RESUMO
We aimed to evaluate dendritic cell (DC) tumor vaccines for preventing liver cancer recurrence and metastasis. DCs were induced from mononuclear cells in the peripheral blood with recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) and recombinant human interleukin 4 (rhIL-4), followed by sensitization with lysis of autologous liver cancer cells. One hundred and sixty patients with hepatocellular carcinoma were randomly divided into two groups of 80. One group was treated postoperatively with six cycles of the DC tumor vaccine. The other group was treated postoperatively with six cycles of FOLFOX 6, beginning 1 week after surgery. After treatment with DC tumor vaccines, the levels of CD3+, CD4+, and CD8+, the ratio of CD4+ to CD8+ DC, and the serum levels of IL-12 and IFN-γ were significantly increased both in comparison to the pre-treatment levels (P < 0.001) and to the chemotherapy group (P < 0.001). After a postoperative follow-up of 18 months, the metastatic recurrence rate in the DC tumor vaccine group was significantly lower than that in the chemotherapy group (17.50 vs 48.75%, P < 0.005), and the survival rate of the patients in the DC tumor vaccine group was higher than that of the chemotherapy treatment group (86.25 vs 52.50%, P < 0.005). Treatment with DC tumor vaccines was safe and feasible. It can enhance the immunity of the patients, reduce the rates of metastasis and recurrence, and improve survival rates. This is a promising treatment for the prevention of postoperative recurrence in patients with liver cancer.
Assuntos
Vacinas Anticâncer/imunologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Células Dendríticas/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Antígenos de Superfície/metabolismo , Biomarcadores , Vacinas Anticâncer/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Citocinas/sangue , Células Dendríticas/metabolismo , Feminino , Seguimentos , Humanos , Imunofenotipagem , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
This study investigated the effects of CpG ODN1826 plus radiotherapy (RT) on tumor growth and angiogenesis of subcutaneous tumor in a rat model. Four treatment groups were tested in which rats were injected with 100 µL CpG ODN1826 (1 µg/µL) or 100 µL vehicle, with and without exposure to 8 Gy after 2 h. At 7 days after inoculation of lung cancer cells, drugs were injected in the tumor and radiation was administered over 5 days, after which the rate of tumor inhibition was calculated. Expression of VEGF-C in tumor tissue was seen in 10, 50, 80, and 100% of tumors in the CpG ODN1826 + RT, CpG ODN1826, vehicle + RT, and vehicle alone groups, respectively, while positive expression of NRP-1 was seen in 10, 40, 90, and 100% of tumors. The decreases in expression of VEGF-C mRNA in the CpG ODN1826 + RT and CpG ODN1826 groups compared with the NS + RT and NS groups were significant (P < 0.01), as were the decreases in NRP-1 mRNA in the CpG ODN1826 + RT group compared with the CpG ODN1826 group (P < 0.01). Thus, CpG ODN1826 can significantly inhibit tumor growth in a rat model, the mechanism of which may be related to inhibition of the expression of VEGF-C and NRP-1, which have an inhibitory effect on angiogenesis.
Assuntos
Oligodesoxirribonucleotídeos/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neuropilina-1/genética , Oligodesoxirribonucleotídeos/administração & dosagem , RNA Mensageiro/genética , Ratos , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Fator C de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The aim of this study was to investigate the impacts of positive acceleration (+Gz) on the gastric mucosal tissues in cases of acute gastric mucosal injury and to explore the role of oxygen free radicals. Thirty Sprague Dawley rats were randomly divided into the absolute ethanol control group (A group), absolute ethanol +5Gz group (B group), absolute ethanol +10Gz group (C group). Following centrifugation, the gastric tissues of each group were studied for the presence of gastric mucosal injuries and morphological changes. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) contents were simultaneously investigated. Degree of gastric mucosal injuries were as follows: C group (visually 49.080 ± 10.254, under light microscopy 9.400 ± 2.011) > B group (visually 23.654 ± 9.678, under light microscopy 5.000 ± 1.054) > A group (visually 11.410 ± 3.742, under light microscopy 3.800 ± 1.399). The gastric mucosal MDA content (0.376 ± 0.084 vs 0.235 ± 0.044) was significantly higher in the C group than in the A group, whereas the SOD content (8.852 ± 1.001 vs 10.694 ± 0.965) was lower than that in the A group. However, the MDA and SOD contents did not change much in the B group. Our results suggest that the +Gz exposure might aggravate the acute gastric mucosal injury, and changes in MDA and SOD contents in the gastric tissues indicated that the oxygen free radicals play an important role in this regard.