Profile of Daily Life in Children with Brain Tumors: An Assessment of PedsQL 4.0 Generic Core Scales before and after Treatment

BACKGROUND: Pediatric brain tumors are the most common solid tumor and cause of death among all childhood cancers. In America, brain tumor prevalence is 21.42/100.000 population. Even though survival rate is improving, the impact of treatment for long-term quality of life is still a challenge. AIM: We aimed to investigate quality of life score using PedsQL 4.0 Generic Core Scales. METHODS: The data collected based on the inclusion criteria from patient’s medical records 2015–2017 period on January 2018–May 2018 in Siloam Hospital, Lippo Village, Karawaci. Twenty-six brain tumor pediatric patients with surgical treatment were evaluated using PedsQL 4.0 Generic Core Scales. The evaluation included before and after condition of the patient. PedsQL 4.0 Generic Core Scales were divided into four categories; physical function, emotional function, social function, and school function. They were analyzed statically using Wilcoxon test with p < 0.05 considered as statistically significant. RESULTS: The result showed that before treatment score of PedsQL 4.0 Generic Core Scales was classified as medium functioning (58.54/92) and after treatment score of PedsQL 4.0 Generic Core Scales was classified as intermediate functioning (37.3/92). CONCLUSION: The conclusion is that patient after treatment (surgery, chemotherapy, and radiation) shows improved quality of life score using PedsQL 4.0 Generic Core Scales

Protective Effects of Propolis Extract in a Rat Model of Traumatic Brain Injury via Hsp70 Induction

BACKGROUND: Traumatic brain injury (TBI) is one of the major global health problems. Secondary brain injury is a complex inflammation cascades process that causes brain cell apoptosis. Propolis is a natural product that has neuroprotective property. AIM: This study aimed to investigate the effect of propolis toward Hsp70 expression with apoptosis marker in brain tissue after TBI. METHODS: Thirty-three Sprague Dawley rats were randomised into three treatments group, i.e. sham-operated controls, closed head injury (CHI), and CHI with propolis extract (treatment group). In the treatment group, propolis was given 200 mg/kg per oral for 7 days then harvested brain tissues after sacrificed by cervical dislocation at day 8. We investigated Hsp70, Caspase 3, apoptosis-inducing factor (AIF), and TUNEL assay expression using immunohistochemistry staining. Statistical test using one-way ANOVA test and Tukey HSD as post hoc test. RESULTS: Mean of positive Hsp70 stained cells in group 1 was 6.82 ± 2.14, group 2 was 3.91 ± 2.26, and group 3 was 9.64 ± 3.53 with a significant difference of Hsp70 expression distribution within groups (p = 0.0001). Mean of positive caspase 3 stained cells in group 1 was 5.45 ± 2.30, group 2 was 13.82 ± 2.44, and group 3 was 7.03 ± 1.54 with a significant difference of caspase3 expression distribution within groups (p=0.0001). Mean of positive AIF stained cells in group 1 was 5.36 ± 2.11, group 2 was 12.82 ± 1.40, and group 3 was 8.09 ± 1.81 with a significant difference of AIF expression distribution within groups (p = 0.0001). Mean of positive TUNEL assay stained cells in group 1 was 4.82 ± 2.04, group 2 was 11.55 ± 1.51, and group 3 was 7.64 ± 1.96 with a significant difference of TUNEL test expression distribution within groups (p = 0.0001). CONCLUSION: Propolis may protect brain cell from apoptosis after injury by maintaining Hsp70 expression in addition to antioxidant and anti-inflammatory

Efficacy of Neuroprotection from Curcumin through Heat Shock Protein 70 Induction in Traumatic Brain Injury – Rat Model

BACKGROUND: Traumatic brain injury (TBI) is the most common problem that caused morbidity and mortality in the world. Secondary brain injury is a complex cascade that causes brain cell apoptosis. Curcumin is a natural product that has neuroprotective properties. AIM: This study aimed to investigate the effect of curcumin toward heat shock protein 70 (HSP 70) expression against the expression apoptosis marker (apoptosis-inducing factor [AIF], caspase-3, and TUNEL assay) in brain tissue after TBI. METHODS: Thirty-three Sprague Dawley rats were randomized into three treatment groups, that is, sham-operated controls, closed head trauma (CHT), and CHT with curcumin extract (treatment group). In the treatment group, curcumin was given 500 mg/kg per oral for 7 days, then brain tissues were investigated (marker AIF, caspase-3, TUNEL assay, and HSP 70) through immunohistochemistry. Statistical test using one-way ANOVA test and Tukey honestly significant difference as post hoc test. RESULTS: The mean of positive AIF stained cells in Group A was 5.36 ± 2.11, Group B was 12.82 ± 1.40, and Group C was 3.82 ± 1.40, with a significant difference of AIF expression between Groups C and B (p < 0.05). Mean of positive caspase-3 stained cells in Group A was 5.45 ± 2.30, Group B was 13.82 ± 2.44, and Group C was 3.82 ± 1.54, with a significant difference of caspase-3 expression between Groups C and B (p < 0.05). Mean of positive TUNEL assay stained cells in Group A was 4.82 ± 2.04, Group B was 11.55 ± 1.51, and Group C was 3.55 ± 1.70, with a significant difference between Groups C and B (p < 0.05). Mean of positive HSP 70 stained cells in Group A was 6.82 ± 2.14, Group B was 3.91 ± 2.26, and Group C was 10.27 ± 2.45 with a significant difference of HSP 70 expression distribution within groups (p < 0.05). CONCLUSION: Curcumin may protect brain cells from apoptosis after close head trauma by upregulated HSP 70 expression

Efficacy of Minocycline in Neural Stem Cells Proliferation after Traumatic Brain Injury

BACKGROUND: Neuroinflammation is an important secondary injury mechanism that contributes to neurological impairments after traumatic brain injury (TBI). There is a robust evidence that neuroinflammation will diminish neurogenesis after TBI. Therefore, strategies to attenuate the inflammatory responses are potential to increase neurogenesis following TBI. Minocycline, a second-generation tetracycline antibiotic derivate, has potent anti-inflammatory effect by reducing microglial activation and suppressing some pro-inflammatory cytokines. AIM: The aim of this study is to investigate if minocycline could enhance neurogenesis after TBI. METHODS: Thirty Sprague Dawley rats were randomized into three treatments group, i.e., sham-operated controls, closed head injury (CHI), and CHI with minocycline. We used the modified Feeney’s weight-drop model for making CHI. For the treatment group, we gave minocycline per oral (50 mg/kg) twice daily for the first 2 days followed by 25 mg/kg once daily for 3 consecutive days. Animals were sacrificed on day 5. To assess the proliferation capacity of neural stem cells (NSC), we performed immunohistochemistry staining with SOX2, brain-derived neurotropic factor (BDNF), and NFR. Cell counts were carried out using light microscope with 1000 times magnification in 20 high-power fields. RESULTS: SOX2, NF-E2-related factor 2 (NRF-2), and BDNF were upregulated in the CHI group compared to the sham-operated group (p < 0.05). NRF-2, BDNF, and SOX2 were upregulated also significantly in the CHI+ minocycline group compared to the sham-operated group and the CHI group (p < 0.05). CONCLUSION: Minocycline increased the proliferation capacity of NSC

The effect of intranasal administration of ACTH analogue toward neural progenitor/stem cells proliferation after traumatic brain injury

Traumatic brain injury (TBI) is a major health problem because of its high mortality and long-term disability worldwide. Neural progenitor/stem cells (NPSCs) that survive in certain parts of the brain, enable brain to produce new neurons and glia. ACTH4-10Pro8-Gly9-Pro10 has a modulation effect on the expression and activation of the BDNF/TrkB system in the hippocampus area. The BDNF/TrkB pathway system is a potential therapeutic target toward NPSCs proliferation after TBI. Thirty male Sprague-Dawley rats were divided into three groups, i.e A=sham-operated controls; B=TBI; C=TBI+intranasal ACTH4-10Pro8-Gly9-Pro10 administration. After 24 h, rats’ brains were immunohistochemically processed, to observe the number of cells expressing mBDNF, TrkB, and SOX2 in the subgranular zone(SGZ) of the hippocampus dentate gyrus(DG). Data were analyzed with SPSS 17, ANOVA, Post Hoc Tukey HSD test, with p value < 0,05. Mean expression of BDNF group C=16.33 ± 2.83 increased significantly compared to group A=8.33 ± 1.32(p=0.0001) and group B=5.89 ±1.69(p=0.0001). Mean expression of TrkB group C=17.00 ± 1.58 increased significantly compared to group A=4.33 ± 1.73(p=0.0001) and group B=5.89 ± 2.47(p=0.0001), TrkB expression in group B increased insignificantly compared to group A (p= 0.234). Mean expression of SOX2 in group C=12.56 ± 2.07 increased significantly compared to group B = 8.89 ±2.318(p=0.0001) and group A=4.89 ± 2.42(p=0.0001). ACTH4-10Pro8-Gly9-Pro10 can increase the expression of BDNF and TrkB, and the proliferation of NPSCs in the subgranular zone (SGZ) of the hippocampus dentate gyrus (DG)

Clinicopathological associations and prognostic values of IDH1 gene mutation, MGMT gene promoter methylation, and PD-L1 expressions in high-grade glioma treated with standard treatment

Introduction:&nbsp;the objective was to evaluate the impact of IDH1 R132H mutation, MGMT methylation and PD-L1 expression in high grade glioma that received standard therapy (surgery, radiation and chemotherapy) to overall survival (OS). Methods:&nbsp;this is a retrospective study of 35 high grade glioma cases. Genotyping of IDH1 gene alteration on the mutation hotspot R132 (Sanger sequencing method with Applied Biosystems 3500 Genetic Analyzer), EZ DNA Methylation-Gold kit (Zymo Research) is used to study the methylation, Cell line BT549 (ATCC HTB-122) and HCT-116 (ATCC CCL-247) were used as unmethylated control and partially methylated control respectively. Anti-human PD-L1 antibody clone E1L3N®&nbsp;from Cell Signalling Technology (USA) and Rabbit XP®&nbsp;were used to see PDL-1 expression. Results:&nbsp;anaplastic astrocytoma cases had more MGMT promoter methylation (50%) than glioblastoma multiforme (GBM) (20%), more IDH1 R132H mutation (42%) than GBM (4.3%). Immunohistochemistry tumor proportion score method (TPS) identified 17% and 8.7% were PD-L1 positive in AA and GBM groups, respectively. Cases with IDH1 R132H mutation and MGMT methylation still showed better OS although with high PD-L1 expression. Conclusion:&nbsp;IDH1 R132H mutation and MGMT methylation were good prognostic markers. High expression of PD-L1 apparently might not indicate poor overall survival in the presence of IDH1 R132 mutation and MGMT methylation