Significance of LRP and PPAR-gamma Expression in Lipomatous Soft Tissue Tumors.

BACKGROUND: Molecular mechanism of differentiation in lipogenic tumor is still unknown in detail. Low-density lipoprotein receptor-related protein (LRP) and peroxisome proliferator-activated receptor gamma (PPAR-gamma), representative regulatory molecules of lipogenic differentiation, have been reported today as multi-functional molecules and to modulate tumorigenesis in various kind of cancer. To date, diagnostic and therapeutic significance of the expression of these molecules in lipogenic tumors are not defined. METHODS: The immunohistochemical expression status of LRP and PPAR-gamma in various grades of 54 lipogenic tumors was analyzed. Correlation between the expression levels and the differentiation of the tumors was confirmed. For statistical analyses, the Kruskal-Wallis test, the Steel-Dwass test and the Mann-Whitney U test were used. RESULTS: LRP and PPAR-gamma expression was detected in 50 (92.6%) and 44 (81.5%) cases, respectively. The expression level in LRP was significantly higher in cases with well differentiated liposarcoma, pleomorphic liposarcoma and dedifferentiated liposarcoma than in lipoma. Compared with lipoma or well differentiated liposarcoma, significant elevation in expression level of PPAR-gamma was confirmed in myxoid liposarcoma, pleomorphic liposarcoma, dedifferentiated liposarcoma and the differentiated area of dedifferentiated liposarcoma. CONCLUSION: The up-regulation of LRP and PPAR-gamma in higher grade cases, i.e. less differentiated tumors than in low grade cases was shown, suggesting the candidate role of these molecules as tumor progression modulators rather than regulatory molecules of differentiation in lipogenic tumors.

Effects of CD44 antibody-- or RGDS peptide--immobilized magnetic beads on cell proliferation and chondrogenesis of mesenchymal stem cells.

We evaluated the efficacy of a novel mesenchymal stem cell (MSC) delivery system using an external magnetic field for cartilage repair in vitro. MSCs were isolated from the bone marrow of Sprague Drawley rats and expanded in a monolayer. To use the MSC delivery system, two types of MSC-magnetic bead complexes were designed and compared. Expanded MSCs were combined with small-sized (diameter: 310 nm) carboxyl group-combined (0.01-0.04 micromol/mg) magnetic beads, Ferri Sphere 100C, through either anti-rat CD44 mouse monoclonal antibodies or a synthetic cell adhesion factor, arginine (R)-glycine (G)-aspartic acid (D)-serine (S) (RGDS) peptide. Both cell complexes were successfully created, and were able to proliferate in monolayer culture up to at least day 7 after separation of magnetic beads from the cell surface, although the proliferation of the complexes was slower in the early period of culture than that of non-labeled rat MSCs (after 7 days of culture: proliferation of CD44 antibody-bead complexes, approximately 50%; RGDS peptide-bead complexes, 70% versus non-labeled rat MSCs, respectively). These complexes were seeded onto culture plates with or without an external magnetic force (magnetic flux density was 0.20 Tesla at a distance of 2 mm from plate base) generated by a neodymium magnet, and supplemented with chondrogenic differentiation medium. Both complexes could be attached and gathered effectively under the influence of the external magnet, and CD44-bead complexes could effectively generate chondrogenic matrix in monolayer culture. In a three-dimensional culture system, the production of a dense chondrogenic matrix and the expression of type II collagen and aggrecan mRNA were detected in both complexes, and the chondrogenic potential of these complexes was only a little less than that of rat MSCs alone. Thus, we conclude that due to the fact that MSC-RGDS peptide-bead complexes are composed using a biodegradable material, RGDS peptide, as a mediator, the RGDS peptide-bead complex is more useful for minimally invasive clinical applications using our design of magnetic MSC delivery system than CD44 antibody-beads.

Acetabular osteosarcoma treated by irradiation-vascularized hybrid bone graft.

BACKGROUND: Periacetabular reconstruction after malignant bone tumor resection to preserve limb function is extremely challenging. The optimal reconstruction method has not yet received consensus and the functional outcomes still remain unsatisfactory. CASE REPORT: A thirteen-year-old girl who was suffering from acetabular osteosarcoma was treated with wide excision of the tumor, followed by periacetabular reconstruction with an autogenous extracorporeal irradiated osteoarticular graft combined with a vascularized fibula graft. Incorporation of the irradiated pelvic bone was achieved despite infection and limb function turned out to be acceptable. CONCLUSION: This is the first report on an irradiation-vascularized hybrid autograft to reconstruct massive bone loss in primary limb-sparing surgery.

Histological findings in a human autogenous pasteurized bone graft.

BACKGROUND: Autogenous bone graft after pasteurization is one of the most valuable procedures for reconstruction of large bone defects following excision of malignant musculoskeletal tumors. To date, there have been no documented histological reports on pasteurized bone grafts, apart from short-term histological results. CASE REPORT: We treated a 27-year-old male with a periosteal chondrosarcoma of the tibia by wide excision and reimplantation of the large pasteurized bone. Biopsy specimens harvested from the pasteurized bone over 3 years after reimplantation were evaluated histologically. The graft cortices remained totally necrotic with empty osseous lacuna, whereas the architecture of the acellular cortical bones was still maintained without microfractures. Deposited seams of woven bone existed focally on the surface of the acellular trabeculae. CONCLUSION: Our medium-term histological outcome suggests the limitations of incorporating a pasteurized hone graft, but also advocates its role as a useful temporary material for the reconstruction of massive bone defects.

Evaluation of systemic chemotherapy with magnetic liposomal doxorubicin and a dipole external electromagnet.

The development of an active drug delivery system is an attractive approach to increase the targetability of anticancer agents. In the present study, we examined the efficiency of systemic chemotherapy with small magnetic liposomes containing doxorubicin (magnetic DOX liposomes) and an externally applied electromagnetic force in osteosarcoma-bearing hamsters. Syrian male hamsters inoculated with osteosarcoma, OS515, in the limb were studied 7 days after inoculation. The efficiency of this system was evaluated by measuring the tissue distribution and tumor-suppressing effects of DOX on primary tumor growth and lung metastases. A DC dipole electromagnet was used, and the hamster's tumor-bearing limb was placed between 2 poles after the i.v. administration of liposomes. The dose of DOX and the magnetic field strength were fixed at 5 mg/kg and 0.4 T, respectively. Administration of magnetic DOX liposomes followed by 60 min application of magnetic field produced a 3- to 4-fold higher maximum DOX concentration in the tumor. This newly designed systemic chemotherapy significantly suppressed primary tumor growth for at least 2 weeks, though other DOX treatments also suppressed compared to control. Histologic examination confirmed a greater antitumor effect of this systemic chemotherapy compared to standard methods. In addition, this approach significantly suppressed lung metastases measured at 3 weeks posttreatment. These results suggest that this systemic chemotherapy can effectively reduce primary tumor growth and suppress lung metastasis due to increased targeting of DOX. Such targeted drug delivery for anticancer agents would provide clinical advantages compared to current methods.

Articular cartilage repair using tissue engineering technique--novel approach with minimally invasive procedure.

Articular cartilage has very limited potential to spontaneously heal, because it lacks vessels and is isolated from systemic regulation. Although there have been many attempts to treat articular cartilage defects, such as drilling, microfracture techniques, soft tissue grafts or osteochondral grafts, no treatment has managed to repair the defects with long-lasting hyaline cartilage. Recently, a regenerative medicine using a tissue engineering technique for cartilage repair has been given much attention in the orthopedic field. In 1994, Brittberg et al. introduced a new cell technology in which chondrocytes expanded in monolayer culture were transplanted into the cartilage defect of the knee. As a second generation of chondrocyte transplantation, since 1996 we have been performing transplantation of tissue-engineered cartilage made ex vivo for the treatment of osteochondral defects of the joints. This signifies a concept shift from cell transplantation to tissue transplantation made ex vivo using tissue engineering techniques. We have reported good clinical results with this surgical treatment. However, extensive basic research is vital to achieve better clinical results with this tissue engineering technique. This article describes our recent research using a minimally invasive tissue engineering technique to promote cartilage regeneration.