Verena Jendrossek

Verena Jendrossek
University of Duisburg-Essen | uni-due · Institute of Cell Biology (Cancer Research), Department of Molecular Cell Biology

Dr. rer. nat., PhD

About

296
Publications
21,878
Reads
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6,465
Citations
Additional affiliations
June 2007 - present
University of Duisburg-Essen
Position
  • Head of Department
December 2001 - May 2007
Universitätsklinikum Tübingen
Position
  • Principal Investigator

Publications

Publications (296)
Article
Full-text available
Glioblastoma multiforme (GBM) is the most aggressive tumor of the central nervous system with a poor prognosis. In the treatment of GBM tumors, radiotherapy plays a major role. Typically, GBM tumors cannot be cured by irradiation because of intrinsic resistance machanisms. An escalation of the irradiation dose in the GBM tumor is difficult due to t...
Article
Full-text available
Aberrant activation of the phosphatidyl-inositol-3-kinase/protein kinase B (AKT) pathway has clinical relevance to radiation resistance, but the underlying mechanisms are incompletely understood. Protection against reactive oxygen species (ROS) plays an emerging role in the regulation of cell survival upon irradiation. AKT-dependent signaling parti...
Article
Full-text available
Oncogenic mutations in metabolic genes and associated oncometabolite accumulation support cancer progression but can also restrict cellular functions needed to cope with DNA damage. For example, gain-of-function mutations in isocitrate dehydrogenase (IDH) and the resulting accumulation of the oncometabolite D-2-hydroxyglutarate (D-2-HG) enhanced th...
Article
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Malignant pleural mesothelioma (MPM) is a rare type of cancer with a grim prognosis. So far, no targetable oncogenic mutation was identified in MPM and biomarkers with predictive value toward drug sensitivity or resistance are also lacking. Nintedanib (BIBF1120) is a small-molecule tyrosine kinase inhibitor that showed promising efficacy preclinica...
Article
Full-text available
In prostate cancer (PCa), a characteristic stromal–epithelial redistribution of the membrane protein caveolin 1 (CAV1) occurs upon tumor progression, where a gain of CAV1 in the malignant epithelial cells is accompanied by a loss of CAV1 in the tumor stroma, both facts that were correlated with higher Gleason scores, poor prognosis, and pronounced...
Chapter
Autophagy is a dynamic process that can be monitored in multiple ways, both in vitro and in vivo. Studies in mice are a widely used tool to understand multiple diseases and conditions where autophagy plays a role, and therefore autophagic flux measurement in tissues of rodent models are of utmost importance. Here, we present some assays successfull...
Chapter
Autophagy is an intracellular degradation process that maintains the cellular homeostasis and it is regulated in multiple ways, both in health and disease. Assessment of autophagic flux in cells is an important approach for understanding the function of autophagy in biological contexts. Here, we describe a new tool for the qualitative and quantitat...
Article
Full-text available
Resistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains a perpetual clinical challenge. The underlying mechanisms are manifold and demand for comprehensive, cancer entity- and subtype-specific examination. In the present study, resistance against radiotherapy was systematically a...
Article
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To enable rapid proliferation, colorectal tumor cells up-regulate epidermal growth factor receptor (EGFR) signaling and aerobic glycolysis, resulting in substantial lactate release into the tumor microenvironment and impaired anti-tumor immune responses. We hypothesized that a nutritional intervention designed to reduce aerobic glycolysis may boost...
Article
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Tumor hypoxia and hypoxic adaptation of cancer cells represent major barriers to successful cancer treatment. We revealed that improved antioxidant capacity contributes to increased radioresistance of cancer cells with tolerance to chronic-cycling severe hypoxia/reoxygenation stress. We hypothesized, that the improved tolerance to oxidative stress...
Article
Background The improvement of anticancer-therapy results in a greater amount of long-term survivors after radiotherapy. Therefore, the understanding of cardiotoxicity after irradiation is of increasing importance. Long-term adverse cardiovascular events may become evident years or decades after radiotherapy. The relative contribution of irradiation...
Article
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Cancer bioenergetics fuel processes necessary to maintain viability and growth under stress conditions. We hypothesized that cancer metabolism supports the repair of radiation-induced DNA double-strand breaks (DSBs). We combined the systematic collection of metabolic and radiobiological data from a panel of irradiated cancer cell lines with mathema...
Article
Tumor hypoxia is a major biological factor that drives resistance to chemotherapy and radiotherapy. We previously demonstrated that the pro-oxidative drug dihydroartemisinin (DHA) efficiently targeted normoxic and hypoxic cancer cells. Although well studied in normoxia, the mechanism behind DHA-mediated cytotoxicity in hypoxia is insufficiently exp...
Conference Paper
p>Flexibility and reprogramming of cancer metabolism supports cancer progression and therapy resistance. In previous work we described opportunities for overcoming environment-induced resistance to ionizing radiation (IR) by pharmacologic inhibition of metabolic processes [1,2,3]. Here, we hypothesized that certain aspects of cancer metabolism will...
Article
Full-text available
Hypoxia, a characteristic of most human solid tumors, is a major obstacle to successful radiotherapy. While moderate acute hypoxia increases cell survival, chronic cycling hypoxia triggers adaptation processes, leading to the clonal selection of hypoxia-tolerant, apoptosis-resistant cancer cells. Our results demonstrate that exposure to acute and a...
Article
Full-text available
Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective al...
Article
Radiotherapy plays a key role in the management of lung cancer patients in curative and palliative settings. Traditionally, radiotherapy was either given alone or in combination with surgery, classical cytotoxic chemotherapy, or both. Technical and physical innovations achieved during the last two decades have helped to enhance the accuracy of radi...
Conference Paper
Introduction: Balancing redox-homeostasis and energy metabolism allows cancer cells exposed to chemotherapy or radiotherapy to ensure DNA repair and survival. Our work revealed that adaptive changes in antioxidant defense and cancer cell metabolism in adverse environments enhance cancer cell radioresistance and create exploitable therapeutic metabo...
Article
Full-text available
Synonymous mutations are generally disregarded by genomic analyses because they are considered non-pathogenic. We identified and characterized a somatic synonymous mutation in the epigenetic modifier and tumor suppressor BAP1, resulting in exon skipping and complete protein inactivation. This radically altered the prognosis of a clear-cell renal ce...
Article
The efficacy of radiotherapy depends not only on DNA damage but also on ROS production, both induced by ionizing radiation. Massive ROS production can induce cell death or activate protective pathways such as Keap1/Nrf2 pathway, which regulates intracellular cysteine availability through upregulation of SLC7A11, a subunit of xCT transporter, and su...
Article
Full-text available
Various types of human cancers were characterized by an altered expression of epithelial or stromal caveolin-1 (CAV1). However, the clinical significance of CAV1 expression in penile cancer remains largely unknown. Here the expression patterns of CAV1 were analyzed in a retrospective cohort (n=43) of penile squamous cell carcinomas (SCC). Upon peni...
Article
Full-text available
Cancer resistance to chemotherapy, radiotherapy and molecular-targeted agents is a major obstacle to successful cancer therapy. Herein, aberrant activation of the phosphatidyl-inositol-3-kinase (PI3K)/protein kinase B (Akt) pathway is one of the most frequently deregulated pathways in cancer cells and has been associated with multiple aspects of th...
Article
Full-text available
The ectonucleoside triphosphate diphosphohydrolase (CD39)/5' ectonuclotidase (CD73)-dependent purinergic pathway emerges as promising cancer target. Yet, except for own previous work revealing a pathogenic role of CD73 and adenosine in radiation-induced lung fibrosis, the role of purinergic signaling for radiotherapy outcome remained elusive. Here...
Conference Paper
Background: Fractionated radiotherapy (RT) is integral part of standard treatment for locally advanced lung cancer. However radiation-induced lung disease limits the application of curative radiation doses and therapy intensification efforts of concurrent chemoradiotherapy, leading to fatal outcomes by local recurrence or metastatic disease even wh...
Article
Full-text available
Radiotherapy (RT) is applied in 45–60% of all cancer patients either alone or in multimodal therapy concepts comprising surgery, RT and chemotherapy. However, despite technical innovations approximately only 50% are cured, highlight a high medical need for innovation in RT practice. RT is a multidisciplinary treatment involving medicine and physics...
Article
Full-text available
Human lungs bear their own reservoir of endogenous mesenchymal stem cells (MSCs). Although described as located perivascular, the cellular identity of primary lung MSCs remains elusive. Here we investigated the vascular nature of lung‐resident MSCs (LR‐MSCs) using healthy human lung tissue. LR‐MSCs predominately reside within the vascular stem cell...
Article
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Cellular senescence is a key process in physiological dysfunction developing upon aging or following diverse stressors including ionizing radiation. It describes the state of a permanent cell cycle arrest, in which proliferating cells become resistant to growth-stimulating factors. Senescent cells differ from quiescent cells, which can re-enter the...
Article
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Background: Glioblastoma is a rapidly proliferating tumor. Patients bear an inferior prognosis with a median survival time of 14-16 months. Proliferation and repopulation are a major resistance promoting factor for conventionally fractionated radiotherapy. Tumor-Treating-Fields (TTFields) are an antimitotic modality applying low-intensity (1-3 V/c...
Article
Full-text available
Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons a...
Article
Full-text available
The integral membrane protein caveolin-1 (CAV1) plays a central role in radioresistance-mediating tumor–stroma interactions of advanced prostate cancer (PCa). Among the tumor–stroma, endothelial cells (EC) evolved as critical determinants of the radiation response. CAV1 deficiency in angiogenic EC was already shown to account for increased apoptosi...
Article
Full-text available
Radiotherapy (RT) is a central component of standard treatment for many cancer patients. RT alone or in multimodal treatment strategies has a documented contribution to enhanced local control and overall survival of cancer patients, and cancer cure. Clinical RT aims at maximizing tumor control, while minimizing the risk for RT-induced adverse late...
Article
Full-text available
Radiotherapy (RT) is part of standard cancer treatment. Innovations in treatment planning and increased precision in dose delivery have significantly improved the therapeutic gain of radiotherapy but are reaching their limits due to biologic constraints. Thus, a better understanding of the complex local and systemic responses to RT and of the biolo...
Article
Full-text available
Increasing evidence indicates that the heterogeneous tumor stroma supports therapy resistance at multiple levels. Fibroblasts, particularly cancer-associated fibroblasts (CAFs) are critical components of the tumor stroma. However, the impact of CAFs on the outcome of radiotherapy (RT) is poorly understood. Here, we investigated if and how fibroblas...
Conference Paper
P23-5-jD Fragestellung: Die erhöhte Tumorheterogenität und Therapieresistenz in hypoxischen Tumoren sind bedeutende Hindernisse für eine effektive Strahlentherapie. Unsere Vorarbeiten zeigen, dass die Adaptation von Tumorzellen gegenüber zyklischer schwerer Hypoxie und intermittierender Reoxygenierung (chronisch-zyklische Hypoxie) die zelluläre An...
Article
Full-text available
Extracellular adenosine is a potent endogenous immunosuppressive mediator critical to the maintenance of homeostasis in various normal tissues including the lung. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonu...
Article
Full-text available
Tumour resistance to chemo- and radiotherapy, as well as molecularly targeted therapies, limits the effectiveness of current cancer treatments. We previously reported that the radiation response of human prostate tumours is critically regulated by CAV1 expression in stromal fibroblasts and that loss of stromal CAV1 expression in advanced tumour sta...
Article
Full-text available
DNA- and histone-related research frequently comprises the quantitative analysis of protein modifications, such as histone phosphorylation. Analysis of accumulation and disappearance of protein foci are used to monitor DNA damage and repair kinetics. If the protein of interest doesn’t accumulate in foci, laser micro-irradiation of single nuclei pro...
Article
INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treate...
Article
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In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to h...
Article
Full-text available
Proton beam therapy is increasingly applied for the treatment of human cancer, as it promises to reduce normal tissue damage. However, little is known about the relationship between linear energy transfer (LET), the type of DNA damage, and cellular repair mechanisms, particularly for cells irradiated with protons. We irradiated cultured cells deliv...
Article
High tumor heterogeneity and increased therapy resistance acquired in a hypoxic tumor microenvironment remain major obstacles to successful radiotherapy. Others and we have shown that adaptation of cancer cells to cycling severe hypoxia and intermittent reoxygenation stress (chronic-cycling hypoxia) increases cellular antioxidant capacity thereby s...
Article
Full-text available
The survival kinase protein kinase B (Akt) participates in the regulation of essential subcellular processes, e.g., proliferation, growth, survival, and apoptosis, and has a documented role in promoting resistance against genotoxic stress including radiotherapy, presumably by influencing the DNA damage response and DNA double-strand break (DSB) rep...
Conference Paper
Purpose: Malignant progression of cancer cells is associated with re- duced sensitivity to reactive oxygen species (ROS) amongst others by up-regulation of the cellular antioxidant defense systems . In our hands adaptation to chronic anoxia/reoxygenation stress involved glu- tamine-dependent upregulation of cellular glutathione (GSH) levels leading...
Conference Paper
Introduction: Tumor hypoxia remains a major obstacle to successful radiotherapy . Our previous work revealed that adaptation to repeated cycles of chronic severe hypoxia and intermittent reoxygenation pro- motes tolerance to reactive oxygen species and radioresistance . Adap- tation involved a complex reprogramming of cell metabolism leading amongs...
Poster
The quantitative analysis of cells and foci plays a key role in various cell biological methods. In the field of radiation biology and molecular radiation oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction is detected by the analysis of protein clusters or phosphorylated proteins recruited...
Conference Paper
Full-text available
Introduction Hadron therapy is producing promising clinical results worldwide. The major advantages are its ability to kill radio-resistant tumour and its anti-metastatic activity. In contrast cells irradiated with gamma rays have been shown to increase the metastatic potential of cancer cells. Poly (ADP-ribose) polymerase-1(PARP-1) inhibitors have...
Conference Paper
Full-text available
Introduction Hypoxia-mediated resistance of solid tumours to ionising radiation is a major obstacle to successful radiotherapy. We showed previously that chronic cycling hypoxia drives the evolution of anoxia/reoxygenation-tolerant (ART) cancer cells with increased resistance to ionising radiation. Radiation resistance of ART cancer cells was assoc...
Conference Paper
Full-text available
Introduction Radiotherapy (RT) is part of standard treatments for locally advanced lung cancer. Biological factors such as intrinsic or microenvironment-mediated radiation resistance and tumour immune escape limit the success of lung cancer RT. Moreover, adverse late effects in the highly radiosensitive lung such as pulmonary fibrosis limit the use...
Conference Paper
Full-text available
Introduction Melanoma progression is often associated with the growth of anatomically critical metastases that require immediate therapy response, e.g. in the brain. In such situations, systemic drugs are often sequentially combined with radiotherapy. However, there is a lack of clinical and preclinical studies that systematically examine the poten...
Article
Full-text available
Pronounced resistance of lung cancer cells to radiotherapy and chemotherapy is a major barrier to successful treatment. Herein, both tumor hypoxia and the upregulation of the cellular antioxidant defense systems observed during malignant progression can contribute to radioresistance. We recently found that exposure to chronic cycling severe hypoxia...
Article
Full-text available
Genetic alterations driving aberrant activation of the survival kinase Protein Kinase B(Akt) are observed with high frequency during malignant transformation and cancer progression. Oncogenic gene mutations coding for the upstream regulators or Akt, e.g., growth factor receptors, RAS and phosphatidylinositol-3-kinase (PI3K), or for one of the three...
Conference Paper
Purpose: Hypoxia drives resistance to radio- and chemotherapy of solid tumours and goes along with poor clinical outcome. We recently demon- strated that adaptation to chronic cycling hypoxia involves complex changes in cellular antioxidant defence, mitochondrial function and cell metabolism. Metabolic adaptation involved glutamine-dependent up-reg...
Article
Aims: Radiation-induced normal tissue toxicity often precludes the application of curative radiation doses. Here we investigated the therapeutic potential of Ccl2 signaling inhibition to protect normal lung tissue from radiotherapy (RT)-induced injury. Results: RT-induced vascular dysfunction and associated adverse effects can be efficiently ant...