The glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly affect the immune system, but the mechanisms driving these interactions are not completely clear. Here, we demonstrate that the polyamine metabolite spermidine (SPD) was elevated in the GBM tumor microenvironment.
View Article and Find Full Text PDFThe glioblastoma microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine is elevated in the glioblastoma tumor microenvironment.
View Article and Find Full Text PDFUnlabelled: Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences.
View Article and Find Full Text PDFIntratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistance and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and, ultimately, the treatment response. However, little is known about how germline mutations affect the tumoral microenvironment.
View Article and Find Full Text PDFUnlabelled: In multiple types of cancer, an increased frequency in myeloid-derived suppressor cells (MDSC) is associated with worse outcomes and poor therapeutic response. In the glioblastoma (GBM) microenvironment, monocytic (m) MDSCs represent the predominant subset. However, the molecular basis of mMDSC enrichment in the tumor microenvironment compared with granulocytic (g) MDSCs has yet to be determined.
View Article and Find Full Text PDFMyeloid-derived suppressor cells (MDSC) that block antitumor immunity are elevated in glioblastoma (GBM) patient blood and tumors. However, the distinct contributions of monocytic (mMDSC) versus granulocytic (gMDSC) subsets have yet to be determined. In mouse models of GBM, we observed that mMDSCs were enriched in the male tumors, whereas gMDSCs were elevated in the blood of females.
View Article and Find Full Text PDFBACKGROUNDMyeloid-derived suppressor cells (MDSCs) are elevated in the circulation of patients with glioblastoma (GBM), present in tumor tissue, and associated with poor prognosis. While low-dose chemotherapy reduces MDSCs in preclinical models, the use of this strategy to reduce MDSCs in GBM patients has yet to be evaluated.METHODSA phase 0/I dose-escalation clinical trial was conducted in patients with recurrent GBM treated 5-7 days before surgery with low-dose chemotherapy via capecitabine, followed by concomitant low-dose capecitabine and bevacizumab.
View Article and Find Full Text PDFGlioblastoma (GBM) remains uniformly lethal, and despite a large accumulation of immune cells in the microenvironment, there is limited antitumor immune response. To overcome these challenges, a comprehensive understanding of GBM systemic immune response during disease progression is required. Here, we integrated multiparameter flow cytometry and mass cytometry TOF (CyTOF) analysis of patient blood to determine changes in the immune system among tumor types and over disease progression.
View Article and Find Full Text PDFThe circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM).
View Article and Find Full Text PDFBackground: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis.
View Article and Find Full Text PDFObject: Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).
View Article and Find Full Text PDFPurpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas.
Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study.
Postgrad Med J
September 2010
Objective: To report the evidence for and challenges to the validity of Sheffield Peer Review Assessment Tool (SPRAT) with paediatric Specialist Registrars (SpRs) across the UK as part of Royal College of Paediatrics and Child Health workplace based assessment programme.
Design: Quality assurance analysis, including generalisability, of a multisource feedback questionnaire study.
Setting: All UK Deaneries between August 2005 and May 2006.
Objective: To report the evidence for and challenges to the validity of Sheffield Peer Review Assessment Tool (SPRAT) with paediatric Specialist Registrars (SpRs) across the UK as part of Royal College of Paediatrics and Child Health workplace based assessment programme.
Design: Quality assurance analysis, including generalisability, of a multisource feedback questionnaire study.
Setting: All UK Deaneries between August 2005 and May 2006.
The effects of the calcimimetic drug Cinacalcet were assessed in six children with uncontrolled hyperparathyroidism secondary to stage 5 chronic kidney disease (CKD). Data were collected retrospectively regarding bone biochemistry and medications. Patients were between the ages of 11 months and 14 years on commencing Cinacalcet at initial doses of 0.
View Article and Find Full Text PDFThis study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids.
View Article and Find Full Text PDFBackground: Prognostic factors and outcome are incompletely known in childhood mesangiocapillary glomerulonephritis (MCGN). This study aimed to correlate renal outcome with clinical and histopathological variables.
Methods: We conducted a two-centre retrospective analysis of children with MCGN.
Nephrol Dial Transplant
February 2003
Background: Optimal immunosuppressive drug therapy requires that efficacy be balanced against toxicity. We have performed in vitro assays of cyclosporin (CsA) efficacy in children awaiting renal transplantation.
Methods: Peripheral blood mononuclear cells (PBMC) from 13 children awaiting renal transplantation and 10 healthy paediatric controls ("responders") were incubated in the presence of CsA (0-250 ng/ml).
This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids.
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