Immunology Meets Bioengineering: Improving the Effectiveness of Glioblastoma Immunotherapy

Fekrirad, Zahra; Behrooz, Amir Barzegar; Ghaemi, Shokoofeh; Khosrojerdi, Arezou; Zarepour, Atefeh; Zarrabi, Ali; Arefian, Ehsan; Ghavami, Saeid

doi:10.3390/cancers14153698

Cited by 11 publications

(5 citation statements)

References 236 publications

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“…Many chemotherapy approaches are not effective towards reaching the desired outcomes in GBM patient treatment [72,73] . Our team has recently investigated the efficiency and mechanisms of combination Simva and TMZ treatments in GBM and showed that Simva sensitizes GBM cells to TMZ-induced apoptosis [10,20,22].…”

Section: Discussionmentioning

confidence: 99%

“…TMZ resistance, as a major problem in GBM patient therapeutic strategies, has been investigated for years. Moreover, several compounds and drugs were utilized to enhance the efficacy of TMZ while attenuate the resistance to TMZ to achieve the best approach to treat GBM patients [72][73][74]. Recent investigations have showed that taking statins for a long period of time, could potentially increase the survival of the cancer patients (including GBM) and improve their response to different chemotherapy medications [9,[75][76][77].…”

Section: Discussionmentioning

confidence: 99%

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Temozolomide, Simvastatin and Acetylshikonin Combination Induces Mitochondrial Dependent Apoptosis in GBM Cells which is Regulated by Autophagy

Hajiahmadi¹,

Lorzadeh²,

Iranpour³

et al. 2023

Preprint

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Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have more effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple combination therapy of TMZ, Simvastatin (Simva), and Acetylshikonin (ASH) and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that TMZ/Simva/ASH combination therapy significantly induced more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and induced caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to partial inhibition of autophagy flux (accumulation of LC3β-II and decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for more effective treatment of GBM but further investigations are required for better identification of the mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Temozolomide, Simvastatin and Acetylshikonin Combination Induces Mitochondrial Dependent Apoptosis in GBM Cells which is Regulated by Autophagy

Hajiahmadi¹,

Lorzadeh²,

Iranpour³

et al. 2023

Preprint

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“…Several immunotherapy combinations with oncolytic viruses are developing to foster outcomes and minimize adverse effects [ 30 ]. For example, immune checkpoint inhibitors (ICIs) [ 31 ], Chimeric Antigen Receptor T therapy (CAR-T) cells [ 32 ], vaccine therapies [ 33 ], focused ultrasound therapy [ 34 , 35 ], and novel bioengineered nanoparticles [ 36 ] are all in the pipeline for GB treatment.…”

Section: Introductionmentioning

confidence: 99%

Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies

Hamad

Yusubalieva

Baklaushev

et al. 2023

Viruses

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Glioblastoma is the most aggressive form of malignant brain tumor. Standard treatment protocols and traditional immunotherapy are poorly effective as they do not significantly increase the long-term survival of glioblastoma patients. Oncolytic viruses (OVs) may be an effective alternative approach. Combining OVs with some modern treatment options may also provide significant benefits for glioblastoma patients. Here we review virotherapy for glioblastomas and describe several OVs and their combination with other therapies. The personalized use of OVs and their combination with other treatment options would become a significant area of research aiming to develop the most effective treatment regimens for glioblastomas.

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“…Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with a poor prognosis [ 1 , 2 ]. It is urgently necessary to develop new therapeutic strategies for GBM with approved treatments due to its poor survival rates [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach

Behrooz

Latifi-Navid

Rosa

et al. 2023

Cancers

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The most aggressive primary malignant brain tumor in adults is glioblastoma (GBM), which has poor overall survival (OS). There is a high relapse rate among patients with GBM despite maximally safe surgery, radiation therapy, temozolomide (TMZ), and aggressive treatment. Hence, there is an urgent and unmet clinical need for new approaches to managing GBM. The current study identified modules (MYC, EGFR, PIK3CA, SUZ12, and SPRK2) involved in GBM disease through the NeDRex plugin. Furthermore, hub genes were identified in a comprehensive interaction network containing 7560 proteins related to GBM disease and 3860 proteins associated with signaling pathways involved in GBM. By integrating the results of the analyses mentioned above and again performing centrality analysis, eleven key genes involved in GBM disease were identified. ProteomicsDB and Gliovis databases were used for determining the gene expression in normal and tumor brain tissue. The NetworkAnalyst and the mGWAS-Explorer tools identified miRNAs, SNPs, and metabolites associated with these 11 genes. Moreover, a literature review of recent studies revealed other lists of metabolites related to GBM disease. The enrichment analysis of identified genes, miRNAs, and metabolites associated with GBM disease was performed using ExpressAnalyst, miEAA, and MetaboAnalyst tools. Further investigation of metabolite roles in GBM was performed using pathway, joint pathway, and network analyses. The results of this study allowed us to identify 11 genes (UBC, HDAC1, CTNNB1, TRIM28, CSNK2A1, RBBP4, TP53, APP, DAB1, PINK1, and RELN), five miRNAs (hsa-mir-221-3p, hsa-mir-30a-5p, hsa-mir-15a-5p, hsa-mir-130a-3p, and hsa-let-7b-5p), six metabolites (HDL, N6-acetyl-L-lysine, cholesterol, formate, N, N-dimethylglycine/xylose, and X2. piperidinone) and 15 distinct signaling pathways that play an indispensable role in GBM disease development. The identified top genes, miRNAs, and metabolite signatures can be targeted to establish early diagnostic methods and plan personalized GBM treatment strategies.

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Immunology Meets Bioengineering: Improving the Effectiveness of Glioblastoma Immunotherapy

Cited by 11 publications

References 236 publications

Temozolomide, Simvastatin and Acetylshikonin Combination Induces Mitochondrial Dependent Apoptosis in GBM Cells which is Regulated by Autophagy

Temozolomide, Simvastatin and Acetylshikonin Combination Induces Mitochondrial Dependent Apoptosis in GBM Cells which is Regulated by Autophagy

Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies

Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach

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