ABSTRACT
PURPOSE: Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group 1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/therapy , Dacarbazine/analogs & derivatives , Glioma/therapy , Hyperbaric Oxygenation , Animals , Apoptosis , Brain Neoplasms/pathology , Cell Line, Tumor , Combined Modality Therapy/methods , Dacarbazine/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Glioblastoma/pathology , Glioblastoma/therapy , Rats , Rats, Wistar , TemozolomideABSTRACT
PURPOSE: Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.
OBJETIVO: A temozolomida (TMZ) tem atividade anti-tumoral em pacientes com glioma maligno. Oxigênio hiperbárico (HBO) pode aumentar a eficácia de terapias que são limitadas devido a um microambiente do tumor hipóxico. Foram examinados os efeitos combinados de TMZ-HBO em um modelo de glioma em rato. MÉTODOS: Após a injeção estereotáxica de células de glioma de rato C6/LacZ no cérebro de ratos Wistar, os ratos foram distribuídos aleatoriamente em três grupos de tratamento: Grupo 1: tratamento de controle. Grupo 2: TMZ sozinho. Grupo 3: uma combinação de TMZ e HBO. Os ratos foram sacrificados 18 dias após o tratamento. Foram avaliados o número de vasos intra-/peri-tumoral, proliferação microendotelial, imunohistoquímica e área necrótica . RESULTADOS: O tecido tumoral foi marcado apenas esparsamente com GFAP. O tratamento com temozolomida diminuiu significativamente o tecido intratumoral e a área total do tumor. O nível de Ki67 foi significativamente diminuído no tecido do tumor do grupo 3. Além disso, a superfície necrótica total / volume total do tumor (%) diminuiu significativamente no tecido do tumor do grupo 3 em comparação com grupo 1 e 2. CONCLUSÃO: A combinação de oxigênio hiperbárico com temozolomida produziu uma redução importante no crescimento do glioma podendo ser abordagem eficaz para o tratamento do glioblastoma.
Subject(s)
Animals , Rats , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/therapy , Dacarbazine/analogs & derivatives , Glioma/therapy , Hyperbaric Oxygenation , Apoptosis , Brain Neoplasms/pathology , Cell Line, Tumor , Combined Modality Therapy/methods , Disease Models, Animal , Drug Evaluation, Preclinical , Dacarbazine/therapeutic use , Glioblastoma/pathology , Glioblastoma/therapy , Rats, WistarABSTRACT
PURPOSE: Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.(AU)
OBJETIVO: A temozolomida (TMZ) tem atividade anti-tumoral em pacientes com glioma maligno. Oxigênio hiperbárico (HBO) pode aumentar a eficácia de terapias que são limitadas devido a um microambiente do tumor hipóxico. Foram examinados os efeitos combinados de TMZ-HBO em um modelo de glioma em rato. MÉTODOS: Após a injeção estereotáxica de células de glioma de rato C6/LacZ no cérebro de ratos Wistar, os ratos foram distribuídos aleatoriamente em três grupos de tratamento: Grupo 1: tratamento de controle. Grupo 2: TMZ sozinho. Grupo 3: uma combinação de TMZ e HBO. Os ratos foram sacrificados 18 dias após o tratamento. Foram avaliados o número de vasos intra-/peri-tumoral, proliferação microendotelial, imunohistoquímica e área necrótica . RESULTADOS: O tecido tumoral foi marcado apenas esparsamente com GFAP. O tratamento com temozolomida diminuiu significativamente o tecido intratumoral e a área total do tumor. O nível de Ki67 foi significativamente diminuído no tecido do tumor do grupo 3. Além disso, a superfície necrótica total / volume total do tumor (%) diminuiu significativamente no tecido do tumor do grupo 3 em comparação com grupo 1 e 2. CONCLUSÃO: A combinação de oxigênio hiperbárico com temozolomida produziu uma redução importante no crescimento do glioma podendo ser abordagem eficaz para o tratamento do glioblastoma.(AU)