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Introduction The effects of single-fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA) and immune checkpoint inhibitors (ICI) are insufficiently studied. Methods and materials Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n= 43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60 to 100%. Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE). Results One hundred and ninety-four targets were irradiated. The median number of targets at first sf-GKRS was two. The median prescription dose was 22.0 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC rates at 12 and 18 months were 97% and 90%. Median OS from the first sf-GKRS was 15.7 months. Low serum albumin (HR for death 5.3), corticosteroid use pre-sf-GKRS (HR for death 5.8) and KPS < 80 (HR for death 9.1) were independently associated with worse OS. No further prognostic information was gleaned from MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases. Other prognostic scores for BM radiosurgery, including DS-GPA, renal-GPA, LLV-SIR and CITV-SIR, again, did not add further prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within 1 month of sf-GKRS. Conclusions We identified albumin, corticosteroid use and KPS as independent prognostic factors for sf-GKRS of clear cell RCC BM. Studies focusing on the prognostic significance of albumin in sf-GKRS are rare. Further studies with a larger number of patients are warranted to confirm the above analytical outcome. Also, in keeping with previous studies, our data showed optimal rates of local tumour control and limited toxicity post radiosurgery, rendering GKRS the tool of choice in the management of RCC BM.

Traumatic brain injury (TBI) is one of the important reason of morbidity and mortality. While the primary injury due to mechanical impact is unavoidable, the secondary injury which is formed as a result of primary injury and thought to occur due to neuroinflammation in the forefront can be prevented and by this way mortality and morbidity can be reduced. High mobility group box-1 (HMGB1) is a protein that triggers the neuroinflammatory process by being released from the nucleus of necrotic tissues after primary injury. The aim of this study is to investigate the effects of HMGB1 on its receptors TLR4 and RAGE, cerebral edema, blood-brain barrier, oxidative stress and apoptosis causing secondary damage in an experimental traumatic brain injury model. Weighing between 280–320 g, 10 to 12 weeks-old, a total of 30 adult male Sprague-Dawley rats were used for the experiments. The rats were randomly assigned to 3 groups: 1) Control, 2) TBI and 3) TBI + ethyl pyruvate group (n = 10 per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. Brain samples were harvested from pericontusional area at 24 h after TBI. HMGB1, TLR4, RAGE, occludin, claudin-5, ZO-1 levels are investigated by western blot analyses and immunohistochemistry examinations. HMGB-1, TLR4 and RAGE expressions increased after TBI. Major tight junction proteins in the blood-brain barrier: occludin, claudin-5 and ZO-1 expressions decreased after TBI. Brain edema increased after TBI. Also, proapoptotic bax and active caspase 3 expressions increased, antiapoptotic bcl-2 levels decreased after TBI. Total oxidant status and oxidative stress increased, total antioxidant status decreased after TBI. HMGB-1 protein plays a key role in the pathophysiology of traumatic brain injury.

Background: The importance of pre-treatment Diffusion Tensor Imaging (DTI) parameters in determining the response to treatment after radiosurgery in patients with meningioma has not yet been clearly revealed. Objective: This study was conducted to determine tumor volume changes in terms of radiological response in patients with meningioma treated with Gamma Knife Radiosurgery (GKR) and to analyze the relationship between Total Tumor Volume (TTV) and Diffusion Tensor Imaging (DTI) parameters. In addition, we investigated whether the response to treatment can be predicted by pre-radiosurgery DTI findings. Methods: Fifty-four patients were assessed using MRI and DTI before and after GKR. Mean Diffusivity (MD), Fractional Anisotropy (FA), Radial Diffusivity (RD), and TTV of tumour were determined. Patients with 10% or more decrease in TTV after GKR were classified as group 1 and those with less than 10% decrease in volume or increase in volume were considered group 2. The relationships between MD, RD, and FA values and TTV were investigated. Results: A decrease of 46.34% in TTV was detected in group 1 after GKR, while TTV increased by 42.91% in group 2. The lowest pre-treatment FA value was detected in group 1. In addition, after GKR, FA values showed a significant increase in group 1. MD and RD values increased in both groups after radiosurgery. There was a negative correlation between pre-treatment FA, RD, and MD values after radiosurgery. Conclusions: Detection of low FA values due to the poor fiber content in meningioma before radiosurgery may be a guide in predicting the response to treatment. Further studies are required to have a better understanding of the relationship between pre- and post-treatment follow-up FA values and tumor volume in determining the efficacy of GKR in patients with meningioma.

The outbreak of Novel Coronavirus 2019 (COVID-19) represents a global threat to the public healthcare. The viral spike (S) glycoprotein is the key molecule for viral entry through interaction with angiotensin converting enzyme 2 (ACE2) receptor molecules present on the cell membranes. Moreover, it has been established that COVID-19 interacts and infects brain cells in humans via ACE2. Therefore in the light of these known facts we hypothesized that viral S protein molecule may bind to the other overexpressed receptor molecules in glioma cells and may play some role in glioma tumorogenesis. Thus we leverage docking analysis (HEX and Z-DOCK) between viral S protein and epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptors (VEGFR) and hepatocyte growth factor receptors (HGFR/c-MET) to investigate the oncogenic potential of COVID-19. Our findings suggested higher affinity of Viral S protein towards EGFR and VEGFR. Although, the data presented is preliminary and need to be validated further via molecular dynamics studies, however it paves platform to instigate further investigations on this aspect considering the aftermath of COVID-19 pandemic in oncogenic perspective.

Background:The long-term benefits of local therapy in metastatic renal cell carcinoma (mRCC) have been widely documented. In this context, single fraction gamma knife radiosurgery (SF-GKRS) is routinely used in the management of brain metastases. However, SF-GKRS is not always feasible due to volumetric and regional constraints. We intend to illustrate how a dose-volume adaptive hypofractionated GKRS technique based on two concurrent dose prescriptions termed rapid rescue radiosurgery (RRR) can be utilized in this particular scenario.Case Description:A 56-year-old man presented with left-sided hemiparesis; the imaging showed a 13.1 cc brain metastasis in the right central sulcus (Met 1). Further investigation confirmed the histology to be a metastatic clear cell RCC. Met 1 was treated with upfront RRR. Follow-up magnetic resonance imaging (MRI) at 10 months showed further volume regression of Met 1; however, concurrently, a new 17.3 cc lesion was reported in the boundaries of the left frontotemporal region (Met 2) as well as a small metastasis (Results:Gradual and sustained tumor ablation of Met 1 and Met 2 was demonstrated on a 20 months long follow- up. The patient succumbed to extracranial disease 21 months after the treatment of Met 1 without evidence of neurological impairment post-RRR.Conclusion:Despite poor prognosis and precluding clinical factors (failing systemic treatment, eloquent location, and radioresistant histology), RRR provided optimal tumor ablation and salvage of neurofunction with limited toxicity throughout follow-up.

Background: Cases of gliomas coexisting with multiple sclerosis (MS) have been described over the past few decades. However, due to the complex clinical and radiological traits inherent to both entities, this concurrent phenomenon remains difficult to diagnose. Much has been debated about whether this coexistence is incidental or mirrors a poorly understood neoplastic phenomenon engaging glial cells in the regions of demyelination. Case Description: We present the case of a 41-year-old patient diagnosed with a left-sided frontal contrast enhancing lesion initially assessed as a tumefactive MS. Despite systemic treatment, the patient gradually developed signs of mass effect, which led to decompressive surgery. The initial microscopic evaluation demonstrated the presence of MS and oligodendroglioma; the postoperative evolution proved complex due to a series of MS-relapses and tumor recurrence. An ulterior revaluation of the samples for the purpose of this report showed an MS-concurrent anaplastic astrocytoma. We describe all relevant clinical aspects of this case and review the medical literature for possible causal mechanisms. Conclusion: Although cases of concurrent glioma and MS remain rare, we present a case illustrating this phenomenon and explore a number of theories behind a potential causal relationship.

Background: Gamma knife stereotactic radiosurgery is, compared with surgical treatment, a less invasive treatment option for patients with trigeminal neuralgia (TN). Aim: In this report, we analyzed the effect and safety of gamma knife radiosurgery performed in patients with TN. Materials and Methods: We retrospectively reviewed patients who underwent gamma knife radiosurgery for TN between June 2014 and January 2017. All patients were treated with Leksell Gamma Knife Model C (Elekta, Stockholm, Sweden) with a prescription dose of 40 Gy with a 50% isodose line. The follow-up of the patients was performed 1 week after the procedure and after every 3 months. The pain score of the patients was recorded using the visual analog scale (VAS). Complications were also reviewed. Statistical Analysis: Statistical analysis was performed using the Statistical Package for the Social Sciences software for Windows, version 23.0. Results: Twenty-four patients (10 males, 14 females) were included in the study. The median age of the patients was 62.5 years (range, 34–91 years). The pre-gamma knife median VAS was 10 (range, 5–10), and the median VAS was 1 (range, 0–10) during the last follow-up. The pain decreased in 16 (76%) patients. Two patients (9%) had treatment-related complications. One patient developed hypoesthesia along the dermatome of the maxillary branch of the fifth cranial nerve and another patient developed facial paresis, which recovered after the usage of steroids for 3 months. Conclusion: Gamma knife radiosurgery is an effective and safe treatment for patients with TN with an acceptable pain control rate.

Background: Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor. Over the last few years, studies have identified many genetical and phenotypical molecular situations for developing new treatment modalities in patients with GBM. Nevertheless, main problem for the GBM is radio-chemotherapy resistance and relapse after the surgery. The identification of glioma stem cells and microenvironmental influences has created a paradigm shift in targets of therapy. Current studies have shown that glioma stem cell is responsible for aggressiveness, recurrence and resistance to therapy of GBM. GBM stem cell isolated from human GBM multiforme fresh tissue samples is important both for curative therapeutic options and personalized targeted therapy. The purpose of this study was to determine the most suitable isolation method of GBM stem cells (GSCs). Methods: Tumor tissue sample was obtained during the surgical resection of lesion in patients with the diagnosis of GBM. Tumor stem cell isolation from tissue was performed in three different ways: 1) GBM cell isolation with trypsin; 2) GBM cell isolation with brain tumor dissociation Kit (BTD Kit); and 3) GBM cell isolation with tumor dissociation enzyme (TDE). Results: We showed that GSCs were isolated from tumor specimen using flow cytometry and immunofluorescence staining. Our study showed that isolation with BTD Kit is the most suitable method to isolate GBM tissue-derived glial tumor stem cells. Conclusions: The development of alternative personalized therapies targeting brain tumor stem cell is urgently needed. It is important to understand the fundamental mechanisms of driving stem cells. If their life cycle mechanisms can be identified, we can control the growth of GBM. J Clin Med Res. 2019;11(6):415-421 doi: https://doi.org/10.14740/jocmr3781

Up until, June 13, 2020, 7,500,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 400,000 deaths, across 216 countries, have been confirmed by the World Health Organization (WHO) With reference to the two previous beta-CoV outbreaks (SARS-CoV and middle east respiratory syndrome [MERS]), this paper examines the pathophysiological and clinical similarities seen across all three CoVs, with a special interest in the neuroinvasive capability and subsequent consequences for patients with primary or metastatic brain tumors More widely, we examine the lessons learned from the management of such large-scale crises in the past, specifically looking at the South Korean experience of MERS and the subsequent shift in disaster management response to SARS-CoV-2, based on prior knowledge gained We assess the strategies with which infection prevention and control can, or perhaps should, be implemented to best contain the spread of such viruses in the event of a further likely outbreak in the future [ABSTRACT FROM AUTHOR] Copyright of Surgical Neurology International is the property of Scientific Scholar LLC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Background Prognosis of patients with melanoma brain metastasis is poor despite various chemotherapeutic agents. Researchers focus on finding effective treatment with a low risk of toxicity. Thymoquinone (TQ) has been found to be effective on different types of cancer. However, no data exist regarding the effect of TQ in intracerebral melanoma. The purpose of this study was to assess the effect of TQ in B16-F10 melanoma cell in vitro and intracerebral melanoma in vivo. Methods The mechanisms of efficacy were investigated using adenosine triphosphate assay for cytotoxicity, flow cytometry, and acridine orange staining for apoptosis, comet assay for genotoxicity, CM-H2DCF-DA (2,7-dichlorodihydrofluorescein) for intracellular reactive oxygen species (ROS) generation and ELISA methods for inflammatory cytokines. Western blotting was performed to assess the expressions of p-JAK2, p-STAT3, caspase-3, Bax, Bcl-2, and survivin. In addition, the effect of TQ was investigated in a model system of intracerebral melanoma in syngeneic mice. Results The median survival was improved by TQ in mice with intracerebral melanoma compared with the control group (16 days vs 9 days; P = 0.008). Cytotoxicity was enhanced by TQ in B16-F10 cells in a dose-dependent manner. TQ also induced apoptosis, DNA damage, and increased intracellular ROS. TQ inhibited p-STAT3, resulting in apoptosis through regulation of proapoptotic and antiapoptotic proteins. Conclusions Our findings suggest that TQ would be an effective treatment in intracerebral metastatic lesions. This warrants further investigation.

Background Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. Methods Twenty-nine retrospective studies investigating SRS for BSM were reviewed. Results The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). Conclusions Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04–2.8 cc does not predict for toxicity.

Brain metastasis is a serious complication in patients with systemic cancer. The main goal of the treatment in patients with brain metastasis is to control the disease in the brain, to prevent death from neurological disease and provide a satisfactory quality of life. Management of a patient with brain metastasis is important and sometimes demanding, and several factors such as tumor histology, status of primary disease, number of brain lesions, size of lesions, and performance status may influence the decision making process. We reviewed the neurosurgical treatment modalities in patients with metastatic brain tumor and suggested a treatment paradigm for different clinical conditions. The PubMed database was searched using combinations of search terms and synonyms for "management of brain metastasis," "stereotactic radiosurgery for brain metastasis," and "surgery for brain metastasis" between January 1, 1990, and January 1, 2018. This review would guide physicians to solve challenging problems in the treatment of patients with brain metastasis. In summary, local aggressive treatments such as surgical resection and stereotactic radiosurgery are reasonable in patients with limited intracranial disease, controlled primary disease, and high performance status. Besides, WBRT is still the standard treatment in patients with low performance score and leptomeningeal dissemination of cancer.

Objective The open door laminoplasty technique has been previously used to treat cervical spondylotic myelopathy. We adapted this technique for the removal of spinal tumors all along the spinal axis. Methods Between January 2002 and January 2003, 17 patients with various intraspinal lesions underwent open door laminoplasty. The thoracal level was involved in 10 cases, the cervical level in 3 patients and the lumbar level in 4. Location of the tumor was intradural-intramedullary in 7, intradural-extramedullary in 6 and extradural in 4 patients. The histological diagnoses were 4 astrocytomas, 2 meningiomas, 3 neurinomas, 2 ependymomas and one case each with Ewing's sarcoma, metastasis, abcess, hemangioblastoma, arachnoid cyst and lipoma. Results All lesions were exposed using the open door laminoplasty technique and were successfully removed for intraspinal mass lesions. An average of 3.7 level laminoplasty was performed. Neither spinal malalignment on the coronal plane nor displacement of bone flap (laminoplasty flap) were observed on postoperative CT and MR examinations. No complications due to laminoplasty were encountered. The mean follow-up was 30 months (range 22-48 months). Conclusion Open door laminoplasty is a simple procedure and has two main advantages over the classical laminectomy procedure; a lower incidence of spinal deformities with or without neurological deficits and an absence of epidural scar tissue. This procedure can be used in all spinal cases with intraspinal mass lesions.

OBJECT Brain metastases are the most common intracranial neoplasms and are on the increase. As radiation side effects are increasingly better understood, more patients are being treated with surgery alone with varying outcomes. The authors previously reported that en bloc resection of a single brain metastasis was associated with decreased incidences of leptomeningeal disease and local recurrence compared with piecemeal resection. However, en bloc resection is often feared to cause an increased incidence of postoperative complications. This study aimed to answer this question. METHODS The authors reviewed data from patients with a previously untreated single brain metastasis, who were treated with resection at The University of Texas M.D. Anderson Cancer Center (1993–2012). Data related to the patient, tumor, and methods of resection were obtained. Discharge Karnofsky Performance Scale (KPS) scores and 30-day postoperative complications were noted. Complications were considered major when they persisted for longer than 30 days, resulted in hospitalization or prolongation of hospital stay, required aggressive treatment, and/or were life threatening. RESULTS During the study period, 1033 eligible patients were identified. The median age was 58 years, 83% had a KPS score greater than 70, and 81% were symptomatic at surgery. Sixty-two percent of the patients underwent en bloc resection of their tumor, and 38% underwent piecemeal resection. There were significant differences between the 2 groups in terms of preoperative tumor volume, tumor functional grade, and symptoms at presentation, among others. The overall complication rates were 13% for patients undergoing en bloc resection and 19% for patients undergoing piecemeal resection (p = 0.007). The incidences of major complications and neurological complications were also significantly different. There was a trend in the same direction for major neurological complications, although it was not significant. Among patients undergoing piecemeal resection of tumors in eloquent cortex, 24% had complications (13% had major, 18% had neurological, 9% had major neurological, and 13% had select neurological complications; 4% died within 1 month of surgery). Among those undergoing en bloc resection of such tumors, 11% had complications (6% had major, 8% had neurological, 4% had major neurological, and 4% had select neurological; 2% died within 1 month of surgery). The differences in overall, major, neurological, and select neurological complications were statistically significant, but 1-month mortality and major neurological complications were not. In addition, within subcategories of tumor volume, the incidence of various complications was generally higher for patients undergoing piecemeal resection than for those undergoing en bloc resection. CONCLUSIONS The authors' results indicate that postoperative complication rates are not increased by en bloc resection, including for lesions in eloquent brain regions or for large tumors. This gives credence to the idea that en bloc resection of brain metastases, when feasible, is at least as safe as piecemeal resection.

WOS: 000329981700003, PubMed ID: 24211227, Background: The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. Methods: This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n = 306) were included solely from 38 centers. Results: Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). Conclusions: Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment. (C) 2013 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. All rights reserved.

Treatment of tumors metastatic to the brainstem with stereotactic radiosurgery (SRS) has not been widely studied.To identify the effects of SRS on patients with brainstem metastases by assessing duration of local progression-free survival (LPFS) and overall survival.We retrospectively reviewed clinical data collected from 60 patients undergoing linear accelerator-based SRS for tumors metastatic to the brainstem between August 1994 and December 2007. The LPFS and overall survival were calculated with the Kaplan-Meier method. Prognostic factors were evaluated with the log-rank test and Cox proportional hazards model.The median age of patients was 61 years (range, 39-85 years); the median treated lesion volume was 1.0 mL (range, 0.1-8.7 mL); and the median SRS dose was 15 Gy (range, 8-18 Gy). The median overall survival interval after SRS was 4 months (95% confidence interval, 3.4-4.9 months); crude local tumor control was 76%; and median LPFS was 5.7 months (95% confidence interval, 3.0-8.4 months). Shorter overall survival was associated with a pretreatment tumor volume ≥4 mL (P.001) and male sex (P = .03). Shorter LPFS was associated with a pretreatment tumor volume ≥4 mL (P = .008), a melanoma primary tumor (P = .002), and the presence of necrosis in pre-SRS magnetic resonance imaging (P = .04). A Basic Score for Brain Metastases of 2 to 3 vs 1 (P = .007) and a Score Index for Radiosurgery5 (P = .003) were significantly associated with longer survival. Twelve patients (20%) developed SRS-related complications.Stereotactic radiosurgery provides noninvasive treatment and favorable local tumor control for patients with brainstem metastases.

Melanoma is a common and deadly tumor that upon metastasis to the central nervous system (CNS) has median survival duration of less than 5 months. Activation of the signal transducer and activator of transcription 3 (STAT3) has been identified as a key mediator that drives the fundamental components of melanoma. We hypothesized that WP1066, a novel inhibitor of STAT3 signaling, would enhance the antitumor activity of cyclophosphamide (CTX) against melanoma, including disease within the CNS. The mechanisms of efficacy were investigated by tumor- and immune-mediated cytotoxic assays, in vivo evaluation of the reduction of regulatory T cells (Tregs) and by determining intratumoral p-STAT3 expression by immunohistochemistry. Combinational therapy of WP1066, with both metronomic and cytotoxic dosing of CTX, was investigated in a model system of systemic and intracerebral melanoma in syngeneic mice. Inhibition of p-STAT3 by WP1066 was enhanced with CTX in a dose-dependent manner. However, in mice with intracerebral melanoma, the greatest therapeutic benefit was seen in animals treated with cytotoxic CTX dosing and WP1066, whose median survival time was 120 days, an increase of 375%, with 57% long-term survivors. This treatment efficacy correlated with p-STAT3 expression levels within the tumor microenvironment. The efficacy of the combination of cytotoxic dosing of CTX with WP1066 is attributed to the direct tumor cytotoxic effects of the agents and has the greatest therapeutic potential for the treatment of CNS melanoma.

Purpose: Cytomegalovirus (CMV) has been ubiquitously detected within high-grade gliomas, but its role in gliomagenesis has not been fully elicited. Experimental Design: Glioblastoma multiforme (GBM) tumors were analyzed by flow cytometry to determine CMV antigen expression within various glioma-associated immune populations. The glioma cancer stem cell (gCSC) CMV interleukin (IL)-10 production was determined by ELISA. Human monocytes were stimulated with recombinant CMV IL-10 and levels of expression of p-STAT3, VEGF (vascular endothelial growth factor), TGF-β, viral IE1, and pp65 were determined by flow cytometry. The influence of CMV IL-10–treated monocytes on gCSC biology was ascertained by functional assays. Results: CMV showed a tropism for macrophages (MΦ)/microglia and CD133+ gCSCs within GBMs. The gCSCs produce CMV IL-10, which induces human monocytes (the precursor to the central nervous system MΦs/microglia) to assume an M2 immunosuppressive phenotype (as manifested by downmodulation of the major histocompatibility complex and costimulatory molecules) while upregulating immunoinhibitory B7-H1. CMV IL-10 also induces expression of viral IE1, a modulator of viral replication and transcription in the monocytes. Finally, the CMV IL-10–treated monocytes produced angiogenic VEGF, immunosuppressive TGF-β, and enhanced migration of gCSCs. Conclusions: CMV triggers a feedforward mechanism of gliomagenesis by inducing tumor-supportive monocytes. Clin Cancer Res; 17(14); 4642–9. ©2011 AACR.

Glioblastoma multiforme (GBM) is a lethal cancer that responds poorly to radiotherapy and chemotherapy. Glioma cancer stem cells (gCSCs) have been shown to recapitulate the characteristic features of GBM and to mediate chemotherapy and radiation resistance. Immunotherapeutic targeting of this cell population holds therapeutic promise but must be considered in the context of the immunosuppressive properties mediated by the gCSC. Recent findings have indicated that this goal will be challenging because the gCSC can suppress both the innate and adaptive immune systems by a variety of gCSC-secreted products and cell-membrane interactions. In this review article, we will attempt to reconcile the disparate research findings regarding the potential of immune targeting of the gCSC and propose several novel solutions.

We aimed to investigate if the outcome of the patients with intracranial aneurysm could be predicted by fuzzy logic approach. Two hundred and forty two patients with the diagnosis of intracranial aneurysm were assessed retrospectively between January, 2001 and December 2005 We recorded World Federation of Neurological Surgeons Scale (WFNSS), Fisher Scale and age at admission and Glasgow Outcome Score (GOS) at discharge from hospitalization for all the patients We developed fuzzy sets by dividing WFNSS into four groups as good, fair, bad and very bad; age into three groups as young, middle and old, Fisher scale into three groups as few. moderate and large; outcome score Into four groups as bad, fair, good and very good. We calculated the Outcome of the patient with these sets by fuzzy model. Predicted Outcome by fuzzy logic approach correlated with observed outcome scores of the patients (p > 0.05), including 95% confidence interval. We showed that outcome of the patients with aneurysm can be predicted by fuzzy logic approach, accurately (C) 2009 Elsevier Ltd. All rights reserved