94 results match your criteria: "University Cancer Center Frankfurt UCT[Affiliation]"

Autophagy is an important survival mechanism that allows recycling of nutrients and removal of damaged organelles and has been shown to contribute to the proliferation of acute myeloid leukemia (AML) cells. However, little is known about the mechanism by which autophagy- dependent AML cells can overcome dysfunctional autophagy. In our study we identified autophagy related protein 3 (ATG3) as a crucial autophagy gene for AML cell proliferation by conducting a CRISPR/Cas9 dropout screen with a library targeting around 200 autophagy-related genes.

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Article Synopsis
  • Intracranial hemorrhage (ICH) significantly increases mortality risk in newly diagnosed acute myeloid leukemia (AML) patients undergoing intensive chemotherapy and platelet transfusions, as shown in a study of 423 patients from 2007 to 2019.
  • Out of the patients studied, 4% experienced ICH during their hospital stay, with one-quarter of those cases resulting in death; ICH notably reduced overall survival, averaging 20.1 months compared to 104.8 months for others.
  • Key risk factors for ICH included being female, having severe low platelet counts, and low fibrinogen levels, indicating a need for further protective measures and potential underlying genetic issues linking AML and bleeding risks.
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Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial.

Eur J Nutr

February 2022

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Schleusenweg 2-16, 60528, Frankfurt/Main, Germany.

Purpose: The prospective, randomized ERGO2 trial investigated the effect of calorie-restricted ketogenic diet and intermittent fasting (KD-IF) on re-irradiation for recurrent brain tumors. The study did not meet its primary endpoint of improved progression-free survival in comparison to standard diet (SD). We here report the results of the quality of life/neurocognition and a detailed analysis of the diet diaries.

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Treatment-related complications contribute substantially to morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Although AML patients are susceptible to fluid overload (FO) (e.g.

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Neurocognitive deficits in patients suffering from glioma in speech-relevant areas of the left hemisphere.

Clin Neurol Neurosurg

August 2021

Department of Neurosurgery, University Hospital Frankfurt, Goethe University, Schleusenweg 2-16, 60528 Frankfurt/Main, Germany; University Cancer Center Frankfurt (UCT), University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Stiftung des öffentlichen Rechts, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address:

Objective: Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere.

Methods: Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study.

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Activating transcription factor 4 mediates adaptation of human glioblastoma cells to hypoxia and temozolomide.

Sci Rep

July 2021

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.

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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Minimized combinatorial CRISPR screens identify genetic interactions in autophagy.

Nucleic Acids Res

June 2021

Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage.

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Local anesthetics are commonly administered by nuchal infiltration to provide a temporary interscalene brachial plexus block (ISB) in a surgical setting. Although less commonly reported, local anesthetics can induce central nervous system toxicity. In this case study, we present three patients with acute central nervous system toxicity induced by local anesthetics applied during ISB with emphasis on neurological symptoms, key neuroradiological findings and functional outcome.

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Acute kidney injury (AKI) complicates the clinical course of hospitalized patients by increasing need for intensive care treatment and mortality. There is only little data about its impact on AML patients undergoing intensive induction chemotherapy. In this study, we analyzed the incidence as well as risk factors for AKI development and its impact on the clinical course of AML patients undergoing induction chemotherapy.

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Article Synopsis
  • In 2008, guidelines were established for researching autophagy, which has since gained significant interest and new technologies, necessitating regular updates to monitoring methods across various organisms.
  • The new guidelines emphasize selecting appropriate techniques to evaluate autophagy while noting that no single method suits all situations; thus, a combination of methods is encouraged.
  • The document highlights that key proteins involved in autophagy also impact other cellular processes, suggesting genetic studies should focus on multiple autophagy-related genes to fully understand these pathways.
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Single-shot bevacizumab for cerebral radiation injury.

BMC Neurol

February 2021

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.

Background: Cerebral radiation injury, including subacute radiation reactions and later stage radiation necrosis, is a severe side effect of brain tumor radiotherapy. A protocol of four infusions of the monoclonal antibody bevacizumab has been shown to be a highly effective treatment. However, bevacizumab is costly and can cause severe complications including thrombosis, bleeding and gastrointestinal perforations.

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Introduction: Gliomatosis cerebri (GC) is defined by diffuse, widespread glial tumor growth affecting three or more cerebral lobes. Previous studies in gliomas found no distinct histological or molecular GC subtype, yet the presence of GC is associated with worse median overall survival (OS). Here, we explored whether differing therapeutic strategies in first-line treatment could account for this.

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In brain tumor surgery, injury to cerebellar connectivity pathways can induce a neurodegenerative disease called hypertrophic olivary degeneration (HOD), along with a disabling clinical syndrome. In children, cerebellar mutism syndrome (CMS) is another consequence of damage to cerebello-thalamo-cortical networks. The goal of this study was to compare paravermal trans-cerebellar to other more midline or lateral operative approaches in their risk of causing HOD on MR-imaging and CMS.

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Increased occurrence of status epilepticus in patients with brain metastases and checkpoint inhibition.

Oncoimmunology

November 2020

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.

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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The ERGO2 (Ernaehrungsumstellung bei Patienten mit Rezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pH), and adenosine triphosphate (ATP) were non-invasively determined. 50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD.

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Purpose: Perfusion-weighted MRI (PWI) and O-(2-[F]fluoroethyl-)-l-tyrosine ([F]FET) PET are both applied to discriminate tumor progression (TP) from treatment-related changes (TRC) in patients with suspected recurrent glioma. While the combination of both methods has been reported to improve the diagnostic accuracy, the performance of a sequential implementation has not been further investigated. Therefore, we retrospectively analyzed the diagnostic value of consecutive PWI and [F]FET PET.

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Objectives: Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections.

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Cetuximab-Mediated Protection from Hypoxia- Induced Cell Death: Implications for Therapy Sequence in Colorectal Cancer.

Cancers (Basel)

October 2020

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany.

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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Benefits of glioma resection in the corpus callosum.

Sci Rep

October 2020

Department of Neurosurgery, Goethe University Hospital, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.

Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating the corpus callosum rarely undergo tumor resection and mostly present in a poor neurological state. We aimed at investigating the benefit of glioma resection in the corpus callosum, hypothesizing neuropsychological deficits were mainly caused by tumor presence. Between 01/2017 and 1/2020, 21 patients who underwent glioma resection in the corpus callosum were prospectively enrolled into this study.

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Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis.

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Background: With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas.

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Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death.

Cancers (Basel)

August 2020

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany.

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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Conceptual framework for precision cancer medicine in Germany: Consensus statement of the Deutsche Krebshilfe working group 'Molecular Diagnostics and Therapy'.

Eur J Cancer

August 2020

University Comprehensive Cancer Center Hamburg, Department of Oncology, Hematology with Section Bone Marrow Transplantation and Pneumology, University Medical Center Hamburg-Eppendorf, Germany. Electronic address:

Precision cancer medicine (PCM) holds great promises to offer more effective therapies to patients based on molecular profiling of their individual tumours. Although the PCM approach seems intuitive, multiple conceptional and structural challenges interfere with the broad implementation of PCM into clinical practice. Accordingly, concerted national and international efforts are needed to guide the further development and broad adoption of PCM in Germany.

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Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC.

Int J Cancer

October 2020

Department of Hematology and Oncology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, Berlin, 12203, Germany.

Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10).

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