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Your search keyword '"Matthias, Kappler"' showing total 2 results
Start Over Author "Matthias, Kappler" Publisher biomed central
2 results on '"Matthias, Kappler"'

1. Identification of lymphocyte cell-specific protein-tyrosine kinase (LCK) as a driver for invasion and migration of oral cancer by tumor heterogeneity exploitation

Author

Mechthild Hatzfeld, Monika Haemmerle, Markus Glaß, Tony Gutschner, Matthias Kappler, W.G. Ballhausen, Alexander W. Eckert, Lisa Müller, Jonas Weiße, Julia Rosemann, Danny Misiak, and Stefan Hüttelmaier

Subjects
0301 basic medicine, Cancer Research, Cellular differentiation, Dasatinib, Antineoplastic Agents, Biology, Clonal heterogeneity, HNSCC, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Invasion, Cell Movement, Cell Line, Tumor, medicine, Humans, Neoplasm Invasiveness, RC254-282, Matrigel, Research, EMT, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, medicine.disease, ITH, 030104 developmental biology, Oncology, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Carcinoma, Squamous Cell, Molecular Medicine, Mouth Neoplasms, OSCC, Transcriptome, Tyrosine kinase, Proto-oncogene tyrosine-protein kinase Src, medicine.drug, Src
Abstract

Background Cancer metastases are the main cause of lethality. The five-year survival rate for patients diagnosed with advanced stage oral cancer is 30%. Hence, the identification of novel therapeutic targets is an urgent need. However, tumors are comprised of a heterogeneous collection of cells with distinct genetic and molecular profiles that can differentially promote metastasis making therapy development a challenging task. Here, we leveraged intratumoral heterogeneity in order to identify drivers of cancer cell motility that might be druggable targets for anti-metastasis therapy. Methods We used 2D migration and 3D matrigel-based invasion assays to characterize the invasive heterogeneity among and within four human oral cancer cell lines in vitro. Subsequently, we applied mRNA-sequencing to map the transcriptomes of poorly and strongly invasive subclones as well as primary tumors and matched metastasis. Results We identified SAS cells as a highly invasive oral cancer cell line. Clonal analysis of SAS yielded a panel of 20 subclones with different invasive capacities. Integrative gene expression analysis identified the Lymphocyte cell-specific protein-tyrosine kinase (LCK) as a druggable target gene associated with cancer cell invasion and metastasis. Inhibition of LCK using A-770041 or dasatinib blocked invasion of highly aggressive SAS cells. Interestingly, reduction of LCK activity increased the formation of adherens junctions and induced cell differentiation. Conclusion Analysis of invasive heterogeneity led to the discovery of LCK as an important regulator of motility in oral cancer cells. Hence, small molecule mediated inhibition of LCK could be a promising anti-metastasis therapy option for oral cancer patients.

Published
2021

2. The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort.

Author

Carolin, Kröner, Matthias, Kappler, Ann-Christin, Grimmelt, Gudrun, Laniado, Benjamin, Würstl, and Matthias, Griese

Subjects
CYSTIC fibrosis, DISEASE exacerbation, RESPIRATORY diseases, NUCLEOTIDE sequence, ASPERGILLOSIS, C-reactive protein, PATIENTS
Abstract

Background The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. Methods The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. Results In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. Conclusions This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients. [ABSTRACT FROM AUTHOR]

Published
2013
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