Somatic structural variations in pediatric brain tumors.

Pediatrics brain tumors are the second most frequent malignancy in children, and the most common cause of cancer-related deaths in both the 0-14-year and the 15-24-year age group. Although, pediatrics high-grade glioma (pHGG) is a histologically similar tumor to that arising in adults, these are distinct biological diseases, differing in copy number profiles and driver genetic alterations. Recent sequencing initiatives have conclusively shown the existence of subgroups of HGG marked by distinct driver mutations, which are significantly enriched in young children (H3F3A K27M), teenagers and young adults (H3F3A G34R/V), and middle- aged adults (IDH1/2). Structural rearrangements resulting in novel fusion genes are strongly associated with cancer, and numerous examples exist in both adult and childhood malignancies. Although, only few have been described in pHGG. Structural variants (SV) frequently result in chimeric proteins targetable by novel therapeutic approaches, an outcome desperately needed in pHGG.

PART1 and hsa-miR-429-Mediated SHCBP1 Expression Is an Independent Predictor of Poor Prognosis in Glioma Patients.

Gliomas are the most common primary brain tumors. Because of their high degree of malignancy, patient survival rates are unsatisfactory. Therefore, exploring glioma biomarkers will play a key role in early diagnosis, guiding treatment, and monitoring the prognosis of gliomas. We found two lncRNAs, six miRNAs, and nine mRNAs that were differentially expressed by analyzing genomic data of glioma patients. The diagnostic value of mRNA expression levels in gliomas was determined by receiver operating characteristic (ROC) curve analysis. Among the nine mRNAs, the area under the ROC curve values of only CEP55 and SHCBP1 were >0.7, specifically 0.834 and 0.816, respectively. Additionally, CEP55 and SHCBP1 were highly expressed in glioma specimens and showed increased expression according to the glioma grade, and outcomes of high expression patients were poor. CEP55 was enriched in the cell cycle, DNA replication, mismatch repair, and P53 signaling pathway. SHCBP1 was enriched in the cell cycle, DNA replication, ECM receptor interaction, and P53 signaling pathway. Age, grade, IDH status, chromosome 19/20 cogain, and SHCBP1 were independent factors for prognosis. Our findings suggest the PART1-hsa-miR-429-SHCBP1 regulatory network plays an important role in gliomas.

Recent perspectives of molecular aberrations in pediatric high-grade glioma.

Pediatric high-grade glioma (HGG), including diffuse intrinsic pontine glioma (DIPG) are highly aggressive tumors with no effective cures. Lack of understanding of the molecular biology of these tumors, in part due to lack of well-characterized pre-clinical models, is a great challenge in the development of novel therapies. Recent studies have shown that pediatric HGG short-term cell cultures retain many of the tumor characteristics in vivo and at present one of the best choices for in-vivo experimental studies. The present review article would put light on novel genetic and epigenetic changes in pediatric HGG that might, act as a gold standard potential biomarkers and/or therapeutic targets in near future.

Ubiquitin ligase RNF5 serves an important role in the development of human glioma.

The ubiquitin ligase ring finger protein 5 (RNF5) has previously been associated with the development of breast cancer. Patients with breast cancer and high RNF5 expression have been demonstrated to have a shorter survival time compared with patients with low RNF5 expression. However, the role of RNF5 in human glioma has not been determined. The present study analyzed the role of RNF5 in gliomas using bioinformatics analysis. The results revealed that RNF5 was differentially expressed in non-cancerous brain tissues and different grades of glioma. Furthermore, a high RNF5 expression in patients with glioma was associated with an improved prognosis compared with patients with low expression. Gene Set Enrichment Analysis revealed that RNF5 was particularly associated with 'Wnt signaling pathway', 'apoptosis', 'focal adhesion' and 'cytokine-cytokine receptor interaction' in patients with glioma. Additionally, 4 potential ubiquitination substrates for RNF5 were predicted, including sorting nexin 10, proprotein convertase subtilisin/kexin type 1, leucine rich glioma inactivated 1 and solute carrier family 39 member 12. These findings provided the basis for further investigation on the role of RNF5 in tumors.

Overexpression of CD155 relates to metastasis and invasion in osteosarcoma.

The rapid development of metastatic lesions remains the leading cause of mortality for patients with osteosarcoma. CD155 serves a key role in cancer cell migration, invasion and metastasis. However, the function and mechanism of CD155 has not been explored in osteosarcoma metastasis. In the present study, we found that CD155 was significantly upregulated in lung metastatic tissue and the highly metastatic cell line K7M2-WT (K7M2) of osteosarcoma. Overexpression of CD155 in K7M2 cells enhanced lung metastasis, while inhibition of CD155 by an anti-CD155 monoclonal antibody reduced metastasis. Blocking of CD155 also decreased migration and invasion of K7M2 cells in vitro. A western blot analysis revealed that blocking of CD155 inhibits metastasis by downregulating focal adhesion kinase (FAK) and phosphorylated FAK (pFAK) in osteosarcoma. The results revealed that CD155 serves a crucial role in the metastasis of osteosarcoma by regulating FAK and may provide a novel molecular target for therapeutic intervention in metastatic osteosarcoma.

Pediatric skull fractures and intracranial injuries.

The determination of plausibility of an injury arising from a fall leading to head trauma is a great challenge especially in young children. The present review is aimed to discuss important developments in the filed of head trauma cases especially in children. We explored various studies pertaining to head trauma injuries in children by exploring mainly PubMed, Google scholar and some library periodicals available in our library. Studies in the recent past explored the head injuries as a result of a low height fall. However, there are great amount of difficulties in assessment of height with certainty that caused head injuries like skull fracture or intracranial injury. Biomechanical thresholds have been estimated for young children for injuries such as skull fracture, but they have not been assessed against the injuries observed in a clinical setting. So, this review discusses current aspects of pediatric head injuries ranging from a minor head injury to a skull fracture. The present review concludes that recording full details of cause of head trauma such as fall height is essential for proper treatment planning and efficient management.

Interleukin-24 inhibits osteosarcoma cell migration and invasion via the JNK/c-Jun signaling pathways.

Approximately 25% of osteosarcoma patients present with clinically detectable metastatic disease at the time of initial diagnosis. High-dose chemotherapy and/or surgery for the treatment of primary metastatic osteosarcoma is ineffective, and <20% of patients will survive 5 years from diagnosis. Therefore, the treatment of metastases is critical for the improvement of the prognosis of primary metastatic osteosarcoma patients. We have previously observed that overexpression of interleukin-24 (IL-24) inhibits neuroblastoma cell proliferation, migration and invasion in vitro. The present study investigated whether IL-24 may be a novel agent for osteosarcoma metastasis-suppressive treatment. It was observed that IL-24 is able to inhibit migration and invasion in spontaneously metastasizing human 143B osteosarcoma cells via the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway. IL-24 was effective in inhibiting JNK and c-Jun phosphorylation to downregulate matrix metalloproteinase (MMP)-2 and MMP-9, which contributed to the suppression of cell migration and invasion. It was concluded that IL-24 may be a potent agent in the inhibition of highly metastatic 143B osteosarcoma cells, and IL-24 may have translational potential as an effective therapeutic agent for the treatment of metastatic osteosarcoma.

PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma.

Accumulating evidence has shown that PI3K/Akt pathway is frequently hyperactivated in osteosarcoma (OS) and contributes to tumor initiation and progression. Altered phenotype of glucose metabolism is a key hallmark of cancer cells including OS. However, the relationship between PI3K/Akt pathway and glucose metabolism in OS remains largely unexplored. In this study, we showed that elevated Hexokinase-2 (HK2) expression, which catalyzes the first essential step of glucose metabolism by conversion of glucose into glucose-6-phosphate, was induced by activated PI3K/Akt signaling. Immunohistochemical analysis showed that HK2 was overexpressed in 83.3% (25/30) specimens detected and was closely correlated with Ki67, a cell proliferation index. Silencing of endogenous HK2 resulted in decreased aerobic glycolysis as demonstrated by reduced glucose consumption and lactate production. Inhibition of PI3K/Akt signaling also suppressed aerobic glycolysis and this effect can be reversed by reintroduction of HK2. Furthermore, knockdown of HK2 led to increased cell apoptosis and reduced ability of colony formation; meanwhile, these effects were blocked by 2-Deoxy-d-glucose (2-DG), a glycolysis inhibitor through its actions on hexokinase, indicating that HK2 functions in cell apoptosis and growth were mediated by altered aerobic glycolysis. Taken together, our study reveals a novel relationship between PI3K/Akt signaling and aerobic glycolysis and indicates that PI3K/Akt/HK2 might be potential therapeutic approaches for OS.

[Histological characteristics of the prostate in men who receive re-TURP for benign prostatic hyperplasia and their clinical significance].

OBJECTIVE: To investigate the pathohistological characteristics of the prostate tissues in patients who receive a second TURP and to evaluate their clinical significance. METHODS: We collected surgical specimens from 50 cases of TURP (the control group) and another 50 cases of re-TURP (the re-TURP group), detected the expressions of CD34, vascular endothelial growth factor (VEGF) and androgen receptor (AR) in the prostate tissues by immunohistochemistry (S-P), and determined microvessel density (MVD) and the expressions of VEGF and AR. We performed statistical analyses on the results obtained from the specimens of the control group as well as from those of the first and second operations of the re-TURP group. RESULTS: VEGF and AR expressed in all the specimens. The expressions of VEGF and AR and MVD were significantly higher in the re-TURP group than in the controls (P < 0.05), but showed no significant differences between the first and second operations in the re-TURP group (P > 0.05). Positive correlations were found between the expressions of AR and VEGF, VEGF and MVD, and AR and MVD (r = 0.650, 0.705 and 0.525, P < 0.05). CONCLUSION: Increased AR, VEGF and MVD in the prostatic tissues may be one of the important causes of recurrence of BPH after TURP, and could be considered as the risk factors for postoperative recurrence and targeted indicators for preventive measures.