A5041805461- Heat shock proteins research
- Protein Structure and Dynamics
- ATP Synthase and ATPases Research
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Chemokine receptors and signaling
- Radiation Therapy and Dosimetry
- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- thermodynamics and calorimetric analyses
- Esophageal Cancer Research and Treatment
- Immune Cell Function and Interaction
- Toxin Mechanisms and Immunotoxins
- Endoplasmic Reticulum Stress and Disease
- Medical Imaging Techniques and Applications
- Nanoparticle-Based Drug Delivery
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- Gastrointestinal Tumor Research and Treatment
- Effects of Radiation Exposure
- RNA modifications and cancer
- Advanced Radiotherapy Techniques
Klinikum rechts der Isar
2015-2024
Technical University of Munich
2015-2024
Klinik und Poliklinik für Strahlentherapie und Radioonkologie
2010-2023
München Klinik
2022-2023
Institute of Clinical Cancer Research
2021
German Cancer Research Center
2015-2017
Heidelberg University
2015-2017
Deutschen Konsortium für Translationale Krebsforschung
2015-2017
Helmholtz Zentrum München
2014-2017
University Hospital Regensburg
2006
Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation by optical properties, an effect causes spectral corruption. Predictions of the variations light are challenging since spatial distribution properties cannot be resolved high resolution or accuracy current methods. Spectral corruption has fundamentally limited quantification and optoacoustic methods impeded long sought-after goal imaging blood oxygen saturation (sO2) deep...
We examined the prognostic value of tumour-infiltrating lymphocytes (TILs) in patients with squamous cell carcinoma head and neck (SCCHN) after surgery postoperative cisplatin-based chemoradiotherapy. FFPE-tissue originating from 161 treated 8 DKTK partner sites was immunohistochemically stained for CD3 CD8. Their expression correlated clinicopathological characteristics as well overall survival (OS), local progression-free (LPFS) distant metastases free-survival (DMFS), also context...
Immunization of mice with a 14-mer peptide TKDNNLLGRFELSG, termed “TKD,” comprising amino acids 450–461 (aa ) in the C terminus inducible Hsp70, resulted generation an IgG1 mouse mAb cmHsp70.1. The epitope recognized by cmHsp70.1 mAb, which has been confirmed to be located TKD sequence SPOT analysis, is frequently detectable on cell surface human and tumors, but not isogenic cells normal tissues, membrane Hsp70 might thus serve as tumor-specific target structure. As shown for associated...
We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), PD-L1+ cells in patients with squamous cell carcinoma head neck (SCCHN) treated surgery postoperative chemoradiotherapy (CRT). FFPE samples from 161 were immunohistochemically stained for PD-1, CD8 PD-L1. The immune marker expression was correlated clinicopathologic characteristics, overall survival (OS), local progression-free (LPFS) distant metastases free-survival (DMFS), also context HPV16 DNA/p16...
Heat shock protein 70 (Hsp70) is frequently found on the plasma membrane of a large number malignant tumors including non-small cell lung cancer (NSCLC) and gets released into blood circulation in lipid vesicles. On one hand (m)Hsp70-positive phenotype correlates with high aggressiveness tumor, other hand, mHsp70 serves as target for natural killer (NK) cells that had been pre-stimulated Hsp70-peptide TKD plus low dose interleukin-2 (TKD/IL-2). Following activation, NK show an up-regulated...
Heat shock protein 70 (Hsp70) which is expressed on the plasma membrane of highly aggressive tumors including non-small cell lung carcinoma and glioblastoma multiforme serves as a target for Hsp70-targeting NK cells. Herein, we aimed to investigate antitumor effects combined therapy consisting ex vivo Hsp70-peptide TKD/IL-2-activated cells in combination with mouse/human anti-PD-1 antibody syngeneic xenograft cancer mouse model. Mice Hsp70 positive GL261 or human A549 were sham-treated PBS...
Abstract Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which selectively expressed on high-risk tumors serves as target for mHsp70-targeting natural killer (NK) cells. Patients advanced mHsp70-positive NSCLC may therefore benefit from therapeutic intervention involving NK The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy ex vivo–activated cells in patients after...
Tumor but not normal cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface (mHsp70) from where can be actively released. Therefore, membrane soluble Hsp70 (sHsp70) were investigated as potential tumor biomarkers for monitoring the outcome of radiation therapy. Biopsies blood collected patients with squamous carcinoma head neck (SCCHN) at different time points (before, during therapy in follow-up period). expression was determined single suspensions...
The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in the cytosol and integrated plasma membrane of tumor cells via lipid anchorage. Following stress such as non-lethal irradiation Hsp70 synthesis up-regulated. Intracellular located known to exert cytoprotective properties, however, less about (m)Hsp70. Herein, we investigate role mHsp70 sensitivity towards sublines that differ their cytosolic and/or levels. isogenic human colon carcinoma CX+ with stable...
Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56 + formalin‐fixed paraffin embedded (FFPE) tumor specimens patients with SCCHN ( N = 145) as potential indicators for survival disease recurrence. All received radical surgery postoperative cisplatin‐based radiochemotherapy (RCT)....
Abstract Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. Membrane‐bound 70 kDa heat shock protein (mHsp70) is ubiquitously expressed on the cell membrane of various tumor types but not normal cells and therefore provides a tumor‐specific target. The serine protease granzyme B (GrB) that produced an effector molecule by activated T NK has been shown to specifically target mHsp70 cells. Following binding...
Triple-negative breast cancer (TNBC) a highly aggressive tumor entity with an unfavorable prognosis, is treated by multimodal therapies, including ionizing radiation (IR). Radiation-resistant cells, as well induced normal tissue toxicity, contribute to the poor clinical outcome of disease. In this study, we investigated potential novel hybrid iron oxide (Fe3O4)-gold (Au) nanoparticles (FeAuNPs) functionalized heat shock protein 70 (Hsp70) tumor-penetrating peptide (TPP) and coupled via PEG4...
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials α<sub>v</sub>β<sub>3</sub> integrin–targeted molecular technologies PDAC using genetically engineered mouse models. <b>Methods:</b> Immunohistochemistry and Western blot were used characterization expression in murine human PDAC. We applied IntegriSense 680 fluorescence...
Abstract High precision in vivo PET/CT imaging of solid tumors improves diagnostic credibility and clinical outcome patients. An epitope the oligomerization domain Hsp70 is exclusively exposed on membrane a large variety tumor types, but not normal cells, thus provides universal tumor-specific target. Here we developed novel PET tracer TPP-PEG24-DFO[89Zr] based cell–penetrating peptide probe TPP, which specifically recognizes (mHsp70) cells. The implemented PEG24 moiety supported stability...
Membrane heat shock protein 70 (mHsp70) is indicative of high-risk tumors and serves as a tumor-specific target for natural killer (NK) cells stimulated with Hsp70 peptide (TKD) Interleukin(IL)-2. Radiochemotherapy (RCT), mHsp70-targeting NK cells, programmed death(PD)-1 inhibition were combined to improve the efficacy immune in non-small cell lung carcinoma (NSCLC) patient.Following simultaneous RCT (64.8 Gy), patient inoperable NSCLC (cT4, cN3, cM0, stage IIIb) was treated 4 cycles...
Abstract Purpose: Barrett's esophagus represents an early stage in carcinogenesis leading to esophageal adenocarcinoma. Considerable evidence supports a major role for chronic inflammation and diverse chemokine pathways the development of Experimental Design: Here we utilized IL1β transgenic mouse model adenocarcinoma human patient imaging analyze importance CXCR4-expressing cells during carcinogenesis. Results: overexpression induces recapitulates progression CXCR4 expression is increased...
Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several techniques. Due to the possibility surface modification, nanoparticles are predestined facilitate molecular tumor targeting. this work, we demonstrate feasibility anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold (cmHsp70.1-AuNPs) tumor-specific...
In contrast to normal cells, tumor cells of multiple entities overexpress the Heat shock protein 70 (Hsp70) not only in cytosol, but also present it on their plasma membrane a tumor-specific manner. Furthermore, Hsp70-positive actively release Hsp70 small extracellular vesicles with biophysical characteristics exosomes. Due conformational changes lipid environment, most commercially available antibodies fail detect membrane-bound and vesicular Hsp70. To fill this gap assess role circulation...
Although it has been established that cannabidiol (CBD), the major non-psychoactive constituent of cannabis, exerts antitumoral activities, exact mechanism(s) via which tumor cells are killed by CBD not well understood. This study provides new insights into potential mechanisms CBD-induced mutual antagonism apoptosis and macroautophagy using wild type (HCT116 p53wt, LS174T p53wt), knockout p53-/-) mutant (SW480 p53mut) human colorectal cancer (CRC). causes a more pronounced loss in viability...
Abstract Purpose 68 Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvβ6-integrin for imaging of carcinomas. 177 Lu-D0301 a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability. We therefore evaluated the impact different protection strategies on biodistribution both agents normal and tumor-bearing mice. Methods Ex-vivo (90 min p.i.) 24 h was determined healthy C57BL/6N...
The major stress-inducible heat shock protein 70 (Hsp70) is frequently present on the cell surface of human tumours, but not normal cells. Herein, binding characteristics cmHsp70.1 mouse monoclonal antibody (mAb) were evaluated in vitro and a syngeneic tumour model. More than 50% CT26 colon carcinoma cells express Hsp70 their at 4°C. After temperature shift to 37°C, cmHsp70.1-fluorescein isothiocyanate mAb translocates into early endosomes lysosomes. Intraoperative near-infrared fluorescence...
Background We have previously used a unique mouse monoclonal antibody cmHsp70.1 to demonstrate the selective presence of membrane-bound form Hsp70 (memHsp70) on variety leukemia cells and single cell suspensions derived from solid tumors different entities, but not non-transformed or corresponding 'healthy' tissue. This can be image in vivo target them for antibody-dependent cellular cytotoxicity. Tumor-specific expression memHsp70 therefore has potential exploited theranostic purposes....