MIF is a progesterone analogue and is known as a potent progesterone antagonist. Although MIF has been known to inhibit prostate cancer cell growth, its molecular mechanisms are not yet clear. In the present study, when the cells were treated for 2-4 days with 5-40 $\mu$M of MIF, the growth and viability of LNCaP cells were significantly decreased in a dose- and time-dependent manner. When the cells, cultivated in a normal 2 mM calcium concentration medium, were treated with 15 $\mu$M MIF for 1 day, the intracellular calcium level increased by 26% compared to the control. Similar results were also found in cells located in the calcium-free reaction buffer, indicating that MIF induced the increase of intracellular Ca$^{2+}$ levels, regardless of the presence of calcium in the surrounding medium. In the cells treated with various concentrations of MIF, the intracellular calcium levels increased in a dose dependent manner. Cells treated with MIF revealed typical early apoptotic signs, i.e., chromosome condensation and nuclei fragmentation. In cells treated with 40 11M MIF, Bcl-2 decreased to 19% of the control. The expression of Bax increased to almost 2 fold of the control. These results demonstrated very clearly that MIF treatment blocks the expression of Bcl-2 but stimulates the expression of Bax. According to the results of the present investigation, the apoptotic mechanism of MIF is triggered by intracellular modulation.
Lee Sang-wook;Kim Gwi Eon;Chung Kap Soo;Lee Chang Geol;Seong Jinsil;Suh Chang Ok
Radiation Oncology Journal
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v.16
no.4
/
pp.455-467
/
1998
Purpose : To evaluate influences associated with radiation treatment planning obtained with the patient breathing freely. Materials and Methods : We compared reduction or elimination of planning target volume (PTV) margins with 2-D conventional plan with inclusion of PTV margins associated with breathing with 3-D conformal therapy. The respiratory non gated 3-D conformal treatment plans were compared with respiratory gated conventional 2-D plans in 4 patients with hepatocellular carcinomas. Isodose distribution, dose statistics, and dose volume histogram (DVH) of PTVs were used to evaluate differences between respiratory gated conventional 2-D plans and respiratory non gated 3-D conformal treatment plans. In addition. the risk of radiation exposure of surrounding normal liver and organs are evaluated by means of DVH and normal tissue complication probabilities (NTCPs). Results : The vertical movement of liver ranged 2-3 cm in all patients. We found no difference between respiratory gated 2-D plans and 3-D conformal treatment plans with the patients breathing freely. Treatment planning using DVH analysis of PTV and the normal liver was used for all patients. DVH and calculated NTCP showed no difference in respiratory gated 2-D plans and respiratory non gated 3-D conformal treatment plans. Conclusion : Respiratory gated radiation therapy was very important in hepatic tumors because radiation induced hepatitis was dependent on remaining normal liver volume. Further investigational studies for respiratory gated radiation.
Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.
This study was designed to observe the effect of green tea on colon tumor incidence and biomarkers of colon carcinogenesis in 1, 2-dimethlhydrazine-treated rats. Male Sprague Dawley rats at 7 weeks of age were divided into two groups: control and green tea(GT) groups. Control rats had distilled water as drinking water but GT group received green tea extracts(2.5%, w/v water) as drinking water throughout the experiment periods. All rats were fed the experimental diet containing 15% fat by weight for 20 weeks. and were i.m. injected with DMH for 6 weeks to give total dose of 180mg/kg body weight. Tumor incidence was reduced in GT group (39%) compared with control group (56%) Green tea significantly reduced cell proliferation (total cells per crypt, crypt length and proliferative zone) in colonic mucosa and also significantly reduced the levels of preformed prostalandin E2(PGE2) and thromboxance B2(TXB2) in colonic mucosa but the fatty acid profile of total lipid in colonic mucosa was not significantly influenced by green tea. However the relative percent of C20:4 and the levels f preformed PGE2 and TXB2. were significantly higher in tumor tissue compared with normal surrounding mucosa.Green tea increased the fecal excretion of total bile acid but not scondary bile acid which is known as one of promoters for colon cancer,. These results suggest that green tea could have preventive effect against colon cancer when consumed daily by influencing on antioxidant effect and the metabolism of arachidonic acid.
Objectives: The goal of this study is to identify the distribution of the foliar fluorine content of vegetation surrounding the area where hydrofluoric acid was accidently released in Gumi, Gyeongsangbuk-do on September 27, 2012. In addition, it also aims to estimate the concentration of hydrogen fluoride in the air on the day of the accident. Methods: Samples of plant leaves were collected on October 7, 2012 within 1 km from the site where the accident occurred. These samples were analyzed for soluble fluorine ion with an ion selective electrode. The ambient concentration of hydrogen fluoride was calculated using the fluoride content in the plant via the dose-rate equation (${\Delta}F$=KCT). Results: The arithmetic and geometric means of the concentrations were 2158.2 and 1183.7mg F $kg^{-1}$ for leaves and, 2.4 and 1.1 ppm HF for the air, respectively. The highest concentration of hydrogen fluoride in the air was 14.7 ppm, which is higher than the maximum concentration reported by the government (1 ppm) and the exposure limit (ceiling, 3 ppm). The concentrations of both fluorine and hydrogen fluoride decreased with increasing distance from the accident site and showed a significant decrease outside of a 500m radius from the site (p <0.05). Conclusions: The area around the accident site was highly polluted with hydrogen fluoride according to the results of this study. Considering the persistency of hydrogen fluoride in the environment, long-term monitoring and environmental impact assessment should be pursued.
Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.
Kim, In-Deok;Kang, Kum-Suk;Kwon, Ryun-Hee;Ha, Bae-Jin
Toxicological Research
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v.23
no.4
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pp.347-352
/
2007
The protective effects of Rubus coreanum Miquel (RCM) extract against LPS-induced hepatotoxicity were studied in rats. Squrague-Dawley rats were intraperitoneally administered the RCM at 100 mg/kg per day for three weeks. Then single dose of LPS (5 mg/kg) was injected into rats. Four hours later, they were anesthesized with ether and dissected. We examined the levels of glutamate oxaloacetate transaminase (AST), glutamate pyruvate transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in sera, superoxide dismutase (SOD) in mitochondrial fraction and catalase (CAT), glutathione peroxidase (GPx) in liver homogenate. LPS-treatment markedly increased the levels of AST, ALT, ALP, LDH and significantly decreased those of SOD, CAT and GPx. But RCM-pretreatment decreased the levels of AST, ALT, ALP and LDH by 57.9%, 37.4%, 62% and 69% respectively and increased those of SOD, CAT and GPx by 82.9%, 64.2% and 96.7% respectively. Subsequently, the protective effects of RCM was evaluated through histopathological examination of liver tissue. The LPS treatment increased the state of necrosis and cirrhosis surrounding the central veins (CV) and sinusoid, but RCM-treatment decreased the state of necrosis and cirrhosis in the liver tissue. These results demonstrated that protective effects of RCM against LPS-induced hepatotoxicity.
For the induction of arthropathy, 5% hydrogen peroxide($H_2O_2$) was injected for 5 weeks into the intraarticular space of the New Zealand white rabbits to damage articular cartilage. Alginic acid of low molecular weight (2%) made from macromolecular alginate treated with enzyme was administered into articular space at the dose of 5 mg/kg twice a week for 3 and 6 weeks using 1 ml syringe and 26 G needle. Saline was injected for the control. Tissues surrounding the articulation were obtained for the measurements of superoxide dismutase(SOD) activity as a major antioxidant enzyme and malondialdehyde (MDA) as a lipid peroxidation level. Histopathologic examination on the surface of articular cartilage was carried out. Data showed that injection of hydrogen peroxide for 5 weeks had led to the induction of free radical damage and of articular cartilage change as confirmed by microscopic observation. The application of hydrogen peroxide caused a gradual increase in the SODs and MDA. These patterns were similar after 3 and 6 weeks of alginate treatment. Furthermore, microscopic examinations revealed that hydrogen peroxide caused flaking, fibrillation, fissuring, denudation, and hypocellularity in the articular surfaces. In conclusion, lipid peroxidation was demonstrated in the articular cartilage by the administration of hydrogen peroxide in the rabbit model. This lipid peroxidation could be caused by oxygen free radicals. The histologic and enzymatic correlations on lipid peroxidation in the articulation have provided a better understanding of arthropathy. It is possible to take advantage of these findings to evaluate effective alginate dosage more efficiently.
Background and Objective: Coptidis Rhizoma is a medicinal herb known for its antioxidant and anti-inflammatory effect. The purpose of this study was to examine the effects of CR on the experimental burn elicitation in vitro and in vivo. Material and Methods: In order to know the antioxidant effect on skin cell of mice after burn elicitation, superoxide dismutase (SOD) activity was measured. In vitro, the RAW 264.7 macrophage cells were treated with lipopolysaccharides for experimental inflammation. iNOS mRNA expression was observed after CR-treatment. In order to know effects on the skin regeneration in the burned mice, we counted the nitric oxide (NO) in blood. We also observed the histological structure in the epidermal basal layer and the dermal section, and we studied changes of angiogenesis in the capillaries surrounding the basal layer and dermal papilla. The changes of transcription of iNOS mRNA (inducible nitric oxide synthase mRNA) and changes of NF-${\kappa}$B (nuclear factor ${\kappa}$B) p65 positive reaction were also observed to investigate the changes of the stress in the skin. Results: The results indicated that CR has significant effects on the antioxidant effect on skin cells of mice after burn elicitation by increasing SOD activity in the in vitro test. It seemed that CR decreased the amount of NF-${\kappa}$B which induced the iNOS mRNA dose-dependently and suppress activating NO and angiogenesis. Furthermore, CR facilitated the process of skin recovery after experimental burn. Conclusion: CR can be applied for burned skin via antioxidant effect and skin regeneration.
The authors evaluated 14 patients from July 1999 to February 2004 treated with total keloidectomy followed by postoperative radiation treatment, delivered within 24 hours or 24-36 hours after surgery. The total dose of radiation was 1200 cGy in three fractions for 4-5 days. Among the 14 patients treated, 8 patients were evaluated for following-up. The age range of these patients were from 22 to 44 years old, with the average age of 30 years. The site of keloid lesions consisted; 6 on the ear lobe, 5 on the anterior chest and 1 on the upper arm. The mean follow-up period was 29.9 months. The recurrence was evaluated with photogrammetric analysis and skin color analysis. The photogrammetric analysis was performed with planimetry for the comparison of the ratio of the reduced size to the preoperative size. The mean value of the relative size of reduction was 55% and the ratio of the ear lobes were greater than the ratio of the chests. The skin color analysis was performed with chromameter CR-300 for the analysis of color difference (E) between the surrounding normal skin and the lesion. The larger the recurred size was, similar to the original size, the larger the E value was, so the E value posses the probability of predictable objective tool of recurrence. Although verifying the effectiveness of radiation therapy following keloidectomy need more cases and long term follow-up evaluation, this therapeutic modality seems very effective in reducing the keloid size, especially in the ear lobe.
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