A5066285269- Chronic Myeloid Leukemia Treatments
- Advanced Breast Cancer Therapies
- Fibroblast Growth Factor Research
- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- Eosinophilic Disorders and Syndromes
- Bladder and Urothelial Cancer Treatments
- Colorectal Cancer Treatments and Studies
- Neuroendocrine Tumor Research Advances
- NF-κB Signaling Pathways
- Viral-associated cancers and disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Acute Lymphoblastic Leukemia research
- Lymphoma Diagnosis and Treatment
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Kruppel-like factors research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Renal cell carcinoma treatment
- Radiomics and Machine Learning in Medical Imaging
- Mycobacterium research and diagnosis
- CNS Lymphoma Diagnosis and Treatment
- Autoimmune Neurological Disorders and Treatments
- Genomics, phytochemicals, and oxidative stress
Bayer (Germany)
2015-2021
Bayer (United States)
2020-2021
Bayer (Switzerland)
2021
Charité - Universitätsmedizin Berlin
2010-2015
Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous diagnostic category with distinct molecular subtypes that can be defined by gene expression profiling. However, even within these subtypes, heterogeneity prevails. To further elucidate the pathogenesis of entities, we determined tumor suppressor phosphatase and tensin homolog (PTEN) in 248 primary DLBCL patient samples. These analyses revealed loss PTEN was detectable 55% germinal center B-cell-like (GCB) DLBCLs, whereas this...
The protease activity of the paracaspase Malt1 contributes to antigen receptor-mediated lymphocyte activation and lymphomagenesis. is required for optimal NF-κB activation, but little known about responsible substrate(s). Here we report that cleaved family member RelB after Arg-85. cleavage induced its proteasomal degradation specifically controlled DNA binding RelA- or c-Rel–containing complexes. Overexpression inhibited expression canonical target genes led impaired survival diffuse large...
Thyroid dysfunction is a well-known adverse effect of first-generation tyrosine kinase inhibitors (TKIs), like sunitinib. The aim this study was to investigate the second-generation TKIs on thyroid function.We retrospectively assessed TKI imatinib and nilotinib dasatinib function tests in 73 Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia patients.Overall, 33 (45%) had one or more test abnormalities during follow-up. Hypothyroidism hyperthyroidism were found 18 (25%)...
4513 Background: Activation of FGFR signaling is involved in a variety malignancies including advanced urothelial cancer (UC). Rogaratinib an oral pan-FGFR kinase inhibitor. We report here the results from phase I expansion cohort UC patients prescreened for FGFR1-3 mRNA expression levels with particular attention to activity (pts) evidence activating mutations potential resistance genes, PIK3CA and RAS. (NCT01976741) Methods: Pts carcinomas were selected based on high biopsy specimens....
3108 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions encode tropomyosin (TRK) fusion proteins, which are oncogenic drivers in various tumor types. Larotrectinib is a first-in-class, highly selective, CNS-active TRK inhibitor approved to treat adult and pediatric patients with cancer. demonstrated an objective response rate (ORR) of 78% median progression-free survival (PFS) 36.8 months integrated analysis 175 non-primary CNS cancer (McDermott et al, ESMO 2020). We...
Additional chromosomal aberrations in Philadelphia chromosome-positive chronic myeloid leukemia are non-random and strongly associated with disease progression, but their prognostic impact effect on treatment response is not clear. Point mutations the BCR-ABL kinase domain probably most common mechanisms of imatinib resistance.We assessed influence additional to second-generation tyrosine inhibitor nilotinib after imatinib-failure. Standard cytogenetic analysis metaphases was performed...
To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, expansion to clinical benefit at the recommended phase II (RP2D). Two I dose-escalation studies evaluated two dosing schedules: 3 days on/4 off or 4 weeks on/2 off. The included small-cell lung cancer (SCLC), ovarian cancer, tumour mutations involving CDK signalling pathway. Ten were evaluable schedule (terminated following limited tolerability) 47 cohorts. On schedule, RP2D...
494 Background: Activation of FGFR signaling is involved in a variety malignancies including advanced urothelial cancer (UC). Rogaratinib an oral pan-FGFR kinase inhibitor. We report here the results from phase I expansion cohort UC patients prescreened for FGFR1-3 mRNA expression levels and activating mutations. (NCT01976741) Methods: Patients with carcinomas were selected based on high biopsy specimens. Selected treated rogaratinib 800mg twice daily until tumour progression, untolerable...
This phase Ib/II study evaluated safety, pharmacokinetics, maximum tolerated dose (MTD), and efficacy of the pan-cyclin-dependent kinase inhibitor roniciclib with cisplatin-etoposide (CIS-ETOP) or carboplatin-etoposide (CARBO-ETOP) in patients extensive-disease small-cell lung cancer (ED-SCLC).In this open-label, non-randomized study, previously untreated ED-SCLC received twice daily (BID) a 3 days on/4 off schedule. Cisplatin 75 mg/m2 carboplatin (AUC5) was administered on day 1, etoposide...
NTRK gene fusions are targetable oncogenic drivers independent of tumor type. Prevalence varies from highly recurrent in certain rare tumors to <1% common cancers. The selective TRK inhibitor larotrectinib was shown be active adult and pediatric patients with harboring fusions.We examined the techniques used by local sites detect enrolled clinical trials larotrectinib. We also report characteristics detected different types.The analysis included 225 19 types. Testing methods were...
e15091 Background: CDK 8 /CDK19 are kinases involved in transcriptional control of embryonic development and cellular homeostasis via the mediator complex. They also described to maintain tumor dedifferentiation stem cell properties. A variety cancer cells hijack complex targeting cancer-specific gene transcription CDK8/19 inhibition has potential for treatment solid tumors. RVU120 (SEL120) is a selective inhibitor with preclinical efficacy hematologic malignancies types (Rzymski et al....
e20661 Background: FGFR1 gene amplifications are observed in squamous (sq) non-small cell lung cancer (NSCLC) and may suggest tractable oncogenic dependency. However, their value predicting clinical activity of FGFR inhibitors is unclear. We explored tumor FGFR1-3 mRNA expression levels to select patients (pts) for treatment with rogaratinib, an oral, potent, small-molecule inhibitor FGFR1-4. The first-in-human study rogaratinib included pts all NSCLC histologies. Methods: Pts refractory...
527 Background: Aberrant activation of the fibroblast growth factor receptor (FGFR) pathway is implicated in many cancers, including UC. In a recent Phase I dose-escalation study, rogaratinib, an oral pan-FGFR1-4 inhibitor, demonstrated favorable efficacy and safety pts with solid cancers selected based on FGFR1-3 mRNA overexpression. We report results from expansion cohort rogaratinib UC by overexpression and/or FGFR3-activating mutations (NCT01976741). Methods: Pts advanced/metastatic were...
Allogeneic stem cell transplant recipients are prone to infections by various organisms. Tuberculosis (TB) represents a rare infectious complication, especially in countries non-endemic for TB.Here, we report the case of German patient with exposure TB decades before he was diagnosed disseminated as well synchronous Epstein-Barr virus associated lymphoproliferative disorder and cytomegalovirus infection after allogeneic transplantation refractory acute myeloid leukemia. Tuberculostatic...
Limbic encephalitis is an inflammatory disease of the central nervous system characterized by diverse neurologic symptoms including mnestic disturbances, hallucinations, and seizures as well behavioral like depression, personality changes, acute confusional states resembling dementia. Several antibodies have been described in pathogenesis limbic encephalitis. It often a paraneoplastic syndrome associated with small cell lung cancer, breast or Hodgkin’s lymphoma among others. Here, we report...
3114 Background: Larotrectinib is a highly selective, CNS-active tropomyosin receptor kinase (TRK) inhibitor that demonstrated rapid and durable responses in three phase I/II single-arm studies of patients (pts) with TRK fusion cancer. In the growth modulation index (GMI) can be used to provide comparative analysis. GMI an intra-patient comparison uses pts as their own control by comparing progression-free survival (PFS) on current therapy time progression or treatment failure (TTP) most...