystic Fibrosis.
- Author
-
Kellermann, Gesa, anastasiadis, aristotelis G., Dräger, Desirée L., Prall, Friedrich, and Hakenberg, Oliver W.
- Subjects
GENETIC disorders ,LUNG diseases ,PANCREATIC diseases ,COLLAGEN diseases ,RETENTION of urine - Abstract
Cystic fibrosis (CF) is an autosomal recessive genetic disease, which is characterized by the production of thick mucus in exocrine glands. The main cause for morbidity and mortality in CF patients is respiratory failure. The gastrointestinal system is also commonly affected. Urologic manifestations of CF include infertility and azoospermia, nephrolithiasis, and stress urinary incontinence. In this report, we describe a 33-year-old male, who presented with recurrent urinary retention due to prostatic enlargement despite his young age. After transurethral resection, the voiding problems resolved. Histopathological examination, however, revealed a severe pseudocystic mucoid degeneration of the prostatic matrix as a cause of his subvesical obstruction. Although these structural changes are most probably due to his underlying disease, detailed histologic features have not been described in the literature. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
38. The HROC-Xenobank—A High Quality Assured PDX Biobank of >100 Individual Colorectal Cancer Models.
- Author
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Matschos, Stephanie, Bürtin, Florian, Kdimati, Said, Radefeldt, Mandy, Krake, Susann, Prall, Friedrich, Engel, Nadja, Krohn, Mathias, Micheel, Bianca, Kreutzer, Michael, Mullins, Christina Susanne, and Linnebacher, Michael
- Subjects
DISEASE clusters ,XENOGRAFTS ,TISSUE banks ,IN vivo studies ,GENETIC mutation ,CARCINOGENESIS ,DNA fingerprinting ,COLORECTAL cancer ,CANCER patients ,MOLECULAR biology ,GENE expression profiling ,COLLECTION & preservation of biological specimens ,TRANSLATIONAL research ,HISTOLOGY ,CRYOPRESERVATION of organs, tissues, etc. - Abstract
Simple Summary: Considering recent research, it was established that the best experimental models to conserve biological features of human tumors and to predict individual clinical treatment success are patient-derived xenografts (PDX). Their recognized and growing importance for translational research, especially for late-stage preclinical testing of novel therapeutics, necessitates a high number of well-defined PDX models from individual patients' tumors. The starting platform for the Hansestadt Rostock colorectal cancer (HROC)-Xenobank was the assortment of colorectal tumor and normal tissue samples from patients stored in our university biobank. Based on our research group's large biobank of colorectal cancers (CRC), we here describe the ongoing activity of establishing a high quality assured PDX biobank for more than 100 individual CRC cases. This includes sufficient numbers of vitally frozen (n > 30 aliquots) and snap frozen (n > 5) backups, "ready to use". Additionally, PDX tumor pieces were paraffin embedded. At the current time, we have completed 125 cases. This resource allows histopathological examinations, molecular characterizations, and gene expression analysis. Due to its size, different issues of interest can be addressed. Most importantly, the application of low-passage, cryopreserved, and well-characterized PDX for in vivo studies guarantees the reliability of results due to the largely preserved tumor microenvironment. All cases described were molecularly subtyped and genetic identity, in comparison to the original tumor tissue, was confirmed by fingerprint analysis. The latter excludes ambiguity errors between the PDX and the original patient tumor. A cancer hot spot mutation analysis was performed for n = 113 of the 125 cases entities. All relevant CRC molecular subtypes identified so far are represented in the Hansestadt Rostock CRC (HROC)-Xenobank. Notably, all models are available for cooperative research approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
39. High-degree tumor budding and podia-formation in sporadic colorectal carcinomas with K-ras gene mutations.
- Author
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Prall, Friedrich and Ostwald, Christiane
- Subjects
COLON cancer ,TUMORS ,HYPOTHESIS ,GENETICS - Abstract
Summary: In vitro ras activation enhances the epithelial-mesenchymal transition of colorectal carcinoma cells. But ras effects are known to be highly dependant on cell types and the tissue context. Therefore, this study was made to test the hypothesis that in clinical colorectal carcinoma specimens, aggressive invasion phenotypes, specifically tumor budding and podia formation, would correlate with K-ras gene mutations. In a series of 95 clinically sporadic primary colorectal carcinomas collected ad hoc, tumor budding and podia formation were counted using pan-cytokeratin immunohistochemistry, and K-ras gene mutations in codons 12 and 13 were determined. Consistent with the hypothesis, tumor budding and podia formation were observed to be significantly higher in the 32 (34.7%) of the tumors with K-ras gene mutations (29mutations in codon 12, 3 in codon 13), and this correlation was observed independent of the patterns of invasion (expansive versus infiltrative). Microsatellite status, numbers of losses of heterozygosity, adenomatous polyposis coli and p53 gene mutations, and degree of promoter methylations (CIMP status) were not associated with K-ras gene mutations. Besides their effects on the tumor cell cycles, oncogeneic K-ras gene mutations in colorectal carcinomas could be important for aggressive tumor invasion. This may be important in metastasizing disease and could provide a rationale for developing drugs that interrupt ras-signaling cascades. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
40. p16INK4a promoter methylation and 9p21 allelic loss in colorectal carcinomas: relation with immunohistochemical p16INK4a expression and with tumor budding.
- Author
-
Prall, Friedrich, Ostwald, Christiane, Weirich, Volker, and Nizze, Horst
- Subjects
CANCER ,REGRESSION analysis ,ONCOLOGY ,GENES - Abstract
Summary: In colorectal carcinomas, p16
INK4a inactivation is known to occur by allelic loss and by promoter methylation, but mutations are rare. p16INK4a is up-regulated in tumor buds, and the consequent shutdown of proliferation may be a prerequisite for tumor budding. Fifty-seven colorectal carcinomas from a consecutive series were investigated. Using DNA from tissue homogenates, p16INK4a promoter methylation was seen in 17 of 57 tumors by methylation-specific polymerase chain reaction, and this could be confirmed using DNA from laser-capture microdissected material in 16 of these cases. A total loss of immunohistochemical p16INK4a expression was seen in 6 of 17 tumors with promoter methylation. Quantification of immunohistochemical p16INK4a expression for the remaining 11 cases revealed statistically lower frequencies of expression as compared with cases without p16INK4a promoter methylation. 9p21 allelic loss was observed in 9 cases, but p16INK4a expression in these carcinomas was not reduced. Attempted linear regression of p16INK4a expression in tumor buds on the degree of tumor budding, as counted on pan-cytokeratin immunostains, did not show a correlation. p16INK4a promoter methylation can completely abrogate p16INK4a expression in colorectal carcinomas. In many cases, however, it has an appreciable but only modulatory influence on p16INK4a expression. Possibly, methylations are heterozygous, and/or mosaic in colorectal carcinomas and/or methylations are not totally stable but can be lost between carcinoma cell replication cycles. Up-regulation of p16INK4a does not seem to be a strict requirement for tumor budding, hence, the absence of a correlation. [Copyright &y& Elsevier]- Published
- 2006
- Full Text
- View/download PDF
41. Tumour-Derived Cell Lines and Their Potential for Therapy Prediction in Patients with Metastatic Colorectal Cancer.
- Author
-
Wagner, Sandra, Beger, Nicola T., Matschos, Stephanie, Szymanski, Antonia, Przybylla, Randy, Bürtin, Florian, Prall, Friedrich, Linnebacher, Michael, and Mullins, Christina S.
- Subjects
GENETIC mutation ,SEQUENCE analysis ,XENOGRAFTS ,ANIMAL experimentation ,METASTASIS ,COLORECTAL cancer ,FLUOROURACIL ,CANCER patients ,DESCRIPTIVE statistics ,CELL lines ,OXALIPLATIN ,MICE - Abstract
Simple Summary: Colorectal cancer is a global issue with millions of patients in need for new treatment options. Surgical resection is often the first clinical intervention and can be, especially for primary tumours, curative. However, advanced tumours, recurrences, and metastases require drug treatment. Our aim was to compare material of primary tumours and corresponding metastases to draw conclusions from the first one to the latter. The feasibility of therapy prediction using the primary tumour material for the metastatic situation creates a time window for functional testing, which can realistically be integrated into the strict timeframe of clinical procedures. A reliable treatment recommendation, based on the tumour drug response, would improve treatment success in patients with metachronous metastases and spare them from unnecessary side effects of unsuccessful therapies. The prognosis of metastatic colorectal cancer (CRC) remains poor. Patients and physicians are in need of individual therapies and precise response predictions. We investigated the predictive capacity of primary tumour material for treatment response of metastases. Mutational landscapes of primary tumours and corresponding metastases of 10 CRC patients were compared. Cell line characteristics and chemosensitivity were investigated pairwise for primary and metastatic tumours of four patients. PDX models of one patient were treated in vivo for proof of concept. Driver mutations did not differ between primaries and metastases, while the latter accumulated additional mutations. In vitro chemosensitivity testing revealed no differences for responses to 5-FU and oxaliplatin between primary and metastatic cell lines. However, irinotecan response differed significantly: the majority of metastases-derived cell lines was less sensitive to irinotecan than their matching primary counterpart. Therapy recommendations based on these findings were compared to clinical treatment response and mostly in line with the predicted outcome. Therefore, primary tumour cell models seem to be a good tool for drug response testing and conclusion drawing for later metastases. With further data from tumour-derived cell models, such predictions could improve clinical treatment decisions, both recommending likely effective therapeutic options while excluding ineffective treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. Tubular invasion and the morphogenesis of tumor budding in colorectal carcinoma.
- Author
-
Prall, Friedrich, Ostwald, Christiane, and Linnebacher, Micheal
- Published
- 2009
- Full Text
- View/download PDF
43. Increased Diagnostic Certainty of Periprosthetic Joint Infections by Combining Microbiological Results with Histopathological Samples Gained via a Minimally Invasive Punching Technique.
- Author
-
Enz, Andreas, Becker, Johanna, Warnke, Philipp, Prall, Friedrich, Lutter, Christoph, Mittelmeier, Wolfram, and Klinder, Annett
- Subjects
JOINT infections ,CERTAINTY ,BIOPSY - Abstract
Background: The diagnosis of low-grade infections of endoprostheses is challenging. There are still no unified guidelines for standardised diagnostic approaches, recommendations are categorised into major and minor criteria. Additional histopathological samples might sustain the diagnosis. However, ambulatory preoperative biopsy collection is not widespread. Method: 102 patients with hip or knee endoprosthesis and suspected periprosthetic joint infection (PJI) were examined by arthrocentesis with microbiological sample and histopathological punch biopsy. The data were retrospectively analysed for diagnosis concordance. Results: Preoperative microbiology compared to intraoperative results was positive in 51.9% (sensitivity 51.9%, specificity 97.3%). In comparison of preoperative biopsy to intraoperative diagnostic results 51.9% cases were positive (sensitivity 51.9%, specificity 100.0%). The combination of preoperative biopsy and microbiology in comparison to intraoperative results was positive in 70.4% of the cases (sensitivity 70.4%, specificity 97.3%). Conclusion: The diagnosis of PJI is complex. One single method to reliably detect an infection is currently not available. With the present method histopathological samples might be obtained quickly, easily and safely for the preoperative detection of PJI. A combination of microbiological and histopathological sampling increases the sensitivity up to 18.5% to detect periprosthetic infection. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
44. Integrated Biobanking and Tumor Model Establishment of Human Colorectal Carcinoma Provides Excellent Tools for Preclinical Research.
- Author
-
Mullins, Christina S., Micheel, Bianca, Matschos, Stephanie, Leuchter, Matthias, Bürtin, Florian, Krohn, Mathias, Hühns, Maja, Klar, Ernst, Prall, Friedrich, and Linnebacher, Michael
- Subjects
CELL lines ,CLINICAL medicine research ,COLON tumors ,MULTIVARIATE analysis ,RECTUM tumors ,SERUM ,TISSUE banks ,XENOGRAFTS ,INDIVIDUALIZED medicine - Abstract
Over the time period from 2006 to 2017, consecutive patients operated on at the University Medical Center Rostock participated in the comprehensive biobanking and tumor-modelling approach known as the HROC collection. Samples were collected using strict standard operating procedures including blood (serum and lymphocytes), tumor tissue (vital and snap frozen), and adjacent normal epithelium. Patient and tumor data including classification, molecular type, clinical outcome, and results of the model establishment are the essential pillars. Overall, 149 patient-derived xenografts with 34 primary and 35 secondary cell lines were successfully established and encompass all colorectal carcinoma anatomic sites, grading and staging types, and molecular classes. The HROC collection represents one of the largest model assortments from consecutive clinical colorectal carcinoma (CRC) cases worldwide. Statistical analysis identified a variety of clinicopathological and molecular factors associated with model success in univariate analysis. Several of them not identified before include localization, mutational status of K-Ras and B-Raf, MSI-status, and grading and staging parameters. In a multivariate analysis model, success solely correlated positively with the nodal status N1 and mutations in the genes K-Ras and B-Raf. These results imply that generating CRC tumor models on the individual patient level is worth considering especially for advanced tumor cases with a dismal prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
45. ROCK2 inhibition triggers the collective invasion of colorectal adenocarcinomas.
- Author
-
Libanje, Fotine, Raingeaud, Joel, Luan, Rui, Thomas, ZoéAp, Zajac, Olivier, Veiga, Joel, Marisa, Laetitia, Adam, Julien, Boige, Valerie, Malka, David, Goéré, Diane, Hall, Alan, Soazec, Jean‐Yves, Prall, Friedrich, Gelli, Maximiliano, Dartigues, Peggy, and Jaulin, Fanny
- Subjects
GUANINE nucleotide exchange factors ,CANCER cell migration ,WAR - Abstract
The metastatic progression of cancer is a multi‐step process initiated by the local invasion of the peritumoral stroma. To identify the mechanisms underlying colorectal carcinoma (CRC) invasion, we collected live human primary cancer specimens at the time of surgery and monitored them ex vivo. This revealed that conventional adenocarcinomas undergo collective invasion while retaining their epithelial glandular architecture with an inward apical pole delineating a luminal cavity. To identify the underlying mechanisms, we used microscopy‐based assays on 3D organotypic cultures of Caco‐2 cysts as a model system. We performed two siRNA screens targeting Rho‐GTPases effectors and guanine nucleotide exchange factors. These screens revealed that ROCK2 inhibition triggers the initial leader/follower polarization of the CRC cell cohorts and induces collective invasion. We further identified FARP2 as the Rac1 GEF necessary for CRC collective invasion. However, FARP2 activation is not sufficient to trigger leader cell formation and the concomitant inhibition of Myosin‐II is required to induce invasion downstream of ROCK2 inhibition. Our results contrast with ROCK pro‐invasive function in other cancers, stressing that the molecular mechanism of metastatic spread likely depends on tumour types and invasion mode. Synopsis: Metastatic progression is initiated by local invasion of the peritumoral stroma, but the mechanisms underlying cancer cell migration remain unclear. Here, histological analyses of human primary colorectal carcinomas (CRC) combined with screenings of live ex vivo 3D cultures determine the mode of dissemination and identify the Rho‐GTPase signalling effectors involved. Conventional CRC cells invade collectively as differentiated epithelial glands with retained apico‐basolateral polarity.ROCK2 kinase inhibition triggers leader‐cell formation and dissemination of patient‐derived xenograft explants.ROCK2 blocks guanine exchange factor FARP2 recruitment to the apical junctional complex.FARP2 activation and Myosin‐II inhibition cooperate in collective invasion. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
46. PD-L1 expression in tumour buds of colorectal carcinoma.
- Author
-
Prall, Friedrich and Hühns, Maja
- Subjects
- *
COLON cancer , *MACROPHAGES , *IMMUNOLOGY , *LIGANDS (Biochemistry) , *CANCER - Abstract
The article discusses the occurrence of antiprogrammed death ligand 1 in colorectal carcinoma tumor buds. Topics covered include the impact of the ligand on tumor responses and pathologists' optimism about the study of the different kinds of cancer. Also mentioned is the immunological ignorance of cells found in macrophage-poor colorectal carcinomas.
- Published
- 2016
- Full Text
- View/download PDF
47. Mo1628 - The HROC Collection and Matching Pairs of Colorectal Cancer Models (PDX and Cell Lines) from Primaries and Metastases.
- Author
-
Linnebacher, Michael, Maletzki, Claudia, Mullins, Christina S., Gock, Michael, Huehns, Maja, Prall, Friedrich, and Klar, Ernst
- Published
- 2017
- Full Text
- View/download PDF
48. Tu2062 Establishment and Characterization of Three Microsatellite-Instable Cell Lines Derived From Sporadic and Inherited Primary Colorectal Carcinomas.
- Author
-
Maletzki, Claudia, Klar, Ernst, Prall, Friedrich, and Linnebacher, Michael
- Published
- 2012
- Full Text
- View/download PDF
49. Cryopreservation of human colorectal carcinomas prior to xenografting.
- Author
-
Linnebacher M, Maletzki C, Ostwald C, Klier U, Krohn M, Klar E, Prall F, Linnebacher, Michael, Maletzki, Claudia, Ostwald, Christiane, Klier, Ulrike, Krohn, Mathias, Klar, Ernst, and Prall, Friedrich
- Abstract
Background: Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity.Methods: Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days).Results: Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation.Conclusions: Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
50. Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST)
- Author
-
Daniels, Marc, Lurkin, Irene, Pauli, Roland, Erbstößer, Erhard, Hildebrandt, Uwe, Hellwig, Karsten, Zschille, Uwe, Lüders, Petra, Krüger, Gabriele, Knolle, Jürgen, Stengel, Bernd, Prall, Friedrich, Hertel, Kay, Lobeck, Hartmut, Popp, Brigitte, Theissig, Franz, Wünsch, Peter, Zwarthoff, Ellen, Agaimy, Abbas, and Schneider-Stock, Regine
- Subjects
- *
GENETIC mutation , *GASTROINTESTINAL stromal tumors , *EXONS (Genetics) , *GROWTH factors , *CANCER genetics , *TUMOR proteins - Abstract
Abstract: Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (∼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
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