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639 results on '"Gütgemann, A."'

3. Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis

Author

Leimkühler, Nils B., Gleitz, Hélène F.E., Ronghui, Li, Snoeren, Inge A.M., Fuchs, Stijn N.R., Nagai, James S., Banjanin, Bella, Lam, King H., Vogl, Thomas, Kuppe, Christoph, Stalmann, Ursula S.A., Büsche, Guntram, Kreipe, Hans, Gütgemann, Ines, Krebs, Philippe, Banz, Yara, Boor, Peter, Tai, Evelyn Wing-Yin, Brümmendorf, Tim H., Koschmieder, Steffen, Crysandt, Martina, Bindels, Eric, Kramann, Rafael, Costa, Ivan G., and Schneider, Rebekka K.

Published
2021
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4. NLRP3-induced systemic inflammation controls the development of JAK2V617F mutant myeloproliferative neoplasms

Author

Koerber, Ruth-Miriam, primary, Krollmann, Calvin, additional, Cieslak, Kevin, additional, Tregel, Elisabeth, additional, Brümmendorf, Tim H., additional, Koschmieder, Steffen, additional, Griesshammer, Martin, additional, Gütgemann, Ines, additional, Brossart, Peter, additional, Skoda, Radek C., additional, Kolbe, Carl Christian, additional, Latz, Eicke, additional, Wolf, Dominik, additional, and Teichmann, Lino L., additional

Published
2024
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5. Recommendation of a standardized broth microdilution method for antimicrobial susceptibility testing of Avibacterium paragallinarum and resistance monitoring

Author

Gütgemann, Franziska, primary, Heuvelink, Annet, additional, Müller, Anja, additional, Churin, Yury, additional, Buter, Rianne, additional, Jung, Arne, additional, Feberwee, Anneke, additional, Wiegel, Jeanine, additional, Kumm, Franziska, additional, Braun, Ann Sophie, additional, Yue, Min, additional, Soriano-Vargas, Edgardo, additional, Swanepoel, Stefan, additional, Botteldoorn, Nadine, additional, Kirchner, Miranda, additional, and Kehrenberg, Corinna, additional

Published
2024
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9. Neuropilin2 in Mesenchymal Stromal Cells as a Potential Novel Therapeutic Target in Myelofibrosis.

Author

Vosbeck, Karla, Förster, Sarah, Mayr, Thomas, Sahu, Anshupa, Haddouti, El-Mustapha, Al-Adilee, Osamah, Körber, Ruth-Miriam, Bisht, Savita, Muders, Michael H., Nesic, Svetozar, Buness, Andreas, Kristiansen, Glen, Schildberg, Frank A., and Gütgemann, Ines

Subjects
IN vitro studies, OSTEOBLASTS, DATA analysis, RESEARCH funding, MESENCHYMAL stem cells, CELL proliferation, FISHER exact test, RETROSPECTIVE studies, DESCRIPTIVE statistics, MICE, IMMUNOHISTOCHEMISTRY, RNA, GENE expression, CELL lines, WESTERN immunoblotting, ENDOTHELIAL cells, STATISTICS, MYELOFIBROSIS, STAINS & staining (Microscopy), CELL receptors, SEQUENCE analysis, TRANSFORMING growth factors-beta
Abstract

Simple Summary: Bone marrow (myelo-) fibrosis in myeloproliferative neoplasms is associated with poor prognosis and treatment failure emphasizing the importance of investigating novel treatment approaches outside the JAK pathway. This study investigates the role of neuropilin 2 (NRP2) in myelofibrosis and bone formation, identifies the type of stromal cells expressing and upregulating NRP2 and outcomes when NRP2 is lost. Our results suggest that NRP2 is an interesting molecular druggable target in myeloproliferative neoplasm. Bone marrow fibrosis in myeloproliferative neoplasm (MPN), myelodysplastic syndromes (MDS), MPN/MDS overlap syndromes and acute myeloid leukemia (AML) is associated with poor prognosis and early treatment failure. Myelofibrosis (MF) is accompanied by reprogramming of multipotent bone marrow mesenchymal stromal cells (MSC) into osteoid and fiber-producing stromal cells. We demonstrate NRP2 and osteolineage marker NCAM1 (neural cell adhesion molecule 1) expression within the endosteal niche in normal bone marrow and aberrantly in MPN, MDS MPN/MDS overlap syndromes and AML (n = 99), as assessed by immunohistochemistry. Increased and diffuse expression in mesenchymal stromal cells and osteoblasts correlates with high MF grade in MPN (p < 0.05 for NRP2 and NCAM1). Single cell RNA sequencing (scRNAseq) re-analysis demonstrated NRP2 expression in endothelial cells and partial co-expression of NRP2 and NCAM1 in normal MSC and osteoblasts. Potential ligands included transforming growth factor β1 (TGFB1) from osteoblasts and megakaryocytes. Murine ThPO and JAK2V617F myelofibrosis models showed co-expression of Nrp2 and Ncam1 in osteolineage cells, while fibrosis-promoting MSC only express Nrp2. In vitro experiments with MC3T3-E1 pre-osteoblasts and analysis of Nrp2−/− mouse femurs suggest that Nrp2 is functionally involved in osteogenesis. In summary, NRP2 represents a potential novel druggable target in patients with myelofibrosis. [ABSTRACT FROM AUTHOR]

Published
2024
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10. The EMT transcription factor Zeb2 controls adult murine hematopoietic differentiation by regulating cytokine signaling

Author

Li, Jin, Riedt, Tamara, Goossens, Steven, Carrillo García, Carmen, Szczepanski, Sabrina, Brandes, Maria, Pieters, Tim, Dobrosch, Linne, Gütgemann, Ines, Farla, Natalie, Radaelli, Enrico, Hulpiau, Paco, Mallela, Nikhil, Fröhlich, Holger, La Starza, Roberta, Matteucci, Caterina, Chen, Tong, Brossart, Peter, Mecucci, Cristina, Huylebroeck, Danny, Haigh, Jody J., and Janzen, Viktor

Published
2017
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14. Prognostic profiling of the immune cell microenvironment in Ewing´s Sarcoma Family of Tumors

Author

David Stahl, Andrew J Gentles, Ralf Thiele, and Ines Gütgemann

Subjects
cibersort, tumor-infiltrating immune cells, tumor microenvironment, ewing´s sarcoma family of tumors, hif1α, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Ewing´s Sarcoma Family of Tumors (ESFT) are clinically aggressive bone and soft tissue tumors in children and young adults. Analysis of the immune tumor microenvironment (TME) provides insight into tumor evolution and novel treatment options. So far, the scarcity of immune cells in ESFT has hindered a comprehensive analysis of rare subtypes. We determined the relative fraction of 22 immune cell types using 197 microarray gene expression datasets of primary ESFT tumor samples by using CIBERSORT, a deconvolution algorithm enumerating infiltrating leucocytes in bulk tumor tissue. The most abundant cells were macrophages (mean 43% of total tumor-infiltrating leukocytes, TILs), predominantly immunosuppressive M2 type macrophages, followed by T cells (mean 23% of TILs). Increased neutrophils, albeit at low number, were associated with a poor overall survival (OS) (p = .038) and increased M2 macrophages predicted a shorter event-free survival (EFS) (p = .033). High frequency of T cells and activated NK cells correlated with prolonged OS (p = .044 and p = .007, respectively). A small patient population (9/32) with combined low infiltrating M2 macrophages, low neutrophils, and high total T cells was identified with favorable outcome. This finding was confirmed in a validation cohort of patients with follow up (11/38). When comparing the immune TME with expression of known stemness genes, hypoxia-inducible factor 1 α (HIF1α) correlated with high abundance of macrophages and neutrophils and decreased T cell levels. The immune TME in ESFTs shows a distinct composition including rare immune cell subsets that in part may be due to expression of HIF1α.

Published
2019
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16. Supplementary Figure Legend from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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17. Supplementary Figure 2 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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18. Supplementary Figure 4 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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19. Supplementary Figure 1 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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20. Supplementary Figure 7 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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21. Supplementary Methods from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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22. Supplementary Figure 5 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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23. Supplementary Figure 3 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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24. Supplementary Figure 6 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Morales-Kastresana, Aizea, primary, Sanmamed, Miguel F., primary, Rodriguez, Inmaculada, primary, Palazon, Asis, primary, Martinez-Forero, Ivan, primary, Labiano, Sara, primary, Hervas-Stubbs, Sandra, primary, Sangro, Bruno, primary, Ochoa, Carmen, primary, Rouzaut, Ana, primary, Azpilikueta, Arantza, primary, Bolaños, Elixabet, primary, Jure-Kunkel, Maria, primary, Gütgemann, Ines, primary, and Melero, Ignacio, primary

Published
2023
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27. Supplementary Figure 3 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 946K, Anti-CTLA-4 mAb treatment fails to extend survival of c-myc OVA tg+

Published
2023
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28. Supplementary Figure 7 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 953K, TILs recognize unknown antigens in JMJ cell lines.

Published
2023
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29. Supplementary Methods from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 129K

Published
2023
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30. Data from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

Purpose: Immunostimulatory monoclonal antibodies (ISmAb) that unleash antitumor immune responses are showing efficacy in cancer clinical trials. Anti-B7-H1 (PD-L1) monoclonal antibodies (mAb) block a critical inhibitory pathway in T cells, whereas anti-CD137 and OX40 mAbs provide T-cell costimulation. A combination of these ISmAbs (anti-CD137 + anti-OX40 + anti-B7-H1) was tested using a transgenic mouse model of multifocal and rapidly progressing hepatocellular carcinoma, in which c-myc drives transformation and cytosolic ovalbumin (OVA) is expressed in tumor cells as a model antigen.Experimental Design: Flow-cytometry and immunohistochemistry were used to quantify tumor-infiltrating lymphocytes (TIL) elicited by treatment and assess their activation status and cytolytic potential. Tolerance induction and its prevention/reversal by treatment with the combination of ISmAbs were revealed by in vivo killing assays.Results: The triple combination of ISmAbs extended survival of mice bearing hepatocellular carcinomas in a CD8-dependent fashion and synergized with adoptive T-cell therapy using activated OVA-specific TCR-transgenic OT-1 and OT-2 lymphocytes. Mice undergoing therapy showed clear increases in tumor infiltration by activated and blastic CD8+ and CD4+ T lymphocytes containing perforin/granzyme B and expressing the ISmAb-targeted receptors on their surface. The triple combination of ISmAbs did not result in enhanced OVA-specific cytotoxic T lymphocyte (CTL) activity but other antigens expressed by cell lines derived from such hepatocellular carcinomas were recognized by endogenous TILs. Adoptively transferred OVA-specific OT-1 lymphocytes into tumor-bearing mice were rendered tolerant, unless given the triple mAb therapy.Conclusion: Extension of survival and dense T-cell infiltrates emphasize the translational potential of combinational immunotherapy strategies for hepatocellular carcinoma. Clin Cancer Res; 19(22); 6151–62. ©2013 AACR.

Published
2023
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31. Supplementary Figure 6 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 2976K, HCC cell lines derived from c-myc OVA tg+ mice express OVA and functional antigen presenting molecules.

Published
2023
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32. Supplementary Figure 4 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 1620K, Combo3 treatment induces infiltrates of blastic T lymphocytes and increases the CD8/Treg ratio.

Published
2023
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33. Supplementary Figure 5 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 2166K, Granzyme B, perforin and FasL are upregulated on CD8+ T cells after Combo3 treatment.

Published
2023
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34. Supplementary Figure Legend from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 109K

Published
2023
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35. Supplementary Figure 1 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 1818K, Activated T cells and tumor infiltrating lymphocytes express PD-1, B7-H1 (PD-L1), CD137 and OX40.

Published
2023
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36. Supplementary Figure 2 from Combined Immunostimulatory Monoclonal Antibodies Extend Survival in an Aggressive Transgenic Hepatocellular Carcinoma Mouse Model

Author

Ignacio Melero, Ines Gütgemann, Maria Jure-Kunkel, Elixabet Bolaños, Arantza Azpilikueta, Ana Rouzaut, Carmen Ochoa, Bruno Sangro, Sandra Hervas-Stubbs, Sara Labiano, Ivan Martinez-Forero, Asis Palazon, Inmaculada Rodriguez, Miguel F. Sanmamed, and Aizea Morales-Kastresana

Abstract

PDF file - 4662K, Three week old mice present established multifocal hepatocellular carcinomas and neonatal mice express OVA mRNA in their livers.

Published
2023
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41. Proposal of a Method for Harmonized Broth Microdilution Antimicrobial Susceptibility Testing of Avibacterium gallinarum

Author

Franziska Gütgemann, Anja Müller, Yury Churin, Arne Jung, Franziska Kumm, Annet Heuvelink, Min Yue, and Corinna Kehrenberg

Subjects
Microbiology (medical), Anti-Infective Agents, Humans, Reproducibility of Results, Microbial Sensitivity Tests, Pasteurellaceae, Clinical Veterinary Microbiology, Anti-Bacterial Agents
Abstract

Avibacterium (Av.) gallinarum is an opportunistic pathogen in poultry, which, however, has also been associated with human disease. There is currently no approved method for antimicrobial susceptibility testing of this pathogen, so this study aimed at developing a harmonized broth microdilution method for Av. gallinarum that is suitable for diagnostic laboratories. For this, the Av. gallinarum CCUG 12391(T) type strain and 42 field isolates were collected and their species was confirmed by using a species-specific PCR assay and biochemical reactions. To select epidemiologically unrelated isolates, ApaI macrorestriction analysis was performed. Preliminary growth experiments were conducted with six culture media, and based on the results, four media were selected to compile growth curves with four isolates. Independent repetitions of MIC determinations were then performed to evaluate the reproducibility of the values. Cation-adjusted Mueller-Hinton broth (CAMHB) was initially selected as broth medium, but did not show sufficient homogeneity of MICs. Therefore, CAMHB plus 1% chicken serum and 0.0025% NADH was selected and showed a good homogeneity of MICs after 20 h and 24 h of incubation at 35 ± 2°C. This was reflected in essential MIC agreements ranging between 96% and 100%. Testing of a larger Av. gallinarum collection (n = 43) revealed that easily readable MICs could be obtained for the type strain and all isolates. Some Av. gallinarum showed elevated MICs of enrofloxacin (n = 35), nalidixic acid (n = 35), penicillin (n = 2), tetracycline (n = 19), and/or trimethoprim-sulfamethoxazole (n = 1). By using PCR analyses, the following antimicrobial resistance genes were detected: bla(TEM), dfrA14, sul2, tet(B), tet(H). The study demonstrated that the proposed medium is suitable for a harmonized broth microdilution susceptibility testing of Av. gallinarum with a recommended incubation time of 20 to 24 h.

Published
2022
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42. Stemness Correlates Inversely with MHC Class I Expression in Pediatric Small Round Blue Cell Tumors

Author

Linda Müller, Maik Kschischo, Christian Vokuhl, David Stahl, and Ines Gütgemann

Subjects
Cancer Research, Oncology, stemness, MHC class I, pediatric tumors, small round blue cell tumors
Abstract

Recently, immunotherapeutic approaches have become a feasible option for a subset of pediatric cancer patients. Low MHC class I expression hampers the use of immunotherapies relying on antigen presentation. A well-established stemness score (mRNAsi) was determined using the bulk transcriptomes of 1134 pediatric small round blue cell tumors. Interestingly, MHC class I gene expression (HLA-A/-B/-C) was correlated negatively with mRNAsi throughout all diagnostic entities: neuroblastomas (NB) (n = 88, r = −0.41, p < 0.001), the Ewing’s sarcoma family of tumors (ESFT) (n = 117, r = −0.46, p < 0.001), rhabdomyosarcomas (RMS) (n = 158, r = −0.5, p < 0.001), Wilms tumors (WT) (n = 224, r = −0.39, p < 0.001), and central nervous system-primitive neuroectodermal tumors CNS-PNET (r = −0.49, p < 0.001), with the exception of medulloblastoma (MB) (n = 76, r = −0.24, p = 0.06). The negative correlation of MHC class I and mRNAsi was independent of clinical features in NB, RMS, and WT. In NB and WT, increased MHC class I was correlated negatively with tumor stage. RMS patients with a high expression of MHC class I and abundant CD8 T cells showed a prolonged overall survival (n = 148, p = 0.004). Possibly, low MHC class I expression and stemness in pediatric tumors are remnants of prenatal tumorigenesis from multipotent precursor cells. Further studies are needed to assess the usefulness of stemness and MHC class I as predictive markers.

Published
2022

49. Nestin expression in osteocytes following myeloablation and during bone marrow metastasis.

Author

Koerber, Ruth‐Miriam, Schneider, Rebekka K., Pritchard, Jessica Ellen, Teichmann, Lino L., Schumacher, Udo, Brossart, Peter, and Gütgemann, Ines

Subjects
INTERMEDIATE filament proteins, BONE marrow, NESTIN, STEM cell niches, OSTEOCYTES, MYELOFIBROSIS
Abstract

Summary: Nestin is an intermediate filament protein, which was originally detected in neuroepithelial stem cells. Besides its use as a phenotypic marker of mesenchymal stem cells in the hematopoeitic stem cell niche, the functional interpretation of nestin+ cells remains elusive. We investigated the cellular expression of nestin in bone marrow trephine biopsies of MPN patients, following myeloablation at a stage of hypocellularity during early regeneration. Here, nestin is highly expressed in mature osteocytes, arteriolar endothelial and perivascular cells and small capillaries within the bone marrow space, but not in sinusoid lining cells. This is in stark contrast to nestin expression pattern in myeloproliferative neoplasms that show hypercellularity due to oncogenic driver mutations. Here, nestin is expressed exclusively in endothelial cells of arterioles, but not in osteocytes or small capillaries. Thus, the pattern of nestin expression following myeloablation inversely correlates with cellularity in the bone marrow. This nestin expression pattern is mimicking early postnatal transcriptional programming during bone marrow development. We show that nestin expression in osteocytes occurs across different species following transplant and also in bone marrow metastasis. [ABSTRACT FROM AUTHOR]

Published
2023
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