Re-thinking congenital piriform aperture stenosis: Modern imaging demonstrates narrowing of the full nasal cavity length.

OBJECTIVE: Measure the width of the nasal cavity in cases of piriform aperture stenosis using computerised tomography scans. METHODS: Retrospective study performed at a paediatric tertiary referral centre in Australia. Comparison nasal cavity widths (measured on computerised tomography scans in the axial plane) at the piriform aperture, choana and points 25, 50 and 75% along the length of nasal cavity, between cases with piriform aperture stenosis and controls. RESULTS: In cases of piriform aperture stenosis the piriform aperture along with the nasal cavity is statistically significantly narrower than controls, measured at 25, 50 and 75% along the distance between the piriform aperture and the choana. CONCLUSION: This modern imaging review has illustrated the need for a change in the treatment paradigm for neonates with this condition, suggesting the need for further investigation of techniques that treat narrowing beyond the aperture.

CD15 Expression Does Not Identify a Phenotypically or Genetically Distinct Glioblastoma Population.

UNLABELLED: : Recent research has focused on the hypothesis that the growth and regeneration of glioblastoma (GB) is sustained by a subpopulation of self-renewing stem-like cells. This has led to the prediction that molecular markers for cancer stem cells in GB may provide a treatment target. One candidate marker is CD15: we wanted to determine if CD15 represented a credible stem cell marker in GB. We first demonstrated that CD15-positive (CD15+) cells were less proliferative than their CD15-negative (CD15-) counterparts in 10 patient GB tumors. Next we compared the proliferative activity of CD15+ and CD15- cells in vitro using tumor-initiating primary GB cell lines (TICs) and found no difference in proliferative behavior. Furthermore, TICs sorted for CD15+ and CD15- were not significantly different cytogenetically or in terms of gene expression profile. Sorted single CD15+ and CD15- cells were equally capable of reconstituting a heterogeneous population containing both CD15+ and CD15- cells over time, and both CD15+ and CD15- cells were able to generate tumors in vivo. No difference was found in the phenotypic or genomic behavior of CD15+ cells compared with CD15- cells from the same patient. Moreover, we found that in vitro, cells were able to interconvert between the CD15+ and CD15- states. Our data challenge the utility of CD15 as a cancer stem cell marker. SIGNIFICANCE: The data from this study contribute to the ongoing debate about the role of cancer stem cells in gliomagenesis. Results showed that CD15, a marker previously thought to be a cancer stem-like marker in glioblastoma, could not isolate a phenotypically or genetically distinct population. Moreover, isolated CD15-positive and -negative cells were able to generate mixed populations of glioblastoma cells in vitro.

NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature.

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches. Neuroglia (NG)-2 is a transmembrane proteoglycan expressed by NG2+ progenitors and is strongly linked to cell proliferation in the normal brain. By using NG2 as a biomarker we identify a GBM cell population (GBM NG2+ cells) with robust proliferative, clonogenic, and tumorigenic capacity. We show that a significant proportion (mean 83%) of cells proliferating in the tumor mass express NG2 and that over 50% of GBM NG2+ cells are proliferating. Compared with the GBM NG2- cells from the same tumor, the GBM of NG2+ cells overexpress genes associated with aggressive tumorigenicity, including overexpression of Mitosis and Cell Cycling Module genes (e.g., MELK, CDC, MCM, E2F), which have been previously shown to correlate with poor survival in GBM. We also show that the coexpression pattern of NG2 with other glial progenitor markers in GBM does not recapitulate that described in the normal brain. The expression of NG2 by such an aggressive and actively cycling GBM population combined with its location on the cell surface identifies this cell population as a potential therapeutic target in a subset of patients with GBM.

Glioblastoma cell lines derived under serum-free conditions can be used as an in vitro model system to evaluate therapeutic response.

We provide evidence that six glioblastoma cell lines derived and maintained under serum-free conditions secrete VEGF and four also expressed VEGF(R2). Expression of VEGF(R2) was associated with reduced proliferation in response to anti-VEGF antibodies. Spontaneous loss of VEGF(R2) over passage was associated with loss of this anti-proliferative effect. Gain of expression of VEGF(R2) was not associated with the acquisition of responsiveness to anti-VEGF antibodies. Secretion of PDGF was absent in 5/6 of our cell lines and none of the cell lines had reduced proliferation in response to anti-PDGF antibodies suggesting that PDGF autocrine signalling was unlikely to be significant in tumour proliferation. These data are consistent with published clinical trials suggesting that glioblastoma cell lines derived under serum-free conditions have the potential for use in drug screening and individualising patient therapy.