Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes

Abstract Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.7%) pediatric gliomas, 8 of 8 (100%) patient derived orthotopic xenograft (PDOX) mouse models, and in both CD133+ and CD133− glioma cells. We demonstrated that lentiviral-shRNA mediated silencing of suppressed cell proliferation in vitro in cells derived from 3 independent PDOX models and eliminated tumor-forming capacity of CD133+ and CD133− cells derived from 2 PDOX models in mouse brains. Gene expression profiling showed that most of the molecular targets of BMI1 ablation in CD133+ cells were different from that in CD133- cells. Importantly, we found that silencing BMI1 in CD133+ cells derived from 3 PDOX models did not affect most of the known genes previously associated with the activated BMI1, but modulated a novel set of core genes, including RPS6KA2, ALDH3A2, FMFB, DTL, API5, EIF4G2, KIF5c, LOC650152, C20ORF121, LOC203547, LOC653308, and LOC642489, to mediate the elimination of tumor formation. In summary, we identified the over-expressed BMI1 as a promising therapeutic target for glioma stem cells, and suggest that the signaling pathways associated with activated BMI1 in promoting tumor growth may be different from those induced by silencing BMI1 in blocking tumor formation. These findings highlighted the importance of careful re-analysis of the affected genes following the inhibition of abnormally activated oncogenic pathways to identify determinants that can potentially predict therapeutic efficacy.http://deepblue.lib.umich.edu/bitstream/2027.42/110124/1/40478_2014_Article_160.pd

Eosinophilic granuloma of the cervicothoracic junction

✓ A case is reported of eosinophilic granuloma at the cervicothoracic junction presenting with profound quadriparesis preoperatively. The patient underwent excision via an anterior approach, with splitting of the sternum to gain access to the T-1 vertebra. Postoperatively, he has had an excellent return of function.</jats:p

Symptomatic Congenital Spinal Stenosis in a Child

Abstract A case of congenital lumbar stenosis producing lower extremity spasticity and bladder dysfunction in a young child is presented. Myelography demonstrated a marked stenosis of the spinal canal at L-2, L-3, and decompressive laminectomy resulted in a marked improvement in symptoms. A discussion of lumbar stenosis in general illustrates that it is extremely rare for this condition to become symptomatic during childhood. The literature on congenital lumbar stenosis is reviewed.</jats:p

Dural inversion procedure for moyamoya disease

✓ A variety of surgical procedures have been proposed for the treatment of moyamoya disease, but few have used the potential of the middle meningeal artery to any great extent. During the period of spontaneous collateral formation, patients with this disease are at risk for the development of transient ischemic attacks and strokes. Surgical treatments aimed at increasing collateral flow to the brain from the external carotid system have included both direct and indirect anastomotic methods. In this report, the authors describe a technique that used the middle meningeal artery circulation as a source of collateral blood supply by inverting dural flaps that are located on a large meningeal vessel, allowing the richly vascularized outer dural surface to contact a large surface area of the ischemic cortex. An extensive degree of revascularization was observed.</jats:p

Atlanto-axial rotational limitation secondary to osteoid osteoma of the axis

✓ An unusual case of atlanto-axial rotational limitation secondary to an osteoid osteoma of the axis is presented. Transoral microsurgical resection followed by physical therapy improved the clinical symptoms. This case illustrates several unique problems within the cervical spine as well as the efficacy of the transoral approach to the axis.</jats:p