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To investigate the safety of combined Wilms tumor 1 peptide vaccination and temozolomide treatment of glioblastoma, a phase I clinical trial was designed. Seven patients with histological diagnosis of glioblastoma underwent concurrent radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1 peptide vaccination 1 week after the end of combined concurrent radio/temozolomide therapy, and administration was continued once per week for 7 weeks. Temozolomide maintenance was started and performed for up to 24 cycles, and the observation period for safety encompassed 6 weeks from the first administration of maintenance temozolomide. All patients showed good tolerability during the observation period. Skin disorders, such as grade 1/2 injection-site reactions, were observed in all seven patients. Although grade 3 lymphocytopenia potentially due to concurrent radio/temozolomide therapy was observed in five patients (71.4 %), no other grade 3/4 hematological or neurological toxicities were observed. No autoimmune reactions were observed. All patients are still alive, and six are on Wilms tumor 1 peptide vaccination without progression, yielding a progression-free survival from histological diagnosis of 5.2-49.1 months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12 injections by the patient's request. The safety profile of the combined Wilms tumor 1 peptide vaccination and temozolomide therapy approach for treating glioblastoma was confirmed.

Musashi1 (MSI1) is an evolutionarily conserved RNA-binding protein, selectively expressed in neural stem cells (NSCs) and considered a versatile marker for normal NSCs and tumor cell diagnosis. Here, we examined MSI1 expression in primary pediatric brain tumors, medulloblastomas and ependymomas, by double immunostaining with lineage phenotypic markers (Lin). These tumors highly express MSI1 and are heterogeneous, containing both MSI1+/Lin- tumor cells in regions of relatively high cellularity and proliferative activity and MSI1+/Lin+ tumor cells in regions of lower cellularity. These findings suggest that MSI1 may be a useful marker for characterizing tumor heterogeneity and for examining in situ the analogy between normal NSCs and MSI1+ cells in pediatric brain tumors. This test could be easily applied to routine clinical diagnosis., (Copyright (c) 2007 S. Karger AG, Basel.)

Purpose: We evaluated the clinical usefulness of the Cho/Cr ratio of proton MR spectroscopy(1H-MRS) to differentiate residual/recurrent glioma from non-neoplastic lesions., Patients and Methods: 20 cases of glioma were involved in this study(astrocytoma grade I-II: 7, oligodendroglioma: 1, astrocytoma grade III: 2, glioblastoma: 10). Seven of the patients underwent surgical resection only, 4 underwent surgical resection and radiotherapy(40-60 Gy), and 9 underwent surgical resection and radiotherapy with concurrent chemotherapy(14-60 Gy). 1H-MRS was performed on a 1.5 Tesla clinical MR unit using a 3D-chemical shift imaging sequence(1500 msec/270 msec/1 (TR/TE/excitations), and the Cho/Cr ratio was calculated in the voxel where neoplastic lesion was most suspected on MRI. The presence of lactate + lipid peak was also evaluated. All spectra were obtained after the contrast enhanced study., Results: Cho/Cr ratios were significantly higher in cases of residual/recurrent tumors(mean +/- SD = 1.70 +/- 0.96) than in non-neoplastic lesions(mean +/- SD = 1.04 +/- 1.16) (Mann-Whitney U-test p = 0.047). If a Cho/Cr ratio of more than 1.5 was used as a marker of tumor presence, its sensitivity was 64%, specificity 83%, and accuracy 70%. One false-positive case that of radiation necrosis whose spectrum showed a high Cho/Cr ratio with markedly elevated lactate + lipid peak., Conclusion: The Cho/Cr ratio of 1H-MRS provides additional information to MRI in differentiating residual/recurrent gliomas from non-neoplastic lesions.