The long-term results obtained in a series of 174 patients operated on for spinal meningiomas are critically analyzed. This series was similar to those of other authors with regard to age, sex, location of the tumors, and clinical presentation. Before surgery, about 70% of the patients were included in Groups I and II (mild neurological impairment), and about 30% of the patients were classified in Groups III and IV (significant to severe neurological impairment, up to paraplegia). Complete tumor removal was achieved in 96.5% of the patients, and surgical mortality was about 1%. Microsurgical technique, which was adopted in the last 29 cases, proved to be very effective in reducing undue damage to the spinal cord and in minimizing the postoperative neurological deficits. Of the 174 patients who underwent surgery, 156 underwent late follow-up study for an average of 15 years (2 patients died in the immediate postoperative period, and 16 patients were lost to follow-up). Twenty-nine patients died of causes unrelated to the spinal meningioma; of the remaining 126 patients, 92% were categorized in Groups I and II, and only 8% in Groups III and IV. The rate of recurrence was 6% (9 patients) among the 150 patients who had complete tumor removal, and the rate of regrowth was 17% (1 patient with anaplastic meningioma) among the 6 patients treated by subtotal removal. The early diagnosis of the disease and the use of microsurgical technique appeared as the most relevant factors for further improvement of the surgical results.
Our results appear to demonstrate that the procedures of ex vivo expansion of autologous mesenchymal stem cells and of transplantation into the spinal cord of humans are safe and well tolerated by ALS patients.
Our results demonstrate that direct injection of autologous expanded MSCs into the spinal cord of ALS patients is safe, with no significant acute or late toxicity, and well tolerated. The clinical results seem to be encouraging.
High-grade gliomas (HGG) have a poor outcome, however, prognostic subgroups of patients may be individuated by some clinico-biological parameters. It was recently demonstrated that the main response of HGG to therapy is autophagic death. Autophagy is involved in tumor suppression, and is defective in HGG, in which we previously found an underexpression of beclin 1 autophagic gene protein product. Underexpression of Beclin 1 protein has been correlated to poor patient outcome in other tumor types. In this paper, the prognostic role of Beclin 1 expression in HGG patients was investigated. We first evaluated the tumor cell cytoplasmic expression of Beclin 1 protein (BPCE), in a sample of 76 HGG by immunohistochemistry, and compared it with cell proliferation and apoptosis. We found high BPCE score positively correlated with apoptosis, and negatively with cell proliferation (p < 0.05). We then correlated BPCE score with survival and other prognostic parameters (histological grading, MGMT gene methylation status, age, patient performance status according to the Karnofski classification (KPS), extent of surgery, radiation therapy (RT) modality, temozolomide chemotherapy (TMZ CHT), and optimal/suboptimal post-surgical treatment). Forty-seven (61.8%) and twenty-nine (38.2%) patients showed high and low BPCE scores, respectively. BPCE showed statistically significant correlations with survival both at the univariate (p = 0.03) and multivariate analysis (p = 0.037). High BPCE was also positively correlated with high KPS values (p = 0.023), and with the accomplishment of an optimal postoperative therapy (p = 0.037). Furthermore, among patients showing a MGMT methylated gene, survival was significantly higher in cases with a higher BPCE score. BPCE score might be added to pathological evaluation of HGG for prognostic purposes.
Glioblastomas (GBMs), the most common primary malignancies of the central nervous system, are highly aggressive and heterogeneous, and remain a dramatic therapeutic challenge. Markers mirroring the complex molecular profile of GBMs that are predictive of patient outcomes are needed to define novel multi-targeted treatment strategies. Resistance to current GBM therapies is partly due to a subpopulation of stem-like and other self-renewing cells (hereafter called glioma stem-like cancer cells, GSCC), which are therefore of key interest as therapeutic entry points. Wnt and Hedgehog are among the main pathways involved in GSCC renewal. β-catenin and Gli1 are markers of Wnt and Hedgehog activation respectively and both pathways are known to be altered in gliomas. To date, there are no investigations of Gli1 protein expression in GBM tissue, and recently a high expression of β-catenin has been found to have a poor prognostic impact in GBM patients in a study. We have therefore quantified the positivity for β-catenin, Gli1, as well as Ki-67, p53, and EGFR proteins on immunohistochemically-stained GBM sections from 106 patients in an investigation for potential predictive biomarkers. Correlation between these markers and survival was evaluated by pair-wise Pearson correlation coefficient and by bi-dimensional hierarchical clustering, followed by survival estimations using linear regression models and classification trees. We demonstrated that both β-catenin and, for the first time, Gli1 proteins are highly predictive markers of short survival, being found in 75 and 90% of the highly predictive trees, respectively, whereas Ki-67, p53 and EGFR were under 30% and thus, not considered as predictive. Our results indicate a role of β-catenin and Gli1 in GBM malignant behaviour, and suggest that inhibiting members of Wnt and Hedgehog pathways could be a valuable therapeutic strategy for GBM patients.
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