AGR2 Gene Expression in Glioblastoma: A Novel Molecular Potential Target for Diagnosis and Treatment.

AIM: To assess anterior gradient protein 2 (AGR2) gene expression in patients with human glioblastoma (GBM) in comparison to levels in healthy brain tissues. MATERIAL AND METHODS: We evaluated the expression levels of AGR2 gene in 34 tissue samples: 29 of them were derived from patients with glioblastoma (GBM group) and 5 were derived from patients with mesial temporal lobe epilepsy (control group). Moreover, in order to demonstrate the AGR2 gene expression, we performed RNA isolation from tissue samples, cDNA acquisition from RNA via reverse transcription and the demonstration of gene expression via real-time polymerase chain reaction. We therefore confirmed findings of both groups. RESULTS: The mean age of the GBM and control groups were 53.1 ± 12.82 years and 40.4 ± 10.92 years respectively. AGR2 gene expression levels of the GBM group were significantly higher than those of the control group (p < 0.01). There were no significant differences of AGR2 gene expression levels across age groups, levels of glucose, urea, creatinine, white blood cell count (WBC), neutrophil, lymphocyte, hemoglobin, platelet, thyroid-stimulating hormone (TSH), T3 and T4 in GBM group (p > 0.05). CONCLUSION: AGR2 gene expression was significantly higher in patients with GBM. Thus, AGR2 gene can be considered as a potential therapeutic target.

The Evaluation of Survivin and Bcl-2 Expression on the Medical Radiation Doses for Neural Tube Defect Development.

AIM: To investigate the effects of different radiation doses on the development of the neural tube defect in chick embryos using computed tomography (CT), and assess its correlation with survivin and Bcl-2 expressions. MATERIAL AND METHODS: A total of 150 chicken eggs were used and grouped into five categories. In Group 1 (n=30), the embryos were not exposed to radiation. In Group 2 (n=30), the embryos were irradiated using lung cancer screening chest CT protocol. In Groups 3 and 4 (n=30 each), the abdominopelvic and adult routine head CT protocols, respectively, were used to irradiate the embryos. In Group 5 (n=30), the embryos were irradiated using adult brain perfusion CT protocol. Subsequently, the embryos were examined under a stereomicroscope to assess the presence of neural tube developmental abnormalities. Moreover, immunohistochemical staining was performed to determine the survivin and Bcl-2 expression levels. RESULTS: The risk of developing neural tube defect increased with the amount of exposed radiation. Moreover, no significant correlation was observed between the survivin and Bcl-2 expression levels and the radiation dose. CONCLUSION: Overall, the results of this study indicate that the radiation from CT may cause neural tube defect in chicken embryos.

Effects of Different Therapeutic Radiation Doses on the Development of Neural Tube Defects in Chick Embryos and the Correlation with Bone Morphogenetic Protein 4 and 7 Expression Levels.

AIM: To investigate the effects of different therapeutic radiation doses on the prevalence of neural tube defects (NTDs) in chick embryos and bone morphogenetic protein (BMP) 4 and BMP7 expression levels. MATERIAL AND METHODS: The chick embryos (n=143) were derived from fertile, specific pathogen-free eggs of domestic fowl. The presence of NTDs was analyzed using a stereomicroscope, and BMP4 and BMP7 expression levels were assessed by immunohistochemical staining. The chick embryos were divided into five groups: control (no radiation exposure) (n=23), exposure to thorax computerized tomography (CT) (n=30); exposure to abdominopelvic CT (n=30), exposure to cranium CT (n=30), and exposure to brain perfusion CT (n=30). RESULTS: The prevalence of NTDs and BMP4 and BMP7 expression levels in the different groups were compared. In the cranium CT dose group, both the NTD prevalence (20%, p=0.002) and BMP7 (p=0.031) expression levels were significantly higher than those in the other groups. However, none of the medical doses of irradiation altered BMP4 expression levels (p=0.242). No NTDs were detected in the thorax CT and abdominopelvic CT groups. CONCLUSION: Exposure to irradiation at cranium CT doses may induce the development of NTDs and increase BMP7 expression. Dose radiation exposure using thorax CT and abdominopelvic CT protocols does not appear to induce NTDs.

Effect of Cetuximab on the Development of Epidural Fibrosis Based on CD105 and Osteopontin Immunohistochemical Staining.

STUDY DESIGN: The effect of cetuximab on the development of epidural fibrosis (EF) was assessed using immunohistochemical methods as well as antibodies for CD105 and osteopontin (OPN). OBJECTIVE: The goal of this study was to assess of EGFR inhibition for the postoperative treatment of fibrosis. SUMMARY OF BACKGROUND DATA: EF is one of most common causes of failed back surgery syndrome, which occurs after laminectomy. Numerous causes and mechanisms have been proposed to explain its development after laminectomy. Many agents have been tested to prevent the development of EF. EGFR, a multi-functional transmembrane glycoprotein, causes cell growth, proliferation, and EF by interacting with epidermal growth factor and TGF-ß1. The inhibition of postoperative fibrosis using cetuximab, an epidermal growth factor receptor blocker, is theoretically possible. However, this has not been tested to date. METHODS: Sixteen Wistar-Albino rats were divided into two groups, namely, control and cetuximab groups. L1-2 laminectomy alone was performed in both groups, and topical cetuximab was applied to the treatment group. After 6 weeks, rats were sacrificed and examined histopathologically and immunohistochemically; EF tissue was also graded. Statistical significance was accepted at P < 0.05. RESULTS: Fibroblast counts and fibrosis density, determined by histopathologic examination, and EF, according to immunohistochemical assessment based on CD105, were found to be higher in the treatment group than in the control group, and this was statistically significant (P < 0.001). Based on OPN staining, the results were consistent with classical methods, and no significant difference was detected among the groups (P = 0.358). CONCLUSION: Our study revealed that cetuximab inhibits the development of EF and that CD105, and not OPN, is a reliable marker for grading EF. In addition, cetuximab did not result in toxic, systemic side effects in surrounding tissues. LEVEL OF EVIDENCE: N/A.

Impact of sorafenib on epidural fibrosis: An immunohistochemical study.

AIM: To determine if sorafenib, an antineoplastic agent, could prevent the development of spinal epidural fibrosis (EF). METHODS: The study used CD105 and osteopontin antibodies in an immunohistochemical approach to quantify EF that occurred as a consequence of laminectomy in rats. Wistar albino rats (n = 16) were divided into two groups: control (L1-2 level laminectomy only) and sorafenib treatment (L1-2 level laminectomy + topical sorafenib). The animals were euthanatized after 6 wk, and the EF tissues were examined for histopathological changes after immunohistochemical staining. The EF grades were assigned to the tissues, and the treatment and control groups were compared. RESULTS: The EF thickness, inflammatory cell density, and arachnoid adherences determined by light microscopy were significantly higher in the control group compared to the sorafenib-treated group. Based on fibrosis scores, the extent of EF in the treatment group was significantly lower than in the controls. Immunohistochemical staining for CD105 to identify microvessels revealed that the EF grades based on vessel count were significantly lower in the treatment group. Staining for osteopontin did not show any significant differences between the groups in terms of the extent of EF. The staging of EF based on vascular counts observed after immunohistochemical staining for CD105, but not for osteopontin, was compatible with conventional staging methods. Neither toxic effects on tissues nor systemic side effects were observed with the use of sorafenib. CONCLUSION: Local administration of sorafenib significantly reduced post-laminectomy EF. Decreased neovascularization in spinal tissue may be due to the sorafenib-induced inhibition of vascular endothelial growth factor.

Morphometric Analysis of the Effects of Manuka Honey on Vasospastic Femoral Arteries in Rats: An Experimental Study.

OBJECTIVES: The aim of this study was to determine if Manuka honey, a potent anti-inflammatory and antioxidant agent, had any effect on the development of vasospasm in an experimental subarachnoidal hemorrhage model constructed in rat femoral arteries. METHODS: Twenty-four Wistar Albino strain rats were divided into 3 groups: Group 1 was the control group (n=8), Group 2 was the vasospasm group (n=8), and group 3 was the treatment group (n=8). The wall thickness (W) of the femoral arteries and the luminal diameter (L) were measured using morphometric methods. The data were analyzed with statistical software. The Mann-Whitney U-test was used to compare independent groups and Bonferroni post hoc analysis was used for multiple comparison tests. Significance for all of the results was established at p<0.05. RESULTS: A statistically significant intergroup difference was detected in the mean L and W (p<0.001, p=0.001, respectively). The mean L value in Group 2 was statistically significantly less than that of Groups 1 and 3, while the mean W value was significantly greater (p<0.001 for all). However, no statistically significant difference was detected between Groups 1 and 3 with respect to the mean L and W values (p=0.064, p=0.954, respectively). CONCLUSION: Manuka honey exerts an antioxidant and anti-inflammatory effect via inhibition of inflammatory cytokines, including plasma tumor necrosis factor alpha, interleukin (IL)-1 beta, IL-6, and the lipid peroxidation level. This study statistically demonstrated that the anti-inflammatory and antioxidant properties of Manuka honey successfully inhibited the development of vasospasm in an experimentally induced vasospasm model in the femoral arteries of rats.

Temperament and Character Profile in Failed Back Surgery Syndrome: A Cross-Sectional Clinical Study.

AIM: Some psychometric properties may predict the development of failed back surgery syndrome (FBSS). The aim of this study was to determine the pain, disability, and depression severity in patients diagnosed with FBSS, and to determine the temperament and character subgroups in comparison with control group. MATERIAL AND METHODS: Thirty-eight patients diagnosed with FBSS, and 35 patients with favourable outcome after lumbar spinal surgery were included to the study. Pain intensity, disability, depression scores, temperament and character profile were determined by the visual analogue scale (VAS), Roland Morris Disability Index, Beck Depression Inventory, and Temperament and Character Inventory. RESULTS: Pain intensity, disability, and depression scores were higher in the FBSS group (p < 0.001). There were no significant differences between temperament and character subgroups between study groups except one of the temperament subgroup, reward dependence (p=0.05). There was a negative correlation between self-directedness and leg pain severity in the FBSS group (p=0.01, r=-0.400). CONCLUSION: No significant differences were found between the FBSS and control groups with respect to temperament and character profile but FBSS was the cause of severe pain, disability, and higher depression scores. This group of patients must therefore be evaluated psychiatrically and should also be subjected to a clinical examination, and they should be managed using a multidisciplinary approach.