Treadmill exercise and wheel exercise improve motor function by suppressing apoptotic neuronal cell death in brain inflammation rats.

Brain inflammation is involved in many brain disorders, such as brain ischemic injury, Alzheimer diseases, and Parkinson disease. Physical exercise has been recommended for the prevention and treatment of many brain inflammatory diseases. In the present study, the effects of exercise on motor function in relation with apoptotic neuronal cell death following neuroinflammation were investigated. Moreover, we compared the effect of forced exercise with voluntary exercise on neuroinflammation-induced motor malfunction. For this study, rota-rod test, vertical pole test, foot fault test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for Bcl-2 and Bax were performed. Lipopolysaccharide was intraventricular infused for induction of brain inflammation. Treadmill exercise and wheel exercise were conducted during 6 weeks. In the present results, Treadmill exercise and wheel exercise alleviated brain inflammation-induced motor impairments by suppressing apoptotic neuronal cell death in the motor cortex. These effects of treadmill exercise and wheel exercise were similarly appeared.

Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo.

Even with aggressive treatment involving radiation therapy plus temozolomide (TMZ), the prognosis for glioblastoma remains poor. We investigated the potential for targeting signal transducer and activator of transcription-3 (STAT3) to improve the therapeutic outcome in glioblastoma. We evaluated the preclinical potential of a STAT3 inhibitor, Cpd188, combined with temozolomide and radiation using in vitro assays with two established glioblastoma cell lines (U251 and U87) and two patient-derived glioblastoma cell lines (GBL12 and GBL28) as well as in vivo studies with nude mice bearing intracranial U251 xenografts. Cpd188 potentiated the radiosensitizing effect of TMZ in U251 cells, which have high p-STAT3 expression levels. The enhanced radiosensitizing effects of TMZ were associated with impaired DNA damage repair, apoptosis and reversion of the epithelial-mesenchymal transition (EMT). Cpd188 delayed in vivo tumor growth alone and in combination with radiation and TMZ. We also confirmed the radiosensitizing effect of Cpd188 in GBL28 cells, which were originated from a patient with a high level of STAT3 expression and unmethylated MGMT. Targeting STAT3 using Cpd188 could be a viable therapeutic approach for improving the outcome of current standard therapy in glioblastoma patients with high p-STAT3 expression.

Radial displacement of clinical target volume in node negative head and neck cancer.

PURPOSE: To evaluate the radial displacement of clinical target volume in the patients with node negative head and neck (H&N) cancer and to quantify the relative positional changes compared to that of normal healthy volunteers. MATERIALS AND METHODS: Three node-negative H&N cancer patients and five healthy volunteers were enrolled in this study. For setup accuracy, neck thermoplastic masks and laser alignment were used in each of the acquired computed tomography (CT) images. Both groups had total three sequential CT images in every two weeks. The lymph node (LN) level of the neck was delineated based on the Radiation Therapy Oncology Group (RTOG) consensus guideline by one physician. We use the second cervical vertebra body as a reference point to match each CT image set. Each of the sequential CT images and delineated neck LN levels were fused with the primary image, then maximal radial displacement was measured at 1.5 cm intervals from skull base (SB) to caudal margin of LN level V, and the volume differences at each node level were quantified. RESULTS: The mean radial displacements were 2.26 (±1.03) mm in the control group and 3.05 (±1.97) in the H&N cancer patients. There was a statistically significant difference between the groups in terms of the mean radial displacement (p = 0.03). In addition, the mean radial displacement increased with the distance from SB. As for the mean volume differences, there was no statistical significance between the two groups. CONCLUSION: This study suggests that a more generous radial margin should be applied to the lower part of the neck LN for better clinical target coverage and dose delivery.

Feasibility of deformation-independent tumor-tracking radiotherapy during respiration.

To evaluate the feasibility of tumor-tracking radiotherapy that does not consider tumor deformation during respiration. Four-dimensional computed tomography (4D-CT) data, which considers 10 phases of the respiration cycle, were acquired in 4 patients with lung cancer and 4 patients with liver cancer. Initial treatment plans were established at the end of the inhalation phase (phase 1). As a simulation of deformation-free tumor-tracking radiotherapy, the beam center of the initial plan was moved to the tumor center for all other phases, and the tumor shape acquired from phase 1 was used for all 10 phases. The feasibility of this method was analyzed based on assessment of equivalent uniform dose (EUD), homogeneity index (HI) and coverage index (COV). In photon radiation treatment, movement-induced dose reduction was not particularly significant, with 0.5%, 17.3% and 2.8% average variation in EUD, HI and COV, respectively. In proton radiation treatment, movement-induced dose reduction was more significant, with 0.3%, 40.5% and 2.2% average variation in EUD, HI and COV, respectively. Proton treatment is more sensitive to tumor movement than is photon treatment, and that it is reasonable to disregard tumor deformation during photon therapy employing tumor-tracking radiotherapy.

Short-term effects of combined serial casting and botulinum toxin injection for spastic equinus in ambulatory children with cerebral palsy.

PURPOSE: The purpose of this paper is to test the hypothesis that combination therapy of serial cast and botulinum toxin type A (BTX-A) injection can further enhance the effects of a BTX-A injection in ambulant children with cerebral palsy (CP) who have an equinus foot. MATERIALS AND METHODS: Children in group A (30 legs of 21 children) received a serial casting application after an injection of BTX-A, and children in group B (25 legs of 17 children) received only a BTX-A injection. Assessments were performed before the intervention and 1 month after the intervention. RESULTS: After the intervention, there were significant improvements in tone, dynamic spasticity, and passive range of motion (ROM) in both groups. However, the changes were greater in group A than in group B. Dimension D (standing) in Gross Motor Function Measure (GMFM)-66 was significantly improved in group A but not in group B. On the other hand, there were no significant changes in dimension E (walking, running, jumping) in GMFM-66 in either group. CONCLUSION: The results of our study suggest that a serial casting application after BTX-A injection can enhance the benefits of BTX-A injection in children with cerebral palsy.