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Yahya, Farah, DJIMRABEYE Alngar, TOUATI Lina, et al. "Cystic glioblastoma mimicking toxoplasmosis in a young adult: A case report." World Journal of Advanced Research and Reviews 19, no. 3 (2023): 585–88. https://doi.org/10.5281/zenodo.11668458.
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Glioblastoma multiform it is most frequent brain tumor which highly malignancy, also there is rare cases presentation for solitary cystic glioblastoma (GBM) form which is mimicking infection, especially toxoplasmosis. In our case report highlighted the gold stone of the clinical feature identifying of cystic GBM to ensure early diagnosis and treatment.
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Ashing, Liz, Ashley Nelson, Zefanias Ngove, and Aundrea Crain. "Bavachin Suppresses Cell Growth and Enhances Temozolomide Efficacy in U-87 MG Glioblastoma Cells." American Journal of Undergraduate Research 21, no. 3 (2024): 63–71. https://doi.org/10.33697/ajur.2024.126.
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Glioblastoma multiform (GBM) is a lethal cancer affecting the central nervous system. Existing treatment methods for GBM include chemotherapy, radiation, and surgery. Temozolomide is a common chemotherapy treatment for GBM but causes unwanted side effects, as do most chemotherapy treatments. To decrease the harmful side effects of chemotherapy, research has turned to exploring natural compounds to treat cancer. In this study, the natural compound bavachin was investigated to determine cytotoxicity in GBM cells. Bavachin has been tested in many cell lines but not glioblastoma. A sulforhodamine B (SRB) assay, trypan blue counting, and a tumorsphere assay were used to test the hypothesis in this study. It was found that bavachin suppressed glioblastoma cell and tumorsphere viability, had a synergistic interaction with temozolomide, and ornithine decarboxylase was identified as a potential target in silico. This study demonstrated the ability of bavachin to suppress the growth of U-87 MG glioblastoma cells and enhance temozolomide efficacy. These findings demonstrated that bavachin is a potential treatment for GBM based on its ability to suppress cell growth. KEYWORDS: Glioblastoma Multiforme; Temozolomide; Bavachin; Flavonoid; Tumorspheres; Cell Viability; Cancer; Apoptosis; Psoralea corylifolia
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Yahya Farah, Alngar DJIMRABEYE, Lina TOUATI, et al. "Cystic glioblastoma mimicking toxoplasmosis in a young adult: A case report." World Journal of Advanced Research and Reviews 19, no. 3 (2023): 585–88. http://dx.doi.org/10.30574/wjarr.2023.19.3.1595.
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Glioblastoma multiform it is most frequent brain tumor which highly malignancy, also there is rare cases presentation for solitary cystic glioblastoma (GBM) form which is mimicking infection, especially toxoplasmosis. In our case report highlighted the gold stone of the clinical feature identifying of cystic GBM to ensure early diagnosis and treatment.
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K, Tanti Ajoe, and Martin M. "Medical Rehabilitation of Glioblastoma Multiform: Case Report." Indonesian Journal of Physical Medicine & Rehabilitation 7, no. 01 (2019): 36. http://dx.doi.org/10.36803/ijpmr.v7i01.132.
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Introduction: Glioblastoma Multiform (GBM) is the most common malignant primary brain tumor. Early rehabilitation program is needed to increasing the independency and the quality of life.Methods: Case presentation of a woman, age 31 years, diagnosed with GBM. Subject has chronic headache by visual analog scale (VAS) was 5 to 6 and progressive of vision loss (0/0), short and intermediate memory loss, the average of limb strength by manual muscle test were four, and immobilization on bedsince one and half year. The first day after craniotomy, patient has Rehabilitation Program; cryotherapy for decreased the pain, therapeutic exercise, and cognitive stimulation exercise for 5 week.Results: After 5 weeks of rehabilitation program, patient has reduced the pain measured by VAS was 0, improved the memory, and be able to ambulationConclusion: Patient post GBM post craniotomy need to have comprehensive rehabilitation program to reduce pain, improve memory and ambulation.Keywords: Glioblastoma Multiform, Rehabilitation Medicine Program
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Yazıcı, Emine, Aleyna Gezen, Ece Oylumlu, and Gamze Tanrıöver. "Glioblastoma multiform tedavisindeki birincil engel: Kan beyin bariyeri." Ege Tıp Dergisi 64, no. 1 (2025): 184–92. https://doi.org/10.19161/etd.1621826.
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Dünya Sağlık Örgütü tarafından derece 4 astrositom olarak sınıflandırılan Glioblastoma Multiform (GBM), merkezi sinir sisteminin en agresif ve yaygın görülen primer beyin tümörüdür. Klinikteki GBM hastaları için mevcut tedavi; rezeksiyonun ardından eş zamanlı uygulanan radyoterapi ve kemoterapiyi içermektedir. Glioblastoma Multiform tedavisindeki bu yaklaşımların etkinliği; tümör heterojenliği, glioma kök hücreleri, DNA hasar onarım mekanizmaları ve kan-beyin bariyeri gibi faktörler nedeniyle yetersiz kalmaktadır. Temozolomid, lipofilik bir ajan olması nedeniyle kan-beyin bariyerini kolaylıkla geçebilmekte ve bu özelliği sayesinde glioma tedavisinde etkili bir ajan olarak kullanılmaktadır. Bununla birlikte, hastaların büyük bir kısmında nüks meydana gelmekte ve bu hastalar Temozolomid’e uzun süre maruz kaldığı için tedaviye direnç geliştirmektedir. Günümüzde, nüks eden GBM hastaları için farklı bir tedavi yaklaşımı söz konusu değildir. Bu yüzden, hasta sağkalımını uzatacak yeni ajanların araştırılması son derece önemlidir. Terapötik ajanların merkezi sinir sistemine iletimi, kan-beyin bariyeri tarafından engellenmekte ve beyindeki hedeflenen bölgelere erişim, GBM için yeni ilaçların geliştirilmesinde en büyük zorluklardan birini oluşturmaktadır. Beyin tümörleri tedavisinde kan-beyin bariyerinin ilaç geçirgenliği heterojen bir yapı sergilemektedir. Sonuç olarak, bu bariyer geçirgenliğinin modüle edilmesi ve ilaç biyoyararlanımını artırmayı hedefleyen çeşitli stratejiler geliştirilmelidir. Kan-beyin bariyerinin aşılması, hedefe yönelik tedavi yaklaşımlarında dikkate alınması gereken önemli bir konudur. Bu derleme, kan-beyin bariyerinin GBM ile ilişkisini inceleyerek, konuya dair güncel bilgileri ayrıntılı bir şekilde sunmayı amaçlamaktadır.
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Goodarzi, Arash, Mehdi Khanmohammadi, Arman Ai, et al. "Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model." Molecular Biology Reports 47, no. 10 (2020): 7783–95. http://dx.doi.org/10.1007/s11033-020-05855-z.
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Abstract Glioblastoma multiform (GBM) is known as an aggressive glial neoplasm. Recently incorporation of mesenchymal stem cells with anti-tumor drugs have been used due to lack of immunological responses and their easy accessibility. In this study, we have investigated the anti-proliferative and apoptotic activity of atorvastatin (Ator) in combination of mesenchymal stem cells (MSCs) on GBM cells in vitro and in vivo. The MSCs isolated from rats and characterized for their multi-potency features. The anti-proliferative and migration inhibition of Ator and MSCs were evaluated by MTT and scratch migration assays. The annexin/PI percentage and cell cycle arrest of treated C6 cells were evaluated until 72 h incubation. The animal model was established via injection of C6 cells in the brain of rats and subsequent injection of Ator each 3 days and single injection of MSCs until 12 days. The growth rate, migrational phenotype and cell cycle progression of C6 cells decreased and inhibited by the interplay of different factors in the presence of Ator and MSCs. The effect of Ator and MSCs on animal models displayed a significant reduction in tumor size and weight. Furthermore, histopathology evaluation proved low hypercellularity and mitosis index as well as mild invasive tumor cells for perivascular cuffing without pseudopalisading necrosis and small delicate vessels in Ator + MSCs condition. In summary, Ator and MSCs delivery to GBM model provides an effective strategy for targeted therapy of brain tumor.
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Litak, Jakub, Wiesława Grajkowska, Justyna Szumiło, et al. "PD-L1 Expression Correlated with p53 Expression in Pediatric Glioblastoma Multiforme." Brain Sciences 11, no. 2 (2021): 262. http://dx.doi.org/10.3390/brainsci11020262.
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High-grade gliomas are infrequent in the pediatric population compared to adults, nevertheless, mortality and morbidity caused by malignant gliomas in this group of patients remain significant. PD-L1 and PD-1 Immune checkpoints (IC) molecules maintain immunological balance between activation and suppression. Eighteen patients with a histopathological diagnosis of pediatric glioblastoma multiforme (GBM, WHO IV) were studied. In total, PD-L1 expression was detected in 8 patients (44%). The molecular aspect of IC and immunotherapy targeted on PD-1/PD-L1 axis in pediatric population may be a promising adjuvant therapy in pediatric glioblastoma multiform treatment, however, this subject requires further investigation.
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Naveenkumr., R., A. Nagarathna., and V. K. Prathiba. "A Review of Glioblastoma Tumor Image Segmentation Techniques." Journal of Medical Surgical Nursing Practice and Research 2, no. 2 (2020): 20–24. https://doi.org/10.5281/zenodo.3750733.
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The heterogeneous and persistent growth of tumor cells in glioblastoma multiform is an intricate confrontation for brain tumor treatment. The advanced therapies with improved precision are effective in mapping the tumor cells and helpful in combating the brain tumor. The multimodality image processing has become more popular in brain tumor quantification; it includes image segmentation as essential step adopted for standard treatment plans. To reduce the manual segmentation procedure and to optimization in targeted treatments are major key issues are still needs to focus for effective image segmentation. This paper highlights the primary clinical therapies applied for different stage of glioblastoma multiform and processing of multimodal information. The recent glioblastoma multiform segmentation techniques are discussed with key features of mapping probability and prediction capabilities.
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Alshabi, Ali Mohamed, Basavaraj Vastrad, Ibrahim Ahmed Shaikh, and Chanabasayya Vastrad. "Identification of Crucial Candidate Genes and Pathways in Glioblastoma Multiform by Bioinformatics Analysis." Biomolecules 9, no. 5 (2019): 201. http://dx.doi.org/10.3390/biom9050201.
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The present study aimed to investigate the molecular mechanisms underlying glioblastoma multiform (GBM) and its biomarkers. The differentially expressed genes (DEGs) were diagnosed using the limma software package. The ToppGene (ToppFun) was used to perform pathway and Gene Ontology (GO) enrichment analysis of the DEGs. Protein-protein interaction (PPI) networks, extracted modules, miRNA-target genes regulatory network and TF-target genes regulatory network were used to obtain insight into the actions of DEGs. Survival analysis for DEGs was carried out. A total of 590 DEGs, including 243 up regulated and 347 down regulated genes, were diagnosed between scrambled shRNA expression and Lin7A knock down. The up-regulated genes were enriched in ribosome, mitochondrial translation termination, translation, and peptide biosynthetic process. The down-regulated genes were enriched in focal adhesion, VEGFR3 signaling in lymphatic endothelium, extracellular matrix organization, and extracellular matrix. The current study screened the genes in the PPI network, extracted modules, miRNA-target genes regulatory network, and TF-target genes regulatory network with higher degrees as hub genes, which included NPM1, CUL4A, YIPF1, SHC1, AKT1, VLDLR, RPL14, P3H2, DTNA, FAM126B, RPL34, and MYL5. Survival analysis indicated that the high expression of RPL36A and MRPL35 were predicting longer survival of GBM, while high expression of AP1S1 and AKAP12 were predicting shorter survival of GBM. High expression of RPL36A and AP1S1 were associated with pathogenesis of GBM, while low expression of ALPL was associated with pathogenesis of GBM. In conclusion, the current study diagnosed DEGs between scrambled shRNA expression and Lin7A knock down samples, which could improve our understanding of the molecular mechanisms in the progression of GBM, and these crucial as well as new diagnostic markers might be used as therapeutic targets for GBM.
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Berthier, Sylvie, Louis Larrouquère, Pierre Champelovier, et al. "A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent." Cancers 11, no. 1 (2018): 12. http://dx.doi.org/10.3390/cancers11010012.
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Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.
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Allingham-Hawkins, Diane, Andrew Lea, and Susan Levine. "DecisionDx-GBM Gene Expression Assay for Prognostic Testing in Glioblastoma Multiform." PLoS Currents 2 (October 12, 2010): RRN1186. http://dx.doi.org/10.1371/currents.rrn1186.
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Ihtasham Ali, Abdul Salam, and Talha Saleem. "Use of Lipid-Based Nanoparticles for the Treatment of Glioblastoma Multiform; A Review." Physical Education, Health and Social Sciences 3, no. 1 (2025): 370–92. https://doi.org/10.63163/jpehss.v3i1.222.
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A malignant brain tumor with a dismal prognosis and few available treatments is glioblastoma multiforme (GBM). The blood-brain barrier (BBB) poses challenges for therapeutic agents reaching the tumor site. Lipid-based nanoparticles (LBNPs) have emerged as a promising solution to get better outcomes in GBM therapy. LBNPs include liposomes, lipid nanoparticles (LNP), solid lipid nanoparticles (SLPs), lipid Nano emulsion (LNE), and nanostructured lipid carrier (NLC). The compromised BBB restricts the amount of medication that can flow through it and prevents it from reaching the tumor location. This review discusses the status of LNPs in GBM treatment, their types, and mechanisms of action, advantages and challenges, including toxicity, reproducibility and targeting ability. The review also explores the combination of LNPs with radiation therapy and immunotherapy to enhance therapy results.
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Amirpour, Zeinab, Arezoo Bahari, Behrad Nafisi, Koorosh Rahmani, and Shokouh Taghipour Zahir. "Prognosis and Survival Study in Patients with Glioblastoma Multiform and Its Relationship with EGFR Expression." Iranian Journal of Neurosurgery 6, no. 3 (2020): 113–20. http://dx.doi.org/10.32598/irjns.6.3.2.
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Background and Aim: Glioblastoma multiforme (GBM) is the most common malignant and invasive tumor of the brain. The relation between prognosis and survival of GBM patients with Epidermal Growth Factor Receptor (EGFR) expression is challenging. Thus, we aimed to evaluate the prognosis and survival of patients with GBM and its relationship with EGFR expression. Materials and Methods: This single-arm cohort study was conducted on 70 patients with GBM during 2012-2018 in Shahid Rahnemoon and Mortaz hospitals. The immunohistochemistry technique was applied to paraffin blocks of brain tumors for examining EGFR expression. Other data were extracted from medical records. To determine the survival rate, the Kaplan–Meier curves were used. A chi-square test was used for the analysis of data. Statistically, p-value <0.05 was assumed significant. Results: The mean survival of patients with GBM was 22.3 ± 2.5 months (95% CI=17.41 - 27.10). In addition, 1, 2- and 5-year survival rates were 90%, 30% and 5%, respectively. The mean survival of patients with negative and positive EGFR was 27.4±7.3 and 20.6±2.4 months, respectively. Besides, 11.1% and 14.3% of patients in negative and positive EGFR groups were alive. There was no significant difference in patient’s survival in terms of EGFR expression (p=0.36). No significant difference was seen between the two groups (EGFR positive and negative groups), regarding the frequency of age, sex, tumor’s anatomical location, and place of living (p>0.05). Conclusion: Based on our study, it seems that the GBM tumor was associated with poor prognosis and a low survival rate. It was also found that the expression of the EGFR gene did not affect the survival rate of patients with GBM. Therefore, its use as a predictor factor for survival and prognosis is questionable.
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Yuan, Tony. "Overview of Retroviral Transduction of HSV-TK Gene in the Gene Suicide Therapy for Glioblastoma Multiform." Theoretical and Natural Science 74, no. 1 (2024): 9–19. https://doi.org/10.54254/2753-8818/2024.la18760.
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Glioblastoma Multiform (GB) is the most malignant tumor of the brain. The treatment of GBM is a challenging task worldwide, and the prognosis of GBM remains poor, thus demanding the research of new and improved therapies. One new approach in treating GBM is through the transduction of the Herpes simplex Virus Thymidine Kinase (HSV-TK) gene, followed by ganciclovir (GCV) administration. During GBM treatment, the HSV-TK gene is first delivered into the host by retroviruses, one of the most commonly used vectors in said therapy due to their ability to selectively modify actively dividing cancer cells. Following the expression of HSV-TK, the HSV-TK enzyme catalyzes the phosphorylation of GCV into a cytotoxic metabolite, leading to the apoptosis of the target cell. Moreover, a phenomenon observed in cancer cells during gene suicide therapy named the"bystander effect" further enhanced CV cytotoxicity. Said effect enables the transfer of GCV-3P to surrounding cancer cells without HSV-TK transduction and expression, elevating cytotoxic effects throughout the tumor. However, due to the heterogeneous nature of GBM, relapse of the tumor is almost certain after HSV-TK therapy. Additionally, tumor-associated macrophages in the tumor microenvironment (TME) of GBM further enhance treatment difficulty. Further research should go towards understanding the TME of GBM to personalize better and design more effective treatments.
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Alizadeh, Mohammadreza, Nima Broomand Lomer, Mobin Azami, et al. "Radiomics: The New Promise for Differentiating Progression, Recurrence, Pseudoprogression, and Radionecrosis in Glioma and Glioblastoma Multiforme." Cancers 15, no. 18 (2023): 4429. http://dx.doi.org/10.3390/cancers15184429.
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Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient follow-up after treatment (surgery and chemoradiation) is still challenging for differentiation between tumor progression/recurrence, pseudoprogression, and radionecrosis. Radiomics emerges as a promising tool in initial diagnosis, grading, and survival prediction in patients with glioma and can help differentiate these post-treatment scenarios. Preliminary published studies are promising about the role of radiomics in post-treatment glioma/GBM. However, this field faces significant challenges, including a lack of evidence-based solid data, scattering publication, heterogeneity of studies, and small sample sizes. The present review explores radiomics’s capabilities in following patients with glioma/GBM status post-treatment and to differentiate tumor progression, recurrence, pseudoprogression, and radionecrosis.
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Zadran, Sohila, Francoise Remacle, and Raphael Levine. "Surprisal Analysis of Glioblastoma Multiform (GBM) MicroRNA Dynamics Unveils Tumor Specific Phenotype." PLoS ONE 9, no. 9 (2014): e108171. http://dx.doi.org/10.1371/journal.pone.0108171.
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Sudibio, Sudibio, Jellyca Anton, Handoko Handoko, et al. "Outcome Analysis and Prognostic Factors in Patients of Glioblastoma Multiforme: An Indonesian Single Institution Experience." Open Access Macedonian Journal of Medical Sciences 9, B (2021): 1410–16. http://dx.doi.org/10.3889/oamjms.2021.7502.
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Aims: This study was done to assess the survival of patients with glioblastoma multiform and to identify factors that can affect patient survival.
 Materials and methods: From January 2015 to December 2019, 55 patients with histopathologically confirmed glioblastoma multiform and received adjuvant radiation/chemoradiation in our department were retrospectively analyzed.
 Results: The median overall survival (OS) for entire cohort was 13 months and 1-year OS and 2-year OS rate were 52.7% and 3.6% with the mean follow-up period was 12 months. In univariate analysis, age (≤50 years vs >50 years, p=0.02), performance status (≥90 vs 70-80 vs <70, p<0.001), RTOG RPA classification (class III vs class IV vs class V-VI, p<0.001), parietal lobes tumor site (vs others, p=0.02), residual tumor volume (≤20.4cm3 vs >20.4cm3, p=0.001) and time to initiate adjuvant therapy (<4 weeks vs 4-6 weeks vs >6 weeks, p=0.01) were significantly affect overall survival. In multivariate analysis, RTOG RPA classification and involvement of parietal lobes were independent prognostic factors for overall survival.
 Conclusions: RTOG RPA classification that consisted of age and performance status is an independent prognostic factor for the clinical outcome of GBM. Besides this well-known factor, we also identified the involvement of parietal lobe gives a strong negative influence on survival of GBM patients.
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Bruna-Mejías, Alejandro, Vicente Silva-Bravo, Laura Moyano Valarezo, et al. "The Adverse Effects and Use of Bevacizumab in Patients with Glioblastoma: A Systematic Review and Meta-Analysis." Pharmaceuticals 18, no. 6 (2025): 795. https://doi.org/10.3390/ph18060795.
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Background: A glioblastoma (GBM) is a type of tumor originating from the glial brain cells, the astrocytes, and thus belongs to the astrocytoma group. Bevacizumab (BV) is a treatment for GBM. BV is the active ingredient in the drugs Avastin®, Alymsys®, Mvasi® and ZiraBev®. It is currently approved as second-line treatment for GBM recurrence in combination with radiotherapy, and as first-line treatment for other cancers, including advanced colorectal cancer, metastatic breast cancer and advanced non-small-cell lung cancer. The objective of this systematic review was to analyze the scientific evidence from the science-based literature on the therapeutic effect and adverse effects of the drug BV in patients with GBM or GBM multiforme. Methods: We systematically searched electronic databases for the literature search, including the MEDLINE (via PubMed), SCOPUS, Google Scholar, the Cumulative Index to Nursing and Allied Health Literature and Web of Science databases, covering records from their earliest data to December 2024. Randomized or controlled clinical trials that were published in English or Spanish were included. The following keywords were used in different combinations: “Bevacizumab therapy”, “Bevacizumab pharmaceutical”, “Glioblastoma”, “Glioma” and “multiform glioblastoma”. Results: The use of Bevacizumab has been extensively studied in the scientific literature, with beneficial effects in symptom control. However, the adverse effects of BV vary across different types of carcinomas, which is why it has already been established that these adverse effects must be taken into consideration. In our meta-analysis of adverse effects, we found 14 adverse effects and estimated their prevalence, with an average of 19% (CI: 4 to 44%). The most significant vascular adverse effect was thromboembolism, which led to a greater number of complications for patients with GBM. Finally, the most common adverse effects were nausea, vomiting, fatigue and hypertension. Conclusions: While the beneficial properties of this pharmacological therapy have been observed, its adverse effect profile requires constant evaluation, as it includes vascular, blood and symptomatic adverse effects, which must be analyzed on a case-by-case basis and with great attention, especially in the case of more serious complications such as thromboembolic events.
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Shi, Tingyu, Jun Zhu, Xiang Zhang, and Xinggang Mao. "The Role of Hypoxia and Cancer Stem Cells in Development of Glioblastoma." Cancers 15, no. 9 (2023): 2613. http://dx.doi.org/10.3390/cancers15092613.
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Glioblastoma multiform (GBM) is recognized as the most malignant brain tumor with a high level of hypoxia, containing a small population of glioblastoma stem like cells (GSCs). These GSCs have the capacity of self-renewal, proliferation, invasion and recapitulating the parent tumor, and are major causes of radio-and chemoresistance of GBM. Upregulated expression of hypoxia inducible factors (HIFs) in hypoxia fundamentally contributes to maintenance and progression of GSCs. Therefore, we thoroughly reviewed the currently acknowledged roles of hypoxia-associated GSCs in development of GBM. In detail, we recapitulated general features of GBM, especially GSC-related features, and delineated essential responses resulted from interactions between GSC and hypoxia, including hypoxia-induced signatures, genes and pathways, and hypoxia-regulated metabolic alterations. Five hypothesized GSC niches are discussed and integrated into one comprehensive concept: hypoxic peri-arteriolar niche of GSCs. Autophagy, another protective mechanism against chemotherapy, is also closely related to hypoxia and is a potential therapeutic target for GBM. In addition, potential causes of therapeutic resistance (chemo-, radio-, surgical-, immuno-), and chemotherapeutic agents which can improve the therapeutic effects of chemo-, radio-, or immunotherapy are introduced and discussed. At last, as a potential approach to reverse the hypoxic microenvironment in GBM, hyperbaric oxygen therapy (HBOT) might be an adjuvant therapy to chemo-and radiotherapy after surgery. In conclusion, we focus on demonstrating the important role of hypoxia on development of GBM, especially by affecting the function of GSCs. Important advantages have been made to understand the complicated responses induced by hypoxia in GBM. Further exploration of targeting hypoxia and GSCs can help to develop novel therapeutic strategies to improve the survival of GBM patients.
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Pournajaf, Safura, Nastaran Afsordeh, and Mohammad Hossein Pourgholami. "In vivo C6 glioma models: an update and a guide toward a more effective preclinical evaluation of potential anti-glioblastoma drugs." Reviews in the Neurosciences 35, no. 2 (2023): 183–95. http://dx.doi.org/10.1515/revneuro-2023-0067.
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Abstract Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations.
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Naryzhny, Stanislav, Natalia Ronzhina, Elena Zorina, et al. "Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers." International Journal of Molecular Sciences 22, no. 12 (2021): 6533. http://dx.doi.org/10.3390/ijms22126533.
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Haptoglobin (Hp) is a blood plasma glycoprotein that plays a critical role in tissue protection and the prevention of oxidative damage. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein and is the subject of research as a potential biomarker of many diseases, including malignant neoplasms. The Human Hp gene is polymorphic and controls the synthesis of three major phenotypes—homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual’s predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). Glioblastoma multiform (GBM) is the most malignant primary brain tumor. In our study, we have analyzed the state of Hp proteoforms in plasma and cells using 1D (SDS-PAGE) and 2D electrophoresis (2DE) with the following mass spectrometry (LC ES-MS/MS) or Western blotting. We found that the levels of α2- and β-chain proteoforms are up-regulated in the plasma of GBM patients. An unprocessed form of Hp2-2 (PreHp2-2, zonulin) with unusual biophysical parameters (pI/Mw) was also detected in the plasma of GBM patients and glioblastoma cells. Altogether, this data shows the possibility to use proteoforms of haptoglobin as a potential GBM-specific plasma biomarker.
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Dr., Mohammed Muneam Duhis. "Advances in Neurosurgical Techniques for Resection of Glioblastoma Multiforme: A Comprehensive Study." Sarcouncil Journal of Medical Sciences 4, no. 4 (2025): 24–30. https://doi.org/10.5281/zenodo.15277416.
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The advances in neurosurgical techniques for the resection of glioblastoma multiform (GBM) have created a mismatched emphasis on extensive tumor resection versus neurological preservation. Advanced imaging technologies, especially intraoperative MRI and CT scan, have taken center stage in this research, as they give better surgical confidence in the delineation of tumor margins. The study was a retrospective cohort that focused on the outcomes of surgical resection of glioblastoma in multi-hospitals in Iraq for about a twelve-month period from 2024 to 2025, with a total of 165 cases recruited who met the diagnosis of GBM. Fluorescence-guided surgery proves to be a highlight, whereby it assists the surgeon to differentiate between tumor and normal tissues, thus enhancing resection with less collateral injury to the brain parenchyma. The advent of robotics and greater performance of neuronavigation have further contributed to the accuracy and skill of the surgeon, but nevertheless, the infiltrative kind of GBM contrasts with gross removal. The study suggests that gross total resection improves the prognosis of patients, which corresponds with what the literatures suggest-that: the extent of resection correlates with survival rates. Even with advances in technology, however, the GBM prognosis still remains grim, as seen from the median survival rate. The study further mentions the advantages of minimally invasive approaches in endoscopic or keyhole surgery for quicker recovery and better quality of life. Together with laser ablation and ultrasound, these methods allow exact destruction of the tumor with minimal collateral injury. The authors call for further research and innovations, with an emphasis on a multidisciplinary approach that combines extreme surgical precision with complete teamwork in patient care to achieve the best outcomes possible for patients with GBM
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Relave, Emmanuelle T., Rayane Hedna, Attilio Di Maio, et al. "Therapeutic Contribution of Tau-Binding Thiazoloflavonoid Hybrid Derivatives Against Glioblastoma Using Pharmacological Approach in 3D Spheroids." International Journal of Molecular Sciences 25, no. 21 (2024): 11785. http://dx.doi.org/10.3390/ijms252111785.
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Growing evidence has unveiled the pathological significance of Tau in many cancers, including the most aggressive and lethal brain tumor glioblastoma multiform (GBM). In this regard, we have recently examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau-overexpressing GBM cells. Here, we evaluated the anticancer activities of the two lead compounds 2 and 9 using multi-cellular spheroids (MCSs) which represent an easy 3D human cell model to mimic GBM organization, physical constraints and drug penetration. The two compounds reduced cell evasion from spheroids up to three times, especially for Tau-expressing cells. As a first step towards a therapeutic approach, we quantified the effects of these compounds on MCS growth using two complementary protocols: single and repeated treatments. A single injection with compound 9 slowed down the growth of MCSs formed with U87 shCTRL cells by 40% at 10 µM. More interestingly, multiple treatment with compound 9 slowed the growth of U87 shCTRL spheroids by 40% at a concentration of 5 µM, supporting the increased bioavailability of compound 9 within MCSs. In conclusion, compound 9 deserves particular attention as promising candidate for specifically targeting Tau-expressing cancers such as GBM.
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Cheung, Eva Y. W., Ricky W. K. Wu, Albert S. M. Li, and Ellie S. M. Chu. "AI Deployment on GBM Diagnosis: A Novel Approach to Analyze Histopathological Images Using Image Feature-Based Analysis." Cancers 15, no. 20 (2023): 5063. http://dx.doi.org/10.3390/cancers15205063.
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Background: Glioblastoma (GBM) is one of the most common malignant primary brain tumors, which accounts for 60–70% of all gliomas. Conventional diagnosis and the decision of post-operation treatment plan for glioblastoma is mainly based on the feature-based qualitative analysis of hematoxylin and eosin-stained (H&E) histopathological slides by both an experienced medical technologist and a pathologist. The recent development of digital whole slide scanners makes AI-based histopathological image analysis feasible and helps to diagnose cancer by accurately counting cell types and/or quantitative analysis. However, the technology available for digital slide image analysis is still very limited. This study aimed to build an image feature-based computer model using histopathology whole slide images to differentiate patients with glioblastoma (GBM) from healthy control (HC). Method: Two independent cohorts of patients were used. The first cohort was composed of 262 GBM patients of the Cancer Genome Atlas Glioblastoma Multiform Collection (TCGA-GBM) dataset from the cancer imaging archive (TCIA) database. The second cohort was composed of 60 GBM patients collected from a local hospital. Also, a group of 60 participants with no known brain disease were collected. All the H&E slides were collected. Thirty-three image features (22 GLCM and 11 GLRLM) were retrieved from the tumor volume delineated by medical technologist on H&E slides. Five machine-learning algorithms including decision-tree (DT), extreme-boost (EB), support vector machine (SVM), random forest (RF), and linear model (LM) were used to build five models using the image features extracted from the first cohort of patients. Models built were deployed using the selected key image features for GBM diagnosis from the second cohort (local patients) as model testing, to identify and verify key image features for GBM diagnosis. Results: All five machine learning algorithms demonstrated excellent performance in GBM diagnosis and achieved an overall accuracy of 100% in the training and validation stage. A total of 12 GLCM and 3 GLRLM image features were identified and they showed a significant difference between the normal and the GBM image. However, only the SVM model maintained its excellent performance in the deployment of the models using the independent local cohort, with an accuracy of 93.5%, sensitivity of 86.95%, and specificity of 99.73%. Conclusion: In this study, we have identified 12 GLCM and 3 GLRLM image features which can aid the GBM diagnosis. Among the five models built, the SVM model proposed in this study demonstrated excellent accuracy with very good sensitivity and specificity. It could potentially be used for GBM diagnosis and future clinical application.
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Xiu, Joanne, Rebecca Anne Feldman-Moreno, David Arguello, et al. "Biomarker analysis of glioblastoma and potential implications for therapy." Journal of Clinical Oncology 31, no. 15_suppl (2013): 2041. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.2041.
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2041 Background: Glioblastoma multiform (GBM), the most aggressive CNS cancer, has limited effective therapeutic options, with underlying molecular heterogeneity contributing to the differences in treatment response. Our study was designed to interrogate biomarkers from a large cohort of GBM patients to seek therapeutic implications. Methods: Data was analyzed from 570 high grade astrocytoma patients (vast majority GBM) who received tumor profiling at Caris Life Sciences from 2009 to 13. Test methodologies included IHC, FISH, CISH, Sanger SEQ, MGMT promoter methylation and NextGen SEQ (Illumina TruSeq). Results: In our patient cohort, 59% had MGMT methylation and 70% had negative MGMT IHC, predicting potential response to temozolomide. Protein expression for ERCC1, TOPO1, and TS was 53% negative, 49% positive, and 37% negative, indicating potential benefit from cisplatin, irinotecan and fluorouracil, respectively. Drug pumps PGP and MRP1, were positive by IHC in 10% and 67% of patients, suggesting possible resistance to etoposide, vinca alkaloids and methotrexate. For targeted therapies, c-Kit IHC was positive in 7% patients, mutated in 6% and PDGFRA IHC was positive in 27%, indicating potential benefit from imatinib and other TKI’s. RAS/RAF and PIK3CA/mTOR pathway activation was also noted with BRAF, KRAS, PIK3CA mutations and PTEN loss, observed in 8%, 3%, 7% and 10% of cases, respectively. TS negativity was seen in 91% of MGMT methylated patients and in 37% of MGMT unmethylated patients (p = 0.025, student’s t-test), revealing a possible novel combination therapy of fluoropyrimidines with temozolomide for a select cohort. Similarly, biomarker profiles of molecular subgroups defined by EGFR amplification (44% in our cohort) and IDH1, p53 mutations will be analyzed for therapeutic implications. Conclusions: By profiling tumor biomarkers from a large cohort of GBM patients using validated assays in a single facility, we demonstrate the vast molecular heterogeneity of GBM and highlight the importance of individualized therapy based on a patient’s unique tumor profile. Incorporating a comprehensive biomarker analysis into clinical management of this aggressive cancer allows for an informed selection of more effective therapies.
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Perez, T., R. Berges, H. Maccario, D. Braguer, and S. Honoré. "P11.06 Non epigenetic effect of vorinostat in glioblastoma cells." Neuro-Oncology 21, Supplement_3 (2019): iii43. http://dx.doi.org/10.1093/neuonc/noz126.152.
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Abstract BACKGROUND Glioblastoma multiform (GBM) is the most frequent primitive brain tumor. GBM has a high recurrence and mortality. Histone deacetylase (HDAC) inhibitors have evoked great interest because they are able to change transcriptomic profiles to promote tumor cell death but also show undesirable side effects due to the lack of selectivity.We show new properties of low dose vorinostat, which inhibits cytoplasmic HDAC6 and display interesting non-epigenetics effects, especially on the microtubular cytoskeleton. MATERIAL AND METHODS We used murine (GL261) and human (U87 and GBM6 stem cells) cellular models. The cell proliferation was assessed by MTT tests, the migration by the 24 hours Transwell technic and by wound/healing tests. The expression levels of proteins of interest were assessed by Western Blot. Microtubules dynamics were assessed by time-lapse videomicroscopy. The synergy between drugs was tested by Loewe model. RESULTS Vorinostat inhibited the proliferation and the migration of the three cell lines mentioned above at level below the EC50.Vorinostat induces tubulin acetylation and alpha-tubulin c-terminal detyrosination that signed microtubular stabilization and these effects are independent of histone acetylation (HADC3). Interestingly, vorinostat decreases EB1 expression (a bad prognostic factor in GBM) and decreases microtubule dynamics. Moreover, vorinostat decreases neural markers such as GFAP, beta3-tubulin and CNPase and increases mural markers expression such as SMA/EGFR and PDGFR. Finally, it showed a synergy combined with erlotinib. CONCLUSION Low dose vorinostat, which do not affect histone désacetylase, has antitumor effect on glioblastoma cells by a new mechanism involving microtubule cytoskeleton. Interestingly, combination of low doses vorinostatand erlotinibshowed a strong synergy. Low dose, vorinostat could therefore represent an interesting therapeutic option and fewer side effects and that could be used to increased GBM patient sensitivity to erlotinib.
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Hedna, Rayane, Attilio DiMaio, Maxime Robin, et al. "2-Aminothiazole-Flavonoid Hybrid Derivatives Binding to Tau Protein and Responsible for Antitumor Activity in Glioblastoma." International Journal of Molecular Sciences 24, no. 20 (2023): 15050. http://dx.doi.org/10.3390/ijms242015050.
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Tau protein has been described for several decades as a promoter of tubulin assembly into microtubules. Dysregulation or alterations in Tau expression have been related to various brain cancers, including the highly aggressive and lethal brain tumor glioblastoma multiform (GBM). In this respect, Tau holds significant promise as a target for the development of novel therapies. Here, we examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau binding, Tau fibrillation, and cellular effects on Tau-expressing cancer cells. By spectrofluorometric approach, we found that two compounds, 2 and 9, demonstrated high affinity for Tau and exhibited a strong propensity to inhibit Tau fibrillation. Then, the biological activity of these compounds was evaluated on several Tau-expressing cells derived from glioblastoma. The two lead compounds displayed a high anti-metabolic activity on cells related to an increased fission of the mitochondria network. Moreover, we showed that both compounds induced microtubule bundling within newly formed neurite-like protrusions, as well as with defection of cell migration. Taken together, our results provide a strong experimental basis to develop new potent molecules targeting Tau-expressing cancer cells, such as GBM.
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Kim, Hyo In, Se Hyang Hong, Jin Mo Ku, et al. "Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes." Nutrients 12, no. 1 (2020): 196. http://dx.doi.org/10.3390/nu12010196.
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Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. Gardenia jasminoides (GJ) is flavonoid abundant with beneficial effects on inflammation, metabolic diseases, and cancers. In this study, we investigated the synergistic combination of GJ and cisplatin (CDDP) in U87MG and U373MG GBM cells. GJ and CDDP both showed cytotoxicity in U87MG cells, however GJ did not affect viability of normal astrocytes while CDDP displayed high toxicity. Cytotoxic effect of GJ and CDDP was related in apoptosis when confirmed by Western blot assays on cleaved caspase-3, caspase-9, and PARP. Moreover, GJ and CDDP showed synergistic combination in cell death of GBM cells, which was further confirmed by Western blot assays of apoptosis factors and also flow cytometry of Annexin V. Analysis on autophagy factors showed that GJ/CDDP combination induced autophagy, and through inhibition of autophagy, we could confirm autophagy is crucial to cytotoxicity of GJ/CDDP in GBM cell lines. The autophagy-mediated apoptosis of GJ/CDDP was dependent on the AKT/mTOR pathway. Overall, our results suggest GJ/CDDP combination as an effective yet safe therapeutic approach to GBMs.
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Utley, Kaylyn, Jens Reuter, Lei Li, Devon Evans, Jeffrey Florman, and Stanley Chaleff. "RARE-23. NOVEL NF1 MUTATIONS IN TWO OCCURRENCES OF GLIOBLASTOMA MULTIFORM IN A PATIENT WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME." Neuro-Oncology 22, Supplement_3 (2020): iii447. http://dx.doi.org/10.1093/neuonc/noaa222.734.
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Abstract Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare cancer predisposition syndrome in children. Its main associated tumor types include brain and CNS tumors, hematologic malignancies, intestinal polyps and colorectal tumors, and other malignancies. Tumor genesis within this population is highly complex and poorly understood. We describe a case of a patient with two occurrences of glioblastoma multiforme (GBM), each with unique NF1 mutations. The patient is a female with CMMRD who was first diagnosed with GBM of the right frontal lobe in 2015. She subsequently underwent gross total resection, radiation to the field and concomitant and maintenance therapy with Temozolomide and Everolimus, due to high suspicion for NF-1. Genetic studies didn’t show NF-1, instead revealing a diagnosis of CMMRD. Molecular testing of the GBM showed a high mutational burden and an NF1 mutation. Later, screening revealed stage IV colon cancer, for which she underwent subtotal colectomy, partial liver resection and chemotherapy. Molecular testing from the colon cancer found a hypermutant malignancy without mutations in NF1. Surveillance imaging detected a mass at the original site of her GBM, for which she had a resection. Notably, the genetic profile of the second tumor substantially different from the original tumor and the colon cancer sample, but had new mutations in NF-1. These findings highlight the significant variability in the genetic profiles of tumors in the context of CMMRD. It is also worth considering that NF1 is one of the first in a cascade of mutations leading to GBM in these patients.
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Barekatain, Yasaman, Jeffrey Ackroyd, Victoria Yan, et al. "Abstract 2395: Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine." Cancer Research 82, no. 12_Supplement (2022): 2395. http://dx.doi.org/10.1158/1538-7445.am2022-2395.
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Abstract Homozygous deletion of the CDK2NA locus frequently results in the co-deletion of methylthioadenosine phosphorylase (MTAP) in many fatal cancers such as glioblastoma multiform (GBM). In cell culture, cell lines with MTAP-deletions show elevations of its substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit PRMT5, which sensitizes MTAP-deleted cell lines to PRMT5 and MAT2A inhibition. While extensively corroborated in vitro, the clinical efficacy of these strategies ultimately relies on equally significant accumulations of MTA in human tumors. In this work, using comprehensive metabolomic profiling, we show that MTA is primarily secreted, resulting in exceedingly high levels of extracellular MTA in vitro. We further show that primary human glioblastoma tumors minimally accumulate MTA in vivo, which is likely explained by the metabolism of MTA by MTAP-competent stromal cells. Together, these findings highlight the metabolic discrepancies between in vitro models and primary human tumors and should thus be carefully considered in the development of the precision therapies targeting MTAPhomozygous deleted GBM. Citation Format: Yasaman Barekatain, Jeffrey Ackroyd, Victoria Yan, Sunada Khadka, Ko-Chien Chen, Raghu Kalluri, John de Groot, Jason Huse, Florian muller. Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2395.
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HU, Yu-hua, Li-Jie YU, En-de SHAO, Jian-liang WU та Jian-wen JI. "The regulating role of mutant IκBα in expression of TIMP-2 and MMP-9 in human glioblastoma multiform". Chinese Medical Journal 122, № 2 (2009): 205–11. http://dx.doi.org/10.3760/cma.j.issn.0366-6999.2009.02.018.
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Background Our previous studies demonstrated that mutant IκBα (IκBαM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IκBαM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IκBαM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM. Methods We established the following four GBM cell lines stably expressing IκBαM by plasmid construction, gene transfection and screening for IκBαM protein expression: mutant IκBα-transfected cells (G36δ-M), wild-type IκBα-transfected cells (G36δ-W), empty plasmid transfected cells (G36δ-P) and untransfected cells (G36δ). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods. Results The results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36δ-M group at both the RNA and protein levels compared with the G36δ-W group, G36δ-P group and G36δ group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36δ-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups. Conclusions Our findings indicate that IκBαM inhibits the activation of NF-κB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IκBαM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.
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Mokgautsi, Ntlotlang, Ya-Ting Wen, Bashir Lawal та ін. "An Integrated Bioinformatics Study of a Novel Niclosamide Derivative, NSC765689, a Potential GSK3β/β-Catenin/STAT3/CD44 Suppressor with Anti-Glioblastoma Properties". International Journal of Molecular Sciences 22, № 5 (2021): 2464. http://dx.doi.org/10.3390/ijms22052464.
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Despite management efforts with standard surgery, radiation, and chemotherapy, glioblastoma multiform (GBM) remains resistant to treatment, which leads to tumor recurrence due to glioma stem cells (GSCs) and therapy resistance. In this study, we used random computer-based prediction and target identification to assess activities of our newly synthesized niclosamide-derived compound, NSC765689, to target GBM oncogenic signaling. Using target prediction analyses, we identified glycogen synthase kinase 3β (GSK3β), β-Catenin, signal transducer and activator of transcription 3 (STAT3), and cluster of differentiation 44 (CD44) as potential druggable candidates of NSC765689. The above-mentioned signaling pathways were also predicted to be overexpressed in GBM tumor samples compared to adjacent normal samples. In addition, using bioinformatics tools, we also identified microRNA (miR)-135b as one of the most suppressed microRNAs in GBM samples, which was reported to be upregulated through inhibition of GSK3β, and subsequently suppresses GBM tumorigenic properties and stemness. We further performed in silico molecular docking of NSC765689 with GBM oncogenes; GSK3β, β-Catenin, and STAT3, and the stem cell marker, CD44, to predict protein-ligand interactions. The results indicated that NSC765689 exhibited stronger binding affinities compared to its predecessor, LCC09, which was recently published by our laboratory, and was proven to inhibit GBM stemness and resistance. Moreover, we used available US National Cancer Institute (NCI) 60 human tumor cell lines to screen in vitro anticancer effects, including the anti-proliferative and cytotoxic activities of NSC765689 against GBM cells, and 50% cell growth inhibition (GI50) values ranged 0.23~5.13 μM. In summary, using computer-based predictions and target identification revealed that NSC765689 may be a potential pharmacological lead compound which can regulate GBM oncogene (GSK3β/β-Catenin/STAT3/CD44) signaling and upregulate the miR-135b tumor suppressor. Therefore, further in vitro and in vivo investigations will be performed to validate the efficacy of NSC765689 as a novel potential GBM therapeutic.
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Smith, Nataliya, Debra Sauders, Rheal Towner, and Michelle Zalles. "EXTH-07. OPTIMIZATION OF TARGETING ELTD1 IN GLIOBLASTOMA USING A MOLECULAR TARGETING APPROACH." Neuro-Oncology 21, Supplement_6 (2019): vi83. http://dx.doi.org/10.1093/neuonc/noz175.341.
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Abstract The standard of care for glioblastoma multiform (GBM), an aggressive form of cancer, has not significantly increased the prognosis for patients. ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain containing protein 1), a biomarker for angiogenesis, was found to be highly expressed in human high-grade gliomas. Novel treatments targeting ELTD1 with polyclonal (pAb) and monoclonal (mAb) antibodies were effective as a potential cancer therapy in a G55-xenograft mouse model. While our studies have demonstrated that the blood brain barrier (BBB) was leaky around the tumor region, other studies have shown that the BBB is not equally disrupted in GBM patients, therefore suggesting that the mAb may have difficulty crossing the BBB and infiltrating the tumor due to its size. To overcome these limitations, this study focused on the optimization of targeting ELTD1 by using an optimized svFc antibody fragment derived from our mAb against ELTD1. Immunocompromised mice were intracerebrally injected with human-G55 cells. Morphological MRI was used to monitor and calculate tumor volumes. Treatments using IgG, anti-ELDT1 mAb or fragment upon tumor detection. Vascular perfusion images were obtained to examine vascular alterations. Molecular targeting imaging (mtMRI) was conducted to assess the binding specificity of our antibodies against the tumor region. Targeting ELTD1 with varying antibodies (anti-ELTD1 mAb and scFv fragment) resulted in increased survival and decreased tumor volumes in a G55 xenograft GBM mouse model. Additionally, through the use of mtMRI, we determined altered levels of binding specificity against the tumor region using three different anti-ELTD1 attached probes (monoclonal and scFv fragment antibodies). Our data suggest that the optimization of an anti-ELTD1 therapy could be used to better target angiogenesis in glioblastomas.
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Karami, Golestan, Marco Giuseppe Orlando, Andrea Delli Pizzi, Massimo Caulo, and Cosimo Del Gratta. "Predicting Overall Survival Time in Glioblastoma Patients Using Gradient Boosting Machines Algorithm and Recursive Feature Elimination Technique." Cancers 13, no. 19 (2021): 4976. http://dx.doi.org/10.3390/cancers13194976.
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Despite advances in tumor treatment, the inconsistent response is a major challenge among glioblastoma multiform (GBM) that lead to different survival time. Our aim was to integrate multimodal MRI with non-supervised and supervised machine learning methods to predict GBM patients’ survival time. To this end, we identified different compartments of the tumor and extracted their features. Next, we applied Random Forest-Recursive Feature Elimination (RF-RFE) to identify the most relevant features to feed into a GBoost machine. This study included 29 GBM patients with known survival time. RF-RFE GBoost model was evaluated to assess the survival prediction performance using optimal features. Furthermore, overall survival (OS) was analyzed using univariate and multivariate Cox regression analyses, to evaluate the effect of ROIs and their features on survival. The results showed that a RF-RFE Gboost machine was able to predict survival time with 75% accuracy. The results also revealed that the rCBV in the low perfusion area was significantly different between groups and had the greatest effect size in terms of the rate of change of the response variable (survival time). In conclusion, not only integration of multi-modality MRI but also feature selection method can enhance the classifier performance.
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Amereh, Meitham, Amir Seyfoori, Briana Dallinger, Mostafa Azimzadeh, Evan Stefanek, and Mohsen Akbari. "3D-Printed Tumor-on-a-Chip Model for Investigating the Effect of Matrix Stiffness on Glioblastoma Tumor Invasion." Biomimetics 8, no. 5 (2023): 421. http://dx.doi.org/10.3390/biomimetics8050421.
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Glioblastoma multiform (GBM) tumor progression has been recognized to be correlated with extracellular matrix (ECM) stiffness. Dynamic variation of tumor ECM is primarily regulated by a family of enzymes which induce remodeling and degradation. In this paper, we investigated the effect of matrix stiffness on the invasion pattern of human glioblastoma tumoroids. A 3D-printed tumor-on-a-chip platform was utilized to culture human glioblastoma tumoroids with the capability of evaluating the effect of stiffness on tumor progression. To induce variations in the stiffness of the collagen matrix, different concentrations of collagenase were added, thereby creating an inhomogeneous collagen concentration. To better understand the mechanisms involved in GBM invasion, an in silico hybrid mathematical model was used to predict the evolution of a tumor in an inhomogeneous environment, providing the ability to study multiple dynamic interacting variables. The model consists of a continuum reaction–diffusion model for the growth of tumoroids and a discrete model to capture the migration of single cells into the surrounding tissue. Results revealed that tumoroids exhibit two distinct patterns of invasion in response to the concentration of collagenase, namely ring-type and finger-type patterns. Moreover, higher concentrations of collagenase resulted in greater invasion lengths, confirming the strong dependency of tumor behavior on the stiffness of the surrounding matrix. The agreement between the experimental results and the model’s predictions demonstrates the advantages of this approach in investigating the impact of various extracellular matrix characteristics on tumor growth and invasion.
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Rahane, Chinmay Satish, Arne Kutzner, and Klaus Heese. "A cancer tissue-specific FAM72 expression profile defines a novel glioblastoma multiform (GBM) gene-mutation signature." Journal of Neuro-Oncology 141, no. 1 (2018): 57–70. http://dx.doi.org/10.1007/s11060-018-03029-3.
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Perez, Joshua, Javier Fierro, Rocio Aguilar, and Huanyu Dou. "OTME-18. Targeted CRISPR/Cas9 gene-editing regulates the brain tumor environment." Neuro-Oncology Advances 3, Supplement_2 (2021): ii17. http://dx.doi.org/10.1093/noajnl/vdab070.069.
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Abstract Glioblastoma multiform (GBM) is the most common malignant brain tumor. Recent immunotherapy has demonstrated potential to treat GBM. However, the immune suppressive tumor environment in the brain represents a significant barrier for the treatment of GBM. Overexpression of programmed death ligand-1 (PD-L1) in GBM tumor cells and macrophages plays a key role in GBM vitality, proliferation, and migration, while also suppressing the immune system. We developed a CRISPR/Cas9 gene-editing system to delete whole cell PD-L1. Human PD-L1 targeted sgRNA were cloned into CRISPR/Cas9 plasmids with or without an HDR templet. CRISPR/Cas9 were treated to human GBM U87 cells for 15, 30, 60, 120 and 240 minutes. The intracellular concentration of CRISPR/Cas9 exhibited a time-dependent increases. A GFP tagged CRISPR/Cas9 plasmid was developed to test the transfection efficacy. Higher levels of GFP+ U87 cells were observed at day 3. CRISPR/Cas9 showed a greater PD-L1 knockout at day 3. The PD-L1 reduction limited the proliferation of U87 cells. A scratch assay showed that PD-L1 deletion inhibited the migration of U87 cells. An in vitro GBM model was developed by co-cultivation of U87 cells and macrophages. CRISPR/Cas9 treated co-cultures changed the ratios of U87 cells and macrophages and polarized tumor associated macrophages (TAM) from M2 toward M1. CRISPR/Cas9 gene-editing effectively deleted PD-L1 in U87 cells. Successful deletion of PD-L1 prevented U87 cells growth and migration, and altered the TAMs plasticity and the tumor environment.
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Burban, Audrey, Ahmad Sharanek, and Arezu Jahani-Asl. "EXTH-52. CO-TARGETING ONCOSTATIN M RECEPTOR USING MONOCLONAL ANTIBODIES IN COMBINATION WITH PRESENT STANDARDS OF CARE FOR GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (2019): vi93. http://dx.doi.org/10.1093/neuonc/noz175.383.
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Abstract Glioblastoma Multiform (GBM) is the most aggressive primary tumor in the adult brain. The present standard of care includes surgical removal of the tumors followed by treatment with Temozolomide (TMZ) and radiation therapy. Despite intense efforts and advances in surgery and combination therapy, the median survival rate for GB patients remain 16 months following diagnosis. EGFRvIII/STAT3 signaling plays critical roles in GBM pathogenesis. We have recently discovered that the tumorigenic capacity of EGFRvIll/STAT3 pathway crucially depends on the cytokine receptor for Oncostatin M (OSMR). OSMR is a required co-receptor of EGFRvIII and a direct transcriptional target of STAT3. Strikingly, OSMR is highly expressed in brain tumor stem cells (BTSCs), a population of self-renewing malignant stem cells within GBM that contribute to tumor growth, recurrence and therapeutic resistance. We have generated therapeutic monoclonal antibodies against OSMR (OSMR mAb) that function as powerful inhibitors of OSMR. Treatment of BTSCs with OSMR mAb resulted in inhibition of OSMR-mediated signaling pathways and significantly impaired the phosphorylation of STAT3. Strikingly, treatment of BTSCs with OSMR mAb significantly attenuated BTSC self-renewal in limiting dilution assay and sensitized their response to tyrosine kinase inhibitors (TKI), ionizing radiation and TMZ. Using patient derived stem cell tumor xenografts, we have shown that OSMR mAb significantly reduced tumor growth compared to IgG control. Together, our findings suggest that targeting OSMR using therapeutic monoclonal antibodies in combination with EGFR inhibitors and/ or the current standard of care may provide a promising therapeutic strategy for glioblastoma.
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Azimi, Parisa, Maryam Bazrgar, Taravat Yazdanian, Mehdi Totonchi, and Abolhassan Ahmadiani. "Cancer/testis antigens FBXO39 and CEP55 expression correlates with survival in GBM patients." PLOS One 20, no. 6 (2025): e0326054. https://doi.org/10.1371/journal.pone.0326054.
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Background Glioblastoma multiform (GBM) is a primary brain malignancy resistant to conventional therapies, with poor survival. Cancer testis antigens (CTAs) are important cancer diagnostic biomarkers and therapeutic targets. Bioinformatics analysis of GBM clinical and molecular data was undertaken to identify and validate the key CTA genes, whose expression correlates with the survival of GBM patients. Methods RNA-seq data of GBM were downloaded from TCGA and CGGA databases to analyze differentially expressed genes (DEGs). Cancer Testis genes (from the CT database), found up and down-regulated in the GBM series compared to normal samples, were determined in both TCGA and CGGA databases. Overall survival (OS) of GBM patients in the TCGA and CGGA databases as a function of the expression of key CTA genes was considered to identify those whose expression significantly predicts patient survival. The predictive values of our candidate genes were then tested using our independent cohort (n = 29) using an RT-qPCR approach. Results Compared to normal brain samples, a total of 2463 and, 6249 up- and 3706 and, 6606 down-regulated genes were found in the TCGA and CGGA, respectively. The intersection between 279 CTAs in the CD database and the up-and-down-regulated genes of both other databases was found in 11 and 8 CTAs, respectively. Using tumor samples from our cohort of 29 patients and an RT-qPCR approach, we found that FBXO39 and CEP55 genes were highly expressed in GBM and that their expression predicted the OS (P < 0.05). Conclusions Our results support the potential use of FBXO39 and CEP55 gene expression measurement as prognostic biomarkers in GBM patients.
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Athanassiou, Helen, Maria Synodinou, Evagelos Maragoudakis, et al. "Randomized Phase II Study of Temozolomide and Radiotherapy Compared With Radiotherapy Alone in Newly Diagnosed Glioblastoma Multiforme." Journal of Clinical Oncology 23, no. 10 (2005): 2372–77. http://dx.doi.org/10.1200/jco.2005.00.331.
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Purpose Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM. Patients and Methods One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m2/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m2 on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53). Results Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild. Conclusion TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.
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Fierro, Javier, joshua Perez, Rocio Aguilar, et al. "IMMU-37. DISRUPTION OF PD-L1 BY ENHANCED TWO-SGRNAS CRISPR/CAS9 IN TREATMENT OF GLIOBLASTOMA." Neuro-Oncology 23, Supplement_6 (2021): vi100. http://dx.doi.org/10.1093/neuonc/noab196.396.
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Abstract Anti-glioblastoma multiform (GBM) immunotherapy poses a great challenge due to immunosuppressive brain tumor environments and the blood brain barrier (BBB). Programmed death ligand 1 (PD-L1) plays a key role in GBM immunosuppression, vitality, proliferation, and migration. Targeting PD-L1 for immunotherapy is a promising new avenue for treating GBM. CRISPR/Cas9 gene editing can be used to knockout both membrane and cytoplasmic PD-L1, leading to an enhanced immunotherapeutic strategy. We identified two sgRNA sequences located on PD-L1 exon 3. The first sgRNA recognized the forward strand of human PD-L1 near the beginning of exon 3 and cuts at approximately base pair 82 (g82). The second sgRNA recognized the reverse strand of exon 3 and cuts at base pair 165 (g165). Two sgRNAs, g82 and g165, created an 83bp deletion in PD-L1 genomic sequence. Two sgRNAs combination with a homology-directed repair template (HDR) was designed to enhance PD-L1 knockout specificity and efficiency. Both g82 and g165 were cloned into one CRISPR/Cas9 plasmid, and was co-transfected with HDR. GFP tagged CRISPR/Cas9 plasmid containing of g82 and g165 (Cas9-g82/165) was loaded into Rhodamine labeled nanoparticles (Cas9-g82/165-NPs) and then treated to GBM U87 cells. The enhanced intracellular uptake and transfection of Cas9-g82/165-NPs were detected by a fluorescence microscopy. T7E1, qRT-PCR and western blot analysis determined that the dual sgRNA CRISPR/Ca9 system knocked out both endogenous (80%) and exogenous (64%) PD-L1 in U87 cells and PD-L1 overexpression U87 cells, respectively. Deletion of PD-L1 reduced U87 migration and proliferation, while PD-L1 overexpression promoted tumor growth and tumor-associated macrophage polarization. Together, deletion of both membrane and cytoplasmic PD-L1 altered the PD-L1-associated immunosuppressive environment and prevented tumor progression and migration. Thus, two-sgRNAs CRISPR/Cas9 gene-editing system is a promising avenue for anti-GBM immunotherapy.
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Jamali Nazari, Ali, Dariush Sardari, Ahmad Reza Vali, and Keivan Maghooli. "Computer Implementation of a New Therapeutic Model for GBM Tumor." Computational and Mathematical Methods in Medicine 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/481935.
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Modeling the tumor behavior in the host organ as function of time and radiation dose has been a major study in the previous decades. Here the effort in estimation of cancerous and normal cell proliferation and growth in glioblastoma multiform (GBM) tumor is presented. This paper introduces a new mathematical model in the form of differential equation of tumor growth. The model contains dose delivery amount in the treatment scheme as an input term. It also can be utilized to optimize the treatment process in order to increase the patient survival period. Gene expression programming (GEP) as a new concept is used for estimating this model. The LQ model has also been applied to GEP as an initial value, causing acceleration and improvement of the algorithm estimation. The model shows the number of the tumor and normal brain cells during the treatment process using the status of normal and cancerous cells in the initiation of treatment, the timing and amount of dose delivery to the patient, and a coefficient that describes the brain condition. A critical level is defined for normal cell when the patient’s death occurs. In the end the model has been verified by clinical data obtained from previous accepted formulae and some of our experimental resources. The proposed model helps to predict tumor growth during treatment process in which further treatment processes can be controlled.
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Chu, Cheng-Wei, Huey-Jiun Ko, Chia-Hua Chou та ін. "Thioridazine Enhances P62-Mediated Autophagy and Apoptosis Through Wnt/β-Catenin Signaling Pathway in Glioma Cells". International Journal of Molecular Sciences 20, № 3 (2019): 473. http://dx.doi.org/10.3390/ijms20030473.
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Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/β-catenin signaling. After THD treatment, Fzd-1 and GSK3β-S9 phosphorylation (inactivated form) was reduced to promote β-catenin degradation, which attenuated P62 inhibition. The autophagy marker LC3-II markedly increased when P62 was released from β-catenin inhibition. Additionally, the P62-dependent caspase-8 activation that induced P53-independent apoptosis was confirmed by inhibiting T-cell factor/β-catenin and autophagy flux. Moreover, treatment with THD combined with temozolomide (TMZ) engendered increased LC3-II expression and caspase-3 activity, indicating promising drug synergism. In conclusion, THD induces autophagy in GBM cells by not only upregulating AMPK activity, but also enhancing P62-mediated autophagy and apoptosis through Wnt/β-catenin signaling. Therefore, THD is a potential alternative therapeutic agent for drug repositioning in GBM.
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Yang, Yi-Ping, Andy Chi-Lung Lee, Liang-Ting Lin, et al. "Strategic Decoy Peptides Interfere with MSI1/AGO2 Interaction to Elicit Tumor Suppression Effects." Cancers 14, no. 3 (2022): 505. http://dx.doi.org/10.3390/cancers14030505.
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Peptide drugs that target protein–protein interactions have attracted mounting research efforts towards clinical developments over the past decades. Increasing reports have indicated that expression of Musashi 1 (MSI1) is tightly correlated to high grade of cancers as well as enrichment of cancer stem cells. Treatment failure in malignant tumors glioblastoma multiform (GBM) had also been correlated to CSC-regulating properties of MSI1. It is thus imperative to develop new therapeutics that could effectively improve current regimens used in clinics. MSI1 and AGO2 are two emerging oncogenic molecules that both contribute to GBM tumorigenesis through mRNA regulation of targets involved in apoptosis and cell cycle. In this study, we designed peptide arrays covering the C-terminus of MSI1 and identified two peptides (Pep#11 and Pep#26) that could specifically interfere with the binding with AGO2. Our Biacore analyses ascertained binding between the identified peptides and AGO2. Recombinant reporter system Gaussian luciferase and fluorescent bioconjugate techniques were employed to determine biological functions and pharmacokinetic characteristics of these two peptides. Our data suggested that Pep#11 and Pep#26 could function as decoy peptides by mimicking the interaction function of MSI1 with its binding partner AGO2 in vitro and in vivo. Further experiments using GMB animal models corroborated the ability of Pep#11 and Pep#26 in disrupting MSI1/AGO2 interaction and consequently anti-tumorigenicity and prolonged survival rates. These striking therapeutic efficacies orchestrated by the synthetic peptides were attributed to the decoy function to C-terminal MSI1, especially in malignant brain tumors and glioblastoma.
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Kamabu, Larrey Kasereka, Oboth Ronald, Okiror Paul, et al. "NCMP-01. EARLY RECURRENCE OF GLIOBLASTOMA MULTIFORM INVOLVING MULTIPLE BRAIN REGIONS ASSOCIATED WITH MUTATIONS IN EXON 4 OF ISOCITRATE DEHYDROGENASE 1 COMPLICATED BY GADOLINIUM-INDUCED ACUTE KIDNEY FAILURE: A CASE REPORT." Neuro-Oncology 26, Supplement_8 (2024): viii216. http://dx.doi.org/10.1093/neuonc/noae165.0854.
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Abstract BACKGROUND Glioblastoma multiform (GBM) remains one of the most aggressive primary brain tumors with high recurrence rates. Case presentation We present a case of a 43-year-old female, Yira, diagnosed with early recurrence of GBM involving multiple brain regions, accompanied by mutations in exon 4 of isocitrate dehydrogenase 1 (IDH1), a marker associated with poor prognosis. Additionally, this case was complicated by gadolinium-induced acute kidney failure on postoperative day 3. The patient initially presented with progressive neurological symptoms, including headache and cognitive decline. Multiplanar multiecho MRI of the brain was performed with IV contrast in orthogonal plane and revealed a moderate sized multilobulated heterogeneously and predominantly peripherally enhancing mass lesion with irregular margins and central non enhancing areas of necrosis arising from the right corona radiata, insular cortex, external capsule, lentiform nucleus, temporal, and frontal white matter with blood products. Perilesional edema was seen. Effacement of sulcal spaces. Right sylvian fissure, compression over right ventricle and midline shift of 8mm toward left side. There was dilatation of the left lateral ventricle with periventricular cerebrospinal fluid ooze. Uncal herniation was right side. On MR spectroscopy large choline, creatinine levels were seen in the lesion with reduced N-acetyl aspartate levels as compared to the normal parenchyma. Findings were suggestive of neoplastic lesion mostly high-grade glioma. Polymerase chain reaction sequencing confirmed missense mutation R132H in exon 4 of isocitrate dehydrogenase 1 gene. Despite maximal safe surgical resection, the patient developed recurrent GBM within three months, with gadolinium-based contrast agent exposure leading to acute kidney injury. CONCLUSION The combination of aggressive tumor behavior and complications from contrast agent administration highlights the challenges in managing recurrent GBM. This case underscores the importance of vigilant monitoring for complications in GBM patients, particularly those with IDH1 mutations, and the need for further research into novel therapeutic strategies.
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Da Fonseca, C. O., and Gilberto Schwartsmann. "Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas." Journal of Clinical Oncology 25, no. 18_suppl (2007): 14037. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.14037.
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14037 Background: Deregulated p21-Ras function, as a result of mutation, overexpresion or growth factor-induced overactivation, contributes to growth of malignant gliomas. Perillyl alcohol (POH) is a monoterpene with preclinical antitumor activity in several types of tumor in rodent models and is currently under phase I and phase II clinical trials. Its proposed mechanism of action involves inhibition of post- translational isoprenylation of small G proteins, including p21-Ras, thereby blocking signal transduction Methods: The intranasal delivery is a practical and non-invasive approach that allows therapeutic agents, which do not cross the blood brain barrier (BBB) to enter the Central Nervous System (CNS), reducing unwanted systemic side effects. Applying this method we performed a phase I / II study with POH intranasal administration in patients with relapsed malignant gliomas after standard treatment: surgery, radiotherapy and chemotherapy. POH was administrated in concentration 0.3% volume/volume (55mg) 4 times daily. Results: Thirty-seven patients enrolled being 29 with glioblastoma multiform (GBM), 5 with grade III astrocytoma (AA) and 3 with anaplastic oligodendroglioma (AO). The results showed that POH is well tolerated and display at 6 months of treatment partial responses in 1 patient (3,4%) with GBM and 1 patient (33,3%) with AO; stable disease in 13 patients (44,8%) with GBM, 3 patients (60%) with AA and 1 patient (33,3%) with AO; progressive response in 15 patient (51,7%) with GBM, 2 patients (40%) with AA e 1 patient (33,3%) with AO. Conclusions: The POH intranasal delivery in a concentration of 0.3% volume/volume (55 mg) is well tolerated, and may prolong survival in patients with relapsed malignant gliomas patients. No significant financial relationships to disclose.
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Neves, Ana, Tânia Albuquerque, Rúben Faria, et al. "Evidence That a Peptide-Drug/p53 Gene Complex Promotes Cognate Gene Expression and Inhibits the Viability of Glioblastoma Cells." Pharmaceutics 16, no. 6 (2024): 781. http://dx.doi.org/10.3390/pharmaceutics16060781.
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Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Conventional therapies are followed by poor patient survival outcomes, so novel and more efficacious therapeutic strategies are imperative to tackle this scourge. Gene therapy has emerged as an exciting and innovative tool in cancer therapy. Its combination with chemotherapy has significantly improved therapeutic outcomes. In line with this, our team has developed temozolomide–transferrin (Tf) peptide (WRAP5)/p53 gene nanometric complexes that were revealed to be biocompatible with non-cancerous cells and in a zebrafish model and were able to efficiently target and internalize into SNB19 and U373 glioma cell lines. The transfection of these cells, mediated by the formulated peptide-drug/gene complexes, resulted in p53 expression. The combined action of the anticancer drug with p53 supplementation in cancer cells enhances cytotoxicity, which was correlated to apoptosis activation through quantification of caspase-3 activity. In addition, increased caspase-9 levels revealed that the intrinsic or mitochondrial pathway of apoptosis was implicated. This assumption was further evidenced by the presence, in glioma cells, of Bax protein overexpression—a core regulator of this apoptotic pathway. Our findings demonstrated the great potential of peptide TMZ/p53 co-delivery complexes for cellular transfection, p53 expression, and apoptosis induction, holding promising therapeutic value toward glioblastoma.
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Kamabu, Larrey Kasereka, Oboth Ronald, Okiror Paul, et al. "HGGL-01 GLIOBLASTOMA MULTIFORM INVOLVING MULTIPLE BRAIN REGIONS ASSOCIATED WITH MUTATIONS IN EXON 4 OF ISOCITRATE DEHYDROGENASE 1 COMPLICATED BY ACUTE KIDNEY FAILURE: A CASE REPORT." Neuro-Oncology Advances 6, Supplement_2 (2024): ii1. http://dx.doi.org/10.1093/noajnl/vdae147.002.
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Abstract Glioblastoma multiform (GBM), WHO grade 4, is the most aggressive primary brain tumor in adults associated with poor prognosis. We present a case of a 43-year-old female, Muyira, diagnosed with GBM involving multiple brain regions and harboring mutations in exon 4 of isocitrate dehydrogenase 1, who subsequently developed acute kidney failure. The patient initially presented with progressive neurological symptoms, including headache and cognitive decline. Multiplanar multiecho MRI of the brain was performed with IV contrast in orthogonal plane and revealed a moderate sized multilobulated heterogeneously and predominantly peripherally enhancing mass lesion with irregular margins and central non enhancing areas of necrosis arising from the right corona radiata, insular cortex, external capsule, lentiform nucleus, temporal, and frontal white matter with blood products. Perilesional edema was seen. Effacement of sulcal spaces. Right sylvian fissure, compression over right ventricle and midline shift of 8mm toward left side. There was dilatation of the left lateral ventricle with periventricular cerebrospinal fluid ooze. Uncal herniation was right side. On MR spectroscopy large choline, creatinine levels were seen in the lesion with reduced N-acetyl aspartate levels as compared to the normal parenchyma. Findings were suggestive of neoplastic lesion mostly high-grade glioma. Polymerase chain reaction sequencing confirmed the presence of missense mutation R132H in exon 4 of isocitrate dehydrogenase 1 gene. Despite maximal safe surgical resection, the patient developed acute kidney failure secondary to the nephrotoxic effects of gadolinium. Management of both the primary brain tumor and renal complication necessitated a multidisciplinary approach involving neurosurgery, oncology, nephrology, and supportive care. Despite aggressive interventions, the patient’s condition deteriorated, highlighting the challenges in managing concurrent life-threatening conditions in patients with advanced GBM.
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Robert, M., C. Leux, C. Gourmelon, M. Campone, and J. Frenel. "Efficacy and Safety of Bevacizumab (Bv) and Irinotecan (I) in Elderly Patients with Recurrent Glioblastoma Multiform (Gbm): a Monocentric Retrospective Study." Annals of Oncology 25 (September 2014): iv143. http://dx.doi.org/10.1093/annonc/mdu330.20.
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Zhai, Xin (Alice), Milagros Suarez Palacios, Zilu Huang, et al. "Abstract 3845: A matching panel of tumor organoids and patient derived orthotopic xenograft mouse models (PDOX) of high-grade gliomas in EGFP-based SCID mice." Cancer Research 85, no. 8_Supplement_1 (2025): 3845. https://doi.org/10.1158/1538-7445.am2025-3845.
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Background: High grade glioma, also known as glioblastoma multiform (GBM) a highly aggressive brain tumor, requires advanced systems to study tumor-stroma interactions. Paired in vitro and in vivo model systems such as 3D organoids and PDOX models derived from EGFP-SCID mice offered a unique opportunity to precisely and rapidly differentiation of mouse (EGFP positive) from human tumor cells, thereby facilitating the visualization and analysis of tumor/normal cell interactions in vitro and in vivo. Methods: EGFP-SCID mice received intra-cranial implantation of pediatric (n=6) and adult (n=6) GBM tumors to form PDOX. Tumor-bearing mouse brains were dissected, and tumor cells were cultured to generate organoids by seeding at cell densities of 1250, 2500, 5000 cells/well and monitored for size and count over 1-21 or 28 days. Immunohistochemistry (IHC) tracked the distribution of EGFP-positive mouse cells and GBM markers, including GFAP, Nestin, Ki67, GFP, CD276+ and so on. Additional staining for lysosomes and nuclei (Hoechst/DIPA) confirmed cellular localization and interactions. Results: Hybrid organoids were successfully generated, integrating mouse and human GBM cells in 12 PDOX models. Organoid size and count varied by cell density and culture duration, with similar growth patterns between pediatric and adult samples. IHC confirmed expression of cellular proliferation (Ki67), glial cells (GFAP), differentiation (SYN), stem cell (Nestin) as well as normal mouse cells (GFP) that were in and surrounding tumor cells. In organoids, EGFP fluorescence revealed dynamic tumor-stroma interactions, with changing proportions of mouse cells and GBM cells over time, reflecting the organoid’s developmental complexity. Conclusion: This EGFP-based organoid and PDOX model system offers a robust platform for studying tumor-stroma interactions and characterizing cellular dynamics in GBM. The system’s integration of IHC provides a detailed view of tumor and stromal components, making it a valuable tool for biological and translational GBM studies. Citation Format: Xin (Alice) Zhai, Milagros Suarez Palacios, Zilu Huang, Jinnan Chen, Tongchao Jiang, Nitin Wadhwani, Michael DeCuypere, Yuchen Du, Xiaonan Li. A matching panel of tumor organoids and patient derived orthotopic xenograft mouse models (PDOX) of high-grade gliomas in EGFP-based SCID mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3845.