• Radiation Oncology Journal
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• v.17 no.1
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• pp.1-8
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• 1999

Purpose : Experimental studies have implicated the wild type p53 In cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancels. Methods : Immunohistochemical analysis with a mouse monoclonal antibody (DO-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at 51. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multi-variate analysis was peformed that included all clinical variables and status of p53 expression. Results : Thirty-seven (67.2$\%$) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 70$\%$ of laryngeal, 66.7$\%$ of oropharyngeal, 66.7$\%$ of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. Conclusions : The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.97-102
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• 2006

Purpose: The prognosis for patients with a Borrmann type IV gastric cancer is extremely poor despite an aggressive surgical approach. We evaluated the clinicopathological features for Borrmann type IV cancers to find treatment strategy. Materials and Methods: The 1098 patients with advanced gastric cancer who underwent surgical resection between 1990 and 2001 were analyzed. These patients were divided into two groups: 81 patients with a Borrmann type IV carcinoma, and 1017 patients with all other types of gastric carcinomas. Results: Patients with a Borrmann type IV carcinoma were younger than those with other types, and female was prevalent (p=0.000). Of the patients with a Borrmann type IV gastric carcinoma, 68 patients (84%) were classified as stage III or IV at the initial diagnosis. The histologic type was commonly undifferentiated and serosal infiltration; nodal involvement and lymphatic invasion were more frequent in patients with a Borrmann type IV than in those with other types of cancer. Multivariate analysis confirmed that the extent of lymph node metastasis was a negative prognostic factor for Borrmann type IV gastric carcinomas. The curability for a Borrmann type IV carcinoma was only 53.1%, and peritoneal dissemination rate was 25.9%. The predominant pattern of recurrence for a Borrmann type IV gastric carcinoma was peritoneal dissemination, and it was significantly different with other types (93.1% vs 55.8%, P<0.05). The 5-year survival rate of patients with a Borrmann type IV gastric carcinoma was significantly lower than those of patients with other types of cancer, even though a curative resection had been accomplished (26% vs 63%, p<0.005). The 5-year survival rates of patients with a Borrmann type IV carcinoma following a curative resection were 44.9%, 24%, and 0% for stages II, III and IV, respectively (p<0.05). Conclusion: Because the prognosis for patients of a Borrmann type IV gastric cancer is extremely poor despite a curative resection, preoperative and/or intraperitoneal chemotherapy should be considered. And diagnostic laparoscopy and peritoneal cytology may be used to play an important role in accurate staging workup. (J Korean Gastric Cancer Assoc 2006;6:97-102)

• The Korean Journal of Food And Nutrition
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• v.25 no.3
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• pp.564-569
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• 2012

Selenium was initially considered toxic to humans, but it was then discovered that selenium is essential for normal life processes. Selenium plays important roles in antioxidants. It is expected that chitosan microcapsules containing nano-selenium will be able to be used as a key material in bio-medical and cosmetic applications. The high concentration of chitosan derivatives guarantees increased antioxidative activity. Both inorganic and organic forms of selenium can be nutritional sources. The antioxidant properties of selenoproteins help prevent cellular damage from free radicals. The objective of this experiment was to study the antioxidative activity of chitosan nano-selenium. Our experiments were divided into five groups, in the presence of various concentrations(0.1%, 0.3%, 0.5%, 0.7%, and 0.9%) of chitosan. We performed an assessment of the antioxidant properties and cytotoxicity of respective concentrations of chitosan nano-selenium. The antioxidant activity was examined by the free radical scavenging activity on 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay. The cytotoxicity effect was measured by means of 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. As a result, the electron donating abilities of 0.1%, 0.3%, 0.5%, 0.7%, and 0.9% of chitosan nano-selenium exhibited effective andioxidant scavenging activity at 12.5 ${\mu}g/m{\ell}$ against DPPH radicals. 0.3% chitosan nano-selenium did not show cytotoxicity on human keratinocytes. In general, the cytotoxicity of 0.1% and 0.9% chitosan nano-selenium showed the lowest effects. Though low cytotoxicity of 0.5% and 0.7% chitosan nano-selenium exhibited 29.67% and 38.4% against human keratinocytes on adding 100 ${\mu}g/m{\ell}$ and 50 ${\mu}g/m{\ell}$, respectively, cell vitality was recovered with 200 ${\mu}g/m{\ell}$. These findings support the notion that chitosan nano-selenium may be useful as a new active ingredient source for bioactive compounds.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.93-97
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• 2009

Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

• Journal of radiological science and technology
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• v.28 no.4
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• pp.333-340
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• 2005

In this study, the radioprotective effects of Grifola umbellata hot water extracts (Gu-extract) on mice were investigated. Single pre-administration of Gu-extract increased the 40-day survival ratio of irradiated mice from 65.5％ to 78.6％. The growth of 3 week old male mice in the irradiated group was slightly retarded as compared to those of the control and Gu-extract treated mice. The average spleen and thymus weights of the irradiated mice were lower than those of the control and Gu-extract treated mice. The weight reduction of testis in the irradiated mice was significant. While it was relatively slight in the Gu-extract treated mice as compared to that of control mice. No significant difference in the weight was observed in heart, kidney or liver among three groups. The leukocytes of the Gu-extract treated mice did not decrease dramatically as in the irradiated group, but recovery patterns were similar in both groups. Reduction of erythrocytes were similar in both groups but its recovery occurred more rapidly in the extract treated group. The glucose level of the Gu-extract treated group did not change during the period examined, while it was still higher in the irradiated group than the level in the control group in two weeks. The cholesterol levels in the irradiated and the Gu-extract treated groups were higher than that of control group on day 7, but decreased to the level of the control group on day 14. No difference was observed in total protein amount of the serum among the three groups. SDS-polyacrylamide gel electrophoresis of the soluble proteins extracted from various organs did not reveal differences to any extent in all groups except in the livers of the irradiated and extract treated groups, in which some proteins were missing or less present.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.163-168
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• 2009

Purpose: This study was a retrospective evaluation of the efficacy of stereotactic radiosurgery (SRS) in patients with >4 metastases to the brain. Materials and Methods: Between January 2004 and December 2006, 68 patients with $\geq$4 multiple brain metastases were included and reviewed retrospectively. Twenty-nine patients received SRS and 39 patients received whole brain radiotherapy (WBRT). Patients with small cell lung cancers and melanomas were excluded. The primary lesions were non-small cell lung cancer (69.0%) and breast cancer (13.8%) in the SRS group and non-small cell lung cancer (64.1%), breast cancer (15.4%), colorectal cancer (12.8%), esophageal cancer (5.1%) in the WBRT group. SRS involved gamma-knife radiosurgery and delivered 10~20 Gy (median, 16 Gy) in a single fraction with a 50% marginal dose. WBRT was delivered daily in 3 Gy fractions, for a total of 30 Gy. After completion of treatment, a follow-up brain MRI or a contrast-enhanced brain CT was reviewed. The overall survival and intracranial progression-free survival were compared in each group. Results: The median follow-up period was 5 months (range, 2~19 months) in the SRS group and 6 months (range, 4~23 months) in the WBRT group. The mean number of metastatic lesions in the SRS and WBRT groups was 6 and 5, respectively. The intracranial progression-free survival and overall survival in the SRS group was 5.1 and 5.6 months, respectively, in comparison to 6.1 and 7.2 months, respectively, in the WBRT group. Conclusion: SRS was less effective than WBRT in the treatment of patients with >4 metastases to the brain.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.67-76
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• 2006

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.449-460
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• 2004

Background : PS-341 is a novel, highly selective and potent proteasome inhibitor, which showed cytotoxicity against some tumor cells. Its anti-tumor activity has been suggested to be associated with modulation of the expression of apoptosis-associated proteins, such as p53, $p21^{WAF/CIP1}$, $p27^{KIP1}$, NF-${\kappa}B$, Bax and Bcl-2. c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) are important modulators of apoptosis. However, their role in PS-341-induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-$3{\beta}$ in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-$3{\beta}$ were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-$3{\beta}$ was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-$3{\beta}$ enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-$3{\beta}$ (DN-GSK-$3{\beta}$). Inactivation of GSK-$3{\beta}$ by pretreatment with lithium chloride or the overexpression of DN-GSK-$3{\beta}$ suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-$3{\beta}$ in lung cancer cells.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.379-385
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• 1997

Purpose : Ovarian dysgerminoma is a highly radiosensitive malignant tumor occurring in young age group. The conventional treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by radiotherapy. We retrospectively analyzed the treatment results of Patients who had received radiotherapy in the era before chemotherapy was widely used. Material and Method : Twenty two patients with ovarian dysgerminoma were treated at the Department of Therapeutic Radiology, Seoul National University Hospital between August, 1980 and May, 1991. Four patients were excluded from this study, because three patients received incomplete treatment and one received combined chemotherapy. Sixteen patients received postoperative radiotherapy and two patients had radical radiotherapy as tumor was unresectable. Median follow-up period was 99 months (range, 51-178) Median age was 22 years (range, 11-42). Among the postoperatively treated patients, three Patients were in stage IA, eight in stage IC, two in stage II, and three in stage III. One patient had Turner's syndrome. Radiotherapy was performed with high energy photon (telecobalt unit or linear accelerator, either 6MV or 10MV), The radiation dose to the whole abdomen was 1950-2100cGy (median, 2000) and 1050-2520cGy was added to the whole pelvis, the total dose to the whole pelvis was 3000-4500cGy (median, 3500). Prophylactic Paraaortic area irradiation was done in six Patients (dose range, 900-1500cGy). One patient who had positive Paraaortic node, received radiation dose of 1620cGy, followed by additional 900cGy to the gross mass with shrinking field. Total dose to the paraaortic node was 4470cGy. Six patients, including one who had paraaortic node metastasis, received Prophylactic irradiation to mediastinum and supraclavicular area (2520cGy). Of the two patients with unresectable tumors who received radical radiotherapy, one was in stage III and the other was in stage IV with left supraclavicular lymph node metastasis. The stage III patient received radiation to the whole abdomen (2000cGy), followed by boost to whole pelvis (2070cGy) and paraaortic area (2450cGy). Stage IV patient received radiation to the whole abdomen (2000cGy), followed by radiation to the whole pelvis and paraaortic area (2400cGy), mediastinum (2520cGy) , and left supraclavicular area (3550cGy) .Results : The 5 year local control rate was $100\%$ in patients who received postoperative adiuvant radiotherapy after total abdominal hysterectomy and bilateral salpingo-oophorectomy. Only one patient in stage III who did not receive prophylactic irradiation to mediastinum developed mediastinal metastasis. but was salvaged by chemotherapy. So. the 5 year overall survival rate uras also $100\%$. Two patients who received radiation only, are alive without disease at 112 and 155 months. Conclusion : Postoperntive adjuvant radiotherapy as well as radical radiotherapy in unresectable ovarian dysgerminoma was very effective. aut chemotherapy is also an effective treatment modality We now recomrneifd chemotherapy for Patients who need to save their ovarian functien and reserve radiotherapv fov chemo-resistant tumor or recurrence alter che motherapy.

• Korean Journal of Agricultural Science
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• v.13 no.1
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• pp.82-89
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• 1986

This experiment was carried out to determine the optimum freezing and thawing rates of the hamster embryos. The female hamsters were induced to superovulate by intraperitoneal injections of 30 i.u. PMSG and mated with males of the same strain of 4 days the PMSG injection. They were killed and embryos were flushed from the oviduct and uterine horn on 3 days after mating. Embryos were flushed with a modified Dulbecco's phosphate-buffered saline and equilibrated with 1.5 M-dimethylsulphoxide by a 3-step procedure. The freezing rates of the samples were $1^{\circ}C/min$ from room temperature to $-6^{\circ}C$ and the samples were seeded at $-6^{\circ}C$. After being held for 3 min at the seeding temperature, the rates were $0.3^{\circ}C/min$ from $-6^{\circ}C$ to $-35^{\circ}C$. From $-35^{\circ}C$ to $-70^{\circ}C$, the rates were divided into $0.1^{\circ}C/min$, $1^{\circ}C/min$ and $10^{\circ}C/min$, respectively. At $-70^{\circ}C$ the samples were plunged directly into liquid nitrogen. The samples were thawed at $4^{\circ}C/min$ and $12^{\circ}C/min$ from $-196^{\circ}C$ to $37^{\circ}C$, and for 2 min in $37^{\circ}C$ water bath, respectively. The average numbers of ovulation points and embryos recovered were 35.1 and 27.0 appearing 77.0% recovery rates. Eight cell embryos in the embryos recovered were 24.8. The survival rates of embryos according to the freezing rates were 55.5~67.7% at $0.1^{\circ}C/min$, 58.8~64.9% at $1^{\circ}C/min$ and 40.5~44.7% at $10^{\circ}C/min$, respectively. The survival rates at $10^{\circ}C/min$ were significantly low. The survival rates of embryos according to the thawing rates were 53.5% at $4^{\circ}C/min$, 53.7% at $12^{\circ}C/min$ and 59.1% in $37^{\circ}C$ water bath. The survival rates, in $37^{\circ}C$ water bath were slightly higher, but we did not find any differences among them. In conclusion, the best freezing rates of hamster embryos were $1^{\circ}C/min$ from the room temperature to $-6^{\circ}C/min$, $0.3^{\circ}C/min$ from $-6^{\circ}C/min$ to $-35^{\circ}C$ and $-0.1^{\circ}C/min$ or $1^{\circ}C/min$ from $-35^{\circ}C$ to $-70^{\circ}C$. The hamster embryos thawed for 2 min in $37^{\circ}C$ water bath showed the best survival rates.