4 results on '"Nikolas Schopow"'
Search Results
2. Identification of Tumor Antigens and Immune Subtypes for the Development of mRNA Vaccines and Individualized Immunotherapy in Soft Tissue Sarcoma
- Author
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Changwu Wu, Yingjuan Duan, Siming Gong, Georg Osterhoff, Sonja Kallendrusch, and Nikolas Schopow
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Cancer Research ,tumor immune microenvironment ,mRNA vaccine ,individualized immunotherapy ,Oncology ,soft tissue sarcoma ,immune subtypes ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,ddc:610 ,Article ,RC254-282 - Abstract
Simple Summary Soft tissue sarcomas (STS) are a group of rare malignant tumors with high tissue heterogeneity and poor prognosis, and which are still without effective individualized immunotherapy approaches. In this study, four potential tumor antigens, six STS immune subtypes, and six functional gene modules were identified. The different immune subtypes have different molecular, cellular, and clinical characteristics. The superiority of mRNA vaccine therapies has been demonstrated during the current pandemic as well as in tumor vaccine studies, and the present study provides guidance for future mRNA vaccine development. Furthermore, in future individualized immunotherapies for STS, it is possible to select different immunotherapies based on the different immune subtypes identified in this study. In fact, the immune subtypes identified in this study explain, to some extent, the failure of immunotherapy for certain STS subtypes in previous clinical trials, and facilitate further understanding of strategy selection for the immunotherapy of STS. To our knowledge, this is the first study to address STS mRNA vaccine development and immunophenotyping. This study provides a theoretical framework for STS mRNA vaccine development and the selection of patients for vaccination and provides a reference for promoting individualized immunotherapy. Abstract Soft tissue sarcomas (STS) are a rare disease with high recurrence rates and poor prognosis. Missing therapy options together with the high heterogeneity of this tumor type gives impetus to the development of individualized treatment approaches. This study identifies potential tumor antigens for the development of mRNA tumor vaccines for STS and explores potential immune subtypes, stratifying patients for immunotherapy. RNA-sequencing data and clinical information were extracted from 189 STS samples from The Cancer Genome Atlas (TCGA) and microarray data were extracted from 103 STS samples from the Gene Expression Omnibus (GEO). Potential tumor antigens were identified using cBioportal, the Oncomine database, and prognostic analyses. Consensus clustering was used to define immune subtypes and immune gene modules, and graph learning-based dimensionality reduction analysis was used to depict the immune landscape. Finally, four potential tumor antigens were identified, each related to prognosis and antigen-presenting cell infiltration in STS: HLTF, ITGA10, PLCG1, and TTC3. Six immune subtypes and six gene modules were defined and validated in an independent cohort. The different immune subtypes have different molecular, cellular, and clinical characteristics. The immune landscape of STS reveals the immunity-related distribution of patients and intra-cluster heterogeneity of immune subtypes. This study provides a theoretical framework for STS mRNA vaccine development and the selection of patients for vaccination, and provides a reference for promoting individualized immunotherapy.
- Published
- 2022
3. Texture analysis parameters derived from T1-and T2-weighted magnetic resonance images can reflect Ki67 index in soft tissue sarcoma
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Anne Kathrin Höhn, Christoph Josten, Katharina Renatus, Nikolas Schopow, Gordian Hamerla, Alexey Surov, Johannes K. M. Fakler, and Hans-Jonas Meyer
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Male ,Proliferation index ,030218 nuclear medicine & medical imaging ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers, Tumor ,medicine ,Humans ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Soft tissue sarcoma ,Area under the curve ,Soft tissue ,Sarcoma ,Magnetic resonance imaging ,Middle Aged ,Prognosis ,medicine.disease ,Magnetic Resonance Imaging ,Ki-67 Antigen ,ROC Curve ,Oncology ,030220 oncology & carcinogenesis ,Ki67 index ,Female ,Surgery ,T2 weighted ,Nuclear medicine ,business ,Follow-Up Studies - Abstract
Background and objectives Texture analysis derived from morphological magnetic resonance (MR) images might be associated with histopathology in tumors. The present study sought to elucidate possible associations between texture features derived from T1-and T2-weighted images with proliferation index Ki67 in soft tissue sarcomas. Methods Overall, 29 patients (n = 13, 44.8% female) with a median age of 52 years were included into this retrospective study. Several soft tissue sarcomas were investigated. Texture analysis was performed on pre-contrast T1-weighted and T2-weighted images using the free available Mazda software. Results The best correlation coefficients with Ki67 index were identified for the following parameters: T1-weighted images “45dgr_RLNonUni (p = 0.50, P = 0.006), T2-weighted images “S (4,0)SumAverg” (p = −0.45, P = 0.02). A ROC analysis was performed for Ki67-index with a threshold of 10%. The highest area under the curve (AUC) was found for the parameter “T1_WavEnHL_s-7” with an AUC of 0.90. For the threshold of Ki67 = 20% the highest AUC was identified for the parameter „T2_S (1,1)Entropy” with an AUC of 0.77. Conclusion Several texture features derived from T1-and T2-weighted images correlated with proliferation index Ki67 and might be used as valuable novel biomarkers in soft tissue sarcomas.
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- 2019
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4. Organotypic slice cultures of human gastric and esophagogastric junction cancer
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Florian Lordick, Achim Aigner, Christian Eckmann, Christian Moebius, Guido Schumacher, Nikolaus Gaßler, Justus Koerfer, Christian Wittekind, Ingo Bechmann, Arved Weimann, Sonja Kallendrusch, Nikolas Schopow, Daniela Geister, Volker Wiechmann, Woubet T. Kassahun, Felicitas Merz, and Christoph Kubick
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0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Esophageal Neoplasms ,esophagogastric junction cancer ,Biopsy ,Drug resistance ,Biology ,Tissue Culture Techniques ,03 medical and health sciences ,Cytokeratin ,Organ Culture Techniques ,0302 clinical medicine ,Stomach Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Precision Medicine ,Chemosensitivity ,Original Research ,Cisplatin ,organotypic slice cultures ,medicine.diagnostic_test ,gastric cancer ,Clinical Cancer Research ,Cancer ,medicine.disease ,Combined Modality Therapy ,personalized treatment ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Histopathology ,Esophagogastric Junction ,Ex vivo ,medicine.drug - Abstract
Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6‐well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki‐67 for proliferation, and cleaved caspase‐3 staining for apoptosis. The slices were analyzed under naive conditions and following 2–4 days in vitro exposure to 5‐FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response.
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- 2016
- Full Text
- View/download PDF
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