Inhibition of Invasion by Polyphenols from Citrus Fruit and Berries in Human Malignant Glioma Cells In Vitro.

BACKGROUND/AIM: The outlook for patients with high grade glioma (HGG) remains dismal. Hence, attention has focused on numerous innovative treatments. Our group has proposed a strategy on the use of a combination of polyphenols, as anti-invasive agents for the management of these neoplasms. MATERIALS AND METHODS: The aim of this study was to evaluate the in vitro effects of citrus flavonoids (tangeretin, nobiletin, naringin and limonin) and berry extracts (chokeberry, elderberry and bilberry) on selected mediators of invasion in 2 HGG cell cultures. RESULTS: The IC50 values could only be determined for tangeretin and chokeberry extract. The rest were non-functional in this context. Immunocytochemistry and flow cytometry results showed that chokeberry extract was most effective in down-regulating the expression of CD44. Similarly, RT-PCR data supported its ability to reduce gene expression of MMP-14 and EGFR. 2D invasion assays confirmed that inhibition is greater with chokeberry extract. CONCLUSION: Both polyphenols have anti-invasive potential but chokeberry extract is a stronger agent for glioma management.

DRAQ7 as an Alternative to MTT Assay for Measuring Viability of Glioma Cells Treated With Polyphenols.

BACKGROUND/AIM: The tetrazolium-based MTT cytotoxicity assay is well established for screening putative anti-cancer agents. However, it has limitations including lack of reproducibility with glioma cells treated with polyphenols. The aim of this study was to evaluate whether a flow cytometric assay with the anthraquinone, DRAQ7, was a better alternative than the colorimetric MTT assay for measuring cell viability. MATERIALS AND METHODS: Two glioma cell lines (IPSB-18, U373) and 1 pancreatic cancer cell line (AsPC-1) were treated with 4 polyphenols, namely red grape seed extract, red clover extract, anthocyanin-rich extract and curcumin. Cell viability was assessed using MTT assay and DRAQ7 staining. RESULTS: Limitations of MTT assay included lack of sensitivity and interference with the structure and absorbance spectra of polyphenols. Also, DMSO was toxic to glioma cells. Microscopic observations of cells treated with polyphenols confirmed the range of IC50 values evaluated by DRAQ7, but not by the MTT assay. CONCLUSION: DRAQ7 is a better alternative than MTT for measuring viability of glioma cells treated with brightly coloured polyphenols.

Lack of Correlation Between Immunohistochemical Expression of SPARC and Invasion in Different Grades of Meningiomas.

BACKGROUND: Grade I meningiomas are generally benign and non-invasive whereas Grade II (atypical) and Grade III (malignant) meningiomas tend to be invasive with a high risk of recurrence. SPARC, secreted protein, acidic and rich in cysteine, is a multifunctional glycoprotein which has been proposed to be a potential diagnostic marker of invasive meningiomas. There has been increased reporting of atypical meningiomas since the current World Health Organization (WHO) included brain invasion as a grading criterion for classification of these particular meningiomas. MATERIALS AND METHODS: The aim of this study was to re-evaluate any correlation between immunohistochemical expression of SPARC in 34 meningiomas of various grades using the current classification (2016). We had previously classified these cases using the 2002 WHO criteria. RESULTS: There is no correlation between expression of SPARC and invasion in different grades of meningioma. CONCLUSION: SPARC does not appear to be a good predictor of invasion in meningiomas.

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

Intraoperative indocyanine green video-angiography as an aid to the microsurgical treatment of spinal vascular malformations.

AIMS AND OBJECTIVES. Intra-operative Indocyanine Green (ICG) video-angiography (ICG-VA) has become an established aid to cerebrovascular surgery. We describe our experience using this technique to define angio-architecture intraoperatively in a range of spinal vascular malformations. METHODS. A retrospective review of notes and imaging was carried out from a prospectively maintained database. Our series comprises 27 patients who underwent surgical treatment between September 2007 and August 2012. We carried out a retrospective review of data from a prospectively maintained database. RESULTS. For slow-flow Type 1 fistulae the ICG videoangiogram demonstrated conclusively that the arteriovenous shunt was obliterated. This is a consideration on the rare occasions where a second fistula is present, an example of which is included in this series. ICG-VA also helps to demonstrate normal vascular anatomy and distinguish these vessels from pathology. For Type II lesions it allowed orientation to the vascular anatomy as demonstrated by the pre-operative angiogram. In one of two cases in this series it ensured to the complete extirpation of a large arteriovenous malformation (AVM). However a second Type II case demonstrated its limitations, as a diffuse intramedullary component could not be identified. Two cases were explored where digital subtraction spinal angiography was not possible and incomplete understanding of the angio-architectures of the lesions were available from Time Resolved dynamic magnetic resonance angiography and/or multi-detector CT angiography. ICG-VA provided invaluable information on alterations in arterio-venous flow that allowed diagnosis and obliteration of the arteriovenous shunts in each case. DISCUSSION. ICG video-angiography is a time-efficient and safe alternative to intra-operative spinal angiography. It provided useful information on haemodynamic changes intraoperatively and completeness of treatment. We discuss its limitations and role in the management of these lesions.

January 2003: 56-year-old female with right frontal tumor of the dura.

The January Case of the Month (COM). A 56 year-old female presented with a 5-month history of dizziness, focal motor seizures and progressive immobility. CT scan showed a large frontal tumor with a meningioma-like pattern. The patient underwent right frontal craniotomy and complete resection of the tumor. Biopsy showed lymphoid infiltrates consisting predominantly of centrocyte-like cells admixed with plasma cells and lymphoid follicles. Immunohistochemistry revealed CD20-positive cells and light chain restriction with reactive T cells. These appearances are characteristic of the MALT-type lymphomas. There was no evidence of systemic lymphoma. The patient is symptom-free 18 months after complete resection. MALT lymphoma is rare but recognized subtype of primary meningeal lymphoma. MALT lymphoma of dura tends to be relatively indolent, with excellent prognosis. It is suggested that meningeal MALT-type lymphoma may follow on from a pre-existing inflammatory process.

Thoracic idiopathic spinal cord herniation at the vertebral body level: a subgroup with a poor prognosis? Case reports and review of the literature.

The authors present two cases of thoracic idiopathic spinal cord herniation (TISCH) occurring at the vertebral body (VB) level in whom adequate surgical reduction failed to reverse symptoms. In the second case, in which TISCH occurred into a VB cavity, presentation was atypical (subacute spinal cord syndrome) and there was persistent postoperative deterioration. In both cases, adequate surgical reduction was achieved via a posterior midthoracic laminectomy, and reduction was maintained by closure of the anterior dural defect by using prosthetic material. Thoracic idiopathic spinal cord herniation occurring at a VB level may be technically well treated by surgical reduction, but the outcome appears less predictable. Herniation that occurs directly into a VB cavity may form a distinct subgroup in which the presentation is atypical and the prognosis worse.