Exposure to Low-Frequency Radiation Changes the Expression of Nestin, VEGF, BCRP and Apoptosis Markers During Glioma Treatment Strategy: An In Vitro Study.

BACKGROUND: Exposure to physical contamination during chemotherapy, including non-ionizing electromagnetic fields, raises concerns about the widespread sources of exposure to this type of radiation. Glioblastoma multiforme (GBM) is an aggressive central nervous system tumor that is hard to treat due to resistance to drugs such as temozolomide (TMZ). OBJECTIVE: Electromagnetic fields (EMF) and haloperidol (HLP) may have anticancer effects. In this study, we investigated the effects of TMZ, HLP, and EMF on GBM cell lines and analyzed the association between non-ionizing radiation and the risk of change in drug performance. METHODS: Cell viability and reactive oxygen species (ROS) generation were measured by MTT and NBT assay, respectively. Then, the expression levels of breast cancer-resistant protein (BCRP), Bax, Bcl2, Nestin, vascular endothelial growth factor (VEGF) genes, and P53, Bax, and Bcl2 Proteins were evaluated by real-time PCR and western blot. RESULTS: Co-treatment of GBM cells by HLP and TMZ enhanced apoptosis in T-98G and A172 cells by increasing the expression of P53 and Bax and decreasing Bcl-2. Interestingly, exposure of GBM cells to EMF decreased apoptosis in the TMZ+HLP group. CONCLUSION: In conclusion, EMF reduced the synergistic effect of TMZ and HLP. This hypothesis that patients who are treated for brain tumors and suffer from depression should not be exposed to EMF is proposed in the present study. There appears to be an urgent need to reconsider exposure limits for low-frequency magnetic fields, based on experimental and epidemiological research, the relationship between exposure to non-ionizing radiation and adverse human health effects.

Chitosan-sialic acid nanoparticles of selenium: Statistical optimization of production, characterization, and assessment of cytotoxic effects against two human glioblastoma cell lines.

According to the favorable antitumor properties of selenium, this study aimed to design a novel form of selenium nanoparticles (Se NPs) functionalized with chitosan (Cs) and sialic acid to assess their antitumor effects on the human glioblastoma cell lines (T98 and A172). Se NPs were synthesized in the presence of chitosan and ascorbic acid (Vc) and the synthesis conditions were optimized using response surface methodology. Se NPs@Cs were obtained with a monoclinic structure with an average diameter of 23 nm under the optimum conditions (reaction time = 30 min, chitosan concentration = 1 % w/v, Vc/Se molar ratio = 5). To modify Se NP@Cs for glioblastoma treatment, sialic acid was used to cover the surface of the NPs. Sialic acid was successfully attached to the surface of Se NPs@Cs, and Se NPs@Cs-sialic acid were formed in the size range of 15-28 nm. Se NPs@Cs-sialic acid were stable for approximately 60 days at 4 ℃. The as-synthesized NPs exerted inhibitory effects on T98 greater than 3 T3 > A172 cells in a dose- and time-dependent manner. Additionally, sialic acid ameliorated the blood biocompatibility of Se NPs@Cs. Taken together, sialic acid improved both the stability and biological activity of Se NPs@Cs.

Comparative Study of Extremely Low-Frequency Electromagnetic Field, Radiation, and Temozolomide Administration in Spheroid and Monolayer Forms of the Glioblastoma Cell Line (T98).

BACKGROUND: Glioblastoma is the most common primary malignant tumor of the central nervous system. The patient's median survival rate is 13.5 months, so it is necessary to explore new therapeutic approaches. OBJECTIVE: Extremely low-frequency electromagnetic field (EMF) has been explored as a noninvasive cancer treatment. This study applied the EMF with previous conventional chemoradiotherapy for glioblastoma. METHODS: In this study, we evaluated the cytotoxic effects of EMF (50 Hz, 100 G), temozolomide (TMZ), and radiation (Rad) on gene expression of T98 glioma cell lines in monolayer and spheroid cell cultures. RESULTS: Treatment with Rad and EMF significantly increased apoptosis-related gene expression compared to the control group in monolayers and spheroids (p<0.001). The expression of apoptotic-related genes in monolayers was higher than the similar spheroid groups (p<0.001). We found that treatment with TMZ and EMF could increase the gene expression of the autophagy cascade markers compared to the control group (p<0.001). Autophagy-related gene expression in spheroids was higher than in the similar monolayer group (p<0.001). We demonstrated that coadministration of EMF, TMZ, and Rad significantly reduced cell cycle and drug resistance gene expression in monolayers and spheroids (p<0.001) compared to the control group. CONCLUSION: The combinational use of TMZ, Rad and, EMF showed the highest antitumor activity by inducing apoptosis and autophagy signaling pathways and inhibiting cell cycle and drug resistance gene expression. Furthermore, EMF increased TMZ or radiation efficiency.

Opioid replacement therapy with methadone or buprenorphine effects on male mice reproduction.

RATIONALE: Opioid use disorders are commonly treated by long-acting agonist opioids including methadone and buprenorphine which could affect various aspects of male reproduction especially spermatogenesis. OBJECTIVES: We aimed to determine whether detoxification with methadone or buprenorphine was associated with reproductive disorders in male mice. METHODS: We orally induced morphine dependence in NMRI male mice, and then performed detoxification programs using either methadone or buprenorphine. Testis architecture and sperm parameters including sperm nuclear DNA integrity, mitochondrial activity, oxidative stress in seminal plasma, and routine sperm parameters were assessed to find the involved mechanisms. RESULTS: The number of Leydig cells and the thickness of germinal epithelium reduced following morphine use and increased differently after detoxification with methadone or buprenorphine. Morphine dependence and detoxification with methadone and buprenorphine had different effects on sperm parameters. Morphine altered chromatin integrity, mitochondrial activity, and oxidative stress in sperm. Detoxification with methadone improved mitochondrial activity but worsened chromatin integrity, whereas detoxification with buprenorphine improved neither chromatin integrity nor mitochondrial activity. Seminal plasma oxidative stress was higher in the treated groups compared to control groups but was comparable among treatment groups. Our study revealed that long-term morphine use followed by detoxification with methadone or buprenorphine impairs testis structure and sperm parameters. Detoxification from morphine use with methadone and buprenorphine led to different preclinical outcomes in semen quality parameters, including chromatin integrity. Therefore, clinical detoxification protocols should be performed more cautiously, considering the desire of the individuals to reproduce.