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[Display omitted] • Comprehensive analysis of novel treatment modalities for Glioblastoma (GBM). • Role of nanocarriers in addressing limitations with conventional GBM therapeutics. • Updates of clinical landscape of novel GBM therapeutics. • Limitations with novel nanoparticles approach in GBM therapeutics. Glioblastoma multiforme (GBM) represents one of the most prevailing and aggressive primary brain tumors among adults. Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood–brain barrier (BBB). Nanotechnology has emerged as a promising avenue for GBM treatment, offering biosafety, sustained drug release, enhanced solubility, and improved BBB penetrability. In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. The conventional and novel treatment modalities for GBM and the potential of nanocarriers to overcome existing limitations are comprehensively covered. Furthermore, the updates in the clinical landscape of GBM therapeutics are presented in addition to the current status of drugs and patents in the same context. Through a critical evaluation of existing literature, the therapeutic prospect and limitations of nanocarrier-based drug delivery strategies are highlighted offering insights into future research directions and clinical translation. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D‐printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days in vitro. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and malignancy. The resulting resistance to anti-angiogenetic therapies urges the identification of new compounds targeting VM. Extracts of natural plants may represent potential therapeutic tools. Among these, components of Ruta graveolens water extract (RGWE) display a wide range of biological activities. To test the effect of RGWE on human GBM and rat glioma cell line VM, tube formation on a gelled matrix was monitored. Quantitative assessment of VM formation shows the clear-cut inhibitory activity of RGWE. Unlike rutin, one of the most abundant extract components, the whole RGWE strongly reduced the migration and invasion of GBM tumor cells. Moreover, RGWE induced cell death of GBM patient-derived cancer stem cells and impaired VM at sub-lethal doses. Overall, our data reveal a marked RGWE-dependent inhibition of GBM cell survival, migration, invasion, and VM formation. Thus, the clear-cut ability of RGWE to counteract GBM malignancy deserves attention, holding the promise to bring natural products to clinical use, thus uncovering new therapeutic opportunities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Glioblastoma is one of the most aggressive and treatment‐resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127‐complexed PEGylated poly(glutamic acid)‐cisplatin (PLG‐PEG/PF127‐CDDP). PLG‐PEG/PF127‐CDDP demonstrated an optimal size of 133.97 ± 12.60 nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half‐maximal (50%) inhibitory concentration (IC50) of 12.61 µg mL−1 at 48 h and a 72.53% ± 1.89% reduction in cell invasion. Furthermore, PLG‐PEG/PF127‐CDDP prolonged the circulation half‐life of cisplatin to 9.75 h in vivo, leading to a more than 50% reduction in tumor size on day 16 post‐treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG‐PEG/PF127‐CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer‐based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most fatal and common malignant brain tumor, excluding metastasis and with a median survival of approximately one year. While solid tumors benefit from newly approved drugs, immunotherapy, and prevention, none of these scenarios are opening for glioblastoma. The key to unlocking the peculiar features of glioblastoma is observing its molecular and anatomical features tightly entangled with the host's central nervous system (CNS). In June 2024, we searched the PUBMED electronic database. Data collection and analysis were conducted independently by two reviewers. Results: A total of 215 articles were identified, and 192 were excluded based on inclusion and exclusion criteria. The remaining 23 were used for collecting divergent molecular pathways and anatomical features of glioblastoma. The analysis of the selected papers revealed a multifaced tumor with extreme variability and cellular reprogramming that are observable within the same patient. All the variability of glioblastoma could be clustered into three pillars to dissect the physiology of the tumor: 1. necrotic core; 2. vascular proliferation; 3. CNS infiltration. These three pillars support glioblastoma survival, with a pivotal role of the neurovascular unit, as supported by the most recent paper published by experts in the field. [ABSTRACT FROM AUTHOR]

Glioblastomas (GBM) are most common types of primary brain tumors and miRNAs play an important role in pathogenesis of glioblastomas. Here, we reported a new miRNA, miR-3154, which regulates glioblastoma proliferation and metastasis. miR-3154 was elevated in glioblastoma tissue and cell lines, and its elevation was associated with grade of glioblastomas. Knockdown of miR-3154 in cell lines weakened ability of proliferation and colony formation, and caused cell cycle arrested and higher percentage of apoptosis. Knockdown of miR-3154 also impaired ability of migration and invasion in glioblastoma cells. In mechanism, miR-3154 bound directly to Tumor Protein P53 Inducible Nuclear Protein 1 (TP53INP1), down-regulating TP53INP1 expression at both mRNA and protein level. Silence of TP53INP1 reversed the effect of miR-3154 knockdown on proliferation and metastasis of glioblastoma cells. These findings show that miR-3154 promotes glioblastoma proliferation and metastasis via targeting TP53INP1. [ABSTRACT FROM AUTHOR]

Gliomas are primary brain tumors and are among the most malignant types. Adult‐type diffuse gliomas can be classified based on their histological and molecular signatures as IDH‐wildtype glioblastoma, IDH‐mutant astrocytoma, and IDH‐mutant and 1p/19q‐codeleted oligodendroglioma. Recent studies have shown that each subtype of glioma has its own specific distribution pattern. However, the mechanisms underlying the specific distributions of glioma subtypes are not entirely clear despite partial explanations such as cell origin. To investigate the impact of multi‐scale brain attributes on glioma distribution, we constructed cumulative frequency maps for diffuse glioma subtypes based on T1w structural images and evaluated the spatial correlation between tumor frequency and diverse brain attributes, including postmortem gene expression, functional connectivity metrics, cerebral perfusion, glucose metabolism, and neurotransmitter signaling. Regression models were constructed to evaluate the contribution of these factors to the anatomic distribution of different glioma subtypes. Our findings revealed that the three different subtypes of gliomas had distinct distribution patterns, showing spatial preferences toward different brain environmental attributes. Glioblastomas were especially likely to occur in regions enriched with synapse‐related pathways and diverse neurotransmitter receptors. Astrocytomas and oligodendrogliomas preferentially occurred in areas enriched with genes associated with neutrophil‐mediated immune responses. The functional network characteristics and neurotransmitter distribution also contributed to oligodendroglioma distribution. Our results suggest that different brain transcriptomic, neurotransmitter, and connectomic attributes are the factors that determine the specific distributions of glioma subtypes. These findings highlight the importance of bridging diverse scales of biological organization when studying neurological dysfunction. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the deadliest primary brain tumors, but its diagnosis and curative therapy still remain a big challenge. Herein, neutrophil‐targeting semiconducting polymer nanotheranostics (SSPNiNO) is reported for second near‐infrared (NIR‐II) fluorescence imaging‐guided trimodal therapy of orthotopic glioblastoma in mouse models. The SSPNiNO are formed based on two semiconducting polymers acting as NIR‐II fluorescence probe as well as photothermal conversion agent, respectively. A thermal‐responsive nitric oxide (NO) donor and an adenosine 2A receptor (A2AR) inhibitor are co‐integrated into SSPNiNO to enable trimodal therapeutic actions. SSPNiNO are surface attached with a neutrophil‐targeting ligand to mediate their effective delivery into orthotopic GBM sites via a "Trojan Horse" manner, enabling high‐sensitive NIR‐II fluorescence imaging. Upon NIR‐II light illumination, SSPNiNO effectively generates heat via NIR‐II photothermal effect, which not only kills tumor cells and induces immunogenic cell death (ICD), but also triggers controlled NO release to strengthen tumor ICD. Additionally, the encapsulated A2AR inhibitor can modulate immunosuppressive tumor microenvironment by blocking adenosine‐A2AR pathway, which further boosts the antitumor immunological effect to observably suppress the orthotopic GBM progression. This study can provide a multifunctional theranostic nanoplatform with cumulative therapeutic actions for NIR‐II fluorescence imaging‐guided effective GBM treatment. [ABSTRACT FROM AUTHOR]

Introduction: The mutated in colorectal cancer (MCC) gene was initially identified as a candidate tumor suppressor gene in colorectal cancer, acting as a negative regulator of cell cycle progression. However, its functional roles in brain tumors, particularly glioblastoma, remain largely unexplored. This study reveals a significant association between MCC status and glioblastoma. Methods: We explored MCC expression in the glioblastoma database, patient samples, and cell lines. We investigated the proliferation and migration of the cell lines in MCC gene knockdown using small interfering RNA. Results: In vitro analyses revealed elevated protein and mRNA levels of MCC in several glioblastoma cell lines (U118MG and T98G). Silencing MCC expression via siRNA-mediated knockdown resulted in increased proliferation and migration of these cell lines. Supporting these findings, analyses of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases confirmed higher MCC expression in glioblastoma tumors than in normal brain tissue. Importantly, we observed that high MCC expression was associated with poor prognosis in glioblastoma patients, highlighting its potential role in disease progression. Additionally, this study identifies a nuclear localization of MCC in the glioblastoma cell line. Discussion: These findings indicate that MCC expression is significantly upregulated in glioblastoma and may play a role in its pathophysiology, warranting further investigation. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further. [ABSTRACT FROM AUTHOR]

α-Pinene (PEN) is a phyto compound present in terpene plants. In traditional medicine, PEN has been used for its anti-inflammatory, pain-relieving, and bronchodilator properties. The effect of PEN in combination with temozolomide (TMZ) in glioblastoma multiforme (GBM) cells has been evaluated. The action of the PEN + TMZ combination on cell migration, soft-agar, and cell death was determined in LN229 and U87MG human glioblastoma cells. In combination, PEN with TMZ showed a synergistic inhibitory effect in the GBM cells. The PEN + TMZ treatment showed a higher fluorescent intensity and reduced the percentage of wound area closure compared to the compound alone. The compounds in combination also resulted in a reduction in single-cell colony formation. To conclude, the study showed that plant-derived PEN enhanced the effectiveness of standard chemotherapeutic, TMZ, in LN229 and U87MG cells. [ABSTRACT FROM AUTHOR]

Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments for control of infectious disease, notably their pivotal role in combating the COVID-19 pandemic. This review focuses on fundamental aspects of the development of mRNA vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, - highlighting key technological advances. The recent, promising success of personalized mRNA vaccines against pancreatic cancer and melanoma illustrates the potential value for other intractable, immunologically resistant, solid tumors, such as glioblastoma, as well as the potential for synergies with a combinatorial, immunotherapeutic approach. The impact and progress in human cancer, including pancreatic cancer, head and neck cancer, bladder cancer are reviewed, as are lessons learned from first-in-human CAR-T cell, DNA and dendritic cell vaccines targeting glioblastoma. Going forward, a roadmap is provided for the transformative potential of mRNA vaccines to advance cancer immunotherapy, with a particular focus on the opportunities and challenges of glioblastoma. The current landscape of glioblastoma immunotherapy and gene therapy is reviewed with an eye to combinatorial approaches harnessing RNA science. Preliminary preclinical and clinical data supports the concept that mRNA vaccines could be a viable, novel approach to prolong survival in patients with glioblastoma. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is a brain tumor characterized by the highest malignancy and the poorest prognoses. RNA binding motif single strand interacting protein 1 (RBMS1) has been implicated to be involved in various cancer progression. This study was conceived to explore the role and the mechanism of RBMS1 in GBM. Materials: RT-qPCR and western blot were used to evaluate RBMS1 expression and examine the transfection efficiency of sh-RBMS1. Cell proliferation was detected using CCK-8 assay and colony formation assay while cell apoptosis was detected with flow cytometry. Cell migration and invasion were detected with wound healing and transwell assay. The activities of MMP2 and MMP9 were detected using gelatin zymography. Western blot was used to measure proliferation-, apoptosis-, ferroptosis- and EMT-related proteins. Lipid peroxidation was detected with TBARS Assay Kit and lipid ROS was detected with a BODIPY 581/591 C11 kit. The total iron level was detected using corresponding assay kits. Results: According to GEPIA database, RBMS1 expression was upregulated in GBM and the present study found that RBMS1 expression was upregulated in GBM cells. After interfering RBMS1, GBM cell proliferation, migration, invasion and EMT process were inhibited while cell apoptosis and ferroptosis were promoted. However, ferroptosis inhibitor Fer-1 partially counteracted the protective effects of RBMS1 knockdown on GBM. Conclusion: Collectively, this study revealed that RBMS1 silence inhibited the malignant progression of GBM possibly through ferroptosis. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. The cleavage factor Im 25 (CFIm25), a crucial component of the CFIm complex, plays a key role in regulating the length of the mRNA 3'-UTR and has been implicated in various cancers, including GBM. This study sought to investigate the regulatory influence of specific microRNAs (miRNAs) on CFIm25 expression in GBM, a highly aggressive brain tumor. Bioinformatics analysis identified miRNA candidates targeting CFIm25 mRNA, and gene expression profiles from the NCBI database (GSE90603) were used for further analysis. Expression levels of CFIm25 and selected miRNAs were assessed using qRT-PCR in GBM clinical samples (n = 20) and non-malignant brain tissues (n = 5). Additionally, the MTT assay was performed to examine the effect of miRNA overexpression on U251 cell viability. Lentivectors expressing the identified miRNAs were employed to experimentally validate their regulatory role on CFIm25 in U251 cell lines, and Western blot analysis was conducted to determine CFIm25 protein levels. We observed significantly increased levels of miR-23, miR-24, and miR-27 expression, associated with a marked reduction in CFIm25 expression in GBM samples compared to non-malignant brain tissues. In particular, overexpression of miR-23, miR-24, and miR-27 in U251 cells resulted in CFIm25 downregulation at both the mRNA and protein levels, while their inhibition increased CFIm25 and reduced cell proliferation. These observations strongly implicate miR-23, miR-24, and miR-27 in regulating CFIm25 expression in GBM, emphasizing their potential as promising therapeutic targets for enhancing treatment responses in glioblastoma. [ABSTRACT FROM AUTHOR]

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant current diagnostic constraints and limited therapeutic strategies. MiRNA dysregulation is present in GBM. The intricate involvement of miRNAs in altering cell proliferation, invasion, and immune escape makes them prospective candidates for identifying and monitoring GBM diagnosis and response to treatment. These miRNAs could play a dual role, acting as both potential diagnostic markers and targets for therapy. By modulating the activity of various oncogenic and tumor-suppressive proteins, miRNAs create opportunities for precision medicine and targeted therapies in GBM. This review centers on the critical role and function of circulating miRNA biomarkers in GBM diagnosis and treatment. It highlights their significance in providing insights into disease progression, aiding in early diagnosis, and potential use as targets for novel therapeutic interventions. Ultimately, the study of miRNA would contribute to improving patient outcomes in the challenging landscape of GBM management. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite an established standard of care including surgical resection, radiation therapy, and chemotherapy, GBM unfortunately is associated with a dismal prognosis. Therefore, researchers are extensively evaluating avenues to expand GBM therapy and improve outcomes in patients with GBM. In this review, we provide a broad overview of novel GBM therapies that have recently completed or are actively undergoing study in clinical trials. These therapies expand across medical, surgical, and radiation clinical trials. We additionally review methods for improving clinical trial design in GBM. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is one of the most aggressive, incurable, and difficult‐to‐treat malignant brain tumor with very poor survival rates. The gold standard in treating GBMs includes neurosurgical resection of the tumor, followed by the chemotherapy and radiotherapy. However, these strategies remain ineffective in treating patients with GBMs, as tumor recurrence always occur in most cases. Therefore, it remains a grand challenge to develop an effective strategy to combat orthotopic glioblastoma with simultaneous imaging capabilities to monitor the therapeutic outcomes. To tackle this challenge, this study demonstrates, for the first time, that a tumor‐specific europium hexaboride (EuB6)‐based nanomedicine surface‐modified with RGD‐K peptide to target αvβ3 integrin receptors overexpressed on the glioblastoma cells. Further, EuB6@RGD‐K NPs are able to exert theranostic capabilities to effectively diagnose and combat difficult‐to‐treat orthotopic glioblastoma tumors using NIR‐II 1064 nm and NIR‐III 1550 nm photodynamic therapy (NIR PDT) effects. In the in vivo experiments, the average half‐life of 55 d for mice treated with EuB6@RGD‐K NPs and exposed to NIR‐III 1550 nm light irradiation is far higher than that of EuB6@RGD‐K NPs exposed to NIR‐II 1064 nm light irradiation (25 d), PBS‐treated mice (20 d) and EuB6@RGD‐K NPs‐treated mice (no light irradiation, 18 d). To the best of our knowledge, this work represents the first example for destructing murine brain tumors via multi‐functional tumor‐specific europium hexaboride‐based nanotheranostic agent to mediate MR imaging‐guided NIR‐II/‐III photodynamic therapy. [ABSTRACT FROM AUTHOR]

Introduction: Primary spinal glioblastoma (GBM) are very rare tumors of the spinal cord, with dismal prognosis and their exact management is controversial. We attempt to formulate treatment guidelines for these extremely rare tumors based on our institutional experience and a comprehensive review of the literature. Materials and methods: In this retrospective study from 2008 to 2020, all the patients diagnosed with primary spinal GBM who underwent surgery at our institution were included. Clinical data were retrieved from case files, outpatient records and telephonic follow-up. Data on postoperative chemoradiation was noted in all the patients. The final diagnosis of spinal GBM was confirmed as per the histopathology reports. Patients who could not be followed up and those with prior history of cranial GBM were excluded from the study. Results: Nine patients were followed up and a median survival of 11 months was noted. Chemotherapy with TMZ and radiotherapy to the whole craniospinal axis significantly improved survival in these patients. The extent of surgical resection was not shown to be significant. Intracranial metastasis was the leading cause of mortality in such patients. Three patients developed documented intracranial metastasis during the course of the disease. Conclusions: Low threshold must be kept in mind in diagnosing patients with high-grade spinal cord intramedullary tumors in view of the rapidly progressing nature of the disease. In case of positive histopathological diagnosis of spinal GBM, the whole craniospinal axis should be imaged and any cranial metastasis which was originally missed during initial workup could be given appropriate radiotherapy. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a highly malignant brain tumor, and glioblastoma stem cells (GSCs) are the primary cause of GBM heterogeneity, invasiveness, and resistance to therapy. Sirtuin 3 (SIRT3) is mainly localized in the mitochondrial matrix and plays an important role in maintaining GSC stemness through cooperative interaction with the chaperone protein tumor necrosis factor receptor-associated protein 1 (TRAP1) to modulate mitochondrial respiration and oxidative stress. The present study aimed to further elucidate the specific mechanisms by which SIRT3 influences GSC stemness, including whether SIRT3 serves as an autophagy substrate and the mechanism of SIRT3 degradation. We first found that SIRT3 is enriched in CD133+ GSCs. Further experiments revealed that in addition to promoting mitochondrial respiration and reducing oxidative stress, SIRT3 maintains GSC stemness by epigenetically regulating CD133 expression via succinate. More importantly, we found that SIRT3 is degraded through the autophagy–lysosome pathway during GSC differentiation into GBM bulk tumor cells. GSCs are highly dependent on glutamine for survival, and in these cells, we found that glutamine deprivation triggers autophagic SIRT3 degradation to restrict CD133 expression, thereby disrupting the stemness of GSCs. Together our results reveal a novel mechanism by which SIRT3 regulates GSC stemness. We propose that glutamine restriction to trigger autophagic SIRT3 degradation offers a strategy to eliminate GSCs, which combined with other treatment methods may overcome GBM resistance to therapy as well as relapse. [ABSTRACT FROM AUTHOR]

Glioblastoma is an aggressive and often fatal brain tumor characterized by poor prognosis and complex genetic underpinnings. Through extensive analysis of glioblastoma datasets on the cBioPortal, this study identifies critical gene mutations and copy number alterations (CNAs) that correlate strongly with patient survival rates. Key findings highlight significant CNAs in chromosomes 20, 19, 10, 1, and 7. Our deep dive into the genetic profiles of deceased patients revealed a notable enrichment of mutations in specific genes, including MUC19, which exhibits higher expression levels in the cerebral cortex--the brain region most frequently affected by glioblastoma. By mapping these genes on GeneMania, we uncovered their functions and potential implications in glioblastoma pathology, such as their involvement in mucus lining and epithelial barriers, focusing on MUC genes, which showed differential expression patterns correlating with patient outcomes. This bioinformatic exploration advances our understanding of glioblastoma's molecular landscape and sets the stage for targeted therapies that could improve prognosis and treatment strategies. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), a primary brain tumor, exhibits remarkable invasiveness and is characterized by its intricate location, infiltrative behavior, the presence of both the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), phenotypic diversity, an immunosuppressive microenvironment with limited development yet rich vascularity, as well as the resistant nature of glioblastoma stem cells (GSCs) towards traditional chemotherapy and radiotherapy. These formidable factors present substantial obstacles in the quest for effective GBM treatments. Following extensive research spanning three decades, the hepatocellular receptor A2 (EphA2) receptor tyrosine kinase has emerged as a promising molecular target with translational potential in the realm of cancer therapy. Numerous compounds aimed at targeting EphA2 have undergone rigorous evaluation and clinical investigation. This article provides a comprehensive account of the distinctive roles played by canonical and non-canonical EphA2 signaling in various contexts, while also exploring the involvement of the EphA2-ephrin A1 signaling axis in GBM pathogenesis. Additionally, the review offers an overview of completed clinical trials targeting EphA2 for GBM treatment, shedding light on both the prospects and challenges associated with EphA2-directed interventions in the domain of cancer therapeutics. [ABSTRACT FROM AUTHOR]

TTFields is a novel FDA-approved technology utilized for treating glioblastoma multiforme (GBM) within the brain. Presently, the effectiveness of therapy is evaluated through MRI imaging at random two-month intervals. Electrical impedance is an important and effective parameter for reflecting changes in tissue properties. In TTFields treatment for brain tumors, electrodes attached to the scalp deliver electric field energy to the tumor region. We hypothesize that these electrodes can also serve as sensors to detect impedance changes caused by tumor alterations in real time, thus continuously assessing the effectiveness of the treatment. In this work, we propose and scrutinize this hypothesis by conducting an in silico study to confirm the potential feasibility of the proposed concept. Our results indicate that the impedance amplitude change measured between opposing TTFields electrode arrays utilizing voltage and frequency of 50 V and 200 kHz (typical TTFields treatment parameters), has enough resolution (> 1mm) and Signal-to-Noise Ratio (> 40 dB) to evaluate tumor size change in the head. The impedance detection technique may be a significant augmentation to TTFields cancer treatment, enabling the continuous evaluation of safety and efficacy throughout the procedure. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor among adults. Despite advancements in multimodality therapy for GBM, the overall prognosis remains poor, with an extremely high risk of recurrence. Currently, there is no established consensus on the optimal treatment option for recurrent GBM, which may include reoperation, reirradiation, chemotherapy, or a combination of the above. Bevacizumab is considered a first-line treatment option for recurrent GBM, as is temozolomide. However, in recurrent GBM, it is necessary to balance the risks and benefits of reirradiation in combination with bevacizumab and temozolomide. Herein, we report the case of a patient with recurrent GBM after standard treatment who benefited from stereotactic radiotherapy followed by bevacizumab and temozolomide maintenance therapy. Following 16 months of concurrent chemoradiotherapy (CCRT), the patient was diagnosed with recurrent GBM by a 3-T contrast-enhanced magnetic resonance imaging (MRI). The addition of localized radiotherapy to the ongoing treatment regimen of bevacizumab, in combination with temozolomide therapy, prolonged the patient's disease-free survival to over 2 years, achieving a significant long-term outcome, with no notable adverse effects observed. This clinical case may provide a promising new option for patients with recurrent GBM. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth and a poor prognosis for patients. Despite advancements in treatment, the median survival time for GBM patients remains low. One of the crucial challenges in understanding and treating GBMs involves its remarkable cellular heterogeneity and adaptability. Central to the survival and proliferation of GBM cells is their ability to undergo metabolic reprogramming. Metabolic reprogramming is a process that allows cancer cells to alter their metabolism to meet the increased demands of rapid growth and to survive in the often oxygen- and nutrient-deficient tumor microenvironment. These changes in metabolism include the Warburg effect, alterations in several key metabolic pathways including glutamine metabolism, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, increased uptake and utilization of glutamine, and more. Despite the complexity and adaptability of GBM metabolism, a deeper understanding of its metabolic reprogramming offers hope for developing more effective therapeutic interventions against GBMs. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common type of primary malignant brain tumor and has a dismal overall survival rate. To date, no GBM therapy has yielded successful results in survival for patients beyond baseline surgical resection, radiation, and chemotherapy. Immunotherapy has taken the oncology world by storm in recent years and there has been movement from researchers to implement the immunotherapy revolution into GBM treatment. Natural killer (NK) cell-based immunotherapies are a rising candidate to treat GBM from multiple therapeutic vantage points: monoclonal antibody therapy targeting tumor-associated antigens (TAAs), immune checkpoint inhibitors, CAR-NK cell therapy, Bi-specific killer cell engagers (BiKEs), and more. NK therapies often focus on tumor antigens for targeting. Here, we reviewed some common targets analyzed in the fight for GBM immunotherapy relevant to NK cells: EGFR, HER2, CD155, and IL-13Rα2. We further propose investigating the Lectin-like Transcript 1 (LLT1) and cell surface proliferating cell nuclear antigen (csPCNA) as targets for NK cell-based immunotherapy. [ABSTRACT FROM AUTHOR]

Like most tumors, glioblastoma multiforme (GBM), the deadliest brain tumor in human adulthood, releases extracellular vesicles (EVs). Their content, reflecting that of the tumor of origin, can be donated to nearby and distant cells which, by acquiring it, become more aggressive. Therefore, the study of EV-transported molecules has become very important. Particular attention has been paid to EV proteins to uncover new GBM biomarkers and potential druggable targets. Proteomic studies have mainly been performed by "bottom-up" mass spectrometry (MS) analysis of EVs isolated by different procedures from conditioned media of cultured GBM cells and biological fluids from GBM patients. Although a great number of dysregulated proteins have been identified, the translation of these findings into clinics remains elusive, probably due to multiple factors, including the lack of standardized procedures for isolation/characterization of EVs and analysis of their proteome. Thus, it is time to change research strategies by adopting, in addition to harmonized EV selection techniques, different MS methods aimed at identifying selected tumoral protein mutations and/or isoforms due to post-translational modifications, which more deeply influence the tumor behavior. Hopefully, these data integrated with those from other "omics" disciplines will lead to the discovery of druggable pathways for novel GBM therapies. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most prevalent cancerous brain tumors. Former studies have reported that exosomes derived from M1‐polarized macrophages (M1 exosomes) inhibit tumor occurrence and development through delivery of tumor suppressor genes. Also, microRNA‐142‐3p (miR‐142‐3p) has been verified to function as a tumor suppressor. GBM cell proliferation was evaluated by Cell Counting Kit‐8 (CCK‐8), colony formation assay and 5‐ethynyl‐2′‐deoxyuridine (EdU) assay; cell apoptosis was determined by flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mechanism investigations were conducted for analyzing the molecular mechanism by which miR‐142‐3p and M1 exosomes affect GBM progression. Upregulation of miR‐142‐3p expression was detected in M1‐polarized macrophages and M1 exosomes. M1 exosomes inhibit GBM cell proliferation and trigger cell apoptosis. Functionally, miR‐142‐3p silencing promotes the proliferation and inhibits the apoptosis of GBM cells treated with M1 exosomes. As for molecular mechanism, miR‐142‐3p inhibits GBM cell growth via targeting high‐mobility group box 1 (HMGB1). In addition, miR‐142‐3p/HMGB1 axis affects GBM cell immune escape through modulation of programmed death‐1/programmed death ligand‐1 (PD‐1/PD‐L1) checkpoint. Our study demonstrated that exosomal miR‐142‐3p from M1‐polarized macrophages suppresses cell growth and immune escape in GBM through regulating HMGB1‐mediated PD‐1/PD‐L1 checkpoint. [ABSTRACT FROM AUTHOR]

Positronium is abundantly produced within the molecular voids of a patient's body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low‐intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu‐doped carbon dots (Cu‐CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p–n type semiconductor having a bandgap of 1.58 eV, a prolonged lifespan of 10.7 µs, and an improved electron‐ and hole‐separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu‐CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu‐CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu‐CDs exhibit excellent permeability through the blood‐brain barrier and potent anti‐tumor activity. Importantly, the Cu‐CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon‐based nanomaterials as sonosensitizers in tumor therapy. [ABSTRACT FROM AUTHOR]

This document discusses the role of LOXL2 in promoting the occurrence and progression of glioma, a type of brain tumor. LOXL2 activates autophagy, a cellular process that promotes tumor growth and resistance to chemotherapy. The specific mechanisms of LOXL2's relationship with histological grade and autophagy's regulation of epithelial-mesenchymal transition (EMT) are still unclear and require further study. The findings suggest that targeting LOXL2 in combination with chemotherapy may be an effective treatment strategy for glioma and potentially other tumors. [Extracted from the article]

Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems. Observation of glioblastoma invasion in subcortical brain regions is challenging. Here the authors develop a Deep3P workflow to enable longitudinal deep imaging of glioblastoma and its microenvironment by combining three-photon microscopy and deep learning-based analysis, unraveling the invasion routes of these tumor cells into and within the white matter. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme, a disease of grade IV astrocytoma, accounts for 60-70% of malignant brain tumors.? Despite its low survival rate, little is known about GBM and its treatment. The purpose of this study was to assess the comparative effectiveness of the most common drugs (temozolomide, carmustine, bevacizumab) in reducing tumor growth within GBM chemotherapy. It was hypothesized that due to their properties as alkylating agents inhibiting growth genes within GBM, temozolomide and carmustine would provide the most reduction in cellular growth mathematically.² VisualPDE simulations were used to model administration of temozolomide, carmustine, bevacizumab, and none in chemotherapy and provide the cellular GBM counts at any given time within five months (60 time points were used). Results showed cell growth reduction by temozolomide and carmustine, but most drastically by bevacizumab, and upon further analysis, a One-Way ANOVA yielded that the difference between at least two chemotherapeutic administrations were statistically significant (F(3, 236)=281.049, p<0.001). A post-hoc Tukey HSD test revealed a significant difference between no administration and each chemotherapeutic administration (TMZ: p<0.001, BCNU: p=0.046, BEV: p<0.001), as well as significant differences compared to bevacizumab, which was drastically more effective than TMZ and BCNU (p<0.001, p<0.001). Thus, it was concluded that BEV provided the optimal treatment in slowing GBM growth with the mathematical model through its ability to regulate proteins and drug resistance, allowing for its integration in future chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: In tackling the daunting challenge of glioblastoma, a severe form of brain tumor, researchers have been exploring ways to disrupt its abnormal energy production, focusing on a molecule called NAD. The drug FK866, known to deplete NAD, shows potential in curbing tumor growth but faces limitations when used alone. This study introduces a novel approach using fluorinated versions of NAD precursors, specifically a compound named F-NR, which when, combined with FK866, significantly boosts its effectiveness against glioblastoma cells. F-NR works by competing with the endogenous metabolism of NR, leading to reduced NAD levels and enhancing FK866's ability to kill cancer cells. Another key finding is the role of SARM1, activated by one of F-NR's metabolites, which contributes to the enhanced cell-killing effect. The sequence of events—NAD depletion followed by energy loss and ultimately, widespread cell death—highlights the potential of this strategy to improve FK866's therapeutic impact. This research not only deepens our understanding of NAD metabolism in glioblastoma but also provides a potential strategy for treating the brain cancer. Glioblastoma, a formidable brain tumor characterized by dysregulated NAD metabolism, poses a significant therapeutic challenge. The NAMPT inhibitor FK866, which induces NAD depletion, has shown promise in controlling tumor proliferation and modifying the tumor microenvironment. However, the clinical efficacy of FK866 as a single drug therapy for glioma is limited. In this study, we aim to disrupt NAD metabolism using fluorinated NAD precursors and explore their synergistic effect with FK866 in inducing cytotoxicity in glioblastoma cells. The synthesized analogue of nicotinamide riboside (NR), ara-F nicotinamide riboside (F-NR), inhibits nicotinamide ribose kinase (NRK) activity in vitro, reduces cellular NAD levels, and enhances FK866's cytotoxicity in U251 glioblastoma cells, indicating a collaborative impact on cell death. Metabolic analyses reveal that F-NR undergoes conversion to fluorinated nicotinamide mononucleotide (F-NMN) and other metabolites, highlighting the intact NAD metabolic pathway in glioma cells. The activation of SARM1 by F-NMN, a potent NAD-consuming enzyme, is supported by the synergistic effect of CZ-48, a cell-permeable SARM1 activator. Temporal analysis underscores the sequential nature of events, establishing NAD depletion as a precursor to ATP depletion and eventual massive cell death. This study not only elucidates the molecular intricacies of glioblastoma cell death but also proposes a promising strategy to enhance FK866 efficacy through fluorinated NAD precursors, offering potential avenues for innovative therapeutic interventions in the challenging landscape of glioblastoma treatment. [ABSTRACT FROM AUTHOR]

Background: Gliomas, particularly glioblastoma multiforme (GBM), are highly aggressive brain tumors that present significant challenges in oncology due to their rapid progression and resistance to conventional therapies. Despite advancements in treatment, the prognosis for patients with GBM remains poor, necessitating the exploration of novel therapeutic approaches. One such emerging strategy is the development of glioma vaccines, which aim to stimulate the immune system to target and destroy tumor cells. Aims: This review aims to provide a comprehensive evaluation of the current landscape of glioma vaccine development, analyzing the types of vaccines under investigation, the outcomes of clinical trials, and the challenges and opportunities associated with their implementation. The goal is to highlight the potential of glioma vaccines in advancing more effective and personalized treatments for glioma patients. Materials and Methods: This narrative review systematically assessed the role of glioma vaccines by including full‐text articles published between 2000 and 2024 in English. Databases such as PubMed/MEDLINE, EMBASE, the Cochrane Library, and Scopus were searched using key terms like "glioma," "brain tumor," "glioblastoma," "vaccine," and "immunotherapy." The review incorporated both pre‐clinical and clinical studies, including descriptive studies, animal‐model studies, cohort studies, and observational studies. Exclusion criteria were applied to omit abstracts, case reports, posters, and non‐peer‐reviewed studies, ensuring the inclusion of high‐quality evidence. Results: Clinical trials investigating various glioma vaccines, including peptide‐based, DNA/RNA‐based, whole‐cell, and dendritic‐cell vaccines, have shown promising results. These vaccines demonstrated potential in extending survival rates and managing adverse events in glioma patients. However, significant challenges remain, such as therapeutic resistance due to tumor heterogeneity and immune evasion mechanisms. Moreover, the lack of standardized guidelines for evaluating vaccine responses and issues related to ethical considerations, regulatory hurdles, and vaccine acceptance among patients further complicate the implementation of glioma vaccines. Discussion: Addressing the challenges associated with glioma vaccines involves exploring combination therapies, targeted approaches, and personalized medicine. Combining vaccines with traditional therapies like radiotherapy or chemotherapy may enhance efficacy by boosting the immune system's ability to fight tumor cells. Personalized vaccines tailored to individual patient profiles present an opportunity for improved outcomes. Furthermore, global collaboration and equitable distribution are critical for ensuring access to glioma vaccines, especially in low‐ and middle‐income countries with limited healthcare resources Conclusion: Glioma vaccines represent a promising avenue in the fight against gliomas, offering hope for improving patient outcomes in a disease that is notoriously difficult to treat. Despite the challenges, continued research and the development of innovative strategies, including combination therapies and personalized approaches, are essential for overcoming current barriers and transforming the treatment landscape for glioma patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavorable clinical prognosis for affected patients. The objective was to analyze the sensitivity of GBM cells to the antimicrobial peptides (AMPs) cathelicidin (LL-37) and protegrin-1 (PG-1), both alone and in combination with chemotherapy, to predict overall survival (OS) in the patients. Methods: The study was conducted on 27 GBM patients treated in the neurosurgical department of the Almazov Medical Research Centre (Saint Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemotherapy, AMPs, and their combinations on brain tumor cells were assessed by an MTT assay using a 50% inhibitory concentration (IC50). Results: In GBM cells from the patients, LL-37 and PG-1 exhibited strong anticancer effects, surpassing those of chemotherapy drugs. These LL-37 and PG-1 anticancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by experiments on rats with C6 glioma, where the intranasal administration of LL-37 (300 μM) and PG-1 (600 μM) increased the life expectancy of the animals to 69 and 55 days, respectively, compared to 24 days in the control group (HR = 4.139, p = 0.0005; HR = 2.542, p = 0.0759). Conclusions: Additionally, the combination of LL-37 and PG-1 with chemotherapy drugs showed that a high IC50 of LL-37 with cisplatin (cutoff > 800 μM) in GBM cells was associated with increased life expectancy (19 vs. 5 months, HR = 4.708, p = 0.0101) and OS in GBM patients. These combinations could be used in future GBM treatments. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. There is a pressing need to develop novel treatment strategies due to the poor targeting effect of current therapeutics. Here, a gold cluster coated with optimized GBM-targeting peptide is engineered, namely NA. NA can efficiently target GBM both in vitro and in vivo. Interestingly, the uptake of NA significantly sensitizes GBM cells to ferroptosis, a form of programmed cell death that can bypass the tumor resistance to apoptosis. This effect is exerted through regulating the HO-1-dependent iron ion metabolism, which is the non-canonical pathway of ferroptosis. The combined treatment of a ferroptosis inducer and NA profoundly inhibited tumor growth in both the GBM spheroid model and a syngeneic mouse model with enhanced ferroptosis levels and excellent biosafety. Importantly, the infiltration of tumoricidal lymphocytes is also significantly increased within tumor. Therefore, NA presents a potential novel nanomaterial-based strategy for GBM treatment. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the most aggressive malignant tumors of the brain. We queried PubMed for articles about molecular predictor markers in GBM. This scoping review aims to analyze the most important outcome predictors in patients with GBM and to compare these factors in terms of absolute months of survival benefit and percentages. Performing a gross total resection for patients with GBM undergoing optimal chemo- and radiotherapy provides a significant benefit in overall survival compared to those patients who received a subtotal or partial resection. However, compared to IDH-Wildtype GBMs, patients with IDH-Mutant 1/2 GBMs have an increased survival. MGMT promoter methylation status is another strong outcome predictor for patients with GBM. In the reviewed literature, patients with methylated MGMT promoter lived approximately 50% to 90% longer than those with an unmethylated MGMT gene promoter. Moreover, KPS is an important predictor of survival and quality of life, demonstrating that we should refrain from aggressive surgery in important brain areas. As new therapies (such as TTFs) emerge, we are optimistic that the overall median survival will increase, even for IDH-Wildtype GBMs. In conclusion, molecular profiles are stronger outcome predictors than the extent of neurosurgical resection for GBM. [ABSTRACT FROM AUTHOR]

Brain tumors display remarkable cellular and molecular diversity, significantly impacting the progression and outcomes of the disease. The utilization of tumor tissue acquired through surgical handheld devices for tumor characterization raises important questions regarding translational research. This study seeks to evaluate the integrity of tissue resected using a microdebrider (MD) in the context of establishing tumor organoids from glioblastomas (GBM). Tumor samples were collected from patients with GBM using both tumor forceps (en bloc) and a MD. The time required to protocol completion and cell viability of paired samples was measured. H&E staining was performed to examine histologic morphology. Ten paired samples were obtained from GBM patients using tumor forceps and the MD. Samples collected with the MD demonstrated significantly shorter processing times compared to those obtained through en bloc resection, with overall means of 31.7 ± 2.4 mins and 38.8±3 mins, respectively (P < 0.001). Cell viability measured at the end of protocol completion was comparable between tissues obtained using both the MD and en bloc, with mean viabilities of 80.2 ± 12.4% and 79.1 ± 12.5%, respectively (P = 0.848). H&E examination of tissues revealed no significant differences in the cellular and histologic characteristics of paired samples obtained using both methods across GBM tumors, nor in the corresponding established organoids. Tumor tissues obtained using the MD and en bloc methods demonstrate a high success rate in establishing GBM organoids, with the MD offering the advantage of significantly reduced processing time. Both methods display comparable cell viability and maintain consistent histologic characteristics in the resected tissue and the corresponding organoids. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumour that has the worst prognosis in adults. Currently, the automatic segmentation of this kind of tumour is being intensively studied. Here, the automatic three‐dimensional segmentation of the GBM is achieved with its related subzones (active tumour, inner necrosis, and peripheral oedema). Preliminary segmentations were first defined based on the four basic magnetic resonance imaging modalities and classic image processing methods (multithreshold Otsu, Chan–Vese active contours, and morphological erosion). After an automatic gap‐filling post processing step, these preliminary segmentations were combined and corrected by a supervised artificial neural network of multilayer perceptron type with a hidden layer of 80 neurons, fed by 30 selected radiomic features of gray intensity and texture. Network classification has an overall accuracy of 83.9%, while the complete combined algorithm achieves average Dice similarity coefficients of 89.3%, 80.7%, 79.7%, and 66.4% for the entire region of interest, active tumour, oedema, and necrosis segmentations, respectively. These values are in the range of the best reported in the present bibliography, but even with better Hausdorff distances and lower computational costs. Results presented here evidence that it is possible to achieve the automatic segmentation of this kind of tumour by traditional radiomics. This has relevant clinical potential at the time of diagnosis, precision radiotherapy planning, or post‐treatment response evaluation. [ABSTRACT FROM AUTHOR]

The present study conducted an extensive review of the literature that describes the molecular pathogenesis of cancer and glioblastoma multiforme (GBM), exploring physiological adaptation resulting from exercise training in the broader context of cancer and brain tumors, with a specific emphasis on GBM, aiming to discern the implications of exercise in improving the quality of life (QoL) of affecting patients. GBM is the predominant aggressive malignant primary brain tumor with a high mortality rate. GBM involves multiple pathways that can be targeted by exercise training. Exercise has shown its value in various other cancer types and offers a promising approach for GBM. Exercise training is regarded as a safe and feasible adjunctive treatment to improve the QoL of patients with brain tumors, including GBM. Nevertheless, further research is required in order to fully elucidate the mechanisms through which exercise affects cellular processes impacted by cancer and its treatments, with a specific focus on GBM. While exercise training guidelines have been established for cancer patients in general, there is currently a lack of specific guidelines tailored to patients with GBM. Clear guidelines are essential to assist clinicians in determining the most appropriate exercise type, intensity and frequency for patients to optimize their rehabilitation process. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme is a very aggressive type of cancer with high mortality and poor prognosis worldwide. Advanced treatment options with an understanding of the molecules and signalling mechanisms involved in this type of cancer have the potential to increase targeted therapy and decrease off-target effects, resistance, and recurrence. Glioblastoma multiforme (GBM) presents a complex tumour microenvironment with numerous cellular components and an extracellular matrix comprising multiple components. A deeper understanding of these components and corresponding signalling pathways can increase the success of immune checkpoint inhibitors in the treatment of GBM. The discovery of specific molecular changes and biomarkers has led to the investigation of tailored treatments for individual patients. Combination therapies targeting multiple pathways or utilizing different modalities are emerging as a promising strategy albeit with challenges in drug delivery to the brain. The review presents a comprehensive update of the various immunomodulatory signalling networks in GBM and highlights the corresponding therapeutic approaches by targeting them. [ABSTRACT FROM AUTHOR]

The competitive HMG-CoA reductase (HMGCR) inhibitors, commonly referred to as "statins," have been shown in preclinical tests to have promise anticancer characteristics in addition to being potent medications that lower cholesterol and lower cardiovascular risk. When combined with other cancer treatment strategies, statins seem to improve the treatment outcome for a variety of malignancies. After surgical resection followed by concomitant radiation and chemotherapy, the median overall survival (OS) for glioblastoma multiforme (GBM), a particularly lethal cerebral tumour, is only about one year. Due to their capacity to inhibit cell growth, survival, migration, metastasis, inflammation, and angiogenesis in both in vitro and in vivo investigations, statins have recently come to light as prospective adjuvant medications for the treatment of GBM. Statins' therapeutic effects on the survival of GBM patients are still debatable, though. When just focusing on the treatment of cancer, specifically GBM, this study intends to analyse and address some of the known effects of statin medicines, including concurrent statin therapy with chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is recognized as the most lethal and most highly invasive tumor. The high likelihood of treatment failure arises fromthe presence of the blood-brain barrier (BBB) and stemcells around GBM, which avert the entry of chemotherapeutic drugs into the tumormass. Objective: Recently, several researchers have designed novel nanocarrier systems like liposomes, dendrimers, metallic nanoparticles, nanodiamonds, and nanorobot approaches, allowing drugs to infiltrate the BBB more efficiently, opening up innovative avenues to prevail over therapy problems and radiation therapy. Methods: Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases, for example, PubMed, Science Direct, Google Scholar, and others, using specific keyword combinations, including "glioblastoma," "brain tumor," "nanocarriers," and several others. Conclusion: This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management. Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed. [ABSTRACT FROM AUTHOR]

Glioblastoma, the most aggressive form of brain tumor, poses significant challenges in terms of treatment success and patient survival. Current treatment modalities for glioblastoma include radiation therapy, surgical intervention, and chemotherapy. Unfortunately, the median survival rate remains dishearteningly low at 12-15 months. One of the major obstacles in treating glioblastoma is the recurrence of tumors, making chemotherapy the primary approach for secondary glioma patients. However, the efficacy of drugs is hampered by the presence of the blood-brain barrier and multidrug resistance mechanisms. Consequently, considerable research efforts have been directed toward understanding the underlying signaling pathways involved in glioma and developing targeted drugs. To tackle glioma, numerous studies have examined kinase-downstream signaling pathways such as RAS-RAF-MEKERK-MPAK. By targeting specific signaling pathways, heterocyclic compounds have demonstrated efficacy in glioma therapeutics. Additionally, key kinases including phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase, cytoplasmic tyrosine kinase (CTK), receptor tyrosine kinase (RTK) and lipid kinase (LK) have been considered for investigation. These pathways play crucial roles in drug effectiveness in glioma treatment. Heterocyclic compounds, encompassing pyrimidine, thiazole, quinazoline, imidazole, indole, acridone, triazine, and other derivatives, have shown promising results in targeting these pathways. As part of this review, we propose exploring novel structures with low toxicity and high potency for glioma treatment. The development of these compounds should strive to overcome multidrug resistance mechanisms and efficiently penetrate the blood-brain barrier. By optimizing the chemical properties and designing compounds with enhanced drug-like characteristics, we can maximize their therapeutic value and minimize adverse effects. Considering the complex nature of glioblastoma, these novel structures should be rigorously tested and evaluated for their efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation. Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression. Specifically, hypoxia is known to activate inducible factors, such as hypoxia-inducible factor 1alpha (HIF-1α), which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators, such as the vascular endothelial growth factor (VEGF). Here, we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data, as potential biomarkers of GBM prognosis and treatment efficacy. We performed a systematic review (Medline/Embase, and Pubmed database search was completed by 16th of April 2024 by two independent teams; PRISMA 2020). We evaluated methods of immunoassays, cell viability, or animal or patient survival methods of the retrieved studies to assess unbiased data. We used inclusion criteria, such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression, other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression, application of immunoassays for protein expression, and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression. We used exclusion criteria, such as data not reporting both HIF-1α and VEGF or prognosis. We included 50 studies investigating in total 1319 GBM human specimens, 18 different cell lines or GBM-derived stem cells, and 6 different animal models, to identify the association of HIF-1α/VEGF immunophenotypes, and with other prognostic factors, clinical and macroscopic data in GBM prognosis and therapeutic approaches. We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors, such as miR-210-3p, Oct4, AKT, COX-2, PDGF-C, PLDO3, M2 polarization, or ALK, leading to unfavorable survival. Reduced HIF-1α/VEGF expression correlates with FIH-1, ADNP, or STAT1 upregulation, as well as with clinical manifestations, like epileptogenicity, and a favorable prognosis of GBM. Based on our data, HIF-1α or VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression. Finally, HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy, including combined first-line treatment with histone deacetylase inhibitors, thimerosal, or an active metabolite of irinotecan, as well as STAT3 inhibitors alone, and resulting in a favorable tumor prognosis and patient survival. These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes. Data limitations may include the use of less sensitive detection methods in some cases. Overall, our data support HIF-1α/VEGF's role as biomarkers of GBM prognosis and treatment efficacy. [ABSTRACT FROM AUTHOR]

Context: Glioma, the most common primary malignant brain tumour, is a grave health concern associated with high morbidity and mortality. Current treatments, while effective to some extent, are often hindered by factors such as the blood--brain barrier and tumour microenvironment. this underscores the pressing need for exploring new pharmacologically active anti-glioma compounds. Methods: this review synthesizes information from major databases, including chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer link and relevant books. Publications were selected without date restrictions, using terms such as 'Hymenocrater spp.,' 'phytochemical,' 'pharmacological,' 'extract,' 'essential oil' and 'traditional uses.' General web searches using Google and Yahoo were also performed. Articles related to agriculture, ecology, synthetic work or published in languages other than english or chinese were excluded. Results: the marine environment has been identified as a rich source of diverse natural products with potent antitumour properties. Conclusions: This paper not only provides a comprehensive review of marine-derived compounds but also unveils their potential in treating glioblastoma multiforme (GBM) based on functional classifications. It encapsulates the latest research progress on the regulatory biological functions and mechanisms of these marine substances in GBM, offering invaluable insights for the development of new glioma treatments. [ABSTRACT FROM AUTHOR]

Purpose: To develop a self‐supervised learning method to retrospectively estimate T1 and T2 values from clinical weighted MRI. Methods: A self‐supervised learning approach was constructed to estimate T1, T2, and proton density maps from conventional T1‐ and T2‐weighted images. MR physics models were employed to regenerate the weighted images from the network outputs, and the network was optimized based on loss calculated between the synthesized and input weighted images, alongside additional constraints based on prior information. The method was evaluated on healthy volunteer data, with conventional mapping as references. The reproducibility was examined on two 3.0T scanners. Performance in tumor characterization was inspected by applying the method to a public glioblastoma dataset. Results: For T1 and T2 estimation from three weighted images (T1 MPRAGE, T1 gradient echo sequences, and T2 turbo spin echo), the deep learning method achieved global voxel‐wise error ≤9% in brain parenchyma and regional error ≤12.2% in six types of brain tissues. The regional measurements obtained from two scanners showed mean differences ≤2.4% and correlation coefficients >0.98, demonstrating excellent reproducibility. In the 50 glioblastoma patients, the retrospective quantification results were in line with literature reports from prospective methods, and the T2 values were found to be higher in tumor regions, with sensitivity of 0.90 and specificity of 0.92 in a voxel‐wise classification task between normal and abnormal regions. Conclusion: The self‐supervised learning method is promising for retrospective T1 and T2 quantification from clinical MR images, with the potential to improve the availability of quantitative MRI and facilitate brain tumor characterization. [ABSTRACT FROM AUTHOR]

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear. Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved. Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling. Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells. [ABSTRACT FROM AUTHOR]