Glioblastoma

This study demonstrated that 68Ga-Cixafor™ PET exhibits a TBR with minimal cortical uptake, significantly enhancing glioma detection compared to conventional imaging methods. This, combined with the potential therapeutic capabilities of CXCR4-targeting radiopharmaceuticals, highlights the promise of 68Ga-Cixafor™ as a valuable tool for not only improved glioma diagnosis but also personalized treatment strategies.

Overall, CXCL12 inhibits tumor growth through several distinct mechanisms: inhibition of cell cycle and migration, as well as impairment of immune checkpoint, thereby stimulating a strong host's immune response. The mechanism(s) that renders CXCL12 a tumor-promoting factor in certain cells and a suppressor in others has remained elusive.

Our results highlight that the radiological features of bGB are not homogenous and can indicate 2 potential subtypes based on their origins. Further studies are mandatory, but CC-type and Hemispheric-type exhibit distinct clinical backgrounds, outcomes, and molecular features.

Both SVZ invasion and MGMT unmethylation negatively influenced the prognosis of patients with IDH wild-type GBM. The clinical model developed in this study accurately predicts the survival outcome, providing a basis and reference for clinical practice.

Finally, imaging a batch of LMNA knockout vs. wildtype astrocytoma spheroids revealed significant differences in their DNA damage response, underscoring the system's sensitivity and throughput. Overall, the fluidic chip design provides a cost-effective, accessible, and efficient solution for high-throughput organoid imaging.

Additionally, ATRX mutations were frequently associated with a more pronounced deviation of the median structures. To statistically validate the associations between MRI and the histopathological features of glioblastomas, further studies with larger cohorts are required.

In IDH-wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS...Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

All of these proteins showed higher levels in both ND_ and R_T0 pre-surgery saliva with respect to CTRL and different modulation after surgery or chemo-radiotherapy combined treatment, suggesting a role as a potential panel of GBM predictive and prognostic biomarkers. These results highlight and confirm that saliva, a biofluid featured for an easily accessible and low invasiveness collection, is a promising source of GBM biomarkers, showing new potential opportunities for the development of targeted therapies and diagnostic tools.

These genes play significant roles in the PI3K-Akt pathway and potentially interact with vitamin D. Molecular docking and single-cell RNA sequencing analyses suggest that vitamin D may improve the prognosis of glioma patients infected with COVID-19 by regulating these key genes and the PI3K-Akt pathway. The findings reveal molecular links between glioma and COVID-19, thereby providing new insights for developing targeted therapeutic strategies.

The combined use of cGAMP and antimiR-25 NCs also increased the expression of markers involved in M1 polarization. These findings offer insights into optimizing antimiR-25/cGAMP NCs for enhancing immune responses in GBM.

Additionally, the activation of metabolic pathways associated with invasiveness, including AKT and NF-κB, was analyzed. Our results suggest that the effects induced by NaF at physiologically high concentrations (0.1-10 µM) in U-87 glioblastoma cells may promote a pro-invasive phenotype.

Despite the reduction of FGFR1 protein and the inhibition of FGF signaling, SPRY2-OE increased cell viability, and knockdown of SPRY2 enhanced the sensitivity to cisplatin. These results demonstrate that the inhibitory effect of SPRY2-OE on FGF signaling is at least in part due to the reduction in FGFR1 levels and the decreased binding of PLCγ1 to the receptor.

These results confirm that HSP90 is a strong pro-survival factor in molecularly heterogeneous gliomas and suggest that epichaperome inhibition with HSP90 inhibitors warrants further investigation for the treatment of gliomas.

We provide evidence that PPAR ligands in combination with CIK cell immunotherapy could be a valuable option for malignant CNS tumors.

This study highlights that FOSL1 is negatively regulated by KLF14 in glioblastoma and suggests that KLF14 overexpression can mitigate tumor growth by inhibiting FOSL1, thus identifying KLF14 as a novel molecular target for treating glioblastoma. Further research into the interplay and regulatory dynamics between KLF14 and FOSL1 under varying stress conditions can enhance the precision of glioblastoma treatment.

These findings indicate that DNA damage response inhibitors can enhance IFN signaling following X-, proton and carbon ion irradiation, with a strong positive dependency on LET.

P1/2, N=34, Recruiting, Universität Münster | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jul 2024 --> Jun 2026

Blocking BER after abasic site formation results in large deletions and TMZ hypersensitization. Our findings reveal potential vulnerabilities of TMZ-resistant tumors.

Thus, DHMBA may have inhibitory effects on the activity of human glioblastoma cells in vitro. This study may provide a new strategy for the treatment of glioblastoma tumors.

Among Ca2+ channels functioning as mechanosensors, the expression levels of TRPC and TRPV families were efficiently increased on the gel with approximately 10 kPa, as well as stemness markers. These data suggest that tumor tissues with the stiffness of 10 kPa effectively trigger the signals for generating CSCs through alterations of membrane structures and Ca2+ influx, which will be beneficial for developing novel therapeutic applications targeting CSCs.

Our results revealed that HSD52 could serve as a promising therapeutic target to overcome TMZ resistance, improving the clinical efficacy of TMZ chemotherapy in GBM.

Finally, we have offered the current attempts of chronotherapy targeting CSCs. Elucidating the molecular regulation of circadian clock gene in CSCs will provide us a novel direction for the development of therapeutics to target CSCs.

Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, modulating its growth through clock-controlled cues, like glucocorticoids.

WTAP plays critical roles in mesenchymal transition of GSCs and formation of TIME, highlighting the therapeutic potential of targeting WTAP and its downstream effectors to enhance the efficacy of immunotherapy.

Furthermore, in the C6 cells only, the BO extract reduced the migration and downregulated the relative mRNA expression of matrix metalloproteinase-2, O6-methylguanine-DNA methyltransferase, nuclear factor-kappa B, interleukin-6 genes, and upregulated caspase-3 gene. These results underscore the promising anti-glioma potential of BO extract, attributed to its diverse bioactive composition.

Tumors in both groups of rats showed a moderate/high expression of the astrocyte marker, GFAP, and the oligodendrocyte marker, OLIG-2, and a low expression of the proliferation marker, Ki-67. However, tumors of the ENU + LY341495 group showed a reduced density of Iba-1+ cells, suggesting a lower extent of neuroinflammation in the tumor microenvironment. These findings strengthen the hypothesis that mGlu3 receptors are candidate drug targets for the treatment of malignant gliomas.

Knocking down the expression of the RAB32 gene significantly inhibited the proliferation, migration and invasion of glioma cells. Our results show that RAB32 is a key factor affecting the prognosis of patients with GBM, and its targeting may provide a new treatment for patients with GBM.

BCP significantly inhibited tumor growth in GL261 tumor-bearing mice with no discernible side effects. These findings indicate that BCP may serve as a potential radiosensitizer for improving RT outcomes in GBM by inhibiting DNA repair, inducing apoptosis, and suppressing anti-apoptotic and survival pathways.

P1, N=10, Completed, Blueprint Medicines Corporation | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> May 2024

Since the stability of plasma and lysosomal membranes is maintained by the presence of the stress-inducible heat shock protein 70 (Hsp70) which has a strong affinity to tumor-specific glycosphingolipids, necrosis occurs predominantly in LN18 cells having a lower membrane Hsp70 expression density than U87 cells. In summary, our findings indicate that the lipid metabolism of tumor cells can affect the radiosensitizing capacity of FF when encountered either as a free drug or as a drug loaded in biomimetic lipid vesicles.

Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.

The probe was also capable of detecting GFAP in spiked serum samples, achieving a recovery rate ranging from 83% to 111%. Notably, a cost-effective paper strip assay was developed, offering significant potential for the visual detection of GFAP under ultraviolet illumination.

Following diagnosis, the typical life expectancy ranges from 12 to 15 months, as current established treatments like surgical intervention, radiotherapy, and chemotherapy using temozolomide exhibit limited effectiveness...We delineate the receptors it binds to and its significance in glioblastoma and other cancer types. Lastly, we examine its role in immunotherapy and the utilization of nanobodies in this domain.

P=N/A, N=54, Completed, University Hospital Muenster | Recruiting --> Completed

With its sped-up epigenetic aging, gcGB presented as the epigenetic oldest GB variant in our cohort. Whereas the correlation between accelerated tumor-intrinsic epigenetic aging and cellular senescence in gcGB stays elusive, fostering epigenetic aging programs in GB might be of interest for future exploration of alternative treatment options in GB patients.

More importantly, we found that Proguanil's inhibitory effect on U87MG cell growth and migration was positively correlated with CSF1R expression, and this effect diminished following CSF1R knockdown and Proguanil demonstrated synergistic effects with CSF1R-targeting positive drugs (BLZ945 and GW2580). Meanwhile, Proguanil targeted CSF1R to inhibit M2-type polarization of tumor-associated macrophages (TAMs) and their proliferation, thus altering the tumor microenvironment while indirectly suppressing the proliferation and migration of U87MG cells. Taken together, these findings suggest that Proguanil may serve as a promising CSF1R antagonist for GBM treatment.

In sum, the preventive effects of MitoQ as a beneficial immune reactive agent and exercise training in rats with C6-induced glioblastoma may be mediated via modulating oxidative stress, inflammatory factors, and down-regulation of the expression of TLR4.

The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM.

Moreover, expression of these PTEN mutations heightened EGFR activity by sequestering EGFR within endomembranes longer and affected its signaling behavior. Through comprehensive studies on global protein phosphorylation and kinase library analyses in cells with the G36E and L42R PTEN mutations, we identified distinct cancer-promoting pathways activated by EGFR, offering targets for treating GBM with these PTEN alterations.

Combination treatment of DPI-201-106 with the CHK1 inhibitor prexasertib or the PARP inhibitor niraparib demonstrated synergistic effects in multiple patient-derived glioblastoma cells both in vitro and in intracranial xenograft mouse models, extending survival of glioblastoma-bearing mice. DPI-201-106 enhances the efficacy of DDR inhibitors to reduce glioblastoma growth. As these drugs have already been clinically tested in humans, repurposing DPI-201-106 in novel combinatorial approaches will allow for rapid translation into the clinic.

The timing of adjuvant TMZ chemoradiotherapy, if commenced within 12 weeks after glioblastoma diagnosis, did not influence OS regardless of EOR or pMGMT methylation status. Clinical judgment should be exercised in optimizing the timing of initiating adjuvant therapy.

Our findings reveal that CCN1 may be an important factor in the enhanced invasiveness and MES phenotype transition of GSCs and highlight the potential to target CCN1 for treating GBM.