Relationship between malignant subtypes of meningioma and clinical outcome.

We evaluated the relationship between histological malignant subtypes (WHO grade II or III) of meningioma and clinical outcome. Of 485 patients treated surgically for intracranial meningioma at our hospital between 1994 and 2004, 49 (10%; 18 male, 31 female) had potentially malignant features. The histological tumor subtypes within this group of patients included: atypical (n=23); clear cell (n=3); chordoid (n=5); rhabdoid (n=16); and anaplastic (n=4). Correlations among prognosis, recurrence, and the following factors were analyzed for each histological subtype: the Simpson grade of surgical resection (grades I-III vs. grade IV), tumor location (convexity vs. other), the Ki-67 index, and use of postoperative radiotherapy. The median value of the Ki-67 index was 16.2% (range: 1.0-57.2%). The surgical resections were of Simpson grades I-III and IV in 43 and six of the 49 patients, respectively. Tumors recurred after the initial surgical resection in 14 of the 49 patients. In view of the relatively high proportion of malignant subtypes (10%), we suggest that all meningiomas should be evaluated for malignancy. The extent of surgical resection, the histological subtype, and the Ki-67 index can help to predict the clinical outcome for meningioma patients.

Metronomic treatment of temozolomide inhibits tumor cell growth through reduction of angiogenesis and augmentation of apoptosis in orthotopic models of gliomas.

Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Temozolomide (TMZ), a methylating agent is one of the most effective chemotherapeutic agents against glioblastoma. To overcome the problem that most of these tumors become resistant to chemotherapeutic regimens within a year, we investigated the antitumor efficacy of metronomic administration of low-dose TMZ in in vitro cell proliferation/cytotoxicity assay and in vivo rat and nude mouse orthotopic glioma model. By in vitro assay, we elucidated that C6/LacZ rat glioma cells were more resistant to metronomic treatment of TMZ than U-87MG human glioblastoma cells and bEnd.3 mouse brain endothelial cells. Compared with the conventional chemotherapeutic regimen of TMZ, we found that frequent administration of TMZ at a low dose (metronomic treatment) markedly inhibited angiogenesis as well as tumor growth in a TMZ-resistant C6/LacZ rat glioma model. In addition, metronomic treatment of TMZ significantly augmented apoptosis of tumor cells in this model. For the TMZ-sensitive U-87MG cells, even with a very low dose of TMZ, which is not effective to reduce tumor mass, the metronomic treatment of TMZ reduced the microvessel density, i.e. angiogenesis, in a nude mouse orthotopic model. In conclusion, for both models, the metronomic treatment of TMZ decreased angiogenesis. Especially, in TMZ-resistant glioma cells, this regimen increased apoptosis of tumor cells and decreased tumor growth. The metronomic treatment of TMZ in orthotopic glioma models demonstrated a successful antiangiogenic effect which can overcome the chemoresistance in conventional TMZ chemotherapy.