Antitumor activity of 5-hydroxy-3',4',6,7-tetramethoxyflavone in glioblastoma cell lines and its antagonism with radiotherapy.

5-Hydroxy-3',4',6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.

Combination treatment for glioblastoma with temozolomide, DFMO and radiation.

PURPOSE: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with dismal prognosis. This tumor is characterized by extensive heterogeneity, thus is difficult to treat and every established or new treatment faces significant hazard of resistance. Temozolomide (TMZ), an oral alkylating agent, is the first-line treatment for GBM, but resistance to TMZ is a major problem. Herewith, we investigated the combined effect of TMZ, difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, and radiation in GBM cell lines. METHODS: We used the U87G, U251MG and T98G GBM cell lines. A linac 6MV accelerator (Varian Medical Systems) was used for cell irradiation. Viability and proliferation of the cells were examined with trypan blue exclusion assay, crystal violet and xCELLigence system. Cell cycle and activation of caspase-8 were evaluated with flow cytometry. RESULTS: The combination treatment resulted in a consistent higher suppression of proliferation in all cell lines treated and induced a significant higher cell cycle arrest in G2/M phase in U251MG and T98G cell lines. In U251MG cells caspase-8 was increased with each treatment alone, however the combination treatment had lower level of caspase-8 induction, suggesting a co-existence of another mechanism of cell death apart from apoptosis. In T98G cells the combination treatment increased the activation of caspase-8. CONCLUSION: Combination treatment with DFMO, TMZ and radiation significantly reduced cell viability in all cell lines tested. Given that both TMZ and DFMO can be administered orally and are related to minimal toxicities, this combination treatment may be a novel treatment strategy for GBM that deserves further investigation.

A new modular nail for the diaphyseal fractures of the humerus.

Over a period of 5 years, 63 traumatic and eight pathological diaphyseal humeral fractures were treated with a new modular humeral nail. The nail is cannulated, square in shape--with concave sides--and has two different extensions that can be used with either the antegrade or the retrograde approach. Adequate rotational and axial stability is provided without the need for distal locking screws in the majority of fractures, while the need for proximal locking screws during the antegrade procedure is abolished. This study aims to present the 'Garnavos' nail and the results of its use, along with proposals and guidelines that should be considered whenever intramedullary nailing is selected for the treatment of diaphyseal humeral fractures.

Prevention of heterotopic ossification in high-risk patients with total hip arthroplasty: the experience of a combined therapeutic protocol.

The combination of radiotherapy and indomethacin for the prevention of heterotopic ossification (HO) in high-risk patients undergoing total hip arthroplasty (THA) has not been reported. The aim of the present study was to present the experience of our department with this combined therapeutic protocol. Fifty-four patients who underwent THA received a single dose of 7 Gy of postoperative radiotherapy and 75 mg of indomethacin for 15 days. Patients were analyzed for clinical and radiographical evidence of HO development at 1 year postoperatively. The overall radiographical incidence of HO was 20.4% (95% CI 10.6-33.5%), while only 1 patient with clinically significant HO was seen. Patients with secondary arthritis due to congenital hip disease had a statistically significantly higher incidence of HO compared with those with osteoarthrosis. The clinical assessment with the Merle d'Aubigné score showed that patients with radiographic documentation of HO had a lower mean score compared with those with no evidence of HO. No treatment-related side effects were seen. Combined radiotherapy and indomethacin was effective in preventing heterotopic ossification after total hip arthroplasty. The evaluation of this efficacy compared with radiotherapy or NSAIDs alone should be the future target of larger randomized designs.