Role of Nitric Oxide in Glioblastoma Therapy: Another Step to Resolve the Terrible Puzzle ?

Glioblastoma Multiforme, the most common and aggressive primary brain tumor, remains incurable despite of the advent of modern surgical and medical treatments. This poor prognosis depends by the recurrence after surgery and intrinsic or acquired resistance to chemotherapy and radiotherapy. Nitric oxide is a small molecule that plays a key roles in glioma pathophysiology. Many researches showing that NO is involved in induction of apoptosis, radiosensitization and chemosensitization. Therefore, NO role, if clarified, may improve the knowledge about this unsolved puzzle called GBM.

Stem cells based therapy in high grade glioma: why the intraventricular route should be preferred?

AIM: Mesenchymal stem cells (MSCs) migrate in response to chemokines and possess extensive tropism for experimental glioma. Antitumor effects have been reported following intracranial and intravenous administration of gene-modified MSCs. Among the different routes for cell transplant, the intraventricular (IV) approach found very little employment in comparison with intraparenchymal, intratumoral and intravenous administration protocols. Nevertheless, IV transplantation offers advantages in terms of cells viability and distribution toward target sites, opening interesting opportunities for its clinical application. METHODS: Using a rat glioma model, we investigated migratory capacity, tumor tropism, distribution and differentiation of MSCs following IV administration. RESULTS: Transplanted MSCs create niches of viable cells in the subventricular zone and can be stimulated to migrate to sites of tumor infiltration. MSCs seemed not to be involved in tumor growth and angiogenesis. CONCLUSION: We speculate that the IV route can be used to achieve a kind of reservoir of self-renewal cells, potentially active against the spread of cancer cells. Further studies are needed to shed light on MSCs distribution close to the ventricular wall, in order to define their lifespan and their capacity to migrate towards new-enhancing foci time after implantation.

Progressive spontaneous occlusion of a cerebellar AVM: pathogenetic hypothesis and review of literature.

Cerebral arteriovenous malformation (AVM) is a complex network of vascular channels consisting of arterial feeders, a nidus and enlarged venous drainage. AVMs usually increase in size with time, but may rarely obliterate; spontaneous angiographic regression occurs in less than 1.5% of cerebral AVMs. Several causes of spontaneous regression have been postulated such us hemodynamic alterations due to hemorrhage, hypercoagulability, atherosclerosis, and tromboembolism from associated aneurysms. In this report we describe a case of spontaneous, complete and asymptomatic occlusion of a left cerebellar hemispheric AVM; angiograms clearly demonstrate a progressive decrease in size of the AVM at follow-up. Thrombosis of the dominant-draining vein caused by turbulent blood flow seemed to be the main driver. Possible mechanisms leading to the occlusion are discussed and a review of the literature is reported.