Impact of extremely low-frequency electromagnetic field (100 Hz, 100 G) exposure on human glioblastoma U87 cells during Temozolomide administration.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an extremely dismal prognosis, a median survival is12 months. Temozolomide (TMZ) is an alkylating agent widely used to treat cancer, resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. Therefore, the present study was carried out to evaluate the potential synergistic effect of 100 µM TMZ and EMF (100 Hz, 100 G) on human glioma cell line U87 U87 cells with four experimental groups (I-IV) were exposed to ELF-EMF and TMZ for 120 and 144 h, as follows: (I) control; (II) ELF-EMF; (III) TMZ; (IV) ELF-PEMFs / TMZ. mRNA expression of genes such as (Nestin,CD133, Notch4 and GFAP) were investigated by Real-time PCR and western blot. We also evaluated, SOD activity, MDA and calcium concentration by ELISA assay. Co-treatment synergistically decreased the expression of Nestin,CD133, and Notch4 and increased the GFAP genes. We also observed an increase in Superoxide dismutase (SOD) activity, Malondialdehyde (MDA) and Ca2+concentration in comparison to controls.TMZ prevents cancer progression not only through the induction of cell death, but also by inducing differentiation in cancer cells. In addition, our data demonstrate ELF-EMF (100 Hz, 100 G) can significantly enhance the effects of TMZ on human glioblastoma U87 cell. These findings may open new window for future studies.

Cytotoxicity of carboplatin on human glioblastoma cells is reduced by the concomitant exposure to an extremely low-frequency electromagnetic field (50 Hz, 70 G).

Glioblastoma multiforme (GBM) is a malignant brain cancer that causes high mortality in patients. GBM responds weakly to the common cancer treatments such as chemotherapy and radiotherapy and even surgery. Carboplatin is an alkylating agent widely used to treat cancer. However, resistance to this drug is a common problem in its use in cancer treatment. Concomitant exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) and carboplatin is one unexplored possibility for overcoming this resistance. Indeed, many lines of evidence show that EMF affects cancer cells and drug action. In this study, we evaluated the effect of concomitant administration of carboplatin and EMF (50 Hz, 70 G) and also concomitant administration of carboplatin and static magnetic field (SMF) (70 G) on human glioma cell line (U-87). The results showed that cotreatment reduced the efficiency of carboplatin in U-87 cells, by decreasing caspase-3 in comparison to drug groups. Overall, EMF reduced the apoptotic effect of carboplatin, possibly through a redox regulation mechanism. Therefore, we have to avoid coadministration of magnetic field (MF) and carboplatin in tumor area, because the MF decreased the toxicity of the drug. However, further studies are needed to reveal the action mechanism of this combination therapeutic method.

Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G).

Glioblastoma multiforme (GBM) is the most malignant brain cancer that causes high mortality in humans. It responds poorly to the most common cancer treatments, such as surgery, chemo- and radiation therapy. Temozolomide (TMZ) is an alkylating agent that has been widely used to treat GBM; resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. In this study, we evaluated the potential synergistic effect of 100µM TMZ and EMF (100Hz, 100G) on two human glioma cells line, i.e., U87 and T98G above single treatments, TMZ or EMF. Co-treatment synergistically enhanced apoptosis in U87 and T98G cells, by increasing the expression of P53, Bax, and Caspase-3 and decreasing that of Bcl-2 and Cyclin-D1. We also observed an increase in reactive oxygen species (ROS) production and the overexpression of the heme oxygenase-1 (HO-1) gene in comparison to controls. In conclusion, since EMF enhanced the apoptotic effect of TMZ, possibly through a redox regulation mechanism, the TMZ/EMF combination may be effective for glioma cancer treating. Further studies are needed to reveal the action mechanism of this possible novel therapeutic approach.

Effects of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) on glioblastoma cells (U87).

The impact of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) at various frequencies and amplitudes was investigated on cell cycle, apoptosis and viability of the Glioblastoma Multiforme (GBM) cell line (U87), in vitro. The GBM is a malignant brain tumor with high mortality in humans and poorly responsive to the most common type of cancer treatments, such as surgery, chemotherapy and radiation therapy. U87 cells with five experimental groups (I-V) were exposed to various ELF-PEMFs for 2, 4 and 24 h, as follows: (I) no exposure, control; (II) 50 Hz 100 ± 15 G; (III) 100 Hz 100 ± 15 G; (IV) 10 Hz 50 ± 10 G; (V) 50 Hz 50 ± 10 G. The morphology properties, cell viability and gene expression of proteins involved in cell cycle regulation (Cyclin-D1 and P53) and apoptosis (Caspase-3) were investigated. After 24 h, the cell viability and Cyclin-D1 expression increased in Group II (30%, 45%), whereas they decreased in Groups III (29%, 31%) and IV (21%, 34%); P53 and Caspase-3 elevated only in Group III; and no significant difference was observed in Group V, respectively, compared with the control (p < 0.05). The data suggest that the proliferation and apoptosis of human GBM are influenced by exposure to ELF-PEMFs in different time-dependent frequencies and amplitudes. The fact that some of the ELF-PEMFs frequencies and amplitudes favor U87 cells proliferation indicates precaution for the use of medical devices related to the MFs on cancer patients. On the other hand, some other ELF-PEMFs frequencies and intensities arresting U87 cells growth could open the way to develop novel therapeutic approaches.

Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients.

BACKGROUND: In recent years, some studies were conducted to evaluate the effects of stem cells from different sources on patients with spinal cord injury (SCI). This study was carried out to evaluate the feasibility and therapeutic potential of autologous bone marrow cell (BMC) transplantation in 11 complete spinal cord injured patients at thoracic level. METHODS AND MATERIALS: This nonrandomized clinical trial compared the results of autologous BMC transplantation into cerebrospinal fluid (CSF) via lumbar puncture (LP) in 11 patients having complete SCI, with 20 patients as control group who received conventional treatment without BMC transplantation. The patients underwent preoperative and follow-up neurological assessments using the American Spinal Injury Association (ASIA) impairment scale. Then, the participants were followed for 12-33 months. RESULTS: Eleven patients with the mean age of 33.2±8.9 years and 20 patients with the mean age of 33.5±7.2 years were enrolled in the study and in the control group, respectively. None of the patients in the study and control group experienced any adverse reaction and complications, neither after routine treatment nor after cell transplantation. Five patients out of 11 (45.5%) in the study group and three patients in the control group (15%) showed marked recovery, but the result was statistically borderline (P=0.095). CONCLUSION: We conclude that transplantation of autologous BMC via LP is a feasible and safe technique, but at the moment, no clear answer can be given regarding the clinical potential, despite a potential tendency to treat SCI patients, observed through statistics.

The role of stem cells in tumor targeting and growth suppression of gliomas.

Glioma remains the most challenging solid organ tumor to treat successfully. Based on the capacity of stem cells to migrate extensively and target invading glioma cells, the transplantation of stem cells as a cell-based delivery system may provide additional tools for the treatment of gliomas. In addition to the use of modified stem cells for the delivery of therapeutic agents, unmodified stem cells have been shown to have growth-suppressing effects on tumors in vitro and in vivo. This review outlines the probable factors involved in tumor tropism and tumor growth suppression, with a specific focus on the use of unmodified stem cells in the treatment of gliomas. Based on these and further future data, clinical trials may be justified.

Effect of atorvastatin on angiogenesis in degenerated intervertebral disc in rat.

STUDY DESIGN: An experimental study to measure the depth of penetration of new vessels in degenerated intervertebral disc in rat. OBJECTIVE: To evaluate the effects of atorvastatin on angiogenesis in experimental disc degeneration in rat. SUMMARY OF BACKGROUND DATA: Back pain is strongly associated with degenerated intervertebral disc and management of this condition is still empirical. Decrease of nucleus nutrition due to loss of vascularity with aging may aggravate the process of disc degeneration. So, angiogenesis may be useful in the healing process of degenerated disc. In this study, we wanted to evaluate the effect of atorvastatin, whose stimulating effect on angiogenesis on other tissues was shown in several studies, on degenerated intervertebral disc in rat. METHODS: Atorvastatin was administered intraperitoneally for 6 weeks in doses of 1, 4, and 8 mg/kg in rats after experimental disc degeneration. The rats intervertebral disc sections were stained immunohistochemically for von Willebrand Factor to evaluate the depth of vessels penetration and degree of vascularity. RESULTS: In the nonoperated control group, the intervertebral discs were avascular. But experimental disc degeneration promoted angiogenesis. In this group, the mean of penetration was 49.25 µ (standard deviation = 19.905). Atorvastatin stimulated angiogenesis after experimental disc degeneration in the rats and the angiogenesis was more significant in the high and medium dose groups than operated control group. High-dose atorvastatin could not inhibit angiogenesis in experimental degenerated disc. There was no any significant difference in degree of vascularity among the groups. CONCLUSION: Atorvastatin stimulates angiogenesis in experimental disc degeneration in rats. But, it does not show a biphasic effect.

Frequency of lumbar intervertebral disc calcification and angiogenesis, and their correlation with clinical, surgical, and magnetic resonance imaging findings.

STUDY DESIGN: This study measured the frequency of lumbar intervertebral disc nucleus pulposus microscopic calcification and angiogenesis in adult patients undergoing discectomy compared to normal cadavers. OBJECTIVE: The results were compared to determine the relationship between disc microscopic calcification with disc degeneration type, histopathological angiogenesis, patients' age, gender, and duration of symptoms. SUMMARY OF BACKGROUND DATA: True frequency of microscopic calcification in normal or degenerated lumbar discs have not been fully defined nor linked to disc degeneration type and angiogenesis. Some studies demonstrated that angiogenesis and calcification are related to each other in several another tissues. METHODS: The frequency of microscopic calcification in specimens of disc nucleus pulpous obtained from 2 groups were measured: specimens were obtained during surgery from 90 consecutive patients of 15 to 50 years old suffering from disc herniation in single level of L4-L5 or L5-S1 between 2005 and 2006, 60 additional specimens of lumbar disc nucleus pulposus were obtained from normal cadavers of the same ages. Calcification was determined microscopically by Von Kossa staining and angiogenesis by H/E, and type of degeneration radiologically by Modic classification. RESULTS: Frequency of microscopic calcification was significantly higher in degenerated disc than normal cadaveric (54.4% vs. 6.7%) and was higher in Modic type III than type I (III: 95.0%, II: 57.4%, I: 13.0%), also prevalence of angiogenesis was significantly higher in patients than cadaveric discs (41.0% vs. 6.7%) and in calcified than noncalcified discs (59.2% vs. 19.5%) (P < 0.001). There was no relationship between disc calcification and patients' gender and level of discectomy. CONCLUSION: Disc nucleus pulposus microscopic calcification is a common event occurring in adult patients suffering from lumbar disc herniation. Mechanisms that link disc degeneration, angiogenesis, and calcification remain a focus for further researches that may be useful in future medical treatments before surgical treatment of lumbar disc herniation.

Skull indices in a population collected from computed tomographic scans of patients with head trauma.

BACKGROUND: It is important to find out the skull's anatomic indices with computed tomography (CT), especially the skull's dimensions according to the patients age and sex, because it can give important results in neurosurgery. We will also describe the skull's parameters among the Kerman population. METHOD: Of the 2000 CT scans taken after head trauma injury in Kerman province from June 2002 to September 2006, we analyzed 1034 good quality films. The most frequent skull dimensions were measured on each film, and the data were computed and analyzed to assess the cranial indices in various ages and sexes. Two types of classifications were carried out: classic method, which uses cranial indices, and posterior fossa angle dimensions as an alternative method. Skull dimensions were statistically analyzed between groups, and any difference greater than 0.05 was considered significant. RESULTS: Of the 1034 films, 871 films belonged to the men and 184 to the women at age older than 5 years and younger than 70 years. Most of the CT films belonged to the patients with age older than 20 years and younger than 40 years in both sexes. Although the rates of various skull types were different according to the method of classification, the most frequent skull type was dolichocephalic followed by mesocephalic and brachycephalic in both sexes. In addition, in both sexes, the frequency of dolichocephaly was greater in children than adults, but brachycephaly was more frequent in adults than children. CONCLUSIONS: With CT scans as an accurate and suitable source of anthropometric evaluation of body dimensions, we found that, in our population, the most frequent skull type is dolichocephalic followed by mesocephalic, which seems to be closer to the Anglo-Saxon population considering the rates of dolichocephaly and mesocephaly.

Incidental findings in brain computed tomography scans of 3000 head trauma patients.

BACKGROUND: Limited reports exist about intracranial incidental findings on computed tomography (CT) imaging. We studied the frequency of incidental findings on 3000 brain CT scans of trauma patients. METHODS: Three thousands standard brain CT scans of trauma patients were evaluated for some incidental findings. Cisterna magna was evaluated in 1500 CT scans. RESULTS: In this study we found 30 incidental abnormalities that include 8 cases of tumor: 3 meningioma, 2 craniopharyngioma, 1 oligodendroglioma, 1 low-grade astrocytoma, and 1 medulloblastoma. Suspect osteoma was found in 3 cases. In 3 cases, abnormal calcification was found in pineal region, basal ganglia, and temporal horn area. Three suspect lipomas were found in midline and near midline of the brain. Arachnoid cyst was found in 7 cases and hydrocephaly in 3 cases. Large cisterna magna (>10 cm(3)) was found in 11 cases. CONCLUSION: Cisterna magna enlargement was the most common incidental finding and brain tumor and arachnoid cyst were next in frequency.