A5022842257- Cancer, Hypoxia, and Metabolism
- Advanced Biosensing Techniques and Applications
- Gene expression and cancer classification
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Glutathione Transferases and Polymorphisms
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Renal cell carcinoma treatment
- Cancer Genomics and Diagnostics
- Economic and Financial Impacts of Cancer
- Systemic Lupus Erythematosus Research
- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
- Hepatitis C virus research
- Metabolomics and Mass Spectrometry Studies
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Metabolism, Diabetes, and Cancer
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- Natural product bioactivities and synthesis
- Protein Degradation and Inhibitors
- Virus-based gene therapy research
- Plant biochemistry and biosynthesis
Heidelberg University
2014-2024
German Cancer Research Center
2014-2024
Pfizer (Germany)
2019-2021
CRUK/MRC Oxford Institute for Radiation Oncology
2016
Medical Research Council
2016
Cancer Research UK
2016
University of Oxford
2016
Oslo University Hospital
2006-2007
Patients with inoperable pancreatic cancer have a dismal prognosis mean life expectancy of 3–6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85–90% pancreas cancer, and immunogenic telomerase peptides been characterised. A phase I/II study was conducted to investigate the safety, tolerability, immunogenecity peptide vaccination. Survival patients also recorded. Forty-eight non-resectable received intradermal injections GV1001 at three dose levels,...
Breast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, less well-understood. Profiling of metabolism-related proteins harbors the potential establish new patient stratification regimes biomarkers promoting individualized therapy. In our study, we aimed examine relationship between metabolism-associated expression profiles clinicopathological characteristics a large cohort breast patients. specimens from 801...
Abstract GRB2 is an adaptor protein of HER2 (and several other tyrosine kinases), which we identified as a novel BECN1 (Beclin 1) interacting partner. co-immunoprecipitated with in breast cancer cell lines and regulates autophagy through mechanism involving the modulation class III PI3Kinase VPS34 activity. In ovo studies CAM (Chicken Chorioallantoic Membrane) model indicated that knockdown, well overexpression loss-of-function mutants (Y52A S86A-R88A) compromised tumor growth. These...
Betulinic acid (BA), a pentacyclic triterpene, represents new therapeutic substance that has potential benefits for treating glioblastoma. Recently, strategies producing BA derivatives with improved properties have evolved. However, few studies examined the combination of or using radiotherapy. The effects two derivatives, NVX-207 and B10, on cellular radiobiological behavior were analyzed glioblastoma cell lines (U251MG, U343MG LN229). Based IC50 values under normoxic conditions, we...
DNA sequencing and RNA are increasingly applied in precision oncology, where molecular tumor boards evaluate the actionability of genetic events individual tumors to guide targeted treatment. To work toward an additional level patient characterization, we assessed abundance activity 27 proteins 134 patients whose had previously undergone whole-exome within Molecularly Aided Stratification for Tumor Eradication Research (MASTER) program National Center Diseases, Heidelberg. Proteomic...
Breast cancer is the most common in women worldwide. The tumor microenvironment contributes to progression by inducing cell dissemination from primary and metastasis. TGF β signaling involved breast specifically elevated during metastatic transformation aggressive cancer. In this study, we performed genomewide correlation analysis of TGFBR 2 expression a panel 51 lines identified that MET coregulated with . This was confirmed at protein level human tissues. Flow cytometric luminal basal‐like...
Uncontrolled proliferation and altered metabolic reprogramming are hallmarks of cancer. Active glycolysis glutaminolysis characteristic features these required for tumorigenesis. A fine balance between cancer metabolism autophagy is a prerequisite homeostasis within cells. Here we show that glutamate pyruvate transaminase 2 (GPT2), which serves as pivot glutaminolysis, highly upregulated in aggressive breast cancers, particularly the triple-negative subtype. Abrogation this enzyme results...
Abstract Hypoxia-induced replication stress is one of the most physiologically relevant signals known to activate ATM in tumors. Recently, interactor (ATMIN) was identified as critical for stress-induced activation response aphidicolin and hydroxyurea. This suggests an essential role ATMIN regulation during hypoxia, which induces stress. However, also has a base excision repair, process that been demonstrated be repressed less efficient hypoxic conditions. Here, we demonstrate dispensable...
Hypoxia as well metabolism are central hallmarks of cancer, and hypoxia-inducible factors (HIFs) metabolic effectors crucial elements in oxygen-compromised tumor environments. Knowledge changes the expression proteins response to HIF function could provide mechanistic insights into adaptation hypoxic stress, tumorigenesis, disease progression. We analyzed time-resolved alterations metabolism-associated protein levels different oxygen potentials across breast cancer cell lines. Effects on...
Aim: Examine the effects of baseline hypertension (HTN) and statin or proton pump inhibitor (PPI) use on sunitinib treatment outcomes in STAR-TOR, a real-world registry. Materials & methods: Presence absence HTN nonuse statins PPIs were determined at registry entry. End points included overall survival (OS) progression-free (PFS). Results: Data from 557 patients. did not affect OS PFS. PFS (median [95% CI]) was longer users (9.4 [6.5–13.6] months) versus nonusers (6.9 [5.7–8.2] (p = 0.0442)....
Reverse-phase protein array (RPPA) technology uses panels of high-specificity antibodies to measure proteins and post-translational modifications in cells tissues. The approach offers sensitive precise quantification large numbers samples has thus found applications the analysis clinical pre-clinical samples. For effective integration into drug development practice, robust assays with consistent results are essential. Leveraging a collaborative RPPA model, we set out assess variability...
Targeted therapies have shown striking success in the treatment of cancer over last years. However, their specific effects on an individual tumor appear to be varying and difficult predict. Using integrative modeling approach that combines mechanistic regression modeling, we gained insights into response mechanisms breast cells due different ligand–drug combinations. The multi-pathway model, capturing ERBB receptor signaling as well downstream MAPK PI3K pathways was calibrated time-resolved...
Aim: Examine outcomes in sunitinib-treated patients by International Metastatic RCC Database Consortium (IMDC) or Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors. Patients & methods: enrolled STAR-TOR registry (n = 327). End points included overall survival, progression-free survival and objective response rate. Results: Overall was similar for IMDC 0 versus 1 (p 0.238) 2 ≥3 0.156), but different MSKCC (0 vs 1, p 0.037; ≥3, 0.001). Progression-free 3 0.306), 0.009). Objective...
Background Heterogeneity of cancer poses a huge challenge for selecting effective treatment. Gene expression data has helped identify different subtypes also breast [1] which led to improved patient stratification and therapeutic strategies. However, treatment the triple negative (TNBC) subtype, develops independent hormone other receptors, still remains challenging due heterogeneity within this subtype [2]. Metabolic transformation in long been discovered but only recently phenomenon gained...
9623 Background Telomerase is a key enzyme in the process of immortalization cancer cells and as such it holds pivotal role carcinogenesis. The catalytic subunit telomerase, hTERT expressed 85–90% pancreatic cancers. We have previously demonstrated that vaccination inoperable patients with telomerase peptide GV1001 combination GM-CSF, results high frequency immune responders (75%). Recently has been focus on imiquimod, an modulator, potential new adjuvant for vaccination. Imiquimod acts via...
4543 Background: K-RAS mutations are found in most adenocarcinoma of the pancreas, and targeting mutant RAS by vaccination may be clinical importance. The present follow-up study was performed to determine whether or not specific T cells were still long term survivors seven nine years after postoperative adjuvant with synthetic peptides Methods: During 1995–98, all together 23 patients recruited into two studies. CTN95002 (n = 10) given a single peptide (100μg) corresponding mutation...
15542 Background: Because peptide vaccines are poorly immunogenic, combination with immunological adjuvants such as GM-CSF, have been given in previous phase I/II studies of the hTERT vaccine GV1001. The objective present study was to compare response after GV1001 treatment, combined different adjuvants. Methods: an open II patients irresectable adenocarcinoma pancreas, 18–75 years old. All received intradermal injection eight times over a period 10 weeks using imiquimod adjuvant treatment...
Background Breast cancer is one of the most common causes death from among women. Significant but yet insufficient progress has been achieved due to introduction targeted therapeutics [1]. Nevertheless, advancing personalized medicine requires a detailed and comprehensive molecular characterization, particularly at protein level. This project aims advance understanding crosstalk between cancer-relevant signaling metabolism.
Reverse-phase protein array (RPPA) technology uses panels of high-specificity antibodies to measure proteins and post-translational modifications in cells tissues. The approach offers sensitive precise quantification large numbers samples has thus found applications the analysis clinical pre-clinical samples. For effective integration into drug development practice, robust assays with consistent results are essential. Leveraging a collaborative RPPA model, we set out assess variability...
631 Background: Sunitinib remains an important treatment option for mRCC, but the effect of comorbidities/comedications on sunitinib outcomes have not been fully explored. Methods: Data were collated from STAR-TOR, ongoing real-world registry. Cutoff date analysis was 19 June 2019. This subgroup assessed presence or absence hypertension (HTN), and use non-use statins proton pump inhibitors (PPIs), determined at time entry to Treatment endpoints overall survival (OS), progression-free (PFS)...
628 Background: Metastatic renal cell carcinoma (mRCC) treatment is partly informed by risk group. The two most commonly used prognostic models, the International RCC Database Consortium (IMDC) and Memorial Sloan-Kettering Cancer Center (MSKCC), stratify patients (pts) into favorable (0 factors [RFs]), intermediate (1–2 RFs) or high (≥3 groups. This study examined real-world outcomes according to IMDC MSKCC RFs in sunitinib-treated pts with mRCC. Methods: Data were extracted on 19 June 2019...