Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein 70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intracranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2-treated NK cells as compared to those subjected to nontreated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2-treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

Background: To date, there has been little agreement on the use of ultrasonographic parameters in predicting the long-term outcome after transplantation. This study evaluates whether ultrasonography of the graft performed in the early stage after transplantation is a valuable predictor for long-term-outcome. Objectives: The aim of this study was to evaluate the association of ultrasonographic parameters (resistive index [RI], pulsatility index[PI], end diastolic velocity [EDV], graft length and graft parenchymal volume) measured within the first week after transplantation with 6 months graft function. Patients and Methods: A cross-sectional study was performed on 91 (46 males and 45 females) living renal transplants between April 2011 and February 2013. All patients underwent an ultrasonography at the first week after transplantation. Intrarenal Doppler indices including RI, PI and EDV were measured at the interlobar artery level and the graft length and parenchymal volume were defined with gray scale ultrasonography. Graft function was estimated at 6months by glomerular filtration rate (GFR). Unpaired t-test and multivariate-linear and logistic regression analysis were used to estimate the relationship between ultrasonographic parameters and GFR. Results: Fourteen patients (15.4%) had impaired graft function after 6 months (GFR less than 60 ml/min/1.73m2). Multivariate linear regression analysis showed significant correlation between GFR at 6 months and RI, PI and EDV with a P value of 0.026, 0.016 and 0.015, respectively. Logistic regression analysis showed that GFR0.7 (odds ratio=2.20, P value=0.004) and PI>1.3 (odds ratio=2.74, P value<0.001) and EDV<9 cm/Sec (odds ratio=1.83, P value=0.03). Conclusions: In this study, kidney transplant recipients with a lower RI and PI and a higher EDV at 1week showed better graft function at 6 months after transplantation. Keywords: Kidney Transplantation; Ultrasonography; Glomerular Filtration Rate