Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

Abstract Background We investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigation Methods Angiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied. Results The results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p Conclusions Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs.</p

Position Paper : Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol

The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new protocol for the diagnosis and treatment of childhood renal tumours, the UMBRELLA SIOP-RTSG 2016 (the UMBRELLA protocol), to continue international collaboration in the treatment of childhood renal tumours. This protocol will support integrated biomarker and imaging research, focussing on assessing the independent prognostic value of genomic changes within the tumour and the volume of the blastemal component that survives preoperative chemotherapy. Treatment guidelines for Wilms tumours in the UMBRELLA protocol include recommendations for localized, metastatic, and bilateral disease, for all age groups, and for relapsed disease. These recommendations have been established by a multidisciplinary panel of leading experts on renal tumours within the SIOP-RTSG. The UMBRELLA protocol should promote international collaboration and research and serve as the SIOP-RTSG best available treatment standard

Smoking Restores Impaired LTD-Like Plasticity in Schizophrenia: a Transcranial Direct Current Stimulation Study

Impaired neuroplastic responses following noninvasive brain stimulation have been reported repeatedly in schizophrenia patients. These findings have been associated with deficits in GABAergic, glutamatergic, and cholinergic neurotransmission. Although various neurophysiological studies have indicated a relationship between nicotine and neuroplasticity in healthy individuals, the present study is the first investigation into the impact of nicotine on LTD-like plasticity in patients with schizophrenia. Cortical excitability and cortical plasticity were explored in 30 schizophrenia patients (17 smoker, 13 nonsmoker) and 45 healthy controls (13 smoker, 32 nonsmoker) by using single-pulse transcranial magnetic stimulation (TMS) before and following cathodal transcranial direct current stimulation (tDCS) applied to the left primary motor cortex. Our analysis revealed abolished LTD-like plasticity in nonsmoking schizophrenia patients. However, these plasticity deficits were not present in smoking schizophrenia patients. In healthy controls, significant MEP reductions following cathodal tDCS were observed in nonsmoking individuals, but only trend-level reductions in smokers. In smoking schizophrenia patients, the severity of negative symptoms correlated positively with reduced neuroplasticity, whereas nonsmoking patients displayed the opposite effect. Taken together, the data of our study support the notion of an association between chronic smoking and the restitution of impaired LTD-like plasticity in schizophrenia patients. Although replication and further research are needed to better understand this relationship, our findings indicate that nicotine intake might stabilize the impaired inhibition–facilitation balance in the schizophrenic brain through a complex interaction between cortical plasticity, and GABAergic and cholinergic neurotransmission, and might explain the reduced prevalence of negative symptoms in this population