In Vivo and In Vitro Biocompatibility Study of CuS Nanoparticles: Photosensitizer for Glioblastoma Photothermal Therapy.

Although photothermal treatment (PTT) has made significant progress in the fight against cancer, certain types of malignant tumors are still difficult to eradicate. PTT uses photothermal transforming agents to absorb NIR light and convert it to thermal energy, causing cancer cell death. In this study, we synthesized alginate (Alg)-coated CuS nanoparticles (CuS@Alg) as photothermal transforming agents to kill glioblastoma cancer cells. Nanoparticles were synthesized via a facile method, then, were characterized with different techniques such as ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Nanoparticles show high stability, and are monodisperse. CuS@Alg was discovered to have a spherical shape, a hydrodynamic size of about 19.93 nm, and a zeta potential of - 9.74 mV. CuS@Alg is able to increase temperature of medium under NIR light. Importantly, in vitro investigations show that PTT based on CuS@Alg has a strong theraputic impact, resulting in much high effectiveness. The LD50 and histopathology assays were used to confirm the NPs' non-toxicity in vivo. Results from an in vivo subacute toxicity investigation showed that the fabricated NPs were perfectly safe to biomedical usage.

Genetic Variations of CARMN Modulate Glioma Susceptibility and Prognosis in a Chinese Han Population.

Background: This study aimed to evaluate the relationship between CARMN polymorphisms and glioma risk and prognosis in a Chinese Han population. Methods: Seven single nucleotide polymorphisms (SNPs) in CARMN were genotyped among 592 glioma patients and 502 healthy controls. Log-additive models were used for risk assessment by the odds ratios (ORs) and 95% confidence intervals (CIs). Univariate and multivariate Cox regression analysis was applied to calculate Hazard ratios (HRs) and 95% CIs for prognosis assessment. Results: CARMN rs13177623 was a protective factor for glioma susceptibility (OR = 0.78, p = 0.043). In addition, rs13177623, rs11168100, rs12654195 and rs17796757 were associated with the risk of glioma among the subgroup stratified by age or gender. We also found that G rs13177623G rs12654195 haplotype was related to the decreased risk of glioma (OR = 0.61, p = 0.005). Importantly, rs13177623 [overall survival (OS): HR = 0.83, p = 0.047, and progression free survival (PFS): HR = 0.82, p = 0.031], rs12654195 (OS: HR = 0.64, p = 0.005 and PFS: HR = 0.65, p = 0.007) and rs11168100 (OS: HR = 0.71, p = 0.035) were associated with a better prognosis for glioma, especially in grade I-II glioma. In patients with grade III-IV glioma, rs17796757 polymorphism presented an improved OS. Conclusion: Our results firstly reported the contribution of CARMN variants (rs11168100, rs12654195, rs13177623, and rs17796757) to the susceptibility and prognosis of glioma in a Chinese Han population, which provided a novel insight on the relationship between CARMN gene and glioma tumorigenesis.

Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.

The ADCY9 genetic variants are associated with glioma susceptibility and patient prognosis.

PURPOSE: Genetic factor is a risk factor in glioma occurrence. This study was designed to detect the effect of ADCY9 polymorphisms on glioma risk and prognosis. METHODS: We performed a case-control study of 1080 participants (584 cases and 496 controls) to assess the relationship of ADCY9 polymorphisms with the risk and prognosis of glioma among the Chinses Han population. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the relationship between ADCY9 variants and glioma risk. The correlation of SNPs with survival was analyzed by the Cox regression model. RESULTS: Our study showed that rs2230742 and rs2531992 polymorphisms played protective roles in glioma susceptibility (OR 0.65, p = 0.001; OR 0.73, p = 0.038, respectively). While rs2230742 significantly increased the susceptibility of III-V grade glioma patients (OR 1.50, p = 0.036). Haplotype analysis revealed that Crs879620Ars2230742Ars2230741 haplotype was related to a significantly decreased glioma risk (OR 0.65, p = 0.002). Notably, rs2531995 and rs879620 polymorphisms significantly enhanced death risk in high-grade glioma patients (hazard ratio [HR] 1.36, p = 0.041; HR 1.37, p = 0.042; respectively). For rs2230742 and rs2531992 SNPs, glioma patients had a worse prognosis (HR 2.30, p = 0.021; HR 2.30, p = 0.021; respectively). We further observed that age, chemotherapy, and surgical scope can affect the glioma prognosis. CONCLUSION: We firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.