End Plate Disproportion and Degenerative Disc Disease: A Case-Control Study

Study DesignCase-control.PurposeTo determine whether a disproportion between two neighboring vertebral end plates is associated with degenerative disc disease.Overview of LiteratureRecently, it has been suggested that disproportion of the end plates of two adjacent vertebrae may increase the risk of disc herniation.MethodsMagnetic resonance (MR) images (n=160) with evidence of grades I-II lumbar degenerative disc disease (modified Pfirrmann's classification) and normal MR images of the lumbar region (n=160) were reviewed. On midsagittal sections, the difference of anteroposterior diameter of upper and lower end plates neighboring a degenerated (in the case group) or normal (in the control group) intervertebral disc was calculated (difference of end plates [DEP]).ResultsMean DEP was significantly higher in the case group at the L5-S1 level (2.73±0.23 mm vs. 2.21±0.12 mm, p=0.03). Differences were not statistically significant at L1-L2 (1.31±0.13 mm in the cases vs. 1.28±0.08 mm in the controls, p=0.78), L2-L3 (1.45±0.12 mm in the cases vs. 1.37±0.08 mm in the controls, p=0.58), L3-L4 (1.52±0.13 mm in the cases vs. 1.49±0.10 mm in the controls, p=0.88), and L4-L5 (2.15±0.21 mm in the cases vs. 2.04±0.20 mm in the controls, p=0.31) levels. The difference at the L5-S1 level did not remain significant after adjusting for body mass index (BMI), which was significantly higher in the patients.ConclusionsEnd plate disproportion may be a significant, BMI-dependent risk factor for lumbar degenerative disc disease

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). METHODS CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

Quality of sunglasses available in the Iranian market; a study with emphasis on sellers′ license

Context: Sunglasses should follow minimum requirements to sufficiently protect eyes. It is not known whether all items obtainable from the market are appropriately designed. Aims: To compare ultraviolet (UV)-protective properties of commercially available sunglasses obtained from authorized and unauthorized Iranian sellers. Settings and Study Design: An analytic-descriptive study performed in a metropolitan area (Tehran). Materials and Methods: Using a UV-visible standard spectrophotometer, the percentage transmittance was scanned between 280 and 400 nm in 348 pairs of nonprescription sunglasses (price range: 20-80 US$) obtained anonymously and randomly from authorized (permitted by the Ministry of Health, 189 pairs) and unauthorized (159 pairs) sellers in the Iranian capital city, Tehran. The Australian/New Zealand Standard (AS/NZS) and the American National Standards Institute [ANSI] standards were followed. Statistical Analysis: Chi-square test, independent samples t-test or Mann-Whitney U-test. Results UV-protective properties of the sunglasses obtained from authorized sellers complied with AS/NZS and ANSI guidelines in 92.6% and 95.2% of items, respectively. The corresponding rates for sunglasses obtained from unauthorized sellers were 0% and 8.2%, respectively (P < 0.001 for both). The rate of defective polarizing capability of lenses was 27.4% in sunglasses obtained from authorized sellers versus 90.4% in sunglasses obtained from unauthorized sellers (P < 0.001). Neither brand nor price played significant contributions to UV protection/lens polarizing capability of sunglasses obtained from authorized sellers. Conclusions: Sunglasses provided by unauthorized sellers are alarmingly unreliable and could be potentially hazardous for the eye. Brand and price do not guarantee optimal protection against UV radiation or polarizing performance of the lens

Expression of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium: a histopathological study

Our objective was to examine the expression rates of p53, Bcl-2 and Bax in endometrial carcinoma, endometrial hyperplasia and normal endometrium. A total of 94 endometrial frozen sections (carcinoma 48, hyperplasia 21, normal tissue 25) were examined immunohistochemically in terms of the expression rates of p53, Bcl-2 and Bax. All of the specimens in the non-malignant groups were positive for Bax, whereas this rate was 85.4% in the group with malignant specimens (p = .03). Conversely, p53 was expressed only in the cancerous group (77.1%, p < .001). The Bcl-2 expression rate was 54.2% in the cancer group, 76.2% in the group with hyperplasia and 60% in the group containing normal tissue (p = .23). Comparing to the non-malignant specimens, the mean Bcl-2/Bax were significantly higher in the malignant group. In conclusion, Bax under-expression, p53 over-expression and a high Bcl-2 to Bax ratio might be associated with endometrial carcinoma. Bcl-2, however, plays no significant role in this regard.Impact statement What is already known on this subject? The p53, Bcl-2 and Bax are the three major genes that regulate apoptosis. Some studies have suggested that these genes may play a role in the pathogenesis of endometrial carcinoma. The available reports, however, are old and inconclusive. What do the results of this study add? Comparing immunohistochemically obtained p53, the Bcl-2 and Bax expression rates between normal endometrial tissue, endometrial specimens with endometrial hyperplasia and specimens with carcinoma showed that Bax under-expression, p53 over-expression and a high Bcl-2 to Bax ratio were associated with malignancy. Using an up-to-date technique to examine the three major regulators of apoptosis at the same time, in a rather large sample size of both normal and abnormal endometrial tissue specimens simultaneously, are the major advantages of the present work. What are the implications of these findings for clinical practice and/or further research? According to our findings, the status of p53, Bcl-2 and Bax expression in the endometrial tissue can be used for risk stratification of endometrial carcinoma for both screening and preventive purposes

Conformal Radiation Therapy for Pediatric Patients with Low-Grade Glioma: Results from the Children\u27s Oncology Group Phase 2 Study ACNS0221

Purpose: To determine the rate of marginal relapse, progression-free survival (PFS), and overall survival (OS) in patients with pediatric low-grade glioma (PLGG) treated with conformal radiation therapy (CRT) with a clinical target volume (CTV) margin of 5 mm in the Children\u27s Oncology Group trial ACNS0221. Methods and Materials: Patients aged 3 to 21 years with unresectable progressive, recurrent, or residual PLGG were eligible for this study. Patients younger than 10 years were required to have received at least 1 chemotherapy course. Patients with neurofibromatosis type I were not eligible. All patients underwent magnetic resonance imaging-based planning and received 54 Gy CRT in 30 fractions with a 5-mm CTV margin. Results: Of 85 eligible patients (median age, 13.6 years) treated between March 2006 and December 2010, 14 were younger than 10 years and 36 received prior chemotherapy. Sixty-six had pilocytic astrocytoma, 15 had other histologic subtypes, and 4 had unbiopsied chiasmatic lesions. Events included 23 relapses (19 central, 4 distant, and no marginal) and 7 deaths. At a median follow-up of 5.15 years, 5-year PFS was 71% ± 6% and OS was 93% ± 4%. Male sex (P =.068) and large tumor size (P =.050) trended toward significance for association with decreased PFS. Age, histology, tumor location, time between diagnosis and study entry, and MIB-1 status were not associated with PFS. OS was negatively associated with male sex (P =.064), non-pilocytic astrocytoma histology (P =.010), and large tumor size (P =.0089). Conclusions: For patients with PLGG, CRT with a CTV margin of 5 mm yields an acceptable PFS and does not lead to a high rate of marginal relapse