scholarly journals Differential Regulation of the EGFR/PI3K/AKT/PTEN Pathway between Low- and High-Grade Gliomas

2021 ◽  
Vol 11 (12) ◽  
pp. 1655
Author(s):  
Alveiro Erira ◽  
Fernando Velandia ◽  
José Penagos ◽  
Camilo Zubieta ◽  
Gonzalo Arboleda

Gliomas represent 70% of all central system nervous tumors and are classified according to the degree of malignancy as low- or high-grade. The permanent activation of the EGFR/PI3K/AKT pathway by various genetic or post-translational alterations of EGFR, PI3KCA, and PTEN has been associated with increased proliferation and resistance to apoptosis. The present study aimed to analyze the molecular/genetic changes in the EGFR/PI3K/AKT/PTEN pathway between low-grade and high-grade gliomas in a sample of Colombian patients. A total of 30 samples were tested for PI3K and PTEN mutations, EGFR, PI3K, and AKT gene amplification, AKT, PI3K, BAX, Bcl2 expression levels, and phosphorylation of AKT and PTEN, EGFR and/or PI3K gene amplification was found in 50% of low-grade and 45% of high-grade ones. AKT amplification was found in 25% of the low-grade and 13.6% of the high-grade. The expression of PI3K, AKT, Bcl2, and BAX was increased particularly to a high degree. AKT phosphorylation was found in 66% of low-grade and 31.8% of high-grade. Increased phosphorylation of PTEN was found in 77% low-grade and 66% high-grade. Our results indicate that alterations in the EGFR/PI3K/AKT/PTEN pathway could be important in the initiation and malignant progression of this type of tumor.

2021 ◽  
pp. 1-8
Author(s):  
Haimei Cao ◽  
Xiang Xiao ◽  
Jun Hua ◽  
Guanglong Huang ◽  
Wenle He ◽  
...  

Objectives: The present study aimed to study whether combined inflow-based vascular-space-occupancy (iVASO) MR imaging (MRI) and diffusion-weighted imaging (DWI) improve the diagnostic accuracy in the preoperative grading of gliomas. Methods: Fifty-one patients with histopathologically confirmed diffuse gliomas underwent preoperative structural MRI, iVASO, and DWI. We performed 2 qualitative consensus reviews: (1) structural MR images alone and (2) structural MR images with iVASO and DWI. Relative arteriolar cerebral blood volume (rCBVa) and minimum apparent diffusion coefficient (mADC) were compared between low-grade and high-grade gliomas. Receiver operating characteristic (ROC) curve analysis was performed to compare the tumor grading efficiency of rCBVa, mADC, and the combination of the two parameters. Results: Two observers diagnosed accurate tumor grade in 40 of 51 (78.4%) patients in the first review and in 46 of 51 (90.2%) in the second review. Both rCBVa and mADC showed significant differences between low-grade and high-grade gliomas. ROC analysis gave a threshold value of 1.52 for rCBVa and 0.85 × 10−3 mm2/s for mADC to provide a sensitivity and specificity of 88.0 and 81.2% and 100.0 and 68.7%, respectively. The area under the ROC curve (AUC) was 0.87 and 0.85 for rCBVa and mADC, respectively. The combination of rCBVa and mADC values increased the AUC to 0.92. Conclusion: The combined application of iVASO and DWI may improve the diagnostic accuracy of glioma grading.


2020 ◽  
Vol 79 (10) ◽  
pp. 1038-1043
Author(s):  
Meaghan Morris ◽  
Meghan Driscoll ◽  
John W Henson ◽  
Charles Cobbs ◽  
LiQun Jiang ◽  
...  

Abstract Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.


2003 ◽  
Vol 20 (2) ◽  
pp. 59-63 ◽  
Author(s):  
Teruo Sasaki ◽  
Hiroshi Arai ◽  
Takaaki Beppu ◽  
Kuniaki Ogasawara

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Pinar Atukeren ◽  
Ahmad Kunbaz ◽  
Okan Turk ◽  
Rahsan Kemerdere ◽  
Mustafa Onur Ulu ◽  
...  

Objective. Endocan has been shown to be a marker for several cancers and may show degree of malignancy. The aim of this study is to assess tissue levels of endocan in common brain tumors, namely, meningiomas, low-grade gliomas (LGGs), and high-grade gliomas (HGGs).Patients and Methods. Endocan was assayed by commercially available enzyme linked immunosorbent assay (ELISA) kits in a total of 50 brain tumors (20 meningiomas, 19 LGGs, and 20 HGGs) and 15 controls. The results were compared to control brain tissues.Results. Each tumor group showed significant higher levels of endocan compared to controls (p<0.05). In addition, endocan levels showed steady increase from the least (meningiomas) to the most (HGGs) malignant tumors and positive correlation was noted between the degree of malignancy and endocan level (p=0.0001).Conclusion. Endocan, a vital molecule for angiogenesis, is expressed in common brain tumors and results suggest that endocan could be a marker for malignancy.


2016 ◽  
Vol 29 (5) ◽  
pp. 400-407 ◽  
Author(s):  
Lamiaa El-Serougy ◽  
Ahmed Abdel Khalek Abdel Razek ◽  
Amani Ezzat ◽  
Hany Eldawoody ◽  
Ahmad El-Morsy

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Li-qiang Liu ◽  
Li-fei Feng ◽  
Cheng-rui Nan ◽  
Zong-mao Zhao

The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR. Survival rates for population of the CREB3L1- and PTN-presenting patients were examined. CREB3L1+ cell counts were decreased with increased PTN+ cells in the low-grade and high-grade glioma tissues as compared with the control. Population proportion of the CREB3L1+-presenting patients decreased from the control to the high-grade glioma and the population of the PTN+-presenting patients increased in low- and high-grade gliomas as compared with the control (both P<0.05). The decrease in the CREB3L1 mRNA expression was associated with the increase in the PTN mRNA expression in the low- and high-grade gliomas (P<0.05). Survival time for patients with CREB3L1− and PTN+ gliomas was shorter than patients with CREB3L1+ and PTN− gliomas in the investigated cohorts (both P<0.05). There was a relationship between the expression levels of both proteins and survival time. CREB3L1 and PTN expression levels serve as biomarkers with utility in grading gliomas. Absence of CREB3L1 and presence of PTN in brain glioma cells correlate with survival time of the glioma patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yuankai Lin ◽  
Jianrui Li ◽  
Zhiqiang Zhang ◽  
Qiang Xu ◽  
Zhenyu Zhou ◽  
...  

Gliomas grading is important for treatment plan; we aimed to investigate the application of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in gliomas grading, by comparing with the three-dimensional pseudocontinuous arterial spin labeling (3D pCASL). 24 patients (13 high grade gliomas and 11 low grade gliomas) underwent IVIM DWI and 3D pCASL imaging before operation; maps of fast diffusion coefficient (D∗), slow diffusion coefficient (D), fractional perfusion-related volume (f), and apparent diffusion coefficient (ADC) as well as cerebral blood flow (CBF) were calculated and then coregistered to generate the corresponding parameter values. We found CBF andD∗were higher in the high grade gliomas, whereas ADC,D, andfwere lower (allP<0.05). In differentiating the high from low grade gliomas, the maximum areas under the curves (AUC) ofD∗, CBF, and ADC were 0.857, 0.85, and 0.902, respectively. CBF was negatively correlated withfin tumor (r=-0.619,P=0.001). ADC was positively correlated withDin both tumor and white matter (r=0.887,P=0.000andr=0.824,P=0.000, resp.). There was no correlation between CBF andD∗in both tumor and white matter (P>0.05). IVIM DWI showed more efficiency than 3D pCASL but less validity than conventional DWI in differentiating the high from low grade gliomas.


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