جستجوی مقالات مرتبط با کلیدواژه "glioblastoma multiforme" در نشریات گروه "پزشکی"

Glioblastoma multiforme is the most common malignant brain tumor that arises with high morbidity, having a rather very poor prognosis with only 5.5% five-year survival. Such tumors exhibit aggressive behavior due to intrinsic heterogeneity, glioma stem cell dynamics, and resistance to conventional and emerging therapies. Epigenetic modifications are highlighted in recent studies to be of importance for DNA methylation and histone modifications in the tumorigenesis and progression of GBM. Additionally, some aberrant signaling pathways have been identified, including Hedgehog, Notch, and Wnt, which might act as both a driving force in the tumor microenvironment and a promising therapeutic target. Improved understanding of the molecular and cellular mechanisms of GBM has led to ongoing efforts toward personalized medicine and novel therapeutic strategies in a continuous quest to improve patient outcomes in this challenging malignancy. The present manuscript reviews the current knowledge of the epigenetic landscape, signaling networks, and resulting treatment implications associated with glioblastoma, hence underlining the urgent need for innovative therapeutic approaches tailored to specific patient profiles.

Glioblastoma multiforme (GBM) is an aggressive cancer with a poor prognosis. Inflammation and angiogenesis are important processes in GBM that are interrelated. In this study, bioinformatic investigations were performed to detect common and key genes in the inflammatory and angiogenesis pathways of GBM. Additionally, relevant long non-coding RNAs (lncRNAs) were recognized as important gene regulators. Consequently, real-time PCR and correlation analyses were used to investigate changes in gene and lncRNA expression levels and explain their relationship. RELA emerged as a common key gene in these biological processes. LINC01366 and LINC01433 were identified as putative RELA regulators in different metabolic pathways using computational assays. According to our findings, the expression levels of RELA, LINC01366 and LINC01433 were found to be significantly upregulated in GBM samples. Correlational studies revealed a significant positive relationship of gene expressions between LINC01366 and LINC01433, indicating that they may have a coordinated effect on GBM biology. Nevertheless, there was no significant correlation between these lncRNAs and RELA. The current study highlights the high expression of LINC01366 and LINC01433 in GBM and emphasizes the importance of studying lncRNAs as putative regulators in the pathophysiology of GBM. Further research is needed to clarify their specific functions, in particular the associated inflammatory and angiogenesis pathways.

Glioblastoma multiforme (GBM) is one of the most invasive types of brain cancer. LncRNAs can be considered a new prognostic and diagnostic biomarker in GBM. This study comprehensively explored the interaction of lncRNAs with mRNAs in the TCGA database and proposed a novel promising biomarker with favorable diagnostic and prognostic values.

The public data of RNA-seq and related clinical data were downloaded from the TCGA database. Differential expression analysis was conducted in R. GO and KEGG signaling pathways were used for enrichment. The STRING database was used for PPI analysis. CE-network was constructed by STAR database. Kaplan-Meier survival analysis and ROC curve analysis to indicate the biomarkers' diagnostic and prognostic values.

Differentially expressed data illustrated that 4428 mRNAs were differentially expressed in GBM. The GO and KEGG pathway analysis showed that the differentially expressed mRNAs were enriched in critical biological processes. The PPI showed that WEE1, BARD1, and CDK6 were the important PPI hubs. The ceRNA network data demonstrated critical lncRNAs. The data revealed that the lncRNA CRNDE, LINC00957, AC072061.1, AC068888.1, and DBH-AS1 are potential diagnostic prognostic biomarkers in the GBM patients.

Altogether, we demonstrated lncRNA, and mRNA interaction and mentioned regulatory networks, considered a therapeutic option in GBM. In addition, we proposed potential diagnostic and prognostic biomarkers for the patients.

Superantigens are bacterial toxins that induce a massive immune response in the host. Superantigen staphylococcal enterotoxin B (SEB) can form a ternary complex with its receptors, MHC class II (MHCII) and TCR, and can be used in tumor-targeting therapy, particularly when cooperating with a specific vector. In this study, SEB was fused to interleukin-13 (IL13), which forms a complex with IL13 receptor α2 (IL13Rα2) overexpressed in glioblastoma multiforme (GBM) cells for therapeutic goals.

Methods :

We designed four fusion proteins based on the arrangement of SEB (N- or C-terminal domain) and provided a flexible inter-domain linker (no or yes), resulting in the formation of SEB-IL13, SEB-L-IL13, IL13-SEB, and IL13-L-SEB, respectively. These fusion proteins were then evaluated for their various physicochemical properties and structural characteristics. Bioinformatics tools were employed to predict, refine, and validate the three-dimensional structure of the fusion proteins. In addition, the fusion proteins were docked with IL13Rα2, MHCII, and TCR receptors through the HADDOCK 2.4 server. The candidate fusion protein was subjected to molecular dynamics simulation.

There were differences among the designed fusion proteins. The model with the N-terminal domain of IL13 and containing an inter-domain linker (IL13-L-SEB) was stable and had a long half-life. The docking analysis revealed that the IL13-L-SEB fusion protein had a higher binding affinity to the IL13Rα2, MHCII, and TCR receptors. Finally, using molecular dynamics simulation through iMODS, acceptable results were obtained for the IL13-L-SEB docked complexes.

The results suggest IL13-L-SEB is a promising novel fusion protein for cancer therapeutic application.

The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells. To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot analysis were conducted. At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that the total protein level of MMP-2 as well as phosphorylation of crucial metastasis-related proteins, including p-JNK and p-mTOR, decreased in auraptene-treated cells. The molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3. Auraptene effectively inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities. Auraptene might serve as a potential anti-metastatic agent against malignant GBM.

The most common form of human primary brain tumor resistant to treatment is glioblastoma multiforme. For brain tumors, it is essential to optimize the treatment regimen with curcumin as a sensitizing agent and adjunctive to traditional or alternative therapy. This study aimed to determine the combined effects of cell death and apoptosis caused by curcumin before and after radiation with hyperthermia on glioblastoma in a monolayer cell culture and spheroid cell model.

The spheroid cells were separately or simultaneously treated with the IC50% concentration of curcumin before and after 2 Gy radiation. Hyperthermia was then applied by incubating the cells at 43 °C for 1 hr. The survival rate of the cells was measured via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Bax, Bcl-2, and caspase-3 expressions were quantified with real-time PCR (RT-PCR).

Cell viability significantly decreased in the curcumin (before) with radiation group (CCM+IR) by 51.12%, and in the radiation, curcumin, and hyperthermia group (IR+ CCM+ H) by 31.01%. The expression level of Bax and caspase-3 significantly increased in the combination of radiation, curcumin, and hyperthermia group (IR+ CCM+ H) by 3.80 ± 0.02 and 5.13 ± 0.12, respectively. The Bcl-2 expression level in the radiation with curcumin and hyperthermia group was 0.41 ± 0.01, compared to the curcumin before radiation group (0.70± 0.05) and the curcumin after radiation group (0.60± 0.02).

Curcumin was more effective on cell death after radiation. It caused a synergistic effect in combination with other adjuvant therapies for glioblastoma spheroid cells.

Minimizing the radiation side effects in cancer therapy has become one of the major challenges in radiotherapy, especially if the cancer is located in vital organs such as the brain. Negative pi-meson-based therapy is one method of radiotherapy that allows cancer to receive a high radiation dose while the surrounding normal tissue receives a low radiation dose. This research aims to analyze negative pi-meson therapy's dose and irradiation time in glioblastoma multiforme.

Simulation-based research is conducted using the PHITS program. The source used is a negative pion beam with an intensity of 2.5 × 108 pions/second with an energy of 30 MeV to 60 MeV with an interval of 1 MeV. The negative pion energy, which has the maximum dose rate in the cancer target area, was optimized to obtain the weighting factors and irradiation time. The irradiation was carried out in 30 fractions with the dose per fraction of 2 Gy.

Irradiation time per fraction obtained was 194.91 seconds. The organ at risks (OARs) analyzed in this research were soft tissue, skin, brain, and cervical spinal cord. The doses received by the OAR are 0.2641 Gy, 0.7645 Gy, 7.3295 Gy, and 0.075 Gy, respectively.

In summary, negative pi-meson therapy has the potential to minimize radiation dose to healthy tissue while cancer still receives high-dose radiation. However, it is necessary to compare negative pi-meson therapy and other radiotherapy methods to determine the strengths and weaknesses of each method.

Glioblastoma, not otherwise specified (NOS), is the most common primary malignant brain tumor. The TRAF3IP2 gene is an upstream regulator responsible for activating multiple proinflammatory pathways that could influence tumor size, angiogenesis, aggressiveness, and metastasis. In the present study, we aimed to investigate and assess the TRAF3IP2 gene expression in brain tumor tissue of patients with glioblastoma, NOS and compare it with non-neoplastic brain tissue. In this case-control study, biopsies were obtained from 15 surgically glioblastoma, NOS removed block samples and 15 non-neoplastic brain tissue samples containing normal white and gray matter as controls. Ribonucleic acid (RNA) was isolated and reverse-transcribed to complementary DNA (cDNA). Quantitative polymerase chain reaction (qPCR) was then carried out to measure TRAF3IP2 gene expression. We evaluated data from 30 cases, divided into two groups: case (N = 15) and control (N = 15). Based on our data, the expression of the TRAF3IP2 gene was 6.95 ± 0.65 times higher in glioblastoma multiforme tissue compared with controls (P < 0.05). We also found no significant difference in TRAF3IP2 gene expression between genders (P = 0.452), and there was no significant correlation between TRAF3IP2 gene expression and age (P = 0.745). The expression of the TRAF3IP2 gene was almost seven times higher in glioblastoma, NOS brain tissue compared with normal brain samples. This finding could have significant clinical and therapeutic implications.

Glioblastoma multiforme (GBM) is an aggressive case of primary brain cancer which remains among the most fatal tumors worldwide. Although, some in vitro and in vivo models have been developed for a better understanding of GBM behavior; a natural model of GBM would improve the efficiency of experimental models of human GBM tumors. We aimed the present study to examine the survival and durability of U87 cells in the brain of wild-type rats.

U87 cells were intracranially implanted in twenty-one wild-type rats. Tumor size and morphology as well as infiltration of immune cells were investigated at three-time points by H&E and immunohistochemistry (IHC).

The results demonstrated that the inoculation of GBM cells led to the infiltration of host defense system cells which caused immunological regression of the tumor mass after six weeks. While the tumors successfully developed without any sign of host defense invasion in the second week of GBM inoculation. Also, a decrease in tumor size and infiltration of immune system cells were observed in the fourth week.

These data remarkably suggest that time plays a crucial role in activating the immune system against human GBM tumors in rats; it shows that the regression of tumor mass depends on a time slope.

 In recent years, many studies have focused on the dysregulation of miRNA expression in cancer. These structures act as oncogenes and suppressors. In the present study, the expression levels of miR-3173-3p and miR-4772-3p were investigated in the tissue of glioblastoma multiforme (GBM) patients and healthy individuals.

 The present study was performed on 50 patients with GBM and 50 healthy individuals as the control group. Real-time PCR technique was used to determine the tissue levels of miR-3173-3p and miR-4772-3p. The biomarker evaluation of miR-3173-3p and miR-4772-3p was assessed using ROC curve analysis.

 The expression level of miR-4772-3p was higher in women with GBM (P-value = 0.03). Increased concentration of miR-3173-3p in tissue of GBM patients showed a significant correlation with a final grade of disease progression (grades III and IV) (P-value = 0.007). ROC curve analysis and cut-off of 0.6939 showed that miR-4772-3p could detect the presence of malignant GBM with 88.89 sensitivity and 100.0 specificity.

 The present study reveals the potential oncogenic role of miR-4772-3p. Moreover, the progression of glioblastoma cancer in the final stages can be assessed by measuring the level of miR-4772-3p in patients’ tissue.

Glioblastoma is the most prevalent and aggressive adult glial tumor. Patients who receive standard treatment have a mean survival of 12-14 months. Zinc is a micronutrient that has shown to have anticancerous effects. In the in vitro studies zinc had antineoplastic effects on gliobalstoma cells. This is a phase II randomized trial in which 60 patients in two groups were evaluated. The zinc group (29 patients) received zinc sulfate supplement 50 mg orally twice a day and the control group (31 patients) who were selected from historical case sreceived no supplements. Mean overall survival in the case and control groups were 9.93 (± 3.29) and 9.0 (± 3.56) months. In the case and control groups, the mean disease-free survival were 9.62 (SD ± 3.37) and 8.26 (SD ± 3.47) months. These differences were not statistically significant. Although overall survival and recurrence-free survival in patients in the case group was higher than the control group, there was no statistically significant difference (P = 0.485). Zinc consumption was associated with better survival, but these differences were not statistically significant, necessitating further studies.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy.

 Brain tumors are all primary central nervous system (CNS) tumors with unclear etiologies and viral infections, especially human herpesviruses, which have emerged as a hot topic for comprehensive research.

 The present study aimed at assessing the molecular epidemiology of varicella-zoster virus (VZV) and its association with microRNA 122 (miR-122) expression in CNS tumor samples.

 Fresh frozen tissue samples were collected from 60 CNS tumor patients and 45 healthy controls. A nested PCR assay was performed to detect the VZV-DNA. Subsequently, the expression level of miR-122 was evaluated in the CNS tumor tissue samples of patients and the brain tissue samples were obtained from healthy controls, using a real-time PCR assay.

 Of 60 patients with CNS tumors, 29 were men and 31 were women. VZV-DNA was detected in 13.3% of the CNS tumor tissue specimens. There was no statistically significant association between the presence of VZV-DNA and different types of CNS tumors (P > 0.05). Furthermore, the expression level of miR-122 was significantly downregulated in the CNS tumor tissue samples obtained from the patients compared with those of the healthy controls (P < 0.05). Additionally, the expression level of miR-122 was significantly lower in the VZV-positive tumor samples as compared with those of the VZV-negative tumor samples and the healthy controls.

 Although VZV plays no direct role in the development of CNS tumors, the virus may affect the biology of CNS tumors by decreasing the expression levels of miR-122, which consequently leads to an increased risk of malignancy. However, the experimental data are not conclusive enough; so, further investigations are needed.

Grade IV neoplasm of the central nervous system, GBM, is associated with poor prognosis and short overall survival.

This study aimed to investigate the effects of conditioned mediums of GBM cell lines on each other.

Conditioned mediums of GBM cell lines were harvested at the 6th, 12th, 24th, and 48th h time points. The cellular and molecular effects of conditioned mediums were evaluated using gold standard techniques such as MTT assay, colony formation assay, wound healing assay, EdU labeling-based flow cytometry, and qRT-PCR.

Our study demonstrated that conditioned medium harvested from U87 or LN229 cells at the 48th h time point exhibited an anti-growth activity on each other by altering the gene expression pattern. Furthermore, the conditioned medium of LN229 decreased the migration capacity of U87 cells, and the conditioned medium of U87 cells significantly suppressed the LN229 proliferation.

Growth-limiting activity achieved by conditioned mediums collected at the 48th h time point positioned them as promising candidates to further investigate their content. It was argued that this initial work provided new insights to expand our current understanding of the roles of GBM cells’ secretome.

Cold Atmospheric Plasma (CAP) has a wide application in medicine that has many biological effects on bacterial, fungal, yeast, and mammalian cells, particularly cancer cells. In this study, the in-vivo anti-tumor effect of an Atmospheric Pressure Jet Plasma (APJP) source is investigated.

The Glioblastoma Multiforme (GBM) tumoric cells have been implanted in the rat brains. Then, cancerian cells are treated by direct CAP and the Temozolomide (TMZ) drug. Positron Emission Tomography (PET) imaging method is used for evaluating the tumor regions.

The PET imaging results showed that the GBM cell has a significant reduction in direct plasma treatment and TMZ drug just. This reduction can be clearly observed just five days after treatment. The calculated Brain to the Background Ratio (BBR) shows that the cancer cells in the plasma method are halved after five days. This amount is comparable to the TMZ method that makes two times decreasing in the cancer cells.

The plasma method can be used as an effective method in treating and removing the GBM cells. Also, CAP has fewer side effects than chemical methods.

Glioblastoma multiforme (GBM) is considered the deadliest human cancer. Temozolomide is now a part of postresection standard chemotherapy for this type of cancer. Unfortunately, resistance to temozolomide is a major obstacle to treatment success. Combination therapy with natural anticancer agents increases the activity of temozolomide against cancer cells.

This study aimed to assess the effects of temozolomide in combination with harmine against GBM cells.

Cancer cells were treated with temozolomide and/or harmine. After 24, 48, 72, and 96 h, the viability of the cells was assessed by the MTT test. The combination index and dose reduction index were determined by CompuSyn software. Tumor invasion potential was investigated by evaluating cell migration, invasion, and adhesion. The real-time PCR technique was done to study the expression pattern of two genes involved in cancer cell invasion. Statistical analysis was performed using one-way analysis of variance and Tukey’s post-hoc test, and differences were considered non-significant at P > 0.05.

After treatment with temozolomide, cell viability showed a concentration- and time-dependent decrease, and the cells’ survival rate decreased. The combination of temozolomide and harmine had a synergistic effect. Also, temozolomide and/or harmine treatment decreased cancer cells’ migration, invasion, and adhesion potentials, as well as the expression of metalloproteinases 2 and 9 in T98G cells.

The combination of temozolomide and harmine can be promising for the successful treatment of GBM.