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  1. Article ; Online: Enhanced Sensitivity to ALDH1A3-Dependent Ferroptosis in TMZ-Resistant Glioblastoma Cells.

    Wu, Yang / Franzmeier, Sophie / Liesche-Starnecker, Friederike / Schlegel, Jürgen

    Cells

    2023  Volume 12, Issue 21

    Abstract: Temozolomide (TMZ) is standard treatment for glioblastoma (GBM); nonetheless, resistance and tumor recurrence are still major problems. In addition to its association with recurrent GBM and TMZ resistance, ALDH1A3 has a role in autophagy-dependent ... ...

    Abstract Temozolomide (TMZ) is standard treatment for glioblastoma (GBM); nonetheless, resistance and tumor recurrence are still major problems. In addition to its association with recurrent GBM and TMZ resistance, ALDH1A3 has a role in autophagy-dependent ferroptosis activation. In this study, we treated TMZ-resistant LN229 human GBM cells with the ferroptosis inducer RSL3. Remarkably, TMZ-resistant LN229 clones were also resistant to ferroptosis induction, although lipid peroxidation was induced by RSL3. By using Western blotting, we were able to determine that ALDH1A3 was down-regulated in TMZ-resistant LN229 cells. Most intriguingly, the cell viability results showed that only those clones that up-regulated ALDH1A3 after TMZ withdrawal became re-sensitized to ferroptosis induction. The recovery of ALDH1A3 expression appeared to be regulated by EGFR-dependent PI3K pathway activation since Akt was activated only in ALDH1A3 high clones. Blocking the EGFR signaling pathway with the EGFR inhibitor AG1498 decreased the expression of ALDH1A3. These findings shed light on the potential application of RSL3 in the treatment of glioblastoma relapse.
    MeSH term(s) Humans ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; ErbB Receptors/metabolism ; Ferroptosis ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Neoplasm Recurrence, Local ; Phosphatidylinositol 3-Kinases ; Temozolomide/pharmacology
    Chemical Substances ErbB Receptors (EC 2.7.10.1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Temozolomide (YF1K15M17Y) ; aldehyde dehydrogenase (NAD(P)+) (EC 1.2.1.5)
    Language English
    Publishing date 2023-10-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12212522
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: 18

    Bayas, Antonios / Menacher, Martina / Lapa, Constantin / Tappe, Dennis / Maurer, Christoph / Liesche-Starnecker, Friederike / Schneider, Hauke / Naumann, Markus

    Lancet (London, England)

    2024  Volume 403, Issue 10427, Page(s) 665–666

    MeSH term(s) Animals ; Humans ; Positron Emission Tomography Computed Tomography ; Borna disease virus/genetics ; Encephalitis ; Fluorodeoxyglucose F18 ; Magnetic Resonance Imaging
    Chemical Substances Fluorodeoxyglucose F18 (0Z5B2CJX4D)
    Language English
    Publishing date 2024-02-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(24)00049-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  3. Book ; Online ; Thesis: Intratumorale Heterogenität von Glioblastomen -

    Mayer, Karoline Elisabeth Verfasser] / [Liesche-Starnecker, Friederike [Akademischer Betreuer] / Schmidt-Graf, Friederike Gutachter] / Wostrack, Maria [Gutachter] / [Liesche-Starnecker, Friederike [Gutachter]

    Subtypenausprägung in Primärtumoren und korrespondierenden Rezidiven

    2022  

    Author's details Karoline Elisabeth Mayer ; Gutachter: Friederike Schmidt-Graf, Maria Wostrack, Friederike Liesche-Starnecker ; Betreuer: Friederike Liesche-Starnecker
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Universitätsbibliothek der TU München
    Publishing place München
    Document type Book ; Online ; Thesis
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  4. Article ; Online: A rare case of H3K27-altered diffuse midline glioma with multiple osseous and spinal metastases at the time of diagnosis.

    Aftahy, A Kaywan / Butenschoen, Vicki M / Hoenikl, Lisa / Liesche-Starnecker, Friederike / Wiestler, Benedikt / Schmidt-Graf, Friederike / Meyer, Bernhard / Gempt, Jens

    BMC neurology

    2023  Volume 23, Issue 1, Page(s) 87

    Abstract: Background: H3K27-altered diffuse midline gliomas are uncommon central nervous system tumors with extremely poor prognoses.: Case presentation: We report the case of a 24-year-old man patient with multiple, inter alia osseous metastases who presented ...

    Abstract Background: H3K27-altered diffuse midline gliomas are uncommon central nervous system tumors with extremely poor prognoses.
    Case presentation: We report the case of a 24-year-old man patient with multiple, inter alia osseous metastases who presented with back pain, hemi-hypoesthesia, and hemi-hyperhidrosis. The patient underwent combined radio-chemotherapy and demonstrated temporary improvement before deteriorating.
    Conclusions: H3K27-altered diffuse midline glioma presents an infrequent but crucial differential diagnosis and should be considered in cases with rapid neurological deterioration and multiple intracranial and intramedullary tumor lesions in children and young adults. Combined radio-chemotherapy delayed the neurological deterioration, but unfortunately, progression occurred three months after the diagnosis.
    MeSH term(s) Child ; Male ; Young Adult ; Humans ; Adult ; Spinal Neoplasms/complications ; Spinal Neoplasms/diagnostic imaging ; Diagnosis, Differential ; Bone and Bones ; Antineoplastic Combined Chemotherapy Protocols ; Glioma
    Language English
    Publishing date 2023-02-28
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2041347-6
    ISSN 1471-2377 ; 1471-2377
    ISSN (online) 1471-2377
    ISSN 1471-2377
    DOI 10.1186/s12883-023-03135-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Online ; Thesis: Implementation der Konfokalen Laserendomikroskopie für digitale Biopsien von Hirntumoren

    Idzikowski, Maria Katharina [Verfasser] / Schlegel, Jürgen [Akademischer Betreuer] / Schlegel, Jürgen [Gutachter] / Liesche-Starnecker, Friederike [Gutachter]

    2023  

    Author's details Maria Katharina Idzikowski ; Gutachter: Jürgen Schlegel, Friederike Liesche-Starnecker ; Betreuer: Jürgen Schlegel
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Universitätsbibliothek der TU München
    Publishing place München
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  6. Book ; Online ; Thesis: The role of aldehyde dehydrogenase 1 in the combined treatment of C6 glioblastoma cells with cold atmospheric plasma and standard radiotherapy

    Gantzkow, Alicia [Verfasser] / Schlegel, Jürgen [Akademischer Betreuer] / Schlegel, Jürgen [Gutachter] / Liesche-Starnecker, Friederike [Gutachter]

    2023  

    Author's details Alicia Gantzkow ; Gutachter: Jürgen Schlegel, Friederike Liesche-Starnecker ; Betreuer: Jürgen Schlegel
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Universitätsbibliothek der TU München
    Publishing place München
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  7. Article: Primary Bone Tumors of the Spine-Proposal for Treatment Based on a Single Centre Experience.

    Lange, Nicole / Jörger, Ann-Kathrin / Ryang, Yu-Mi / Liesche-Starnecker, Friederike / Gempt, Jens / Meyer, Bernhard

    Diagnostics (Basel, Switzerland)

    2022  Volume 12, Issue 9

    Abstract: This study reports a large single-center series of primary bone tumors of the spine (PBTs). We aimed to review the concepts for management, as this kind of tumor represents a very rare entity, and also propose a new treatment algorithm. Retrospective ... ...

    Abstract This study reports a large single-center series of primary bone tumors of the spine (PBTs). We aimed to review the concepts for management, as this kind of tumor represents a very rare entity, and also propose a new treatment algorithm. Retrospective analysis revealed 92 patients receiving surgery for PBTs from 2007 to 2019 at our center. They were analyzed based on surgical management and the course of the disease. A total of 145 surgical procedures were performed (50 cervical, 46 thoracic, 28 lumbar, and 21 sacral). Complete tumor resection was achieved in 65%, of which 22% showed tumor recurrence during follow-up (mean time to recurrence 334 days). The five-year mortality rate was significantly lower after complete resection (3% versus 25% after subtotal resection). Most of the patients improved in their symptoms through surgery. Regarding the tumor entity, the most common PBTs were vertebral hemangiomas (20%), osteoid osteomas (15%), and chordomas (16%). The Enneking graduation system showed a good correlation with the risk of recurrence and mortality. Complete resection in PBTs increased survival rates and remains the method of choice. Thus, quality of life-especially with a higher extent of resection-should be considered.
    Language English
    Publishing date 2022-09-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics12092264
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  8. Article ; Online: ALDH1-Mediated Autophagy Sensitizes Glioblastoma Cells to Ferroptosis.

    Wu, Yang / Kram, Helena / Gempt, Jens / Liesche-Starnecker, Friederike / Wu, Wei / Schlegel, Jürgen

    Cells

    2022  Volume 11, Issue 24

    Abstract: The fatal clinical course of human glioblastoma (GBM) despite aggressive adjuvant therapies is due to high rates of recurrent tumor growth driven by tumor cells with stem-cell characteristics (glioma stem cells, GSCs). The aldehyde dehydrogenase 1 (ALDH1) ...

    Abstract The fatal clinical course of human glioblastoma (GBM) despite aggressive adjuvant therapies is due to high rates of recurrent tumor growth driven by tumor cells with stem-cell characteristics (glioma stem cells, GSCs). The aldehyde dehydrogenase 1 (ALDH1) family of enzymes has been shown to be a biomarker for GSCs, and ALDH1 seems to be involved in the biological processes causing therapy resistance. Ferroptosis is a recently discovered cell death mechanism, that depends on iron overload and lipid peroxidation, and it could, therefore, be a potential therapeutic target in various cancer types. Since both ALDH1 and ferroptosis interact with lipid peroxidation (LPO), we aimed to investigate a possible connection between ALDH1 and ferroptosis. Here, we show that RSL3-induced LPO and ferroptotic cell death revealed RSL3-sensitive and -resistant malignant glioma cell lines. Most interestingly, RSL3 sensitivity correlates with ALDH1a3 expression; only high ALDH1a3-expressing cells seem to be sensitive to ferroptosis induction. In accordance, inhibition of ALDH1a3 enzymatic activity by chemical inhibition or genetic knockout protects tumor cells from RSL3-induced ferroptotic cell death. Both RSL-3-dependent binding of ALDH1a3 to LC3B and autophagic downregulation of ferritin could be completely blocked by ALDH inhibition. Therefore, ALDH1a3 seems to be involved in ferroptosis through the essential release of iron by ferritinophagy. Our results also indicate that ferroptosis induction might be a particularly interesting clinical approach for targeting the highly aggressive cell population of GSC.
    Language English
    Publishing date 2022-12-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11244015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Glioblastoma Relapses Show Increased Markers of Vulnerability to Ferroptosis.

    Kram, Helena / Prokop, Georg / Haller, Bernhard / Gempt, Jens / Wu, Yang / Schmidt-Graf, Friederike / Schlegel, Jürgen / Conrad, Marcus / Liesche-Starnecker, Friederike

    Frontiers in oncology

    2022  Volume 12, Page(s) 841418

    Abstract: Background: Despite the availability of various therapy options and being a widely focused research area, the prognosis of glioblastoma (GBM) still remains very poor due to therapy resistance, genetic heterogeneity and a diffuse infiltration pattern. ... ...

    Abstract Background: Despite the availability of various therapy options and being a widely focused research area, the prognosis of glioblastoma (GBM) still remains very poor due to therapy resistance, genetic heterogeneity and a diffuse infiltration pattern. The recently described non-apoptotic form of cell death ferroptosis may, however, offer novel opportunities for targeted therapies. Hence, the aim of this study was to investigate the potential role of ferroptosis in GBM, including the impact of treatment on the expression of the two ferroptosis-associated players glutathione-peroxidase 4 (GPX4) and acyl-CoA-synthetase long-chain family number 4 (ACSL4). Furthermore, the change in expression of the recently identified ferroptosis suppressor protein 1 (FSP1) and aldehyde dehydrogenase (ALDH) 1A3 was investigated.
    Methods: Immunohistochemistry was performed on sample pairs of primary and relapse GBM of 24 patients who had received standard adjuvant treatment with radiochemotherapy. To identify cell types generally prone to undergo ferroptosis, co-stainings of ferroptosis susceptibility genes in combination with cell-type specific markers including glial fibrillary acidic protein (GFAP) for tumor cells and astrocytes, as well as the ionized calcium-binding adapter molecule 1 (Iba1) for microglial cells were performed, supplemented by double stains combining GPX4 and ACSL4.
    Results: While the expression of GPX4 decreased significantly during tumor relapse, ACSL4 showed a significant increase. These results were confirmed by analyses of data sets of the Cancer Genome Atlas. These profound changes indicate an increased susceptibility of relapsed tumors towards oxidative stress and associated ferroptosis, a cell death modality characterized by unrestrained lipid peroxidation. Moreover, ALDH1A3 and FSP1 expression also increased in the relapses with significant results for ALDH1A3, whereas for FSP1, statistical significance was not reached. Results obtained from double staining imply that ferroptosis occurs more likely in GBM tumor cells than in microglial cells.
    Conclusion: Our study implies that ferroptosis takes place in GBM tumor cells. Moreover, we show that recurrent tumors have a higher vulnerability to ferroptosis. These results affirm that utilizing ferroptosis processes might be a possible novel therapy option, especially in the situation of recurrent GBM.
    Language English
    Publishing date 2022-04-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.841418
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma.

    Prokop, Georg / Wiestler, Benedikt / Hieber, Daniel / Withake, Fynn / Mayer, Karoline / Gempt, Jens / Delbridge, Claire / Schmidt-Graf, Friederike / Pfarr, Nicole / Märkl, Bruno / Schlegel, Jürgen / Liesche-Starnecker, Friederike

    International journal of cancer

    2023  Volume 153, Issue 9, Page(s) 1658–1670

    Abstract: Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor ... ...

    Abstract Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.
    MeSH term(s) Humans ; Glioblastoma/pathology ; Brain Neoplasms/pathology ; Prognosis
    Language English
    Publishing date 2023-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.34665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 576: Show issues

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