المساهمون: Yae Won Park, Kyunghwa Han, Sooyon Kim, Hyuk Kwon, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Jinna Kim, Seok-Gu Kang, Jong Hee Chang, Se Hoon Kim, Seung-Koo Lee, Kang, Seok Gu

مصطلحات موضوعية: Adult, Brain Neoplasms* / diagnosis, Brain Neoplasms* / genetics, Brain Neoplasms* / therapy, Female, Glioblastoma, Glioma* / genetics, Glioma* / pathology, Glioma* / therapy, Humans, Isocitrate Dehydrogenase / genetics, Male, Mutation, Prognosis, Glioma, Isocitrate dehydrogenase, Leptomeningeal metastases, Magnetic resonance imaging, Survival

الوصف: Purpose: To comprehensively investigate prognostic factors, including clinical and molecular factors and treatment modalities, in adult glioma patients with leptomeningeal metastases (LM). Methods: Total 226 patients with LM (from 2001 to 2021 among 1495 grade 2 to 4 glioma patients, 88.5% of LM patients being IDH-wildtype) with complete information on IDH mutation, 1p/19q codeletion, and MGMT promoter methylation status were enrolled. Predictors of overall survival (OS) of entire patients were determined by time-dependent Cox analysis, including clinical, molecular, and treatment data. Subgroup analyses were performed for patients with LM at initial diagnosis and LM diagnosed at recurrence (herein, initial and recurrent LM). Identical analyses were performed in IDH-wildtype glioblastoma patients. Results: Median OS was 17.0 (IQR 9.7-67.1) months, with shorter median OS in initial LM than recurrent LM patients (12.2 vs 20.6 months, P < 0.004). In entire patients, chemotherapy and antiangiogenic therapy were predictors of longer OS, while male sex and initial LM were predictors of shorter OS. In initial LM, higher KPS, chemotherapy, and antiangiogenic therapy were predictors of longer OS, while male sex was a predictor of shorter OS. In recurrent LM, chemotherapy and longer interval between initial glioma and LM diagnoses were predictors of longer OS, while male sex was a predictor of shorter OS. A similar trend was observed in IDH-wildtype glioblastoma. Conclusion: Active chemotherapy and antiangiogenic therapy demonstrated survival benefit in glioma patients with LM. There is consistent female survival advantage, whereas longer interval between initial glioma diagnosis and LM development suggests longer OS in recurrent LM. ; open

العلاقة: JOURNAL OF NEURO-ONCOLOGY; J01629; OAK-2023-02465; OAK-2023-02466; OAK-2023-02467; OAK-2023-02468; OAK-2023-02469; OAK-2023-02470; OAK-2023-02471; OAK-2023-02472; OAK-2023-02473; https://ir.ymlib.yonsei.ac.kr/handle/22282913/196020Test; T202304375; JOURNAL OF NEURO-ONCOLOGY, Vol.162(1) : 59-68, 2023-03

الإتاحة: https://doi.org/10.1007/s11060-022-04233-yTest
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196020Test

المساهمون: Junseong Park, Dongkyu Lee, Jin-Kyoung Shim, Seon-Jin Yoon, Ju Hyung Moon, Eui Hyun Kim, Jong Hee Chang, Su-Jae Lee, Seok-Gu Kang, Kang, Seok Gu

مصطلحات موضوعية: Animals, Brain Neoplasms* / genetics, Brain Neoplasms* / pathology, Cell Line, Tumor, Disease Models, Animal, Glioblastoma* / genetics, Glioblastoma* / pathology, Humans, Neoplasm Invasiveness / genetics, Neoplastic Stem Cells / metabolism, Glioblastoma, mesenchymal stem-like cell, patient-derived tumorsphere, subventricular zone, tumor invasion, ventricle-derived mesenchymal stem-like cells

الوصف: Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM pa tient-derived cells. Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo ex periments. Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investi gated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accel erated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLC induced increases in the invasiveness of GBM TSs. Conclusion: Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates. ; open

العلاقة: YONSEI MEDICAL JOURNAL; J02813; OAK-2023-00499; OAK-2023-00500; OAK-2023-00501; OAK-2023-00502; https://ir.ymlib.yonsei.ac.kr/handle/22282913/194021Test; T202301815; YONSEI MEDICAL JOURNAL, Vol.64(3) : 157-166, 2023-03

الإتاحة: https://doi.org/10.3349/ymj.2022.0430Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/194021Test

المؤلفون: Dubois, Nadège, Berendsen, Sharon, Tan, Katherine, Schoysmans, Laurent, Spliet, Wim, Seute, Tatjana, Bours, Vincent, Robe, Pierre

المصدر: International Journal of Oncology, 61 (4) (2022-10)

مصطلحات موضوعية: STAT5b, glioblastoma, Prognosis, Brain Neoplasms/drug therapy, Brain Neoplasms/genetics, Glioblastoma/genetics, Brain Neoplasms, Oncology, Cancer Research, Human health sciences, Sciences de la santé humaine, Oncologie

الوصف: The copy number and mRNA expression of STAT5b were assessed in samples from the TCGA repository of glioblastomas (GBM). The activation of this transcription factor was analyzed on tissue microarrays comprising 392 WHO 2016 GBM samples from our clinical practice. These data were correlated with patient survival using multivariable Cox analysis and, for a subset of 167 tumors, with signs of tumor invasiveness on the MRI. The effects of STAT5b knockdown by siRNA were assessed on the growth, therapeutic resistance, invasion and migration of GBM cell lines U87, U87‑EGFRVIII and LN18 and primary cultures GM2 and GM3. The activation, but not the copy number or the mRNA expression of nuclear transcription factor STAT5b expression correlated inversely with patient survival independently of IDH1R132H status, age, Karnofsky Performance Score, treatment and tumor volume. STAT5b inhibition neither altered the cell proliferation nor reduced the clonogenic proliferative potency of GBM cells, and did not sensitize them to the cytotoxic effect of ionizing radiation and temozolomide in vitro. STAT5b inhibition significantly increased GBM cell migration, but decreased the invasion of some GBM cells in vitro. There was no correlation between the activation of STAT5b in clinical tumors and the extent of invasion on MRI OF patients. In conclusion, STAT5b is frequently activated in GBM and correlates inversely with patient survival. It does not contribute to the growth and resistance of these tumors, and is thus rather a potential prognostic marker than a therapeutic target in these tumors.

العلاقة: 10.3892/ijo.2022.5414; urn:issn:1019-6439; urn:issn:1791-2423

الوصول الحر: https://orbi.uliege.be/handle/2268/295093Test

المساهمون: Chan Woo Wee, Hong In Yoon, Sea-Won Lee, Do Hoon Lim, Yoon, Hong In

مصطلحات موضوعية: Aged, Antineoplastic Agents, Alkylating / therapeutic use, Brain Neoplasms* / drug therapy, Brain Neoplasms* / genetics, Brain Neoplasms* / radiotherapy, Dacarbazine / adverse effects, Glioblastoma* / drug therapy, Glioblastoma* / genetics, Glioblastoma* / radiotherapy, Humans, Republic of Korea, Surveys and Questionnaires, Temozolomide / therapeutic use, elderly, glioblastoma, radiotherapy, survey, temozolomide

الوصف: Background: To investigate the current variability in radiotherapy practice for elderly glioblastoma patients. Methods: A questionnaire comprising general information on elderly glioblastoma, treatment selection, radiotherapy and 16 clinical case-scenario-based questions (based on age, performance, extent of resection and MGMT promoter methylation) was sent to brain tumor radiation oncologists. Results: Twenty-one responses were recorded. Most (71.4%) stated that 70 years is an adequate cut-off for 'elderly' individuals. The most preferred hypofractionated short-course radiotherapy schedule was 40-45 Gy over 3 weeks (81.3%). The median margin for high-dose target volume was 5 mm (range, 0-20 mm) from the T1-enhancement for short-course radiotherapy. The case-scenario-based questions revealed a near-perfect consensus on 6-week standard radiotherapy plus concurrent/adjuvant temozolomide as the most appropriate adjuvant treatment in good performing patients aged 65-70 years, regardless of surgery and MGMT promoter methylation. Notably, in 75-year-old patients with good performance, the most preferred treatment was 6-week radiotherapy (81.0-90.5%) plus concurrent/adjuvant temozolomide (71.4-95.2%) rather than short-course radiotherapy or radiotherapy alone. Although the use of 3-week short-course radiotherapy increased with age and decreased performance status (all P < 0.05), 6-week radiotherapy was adopted in a significant proportion of responders (14.3-23.8%) even for wheelchair-bound, 75-year-old patients. Temozolomide use was affected by age, performance and MGMT promoter (all P < 0.05). Conclusions: A high level of consensus was observed in treating elderly glioblastoma patients with good performance status. However, the variability increased, especially for older patients and those with poor performance. This study serves as a basis for designing future clinical trials in elderly glioblastoma. ; restriction

العلاقة: JAPANESE JOURNAL OF CLINICAL ONCOLOGY; J01207; OAK-2022-10359; https://ir.ymlib.yonsei.ac.kr/handle/22282913/193306Test; https://academic.oup.com/jjco/article/52/8/843/6572653Test; T9992022535; JAPANESE JOURNAL OF CLINICAL ONCOLOGY, Vol.52(8) : 843-849, 2022-08

الإتاحة: https://doi.org/10.1093/jjco/hyac060Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193306Test
https://academic.oup.com/jjco/article/52/8/843/6572653Test

المساهمون: Seung-Mo Kim, Eun-Jung Lim, Ki-Chun Yoo, Yi Zhao, Jae-Hyeok Kang, Eun-Ji Lim, Incheol Shin, Seok-Gu Kang, Han Woong Lim, Su-Jae Lee, Kang, Seok Gu

مصطلحات موضوعية: Animals, Brain Neoplasms* / genetics, Brain Neoplasms* / metabolism, Brain Neoplasms* / pathology, CD40 Ligand / metabolism, Extracellular Matrix / metabolism, Extracellular Matrix / pathology, Glioblastoma* / genetics, Glioblastoma* / metabolism, Glioblastoma* / pathology, Humans, Mice, Tumor Microenvironment, cluster of differentiation 40 ligand, extracellular matrix remodelling, glioblastoma, lysyl oxidase, mesenchymal stem-like cells

الوصف: Background: The biological function of mesenchymal stem-like cells (MSLCs), a type of stromal cells, in the regulation of the tumour microenvironment is unclear. Here, we investigated the molecular mechanisms underlying extracellular matrix (ECM) remodelling and crosstalk between MSLCs and glioblastomas (GBMs) in tumour progression. Methods: In vitro and in vivo co-culture systems were used to analyze ECM remodelling and GBM infiltration. In addition, clinical databases, samples from patients with GBM and a xenografted mouse model of GBM were used. Results: Previous studies have shown that the survival of patients with GBM from whom MSLCs could be isolated is substantially shorter than that of patients from whom MSLCs could not be isolated. Therefore, we determined the correlation between changes in ECM-related gene expression in MSLC-isolatable patients with that in MSLC non-isolatable patients using gene set enrichment analysis (GSEA). We found that lysyl oxidase (LOX) and COL1A1 expressions increased in MSLCs via GBM-derived clusters of differentiation 40 ligand (CD40L). Mechanistically, MSLCs are reprogrammed by the CD40L/CD40/NFκB2 signalling axis to build a tumour infiltrative microenvironment involving collagen crosslinking. Importantly, blocking of CD40L by a neutralizing antibody-suppressed LOX expression and ECM remodelling, decreasing GBM infiltration in mouse xenograft models. Clinically, high expression of CD40L, clusters of differentiation 40 (CD40) and LOX correlated with poor survival in patients with glioma. This indicated that GBM-educated MSLCs promote GBM infiltration via ECM remodelling in the tumour microenvironment. Conclusion: Our findings provide mechanistic insights into the pro-infiltrative tumour microenvironment produced by GBM-educated MSLCs and highlight a potential therapeutic target that can be used for suppressing GBM infiltration. ; open

العلاقة: CLINICAL AND TRANSLATIONAL MEDICINE; J04026; OAK-2022-06969; https://ir.ymlib.yonsei.ac.kr/handle/22282913/191793Test; T202203291; CLINICAL AND TRANSLATIONAL MEDICINE, Vol.12(8) : e997, 2022-08

الإتاحة: https://doi.org/10.1002/ctm2.997Test
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191793Test

المؤلفون: Mareike, Müller, Staub-Bartelt, Franziska, Julia, Ehrmann, Daniel, Hänggi, Michael, Sabel, Jörg, Felsberg, Marion, Rapp

المصدر: http://lobid.org/resources/99370674912706441Test#!, 153(3):537-545.

مصطلحات موضوعية: Extend of resection, MGMT, Tumor Suppressor Proteins/genetics [MeSH], Brain Neoplasms/genetics [MeSH], Glioblastoma/surgery [MeSH], Humans [MeSH], Subtotal resection, DNA Repair Enzymes/genetics [MeSH], Brain Neoplasms/surgery [MeSH], DNA Modification Methylases/metabolism [MeSH], Glioblastoma, DNA Modification Methylases/genetics [MeSH], Neurooncology, Tumor Suppressor Proteins/metabolism [MeSH], DNA Repair Enzymes/metabolism [MeSH], DNA Methylation [MeSH], Quality of Life [MeSH], Clinical Study, Neoplasm, Residual [MeSH], Glioblastoma/genetics [MeSH], Isocitrate Dehydrogenase [MeSH]

الوصف: Background!#!The impact on survival of complete resection (CR) in patients with malignant glioma and MGMT promoter methylation on adjuvant therapy strategies has been proven in the past. However, it is not known whether a MGMT promoter methylation can compensate a subtotal resection. Therefore, we analyzed the progress of postoperative residual tumor tissue depending on the molecular tumor status.!##!Methods!#!We included all glioblastoma, IDH-wildtype (WHO grade IV) patients with postoperative residual tumor tissue, who were treated at our neurooncological department between 2010 and 2018. Correlation of molecular patterns with clinical data and survival times was performed. The results were compared to patients following CR.!##!Results!#!267 patients with glioblastoma, IDH-wildtype (WHO grade IV) received surgery of whom 81 patients with residual tumor were included in the analysis. MGMT promoter was methylated in 31 patients (38.27%). Median OS and PFS were significantly increased in patients with methylated MGMT promoter (mOS: 16 M vs. 13 M, p = 0.009; mPFS: 13 M vs. 5 M, p = 0.003). In comparison to survival of patients following CR, OS was decreased in patients with residual tumor regardless MGMT methylation.!##!Conclusion!#!Our data confirm impact of MGMT promoter methylation in patients with glioblastoma, IDH-wildtype on OS and PFS. However, in comparison to patients after CR, a methylated MGMT promoter cannot compensate the disadvantage due to residual tumor volume. In terms of personalized medicine and quality of life as major goal in oncology, neuro-oncologists have to thoroughly discuss advantages and disadvantages of residual tumor volume versus possible neurological deficits in CR.

العلاقة: https://repository.publisso.de/resource/frl:6445975Test; https://doi.org/10.1007/s11060-021-03794-8Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279995Test/

الإتاحة: https://doi.org/10.1007/s11060-021-03794-8Test
https://repository.publisso.de/resource/frl:6445975Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279995Test/

المؤلفون: Siller, Sebastian, Lauseker, Michael, Karschnia, Philipp, Niyazi, Maximilian, Eigenbrod, Sabina, Giese, Armin, Tonn, Joerg-Christian

المصدر: http://lobid.org/resources/99370678498306441Test#!, 9(1):35.

مصطلحات موضوعية: Tumor Suppressor Proteins/genetics [MeSH], Aged, 80 and over [MeSH], Methylation-specific polymerase-chain-reaction, Aged [MeSH], Antineoplastic Agents, Alkylating/therapeutic use [MeSH], Methylation status, Cohort Studies [MeSH], Glioblastoma/drug therapy [MeSH], Male [MeSH], Base Sequence [MeSH], Glioblastoma/genetics [MeSH], Sanger sequencing, Adolescent [MeSH], Female [MeSH], Brain Neoplasms/genetics [MeSH], Adult [MeSH], Humans [MeSH], MSP, Linear correlation, DNA Repair Enzymes/genetics [MeSH], Survival Analysis [MeSH], Middle Aged [MeSH], Glioblastoma, DNA Modification Methylases/genetics [MeSH], DNA Methylation [MeSH], Research, CpG Islands [MeSH], Prognosis [MeSH]

الوصف: MGMT-promoter methylation is associated with favorable outcome in glioblastoma. The aim of this study was to determine whether the absolute number of methylated Cytosine-Guanine-dinucleotide-(CpG-)sites within the DMR-2 island of the MGMT-promoter may correlate with outcome in a qualitative or quantitative fashion. In a cohort of newly diagnosed glioblastoma patients treated with stereotactic biopsy or open tumor resection plus concomitant chemoradiotherapy, we assessed MGMT-promoter methylation by methylation-specific polymerase-chain-reaction (MSP). Methylation of the CpG-sites 74-98 within the MGMT-promoter region was additionally analysed by Sanger sequencing, and the total number of methylated CpG-sites was correlated with outcome using proportional hazards models. 215 patients with glioblastoma were identified and stratified per MSP (positive: 53%, negative: 47%). Among MSP-positive tumors, hierarchical clustering identified three subgroups with different methylation rates (median: 80% vs. 52% vs. 47%), indicating a site-dependent methylation propagation. The methylation status of a given CpG-site indicated a neighborhood-dependent methylation propagation. Survival was linearly associated with the cumulative number of methylated CpG-sites. This was particularly true in patients who received at least one adjuvant cycle of temozolomide. Notably, all CpG-sites analyzed contributed similarly to effect size; this enabled a further predictive substratification of MSP-positive tumors with median OS ranging from as low as 17.1 months (< 18 methylated CpG-sites) to as high as 26.2 months (≥ 18 methylated CpG-sites) in the overall cohort. All in all, total number of methylated CpG-sites may correlate with outcome in a linear fashion. Such analysis may therefore add further predictive value to conventional methods of determining the MGMT-promoter status.

العلاقة: https://repository.publisso.de/resource/frl:6464457Test; https://doi.org/10.1186/s40478-021-01134-5Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934240Test/

الإتاحة: https://doi.org/10.1186/s40478-021-01134-5Test
https://repository.publisso.de/resource/frl:6464457Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934240Test/

المؤلفون: Cudalbu, C., Bady, P., Lai, M., Xin, L., Gusyatiner, O., Hamou, M.F., Lepore, M., Brouland, J.P., Daniel, R.T., Hottinger, A.F., Hegi, M.E.

المصدر: Acta neuropathologica communications, vol. 9, no. 1, pp. 133

مصطلحات موضوعية: Adult, Aged, Animals, Brain Neoplasms/diagnostic imaging, Brain Neoplasms/genetics, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Female, Glioblastoma/diagnostic imaging, Glioblastoma/genetics, Glioblastoma/metabolism, Glioblastoma/pathology, Humans, Magnetic Resonance Imaging, Male, Metabolome, Mice, Middle Aged, Neoplasm Invasiveness, Neoplasm Transplantation, Proton Magnetic Resonance Spectroscopy, Transcriptome, 1H MRS at ultra-high fields (UHF), Glioblastoma, Invasion, Patient-derived orthotopic xenografts (PDOX), Tumor host interaction

الوصف: The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes observed in patient derived orthotopic xenografts (PDOX) in the mouse and the corresponding patients' tumors. The evolution of metabolic changes, followed in vivo longitudinally by 1 H Magnetic Resonance Spectroscopy ( 1 H MRS) at ultra-high field, reflected growth and the invasive properties of the human glioblastoma transplanted into the brains of mice (PDOX). Comparison of MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel MRS analyses sampled across different areas of the patients' tumors. Pathway analyses of the transcriptome associated with the metabolite profiles of the PDOX, identified molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling. Specific analysis of expression signatures from the invaded mouse brain, revealed extent of invasion dependent induction of immune response, recapitulating respective signatures observed in glioblastoma. Integrating metabolic profiles and gene expression of highly invasive PDOX provided insights into progression and invasion associated mechanisms of extracellular matrix remodeling that is essential for cell-cell communication and regulation of cellular processes. Structural changes and biochemical properties of the extracellular matrix are of importance for the biological behavior of tumors and may be druggable. Ultra-high field MRS reveals to be suitable for in vivo monitoring of progression ...

وصف الملف: application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34348785; info:eu-repo/semantics/altIdentifier/eissn/2051-5960; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_CB8B36AE633E4; https://serval.unil.ch/notice/serval:BIB_CB8B36AE633ETest; urn:issn:2051-5960; https://serval.unil.ch/resource/serval:BIB_CB8B36AE633E.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_CB8B36AE633E4Test

الإتاحة: https://doi.org/10.1186/s40478-021-01232-4Test
https://serval.unil.ch/notice/serval:BIB_CB8B36AE633ETest
https://serval.unil.ch/resource/serval:BIB_CB8B36AE633E.P001/REF.pdfTest
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_CB8B36AE633E4Test

المؤلفون: Vareecal Joseph, Justin, Blaavand, Mathilde S., Daubon, Thomas, Kruyt, Frank AE., Thomsen, Martin Kristian

المصدر: Vareecal Joseph , J , Blaavand , M S , Daubon , T , Kruyt , F AE & Thomsen , M K 2021 , ' Three-dimensional culture models to study glioblastoma — current trends and future perspectives ' , Current Opinion in Pharmacology , vol. 61 , pp. 91-97 . https://doi.org/10.1016/j.coph.2021.08.019Test

مصطلحات موضوعية: CRISPR, 3D culture, Human pluripotent stem cells (hPSCs), Glioblastoma, Organoid, EGF, Human pluripotent stem, PHENOTYPE, IDENTIFICATION, TUMORS, HUMAN BRAIN-DEVELOPMENT, CEREBRAL ORGANOIDS, DISEASE, GROWTH, STEM-CELL, BFGF, Humans, Tumor Microenvironment, Brain Neoplasms/genetics, Glioblastoma/drug therapy, Organoids

الوصف: Glioblastoma (GBM) is the most prevalent form of primary malignant brain tumor in adults and remains almost invariably lethal owing to its aggressive and invasive nature. There have only been marginal improvements in its bleak survival rate of 12–15 months over the last four decades. The lack of preclinical models that efficiently recapitulate tumor biology and the tumor microenvironment is also in part responsible for the slow phase of translational GBM research. Emerging three-dimensional (3D) organoids and cell culture systems offer new and innovative possibilities for GBM modelling. These 3D models find their application to engineer the disease, screen drugs, establishing live biobank, and explore personalized therapy. Furthermore, these models can also be genetically modified by using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, which would allow one to study the specific role of key genes associated with gliomagenesis. Establishment of a coculture system with GBM cells to understand its invasive behavior is yet another major application of this model. Despite these merits, the organoid models also have certain limitations, including the absence of immune responses and vascular systems. In recent years, major progress has been made in the development and refinement of 3D models of GBM. In this review, we intend to highlight these recent advances and the potential future implications of this rapidly evolving field, which should facilitate a better understanding of GBM biology.

وصف الملف: application/pdf

العلاقة: https://pure.au.dk/portal/da/publications/threedimensional-culture-models-to-studyTest-glioblastoma--current-trends-and-future-perspectives(5c38f0a7-2684-4deb-9e0e-974a82b362a7).html

الإتاحة: https://doi.org/10.1016/j.coph.2021.08.019Test
https://pure.au.dk/portal/da/publications/threedimensional-culture-models-to-studyTest-glioblastoma--current-trends-and-future-perspectives(5c38f0a7-2684-4deb-9e0e-974a82b362a7).html
https://pure.au.dk/ws/files/273706731/1_s2.0_S1471489221001405_main.pdfTest

المؤلفون: Heiland, Pamela, Delev, Daniel, Cipriani, Debora, Neidert, Nicolas, Kellner, Elias, Masalha, Waseem, Mercas, Bianca, Mader, Irina, Reinacher, Peter, Weyerbrock, Astrid, Fung, Christian, Beck, Jürgen, Heiland, Dieter Henrik, Schnell, Oliver

المصدر: http://lobid.org/resources/99370675015906441Test#!, 163(4):937-945.

مصطلحات موضوعية: Glioma/surgery [MeSH], Aged [MeSH], Brain Neoplasms/surgery [MeSH], Postoperative Complications/epidemiology [MeSH], Tumor – Glioma, Original Article - Tumor - Glioma, Corpus Callosum/pathology [MeSH], Glioma/pathology [MeSH], Male [MeSH], Tumor Burden [MeSH], Corpus callosum glioblastoma, Karnofsky Performance Status [MeSH], IDH status, Female [MeSH], Brain Neoplasms/genetics [MeSH], Adult [MeSH], Humans [MeSH], Middle Aged [MeSH], Neurosurgery, Glioblastoma, Extent of resection, Neurosurgical Procedures/methods [MeSH], Corpus Callosum/surgery [MeSH], Molecular diagnosis, Glioma/genetics [MeSH], Neurosurgical Procedures/adverse effects [MeSH], Butterfly glioblastoma, Isocitrate Dehydrogenase/genetics [MeSH], Brain Neoplasms/pathology [MeSH]

الوصف: Background!#!Glioblastoma of the corpus callosum (ccGBM) are rare tumors, with a dismal prognosis marked by a rapid clinical deterioration. For a long time, surgical treatment was not considered beneficial for most patients with such tumors. Recent studies claimed an improved survival for patients undergoing extensive resection, albeit without integration of the molecular profile of the lesions. The purpose of this study was to investigate the effect of biopsy and surgical resection on oncological and functional outcomes in patients with IDH wild-type ccGBM.!##!Methods!#!We performed a retrospective analysis of our institution's database of patients having been treated for high-grade glioma between 2005 and 2017. Inclusion criteria were defined as follows: patients older than 18 years, histopathological, and molecularly defined IDH wild-type glioma, major tumor mass (at least 2/3) invading the corpus callosum in the sagittal plane with a uni- or bilateral infiltration of the adjacent lobules. Surgical therapy (resection vs. biopsy), extent of resection according to the remaining tumor volume and adjuvant treatment as well as overall survival and functional outcome using the Karnofsky Performance Score (KPS) were analyzed.!##!Results!#!Fifty-five patients were included in the study, from which the mean age was 64 years and men (n = 34, 61.8%) were more often affected than women (n = 21, 38.2%). Thirty (54.5%) patients were treated with stereotactic biopsy alone, while 25 patients received tumor resection resulting in 14.5% (n = 8) gross-total resections and 30.9% (n = 17) partial resections. The 2-year survival rate after resection was 30% compared to 7% after biopsy (p = 0.047). The major benefit was achieved in the group with gross-total resection, while partial resection failed to improve survival. Neurological outcome measured by KPS did not differ between both groups either pre- or postoperatively.!##!Conclusions!#!Our study suggests that in patients with corpus callosum glioblastoma, gross-total resection ...

العلاقة: https://repository.publisso.de/resource/frl:6470366Test; https://doi.org/10.1007/s00701-020-04623-zTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966629Test/

الإتاحة: https://doi.org/10.1007/s00701-020-04623-zTest
https://repository.publisso.de/resource/frl:6470366Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966629Test/