Osteoconductivity of bioactive Ti-6Al-4V implants with lattice-shaped interconnected large pores fabricated by electron beam melting.

Additive manufacturing has facilitated the fabrication of orthopedic metal implants with interconnected pores. Recent reports have indicated that a pore size of 600 µm is beneficial for material-induced osteogenesis. However, the complete removal of the metal powder from such small pores of implants is extremely difficult especially in electron beam melting (EBM). We therefore developed a new type of Ti-6Al-4V implant with lattice-shaped interconnected pores measuring 880-1400 µm, which allowed for the easy removal of metal powder. This implant was fabricated by EBM and treated with NaOH, CaCl2, heat, and water (ACaHW treatment) to render the metal surface bioactivity. In the present study, the mechanical and chemical property of the implants and the biocompatibility were evaluated. The SEM and micro-CT images demonstrated the 3D interconnectivity of the porous structures. The average porosity of the porous titanium implant was 57.5%. The implant showed maximum compressive load of 78.9 MPa and Young's modulus of 3.57 GPa which matches that of human cortical bone. ACaHW treatment of the porous Ti-6Al-4V implants induced apatite formation in simulated body fluid in vitro. The ACaHW-treated porous implants harvested from rabbit femoral bone showed direct bonding of bone to the metal surface without interposition of fibrous tissue. The porous ACaHW-treated implant had a higher affinity to the bone than the untreated one. The mechanical strength of implant fixation assessed using the push-out test was significantly higher in the ACaHW-treated implant than in untreated one. FE-SEM analysis and EDX mapping after push-out test of solid implants showed a lot of bone tissue patches on the surface of the ACaHW-treated implant. These results suggest that the new ACaHW-treated Ti-6Al-4V implant with lattice-shaped interconnected pores is a superior alternative to conventional materials for medical application.

STAT3 inhibitor, cucurbitacin I, is a novel therapeutic agent for osteosarcoma.

The development of clinical agents remains a costly and time-consuming process. Although identification of new uses of existing drugs has been recognized as a more efficient approach for drug discovery than development of novel drugs, little screening of drugs that might be used for a rare malignant tumor such as osteosarcoma (OS) has been performed. In this study, we attempted to identify new molecular targeted agents for OS by employing Screening Committee of Anticancer Drugs (SCADS) kits. To screen compounds for OS treatment, their effect on cell viability of the OS cell lines 143B, MG63, HOS, SAOS-2, and HUO9 were evaluated. Candidate drugs were narrowed down based on a global anti-proliferative effect against these five OS cell lines. After excluding cytotoxic compounds and compounds unsuitable for in vivo administration, cucurbitacin I was extracted. Cucurbitacin I has been found to have cytotoxic and anti-proliferative properties against several tumors through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Cucurbitacin I dose- and time-dependently inhibited the proliferation of all five OS cell lines. Following cucurbitacin I treatment, STAT3 was inactivated and analysis of Mcl-1, cleaved PARP and caspase-3 indicated apoptosis induction. Expression of cell cycle regulator proteins, such as phospho-cyclin D1, c-Myc and survivin, were suppressed. Finally, cucurbitacin I potently inhibited the tumor growth of human OS 143B cells in nude mice. Our in vitro and in vivo results suggest that STAT3 inhibition by cucurbitacin I will be an effective and new approach for the treatment of OS.

Impact of plasma fibrinogen levels in benign and malignant soft tissue tumors.

BACKGROUND: Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. OBJECTIVES: The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. METHODS: The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. RESULTS: According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). CONCLUSIONS: We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.