Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients.

Glioblastoma stem cells (GSC) co-exhibiting a tumor-initiating capacity and a radio-chemoresistant phenotype, are a compelling cell model for explaining tumor recurrence. We have previously characterized patient-derived, treatment-resistant GSC clones (TRGC) that survived radiochemotherapy. Compared to glucose-dependent, treatment-sensitive GSC clones (TSGC), TRGC exhibited reduced glucose dependence that favor the fatty acid oxidation pathway as their energy source. Using comparative genome-wide transcriptome analysis, a series of defense signatures associated with TRGC survival were identified and verified by siRNA-based gene knockdown experiments that led to loss of cell integrity. In this study, we investigate the prognostic value of defense signatures in glioblastoma (GBM) patients using gene expression analysis with Probeset Analyzer (131 GBM) and The Cancer Genome Atlas (TCGA) data, and protein expression with a tissue microarray (50 GBM), yielding the first TRGC-derived prognostic biomarkers for GBM patients. Ribosomal protein S11 (RPS11), RPS20, individually and together, consistently predicted poor survival of newly diagnosed primary GBM tumors when overexpressed at the RNA or protein level [RPS11: Hazard Ratio (HR) = 11.5, p<0.001; RPS20: HR = 4.5, p = 0.03; RPS11+RPS20: HR = 17.99, p = 0.001]. The prognostic significance of RPS11 and RPS20 was further supported by whole tissue section RPS11 immunostaining (27 GBM; HR = 4.05, p = 0.01) and TCGA gene expression data (578 primary GBM; RPS11: HR = 1.19, p = 0.06; RPS20: HR = 1.25, p = 0.02; RPS11+RPS20: HR = 1.43, p = 0.01). Moreover, tumors that exhibited unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) or wild-type isocitrate dehydrogenase 1 (IDH1) were associated with higher RPS11 expression levels [corr (IDH1, RPS11) = 0.64, p = 0.03); [corr (MGMT, RPS11) = 0.52, p = 0.04]. These data indicate that increased expression of RPS11 and RPS20 predicts shorter patient survival. The study also suggests that TRGC are clinically relevant cells that represent resistant tumorigenic clones from patient tumors and that their properties, at least in part, are reflected in poor-prognosis GBM. The screening of TRGC signatures may represent a novel alternative strategy for identifying new prognostic biomarkers

Relationship Between [18F]FDOPA PET Uptake, Apparent Diffusion Coefficient (ADC), and Proliferation Rate in Recurrent Malignant Gliomas

Purpose: Diffusion magnetic resonance imaging (MRI) and 6-[18F]fluoro-l-dopa ([18F]FDOPA) positron emission tomography (PET) are used to interrogate malignant tumor microenvironment. It remains unclear whether there is a relationship between [18F]FDOPA uptake, diffusion MRI estimates of apparent diffusion coefficient (ADC), and mitotic activity in the context of recurrent malignant gliomas, where the tumor may be confounded by the effects of therapy. The purpose of the current study is to determine whether there is a correlation between these imaging techniques and mitotic activity in malignant gliomas.Procedures: We retrospectively examined 29 patients with recurrent malignant gliomas who underwent structural MRI, diffusion MRI, and [18F]FDOPA PET prior to surgical resection. Qualitative associations were noted, and quantitative voxel-wise and median measurement correlations between [18F]FDOPA PET, ADC, and mitotic index were performed.Results: Areas of high [18F]FDOPA uptake exhibited low ADC and areas of hyperintensity T2/fluid-attenuated inversion recovery (FLAIR) with low [18F]FDOPA uptake exhibited high ADC. There was a significant inverse voxel-wise correlation between [18F]FDOPA and ADC for all patients. Median [18F]FDOPA uptake and median ADC also showed a significant inverse correlation. Median [18F]FDOPA uptake was positively correlated, and median ADC was inversely correlated with mitotic index from resected tumor tissue.Conclusions: A significant association may exist between [18F]FDOPA uptake, diffusion MRI, and mitotic activity in recurrent malignant gliomas

Pediatric necrobiosis lipoidica: case report and review of the literature

Necrobiosis lipoidica (NL) is a rare, granulomatous disease considered to be associated with diabetes. It is frequently seen in female and middle-aged patients and is rarely observed in children. We present a 14-year-old boy with poorly controlled type 1 diabetes who developed biopsy-proven NL. He had improvement, but not resolution of the plaque with improved glycemic control. Pediatric NL may be associated with diabetes and could be related to poor glycemic control. However, further investigation is warranted in this young population

Pediatric necrobiosis lipoidica: case report and review of the literature

Necrobiosis lipoidica (NL) is a rare, granulomatous disease considered to be associated with diabetes. It is frequently seen in female and middle-aged patients and is rarely observed in children. We present a 14-year-old boy with poorly controlled type 1 diabetes who developed biopsy-proven NL. He had improvement, but not resolution of the plaque with improved glycemic control. Pediatric NL may be associated with diabetes and could be related to poor glycemic control. However, further investigation is warranted in this young population

Comparison of highly purified urinary versus recombinant FSH: Effect on ART outcomes in polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common cause of ovulatory disorders and infertility with high LH to FSH ratio. In order to prevent further increase of LH and follicle atresia, different regimens for ovulation induction have been recommended using FSH alone. Objective: This study was performed in PCOS patients to compare ART outcomes in cycles induced by FSH alone, using either recombinant or urinary products. Materials and Methods: In a randomized trial, from 623 patients who underwent down regulation with GnRH analogue in a long protocol, 160 PCOS patients were randomly divided into two groups of 80. Group A received 150 IU/d recombinant FSH (Gonal-F) and group B 150 IU/d urinary FSH (Fostimon). Results: 33 cases (41.2%) in group A and 36 (45%) in group B achieved clinical pregnancy, which was not significantly different (p=0.67). Total number of oocytes retrieved (13.03±5.56 vs. 14.17±4.89, p=0.17), quality and number of embryos (7.42±3.35 vs. 7.63±3.28, p=0.68) and OHSS rate were similar in group A compared to group B. Endometrial thickness which was 9.66±1.67 mm in group A and 10.36±1.35 mm in group B, showed a significant difference (p=0.004). Conclusion: It seems that in PCOS patients, both pure FSH products used for controlled ovarian hyperstimulation have similar effects on ART outcome and can be used according to availability and patient acceptance without significant differenc

Comparison of highly purified urinary versus recombinant FSH: Effect on ART outcomes in polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a common cause of ovulatory disorders and infertility with high LH to FSH ratio. In order to prevent further increase of LH and follicle atresia, different regimens for ovulation induction have been recommended using FSH alone. Objective: This study was performed in PCOS patients to compare ART outcomes in cycles induced by FSH alone, using either recombinant or urinary products. Materials and Methods: In a randomized trial, from 623 patients who underwent down regulation with GnRH analogue in a long protocol, 160 PCOS patients were randomly divided into two groups of 80. Group A received 150 IU/d recombinant FSH (Gonal-F) and group B 150 IU/d urinary FSH (Fostimon). Results: 33 cases (41.2%) in group A and 36 (45%) in group B achieved clinical pregnancy, which was not significantly different (p=0.67). Total number of oocytes retrieved (13.03±5.56 vs. 14.17±4.89, p=0.17), quality and number of embryos (7.42±3.35 vs. 7.63±3.28, p=0.68) and OHSS rate were similar in group A compared to group B. Endometrial thickness which was 9.66±1.67 mm in group A and 10.36±1.35 mm in group B, showed a significant difference (p=0.004). Conclusion: It seems that in PCOS patients, both pure FSH products used for controlled ovarian hyperstimulation have similar effects on ART outcome and can be used according to availability and patient acceptance without significant difference

Clinicopathologic Study of Calcifying Fibrous Tumor of the Gastrointestinal Tract: A Case Series.

Calcifying fibrous tumor (CFT) is a rare benign mesenchymal lesion known to arise at multiple body sites that may clinically mimic other more aggressive lesions in the gastrointestinal (GI) tract. In this study we describe the clinicopathologic findings of 28 GI tract CFTs. Tumors predominantly arose in middle-aged adults with a slight female predominance. The most commonly involved sites were small bowel and colon, followed by stomach and appendix. Tumors ranged from 0.3 to 9.3 cm (median 1.4 cm), and submucosa was the most commonly involved layer. All tumors were well circumscribed and unencapsulated. Microscopically, tumors were hypocellular and composed of spindle cells with abundant, haphazardly arranged hyalinized collagen. No necrosis and less than one mitosis per 10 HPF were identified in all cases. Calcification was present in most (81%) of the cases. All cases had lymphoplasmacytic inflammatory infiltrates either scattered throughout the lesion with occasional perivascular conglomeration or in the form of lymphoid aggregates. A lymphoplasmacytic cuff was usually present (81%). Immunostains showed variable CD34 immunoreactivity and variable numbers of IgG4-positive plasma cells. The lesional cells were negative for DOG-1, ALK-1, S100, C-kit, Sox10, Melan A, HMB45, desmin, CK7, and CK20, and showed cytoplasmic staining for β-catenin. Follow-up information was available in 5 cases with no recurrences reported to date (mean follow-up, 3 years). CFT is a rare benign tumor that can occur in part of the GI tract and should be distinguished from other mesenchymal tumors due to its low risk of recurrence