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.

Pediatric patellar dislocation.

Acute patellar dislocation affects approximately 1:1000 healthy children 9-15 years of age, and up to 50% are at risk for recurrent dislocations. In adults the condition is associated with long-term complications, such as osteoarthritis and impairment of knee function. However, literature describing the outcome in a pediatric population is sparse. The present review article evaluates the long-term effects on knee function and cartilage quality after traumatic patellar dislocation in childhood, and also to evaluate the reliability of two clinical tests of medio-lateral knee position, in healthy children.

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.

Next Location Prediction Based on an Adaboost-Markov Model of Mobile Users.

As an emerging class of spatial trajectory data, mobile user trajectory data can be used to analyze individual or group behavioral characteristics, hobbies and interests. Besides, the information extracted from original trajectory data is widely used in smart cities, transportation planning, and anti-terrorism maintenance. In order to identify the important locations of the target user from his trajectory data, a novel division method for preprocessing trajectory data is proposed, the feature points of original trajectory are extracted according to the change of trajectory structural, and then important locations are extracted by clustering the feature points, using an improved density peak clustering algorithm. Finally, in order to predict next location of mobile users, a multi-order fusion Markov model based on the Adaboost algorithm is proposed, the model order k is adaptively determined, and the weight coefficients of the 1~k-order models are given by the Adaboost algorithm according to the importance of various order models, a multi-order fusion Markov model is generated to predict next important location of the user. The experimental results on the real user trajectory dataset Geo-life show that the prediction performance of Adaboost-Markov model is better than the multi-order fusion Markov model with equal coefficient, and the universality and prediction performance of Adaboost-Markov model is better than the first to third order Markov models.

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.

Different residue behaviors of four pesticides in mushroom using two different application methods.

Pesticide residue in mushrooms is less known. In this study, the risks of beta-cypermethrin, pyriproxyfen, avermectin, and diflubenzuron in oyster and shiitake mushrooms were evaluated using two different treatments: substrate mixture and surface spraying. Almost all the concentrations of these pesticides at day 90 were higher than 80% of the initial concentrations, while it was less than 45% for all cases within 35 days by spraying. For surface spraying, the residues of beta-cypermethrin were 0.0843-1.22 mg kg-1 in shiitake mushrooms and below 0.005 mg kg-1 in oyster mushrooms; the residues of pyriproxyfen, avermectin, and diflubenzuron were 0.122-4.84, 0.00501-0.111, and 0.0681-1.91 mg kg-1, respectively. The residues of beta-cypermethrin, pyriproxyfen, and diflubenzuron in oyster mushrooms (in shiitake mushrooms) at interval of 0, 3, 5 days (1, 5, 7 days) were below their MRLs in China or Japan. The residue of avermectin in both mushrooms was lower than its limit of detection. These results provide information to safe and proper use of the pesticides in oyster and shiitake mushrooms.

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.

Interleukin-24 inhibits cell migration and invasion in the neuroblastoma cell line SH-SY5Y.

Neuroblastomas are common pediatric solid tumors with a variable clinical course; approximately 50% of patients present with metastatic disease at diagnosis. The development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of metastases during the early stage of tumor development is critical for the improvement of the prognosis of neuroblastoma patients. We previously observed the suppression of neuroblastoma growth in response to overexpression of interleukin-24 (IL-24) in vitro and in vivo. IL-24 exerts its tumor-suppressive effects by multiple mechanisms, including the balance of Bcl-2 family proteins toward the pro-apoptotic pathway and the activation of the caspase cascade. In this study, we used adenovirus-mediated IL-24 (Ad-IL24) to examine the effect of the ectopic production of IL-24 on cell migration and invasion in human neuroblastoma cells. We found that IL-24 effectively inhibits SH-SY5Y neuroblastoma cell migration and invasion by changing subcellular localization and cellular levels of ß-catenin and regulating the levels of proteins associated with cell migration and invasion. Thus, IL-24 should be considered a therapeutic agent that can inhibit primary neuroblastoma growth and that may prevent metastasis.

Adenovirus arming human IL-24 inhibits neuroblastoma cell proliferation in vitro and xenograft tumor growth in vivo.

Data have increasingly shown that interlukin-24 (IL-24) has growth suppression activity and can induce apoptosis in a broad spectrum of tumor cells. However, the therapeutic effect of IL-24 on human neuroblastoma has rarely been explored. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to reveal the effect of adenovirus-mediated IL-24 (Ad-IL24) gene therapy for neuroblastoma. We showed that Ad-IL24 effectively inhibited the proliferation of SH-SY5Y cells in vitro by conspicuously inducing apoptosis. To further explore the molecular mechanism by which Ad-IL24 induced apoptosis in SH-SY5Y tumor cells, we found that Ad-IL24 increased the expression of Bax and promoted the activation of caspase-3, while decreasing Bcl-2 levels. We also demonstrated that Ad-IL24 significantly inhibited tumor growth in vivo in a xenograft neuroblastoma tumor in athymic nude mice. In summary, Ad-IL24 overexpression exerted potent antitumor activity via inducing apoptosis in neuroblastoma cells. Therefore, IL-24 has the potential to serve as an agent for gene therapy in the treatment of neuroblastoma.