Publications by authors named "Hans Urban"

Article Synopsis
  • The study investigates the use of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) as a less invasive alternative to brain biopsies for diagnosing brain tumors and addressing tumor heterogeneity.
  • A total of 33 CSF samples were collected from 30 patients, and shallow whole-genome sequencing was performed, revealing significant somatic copy number aberrations (SCNAs) in brain tumor patients' cfDNA.
  • The findings suggest that cfDNA analysis can effectively identify relevant genomic alterations, offering insights into tumor evolution and heterogeneity, thus enhancing diagnostic accuracy for CNS cancers.
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Glioblastoma, the most frequent primary malignant brain tumour in adults, is characterised by profound yet dynamic hypoxia and nutrient depletion. To sustain survival and proliferation, tumour cells are compelled to acquire metabolic plasticity with the induction of adaptive metabolic programs. Here, we interrogated the pathways necessary to enable processing of nutrients other than glucose.

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In glioblastoma (GB) cells oxidative stress is induced by both, conditions of the tumor microenvironment as well as by therapeutic interventions. Upregulation of superoxide dismutase 1 (SOD1), a key enzyme for oxidative defense and downstream target of mammalian target of rapamycin complex 1 (mTORC1) is a candidate mechanism to sustain survival and proliferation of tumor cells. SOD1 was inhibited by shRNA mediated gene suppression, CRISPR/Cas9 knockout and pharmacological inhibition in human (primary) GB cells.

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Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches. Apoptosis induction in GB cells is inefficient, due to an excess of anti-apoptotic XPO1/Bcl-2-family proteins. We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs).

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Objective: Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population.

Methods: This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017.

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Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care.

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Glioblastoma is an incurable brain tumor with a median survival below two years. Trials investigating targeted therapy with inhibitors of the kinase mTOR have produced ambiguous results. Especially combination of mTOR inhibition with standard temozolomide radiochemotherapy has resulted in reduced survival in a phase II clinical trial.

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Article Synopsis
  • Critically ill COVID-19 patients, particularly those treated with veno-venous ECMO (VV-ECMO), showed a higher incidence of acute neurological symptoms and pathological neuroimaging findings compared to those not on VV-ECMO.
  • The study reviewed data from 440 patients, indicating that VV-ECMO patients had a significantly lower survival rate during hospitalization (15% had VV-ECMO treatment) and experienced acute neurological issues more frequently.
  • Follow-up assessments suggested that while VV-ECMO was associated with acute neurological symptoms, its correlation with severe neuroimaging abnormalities was weak, highlighting complex outcomes for patients with severe COVID-19.
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Purpose: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy.

Methods: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University.

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Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab.

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Superficial siderosis is a consequence of repetitive bleeding into the subarachnoid space, leading to toxic iron and hemosiderin deposits on the surface of the brain and spine. The clinical and radiological phenotypes of superficial siderosis are known to manifest over long time intervals. In contrast, this study defines the "acute superficial siderosis syndrome" and illustrates typical imaging and histopathological findings of this entity.

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Background: The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.

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Article Synopsis
  • The integrated stress response (ISR) helps cells adapt to stressors like nutrient deprivation and oxygen scarcity, mainly through the activation of the protein ATF4.
  • Researchers studied the role of ATF4 in human glioblastoma (GB) cells to see how it affects their survival and resistance to chemotherapy, specifically temozolomide.
  • Findings showed that inhibiting ATF4 made GB cells more sensitive to treatment and increased cell death, suggesting that targeting the ISR could potentially improve therapy effectiveness for glioblastoma.
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Introduction: Combination therapy for melanoma brain metastases (MM) using stereotactic radiosurgery (SRS) and immune checkpoint-inhibition (ICI) or targeted therapy (TT) is currently of high interest. In this collective, time evolution and incidence of imaging findings indicative of pseudoprogression is sparsely researched. We therefore investigated time-course of MRI characteristics in these patients.

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Integration of immune checkpoint inhibitors (ICIs) has improved the efficacy of treatment regimens for various cancers. The array of potential side effects keeps evolving and includes neurological complications. An increased risk of seizures and status epilepticus (SE) has been discussed and appears likely.

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Background: BAY1436032 is a fluorine-containing inhibitor of the R132X-mutant isocitrate dehydrogenase (mIDH1). It inhibits the mIDH1-mediated production of 2-hydroxyglutarate (2-HG) in glioma cells. We investigated brain penetration of BAY1436032 and its effects using H/F-Magnetic Resonance Spectroscopy (MRS).

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Article Synopsis
  • Monoclonal antibodies like cetuximab and bevacizumab are key in treating metastatic colorectal cancer, but their effects in hypoxic conditions (low oxygen) need better understanding.
  • In vitro studies revealed that cetuximab can protect cancer cells under hypoxia, and in mouse models, performing cetuximab treatment before bevacizumab led to better survival rates than vice versa.
  • The results suggest that the order of administering these treatments impacts their effectiveness, with the sequence of cetuximab followed by bevacizumab showing superior benefits by avoiding potential adverse interactions.
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Background: The epidermal growth factor receptor (EGFR) signaling pathway is genetically activated in approximately 50% of glioblastomas (GBs). Its inhibition has been explored clinically but produced disappointing results, potentially due to metabolic effects that protect GB cells against nutrient deprivation and hypoxia. Here, we hypothesized that EGFR activation could disable metabolic adaptation and define a GB cell population sensitive to starvation.

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Glioblastoma (GB) is the most frequent primary brain tumor in adults with a dismal prognosis despite aggressive treatment including surgical resection, radiotherapy and chemotherapy with the alkylating agent temozolomide. Thus far, the successful implementation of the concept of targeted therapy where a drug targets a selective alteration in cancer cells was mainly limited to model diseases with identified genetic drivers. One of the most commonly altered oncogenic drivers of GB and therefore plausible therapeutic target is the epidermal growth factor receptor (EGFR).

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Although bevacizumab initially shows high response rates in gliomas and other tumours, therapy resistance usually develops later. Because anti-angiogenic agents are supposed to induce hypoxia, we asked whether rendering glioma cells independent of oxidative phosphorylation modulates their sensitivity against hypoxia and bevacizumab. LNT-229 glioma cells without functional mitochondria (rho ) and control (rho ) cells were generated.

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Article Synopsis
  • Glioblastomas grow quickly and often create areas with low oxygen (hypoxia) and cell death; EGFR and mTORC1 signaling play key roles in this process and are potential targets for treatment.
  • Research shows that inhibiting EGFR and mTORC1 can have negative effects under tumor conditions, while activating mTORC1 by suppressing its inhibitor TSC2 makes glioma cells more sensitive to cell death caused by low oxygen.
  • This study found that mTORC1 activation leads to increased oxygen consumption and changes in metabolic pathways, suggesting it might help identify glioblastoma patients who could benefit from therapies that induce hypoxia, like bevacizumab.
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