Glioblastoma (GBM) is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs) that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs) were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV). U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm2. Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues.

Background:The glomus jugulare tumor is a slowly growing benign neoplasm originating from neural crest. There is a high morbidity associated with surgical resection of glomus jugulare. Radiosurgery play a relevant role as a therapeutic option in these tumors and its use has grown in popularity. The authors describe a retrospective series of 15 patients and reviewed the literature about the glomus jugulare tumors.Methods:We reviewed retrospectively the data of 15 patients treated with stereotactic linear accelerator stereotactic radiosurgery (LINAC) radiosurgery between 2006 and 2011.Results:The average tumor volume was 18.5 cm3. The radiation dose to the tumor margin ranged between 12 and 20 Gy. The neurological status improved in three patients and remained unchanged in 12 patients. One patient developed a transient 7th nerve palsy that improved after clinical treatment. All tumors remained stable in size on follow-up with resonance magnetic images.Conclusions:The radiosurgery is a safe and effective therapy for patients with glomus jugulare tumor. Despite the short follow-up period and the limited number of patients analyzed, we can infer that radiosurgery produce a tumor growth control with low morbidity, and may be used as a good option to surgical resection in selected cases.

phiC31-mediated gene therapy resulted in an important improvement in IDUA-/- mice, including locomotion, although the obstacles that need to be overcome to enable long-term gene therapy for MPSI are also noted.

Glioblastoma (GBM) is one of the most malignant primary intracranial neoplasms. This review aims to summarize the treatment of elderly patients with newly diagnosed GBM, with a focus on the radiation therapy (RT) approach. The available literature was reviewed, and we describe the most significant results relating to the post-operative approach of elderly GBM patients. Age limitations in randomized phase III studies have restricted the inclusion of elderly patients, and consequently, limited the generalizability of their results to this patient subset. Chronological age should not prohibit the best treatment, but instead, treatment decisions should consider patient functional status. RT showed efficacy and safety in the elderly population, without compromising quality of life. Hypofractionated RT is not inferior to standard RT. Reduction of overall RT schedule length mitigates the difficulties faced by elderly patients, improving treatment adherence. The addition of both concomitant and adjuvant temozolomide to standard RT is superior to either modality alone and should be the treatment of choice in the subset of patients with good/very good prognosis. It is reasonable to offer hypofractionated RT or temozolomide alone for poor prognosis, and best supportive care (BSC) for very poor prognosis elderly GBM patients. Although combined modality treatment is well established for the management of the good prognosis population, different RT schemes require further investigation with randomized controlled trials to determine the best regimen. A robust analysis of the molecular signatures of GBM in elderly patients might reveal opportunities for clinical protocol modifications to customize management in this group of patients.

Objective To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients. Methods We performed a systematic review with network meta-analysis (NMA), including searches on CENTRAL, Medline, EMBASE, CINAHL, clinical trial databases and manual search. Only randomized clinical trials (RCTs) were included. Primary outcomes: overall survival (OS) and adverse events (AE). Secondary outcomes: progression-free-survival (PFS) and quality of life (QoL). We used the Cochrane Risk of Bias (RoB) table for assessing individual studies and CINeMA for evaluating the certainty of the final body of evidence. Results Four RCTs (499 patients) were included. For OS, the estimates from NMA did not provide strong evidence of a difference between the HRTs: 40 Gray (Gy) versus 45 Gy (HR: 0.89; CI 95%: 0.42, 1.91); 34 Gy versus 45 Gy (HR: 0.85; CI 95% 0.43, 1.70); 25 Gy versus 45 Gy (HR: 0.81; CI 95% 0.32, 2.02); 34 Gy versus 40 Gy (HR: 0.95; CI 95% 0.57, 1.61); and 25 Gy versus 34 Gy (HR: 0.95; CI 95% 0.46, 1.97). We performed qualitative synthesis for AE and QoL due to data scarcity and clinical heterogeneity among studies. The four studies reported a similar QoL (assessed by different methods) between arms. One RCT reported grade ≥ 3 AE, with no evidence of a difference between arms. PFS was reported in one study (25 Gy versus 40 Gy), with no evidence of a difference between arms. Conclusion This review found no evidence of a difference between the evaluated HRTs for efficacy and safety.