Toll-like receptors (TLRs) are the first to identify disturbances in the immune system, recognizing pathogens such as bacteria, fungi, and viruses. Since the inflammation process plays an important role in several diseases, TLRs have been considered potential therapeutic targets, including treatment for cancer. However, TLRs' role in cancer remains ambiguous. This study aims to analyze the expression levels of plasmatic cell membrane TLRs (TLR1, TLR2, TLR4, TLR5, and TLR6) in human astrocytomas the most prevalent tumors of CNS different grades (II-IV). We demonstrated that TLR expressions were higher in astrocytoma samples compared to non-neoplastic brain tissue. The gene and protein expressions were observed in GBM cell lines U87MG and A172, proving their presence in the tumor cells. Associated expressions between the known heterodimers TLR1-TLR2 were found in all astrocytoma grades. In GBMs, the mesenchymal subtype showed higher levels of TLR expressions in relation to classical and proneural subtypes. A strong association of TLRs with the activation of cell cycle process and signaling through canonical, inflammasome and ripoptosome pathways was observed by in silico analysis, further highlighting TLRs as interesting targets for cancer treatment.

Desmoplastic Infantile Astrocytoma/Ganglioglioma (DIA/DIG) are rare primary glioneuronal tumors that comprise 0.5-1.0% of all intracranial tumors. While BRAF mutation is found in up to 50% of pediatric gangliogliomas, data for DIA/DIGs is limited. This study was carried out to evaluate the frequency of BRAF V600E mutation in DIA/DIG. All cases of DIA/DIGs diagnosed over 7years (2010-2016) were reviewed retrospectively. The clinical, radiological and histopathological characteristics of these patients were evaluated along with immunohistochemical analysis for glial and neuronal markers. We evaluated presence of BRAF V600E mutation by Sanger sequencing and immunohistochemistry using monoclonal antibody against clone VE1. Eight cases of desmoplastic infantile astrocytoma/ganglioglioma (6 DIGs and 2 DIAs) were evaluated. Four cases were of infantile type (age 10months - 2years) and 4 cases of non-infantile type (age 10-14years). BRAF VE1 IHC was positive in four cases (two DIG and two DIA). All these four cases also showed heterozygous BRAF V600E mutation (T replaced by A at nucleotide position 1799). Sequencing didn't detect BRAF mutation in any additional case. All four cases harboring this mutation were non-infantile (10-14years). Cases with infantile presentation didn't carry this mutation. None of the cases showed recurrence on follow up. Thus BRAF V600E mutation is common in desmoplastic non-infantile astrocytoma/ganglioglioma, but does not affect the prognosis. Identification of BRAF status opens the possibility of targeted therapies for the subset of cases that clinically progress post-resection.

Objective: This study aimed to evaluate neuropsychological consequences in survivors of childhood brain tumor. Method: A case-control study was conducted over a period of 4 months in a tertiary referral center in Kuala Lumpur, Malaysia. Fourteen survivors of childhood brain tumor aged 7-18 years, who were off-treatment for at least 1 year and were in remission, and 31 unrelated healthy controls were recruited. The median age at diagnosis was 8.20 years (range: 0.92-12.96 years). The diagnoses of brain tumors were medulloblastoma, germ cell tumor, pineocytoma, pilocystic astrocytoma, suprasellar germinoma, and ependymoma. Eleven survivors received central nervous system irradiation. Seven tasks were selected from the Amsterdam Neuropsychological Tasks program to evaluate alertness (processing speed), and major aspects of executive functioning, such as working memory capacity, inhibition, cognitive flexibility, and sustained attention. Speed, stability and accuracy of responses were the main outcome measures. Results: Survivors of childhood brain tumor showed statistically significant poorer performance on all tasks compared to healthy controls. Both processing speed and accuracy were impaired in the survivors, in particular under more complex task conditions. The survivors demonstrated deficits in alertness, sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Longer duration off treatment appeared to be correlated with poorer alertness, memory capacity, and inhibition. Conclusion: Survivors of childhood brain tumor in our center showed impaired neuropsychological functioning. Development of less toxic treatment protocols is important to prevent late effects of cognitive deficits in survivors of childhood brain tumor.