Tailored therapeutic strategies for synovial sarcoma: Receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001

We examined efficacy of the mTOR inhibitor RAD001 to seek novel therapies for synovial sarcoma (SS). Although RAD001 had significant anti-tumor effects, its sensitivity differed among cell lines. Phospho-receptor tyrosine kinase (RTK) array analyses revealed c-MET phosphorylation in highly mTOR inhibitor-sensitive cells and PDGFRα (which induces intrinsic resistance to mTOR inhibitor) activation in less sensitive cells. Combined treatment with RAD001 and the PDGFR inhibitor pazopanib showed anti-tumor effects in xenograft models with less sensitive cells. Thus, evaluating activated RTKs in clinical samples may predict sensitivity to mTOR inhibitors, raising the possibility of a tailored therapy for SS.     

Rosai‐dorfman disease with extranodal involvement

Rosai‐Dorfman disease is a rare condition of marrow hematopoietic stem‐cell origin. Patients can show extranodal involvement as well as lymphatic involvement, but only about 5% of extranodal cases involve intracranial lesions. A 53‐year‐old male was admitted to our hospital with bilateral cervical lymphadenopathy. Intracranial tumors and bone lesions were also detected. Cervical lymph node biopsy and intracranial tumor resection were performed, and histopathological examination revealed Rosai‐Dorfman disease. The patient showed good clinical course without significant enlargement of the tumor. This study describes the case of a patient with Rosai‐Dorfman disease presenting with massive cervical lymphadenopathy mimicking malignant neoplasm. Laryngoscope, 124:701–704, 2014     

tRNA cleavage: a new insight

Over the past decades,tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others,holding more than half of all modifications occurring in RNA molecules.Moreover,tRNA was discovered to be a source of various small noncoding RNA species,such as the stress induced angiogenin cleaved tRNA halves(tiRNA)or the miRNA like tRNA derived fragments.tRNA cleavage under stress was fist discovered in bacteria and later was found to be conserved across different species,including mammals.Under cellular stress conditions,tRNA undergoes conformational changes and angiogenin cleaves it into 3′and 5′halves.5′tiRNA halves were shown to repress protein translations.tRNA cleavage is thought of to be a cytoprotective mechanism by which cells evade apoptosis,however some data hints to the opposite;that tiRNA are cytotoxic or at least related to apoptosis initiation.tRNA cleavage also was shown to be affected by tRNA modifications via different enzymes in the cytosol and mitochondria.In this review,we will highlight the biology of tRNA cleavage,show the evidence of it being cytoprotective or a marker of cell death and shed a light on its role in disease models and human diseases as well as possible future directions in this field of RNA research.     

Bone tissue engineering with bone marrow-derived stromal cells integrated with concentrated growth factor in Rattus norvegicus calvaria defect model

Concentrated growth factor (CGF) is an autologous leukocyte-rich and platelet-rich fibrin (L-PRF) biomaterial termed “second-generation platelet concentrate”. CGF contains autologous osteoinductive platelet growth factors and an osteoconductive fibrin matrix. The purpose of this study was to assess the ability of CGF combined with bone marrow stromal cells (BMSCs) to heal critical-size rat calvaria defects in vivo and to modulate the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. In the in-vivo study, the CGF group regenerated bone better than the control group, and combined therapy with CGF and BMSCs almost completely repaired critical-size bone defects within 12 weeks after surgery. In the in-vitro study, the CGF extract, at concentrations between 1 and 10 %, promoted proliferation, osteogenic maturation, and mineralization of hTERT-E6/E7 human MSCs in a dose-dependent manner but had an inhibitory effect at higher concentrations. In conclusion, a CGF extract promoted the proliferation, osteogenic maturation, and mineralization of mesenchymal stem cells in vitro, and combination therapy with CGF and BMSCs resulted in excellent healing of critical-size bone defects in vivo.     

Increase in the number of patients with seizures following the Great East‐Japan Earthquake

In the afternoon of March 11, 2011, Kesennuma City was hit by the Great East‐Japan Earthquake and a devastating tsunami. The purpose of this retrospective study is to document possible changes in the number of patients with distinct neurologic diseases seeking treatment following this disaster. Because of Kesennuma's unique geographical location, the city was isolated by the disaster, allowing for a study with relatively limited population selection bias. Patients admitted for neurologic emergencies from January 14 to May 5 in 2011 (n = 117) were compared with patients in the corresponding 16‐week periods in 2008–2010 (n = 323). The number of patients with unprovoked seizures was significantly higher during the 8‐week period after the earthquake (n = 13) than during the same periods in 2008 (n = 6), 2009 (n = 3), and 2010 (no patients) (p = 0.0062). In contrast, the number of patients treated for other neurologic diseases such as stroke, trauma, and tumors remained unchanged. To our knowledge, this is the first report of an increase in the number of patients with seizures following a life‐threatening natural disaster. We suggest that stress associated with life‐threatening situations may enhance seizure generation.     

Multiplex ligation-dependent probe amplification analysis is useful for detecting a copy number gain of the FGFR1 tyrosine kinase domain in dysembryoplastic neuroepithelial tumors

Journal of Neuro-Oncology - The Appalachian region is a large geographic and economic area, representing 7.69% of the United States (US). This region is more rural, whiter, older, and has a higher...     

New insights into glioma classification based on isocitrate dehydrogenase 1 and 2 gene status

In glioma, mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) genes have been receiving attention. IDH1/2 mutations are frequently found in grade II and III gliomas. These genetic alterations occur very early in gliomagenesis and strongly predict favorable outcome in patients with high-grade gliomas. Despite the evolution of studies on this topic, the underlying mechanism of the IDH1/2 mutations remains unknown. Here, we briefly review the current knowledge of IDH1/2 and discuss molecular diagnostics based on IDH1/2 gene status.