Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB.

Nuclear factor (NF)-κB has been shown to be associated with cancer resistance to radiotherapy (RT), and is constitutively active in the murine osteosarcoma cell line, LM8. Parthenolide has been reported to show antitumor activity through inhibition of the NF-κB pathway. In this study, we investigated the radio-sensitizing activity of parthenolide. We established Luc-LM8, a stable transfectant reporter construct of NF-κB transcriptional activity into LM8. Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were cultured with or without parthenolide treatment, irradiated, and subjected to cell viability and apoptosis assays. In vivo, to investigate whether parthenolide enhances radio-sensitivity of tumors, a tumor growth assay was conducted. Parthenolide enhanced the growth inhibitory effect of RT and induced the apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was significantly suppressed in the mice treated with parthenolide and RT. The present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation. Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing drug for use in cancer RT.

A comparative assessment of synthetic ceramic bone substitutes with different composition and microstructure in rabbit femoral condyle model.

Various bone substitutes with improved biocompatibility have been developed. Because these products vary in composition and microstructure, it is difficult to understand each feature and make an appropriate selection. Three recently developed highly porous ceramic bone substitutes were evaluated, including two made of hydroxyapatite with different structures (Apaceram-AX: 85%-porosity with micropores, NEOBONE: 75%-porosity without micropores) and one composed of beta-tricalcium phosphate (OSferion: 75%-porosity with micropores) in a rabbit model. Apaceram-AX showed gradual degradation, while NEOBONE remaining intact. OSferion was almost completely degraded at 24 weeks. Numerous osteoclasts were detected in materials with micropores, whether Apaceram-AX or OSferion, but not in NEOBONE. These differences of biodegradability seemed to be related to the presence of micropores. The compressive strength of OSferion increased for several weeks and decreased at a level of cancellous bone. The strength of NEOBONE gradually increased and remained at the highest level among three. The strength of Apaceram-AX increased two to three times that of cancellous bone. Surprisingly, the strength of all materials declined during the initial 1 week, suggesting that great care should be taken in the early period after implantation. These findings may help surgeons to select an appropriate porous substitute based on understanding of their features.

Synthetic alginate is a carrier of OP-1 for bone induction.

Bone morphogenetic proteins (BMPs) can induce bone formation in vivo when combined with appropriate carriers. Several materials, including animal collagens and synthetic polymers, have been evaluated as carriers for BMPs. We examined alginate, an approved biomaterial for human use, as a carrier for BMP-7. In a mouse model of ectopic bone formation, the following four carriers for recombinant human OP-1 (BMP-7) were tested: alginate crosslinked by divalent cations (DC alginate), alginate crosslinked by covalent bonds (CB alginate), Type I atelocollagen, and poly-D,L-lactic acid-polyethyleneglycol block copolymer (PLA-PEG). Discs of carrier materials (5-mm diameter) containing OP-1 (3-30 microg) were implanted beneath the fascia of the back muscles in six mice per group. These discs were recovered 3 weeks after implantation and subjected to radiographic and histologic studies. Ectopic bone formation occurred in a dose-dependent manner after the implantation of DC alginate, atelocollagen, and PLA-PEG, but occurred only at the highest dose implanted with CB alginate. Bone formation with DC alginate/OP-1 composites was equivalent to that with atelocollagen/OP-1 composites. Our data suggest DC alginate, a material free of animal products that is already approved by the FDA and other authorities, is a safe and potent carrier for OP-1. This carrier may also be applicable to various other situations in the orthopaedic field.

Bone metastasis of intracranial meningeal hemangiopericytoma.

The authors investigated the clinical and radiological features and the treatment strategy for bone metastasis from a rare tumor, intracranial meningeal hemangiopericytoma. The clinical presentations and characteristic imagings were retrospectively reviewed in 15 bony metastatic lesions of four patients with this tumor. All four cases were initially diagnosed as atypical meningioma, and all of the bone metastases developed more than 10 years after the initial intracranial surgery. The common symptom induced by the metastatic lesions was pain. On plain roentgen films and computed tomography (CT), the involved bones showed thinning and expansion. On bone scintigraphy, a "cold-in-hot" appearance was typically observed. The clinical and radiological findings were diagnosed as bone metastasis from intracranial meningeal hemangiopericytoma. The prognosis after bone metastasis was relatively short compared to the long duration before bone metastases, because of the coexistence of other, visceral, metastasis. Combined with effective radiation therapy, surgical intervention for bone metastasis of this tumor should be carefully considered.