Electrocortical Correlates of Temperament

The aim of this study was to investigate the relationship between three temperament dimensions: strength of excitation, strength of inhibition and mobility measured by Pavlov’s Temperament Survey (PTS), and amplitudes and latencies of evoked brain potentials (N1, P2, N2, P3 & SW) measured by a visual oddball paradigm in two blocks. The participants were female psychology students (N=54) with mean age of 20. Significant positive correlations were determined between amplitudes of N1-P2-N2-P3 components and strength of excitation and mobility in the first and second block, mostly on parietal electrodes, as well as significant negative correlations of amplitudes of N1-P2-N2-P3 components and strength of inhibition. Considering measurement limitations important future study directions have been give

VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma

Abstract Background Vascular endothelial growth factor (VEGF) isoforms, particularly the diffusible VEGF-121, could play a major role in the response of recurrent glioblastoma (GB) to anti-angiogenetic treatment with bevacizumab. We hypothesized that circulating VEGF-121 may reduce the amount of bevacizumab available to target the heavier isoforms of VEGF, which are the most clinically relevant. Methods We assessed the plasma level of VEGF-121 in a brain xenograft model, in human healthy controls, and in patients suffering from recurrent GB before and after bevacizumab treatment. Data were matched with patients’ clinical outcome. Results In athymic rats with U87MG brain xenografts, the level of plasma VEGF-121 relates with tumor volume and it significantly decreases after iv infusion of bevacizumab. Patients with recurrent GB show higher plasma VEGF-121 than healthy controls (p = 0.0002) and treatment with bevacizumab remarkably reduced the expression of VEGF-121 in plasma of these patients (p = 0.0002). Higher plasma level of VEGF-121 was significantly associated to worse PFS and OS (p = 0.0295 and p = 0.0246, respectively). Conclusions Quantitative analysis of VEGF-121 isoform in the plasma of patients with recurrent GB could be a promising predictor of response to anti-angiogenetic treatment

Additional file 2: of VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma

Figure S1. Panels A and B. The panels show the significant correlation between plasma level of VEGF-121 and, respectively, OS (panel A; linear regression test: p = 0.0013; r2 = 0,9417), and PFS (panel B; linear regression test: p = 0.0001; r2 = 0,9913). Panels C and D. The panels show the significant correlation between differential plasma value of VEGF-121 (∆VEGF121: VEGF-121 level at baseline – VEGF-121 level after bevacizumab infusion) and, respectively, OS (panel C; linear regression test: p = 0.0008; r2 = 0,9731), and PFS (panel D; linear regression test: p = 0.0003; r2 = 0,9742). (TIF 1478 kb

Additional file 1: of VEGF-121 plasma level as biomarker for response to anti-angiogenetic therapy in recurrent glioblastoma

Statistical analysis. (DOCX 13 kb

Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts.

The goal of cancer chemotherapy is targeting tumor cells and/or tumor-associated microvessels with the lowest systemic toxicity. Mesenchymal stromal cells (MSCs) are promising vehicles for selective drug delivery due to their peculiar ability to home to pathological tissues. We previously showed that MSCs are able to uptake and subsequently to release the chemotherapeutic compound Paclitaxel (PTX) and to impair the growth of subcutaneous glioblastoma multiforme (GBM) xenografts. Here we used an orthotopic GBM model 1) to assess whether PTX-loaded MSCs (PTX-MSCs) retain a tropism towards the tumor cells in the brain context, and 2) to characterize the cytotoxic damage induced by MSCs-driven PTX release in the tumor microenvironment. METHODS: U87MG GBM cells were fluorescently labeled with the mCherry protein and grafted onto the brain of immunosuppressed rats. In adjacent brain regions, we injected green fluorescent protein-expressing murine MSCs, either loaded with PTX or unloaded. After 1 week survival, the xenografted brain was assessed by confocal microscopy for PTX-induced cell damage. RESULTS: Overall, MSCs showed remarkable tropism towards the tumor. In rats grafted with PTX-MSCs, the nuclei of U87MG cells showed changes that are typically induced by PTX, including multi-spindle mitoses, centrosome number alterations, and nuclear fragmentation. Multi-spindle mitoses resulted in multinucleated cells that were significantly higher in tumors co-grafted with PTX-MSCs than in controls. Nuclear changes did not occur in astrocytes and neurons surrounding the tumor. CONCLUSIONS: MSCs appear particularly suited for anti-neoplastic drug delivery in the brain since PTX-specific damage of GBM cells can be achieved avoiding side effects to the normal tissue

Cytological and histological changes in the urothelium produced by electromotive drug administration (EMDA) and by the combination of intravescical hyperthermia and chemotherapy (thermochemotherapy)

The treatment of non muscle-invasive bladder cancer (NMIBC) encompasses a range of different procedures. Electromotive drug administration (EMDA) and chemo-hyperthermia (C-HT; Synergo) represent a minimally-invasive methods of intravesical instillation of therapeutic agents as mitomycin C (MMC). We selected patients with high grade NMIBC, BCG non responder, treated with EMDA/MMC and C-HT/MMC and we also examined the morphological changes in urine cytology samples. During the period from 2012 to 2014, 110 patients with high grade NMIBC, BCG refractory were selected. All cases examined were classified according to The Paris System Classification as negative for high urothelial carcinoma (NHGUC) or atypical urothelial cells (AUC) with a mean of follow-up of 15 months and the cytological diagnosis were confirmed by histological biopsies. In particular 50 patients were treated with EMDA/MMC and 60 patients underwent to C-HT/MMC. The morphological changes were evaluated in urine samples processed by Thin Prep method. In the 50 patients treated with EMDA/MMC, 35 samples were classified as NHGUC and 15 cases were classified as AUC, while in the 60 patients treated with C-HT/MMC, 43 samples were NHGUC and 17 cases were classified AUC. The increase of cellularity and nuclear size with the alteration of nuclear/cytoplasmatic ratio (N/C) were common in patients treated with EMDA/MMC and C-HT/MMC without clinical and histological evidence of recurrence of neoplasia. The hyperchromasia and irregular nuclear chromatin were rarely observed. The irregular nuclear membrane rarely identified in urine cytology after EMDA/MMC treatment, is a feature present in patients C-HT/MMC treated

Additional file 2: Figure S2. of Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts

Showing assessment of PTX-induced nuclear changes in the brain cell populations. Immunostaining either with GFAP A or with NeuN B showed that the nuclei of astrocytes (arrows in A) and of neurons (arrows in B) lying close to PTX-loaded MSCs do not exhibit those PTX-induced changes that are clearly seen in the nuclei of U87MG tumor cells (arrowheads in A and B). Scale bars = 25 μm. (JPEG 9615 kb