ABSTRACT
PURPOSE: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) alpha and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). MATERIALS AND METHODS: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. RESULTS: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 microM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARalpha and PPARgamma were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARalpha were not increased with FF. However, the mRNA of PPARgamma was increased with FF. CONCLUSION: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARalpha.
Subject(s)
Humans , Catalase , Cell Line , Fenofibrate , Fibric Acids , Hand , HeLa Cells , Hypolipidemic Agents , Ligands , Peroxisomes , Polymerase Chain Reaction , PPAR alpha , PPAR gamma , Radiation Tolerance , Reactive Oxygen Species , RNA, Messenger , Superoxide Dismutase , Superoxides , Uterine Cervical NeoplasmsABSTRACT
PURPOSE: 4DCT scans performed for radiotherapy were retrospectively analyzed to assess the possible benefits of respiratory gating in non-small cell lung cancer (NSCLC) and established the predictive factors for identifying patients who could benefit from this approach. MATERIALS AND METHODS: Three treatment planning was performed for 15 patients with stage I~III NSCLC using different planning target volumes (PTVs) as follows: 1) PTVroutine, derived from the addition of conventional uniform margins to gross tumor volume (GTV) of a single bin, 2) PTVall phases (patient-specific PTV), derived from the composite GTV of all 6 bins of the 4DCT, and 3) PTVgating, derived from the composite GTV of 3 consecutive bins at end-exhalation. RESULTS: The reductions in PTV were 43.2% and 9.5%, respectively, for the PTVall phases vs. PTVroutine and PTVgating vs. PTVall phases. Compared to PTVroutine, the use of PTVall phases and PTVgating reduced the mean lung dose (MLD) by 18.1% and 21.6%, and V20 by 18.2% and 22.0%, respectively. Significant correlations were seen between certain predictive factors selected from the tumor mobility and volume analysis, such as the 3D mobility vector, the reduction in 3D mobility and PTV with gating, and the ratio of GTV overlap between 2 extreme bins and additional reductions in both MLD and V20 with gating. CONCLUSION: The additional benefits with gating compared to the use of patient-specific PTV were modest; however, there were distinct correlations and differences according to the predictive factors. Therefore, these predictive factors might be useful for identifying patients who could benefit from respiratory-gated radiotherapy.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Lung , Retrospective Studies , Tumor BurdenABSTRACT
PURPOSE: The causes of rotator cuff tendon tear were excessive overuse, aging process and impingement syndrome and a lot of research of these factors have been performed. But molecular study of cuff tear or apoptosis of rotator cuff tenocyte is not done until now. In this study, the apoptosis level and apoptosis-related gene expression were investigated in the specimens from the torn margin of a rotator cuff tear, and compared with those from normal portion. MATERIALS AND METHODS: Among patients who underwent arthroscopic shoulder surgery between April 2008 to August 2008, 15 patients with complete rotator cuff tear was investigated. These were 10 men and 5 women. The age were from 48 years to 76 years old (average 61.5 years). The contol group were 2 patients with intact subscapularis tendon. Patients with impingement syndrome, partial tear or tendinitis were excluded from the design of the study. Tendon specimen in the tear margin of supraspinatus or infraspinatus tendon was evaluated using Hematoxylin-Eosinophilic stain, TUNNEL assay and immunohistochemistry for p53, Bcl-2, Bax and JNK1 were performed. RESULTS: TUNNEL assay was positive in 5 cases of the 15 specimens. In these cases, 5.4% of the cells were positive. The apoptosis-related gene such as p53, Bcl-2, Bax and JNK-1, and tear size were evaluated. These correlations were evaluated using a correlation analysis of Spearman correlation analysis. Spearman correlation coefficient between apoptosis and bcl-2, and between apoptosis and p53 were 0.625 and 0.71, respectively. These p values were 0.01 and 0.003, respectively. Spearman correlation coefficient between p53 and tear size, and Bax and tear size were 0.58 and 0.76, respectively. These p values were 0.02 and <0.001, respectively. The apoptosis of control group in normal subscapular tendon is zero. CONCLUSION: The increased apopotic index was correlated with increased bcl-2 and p53 gene in Rotator cuff tear patients. The larger tear showed increased p53 and Bax gene expression. Further research in this area will need to reduce apoptosis in the development of the rotator cuff tear.
Subject(s)
Female , Humans , Male , Aging , Apoptosis , Gene Expression , Genes, p53 , Immunohistochemistry , Rotator Cuff , Shoulder , Tendinopathy , TendonsABSTRACT
PURPOSE: The modification of radiation-induced apoptosis by EGCG, known as antioxidants or oxidants, was studied in mice spleens irradiated with a lethal dose. MATERIALS AND METHODS: Male C57BL/6 mice were divided into control, irradiation-only, and EGCG (100 mg/kg i.p. 1 h before irradiation) pretreatment groups. The mice were irradiated with a single whole-body dose of 7 Gy. The apoptosis in the spleens after irradiation of the lethal dose were analyzed by TUNEL assay. In addition, the expression levels of the Bax and Bcl-2 proteins were quantified using a Western blotting method. RESULTS: The induction of apoptosis was detected in the splenic white pulp. The highest level of apoptosis was detected at 8 hours after irradiation. No significant difference was identified by the apoptotic index (53.9% vs. 52.1%, p=0.328) and relative Bax protein expression (0.86 vs. 0.81, p=0.335), between the irradiation-only and EGCG pretreatment group, respectively. However, a lower Bax/Bcl-2 ratio (1.64 vs. 0.97, p=0.037) and higher relative expression level of Bcl-2 protein (0.57 vs. 0.82, p=0.037) was measured in the EGCG pretreatment group. CONCLUSION: The EGCG pretreatment neither decreased the radiation-induced apoptosis in mice splenocytes, nor induced additional apoptosis.
Subject(s)
Male , Humans , OxidantsABSTRACT
PURPOSE: To evaluate the effectiveness and safety of fentanyl-TTS in the management of radiotherapy induced acute pain and cancer pain treated with radiotherapy. MATERIALS AND METHODS: Our study was open labelled prospective phase IV multi-center study. the study population included patients with more 4 numeric rating scale(NRS) score pain although managed with other analgesics or more than 6 NRS score pain without analgesics. Patients divided into two groups; patients with radiotherapy induced pain (Group A) and patients with cancer pain treated with radiotherapy (Group B). All patients received 25 ug/hr of fentanyl transdermal patch. Primary end point was pain relief; second end points were change in patient quality of life, a degree of satisfaction for patients and clinician, side effects. RESULTS: Between March 2005 and June 2005, 312 patients from 26 participating institutes were registered, but 249 patients completed this study. Total number of patients in each group was 185 in Group A, 64 in Group B. Mean age was 60 years and male to female ratio was 76:24. Severe pain NRS score at 2 weeks after the application of fentanyl was decreased from 7.03 to 4.01, p=0.003. There was a significant improvement in insomnia, social functioning, and quality of life. A degree of satisfaction for patients and clinician was very high. The most common reasons of patients' satisfactions was good pain control. Ninety six patients reported side effect. Nausea was the most common side effect. There was no serious side effect. CONCLUSION: Fentanyl-TTS was effective in both relieving pain with good tolerability and improving the quality of life for patients with radiotherapy induced acute pain and cancer pain treated with radiotherapy. The satisfaction of the patients and doctors was good. There was no major side effect.
Subject(s)
Female , Humans , Male , Academies and Institutes , Acute Pain , Analgesics , Fentanyl , Nausea , Prospective Studies , Quality of Life , Radiotherapy , Sleep Initiation and Maintenance Disorders , Transdermal PatchABSTRACT
PURPOSE: The changed expressions of TGF-beta1, as a key cytokine in the fibrotic process, due to melatonin with potent antioxidative effects, were investigated in the irradiated lung using fibrosis-sensitive C57BL/6 mice. MATERIALS AND METHODS: Female C57BL/6 mice were divided into control irradiation-only, and melatonin (300 mg/kg i.p. 1 hr before irradiation) pretreatment groups. The thoraces of the mice were irradiated with a single dose of 12 Gy. The mRNA expressions of TGF-beta1 in the lung tissue 2 and 4 weeks after irradiation were quantified using semiquantitive RT-PCR, and the cellular origin and expression levels of TGF-beta1 protein were identified using immunohistochemical staining. RESULTS: The relative mRNA expression levels in the irradiation-only and melatonin pretreatment groups 2 and 4 weeks after irradiation were 1.92- and 1.80-fold (p=0.064) and 2.38- and 1.94-fold (p=0.004) increased, respectively compared to those in the control group. Increased expressions of TGF-beta1 protein were prominently detected in regions of histopathological radiation injury, with alveolar macrophages and septal epithelial cells serving as important sources of TGF-beta1 expression. At 2 and 4 weeks after irradiation, the expression levels of protein were 15.8% vs. 16.9% (p=0.565) and 36.1% vs. 25.7% (p=0.009), respectively. CONCLUSION: The mRNA and protein expressions of TGF-beta1 in the lung tissue following thoracic irradiation with 12 Gy were significantly decreased by melatonin pretreatment at 4 weeks. These results indicate that melatonin may have a possible application as an antifibrotic agent in radiation-induced lung injury.
Subject(s)
Animals , Female , Humans , Mice , Epithelial Cells , Fibrosis , Lung Injury , Lung , Macrophages, Alveolar , Melatonin , Radiation Injuries , RNA, Messenger , Thorax , Transforming Growth Factor beta1 , Transforming Growth FactorsABSTRACT
PURPOSE: The changed expressions of TGF-beta1, as a key cytokine in the fibrotic process, due to melatonin with potent antioxidative effects, were investigated in the irradiated lung using fibrosis-sensitive C57BL/6 mice. MATERIALS AND METHODS: Female C57BL/6 mice were divided into control irradiation-only, and melatonin (300 mg/kg i.p. 1 hr before irradiation) pretreatment groups. The thoraces of the mice were irradiated with a single dose of 12 Gy. The mRNA expressions of TGF-beta1 in the lung tissue 2 and 4 weeks after irradiation were quantified using semiquantitive RT-PCR, and the cellular origin and expression levels of TGF-beta1 protein were identified using immunohistochemical staining. RESULTS: The relative mRNA expression levels in the irradiation-only and melatonin pretreatment groups 2 and 4 weeks after irradiation were 1.92- and 1.80-fold (p=0.064) and 2.38- and 1.94-fold (p=0.004) increased, respectively compared to those in the control group. Increased expressions of TGF-beta1 protein were prominently detected in regions of histopathological radiation injury, with alveolar macrophages and septal epithelial cells serving as important sources of TGF-beta1 expression. At 2 and 4 weeks after irradiation, the expression levels of protein were 15.8% vs. 16.9% (p=0.565) and 36.1% vs. 25.7% (p=0.009), respectively. CONCLUSION: The mRNA and protein expressions of TGF-beta1 in the lung tissue following thoracic irradiation with 12 Gy were significantly decreased by melatonin pretreatment at 4 weeks. These results indicate that melatonin may have a possible application as an antifibrotic agent in radiation-induced lung injury.
Subject(s)
Animals , Female , Humans , Mice , Epithelial Cells , Fibrosis , Lung Injury , Lung , Macrophages, Alveolar , Melatonin , Radiation Injuries , RNA, Messenger , Thorax , Transforming Growth Factor beta1 , Transforming Growth FactorsABSTRACT
PURPOSE: The pattern of radioprotection by the combined use of low dose amifostine plus IL-1beta was investigated in mice exposed to an acute whole-body radiation dose of 10 Gy. MATERIALS AND METHODS: Male ICR mice were divided into the control group, the irradiation-only group, the high dose amifostine (400 mg/kg i.p. 30 min before irradiation) group, and the low dose amifostine (200 mg/kg i.p. 30 min before irradiation) plus IL-1beta (5 microgram/kg i.p. 20 h before irradiation) group. The radioprotective effects were evaluated using TUNEL assay and microcolony survival assay at jejunal crypt, bone marrow cell count and CBC in peripheral blood, and survival analysis up to 30 days following irradiation. RESULTS: The apoptotic index (p=0.987), surviving crypt number (p=0.484), and the number of WBCs (p=0.226), RBCs (p=0.544), and platelets (p=0.157) were not significantly different between the high dose amifostine group and the low dose amifostine plus IL-1beta group, although the bone marrow cell count was higher in the combination group. The irradiation-only group was dead within 15 days. However, the survival rate at 30 days in the high dose amifostine and the low dose amifostine plus IL-1beta pretreatments were 61% and 66%, respectively. Moreover, the differences between the two groups were insignificant for both 10 days (p=0.9461) and 30 days (p=0.8030). CONCLUSION: These results indicate that the low dose amifostine plus IL-1beta may be applied as a non-toxic radioprotector, while the high dose amifostine, known as the strongest radioprotector, however, had toxic side effects.