Refine
Has Fulltext
- yes (324)
Is part of the Bibliography
- yes (324)
Year of publication
Document Type
- Journal article (192)
- Doctoral Thesis (131)
- Review (1)
Keywords
- NFATc1 (16)
- apoptosis (15)
- NFAT (10)
- immunohistochemistry (10)
- lymphoma (10)
- Transkriptionsfaktor (9)
- Apoptose (8)
- B-Zell-Lymphom (8)
- CXCR4 (8)
- DLBCL (8)
- Non-Hodgkin-Lymphom (8)
- T-Lymphozyt (7)
- cancer (7)
- prognosis (7)
- Apoptosis (6)
- Lymphom (6)
- T cells (6)
- breast cancer (6)
- gene expression (6)
- glioblastoma (6)
- multiple myeloma (6)
- thymoma (6)
- thymus (6)
- B cells (5)
- Lymphome (5)
- Proliferation (5)
- astrocytoma (5)
- follicular lymphoma (5)
- glioblastoma multiforme (5)
- recurrence (5)
- therapy (5)
- Amplifikation (4)
- Autoaggressionskrankheit (4)
- EGFR (4)
- FISH (4)
- Fluoreszenz-in-situ-Hybridisierung (4)
- Follikuläres Lymphom (4)
- Immunhistochemie (4)
- Immuntherapie (4)
- Krebs <Medizin> (4)
- Microarray (4)
- NF-AT (4)
- Prognose (4)
- Thymom (4)
- Thymus (4)
- amplification (4)
- brain (4)
- chemokine receptor (4)
- expression (4)
- forensic neuropathology (4)
- gene regulation (4)
- mRNA (4)
- machine learning (4)
- metastasis (4)
- relapse (4)
- thymic carcinoma (4)
- transcription factors (4)
- B-Lymphozyten (3)
- Brustkrebs (3)
- CGH (3)
- EBV (3)
- Ependymom (3)
- Genexpression (3)
- Histopathologie (3)
- Hodgkin lymphoma (3)
- Immunglobulin M (3)
- Keimzentrum (3)
- Lymphknoten (3)
- Lymphoma (3)
- Lymphozyten (3)
- MALT1 (3)
- MYC (3)
- Malignes Lymphom (3)
- Medizin (3)
- Myasthenia gravis (3)
- NRF2 (3)
- PET/CT (3)
- Pathologie (3)
- T-cell lymphoma (3)
- adrenocortical carcinoma (3)
- biomarker (3)
- brain tumor (3)
- cerebrospinal fluid (3)
- comparative genomic hybridization (3)
- diffuse large B-cell lymphoma (3)
- flow cytometry (3)
- forensic neurotraumatology (3)
- germinal center (3)
- glioma (3)
- loss of heterozygosity (3)
- melanoma (3)
- monoclonal antibody (3)
- myasthenia gravis (3)
- neuronal differentiation (3)
- poor prognosis (3)
- positron emission tomography (3)
- protein (3)
- surgical oncology (3)
- AICD (2)
- ATF4 (2)
- Angeborene Immunität (2)
- Antigen (2)
- Antikörper (2)
- B-cell lymphoma (2)
- BCL6 (2)
- CD30 (2)
- CRISPR/Cas9 (2)
- CXCR2 (2)
- Colonkrebs (2)
- Cushing’s syndrome (2)
- Deletion (2)
- Differenzierung (2)
- E-cadherin (2)
- EMT (2)
- Epidermaler Wachstumsfaktor-Rezeptor (2)
- Epstein-Barr-Virus (2)
- Expression (2)
- FFPE (2)
- FGFR (2)
- Glioblastoma (2)
- Graft-versus-leukemia (2)
- HNSCC (2)
- Hodgkin (2)
- Humorale Immunität (2)
- Immuncytochemie (2)
- Immunglobuline (2)
- Immunologie (2)
- Immunotherapy (2)
- Immunsystem (2)
- KEAP1 (2)
- Krebs (2)
- LOH (2)
- Lymphogranulomatose (2)
- MALT (2)
- MALT-Lymphom (2)
- MALT-lymphoma (2)
- MPS1 (2)
- Magenkarzinom (2)
- Magenkrebs (2)
- Mammakarzinom (2)
- Mantelzell-Lymphom (2)
- Mantle cell lymphoma (2)
- Maus (2)
- Methylation (2)
- Methylierung (2)
- Mikrosatellitenanalyse (2)
- Mikrosatelliteninstabilität (2)
- Molekularbiologie (2)
- Monoklonaler Antikörper (2)
- Multiple Myeloma (2)
- NAFLD (2)
- NASH (2)
- NHL (2)
- NSCLC (2)
- Nekrose (2)
- Neuroinflammation (2)
- Nfatc1 (2)
- Onkogen (2)
- PD-L1 (2)
- PET (2)
- PTCL (2)
- Plattenepithelcarcinom (2)
- Protein p53 (2)
- Rhabdomyosarcoma (2)
- SC-1 (2)
- Signaltransduktion (2)
- Speicheldrüse (2)
- T-Lymphozyten (2)
- T-Zell-Lymphome (2)
- T-Zellen (2)
- T-cell differentiation (2)
- TAF15 (2)
- TTK (2)
- Thymuskarzinome (2)
- Transkriptionsfaktoren (2)
- Tumor (2)
- Tumorimmunologie (2)
- Tumorsuppressorgen (2)
- USP28 (2)
- VEGF (2)
- alloreactive T cells (2)
- amplicon sequencing (2)
- angiogenesis (2)
- animal model (2)
- antigen (2)
- autoimmune disease (2)
- cancer stem cells (2)
- cancers and neoplasms (2)
- carcinomas (2)
- case report (2)
- cell staining (2)
- cell-cycle arrest (2)
- chemokine (2)
- chromosomal aberration (2)
- classification (2)
- cytotoxic T cells (2)
- development (2)
- discriminant analysis (2)
- endothelial cells (2)
- enzyme-linked immunoassays (2)
- ependymoma (2)
- extranodal (2)
- gastric carcinoma (2)
- gene (2)
- genetic aberrations (2)
- genetische Aberrationen (2)
- grade 3B (2)
- humoral immunity (2)
- imaging (2)
- immune response (2)
- immunohistochemistry techniques (2)
- immunotherapy (2)
- in vivo imaging (2)
- inflammation (2)
- innate immunity (2)
- keratinocytes (2)
- kidneys (2)
- low-grade glioma (2)
- lung cancer (2)
- malignant tumors (2)
- mantle cell lymphoma (2)
- messenger RNA (2)
- miRNA (2)
- mice (2)
- microenvironment (2)
- microsatellite instability (2)
- mitochondrial DNA (2)
- molecular diagnostics (2)
- molecular imaging (2)
- mouse models (2)
- mutation (2)
- mutations (2)
- natural immunity (2)
- natürliche Antikörper (2)
- natürliche Immunität (2)
- neuroinflammation (2)
- obesity (2)
- organoids (2)
- oxidative stress (2)
- p53 (2)
- pancreatic cancer (2)
- plasma cells (2)
- positron emission tomography/computed tomography (2)
- postnatal development (2)
- principal component analysis (2)
- proteomics (2)
- radiotherapy (2)
- rat (2)
- receptor tyrosine kinases (2)
- regression analysis (2)
- regulatory T cells (2)
- senile lymphoproliferation (2)
- signal transduction (2)
- survival (2)
- targeted therapy (2)
- temozolomide (2)
- transcription (2)
- translocation (2)
- tumor immunology (2)
- tumor microenvironment (2)
- tumor suppressor gene (2)
- vestibular schwannoma (2)
- vitamin D (2)
- - (1)
- 16S-rRNA (1)
- 3D ex vivo models (1)
- 3D lung tumor tissue models (1)
- <sup>18</sup>F-FDG (1)
- <sup>68</sup>Ga-Pentixafor (1)
- AD-AID (1)
- ADAM9 (1)
- ADP-ribosylation toxins (1)
- AICDA (1)
- AID-ΔE4a (1)
- AIDS (1)
- AIRE (1)
- AKT-signaling (1)
- ALCL (1)
- ALK-1 (1)
- AMACR (1)
- AOM/DSS (1)
- APECED (1)
- ATF5 (1)
- ATG7 (1)
- ATM (1)
- Aberrationen (1)
- Activation (1)
- Activation induced cell death/AICD (1)
- Adamantiades-Behçet disease (1)
- Adult (1)
- Akute Ösophagusnekrose (1)
- Allogenic hematopoietic stem cell transplantation (1)
- Alpha therapy (1)
- Alter (1)
- Alzheimerkrankheit (1)
- Amplicon Sequencing (1)
- Anergy (1)
- Aneuploidie (1)
- Antibodies (1)
- Antigen CD30 (1)
- Antigen CD8 (1)
- Antiparanodal Autoantibodies (1)
- Aphthae (1)
- Apoptose-Resistenz (1)
- Apoptoseinduktion (1)
- Appendizitis (1)
- Autoantikörper (1)
- Autoimmune diseases (1)
- Autoimmunerkrankung (1)
- Autoimmungastritis (1)
- Autoimmunkrankheit (1)
- Autoimmunregulator (1)
- Autoregulation (1)
- B Lymphocytes (1)
- B cell lymphoma (1)
- B cell malignancies (1)
- B cell receptor (BCR) (1)
- B lymphocytes (1)
- B-Lymphozyt (1)
- B-Lymphozyt-Tumor (1)
- B-MYB (1)
- B-Zell Lymphome (1)
- B-Zell-Leukämie (1)
- B-Zell-Rezeptor (1)
- B-Zellen Differenzierung (1)
- B-cell Lymphome (1)
- B-cell differentiation (1)
- B-cells (1)
- B-lymphocytes (1)
- BAC-Konstrukt (1)
- BAC-construct (1)
- BARB-4 (1)
- BCL1 rearrangement (1)
- BCL1-Rearrangement (1)
- BCL2 (1)
- BIRC7 (1)
- BLIMP1 (1)
- BRMS1 (1)
- Barrett-Ösophagus (1)
- Bauchfellentzündung (1)
- Bauchspeicheldrüsenkrebs (1)
- Bcl-2-Gen (1)
- Bcl-2-gene (1)
- Behçet’s disease (1)
- Bevacizumab (1)
- Bioluminescence imaging (1)
- Biomarker (1)
- Bisphosphonate (1)
- Blasenkrebs (1)
- Blimp-1 (1)
- Blimp1 (1)
- Blinddarmentzündung (1)
- Bone chips (1)
- Bone marrow cells (1)
- Bone marrow transplantantation (1)
- Bone marrow transplantation (1)
- Braak (1)
- Breast-cancer (1)
- Bruton Tyrosine Kinase (1)
- Burkitt (1)
- Burkitt lymphoma (1)
- Burkitt lymphoma (BL) (1)
- B‐cell lymphoma (1)
- C-Myc (1)
- C/EBP (1)
- C/EBP-Beta (1)
- C/EBPβ (1)
- C3 (1)
- CABG-operation (1)
- CBP (1)
- CCR7 (1)
- CD 27 (1)
- CD-Marker (1)
- CD/metabolism (1)
- CD117 (1)
- CD133 (1)
- CD27 (1)
- CD274 (1)
- CD30-Rezeptor (1)
- CD319 (1)
- CD4+ (1)
- CD40 ligand (1)
- CD5-positive B-Lymphozyten (1)
- CD56 (1)
- CD8 (1)
- CD9 (1)
- CFR-1 (1)
- CHAC1 (1)
- CIITA (1)
- CK5 (1)
- COVID-19 (1)
- CRC (1)
- CRISPR-Cas9 (1)
- CRISPR/Cas-Methode (1)
- CS1 (1)
- CSF (1)
- CTL function (1)
- CTNNB1 (1)
- CX5461 (1)
- CXCL5 (1)
- CXCL8 (1)
- CXCR1 (1)
- CXCR4/SDF-1 (1)
- CXCR5 (1)
- CXCR7 (1)
- CYP24A1 (1)
- CYP2W1 (1)
- Calcineurin (1)
- Calcium (1)
- Cancer (1)
- Cancer genetics (1)
- Cancer treatment (1)
- Cancer/Testis Antigene (1)
- Cancer/Testis antigen (1)
- Candida (1)
- Carcinogenese (1)
- Cartilage Oligomeric Matrix Protein (1)
- Caspase 12 (1)
- Ccl2 (1)
- Chains (1)
- Checkpoint-Inhibitor (1)
- Chemokin (1)
- Chemokin CXCL10 (1)
- Chemokine (1)
- Chemokinrezeptor (1)
- Chemotherapy (1)
- Childhood (1)
- Chromosom 9 (1)
- Chromosome 18 (1)
- Chromosomenaberration (1)
- Cisplatin (1)
- Clonality (1)
- Clonality analysis (1)
- Cocktail (1)
- Cushings syndrome (1)
- Cushing’s disease (1)
- Cytogenetik (1)
- Cytotoxizität (1)
- DCIS (1)
- DCR1 (1)
- DEL(5Q) (1)
- DHAP (1)
- DLBCL multilobated (1)
- DLBCL multilobuliert (1)
- DLBL (1)
- DNA hypermethylation (1)
- DNA methylation (1)
- DNA-PK (1)
- DNS-Reparatur (1)
- DOTATOC (1)
- DT40 cells (1)
- DWI (1)
- Defined burkitts lymphoma (1)
- Delta Repertoire (1)
- Dendritic cells (1)
- Dendritische Zelle (1)
- Design (1)
- Diabetes mellitus (1)
- Diagnostik (1)
- Dickdarmkrebs (1)
- Differentielle Genexpression (1)
- Diffuse großzellige B-Zell Lymphome (1)
- Diffuses großzelliges B-Zell Lymphom (1)
- Diphosphonate (1)
- Durchflusszytometrie (1)
- E-Learning (1)
- EAHP/SH bone marrow workshop (1)
- EATCL (1)
- EBER in situ hybridization (1)
- EGF (1)
- EL-4 (1)
- EL-4 Zellen (1)
- ERM proteins (1)
- ETL (1)
- EZH1 (1)
- EZH2 (1)
- Endothel (1)
- Enteropathie-Typ (1)
- Entzündung (1)
- Enzephalitis (1)
- Epidemiological study (1)
- Epigenese (1)
- Epigenetics (1)
- Epigenetik (1)
- Epitope (1)
- Epstein-Ba (1)
- Epstein-Barr virus (1)
- Ewing-Sarkom (1)
- Extrafollikuläre Aktivierung (1)
- Extraocular eye muscles (1)
- F-19 MRI (1)
- FADD (1)
- FARS1 (1)
- FDG PET/CT (1)
- FGF-pathway (1)
- FINCA (1)
- FL (1)
- FL3B (1)
- FLT-PET (1)
- FTIR spectroscopy (1)
- Factor receptor (1)
- Fas (1)
- Fibrin glue (1)
- Fluoreszenzaktivierter Zellsortierer (1)
- Forskolin (1)
- Frequency (1)
- Frühdiagnostik (1)
- Frühphase (1)
- GABP (1)
- GATA-3 (1)
- GFAP (1)
- GIST (1)
- GLP-1 (1)
- GRP78 (1)
- GSH (1)
- Gallium (1)
- Gen-Anordnung (1)
- Genamplifikation (1)
- Gene (1)
- Gene-expression (1)
- Genetik (1)
- Genitoanal region (1)
- Genome wide analysis (1)
- Genregulation (1)
- Gewebemicroarray (1)
- Gewebeverlust (1)
- Glioma stem cells (1)
- Glykosylierung (1)
- Grad 3B (1)
- Grading (1)
- Graft-versus-host-disease (1)
- GvHD (1)
- GvL (1)
- Gvhd (1)
- H. pylori Gastritis (1)
- H.pylori gastritis (1)
- H2O2 (1)
- H3K27me3 (1)
- HD (1)
- HER2 conversion (1)
- HER2 targeted therapy (1)
- HER2-low (1)
- HHV8 (1)
- HNSC (1)
- HPK1 (1)
- HSC (1)
- Hals-Nasen-Ohren-Heilkunde (1)
- Hals-Nasen-Ohren-Tumor (1)
- Hans algorithm (1)
- Harnblasenkarzinom (1)
- Hautlymphom (1)
- Head (1)
- Head and neck cancers (1)
- Heavy chain mutations (1)
- Helicobacter (1)
- Helicobacter pylori (1)
- Helicobacter-pylori-Infektion (1)
- High-resolution (1)
- Hirntumor (1)
- Histologie (1)
- Histone deacetylase inhibition (1)
- Histopathology (1)
- Hitzeschockprotein (1)
- Hodgkin-Lymphom (1)
- Hodgkin´s disease (1)
- Hsp90 (1)
- Human antibodies (1)
- Humane Antikörper (1)
- Hybridom (1)
- Hypercortisolism (1)
- Hypermutation (1)
- Hypopharynxkarzinom (1)
- IDH (1)
- IDH1/2 (1)
- IFN (1)
- IFN-γ (1)
- IGF1R (1)
- IGF2BP3 (1)
- IL-10 (1)
- IL-17 (1)
- IL-2 (1)
- IL-4 (1)
- IL-5 (1)
- IL2 (1)
- IMP3 (1)
- IR (1)
- IRF4 (1)
- Ibrutinib (1)
- IgG4 (1)
- IgM (1)
- IgM isotyp (1)
- Images (1)
- Immun-Checkpoint (1)
- Immunbiologie (1)
- Immunfluoreszenz (1)
- Immunhistologie (1)
- Immunisierung (1)
- Immunität <Medizin> (1)
- Immunmodulation (1)
- Immunology (1)
- Immunoreceptors (1)
- Immunosuppression (1)
- Immunphänotyp (1)
- Immunreaktion (1)
- Immunrezeptoren (1)
- In-vivo (1)
- Inflammation (1)
- Intestinal Intraepithelial Lymphocy (1)
- Intrakranielle Blutung (1)
- Involution (1)
- Iron-oxide (1)
- Irradiation (1)
- Isoformen (1)
- JAK inhibitor (1)
- JNK (1)
- JUN (1)
- KIT (1)
- KRAS (1)
- KRAS biomarker signatures (1)
- Kaposi sarcoma (1)
- Keimzelltumor (1)
- Keimzentrumsreaktion (1)
- Keratine (1)
- Keratinozyt (1)
- Ki-67 (1)
- KiSS1 (1)
- Kidney cancer (1)
- Kiefernekrosen (1)
- Killerzelle (1)
- Kindesalter (1)
- Klarzellsarkom (1)
- Klassifikation (1)
- Klonale Evolution (1)
- Klonalitaetsanalysen (1)
- Klonalität (1)
- Knochenmetastase (1)
- Knochensialoprotein (1)
- Knock-out-Mäuse (1)
- Kolonkarzinom (1)
- Komparative Genomische Hybridisierung (1)
- Komparative genomische Hybridisierung (1)
- Krebstherapie (1)
- Kreuzreaktion (1)
- LESA (1)
- LGA (1)
- LITAF (1)
- LM-1 (1)
- Lagerungsmedium (1)
- Laminin (1)
- Langfristige Prognose (1)
- Larynxkarzinom (1)
- Lateral suboccipital craniectomy (1)
- Lesions (1)
- Leukoplakia (1)
- Leukoplakie (1)
- Lichen planus (1)
- Lichen ruber planus (1)
- Ligand (1)
- Lipom (1)
- Liposarkom (1)
- Lipotoxizität (1)
- Lokalisation (1)
- Low grade Astrocytoma (1)
- Lung-cancer (1)
- Lymph2Cx assay (1)
- Lymphadenitis (1)
- Lymphdrüse (1)
- Lymphocytes (1)
- Lymphomas (1)
- Lymphozyt (1)
- Lymphsystem (1)
- MAGE A3 (1)
- MAGE-A (1)
- MAGE-A-Antigene (1)
- MAGE-A-antigens (1)
- MALT lymphoma (1)
- MALT-Lymphome (1)
- MALT-Typ Lymphome (1)
- MALT-type lymphoma (1)
- MALT1-Gen (1)
- MALT1-gene (1)
- MAPK (1)
- MCL (1)
- MDS (1)
- MEF2D (1)
- MEK/ERK-signaling (1)
- MGMT (1)
- MGMT promoter methylation (1)
- MHC (1)
- MITF-low (1)
- MIZ1 (1)
- MMP2 (1)
- MMP9 (1)
- MRSA (1)
- MTB (1)
- MTCH2 (1)
- MTX (1)
- Malignancies (1)
- Malt (1)
- Mantelzellen (1)
- Mantelzelllymphom (1)
- Marginal zone lymphomas (1)
- Marginalzonen-B-Zell-Lymphom (1)
- Marginalzonen-Lymphome (1)
- Masaoka (1)
- Maschinelles Lernen (1)
- Mediastinum (1)
- Medical research (1)
- Mensch (1)
- Merlin (1)
- Metastases (1)
- Mikroglia (1)
- Mikrosatelliten (1)
- Mikrosatelliten-Instabilität (1)
- Milz (1)
- Mismatch (1)
- Molecular pathogenesis (1)
- Molekulargenetik (1)
- Monoklonaler Antikrper (1)
- Morphometrie (1)
- Mukosa-assoziiertes lymphatisches Gewebe (1)
- Multigentests (1)
- Multiple Sklerose (1)
- Mundhöhlentumor (1)
- Muskelzelle (1)
- Mutation (1)
- MyD88 (1)
- Myasthenia gravi (1)
- Myb-MuvB (1)
- Myc (1)
- Myeloma cells (1)
- Myelomas (1)
- Mykose (1)
- Mysthenia Gravis (1)
- N-Glykosylierungsmotive (1)
- N-glycosylation sites (1)
- NEC (1)
- NET (1)
- NF-KAPPA-B (1)
- NF-\(\kappa\)B pathway (1)
- NF-κB (1)
- NFAT in EAE (1)
- NFATc (1)
- NFATc1 sumoylation (1)
- NFATc1/αA (1)
- NFATc3 (1)
- NFATs (1)
- NFE2L2 (1)
- NFkappaB (1)
- NGS (1)
- NHLRC2 (1)
- NIH-3T3 (1)
- NLPHL (1)
- NORM-1 (1)
- NR3C1 (1)
- NSG (1)
- NSG-SGM3 (1)
- NY-ESO 1 (1)
- Natürliche Killerzelle (1)
- Nebennierenrinde (1)
- Nebennierenrindenkrebs (1)
- Nestin (1)
- Neurodegeneration (1)
- Nicotinischer Acetylcholinrezeptor (1)
- Nierenzellcarcinom (1)
- Nodo-parandopathy (1)
- Non Hodgkin Lymphoma (1)
- Non Hodgkin Lymphome (1)
- Non-Hodgkin Lymphome (1)
- Non-Hodgkin-Lymphome (1)
- Nrf2 (1)
- Nuclear Factor of Activated T cells (NFAT) (1)
- Nuclear expression (1)
- Nur77 (1)
- OBF-1 OCA-B (1)
- OCT-1-deficient mice (1)
- Oncotype DX® (1)
- OncotypeDX (1)
- OncotypeDX\(^{®}\) (1)
- Oral Precancer (1)
- Oral mucosa (1)
- Oral squamous cell carcinoma (1)
- Organoids (1)
- Osteoarthrose (1)
- Osteogeneration (1)
- Osteopontin (1)
- PAI-1 (1)
- PAM-1 (1)
- PAT-LM1 (1)
- PAT-SM6 (1)
- PCDHGC3 (1)
- PCI-32765 (1)
- PD-1 (1)
- PI3K (1)
- PKA (1)
- PLAG1 rearrangement (1)
- POLKADOTS (1)
- PRDI-BF1 (1)
- PRRT (1)
- PTCL NOS (1)
- PTEN (1)
- Paraffin (1)
- Parkinson (1)
- Parkinsons disease (1)
- Parkinson’s disease (1)
- Particles (1)
- Pathohistologie (1)
- Pathway (1)
- Pentixafor (1)
- Phylogenetik (1)
- Phänotyp (1)
- Plaques und Tangels (1)
- Plasmozytom (1)
- Plattenepithelkarzinom (1)
- Polyadenylierung (1)
- Polymerase-Kettenreaktion (1)
- Positron emission tomography (1)
- Positronen-Emissions-Tomografie (1)
- Posttranskriptionelle Regulation (1)
- Pou2af1 (1)
- Primär kutane Marginalzonen-Lymphome (1)
- Primär kutanes Lymphom (1)
- Profiling (1)
- Prog (1)
- Prognosis (1)
- Proliferation index (1)
- Proliferationsindex (1)
- Promoter (1)
- Promotor (1)
- Promotor <Genetik> (1)
- Prophylaxe (1)
- Prostata-DNA-Datenbank (1)
- Prostatakarzinom (1)
- Protein-DNA-Interaktion (1)
- Protein-Protein-Interaktion (1)
- Präkanzerose (1)
- Präkanzerosen (1)
- R-CHOP (1)
- RCC (1)
- RNA Expression (1)
- RNA probe (1)
- RNA-Sequenzierung (1)
- RNAPOL1 (1)
- RNAScope (1)
- ROS (1)
- RPS27 (1)
- RYGB (1)
- Rac (1)
- Raf (1)
- Random Forest (1)
- Rats (1)
- Receptor-Tyrosine Kinases (1)
- Regulatorgen (1)
- Regulatory-cells (1)
- Reifung (1)
- Renal cell carcinoma (1)
- Restriktionsfragmentlängenpolymorphismus (1)
- Retroperitoneum (1)
- Retroviraler Gentransfer (1)
- Rezeptor-Expression (1)
- Rezeptor-Tyrosinkinasen (1)
- Rhabdomyosarkom (1)
- Rheumatoid arthritis (1)
- Rheumatoide Arthritis (1)
- Rho-GTPases (1)
- Ribosomale RNS (1)
- Richter's syndrome (1)
- Richter-Syndrom (1)
- Risiko (1)
- Risikofaktoren (1)
- Risk factors (1)
- Rituximab plus (1)
- Riutximab (1)
- Rotatorenmanschettensyndrom (1)
- S-Phase-Fraktion (1)
- S-phase fraction (1)
- SAM-6 (1)
- SARS-CoV-2 (1)
- SB332235 (1)
- SGN-35 (1)
- SHARP-Screening (1)
- SIV (1)
- SLC7A11 (1)
- SOAT1 (1)
- SSTR (1)
- STEAP-1 (1)
- Sarkom (1)
- Schleimhaut (1)
- Schleimhaut-Ulzera (1)
- Schütteltrauma (1)
- Senile Lymphoproliferation (1)
- Sequenzdaten (1)
- Skelettmuskulatur (1)
- Soft-tissue infection (1)
- Sox9 (1)
- Speicheldrüsenkrebs (1)
- Speiseröhre (1)
- SphK1 (1)
- Spinal dissemination (1)
- Spindle cell (1)
- Spleen (1)
- Sporadic Alzheimer’s disease (1)
- Sporadische Alzheimer-Demenz (1)
- Sprue (1)
- Squamous cell carcinoma (1)
- Staging (1)
- Stammzelltransplantation (1)
- Stanzbiopsie (1)
- Staphylococcus aureus (1)
- Staphylococcus aureus immune response (1)
- Starry Sky (1)
- Sternberg-Riesenzelle (1)
- Sunitinib (1)
- Suppression (1)
- Surgery (1)
- Survival (1)
- Synovialmembran (1)
- Synovialsarkom (1)
- T Lymphocytes (1)
- T Zellen (1)
- T cell differentiation (1)
- T cell receptors (1)
- T helper cells (1)
- T lymphocyte (1)
- T(H)17 cells (1)
- T-Helfer Zellen (1)
- T-Lymphozyt info (1)
- T-Zell-Entwicklung (1)
- T-Zell-Lymphom (1)
- T-Zell-Marker (1)
- T-Zell-Reifung (1)
- T-Zell-Rezeptor (1)
- T-Zelldifferenzierung (1)
- T-cell non-Hodgkin's lymphomas (1)
- T-cell receptor (1)
- T-cell transfer (1)
- T-cells (1)
- T-follicular regulatory cell (1)
- T-lymphocytes (1)
- TAD-A (1)
- TCR signaling cascade (1)
- TGF-alpha (1)
- TP53 (1)
- TP53 mutations (1)
- T\(_{reg}\) and Foxp3 (1)
- Targeted Therapies (1)
- Targets (1)
- Telepathologie (1)
- Temozolomide (1)
- Th (1)
- Th17 (1)
- Therapie (1)
- Thomas (Arzt) (1)
- Thymocytes (1)
- Thymoma (1)
- Thymome (1)
- Thymopoese (1)
- Thymuskrankheit (1)
- Tissue-Microarray-Technik (1)
- Tlymphozyten (1)
- Tolerance (1)
- Toleranz <Biologie> (1)
- Tonsilla (1)
- Tracking (1)
- Transcription factors (1)
- Transcription-factor (1)
- Transkription <Genetik> (1)
- Transkriptionfaktoren (1)
- Transkriptionsfaktor NF-KappaB (1)
- Transkriptionsfaktor info (1)
- Translational research (1)
- Translokation (1)
- Translokation t(11;14)(q13;q32) (1)
- Translokation t(11;18) (1)
- Transplantat-Wirt-Reaktion (1)
- Transplantatabstoßung (1)
- Tregs (1)
- Trisomie (1)
- Tumor Microenvironment (1)
- Tumor Treating Fields (TTFields) (1)
- Tumor-necrosis-factor (1)
- Tumorantigen (1)
- Tumorimmunity (1)
- Tumorimmunität (1)
- Tumornephrektomie (1)
- Tumorprogression (1)
- Tumorzell-Migration (1)
- Tumour markers (1)
- Typ 1 Muskelfasern (1)
- Tyrosine kinase inhibition (1)
- UMAP (1)
- USP8 (1)
- USP9X (1)
- UV-Strahlung (1)
- Urothelkarzinom (1)
- Usage (1)
- Uveitis (1)
- VDR (1)
- VH-JgG Mutationen (1)
- Vascular endothelial Growth Factor (1)
- Venenlagerung (1)
- Verlust der Heterozygosität (1)
- Vielfalt (1)
- Virtual Microscopy (1)
- Virtuelle Mikroskopie (1)
- Vitamin-K-Mangel-Blutung (1)
- Vorhersage (1)
- WHO (1)
- WHO-Klassifikation (1)
- WNT signaling (1)
- WTAP (1)
- Waldeyer-Ring (1)
- Waldeyer´s ring (1)
- Waldeyer’s tonsillar ring (1)
- Wilms tumour (1)
- XIAP (1)
- YAP (1)
- Zellmigration (1)
- Zelltod (1)
- Zellzyklus (1)
- Zentroblastisches Lymphom (1)
- Zytokeratin (1)
- [18F]FDG-PET-CT (1)
- [18F]Fluorodeoxythymidine (1)
- [\(^{68}\)Ga] pentixafor (1)
- [\(^{68}\)Ga]Pentixafor (1)
- \(^{68}\)Ga-Pentixafor (1)
- abdominal lymph node metastases (1)
- aberrations (1)
- abnormalities (1)
- actin (1)
- actin filament (1)
- actin filaments (1)
- activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) (1)
- activation (1)
- acute esophageal necrosis (1)
- acute graft-versus host disease (1)
- acute graft-versus-host disease (1)
- acute lymphoblastic leukemia (1)
- acute lymphocytic leukaemia (1)
- acute myeloid leukaemia (1)
- acute myeloid leukemia (1)
- adenomas (1)
- adenosine kinase (1)
- adhesion (1)
- adrenal glands (1)
- adrenal tumor (1)
- adrenocortical (1)
- adrenocortical cancer (1)
- adrenocortical tissues (1)
- adrenocortical tumors (1)
- affinity (1)
- aggressive B‐cell lymphoma (1)
- allergy (1)
- allogenic stem cell transplantation (1)
- allografts (1)
- alternative splicing (1)
- aluminum granuloma (1)
- aminoacyl‐tRNA synthetases (1)
- amplifications (1)
- amyloidoma (1)
- amyloidosis (1)
- anaplasia (1)
- anaplastic large T-cell-lymphoma (1)
- anaplastic large cell lymphoma (1)
- anaplastic large cell lymphoma (ALCL) (1)
- anaplastic medulloblastoma (1)
- anaplastisch-großzellige T-Zell-Lymphome (1)
- aneuploidy (1)
- aneusomy (1)
- angeborenes Immunsystem (1)
- annecin-V (1)
- anti-CD30 drug conjugate (1)
- anti-inflammatory cytokines (1)
- antibodies (1)
- antibody (1)
- antibody-mediated (1)
- antigen loss (1)
- antigens (1)
- antikörpervermittelt (1)
- antioxidant function (1)
- aortic adventitia (1)
- aortokoronarer Venenbypass (1)
- apoptosis, Myc (1)
- appendicitis (1)
- arteriovenous loop (1)
- atopic dermatitis (1)
- atrial natriuretic peptide (1)
- aurora kinase A polymorphism (1)
- aurorakinase B (1)
- autoantibodies (1)
- autoantibody (1)
- autoantigen (1)
- autoimmune regulator (1)
- autoimmunregulator (1)
- autoimmuns gastitis (1)
- autologous transplantation (1)
- autophagy (1)
- axonally transported proteins (1)
- azacitidine (1)
- b-cell lymphoma of the MALT type (1)
- b-cell lymphomas (1)
- b-cell receptor (1)
- bacterial toxins (1)
- behavior (1)
- benige tumor (1)
- beta-catenin (1)
- binding (1)
- binding proteins (1)
- biofluid (1)
- bioinformatic clustering (1)
- biological sciences (1)
- biomarker prediction (1)
- biopsy (1)
- biosynthesis (1)
- bisphosphonate (1)
- blood–brain barrier (1)
- bone disease (1)
- bone marrow biopsy (1)
- bone marrow cells (1)
- bone marrow–spleen–liver large B‐cell lymphoma (1)
- bone metastases (1)
- bone metastasis (1)
- bone sialoprotein (1)
- boolean in silico models (1)
- botulinum C2 toxin (1)
- breast carcinoma (1)
- buparlisib (1)
- c-MYC (1)
- c-kit (1)
- c-myc (1)
- c/ebp (1)
- cAMP (1)
- cadaver multiorgan preservation (1)
- calcium (1)
- cancer care (1)
- cancer detection (1)
- cancer diagnosis (1)
- cancer metabolism (1)
- cancer of unknown primary (CUP) (1)
- cancer therapy (1)
- cancer treatment (1)
- carcinogenesis (1)
- carcinoma (1)
- carcinoma metastases to pancreas (1)
- cardiac transplantation (1)
- cardiomyocyte proliferation (1)
- cartilage oligomeric matrix protein (1)
- caspase-3 (1)
- catenin (1)
- caveolin-1 (1)
- cell binding (1)
- cell cycle and cell division (1)
- cell death (1)
- cell of origin (1)
- cells (1)
- cellular uptake (1)
- centroblastic lymphoma of the multilobated subtype (1)
- cerebellum (1)
- cerebral cortex (1)
- cerebropulmonary disease (1)
- cetuximab (1)
- checkpoint inhibition (1)
- chemokine receptor-4 (1)
- chemokinereceptor (1)
- childhood (1)
- childhood interstitial lung disease (1)
- children (1)
- children´s interstitial lung disease (chILD) lipoid pneumonia (1)
- cholesterol pneumonia (1)
- cholesterol pneumonitis (1)
- chromatin (1)
- chromosome 18 (1)
- chromosome 9 (1)
- chromosomes (1)
- chronic IBD model (1)
- chronic lymphocytic leukemia (1)
- chronische B-Zell Leukaemie (1)
- chronophin (1)
- classical Hodgkin lymphoma (1)
- cleavage (1)
- clonal evolution (1)
- clonality (1)
- clostridium botulinum (1)
- coactivator OBF-1 (1)
- coated vesicles (1)
- cofilin (1)
- colorectal carcinoma (1)
- combined immunodeficiency (1)
- combined therapy (1)
- complement system (1)
- complex (1)
- confocal Raman imaging (1)
- consensus DNA (1)
- cross-priming (1)
- cross-reaction (1)
- cutaneous T-cell-lymphoma (1)
- cycle (1)
- cyclophsophamide (1)
- cyclosporin A (1)
- cyclosporine A (1)
- cytokeratin (1)
- cytotoxicity (1)
- damage (1)
- damage responses (1)
- deformation (1)
- deletions (1)
- diagnosis (1)
- diagnostics (1)
- diffuse large B-Cell lymphoma (1)
- diffuse large B‐cell lymphoma (1)
- disease (1)
- distinct (1)
- down regulation (1)
- drug abuse (1)
- drug resistance (1)
- drug therapy (1)
- eGFP (1)
- early (1)
- early breast cancer (1)
- early diagnosis (1)
- echocardiography (1)
- ectopic lymphoid follicle (1)
- effector Treg (eTreg) (1)
- egfr (1)
- ejection fraction (1)
- embryonic lethality (1)
- encephalitis (1)
- encephalitis lethargica (1)
- endothelium (1)
- enhancer (1)
- enteropathy-type (1)
- ependyoma (1)
- ephitelial cells (1)
- epigenetics (1)
- epithelial markers (1)
- epithelium (1)
- extracorporeal membrane oxygenation (1)
- extrafollicular activation (1)
- extramedullary disease (1)
- features (1)
- ferroptosis (1)
- fetaler Acetylcholinrezeptor (1)
- fibroblast activation protein (1)
- fixation (1)
- fluorenscence (1)
- fluorescence in situ hybridisation (1)
- fluorescent-in -situ-hybridization (1)
- foetal typ acetylcholine receptor (1)
- follicular T helper cells (1)
- follicular lymphoma reactive germinal centers (1)
- follicular regulatory T cell (1)
- follikuläre Lymphome erhaltene reaktive Keimzentren (1)
- follikuläre regulatorische T-Zelle (1)
- follikulärer (1)
- forecasting (1)
- formalin (1)
- formalin-fixed (1)
- formalin-fixiert (1)
- functional characterization (1)
- fungal infection (1)
- gRNA-only (1)
- gastric bypass (1)
- gastrointestinal infections (1)
- gefitinib (1)
- genetic loci (1)
- genetics (1)
- genomic aberrations (1)
- germinal center formation (1)
- germline mutation (1)
- gesolin function (1)
- glioblastoma multiforme (GBM) (1)
- glucocorticoid excess (1)
- glutaminase inhibition (1)
- goldfish optic nerve (1)
- group 3 (1)
- growth (1)
- growth pattern (1)
- growth patterns (1)
- growth-associated protein (1)
- großzellige (1)
- gut–liver axis (1)
- head and neck (1)
- head and neck cancer (1)
- heart (1)
- heart failure (1)
- heatshockprotein (1)
- helicobacter (1)
- helicobacter pylori (1)
- helper T cells (1)
- helper T-cells (1)
- hematopoiesis (1)
- hematopoietic stem cells (1)
- hemophagocytosis (1)
- hepcidin (1)
- high numbers (1)
- high-dose chemotherapy (1)
- high-resolution analysis (1)
- high-risk Prostate Cancer (1)
- high‐grade B‐cell lymphoma (1)
- hippocampal stem cells (1)
- histopathology (1)
- hnRNP K (1)
- hormones (1)
- human (1)
- human antibodies (1)
- human brain (1)
- human cerebral endothelial cells (1)
- human genome (1)
- human monoclonal antibodies (1)
- human monoclonal antibody LM-1 (1)
- human monoclonal antibody PAM-1 (1)
- humane Antikörper (1)
- humane monoklonale Antikörper (1)
- humaner monoklonaler Antikörper LM-1 (1)
- humaner monoklonaler Antikörper PAM-1 (1)
- humanized hemato-lymphoid mice (1)
- humanized mice (1)
- hybridization (1)
- hyper-IgM syndrome type 2 (HIGM2) (1)
- hypercortisolism (1)
- hypermutation (1)
- iiron transporter (1)
- immune cells (1)
- immune check inhibitor (1)
- immune checkpoint blockade (1)
- immune checkpoint inhibitor (ICI) (1)
- immune evasion (1)
- immune infiltration (1)
- immune system (1)
- immunhistochemical analysis of DLBCL (1)
- immunhistochemisch (1)
- immunhistochemische Analyse von DLBCL (1)
- immunity (1)
- immunocytochemistry (1)
- immunofuorescence double staining (1)
- immunoglobulin promoters (1)
- immunoglobuline (1)
- immunohistochemisty (1)
- immunohistological expression analysis (1)
- immunology and microbiology section (1)
- immunophenotype (1)
- immunotherapeutics (1)
- in silico analysis (1)
- in-situ-Hybridisierung (1)
- in-situ-hybridization (1)
- in-vitro (1)
- in-vivo (1)
- independent predictor (1)
- induction (1)
- induction of apoptosis (1)
- inflammation-induced tissue demage (1)
- innate Immunität (1)
- innate antibody (1)
- integrated stress response (1)
- integrin (1)
- interaction (1)
- interleukin-8 (1)
- interleukins (1)
- intestine (1)
- intracranial bleeding (1)
- intraosseous (1)
- intravascular large B‐cell lymphoma (1)
- invasion (1)
- involution (1)
- involvement (1)
- iron in parkinsonism (1)
- iron model (1)
- iron pathology (1)
- isoforms (1)
- karyotype (1)
- kidney cancer (1)
- kinase (1)
- kinases (1)
- kinetic mechanism (1)
- knock down (1)
- knock out mice (1)
- kolorektales Karzinom (1)
- komparative genomische Hybridisierung (1)
- kras (1)
- kras-Mutation (1)
- large cell transformation (1)
- latency type (1)
- lck (1)
- lesions (1)
- leukemia (1)
- lichen planus (1)
- lineage (1)
- lineage differentiation (1)
- lipid droplets (1)
- lipids (1)
- lipoblastoma (1)
- lipoid pneumonitis (1)
- lipotoxicity (1)
- liquid biopsy (1)
- liraglutide (1)
- livin (1)
- lung fibrosis (1)
- lymph node (1)
- lymph node stromal cells (1)
- lymph node transplantation (1)
- lymphatische Tumoren (1)
- lymphocyte (1)
- lymphocyte activation (1)
- lymphocyte differentiation (1)
- lymphocytes (1)
- lymphohistiocytosis (1)
- lymphoid aggregate (1)
- lymphoid hyperplasia (1)
- lymphoid-tissue (1)
- lymphoid-tissue lymphomas (1)
- lymphomas (1)
- mRNA expression (1)
- mTOR (1)
- major histocompatibility complex (1)
- malignancies (1)
- malt lymphoma (1)
- mammalian cells (1)
- mandible (1)
- mantel cell lymphoma (1)
- marcophages (1)
- marginal zone-B-cell-Lymphoma (1)
- marrow transplantation (1)
- mass cytometry (1)
- mast cells (1)
- mastocytosis (1)
- measles virus (1)
- mediastinum (1)
- medical research (1)
- medicine (1)
- membrane topology (1)
- membrane translocation (1)
- memory B cells (1)
- meningeal inflammation (1)
- meningioma (1)
- mesenchymal markers (1)
- mesenteric lymph node (1)
- mesentery (1)
- messenger-RNA transport (1)
- metabolism (1)
- metagenomics (1)
- metastasis-associated in colon cancer 1 (MACC1) (1)
- methylation (1)
- miR-126 (1)
- miR-21 (1)
- microRNA-221 (1)
- microglia (1)
- microsatellite analysis (1)
- microsatellites (1)
- microvessel permeability (1)
- mikrobielle Diversität (1)
- mild hypothermia (1)
- mitochondriale DNA (1)
- mitochondriale DNA-Deletionen (1)
- mitosis (1)
- mitotane (1)
- mitotic genes (1)
- molecular marker (1)
- molecular subtypes (1)
- monoklonale Antikörper (1)
- monoklonaler Antikörper (1)
- morphometry (1)
- mouse model (1)
- mtDNA (1)
- mucosa-associated lymphatic tissue (1)
- mucosal ulcers (1)
- multifocal growth (1)
- multigene-array (1)
- multilobulierte centroblastische Lymphome (1)
- multiple Sclerosis immunomodulation Natalizumab (1)
- multiple sclerosis (1)
- multivariate Prognoseanalyse (1)
- multivariate data analysis (1)
- multi‐organ disease (1)
- murine homolog (1)
- mutant p53 (1)
- mutational targeting (1)
- myasthenia (1)
- mycosis fungoides (1)
- naive T-cell gene editing (1)
- natural IgG antibody (1)
- natural IgM antibodies (1)
- natural antibodies (1)
- natürliche IgM-Antikörper (1)
- natürlicher IgG-Antikörper (1)
- negative selection (1)
- nephroblastoma (1)
- nervous system (1)
- network (1)
- neurodegeneration (1)
- neurodegenerative disease (1)
- neuroendocrine tumor (1)
- neurogene Schädigung (1)
- neuromelanin (1)
- neuromucular disorders (1)
- neurooncology (1)
- neuropathology (1)
- neuroscience (1)
- neurotoxicity (1)
- neurovascular unit (1)
- neutral loss (1)
- next generation sequencing (1)
- niche (1)
- nicotinic acetylcholine receptor (1)
- nodal (1)
- nodal peripheral T-cell lymphoma (1)
- nodales peripheres T-Zell-Lymphom (1)
- nodular lymphcyte (1)
- non-GCB-Subtyp (1)
- non-GCB-like (1)
- non-Hodgkin lymphoma (1)
- non-hodgkin lymphoma (1)
- non-hodgkin-lymphoma (1)
- non-small cell lung cancer (1)
- noncoding RNAs (1)
- normal adrenal glands (1)
- notch signaling (1)
- nuclear DNA content (1)
- nuclear localization (1)
- nukleare DNA-Inhalt (1)
- nur77 (1)
- obinutuzumab (1)
- octreotide (1)
- olfactory bulb (1)
- oncogene (1)
- organotypic hippocampal slice cultures (OHSC) (1)
- orthotopic xenograft (1)
- osteoarthritis (1)
- osteonecrosis of jaw (1)
- outcomes research (1)
- outreach (1)
- oxidativer Stress (1)
- p300 (1)
- p53 expression (1)
- p53-dependent apoptosis (1)
- p53-inducible regulator (1)
- pFADD (1)
- pan-RCC (1)
- panel sequencing (1)
- panel-sequencing (1)
- panniculitis (1)
- paraffin-eingebettet (1)
- paraffin-embedded (1)
- parathyroid carcinoma (1)
- parkinson’s disease (1)
- pathogenesis (1)
- pathohistology (1)
- pathology (1)
- pathway (1)
- patient access (1)
- patient survival (1)
- pediatric (1)
- pediatric lymphoma (1)
- pembrolizumab (1)
- peptide receptor radionuclide therapy (1)
- peptide receptor radionuclide therapy (PRRT) (1)
- peptide tyrosine tyrosine (PYY) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- peripheral T-cell (1)
- peripheral T-cell lymphoma (1)
- periphere T-Zell-Lymphome (1)
- phosphatase 2A (1)
- phospholipase A(2) (1)
- plasmablasts (1)
- pleural mesothelioma (1)
- polyadenylation (1)
- post-mortem heart recovery (1)
- postencephalitic parkinsonism (1)
- posttranslational modification (1)
- posttranslationale Modifikation (1)
- potentiell therapeutisch relevante Proteine (1)
- precancerous lesions (1)
- precision oncology (1)
- prediction (1)
- primary bone marrow presentation (1)
- primary cell culture (1)
- primary cutaneous follicular B-cell lymphoma (1)
- primary cutaneous lymphoma (1)
- primary cutaneous marginal zone lymphomas (1)
- pro-inflammatory cytokines (1)
- prognostic factor (1)
- prognostic factors (1)
- prognostic marker (1)
- prognostic value (1)
- progressive multiple sclerosis (1)
- proliferation (1)
- prophylaxis (1)
- prostate cancer (1)
- prostate carcinoma (1)
- prostate gland DNA – database (1)
- prostate gland cancer (1)
- protein and mRNA expression (1)
- proteins (1)
- pseudocarcinomatous hyperplasia (1)
- pseudolymphoma (1)
- psoas muscle (1)
- psoriasis (1)
- radiation (1)
- radiation-induced migration (1)
- rag (1)
- raman spectroscopy (1)
- rare SNP (1)
- real world data (1)
- receptor expression (1)
- recurrence-free survival (1)
- refractory/relapsed lymphoma (1)
- regional development (1)
- regulatory T-cells (1)
- renal cancer (1)
- renal cell carcinoma (1)
- repeated surgery (1)
- resistance (1)
- resistance to apoptosis (1)
- restoration (1)
- retroperitoneal tumor (1)
- retroperitoneum (1)
- retroviral gene transfer (1)
- retroviral vector system (1)
- retrovirales Vektorsystem (1)
- reverse transcriptase-polymerase chain reaction (1)
- rhesus monkeys (1)
- rheumatoid arthritis (1)
- rheumatoiden Arthritis (1)
- ribosome (1)
- ribosyltransferase (1)
- risk (1)
- roquin (1)
- rotator-cuff injury (1)
- sFas (1)
- salivary gland (1)
- salivary gland neoplasia (1)
- salivary gland tumor (1)
- salivary gland tumors (1)
- salivary glands (1)
- sarcoma (1)
- scoring system (1)
- selective vulnerability (1)
- selektive Vulnerabilität (1)
- seminoma (1)
- senescence (1)
- senile Lymphoproliferation (1)
- serum (1)
- shaken baby syndrome (1)
- siv (1)
- slice culture (1)
- somatic hypermutation (1)
- somatic mutations (1)
- somatostatine (1)
- spinal-cord-injury (1)
- spleen (1)
- splice variant (1)
- sporadische Alzheimer-Demenz (1)
- squamous tumors (1)
- staphylococcal abscess (1)
- stem cell transplantation (1)
- stem-cells (1)
- stemness (1)
- stomach carcinoma (1)
- storage solution (1)
- stratification (1)
- subventricular zone (1)
- suppression (1)
- suppressor (1)
- surgery (1)
- surgical and invasive medical procedures (1)
- surgical treatment (1)
- systemic sclerosis (1)
- t cells (1)
- t(11;18)(q21;q21) (1)
- t(14;18)-negative follicular lymphoma (1)
- t(14;18)-negative follikuläre Lymphome (1)
- t-SNE (1)
- t-cell maturation (1)
- t-cell-lymphoma (1)
- target (1)
- target validation (1)
- targeted (1)
- targeted combination therapy (1)
- targeted sequencing (1)
- targeted therapies (1)
- tauopathy (1)
- telepathology (1)
- tetraspanin (1)
- tetraspanin protein (1)
- theranostics (1)
- therapeutic target (1)
- therapy response (1)
- thiol starvation (1)
- thymic epithelial tumor (1)
- thymitis (1)
- thymocytes (1)
- thymopoiesis (1)
- tissue preparation (1)
- tissuemicroarray (1)
- tofacitinib (1)
- transcript (1)
- transcription factor FOXP1 (1)
- transcriptional repression (1)
- transcriptome (1)
- transcriptomic analysis (1)
- transformation (1)
- translocation t(11;14)(q13;q32) (1)
- translocation t(11;18) (1)
- transplantation (1)
- trastuzumab (1)
- trastuzumab deruxtecan (1)
- treatment regimens (1)
- treg cells (1)
- triple-negative breast cancer (1)
- trisomy (1)
- tumor (1)
- tumor cell migration (1)
- tumor heterogeneity (1)
- tumor progression (1)
- tumor slice cultures (1)
- tumor specific antibody (1)
- tumor spheroids (1)
- tumor vaccination (1)
- tumor-vessel wall-interface model (1)
- tumorigenesis (1)
- tumormicroenvironment (1)
- tumors (1)
- tumorspecific (1)
- tumorspezifisch (1)
- tumorspezifische Antikörper (1)
- tumour heterogeneity (1)
- typ 1 muscle fibres (1)
- tyrosine kinase inhibitor (TKI) (1)
- uPA (1)
- ubiquitin (1)
- unspezifische Lymphadenitis (1)
- unsupervised clustering (1)
- up regulation (1)
- urinary bladder cancer (1)
- urothelial carcinoma (1)
- vascular wall stem and progenitor cells (1)
- vascularization model (1)
- vasculogenesis (1)
- vemurafenib (1)
- venetoclax (1)
- virus–iron interaction (1)
- visual clustering (1)
- vitamin D receptor (1)
- vitamin k deficiency bleeding (1)
- vitamin metabolism (1)
- von Economo (1)
- whole-exome sequencing (1)
- xxx (1)
- Östrogene (1)
- Überleben (1)
- Überlebenszeit (1)
- ɑ-Synuclein and iron (1)
- α-synuclein-specific T cells (1)
Institute
- Pathologisches Institut (324) (remove)
Sonstige beteiligte Institutionen
- Center for Interdisciplinary Clinical Research, Würzburg University, Würzburg, Germany (1)
- Department of Paediatric Radiology, Institute of Diagnostic and Interventional Radiology, Josef-Schneider-Straße 2, Wuerzburg 97080, Germany (1)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (1)
- Lehrstuhl für Regeneration Muskuloskelettaler Gewebe (1)
- Muskuloskelettales Centrum Würzburg (MCW) (1)
High programmed cell death 1 ligand 1 (PD-L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin- and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti-PD-1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD-L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti-PD-1-based first-line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced-stage or r/r cHL. All but two cases (97%) showed PD-L1 expression by the tumour cells in variable amounts. While MHC-I was rarely expressed in >50% of HRSC, MHC-II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD-L1 and MHC-I/II expression on early response to the highly effective anti-PD-1-based NIVAHL first-line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti-PD-1 first-line cHL treatment.
We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor.
Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients.
Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors.
Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.
Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.
Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.
Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
Background
Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial.
Case presentation
A case of a large retroperitoneal tumor of a 24-month old infant that was clinically suspicious of a malignant tumor is presented. Due to proximity to the right kidney, clinically most probably a nephroblastoma or clear cell sarcoma of the kidney was suspected. Radiological findings were ambiguous. Therefore, the mass was biopsied, and histology revealed an adipocytic lesion. Although mostly composed of mature adipocytes, in view of the age of the patient, the differential diagnosis of a (maturing) lipoblastoma was raised, which was supported by molecular analysis demonstrating a HAS2-PLAG1 fusion. The tumor was completely resected, and further histopathological workup led to the final diagnosis of a 13 cm large retroperitoneal maturing lipoblastoma. The child recovered promptly from surgery and showed no evidence of recurrence so far.
Conclusion
Although rare, lipoblastoma should be included in the differential diagnoses of retroperitoneal tumors in infants and children, and molecular diagnostic approaches could be a helpful diagnostic adjunct in challenging cases.
Background
Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt’s lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma.
Methods
We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics.
Results
We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt’s lymphoma and particularly on ‘double-hit’ MYC and BCL2 transformed lymphomas.
Conclusions
The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.
Hyper-IgM syndrome type 2 (HIGM2) is a B cell intrinsic primary immunodeficiency caused by mutations in AICDA encoding activation-induced cytidine deaminase (AID) which impair immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). Whereas autosomal-recessive AID-deficiency (AR-AID) affects both CSR and SHM, the autosomal-dominant form (AD-AID) due to C-terminal heterozygous variants completely abolishes CSR but only partially affects SHM. AR-AID patients display enhanced germinal center (GC) reactions and autoimmune manifestations, which are not present in AD-AID, suggesting that SHM but not CSR regulates GC reactions and peripheral B cell tolerance. Herein, we describe two siblings with HIGM2 due to a novel homozygous AICDA mutation (c.428-1G > T) which disrupts the splice acceptor site of exon 4 and results in the sole expression of a truncated AID variant that lacks 10 highly conserved amino acids encoded by exon 4 (AID-ΔE4a). AID-ΔE4a patients suffered from defective CSR and enhanced GC reactions and were therefore indistinguishable from other AR-AID patients. However, the AID-ΔE4a variant only partially affected SHM as observed in AD-AID patients. In addition, AID-ΔE4a but not AD-AID patients revealed impaired targeting of mutational hotspot motives and distorted mutational patterns. Hence, qualitative defects in AID function and altered SHM rather than global decreased SHM activity may account for the disease phenotype in these patients.
A Recombinant Fusion Toxin Based on Enzymatic Inactive C3bot1 Selectively Targets Macrophages
(2013)
Background: The C3bot1 protein (~23 kDa) from Clostridium botulinum ADP-ribosylates and thereby inactivates Rho. C3bot1 is selectively taken up into the cytosol of monocytes/macrophages but not of other cell types such as epithelial cells or fibroblasts. Most likely, the internalization occurs by a specific endocytotic pathway via acidified endosomes.
Methodology/Principal Findings: Here, we tested whether enzymatic inactive C3bot1E174Q serves as a macrophage-selective transport system for delivery of enzymatic active proteins into the cytosol of such cells. Having confirmed that C3bot1E174Q does not induce macrophage activation, we used the actin ADP-ribosylating C2I (~50 kDa) from Clostridium botulinum as a reporter enzyme for C3bot1E174Q-mediated delivery into macrophages. The recombinant C3bot1E174Q-C2I fusion toxin was cloned and expressed as GST-protein in Escherichia coli. Purified C3bot1E174Q-C2I was recognized by antibodies against C2I and C3bot and showed C2I-specific enzyme activity in vitro. When applied to cultured cells C3bot1E174Q-C2I ADP-ribosylated actin in the cytosol of macrophages including J774A.1 and RAW264.7 cell lines as well as primary cultured human macrophages but not of epithelial cells. Together with confocal fluorescence microscopy experiments, the biochemical data indicate the selective uptake of a recombinant C3-fusion toxin into the cytosol of macrophages.
Conclusions/Significance: In summary, we demonstrated that C3bot1E174Q can be used as a delivery system for fast, selective and specific transport of enzymes into the cytosol of living macrophages. Therefore, C3-based fusion toxins can represent valuable molecular tools in experimental macrophage pharmacology and cell biology as well as attractive candidates to develop new therapeutic approaches against macrophage-associated diseases.
Acute graft-versus-host disease (aGvHD) is a severe and often life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). AGvHD is mediated by alloreactive donor T-cells targeting predominantly the gastrointestinal tract, liver, and skin. Recent work in mice and patients undergoing allo-HCT showed that alloreactive T-cells can be identified by the expression of α4β7 integrin on T-cells even before manifestation of an aGvHD. Here, we investigated whether the detection of a combination of the expression of T-cell surface markers on peripheral blood (PB) CD8\(^+\) T-cells would improve the ability to predict aGvHD. To this end, we employed two independent preclinical models of minor histocompatibility antigen mismatched allo-HCT following myeloablative conditioning. Expression profiles of integrins, selectins, chemokine receptors, and activation markers of PB donor T-cells were measured with multiparameter flow cytometry at multiple time points before the onset of clinical aGvHD symptoms. In both allo-HCT models, we demonstrated a significant upregulation of α4β7 integrin, CD162E, CD162P, and conversely, a downregulation of CD62L on donor T-cells, which could be correlated with the development of aGvHD. Other surface markers, such as CD25, CD69, and CC-chemokine receptors were not found to be predictive markers. Based on these preclinical data from mouse models, we propose a surface marker panel on peripheral blood T-cells after allo-HCT combining α4β7 integrin with CD62L, CD162E, and CD162P (cutaneous lymphocyte antigens, CLA, in humans) to identify patients at risk for developing aGvHD early after allo-HCT.
NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived Nfatc1β expression, preTCR-positive thymocytes express both Nfatc1β and P1 promoter-derived Nfatc1α transcripts. Inducing NFATc1α activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1β from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes.
Thymome sind die einzigen Tumoren, die reife T-Zellen aus unreifen Vorläuferzellen generieren, wobei die unreifen Thymozytenpopulationen in Thymomen im Vergleich zum Thymus abnorm vermehrt und die reifen Populationen vermindert sind. Zusätzlich weist das Thymomgewebe im Vergleich zum Thymus weniger B-Zellen und Effektor-T-Zellen auf. Bisher ist unbekannt, welche Faktoren die veränderte intratumoröse Zusammensetzung der Zellpopulationen bedingen. Ziel der vorliegenden Arbeit war es daher, Mikromilieufaktoren in Thymomen mit möglichen Auswirkungen auf die intratumoröse Thymopoese zu identifizieren und deren Einfluß auf das periphere Immunsystem zu untersuchen. Im ersten Teil der vorliegenden Arbeit wurde nach Ursachen für die abnorme Thymozytenreifung und die Generierung autoreaktiver T-Zellen in Thymomen gesucht. Als potentielles Autoantigen, das die positive Selektion in Thymomen beeinflussen könnte, wurde das in Thymomen exprimierte Protein p153 als Neurofilament mittleren Molekulargewichtes (NF-M) identifiziert. Mittels T-Zell-Proliferationstests konnte gezeigt werden, daß intratumoröse T-Zellen von Thymompatienten mit Myasthenia gravis (MG) nach Stimulation mit dem mittleren Fragment dieses Proteins (NF-M-B) signifikant höhere Antworten aufwiesen als Thymozyten von Thymitispatienten oder Thymompatienten ohne MG. NF-M-B-reaktive T-Zellen waren charakteristisch für die paraneoplastische MG, wohingegen T-Zell-Antworten gegen ein Azetylcholinrezeptor (AChR)-Fragment bei allen MG-Patienten (Thymitis und Thymom) erhöht waren. Diese Ergebnisse geben einen Hinweis darauf, daß intratumoröses NF-M eine autoantigene Determinante speziell für die paraneoplastische MG darstellt. Das Mikromilieu von Thymomen wurde außerdem mittels cDNA-Arrays und RT-PCR analysiert. Als differentiell exprimierte Gene sind besonders das "Heparin-binding growth-associated molecule" (HB-GAM) und der "B-cell growth factor 1" (BCGF 1) hervorzuheben. Die Expression von HB-GAM zeigte sowohl eine Abhängigkeit vom histologischen Thymomtyp (kortikal > gemischt / medullär) als auch vom MG-Status der Patienten (MG+ > MG-).Umgekehrt wurde für den Faktor BCGF 1 eine signifikante Erhöhung in Thymomen ohne MG gefunden und keine Abhängigkeit vom histologischen Thymomtyp. Die Expression des Chemokins "Interferon-inducible T cell alpha chemoattractant" (I-TAC) war ebenfalls mit dem MG (+)-Status von Thymompatienten signifikant assoziiert. Diese Befunde machen eine Beteiligung von HB-GAM, BCGF 1 und I-TAC an der Pathogenese der paraneoplastischen MG wahrscheinlich. Im Gegensatz dazu wurde die Expression des Chemokins "Thymus-expressed chemokine" (TECK) weder durch den histologischen Thymomtyp noch durch den MG-Status der Patienten beeinflußt. TECK ist vermutlich auch in Thymomen dafür verantwortlich, daß unreife Thymozyten nicht ins Blut gelangen. Im zweiten Teil der vorliegenden Arbeit wurde mit Hilfe von FACS-Analysen und T-Zell-Proliferationsassays der Einfluß von Thymomen auf das periphere Immunsystem untersucht. Es zeigte sich, daß die veränderte Thymopoese und autoreaktive T-Zell-Funktion in Thymomen mit immunologischen Veränderungen im Blut korreliert waren. Der Anteil zirkulierender CD45RA+ CD8+ T-Zellen war bei Thymompatienten im Vergleich zu gesunden Kontrollen signifikant erhöht, in Übereinstimmung mit einer intratumorösen T-Zell-Reifung, die in Richtung der CD8+-Linie verschoben war. Auf funktioneller Ebene war die intratumorös nachweisbare, thymomtypische T-Zell-Autoreaktivität gegen NF-M-B und alpha-AChR (301-398) gleichermaßen im Thymom und Blut zu finden. Diese funktionellen Studien unterstützen die Hypothese, daß die in Thymomen stattfindende Thymopoese das periphere T-Zell-Repertoire verändert. Hinsichtlich des Importes von T-Zellen aus der Peripherie in das Thymom ergaben die funktionellen Assays dagegen, daß T-Zellen, die auf ein fremdes Antigen (Tetanus Toxoid) reagierten, nur innerhalb zirkulierender T-Zellen, nicht aber innerhalb intratumoröser Thymozyten nachweisbar waren. Ebenso fanden sich erhöhte autoreaktive T-Zell-Antworten gegen andere Fragmente des NF-M-Proteins (NF-M-A und NF-M-C) sowie für ein Fragment der delta-Untereinheit des AChR nur im Blut von Thymompatienten. Diese Befunde sprechen dafür, daß die Migration von Effektor-T-Zellen aus der Peripherie ins Thymom vermindert ist. Während die Mechanismen für diese gestörte T-Zell-Rezirkulation ins Thymom ungeklärt sind, bestand eine Korrelation zwischen der Expression des B-Zell-spezifischen Chemokins BLC (B-Lymphocyte chemoattractant) und der Anzahl der B-Zellen, die immunhistochemisch in den entsprechenden Geweben dargestellt wurden. Dieser Befund kann auf eine Rolle von BLC bei der Migration reifer B-Zellen in Thymus- bzw. Thymomgewebe hinweisen. Zusammenfassend konnten im Rahmen der vorliegenden Arbeit Mikromilieufaktoren benannt werden, die von potentieller pathogenetischer Relevanz für die gestörte, nicht-tolerogene Thymopoese innerhalb von Thymomen sind. Zweitens konnte eindeutig gezeigt werden, daß die intratumoröse Thymopoese das periphere Immunsystem beeinflußt und bei MG-assoziierten Thymomen in Richtung auf ein höheres autoreaktives Potential verändert
Actin cytoskeleton deregulation confers midostaurin resistance in FLT3-mutant acute myeloid leukemia
(2021)
The presence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with an unfavorable prognosis. FLT3 inhibitors, such as midostaurin, are used clinically but fail to entirely eradicate FLT3-ITD+AML. This study introduces a new perspective and highlights the impact of RAC1-dependent actin cytoskeleton remodeling on resistance to midostaurin in AML. RAC1 hyperactivation leads resistance via hyperphosphorylation of the positive regulator of actin polymerization N-WASP and antiapoptotic BCL-2. RAC1/N-WASP, through ARP2/3 complex activation, increases the number of actin filaments, cell stiffness and adhesion forces to mesenchymal stromal cells (MSCs) being identified as a biomarker of resistance. Midostaurin resistance can be overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant AML cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate FLT3-ITD+AML. Garitano-Trojaola et al. used a combination of human acute myeloid leukemia (AML) cell lines and primary samples to show that RAC1-dependent actin cytoskeleton remodeling through BCL2 family plays a key role in resistance to the FLT3 inhibitor, Midostaurin in AML. They showed that by targeting RAC1 and BCL2, Midostaurin resistance was diminished, which potentially paves the way for an innovate treatment approach for FLT3 mutant AML.
The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low « 1 in 1 04 T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate andflow cytometry showed a reduction of the immature \(CD4^+/CD8^+\) double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, andfinally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis.
Introduction
Spindle cell rhabdomyosarcoma of the head and neck is a very rare tumor in adults. We report on one case with long-term survival.
Case presentation
A 41-year-old nonsmoking Caucasian man presented in June 2007 with a painless swelling under his tongue. A diagnosis of a soft tissue sarcoma, and a myofibrosarcoma in particular, was made via biopsy. After multimodal treatment, including local and systemic therapy, our patient remained disease-free until September 2010. The local recurrence was treated unsuccessfully with various chemotherapy regimens. In September 2011, our patient underwent surgical resection again, and a spindle cell rhabdomyosarcoma was diagnosed. To analyze the mismatch between the original diagnosis of a myofibrosarcoma and the second diagnosis, the two specimens were reassessed, and a final diagnosis of a spindle cell rhabdomyosarcoma was made. In 2012 and 2013, our patient suffered further recurrences that were surgically treated, and he is still alive with disease six years and 10 months after the initial diagnosis in June 2007.
Conclusions
In adults, the spindle cell rhabdomyosarcoma tumor is very rare in the head and neck region. In contrast to childhood tumors, spindle cell rhabdomyosarcoma in adulthood is often associated with a poor prognosis. In the present case, the radical surgical treatment might have helped to prolong the patient’s overall survival, which has lasted more than six years. To our knowledge, this is the longest overall survival reported so far for this tumor entity in the head and neck region.
Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate–fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.
Orale Plattenepithelkarzinome entwickeln sich häufig aus Präkanzerosen. Trotz der Frühdiagnostik ist es für den Kliniker und den Pathologen meist schwierig eine Präkanzerose, die zur Entartung neigt, rechtzeitig als solche zu erkennen. MAGE-A-Antigene sind Tumorantigene, die nur in malignen Zellen vorkommen. Diese Antigene können dazu dienen, Karzinome früher als solche zu erkennen. Das Ziel dieser Studie war, diese Hypothese zu bestätigen, indem gutartige, präkanzeröse und karzinomatöse Veränderung untersucht wurden. Dazu wurden retrospektiv Biopsien der oralen Schleimhaut (orale Ulzera, Epulitiden, follikuläre Zysten, Lichen planus, Leukolakien, epitheliale Dysplasien und Carcinomata in situ) untersucht. Diese wurden immunhistochemisch mit dem polyklonalen Antikörper MAGE-A 57B angefärbt. Dabei stellte sich heraus, dass MAGE-A-Antigene nicht in gutartigen Veränderungen vorkommen, jedoch zu 33-65% in präkanzerösen und malignen Läsionen. Ein weiteres Ziel umfasste die Untersuchung der kritischen Randbereiche. Hier wurde bei den positv gefärbten Präparaten eine eindeutige Grenze zwischen benigner und maligner Schleimhaut durch die Anfärbung mit mAb-57B sichtbar.
In Lymphozyten wird nach Antigenaktivierung die Expression des Nfatc1-Gens durch Aktivierung des P1-Promoters stark induziert. Dagegen ist die, durch den Promoter P2 vermittelte Expression ebenso wie die der anderen NFAT Faktoren c2 und c3 konstitutiv. Die Akkumulation der dabei gebildeten Isoform NFATc1/αA ist sowohl für Effektorfunktionen wie die Zytokinproduktion sowie die Proliferation und das Überleben der aktivierten Zellen wichtig (Chuvpilo et al., 2002). Um die Expression des Nfatc1-Gens auf Einzelzellebene messen zu können, wurden BAC (bacterial artificial chromosom) transgene Mauslinien generiert, die einen 210kb großen Bereich des Nfatc1-Gens der Maus enthalten. In diesen Lokus wurde ein eGFP-Reportergen innerhalb des allen Isoformen gemeinsamen, dritten Exons integriert. In dieser Arbeit wird durch semiquantitative RT-PCR-Experimente von Gesamt-Milzzellen und TLymphozyten gezeigt, dass in den B6/NFATc1-eGFP-BAC-Reportermäusen die Expression der eGFP-cDNA analog zum endogenen Nfatc1-Lokus der Kontrolle der beiden Promotoren P1 und P2 unterliegt. In Western Blot Experimenten wird in diesen Zellen mittels eines NFATc1α-spezifischen Antikörpers eine induzierbare und CsA-sensitive α-GFP-Isoform - vergleichbar mit der endogenen NFATc1α-Isoform - nachgewiesen. Gleichzeitig zeigen NFATc1-Antikörper das konstitutiv exprimierte GFPβ-Protein. Die Korrelation der Expression von NFATc1 und GFP auf mRNA- und Proteinebene machen in B6/NFATc1-eGFP-BAC-Reportermäusen das GFP-Protein somit zu einem sensitiven und spezifischen Marker der NFATc1-Aktivität. In FACS-Analysen gibt der Anstieg der GFP-Fluoreszenzintensität bei Stimulation von Gesamt- Milzzellen bzw. T-Lymphozyten um bis auf das Dreifache die Induktion von NFATc1 wider. Unter dem Einfluss von CsA verbleibt die GFPFluoreszenzintensität auf dem Niveau unstimulierter Zellen. Die GFPFluoreszenz korreliert darüber hinaus bei Primärstimulation mit der Expression des IL-2-Gens, dessen Promotor mit 5 NFAT-Bindestellen den Prototyp eines NFATc1-Targets darstellt (Serfling et al., 1989). Die Analyse der Koexpression von NFATc1 und GFP mittels Fluoreszenzmikroskopie zeigt in allen stimulierten, GFP-positiven CD4+-Lymphozyten die nukleäre Lokalisation von 75 NFATc1, vor allem von NFATc1α. Die Analyse des GFP-Phänotyps in alloreaktiven T-Zellen zeigt bei Abstoßungsreaktionen in vitro („Mixed Lymphocyte Reactions“) eine selektive Zunahme der Fluoreszenz dieser Zellen um bis auf das Vierfache, was die Rolle von NFATc1 für die Effektorfunktion aktivierter T-Lymphozyten verdeutlicht. GFP und das endogene NFATc1 werden bei Stimulation konventioneller T-Zellen (Tcons, CD4+CD25-FoxP3-) stark exprimiert, während natürliche regulatorische T-Zellen (nTregs, CD4+CD25+FoxP3+) konstant geringe NFATc1- und GFP-Konzentrationen zeigen. In induzierten regulatorischen T-Lymphozyten (iTregs) supprimiert TGF- β konzentrationsabhängig die GFP-Fluoreszenz bis auf das Niveau unstimulierter Lymphozyten. Während in nTregs die Suppression des Nfatc1- Gens im wesentlichen durch FoxP3 erfolgt (Torgerson et al., 2009), scheint dies in iTregs vor allem über den TGF-β Signalweg vermittelt zu werden. Die Analyse der GFP-Expression in den verschiedenen Stadien der TZellentwicklung zeigt weiterhin deutliche Unterschiede in der Aktivität des Nfatc1-Gens. Dies wird durch die starke Aktivität des BAC-Genlokus in CD4- CD8- DN Thymozyten, welche eine sechsfach höhere GFP-Expression aufweisen als CD4+CD8+ DP Zellen, deutlich.
Das Ausmaß und die Bedeutung molekulargenetischer Veränderungen in der Pathogenese gastraler Marginalzonen B-Zell Lymphome (MZBCL) vom MALT-Typ ist derzeit noch unklar. Ein unbekannter Teil dieser niedrig-malignen Lymphome transformiert zu hoch-malignen gastralen „diffusen großzelligen B-Zell Lymphomen“ (DLBCL), jedoch besitzen diese DLBCL nicht die Translokation t(11;18)(q21;q21), die sich dagegen in den gastralen MZBCL vom MALT-Typ als die häufigste Translokation mit noch unklarer Konsequenz etablierte. Um die Pathogenese dieser Tumoren genauer zu analysieren, wurden in dieser Studie 24 gastrale MZBCL vom MALT-Typ mit 39 Mikrosatellitenmarkern auf genomische Aberrationen untersucht. Die gastralen MZBCL vom MALT-Typ können nach unseren Ergebnissen in zwei Gruppen eingeteilt werden, die in ihrer Pathogenese zwei unterschiedliche Wege gehen. Die erste Gruppe beinhaltet die Translokation t(11;18)(q21;q21)–positiven MZBCL vom MALT-Typ. Diese erwerben signifikant weniger genomische Aberrationen als die Translokation t(11;18)(q21;q21)–negativen und transformieren nicht zu DLBCL. Die zweite Gruppe bilden die Translokation t(11;18)(q21;q21)–negativen MZBCL vom MALT-Typ. Diese erlangen im Verlauf ihrer Entwicklung signifikant mehr genomische Aberrationen als die Translokation t(11;18)(q21;q21)–positiven und scheinen ein potenzieller Ursprung für sekundäre hoch-maligne DLBCL zu sein. Der „mutator-pathway“ mit dem Kennzeichen der Mikrosatelliteninstabilität (MSI) spielt nach unseren Erkenntnissen bei den gastralen MZBCL vom MALT-Typ nur eine untergeordnete Rolle, vielmehr ist die chromosomale Instabilität in Form von Deletionen (loss of heterozygosity, LOH) oder Amplifikationen von Bedeutung. Die mit 20,8% der untersuchten Fälle am häufigsten gefundene Aberration war die Amplifikation der Region 3q26.2-27, welche den BCL-6- bzw. den PIK3CA-Genlocus beinhaltet. Auch wurden Amplifikationen des MLL-Genlocus auf 11q23-24 und der Region 18q21 und LOH der Regionen 6q23.3-25.3 und 7q31 gefunden. Beim Vergleich mit den DLBCL stellte sich außerdem heraus, dass Allelverluste auf 6q und 7q frühe Ereignisse in der Progression zu DLBCL zu sein scheinen.