A5037696803- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Gastric Cancer Management and Outcomes
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Lymphoma Diagnosis and Treatment
- Colorectal Cancer Screening and Detection
- Radiomics and Machine Learning in Medical Imaging
- Colorectal and Anal Carcinomas
- Cancer Diagnosis and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
- Gastrointestinal Tumor Research and Treatment
- Ferroptosis and cancer prognosis
- Advanced Breast Cancer Therapies
- Ocular Oncology and Treatments
- Immune Cell Function and Interaction
- Health, psychology, and well-being
- Cutaneous Melanoma Detection and Management
- Interprofessional Education and Collaboration
- Cancer, Lipids, and Metabolism
Charité - Universitätsmedizin Berlin
2020-2024
Freie Universität Berlin
2022-2024
Humboldt-Universität zu Berlin
2022-2024
German Cancer Research Center
2018-2022
University Hospital Heidelberg
2018-2022
Heidelberg University
2018-2022
The University of Texas MD Anderson Cancer Center
2020-2021
European Molecular Biology Organization
2019
Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis colorectal cancers. Recently, this concept challenged discovery MMR‐deficient crypt foci normal mucosa. We aimed to reconstruct carcinogenesis collecting molecular and histology evidence from adenomas carcinomas. determined frequency mutation carriers immunohistochemistry systematic literature analysis. To trace back pathways...
Abstract The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neoantigens. Such neoantigens are abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) neoantigen-inducing translational frameshifts. Here, we develop tool quantify frameshift MSI colorectal endometrial cancer. Our results show that mutation...
Abstract Fatigue is the most prevalent symptom of cancer and its treatments. Changes in intestinal microbiome have been identified chronic fatigue syndrome other neuropsychiatric disorders, patients. However, association between patients with advanced cancers has not evaluated. Understanding connection will provide interventional therapeutic opportunities to manipulate improve patients’ reported outcomes. In this project, we aimed identify associations composition cross-sectional...
Microsatellite-unstable (MSI) tumours show a high load of mutational neoantigens, as consequence DNA mismatch repair deficiency. Consequently, MSI commonly present with dense immune infiltration and develop evasion mechanisms. Whether improved lymphocyte recruitment contributes to the pronounced in is unknown. We analysed density endothelial venules (HEV) postcapillary blood vessels specialised for trafficking, colorectal cancers (CRC). HEV was determined by immunohistochemical staining FFPE...
Deficits in care and impaired patient-safety have been linked to inefficient interprofessional collaborative practice. Interprofessional training wards (IPTW) are an educational intervention which aim enable students trainees from different health professions work self-responsibly order manage the medical treatment rehabilitation of real-life patients together as team. We aimed develop implement Germany´s first IPTW at department Surgery Heidelberg University Hospital.
Immune checkpoint blockade (ICB) shows remarkable clinical effects in patients with metastatic microsatellite-unstable (MSI) cancer. However, markers identifying potential non-responders are missing. We examined the prevalence of Beta-2-microglobulin ( B2M) mutations, a common immune evasion mechanism, stage IV MSI gastrointestinal cancer and its influence on pattern patients’ survival under ICB. Twenty-five metastatic, adenocarcinoma were included. Eighteen received ICB pembrolizumab one...
Lymph node-infiltrating T cells have been of particular interest in classical Hodgkin lymphoma (cHL). High rates complete therapeutic responses to antibody-mediated immune checkpoint blockade, even relapsed/refractory patients, suggest the existence a cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed microenvironment. We asked whether clonally expanded (1) were detectable cHL lymph nodes, (2) showed characteristic phenotypes, (3) by molecule expression....
Uveal melanoma is a rare and aggressive malignancy up to half of all patients will develop metastatic disease despite the effective treatment primary tumor. Insulin-like growth factors I/II play fundamental role in cell migration, proliferation, apoptosis. IMC-A12, mAb specifically targets insulin-like factor type I receptor, has shown promise preclinical studies. We performed multicenter phase II study for with uveal administered IMC-A12 10 mg/kg IV every two weeks until progression or...
Lynch syndrome (LS) is caused by a pathogenic heterozygous germline variant in one of the DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2. LS-associated colorectal carcinomas (CRCs) are characterized MMR deficiency and accumulation multiple insertions/deletions at coding microsatellites (cMS). deficiency-induced variants defined cMS loci have driver function promote tumorigenesis. Notably, PMS2 carriers face only slightly increased risk developing CRC. Here, we investigate whether...
Doublets of everolimus with letrozole or trastuzumab have demonstrated activity against HER2-positive breast cancer, suggesting that the triple combination can synergistic anticancer activity.This first-in-human dose-escalation study (NCT02152943) enrolled patients hormone receptor- positive, (defined by amplification, overexpression, mutation) treatment-refractory advanced cancers to receive escalating doses (3+3 design) daily oral (days 1-21), and intravenous (day 1) every 21 days...
In uveal melanoma (UM), gene expression profiling (GEP) is commonly used to classify metastatic risk into three groups (Class 1A, 1B, and 2). Class 1A patients have a lower of 2% at 5 years compared other groups. We aimed describe clinical features associated with the development metastasis in this low-risk group. This single-center IRB-approved retrospective case series review included all UM between February 2006 March 2019 an archived or fresh specimen classified as 1A. Cox regression...
Abstract The immune system can recognize and attack cancer cells, especially those with a high load of mutation-induced neo antigens. Such antigens are particularly abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) antigen-inducing translational frameshifts. abundance mutational renders MSI cancers sensitive checkpoint blockade. However, the neoantigen landscape...
Abstract Purpose Hematotoxicity is a common side-effect of cytotoxic gastrointestinal (GI) cancer therapies. An unsolved problem to predict the individual risk therefore decide on treatment adaptions. We applied an established biomathematical prediction model and primarily evaluated its predictive value in patients undergoing chemotherapy for GI cancers curative intent. Methods In prospective, observational multicenter study with gastro-esophageal or pancreatic ( n = 28) receiving...
Abstract Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated patterns for their prognostic and predictive impact on maintenance therapy 5‐fluorouracil/folinic acid ± panitumumab. The study was stratified according to (1) number of involved sites (single vs multiple organ metastasis), liver‐limited disease (2) liver metastasis plus one additional site, (3) ≥two sites. Kaplan‐Meier...
4051 Background: Combination of ramucirumab and paclitaxel is a standard second line therapy in gastro-esophageal adenocarcinoma (GEAC) (RAINBOW trial, Wilke et al., 2014). We integrated the PD-L1 inhibitor avelumab into this regimen aiming for synergistic efficacy. Methods: In multicenter phase II trial (NCT03966118) pts with metastatic GEAC, after progression on platinum / fluoropyrimidine based palliative 1 st -line, ECOG 0 or 1, were treated 8 mg/kg (d1,15) + 10 80 mg/m² (d1,8,15), q4w....
The HLA system represents a central component of the antigen presentation machinery. As every patient possesses defined set molecules, only certain antigens can be presented on cell surface. Thus, studying type-dependent improve understanding variation in susceptibility to various diseases, including infectious diseases and cancer. In archival formalin-fixed paraffin-embedded (FFPE) tissue, type is difficult analyze because fragmentation DNA, hindering application commonly used assays that...
Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether detected under regular surveillance (incident cancers) are phenotypically different from at first (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing high-throughput coding microsatellite (cMS) analysis, 28 incident 67 prevalent LS CRCs (n total = 95). Incident...
3528 Background: mRNA expression of amphiregulin ( AREG) and epiregulin EREG) as ligands the epidermal growth factor receptor (EGFR) were associated with response to anti-EGFR directed antibodies in metastatic colorectal cancer (mCRC). Their role for maintenance treatment remained unclear yet was investigated PanaMa trial (panitumumab (Pmab) fluorouracil/folinic acid (FU/FA) vs. FU/FA alone after Pmab+FOLFOX induction therapy RAS wild-type mCRC). Methods: Gene measured isolation 196 248...
e15539 Background: The addition of anti-EGFR antibodies (i.e. Pmab) to maintenance therapy has demonstrated improved progression-free survival (PFS) in patients with RAS wt mCRC, no impact on health related quality life (HRQOL) measured by EORTC-QLQ-C30. Here, we report the specifically assessed dermatology-related (DRQOL) from PanaMa trial (AIO KRK0212). Methods: DRQOL outcomes were using Functional Assessment Cancer Therapy- Epidermal Growth Factor Receptor Inhibitor (FACT-EGFRI),...
•We investigated the longitudinal impact of additional maintenance therapy with Pmab on DRQOL.•During induction therapy, skin toxicity as NCI-CTCAE correlated DRQOL outcomes.•Maintenance was inferior in terms outcomes according to multiple validated measures.•Choice QOL questionnaires clinical trial design should take into account expected drug profiles. BackgroundThe key endpoints for assessment effect metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed...
3539 Background: Patterns of tumor immune cell infiltration in the microenvironment are prognostic biomarkers CRC. Here, spatially resolved was analyzed for and predictive impact patients with RAS wt mCRC treated FU/FA +/- Pmab maintenance after + FOLFOX induction (PanaMa AIO KRK0212 trial). Methods: A total 12 immunological parameters (7 lymphocyte: CD3, CD8, CD45RO, FOXP3, CD20, Granzyme B, Perforin; 4 checkpoint: PD-1, PD-L1, IDO1, LAG3; 1 monocyte: CD163) were quantified...