PGAM4 silencing inhibited glycolysis and chemoresistance to temozolomide in glioma cells.

Gliomas account for about 80% of malignant brain tumors. The incidence of a new brain tumor is 6.4 per 100,000 persons per year with an overall 5-year survival rate of 33.4%. Regardless of the great advances that have been made in recent years, the causes and pathogenesis of glioma remain unclear. Here we study how phosphoglycerate mutase 4 (PGAM4) contributes to glioma. Using a variety of methods to examine glioma cell viability, proliferation, apoptosis, glycolysis, as well as ChIP coanalysis with modified histone H3, we showed that PGAM4 was significantly upregulated in patients with glioma and associated with poor survival. Silencing PGAM4 attenuated cell viability, proliferation, and glycolysis in T98G cells and suppressed tumor growth in vivo, while overexpressing PGAM4 promoted cell viability, proliferation, and glycolysis in U251 cells via regulating glycolysis pathway. Study also revealed that PGAM4 was regulated by EP300-mediated modifications of H3K27ac. PGAM4 silencing inhibited cell viability and proliferation, suppressed tumor growth, and decreased chemoresistance to temozolomide in glioma cells through suppressing glycolysis.

Paeoniflorin Regulates NEDD4L/STAT3 Pathway to Induce Ferroptosis in Human Glioma Cells.

Background: Paeoniflorin is an active component of a widely used traditional Chinese medicine with antitumor activity through ferroptosis induction. It has been reported recently that ferroptosis is emerging in certain types of cancer; however, its relevance in glioma is still not well studied. Methods: CCK8 assay was performed for cell proliferation. Expression of mRNA and protein was tested by qPCR and western blot, respectively. Clinical section samples were detected by IHC. The relationship between NEDD4L and STAT3 was validated by a coimmunoprecipitation assay. Apoptosis was identified by TUNEL assay. A xenograft mouse model was utilized to validate the potential of paeoniflorin toward glioma cancer cells. Results: The data suggested that paeoniflorin could increase NEDD4L expression in glioma cells. The NEDD4L expression level was lower in glioma cancer tissues compared to adjacent normal tissues, and it correlates with poor prognosis. Meanwhile, NEDD4L mediates the ubiquitination of STAT3. Furthermore, increased NEDD4L significantly inhibited cell viability and induced accumulation of intracellular ROS levels, accompanied by decreased expression of key ferroptosis factors Nrl2 and GPX4, while NEDD4L knockdown had a reverse effect, suggesting that ferroptosis could be involved. NEDD4L-induced ferroptosis could be rescued by forced expression of STAT3. A xenograft nude mouse model showed that paeoniflorin inhibits tumor growth and further sensitizes glioma cells to RSL3, another well-known ferroptosis inducer. Conclusions: In summary, this study demonstrated that paeoniflorin might function as an effective drug for glioma by inducing ferroptosis via upregulation of NEDD4L and repression of Nrl2, GPX4, and STAT3.

[Magnetic resonance imaging diagnosis and microsurgical treatment of cavernous sinus hemangiomas].

OBJECTIVE: To summarize the magnetic resonance imaging(MRI)features and microsurgical treatment of cavernous sinus hemangiomas(CSH). METHODS: Twenty-three patients with surgically and pathologically verified CSH were reviewed. All patients underwent computed tomography(CT)and MR scan, 19 cases underwent MR diffusion-weighted imaging(DWI)and 7 underwent single voxel (1)H magnetic resonance spectroscopy((1)HMRS)before operation. The microsurgery through modified pterional approach was performed in 11 cases and 12 cases removal was achieved in combined fronto-temporal preauricular subtemporal approach. Nineteen cases with large tumors were treated by Leksell Gamma knife(LGK)before operation. RESULTS: CSHs were single, large, and spherical/lie gourd-shaped tumors across the inside and outside the sella. CSH showed equal or slightly low signal on T1WI, high signal on T2WI and FLAIR, homogeneous or heterogeneous great enhancement on MR enhancement scan 19 cases showed equal or slightly low signal on DWI, 7 cases showed no NAA, Cr, and Cho peak, and 6 cases showed Lip peak on (1)HMRS. In 23 cases, the tumors were totally removed in 18, subtotally removed in 3, and partially removed in 2. No perioperative death was reported. The postoperative symptoms were improved in 17 cases but remained unchanged in 4 cases two patients suffered from new nervous symptoms after the surgery, which were improved or cured after three weeks of treatment. In 5 patients who had received subtotal or partial removal of the lesions, LGK was performed postoperatively, which resulted in smaller residual tumors in 4 cases and unchanged tumor in one patient. CONCLUSIONS CSH has some unique MRI features, and therefore MRI is helpful to improve the preoperative localization and qualitative diagnosis. The microsurgery through modified pterional approach combined with fronto-temporal preauricular subtemporal approach is an effective procedure for CSH.