Summary Statement. Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines. This demonstrated the potential application of sorafenib in the treatment of osteosarcoma metastasis and radiation resistance. Introduction. More than 20% of patients with osteosarcoma die of the disease within 5 years due to tumour relapse and metastasis. Identifying new treatment that works singly or in combination with conventional therapies is urgently required. We previously found that the Ras/Raf/MAPK pathway was associated with lung metastasis in a 143B inoculated osteosarcoma orthotopic mouse model. 1. Sorafenib, a multi-kinase inhibitor, has shown potent anticancer effect including in osteosarcoma. 2. through the inhibition of Raf-1 and other targets. 3. The aims of this study were to investigate effect of sorafenib on osteosarcoma cell lines with or without activated Ras/Raf/MAPK signalling and to decide whether sorafenib could enhance irradiation on these cells. Materials and Methods. Osteosarcoma cell lines 143B (HOS with Ras gene transfection), HOS and U2OS were used. Clonogenic assay was applied for assessing tumour growth and colony formation with or without treatment. Sorefenib was provided by Bayer gratis.
Extracorporeal irradiation and re-implantation of a bone segment is a technique employed in bone sarcoma surgery for limb salvage in the setting of reasonable bone stock. There is neither consensus nor rationale given for the dosage of irradiation used in previous studies, with values of up to 300Gy applied. We investigated the influence of extracorporeal irradiation on the elastic and viscoelastic properties of bone. Bone specimens were extracted from mature cattle and subdivided into thirteen groups; twelve groups exposed to increasing levels of irradiation and a control group. The specimens, once irradiated, underwent mechanical testing in saline at 37°C. Mechanical properties were calculated by experimental means which included Young's Modulus, Storage Modulus and Loss Modulus. These were all obtained for comparison of the irradiated specimens to the control group. There were non-significant negligible changes in all of the mechanical properties of bone that were assessed with increasing dosage of irradiation. Therefore, we conclude that the overall mechanical effect of high levels of extracorporeal irradiation (300Gy) is minute, and can be administered to reduce the risk of malignancy recurrence.
Acellular porcine super flexor tendon (pSFT) offers a promising solution to replacement of damaged anterior cruciate ligament [1]. It is desirable to package and terminally sterilise the acellular grafts to eliminate any possible harmful pathogens. However, irradiation techniques can damage the collagen ultra-structure and consequently reduce the mechanical properties [2]. The aims of this study were to investigate the effects of irradiation sterilisation of varying dosages on the biomechanical properties of the acellular pSFT. Tendons were decellularised using a previously established protocol [1] and subjected to irradiation sterilisation using either 30 kGy gamma, 55 kGy gamma, 34 kGy E-beam, 15 kGy gamma, 15 kGy E-beam and (15+15) kGy E-beam (fractionated dose). Specimens then underwent stress relaxation and strength testing at 0 and 12 months post sterilisation to determine whether any effect on these properties was progressive. For stress relaxation testing, specimens were analysed using a Maxwell-Wiechert model. For strength testing, the ultimate tensile strength, Young's modulus and failure strain were assessed. Significant differences were found which demonstrated that all irradiation treatments had an effect on the time-independent and time-dependent viscoelastic properties of irradiated tendons compared to per-acetic acid only treated controls. Interestingly, no significant differences were found between the irradiated groups. Similar trends were found for the strength testing properties. No significant differences were found between groups at 0 and 12 months. Tendons retained sufficient biomechanical properties following sterilisation, however it was notable that there were no significant differences between the irradiated groups, as it was believed higher dosages would lead to a greater reduction in the mechanical properties. The changes observed were not altered further after 12 months storage, indicating the acellular pSFT graft has a stable shelf-life.
Low energy irradiation of vitamin E blended UHMWPE is feasible to fabricate total joint implants with high wear resistance and impact strength. Irradiated ultra-high molecular weight polyethylene (UHMWPE), used in the fabrication of joint implants, has increased wear resistance. But, increased crosslinking decreases the mechanical strength of the polymer, thus limiting the crosslinking to the surface is desirable. Here, we used electron beam irradiation with low energy electrons to limit the penetration of the radiation exposure and achieve surface cross-linking.Summary
Introduction
Summary. Photodynamic therapy with ICG lactosome and near-infrared light has phototoxic effects on human breast cancer cells. With the same total energy, phototoxic effects depend on output of irradiation light rather than irradiation time. Introduction. The phototoxic effects of indocyanine green (ICG) and near-infrared light have been studied in various fields. Plasma proteins bind strongly to ICG, which is followed by rapid clearance by the liver, resulting in no tumor selectivity after systemic administration. We have proposed a novel nanocarrier labeled with ICG (ICG lactosome) that has tumor selectivity due to its enhanced permeation and retention (EPR) effect. The aim of this study was to investigate in vitro phototoxic effects and to optimise the irradiation conditions by changing the output and time of near-infrared light as excitation light. Materials and Methods. MDA-MB-231 human breast cancer cells were seeded (2 × 10. 4. cells per well) into 96-well plates. The plates were divided (16 wells/treatment) into the following groups: control/untreated, only ICG lactosome administration (ICG lactosome), only laser irradiation (laser), and ICG lactosome administration plus laser irradiation (photodynamic therapy: PDT). Cells in the control, laser, and PDT groups were incubated in 100 μl medium for 24 h. Cells in the ICG lactosome group were incubated in 100μl medium containing 1 mg ICG lactosome for 24 h. The following day, laser group samples with 100 μl phosphate buffer solution (PBS) and PDT group samples with PBS containing 1 mg ICG lactosome were treated with laser irradiation using a near-infrared medical diode laser (λ = 810 ± 20 nm).
