125I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts.

BACKGROUND: Lung cancer is a fatal disease and a serious health problem worldwide. Patients are usually diagnosed at an advanced stage, and the effectiveness of chemotherapy for such patients is very limited. Iodine 125 seed (125I) irradiation can be used as an important adjuvant treatment for lung carcinoma. The purpose of this study was to examine the role of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on apoptosis. METHODS: 40 mice with A549 lung adenocarcinoma xenografts were randomly divided into 4 groups: control group (n = 10), sham seed (0 mCi) implant group (n = 10), 125I seed (0.6 mCi) implant group (n = 10) and 125I seed (0.8 mCi) implant group (n = 10), respectively. The body weight and tumor volume, were recorded every 4 days until the end of the study. Apoptotic cells were checked by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and activities of caspase-3 and caspase-8 enzyme were tested. Expression of P21, survivin, livin, caspase-9 and proliferating cell nuclear antigen (Ki-67) was detected with immunohistochemical staining. RESULTS: The results of TUNEL staining assays showed that 125I seed irradiation suppresses the growth of lung cancer xenografts in nude mice and induced apoptosis. The activity of caspase-3 and caspase-8 was significantly higher. The expression levels Ki67, survivin and livin were substantially downregulated, while P21 and caspase-9 protein expression were significantly increased following 125I seed irradiation. This study revealed that 125I seed irradiation could significantly change apoptosis-related protein in human lung cancer xenografts. CONCLUSIONS: Overall, our study demonstrates that radiation exposure by 125I seeds could be a new treatment option for lung cancer.

New bone formation around implants inserted on autologous and xenografts irradiated or not with IR laser light: a histomorphometric study in rabbits.

Use of biomaterials and light on bone grafts has been widely reported. This work assessed the influence of low-level laser therapy (LLLT) on bone volume (BV) and bone implant contact (BIC) interface around implants inserted in blocks of bovine or autologous bone grafts (autografts), irradiated or not, in rabbit femurs. Twenty-four adult rabbits were divided in 8 groups: AG: autograft; XG: xenograft; AG/L: autograft + laser; XG/L: xenograft + laser; AG/I: autograft + titanium (Ti) implant; XG/I: xenograft + Ti implant; AG/I/L: autograft + Ti implant + laser; and XG/I/L: xenograft + Ti implant + laser. The animals received the Ti implant after incorporation of the grafts. The laser parameters in the groups AG/L and XG/L were λ=780 nm, 70 mW, CW, 21.5 J/cm 2 , while in the groups AG/I/L and XG/I/L the following parameters were used: λ=780 nm, 70 mW, 0.5 cm 2 (spot), 4 J/cm 2 per point (4), 16 J/cm 2 per session, 48 h interval × 12 sessions, CW, contact mode. LLLT was repeated every other day during 2 weeks. To avoid systemic effect, only one limb of each rabbit was double grafted. All animals were sacrificed 9 weeks after implantation. Specimens were routinely stained and histomorphometry carried out. Comparison of non-irradiated and irradiated grafts (AG/L versus AG and XG/L versus XG) showed that irradiation increased significantly BV on both grafts (p=0.05, p=0.001). Comparison between irradiated and non-irradiated grafts (AG/I/L versus AG/I and XG/I/L versus XG/I) showed a significant (p=0.02) increase of the BIC in autografts. The same was seen when xenografts were used, without significant difference. The results of this investigation suggest that the use of LLLT is effective for enhancing new bone formation with consequent increase of bone-implant interface in both autologous grafts and xenografts.

New Bone Formation around Implants Inserted on Autologous and Xenografts Irradiated or not with IR Laser Light: A Histomorphometric Study in Rabbits

Use of biomaterials and light on bone grafts has been widely reported. This work assessed the influence of low-level laser therapy (LLLT) on bone volume (BV) and bone implant contact (BIC) interface around implants inserted in blocks of bovine or autologous bone grafts (autografts), irradiated or not, in rabbit femurs. Twenty-four adult rabbits were divided in 8 groups: AG: autograft; XG: xenograft; AG/L: autograft + laser; XG/L: xenograft + laser; AG/I: autograft + titanium (Ti) implant; XG/I: xenograft + Ti implant; AG/I/L: autograft + Ti implant + laser; and XG/I/L: xenograft + Ti implant + laser. The animals received the Ti implant after incorporation of the grafts. The laser parameters in the groups AG/L and XG/L were λ=780 nm, 70 mW, CW, 21.5 J/cm 2 , while in the groups AG/I/L and XG/I/L the following parameters were used: λ=780 nm, 70 mW, 0.5 cm 2 (spot), 4 J/cm 2 per point (4), 16 J/cm 2 per session, 48 h interval × 12 sessions, CW, contact mode. LLLT was repeated every other day during 2 weeks. To avoid systemic effect, only one limb of each rabbit was double grafted. All animals were sacrificed 9 weeks after implantation. Specimens were routinely stained and histomorphometry carried out. Comparison of non-irradiated and irradiated grafts (AG/L versus AG and XG/L versus XG) showed that irradiation increased significantly BV on both grafts (p=0.05, p=0.001). Comparison between irradiated and non-irradiated grafts (AG/I/L versus AG/I and XG/I/L versus XG/I) showed a significant (p=0.02) increase of the BIC in autografts. The same was seen when xenografts were used, without significant difference. The results of this investigation suggest that the use of LLLT is effective for enhancing new bone formation with consequent increase of bone-implant interface in both autologous grafts and xenografts.

O uso de biomateriais e luz em enxertos ósseos têm sido relatados. Esse trabalho avaliou a influência do laser baixa potência - LBP no volume ósseo (VO) e superfície de contato osso-implante (COI) ao redor de implantes dentários inseridos em blocos de enxerto bovino ou autólogos incorporados, irradiados ou não, em fêmures de coelho. Vinte e quatro coelhos adultos foram divididos em 8 grupos: EA: enxerto autólogo; EX: enxerto xenógeno; EA/L: enxerto autólogo + laser; EX/L: enxerto xenógeno + laser; EA/I: enxerto autólogo + implante; EX/I: enxerto xenógeno + implante; EA/I/L: enxerto autólogo + implante de titânio + laser; EX/I/L: enxerto xenógeno + implante de titânio + laser. Os animais receberam um implante de titânio após a incorporação dos enxertos. Os parâmetros de laser nos grupos EA/L e EX/L foram λ =780 nm, 70 mW, CW, 21,5 J/cm 2 ), enquanto que nos grupos EA/I/L e EX/I/L os seguintes parâmetros de laser foram utilizados: λ =780 nm, 70 mW, 0,5 cm 2 (spot), 4 J/cm 2 por ponto (4), 16 J/cm 2 por sessão, intervalo de 48 h × 12 sessões, CW, modo contato. O LBP foi repetido a cada 48 h (2 semanas). Para evitar efeito sistêmico apenas um membro de cada coelho foi duplamente enxertado. Todos os animais foram sacrificados 9 semanas após o implante. Os espécimes foram corados rotineiramente e histomorfometria foi realizada. A comparação dos enxertos não-irradiados e irradiados (EA/L versus EA e EX/L versus EX) mostrou que a irradiação aumentou significantemente (p=0,02) o VO para ambos os tipos de enxertos (p=0,05, p=0,001). A comparação dos enxertos não-irradiados e irradiados (EA/I/L versus EA/I e EX/I/L versus EX/I) mostrou um aumento significante (p=0,02) do COI nos enxertos autólogos e xenógenos sem diferença estatística. Os resultados desta investigação sugerem que o uso de LBP é efetivo para aumentar a neoformação óssea com consequente aumento do COI em enxertos autólogos e xenógenos.