• Journal of Chest Surgery
• /
• v.40 no.4 s.273
• /
• pp.264-272
• /
• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Journal of Food Hygiene and Safety
• /
• v.13 no.1
• /
• pp.53-61
• /
• 1998

This study was performed to investigate the antiulcer effects of Opuntia dillenii Haw. on the stomach ulcer induced by restraint and water-immersion stress in rats. For this experiment, 48 male Sprague-Dawley strain were used. The experimental groups were divided into four: a control (C) and 3 Opuntia dillenii Haw. treatment groups (E-1, E-2, E-3). Each dose of Opuntia dillenii Haw. was 30 mg/kg bw (E-1), 60 mgfKg bw (E-2) and 120 mg/kg bw (E-3). The rats were allocated to each group by 12 and observed for 4 weeks. The results were as following: 1. The stomach surface pH in each group showed no significant difference, but the values of Opuntia dillenii Haw. treatment groups were higher than the value of the control group. 2. The gastric wall mucus was increased in all Opuntia dillenii Haw. treatment groups compared with the control group. Especially in E-1 difference was higher (p<0.05) and in E-2 difference was significantly higher (p<0.01). 3. At shear rate 11.25, 45.0, 90.0, $225\;sec^{-1}$, whole blood viscosity and plasma viscosity were measured. Most of the values of Opuntia dillenii Haw. treatment groups were low compared with that of the control group. At shear rate 90.0, $225\;sec^{-1}$ the values of whole blood viscosity in E-1 were significantly low (p<0.05) and at shear rate 11.25, $45.0\;sec^{-1}$, more significant (p<0.01). At shear rate 11.25, 45.0, 90.0, $225\;sec^{-1}$ the values of whole blood viscosity in E-2 were significantly low (p<0.01). At shear rate $90.0\;sec^{-1}$ the value of plasma viscosity in E-1 was significantly low (p<0.05) and at shear rate 90.0, $225\;sec^{-1}$ the values of plasma viscosity in E-2 we resignificantly low (p<0.01). 4. Less severe ulcers were obsered in Opuntia dillenii Haw. treatment groups than in the control group. Especially E-1 groups tissues had only slight ulcers and necrosis of tissue was not observed in this group. From the results of this study, it can be concluded that the oral administratio-n of Opuntia dillenii Haw. results in protection of stomach ulcer by stimulating the secretion of gastric mucus and improving the gastric mucosal microcirculation.

• Neonatal Medicine
• /
• v.18 no.1
• /
• pp.82-88
• /
• 2011

Purpose: This study aims to describe the clinical characteristics of adrenal insufficiency-associated hypotension in preterm infants and the effects of hydrocortisone therapy on their cardiovascular system and serum electrolytes. Methods: Twelve preterm infants less than 32 gestational weeks admitted to neonatal intensive care unit (NICU) of the Seoul National University Bundang Hospital from January 2007 to August 2009 with clinical and laboratory findings suggestive of adrenal insufficiency were analyzed retrospectively. Results: Gestational age was 27.8${\pm}$2.5 weeks and birth weight was 1,110${\pm}$307 g. Postnatal age, postmenstrual age, weight at the onset of adrenal insufficiency-associated hypotension were 19${\pm}$7 day, 30.6${\pm}$2.4 weeks, 1,285${\pm}$365 g. In preterm infants who showed vasopressor resistance, intravenous hydrocortisone was started with a stress dose of 4 mg/kg/day, maintained for 2.2${\pm}$0.7 days, and then tapered. Serum cortisol concentration before hydrocortisone administration was 11.6${\pm}$4.1 mg/dL. Mean blood pressure increased from 25.0${\pm}$5.4 mmHg to 35.0${\pm}$5.3 mmHg, 38.3${\pm}$8.0 mmHg and 41.9${\pm}$6.5 mmHg at time of hydrocortisone administration and 2, 4 and 6 hours after hydrocortisone administration. Urine output increased from 0.9${\pm}$0.6 mL/kg/hr to 4.1${\pm}$3.4 mL/kg/hr. Twelve hours after the administration of hydrocortisone, dopamine requirement decreased from 11.0${\pm}$2.9 $\mu$g/kg/min to 8.0${\pm}$2.3 $\mu$g/kg/min, and to 5.5${\pm}$3.4 ${\mu}g$/kg/min after 24 hours. Serum sodium concentration was increased from 130${\pm}$4 mEq/L to 136${\pm}$4 mEq/L, serum potassium concentration was decreased from 6.1${\pm}$1.1 mEq/L to 4.6${\pm}$0.6 mEq/L before and 12 hours after hydrocortisone administration. Conclusion: In preterm infants with adrenal insufficiency-associated hypotension, hydrocortisone administration improved blood pressure and urine output, decreased vasopressor requirement, and normalized serum electrolyte abnormalities.

• Radiation Oncology Journal
• /
• v.19 no.1
• /
• pp.45-52
• /
• 2001

Purpose : Granulocyle-colony stimulating factor (G-CSF) has been widely used to treat neutropenia caused by chemotherapy or radiotherapy. The efficacy of recombinant human hematopoietic growth factors in improving oral mucositis after chemotherapy or radiotherapy has been recently demonstrated in some clinical studies. This study was designed to determine whether G-CSF can modify the radiation injury of the intestinal mucosa in mice. Materials and Methods : One hundred and five BALB/c mice weighing 20 grams were divided into nine subgroups including G-CSF alone group $(I:10\;{\mu}g/kg\;or\;II:100\;{\mu}g/kg)$, radiation alone group (7.5 or 12 Gy on the whole body), combination group with G-CSF and radiation (G-CSF I or II plus 7.5 Gy, G-CSF I or II plus 12 Gy), and control group. Radiation was administered with a 6 MV linear accelerator (Mevatron Siemens) with a dose rate of 3 Gy/min on day 0. G-CSF was injected subcutaneously for 3 days, once a day, from day -2 to day 0. Each group was sacrificed on the day 1, day 3, and day 7. The mucosal changes of jejunum were evaluated microscopically by crypt count per circumference, villi length, and histologic damage grading. Results : In both G-CSF I and II groups, crypt counts, villi length, and histologic damage scores were not significantly different from those of the control one (p>0.05). The 7.5 Gy and 12 Gy radiation alone groups showed significantly lower crypt counts and higher histologic damage scores compared with those of control one (p<0.05). The groups exposed to 7.5 Gy radiation plus G-CSF I or II showed significantly higher crypt counts and lower histologic damage scores on the day 3, and lower histologic damage scores on the day 7 compared with those of the 7.5 Gy radiation alone one (p<0.05). The 12 Gy radiation plus G-CSF I or II group did not show significant difference in crypt counts and histologic damage scores compared with those of the 12 Gy radiation alone one (p>0,05). Most of the mice in 12 Gy radiation with or without G-CSF group showed intestinal death within 5 days. Conclusion : These results suggest that G-CSF may protect the jejunal mucosa from the acute radiation damage following within the tolerable ranges of whole body irradiation in mice.

• Radiation Oncology Journal
• /
• v.15 no.2
• /
• pp.79-95
• /
• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• Radiation Oncology Journal
• /
• v.14 no.1
• /
• pp.25-31
• /
• 1996

Purpose : To evaluate the potential advantage for 'sandwich' technique radiotherapy compared to Postoperative radiotherapy in resectable rectal cancer. Materials and Methods : Between January 1989 and Mar 1994, 60 patients with resectable rectal cancer were treated at Inje University Seoul and Sanggye Paik Hospital. Fifty one patients were available for analysis: 20 patients were treated with sandwich technique radiotherapy and 31 patients were treated with Postoperative radiotherapy. In sandwich technique radiotherapy(RT), Patients were treated with preoperative RT 1500 cGy/5fx, followed by immediate curative resection. Patients staged as Astler-Coiler B2, C were considered for postoperative RT with 2500-4500 cGy. in postoperative RT total radiation dose of 4500-6120 cGy, 180 cGy daily at 4-Sweets was delivered. Patients were followed for median period of 25 months. Results : The overall 5-year survival rates for sandwich RT group and postoperative RT group were $60\%$ and $71\%$, respectively(p>0.05). The 5-rear disease free survival rates for each group were $63\%$. There was no difference in local failure rate between two groups($11\%$ versus $7\%$) Incidence of distant metastasis was $11\%$(2/20) in the sandwich technique RT group and $20\%$(6/31) in the postoperative RT group(p>0.05). The frequencies of acute and chronic complications were comparable in both groups. Conclusion : The sandwich technique radiotherapy group shows local recurrence and survival similar to those of Postoperative RT alone group but reduced distant metastasis compared to Postoperative RT group. But long term follow-up and large number of patients is needed to make an any firm conclusion regarding the value of this sandwich technique RT.

• Radiation Oncology Journal
• /
• v.14 no.1
• /
• pp.9-15
• /
• 1996

Purpose: The traditional approach with surgery and/or radiotherapy(RT) for advanced head and neck cancer Provides anticipated cure rates of $10-65\%$ depending on stages and sites. Recently, combined modality with chemotherapy have been extensively investigated in attempts to improve survival and local control. We retrospectively analysed our experience of 31 patients with advanced head and neck cancer. Materials and Methods : November 1983 to October 1994. 31 Patients with Stage III and IV squamous cell head and neck cancer were treated with RT. Sixteen patients were treated with RT alone, and IS patients were treated with combined RT plus chemotherapy. All patients were treated with 4-MV LINAC and radiation dose ranged from 5000 cGy to 7760 cGy (median 7010 cGy). In combined group, 7 patients were treated with cisplatin plus 5-FU 2 patients were treated with methotrexate plus leucovorin plus 5-FU plus cisplatin or carboplatin, and 6 patients were treated with cisplatin as a radiosensitizer. Results : Median follow up period was 16 months (range 4-134 months). The major responses (CR+PR) were noted in 10 patient ($66.6\%$) of the RT alone group and 14 patient ($93.3\%$) of the chemoradiation group. There was no statistical difference in CR rate between the two groups The overall survival rates at 5 years were $23.4\%$ in the radiation alone group, $23.5\%$ in the chemoradiation group Disease-free survival rates at 3 years were $44.5\%$ in the radiation alone group, $40\%$ in the chemoradiation group. There was no statistical differences in overall survival rates and disease-free survival rates between the two groups. Local recurrences occurred in $71.5\%$ of the radiation alone group, $72.7\%$ of the chemoradiation group and distant metastasis occurred in $14.4\%$ of radiation alone group, $9.1\%$ of the chemoradiation group. The frequencies of complications were comparable in both groups except hematologic toxicity Conclusion : Total response rates in the combined chemotherapy and radiotherapy was relatively higher than radiotherapy alone. But our result failed to show any survival benefit of the combined chemotherapy and radiotherapy. The accrual of large number of patients and long term follow-un may be necessary to confirm the present result of combined chemotherapy and radiotherapy.

• Radiation Oncology Journal
• /
• v.18 no.2
• /
• pp.133-137
• /
• 2000

Purpose :To investigate whether combined beta-carotene with X-Irradiation has more enhanced radition response than X-irradiation or not, we peformed a experiment about in vitro cytotoxlcity of beta-carotene and/or X-irradiation in the fibrosarcoma cells, tumor growth delay of combined beta-caroten with/or X-irradiation in the mouse fibrosarcoma. Materials and Methods : 2$\%$ emulsion of beta-carotene was serially diluted and used. X-Irradiation was given by 6 MeV linear accelerator. The cytotoxicity of beta-carotene in vitro was evaluated from clonogenic assay. To compare the cytotoxiclty between combined beta-carotene with X-irradiation and X-irradiation group, 2 mg/ml of beta-carotene was contacted to fibrosarcoma (FSall) cells for 1 hour before X-irradiation. For the tumor growth delay, single 20 Gy was given to FSall tumor hearing C3H/N mice whic was classified as beta-crotene with X-irradiation group (n=5) and X-irradiation alone group (n=5). 0.2 ml of 20 mg/kg of beta-carotene were i.p. injected to mice 30 minute before X-irradiation in the beta-crotene with X-irradiation group. The tumor growth delay defined as the time which reach to 1,000 mm$^{3}$ of tumor volume. Results : (1) Cytotoxicity in vitro: 1) survival fraction at beta-carotene concentration of 0.002,0.02,0.2 and 2 mg/ml were 0.69$\pm$0.07, 0.59$\pm$0.08, 0.08$\pm$0.008 and 0.02$\pm$0.006, respectively. 2) each survival fraction at 2, 4, 6 and 8 Gy in the 2 mg/ml of beta-carotene + X-irradiation group were 0.13$\pm$0.05, 0.03$\pm$0.005, 0.01 $\pm$0.002 and 0.009$\pm$0.0008, respectively. But each survival fraction at same irradiation dose in the X-irradiation group were 0.66$\pm$0.05, 0.40$\pm$0.04, 0.11$\pm$0.01 and 0.03$\pm$0.006, respectively(p<0.05). (2) The time which reach to 1,000 mm$^{3}$ of tumor volume of beta-carotene + X-irradiation group and X-irradiation alone group were 18, 19 days, respectively(p>0.05) Conclusion : The contact of beta-caroten to Fsall cells showed mild cytotoxicity which 띤as increased according to concentration. The cytotoxicity of combined beta-carotene with X-irradiation more increased than that of X-irradiation, additionally, And there was significant difference of cytotoxicity between two groups. But there were no significant difference of the growth delay of fibrosarcoma between two groups.

• Radiation Oncology Journal
• /
• v.27 no.3
• /
• pp.126-132
• /
• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Radiation Oncology Journal
• /
• v.25 no.4
• /
• pp.242-248
• /
• 2007

Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.