The tumor necrosis, factor-related, apoptosis-inducing ligand (TRAIL) is regarded as a potentially useful anticancer agent with excellent selectivity for cancer cells. However, a considerable number of cancer cells are resistant to apoptosis induction by TRAIL. Developing strategies to overcome this resistance are important for the successful use of TRAIL for cancer therapy. Here, we revealed that siRNA-mediated downregulation of SIRT1 or SIRT1 inhibitor Amurensin G upregulated DR5 and c-Myc and downregulated c-$FLIP_{L/S}$ and Mcl-1, which was associated with sensitization of TRAIL-resistant MCF-7 cells to TRAIL. This result was followed by the activation of caspases, PARP cleavage, and downregulation of Bcl-2 in both TRAIL-treated MCF-7 cells transfected with SIRT1 siRNA and cells co-treated with Amurensin G and TRAIL. Our results suggest that the induction of DR5 and downregulation of c-FLIP via suppression of SIRT1 expression may be a useful strategy to increase the susceptibility of TRAIL-resistant cancer cells to TRAIL-induced cell death.
The purpose of this study was to investigate the dose-volume indices and radiobiological indices according to the change in dose calculation grid size during the planning of nasopharyngeal cancer VMAT treatment. After performing the VMAT treatment plan using the 3.0 mm dose calculation grid size, dose calculation from 1.0 mm to 5.0 mm was performed repeatedly to obtain a dose volume histogram. The dose volume index and radiobiological index were evaluated using the obtained dose volume histogram. The smaller the dose calculation grid size, the smaller the mean dose for CTV and the larger the mean dose for PTV. For OAR of spinal cord, brain stem, lens and parotid gland, the mean dose did not show a significant difference according to the change in dose calculation grid size. The smaller the grid size, the higher the conformity of the dose distribution as the CI of the PTV increases. The CI and HI showed the best results at 3.0 mm. The smaller the dose calculation grid size, the higher the TCP of the PTV. The smaller the dose calculation grid size, the lower the NTCP of lens and parotid. As a result, when performing the nasopharynx cancer VMAT plan, it was found that the dose calculation grid size should be determined in consideration of dose volume index, radiobiological index, and dose calculation time. According to the results of various experiments, it was determined that it is desirable to apply a grid size of 2.0 - 3.0 mm.
This study has been to examine the occupational exposure levels of Fluorouracil (5-FU) in a hospital and to investigate the most effective cleaning reagent for control. Fluorouracil is one of the cytotoxic drugs which are therapeutic agents used to treat cancer. The health practitioners working in the cytotoxic work room and oncology ward areas are exposed to adverse health risks like cytogenetic and DNA damage from cytotoxic drugs exposure by frequent skin contact from contaminated surfaces. Four kinds of cleaning reagents has been examined to degrade the 5-FU. It was found that 5-FU was only degraded soon after the reaction in 0.5%(w/v) NaClO solution. Therefore, 0.5%(w/v) NaClO solution has been chosen to decompose any residues on the contamination surfaces. A substantial level of contamination was found on the surfaces of cytotoxic work room and oncology ward areas. The contamination ranges of the surfaces in cytotoxic work room and oncology ward areas were from 2.0 to $13.8{\mu}g/m^2$ and 5.39 to $11.53{\mu}g/m^2$ respectively. Consequently, regulation of the occupational exposure limit, procedure of special cleaning, and the use of personal protective equipment are recommended during the manipulation and administration of the drugs to avoid skin contamination from cytotoxic drugs like 5-FU.
Kim, Jung-Hyun;Oh, Doo-Hwan;Zhang, Seok-Am;Lee, Jang-Kyu
Journal of the Korea Academia-Industrial cooperation Society
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v.16
no.6
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pp.4098-4107
/
2015
The purpose of this study was to investigate the effects of 8-week schroth 3-dimensional exercise and ball-sling complex exercise treatment on cobb's angle, abdominal muscle endurance, flexibility and balance in adolescents with idiopathic scoliosis. Thirty subjects with scoliosis were random assignment into one of two experimental groups, either schroth treatment(n=15) or ball-sling complex exercise treatment(n=15). Exercise program was to perform for 8-week and 90min and 3 times per week. The results of this study were as follows; First, cobb's angle was significantly decreased after 8-weeks in schroth treatment(p<.001). And also abdominal muscle endurance(p<.05), flexibility(p<.001) and balance(p<.001) were significantly improve in pre vs. post treatment. Second, the ratio of cobb's angle change was significantly higher in schroth treatment compared to ball-sling complex exercise treatment following 8-weeks(p<.05). These results suggest that although both the schroth treatment and bal-sling complex exercise treatment in adolescents with idiopathic scoliosis can improve on cobb's angle, abdominal muscle endurance, flexibility and balance, but schroth treatment was better than ball-sling complex exercise treatment improving effect of cobb's angle. Therefore, we consider that schroth treatment has more effect of prevention and therapy in idiopathic scoliosis in adolescents.
The body of the fat tissue increased in obese represented by risk factors such as cardiovascular diseases, diabetes, metabolic disease and dyslipidemia. Such metabolic diseases and the like of the cardiovascular and cerebrovascular disease, hypertension, dyslipidemia, increase in the adipose tissue of the pancreas is known to be a risk factor of these diseases. Study on the diagnosis and treatment of pancreatic cancer was conducted actively, case studies on pancreatic steatosis is not much. In this study, divided into a control group diagnosed with pancreatic steatosis as a result of ultrasonography to evaluation the physical characteristics and serologic tests and blood pressure and arterial stiffness. The control group and the test pancreas steatosis age and waist circumference, body mass index, total cholesterol, HDL cholesterol, LDL cholesterol, and systolic and diastolic blood pressure, fasting blood glucose, arterial elasticity is higher in pancreatic steatosis. And the lower ankle brachial stenosis and HDL-cholesterol were lower than the normal control group, so the pancreatic steatosis harmful to blood vessels.(P <0.05). The difference between the control group and it was confirmed that the pancreatic jibanggun statistically significant. In conclusion, pancreatic steatosis at abdominal ultrasound can predict the risk of metabolic diseases, and there was a correlation with cardiovascular disease.
Hyperthermia can enhance the radiation effect as a synergistic reaction in combined X-ray irradiation and hyperthermia; hyperthermia sensitize radioresistant S-phase cells and inhibit cellular recovery from sublethal damage. We fabricated 100 watts, 2450 MHz microwave applicator for hyperthermia and planned the method and condition of heating and measured the temperature by using Agar phantom as a preliminary test. For biological examination, 102 rats were divided into 4 groups as hyperthermia, X-ray irradiation (6Gy-15Gy), combined X-ray and hyperthermia, and normal control groups. Microscopic examination of the rectum and bladder was done and the results were as followings: 1. The microwave generator with 100 watts, 2450MHz magnetron could be heating up to $40^{\circ}{\sim}50^{\circ}C$ for one hour in living tissue. 2. The thermal distribution in tissue equivalent phantom with microwave can be maintained at $40^{\circ}{\sim}44^{\circ}C$ in area of 3cm in depth and 2-10cm in diameter. 3. In Hyperthermia alone group, there was submucosal edema of the rectum but no histologic change in the urinary bladder was seen. 4. The minimal necrosis of the mucosa was appeared in the rectum and bladder after 15 days of 6 Gy and 8 Gy irradiation respectively. The minimal necrosis of the muscle layer of rectum and bladder was appeared after 15 days of 8Gy and 60days of 10Gy irradiation respectively. 5. In combined group of radiation and hyperthermia, thermal enhancement ratio (calculated at necrosis of mucosa and muscle layer) of rectum and bladder was 1.0, and it suggest that there is no change of tolerance dose of normal rectum and bladder.
Purpose: Troglitazone (TRO), a PPAR-$\gamma$ agonist, can reduce heat shock protein (HSP) 70 and increase the antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, which might affect thermal sensitivity. Here, we investigated whether TRO modifies thermal sensitivity in uterine cervical cancer cells, which is most commonly treated by hyperthermia (HT). Materials and Methods: HeLa cells were treated with $5{\mu}M$ TRO for 24 hours before HT at $42^{\circ}C$ for 1 hour. Cell survival was analyzed by clonogenic assay. The expression of HSPs was analyzed by Western blot. SOD and catalase activity was measured and reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate and dihydroethidium. Results: The decreased cell survival by HT was increased by preincubation with TRO before HT. Expression of HSP 70 was increased by HT however, it was not decreased by preincubation with TRO before HT. The decreased Bcl-2 expression by HT was increased by preincubation with TRO. SOD and catalase activity was increased by 1.2 and 1.3 times,respectively with TRO. Increased ROS by HT was decreased by preincubation with TRO. Conclusion: TRO decreases thermal sensitivity through increased SOD and catalase activity, as well as scavenging ROS in HeLa cells.
Purpose : To analyse clinical outcome and prognostic factors according to treatment modality, this paper report our experience of retrospective study of patients with esophageal cancer Materials and Methods : One hundred and ten patients with primary esophageal cancer who were treated in Presbyterian Medical Center from May 1985 to December 1992. We analysed these patients retrospectively with median follow up time of 28 months, one hundred and four patients($95{\%}$) were followed up from 15 to 69 months. In methods, twenty-eight patients were treated with median radiation dose irradiated 54.3Gy only. Fifty-six patients were treated with combined chemoradiotherapy. Sixteen cases of these patients were treated with concurrent chemoradiation and the other patients(forty cases) were treated sequential chemoradiotherapy. In concurrent chemoradiotherapy group, patients received 5-FU continuous IV infusion for 4 days. Cisplatin IV bolus. and concurrent esophageal irradiation to 30 Gy. After that patients received 5-FU continuous IV, Cisplatin bolus injection and Mitomycin-C bolus IV, Bleomycin continuous IV, and irradiation to 20 Gy. In sequential chemoradiotherapy group, the chemotherapy consisted of 5-FU 1,000mg/$m^2$ administered as a continuous 24 hour intravenous infusion during five days and Cisplatin 80-100mg/$m^2$ bolus injected, or Bleomycin, Vinblastine, Cisplatin, Methotrexate were used of 1 or 2 cycles. After preoperative concurrentm chemoradiation twenty-six patients underwent radical esophagectomy. Results : Ninety-three patients could be examined for response assessment, By treatment modality, response rates were $85.1{\%}$ for radiation alone group and $86.3{\%}$ for combined chemoradiation group. But in operation group, after one cycle of concurrent chemoradiation treatment, response rate was $61.9{\%}$. The pathologic complete response were $15.4{\%}$ in operation group. Overall median survival was II months and actuarial 5-year survival rate was $8{\%}$. The median survival interval was 6 months for radiation alone group, 11 months for combined chemoradiation group and 19 months for operation group. And also median survival was 19 months for complete responder group that 8 months for noncomplete responder group. In univariative analysis, statistically significant prognostic factors were tumor size, clinical stage, tumor response, and operation. In multivariative analysis, significantly better survival was associated with clinical stage, tumor response, radiation dose, and operation. Conclusion : Compared with radiotherapy alone, combined multimodality may improve the median survival in patients with localized carcinoma of the esophagus and toxicity is acceptable.
In the present investigation, we studied the modulating effects of (-)-epigallocatechin-3-gallate(EGCG) on the differentiation of mouse C2C12 myoblasts. We found that the strong inhibitory effect of EGCG on DNA methyltransferase-mediated DNA methylation induced transdifferentiation of C2C12 myoblasts into smooth muscle cells demonstrated by both morphological changes and immunofluorescent staining. C2C12 myoblasts treated with EGCG for 4 days expressed smooth muscle ${\alpha}-actin$ protein. Real-time PCR data revealed that smooth muscle ${\alpha}-actin$ mRNA was induced by EGCG treated C2C12 myoblasts in a concentration-dependent manner. Smooth muscle ${\alpha}-actin$ mRNA concentration increased 330% and 490% after 2 and 3 days of 50 ${\mu}M$ of EGCG treatment. The expression of another smooth muscle marker, transgelin, mRNA was also increased up to 9-fold by 4 days of EGCG treatment compared with control in a concentration-dependent manner. These results suggested that C2C12 enables to transdifferentiate into smooth muscle when gene expression patterns are changed by the inhibition of DNA methylation induced by EGCG. In conclusion, transdifferentiation of C2C12 myoblasts into smooth muscle is resulted from the modulating effects of EGCG on DNA methylation which subsequently results in changing the expression pattern of several genes playing a critical role in the differentiation of C2C12 myoblasts.
Kim, Kyung-Pil;Kim, Ji-Hoon;Kim, Eui-Sik;Hwang, Jae-Ha;Kim, Kwang-Seog;Lee, Sam-Yong
Archives of Reconstructive Microsurgery
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v.19
no.2
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pp.97-100
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2010
Purpose: Epidermolysis bullosa is a rare genetic disease, characterized by the presence of extremely fragile skin and formation of recurrent blister resulting from even a minor mechanical injury. Squamous cell carcinoma (SCC) is recognized as a complication of the chronic scarring associated with dystrophic epidermolysis bullosa (DEB). When a soft tissue defect happens in a patient with epidermolysis bullosa, it is difficult to cover it with a skin graft or a flap. We describe the successful use of a pedicled deep inferior epigastric perforator flap for the reconstruction of SCC associated with DEB in the groin. Methods: A 29-year-old man diagnosed with DEB at birth sustained an ulcer increasing in the right groin for the last 7 months. Under general anesthesia, the mass lesion and lymph nodes were removed and the resulting defect was covered with a pedicled deep inferior epigastric perforator flap. Results: The flap survived completely and his postoperative course was uneventful. Histopathological examination revealed a SCC in the right groin and malignant tumor cells in the removed lymph nodes as well. Additional positron emission tomogram showed a malignant lesion in the ileocecal area with regional lymph node metastasis. The patient was referred to an oncologist for chemotheraphy, but the patient refused to take it. During a 4-month follow-up period, there was no recurrence in the right groin. Conclusion: We suggest that perforator flaps can be considered as a reliable alternative for the reconstruction of soft tissue defects in a patient with DEB.
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