Marc-Eric Halatsch

Marc-Eric Halatsch
Kantonsspital Winterthur | KSW · Klinik für Neurochirurgie

MD, PhD
Professor of Neurosurgery, Chief Consultant Neurosurgeon

About

177
Publications
27,023
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4,261
Citations
Citations since 2017
64 Research Items
2715 Citations
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20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500

Publications

Publications (177)
Article
OBJECTIVE Drug repurposing represents a promising strategy to safely accelerate the clinical use of therapeutics with antineoplastic activity. In this study, we examined whether Tumor Treating Fields (TTFields) enhance the biological effects of CUSP9v3, a treatment strategy including nine repurposed drugs, in an in vitro setting of glioblastoma. M...
Article
Importance: Trials often assess primary outcomes of traumatic brain injury at 6 months. Longer-term data are needed to assess outcomes for patients receiving surgical vs medical treatment for traumatic intracranial hypertension. Objective: To evaluate 24-month outcomes for patients with traumatic intracranial hypertension treated with decompress...
Article
Full-text available
In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the m...
Article
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Background The COVID-19 pandemic raised major challenges to the management of patient flows and medical staff resource allocation. To prevent the collapse of medical facilities, elective diagnostic and surgical procedures were drastically reduced, canceled or rescheduled. Methods We recorded all in-hospital treated patients and outpatient clinics...
Article
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Background: Glioblastoma represents the most common primary brain tumor in adults. Despite technological advances, patients with this disease typically die within 1-2 years after diagnosis. In the search for novel therapeutics, drug repurposing has emerged as an alternative to traditional drug development pipelines, potentially facilitating and ex...
Article
CUSP9v3 is a new treatment regimen for glioblastoma. It consists of continuous daily use of 9 drugs repurposed from general medicine. Their primary non-oncology uses are given in parentheses: aprepitant (nausea), auranofin (rheumatoid arthritis), celecoxib (pain), captopril (hypertension), disulfiram (alcohol abuse), itraconazole (fungal infection)...
Article
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The purpose of this study was to assess in vitro whether the biological effects of 5-aminolevulinic acid (5-ALA)-based photodynamic therapy are enhanced by inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL in different glioblastoma models. Pre-clinical testing of a microcontroller-based device emitting light of 405 nm waveleng...
Article
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Background The dismal prognosis of glioblastoma (GBM) may be related to the ability of GBM cells to develop mechanisms of treatment resistance. We designed a protocol called Coordinated Undermining of Survival Paths combining 9 repurposed non-oncological drugs with metronomic temozolomide - version 3 - (CUSP9v3) to address this issue. The aim of th...
Article
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Background: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor...
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Cancers in animals present a large, underutilized reservoir of biomedical information with critical implication for human oncology and medicine in general. Discussing two distinct areas of tumour biology in non-human hosts, we highlight the importance of these findings for our current understanding of cancer, before proposing a coordinated strategy...
Preprint
Full-text available
Purpose: The dismal prognosis of glioblastoma (GBM) may be related to the ability of GBM cells to develop mechanisms of treatment resistance. We designed a protocol called Coordinated Undermining of Survival Paths combining 9 repurposed non-oncological drugs with metronomic temozolomide - version 3 - (CUSP9v3) to address this issue. The aim of this...
Article
This paper presents a short review of data supporting a dexamethasone sparing regimen, SEC, to reduce glioblastoma related brain edema. The conclusion of the reviewed data is that the rationale and risk/benefit ratio favors a pilot study to determine if the three drug regimen of SEC can reduce need for corticosteroid use during the course of gliobl...
Article
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Background In a previous article (https://doi.org/10.1007/s00701-019-03888-3), preliminary results of a survey, aiming to shed light on the number of surgical procedures performed and assisted during neurosurgery residency in Europe were reported. We here present the final results and extend the analyses.Methods Board-certified neurosurgeons of Eur...
Article
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Glioblastoma (GB) is a highly aggressive, difficult to treat brain tumour. Successful treatment, consisting of maximal safe tumour de-bulking, followed by radiotherapy and treatment with the alkylating agent Temozolomide (TMZ), can extend patient survival to approximately 15 months. Combination treatments based on the inhibition of the PI3K pathway...
Article
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Dysregulation of the metabolome is a hallmark of primary brain malignancies. In this work we examined whether metabolic reprogramming through a multi-targeting approach causes enhanced anti-cancer activity in glioblastoma. Preclinical testing of a combined treatment with ONC201/TIC10 and 2-Deoxyglucose was performed in established and primary-cultu...
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Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to t...
Article
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Cancer is a leading cause of death in both adults and children, but in terms of absolute numbers, pediatric cancer is a relatively rare disease. The rarity of pediatric cancer is consistent with our current understanding of how adult malignancies form, emphasizing the view of cancer as a genetic disease caused by the accumulation and selection of u...
Article
BACKGROUND Metabolic dysregulation is a common feature of cancers such as primary brain malignancies. In this work we examined whether a rewiring of the metabolome by a multi-targeting approach would induce enhanced anti-neoplastic activity in glioblastoma. METHODS Preclinical testing of a combined treatment with ONC201/TIC10 and 2-Deoxyglucose wa...
Article
A 71-year-old woman presented to our institution with a 2-week history of concentric bilateral left accentuated visual field loss. Examination of her eyes including funduscopy was normal. A gadolinium-enhanced magnetic resonance tomography showed contrast enhancement of the optic pathway in the T1-weighted sequence that included both optic nerves,...
Article
Background and purpose: Drug repurposing represents a promising approach to safely accelerate the clinical application of therapeutics with anti-cancer activity. In this study, we examined whether inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL enhances the biological effects of the repurposed CUSP9 regimen in an in vitro s...
Article
Purpose Anti-apoptotic and pro-migratory phenotypes are hallmarks of neoplastic diseases, including primary brain malignancies. In this work, we examined whether reprogramming of the apoptotic and migratory machineries through a multi-targeting approach would induce enhanced cell death and enhanced inhibition of the migratory capacity of glioblasto...
Article
Full-text available
The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treat...
Article
BACKGROUND Despite refinements of neurosurgical techniques and emerging adjuvant therapies, patients with recurrent glioblastoma continue to face a dismal prognosis. We report preliminary results of a clinical trial evaluating a protocol of 9 repurposed drugs (aprepitant, minocyclin, disulfiram, celecoxib, sertraline, captopril, itraconazole, riton...
Article
Full-text available
The purpose of this study was to examine whether inhibition of RAC1 would enhance the pro-apoptotic reprogramming of glioblastoma’s cellular circuitry following selective Bcl-2/Bcl-xL inhibition by BH-3 mimetics. Preclinical drug testing and molecular profiling was performed in different glioblastoma model systems including established, primary and...
Article
Full-text available
OBJECTIVE Repurposing represents a promising approach to safely accelerate the clinical application of therapeutics with anti-cancer activity. In this study, we examined whether inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL enhances the biological effects of the repurposed CUSP9 regimen in an in vitro setting of glioblasto...
Article
OBJECTIVE Drug repurposing is a strategy to safely accelerate the clinical application of therapeutics that provide anti-cancer activity. CUSP9 represents such a therapeutic regime which includes nine repurposed drugs along with low-dose temozolomide. In this work, we examined the biological activity of the CUSP9 regimen in an in vitro setting of g...
Preprint
The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treat...
Article
Full-text available
Glioblastoma is the most aggressive tumor of the central nervous system and is manifested by diffuse invasion of glioblastoma stem cells into the healthy tissue, chemoresistance and recurrence. Despite aggressive therapy, consisting of maximal surgical resection, radiotherapy and chemotherapy with temozolomide (Temodal®), life expectancy of patient...
Article
Full-text available
Glioblastoma, the most common primary brain tumour, is also considered one of the most lethal cancers per se. It is highly refractory to therapeutic intervention, as highlighted by the mean patient survival of only 15 months, despite an aggressive treatment approach, consisting of maximal safe surgical resection, followed by radio- and chemotherapy...
Article
Background: Among the various causes of vertigo, the so-called cervicogenic vertigo (CV) has been the most controversial. However, perturbations of proprioceptive signals and abnormal activity of the cervical afferents can induce vertigo. Medial branch blocks (MBBs) are a diagnostic tool designed to test whether a patient's neck pain is mediated b...
Presentation
Erste klinische Erfahrungen mit Gliovac beim Glioblastomrezidiv
Article
Full-text available
Due to the highly invasive nature of Glioblastoma (GB), complete surgical resection is not feasible, while motile tumour cells are often associated with several specific brain structures that enhance treatment-resistance. Here, we investigate the therapeutic potential of Disulfiram and Carbenoxolone, that inhibit two distinct interactions between G...
Article
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The sulfone dapsone is an old antibiotic used for the treatment of mycobacterial and protozoal infections. We postulated before that dapsone might possess biological activity exceeding its anti-infectious properties and that it could potentially be repurposed for the treatment of glioma. To test this hypothesis, we treated established and primary c...
Article
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The PI3K/Akt/mTOR signalling network is activated in almost 90% of all glioblastoma, the most common primary brain tumour, which is almost invariably lethal within 15 months of diagnosis. Despite intensive research, modulation of this signalling cascade has so far yielded little therapeutic benefit, suggesting that the role of the PI3K network as a...
Article
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INTRODUCTION CUSP9v3/v4 uses 9 re-purposed drugs having preclinical data indicating antiglioma effects. We offered compassionate-use CUSP9v3 to 7, CUSP9v4 to 1, heavily pretreated low Karnofsky Performance Score patients with recurrent glioblastoma. CUSP9v3 uses aprepitant, a neurokinin-1 receptor blocker marketed to treat nausea; auranofin, a thio...
Article
INTRODUCTION Malignant gliomas are among the most deadly human cancers. One subtype, diffuse midline glioma (DMG), WHO Grade IV, is characterized by the H3 K27M histone mutation which is mutually exclusive with the favorable MGMT promoter methylation, IDH 1/2 mutation and EGFR amplification. DMGs have limited treatment options: surgery is typically...
Article
Introduction: Novel approaches to treat malignant brain tumors are necessary since these neoplasms still display an unfavorable prognosis. Areas covered: In this review, the authors summarize and analyze recent preclinical data that suggest that targeting intrinsic apoptosis may be a suitable strategy for the treatment of malignant gliomas. They fo...
Article
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Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenc...
Article
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This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resi...
Article
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We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succi...
Article
Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to d...
Article
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Drug combination therapies remain pivotal for the treatment of heterogeneous malignancies, such as glioblastomas. Here, we show a novel lethal interaction between Bcl-xL and c-myc inhibition accomplished by bromodomain protein inhibitors. Established, patient-derived xenograft and stem cell-like glioma cells were treated with the novel bromodomain...
Article
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Malignant gliomas display high levels of the transcription factor c-myc and organize a tumor specific chaperone network within mitochondria. Here, we show that c-myc along with mitochondrial chaperone inhibition displays massive tumor cell death. Inhibition of mitochondrial matrix chaperones and c-myc was established by utilizing genetic as well as...
Article
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One major obstacle in cancer therapy is chemoresistance leading to tumor recurrence and metastasis. Cancer stem cells, in particular glioblastoma stem cells, are highly resistant to chemotherapy, radiation, and immune recognition. In case of immune recognition, several survival mechanisms including, regulation of autophagy, proteases, and cell surf...
Article
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Major histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally sec...
Article
Intraoperative magnetic resonance imaging is a widely accepted method for resection control of glial tumors. Increasingly, it is also used during the resection of skull base tumors. Several studies have independently demonstrated an increase in the extent of resection in these tumors with improved prognosis for the patients. Technical innovations c...
Article
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Background The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. Methods From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompress...
Article
Background The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. Methods From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompres...
Article
Full-text available
Cancer cells display a variety of global metabolic changes, which aside from the glycolytic pathway largely involve amino acid metabolism. To ensure aggressive growth, tumor cells highly depend on amino acids, most notably due to their pivotal need of protein synthesis. In this study, we assessed the overall hypothesis that depletion of asparagine...
Article
Full-text available
To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs) (monocyte, macrophage, microglia, dendritic cells) that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor...
Article
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Protease-mediated degradation of proteins is critical in a plethora of physiological processes. Neutrophils secrete serine proteases including cathepsin G (CatG), neutrophile elastase (NE), and proteinase 3 (PR3) together with lactoferrin (LF) as a first cellular immune response against pathogens. Here, we demonstrate that LF increases the catalyti...
Data
Detection of CatG activity in LF spiked granulocyte-derived supernatant. The indicated granulocyte-derived supernatant (control, PMA, or zymosan) was incubated with or without LF (250 μg/ml) and MARS116. CatG activity was determined by SDS-PAGE and streptavidin-HRP blot. On the same PVDF membrane, LF was detected by using LF-specific antibody. Sup...
Data