• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.476-486
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• 2008

Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.487-494
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• 2008

Background: Chromosome 17p allele losses and mutations of p53 gene are the most common genetic abnormalities in lung cancer. The purposes of this study were to evaluate the factors associated with p53 protein overexpression and to evaluate its prognostic value in patients with pathologic stage I non-small cell lung cancer (NSCLC). Methods: This is a retrospective review for the patients who underwent surgical resection at Samsung Medical Center between Jan 2003 and Jun 2004. Immunohistochemical staining for p53 protein was performed on tumor tissues from patients with lung cancer. The p53 overexpression was evaluated in relation to age, sex, smoking history, histology and pathologic stage by univariate and multivariate analyses. The disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were analyzed using the Kaplan-Meier methods and the differences in DFS, DSS and OS were assessed by using the log-rank tests. Results: A total of 125 patients were included in the analysis and a median frequency of p53 expression in tumor tissue was 10%. The p53 overexpression (${\geq}10%$) was more common in squamous cell carcinoma (66%) than in adenocarcinoma (38%, p=0.002). The p53 overexpression was more common in pathologic stage IB (59%) than in IA (38%, p=0.002). Patients with p53-overexpressing tumor (27 years) smoked more years compared with those without it (20 years, p=0.032). Smoking history ${\geq}25$ pack-years was more common in patients with p53 overexpression (58%) than in those without it (38%, p=0.024). In the multivariate analysis, only histology was significantly associated with p53 overexpression. However, there were no significant differences of DFS, DSS and OS in relation to p53 status. Conclusion: The p53 overexpression was associated with histology, pathologic stage and smoking history in patients with pathologic stage I NSCLC. However, the p53 overexpression was not associated with patient's survival.

• Journal of Aquaculture
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• v.4 no.1
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• pp.31-66
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• 1991

This paper deals with the reproductive ecology e.g., number of the pre-spawning moults, morphological characteristics of the pre-spawning moult the common moult, daily ration druing a molting cycle mating behavior, structures of spermatozoa and spermatophore, structure of vas deferens, mechanisms of the oviposition and brooding into the egg-chambers, a suitable time for the artificial mating and fertilization, time sequence of the oviposition and brooding into egg-chambers from the copulation, responses to temperature and chlorinity on the egg development and hatching, effect of temperatures on duration of egg development, physical mechanism of the egg hatching, to make an attempt for the artificial spawning and brooding to establish a suitable system of the artificial seedling-production for the aquaculture. 1. Females molted commonly $8{\~}10$ times at an interval of $17{\~}18$ days at $28^{\circ}C,\;3.26\~4.35\%_{\circ}$ while the prespawning moltings were $4{\~}5$ times at an interval of $13{\~}14$ days. The suitable state for artificial copulation was within 14 hours elapsed from the prespawning moltings (most suitable state was within 8 hours). Males discharged a gelatinous spermatophore and placed it on the females sternum during copulation. Oviposition was seen $6{\~}17$ hours after copulation. External fertilization was considered to take place at oviposition. Fertilized eggs held in egg-chambers forming between pleopods were about $5000{\~}6000$ in females those sizes about 6.5 cm in body length. 2. Eggs immediately after oviposition were elliptic shape, measuring $0.58{\times}0.48$ mm up to hatching. Their sizes increased with egg development and finally reached $0.85{\times}0.54$ mm up to hatching. The relationship between the long axis of the egg(Y in U) and days elapsed(X) was expressed as Y= 5.60194 + 0.007358X. The eggs performed superficial cleavage and their cleavage furrows became visible at the 4-daughter-nucleus stage. The eggs showed normal development up to hatching at water temperature range of $22{\~}30^{\circ}C$ (optimum temperature : $26{\~}28^{\circ}C$) and at chlorinity range of $0.00\~6.64\%_{\circ}$ (optimun chlorinity : $2.21{\%}_{\circ}$). The relationship between incubation period (Y in days) and water temperature(X in $^{\circ}C$) could be expressed as Y= 50.803-1.3555X. The eggs hatched $12{\~}13$ days after oviposition at $28.0{\~}28.6^{\circ}C$ 3. The pre-spawning moltings were appreciably different in the morphologic structure from those of common moltings. Breeding setae and dresses were formed on the thoracic regions, abdominal epimerae and the bases of the first to fourth pleopods in order to prepare and support oviposition, transfering and supporting eggs in egg-chambers up to hatching. These supplementary breeding organs were observed only at reproductive seasons.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.45-52
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• 1991

The inhibitory effects of GS354 and GS389 on cytosolic $Ca^{2+}$ level ($[Ca^{2+}]_{1}$; measured with fura-2 fluorescence) and muscle tension in vascular smooth muscle of rat thoracic aorta were investigated. Both GS354 and GS389 inhibited the contractions induced by high $K^+$ or by norepinephrine. The vasodilator effect of GS354 was accompanied by a decrease in $[Ca^{2+}]_{1}$. The inhibitory effect on high $K^+-stimulated$ $[Ca^{2+}]_{1}$ was antagonized by a $Ca^{2+}$ channel activator, Bay K8644. However, the inhibitory effect on muscle tension was not antagonized by Bay K8644. These results suggest that GS354 inhibits $Ca^{2+}$ channels to decrease $[Ca^{2+}]_{1}$ and also decreases $Ca^{2+}$ sensitivity of contractile elements. The inhibitory effects of GS389 was accompanied by the increase in tissue fluorescence. This increment was not due to fura-2 fluorescence but to endogeneous pyridine nucleotides, suggesting that GS389 has an effect to inhibit mitochondrial function. Because of this interference, effects of GS389 on $[Ca^{2+}]_{1}$ was obscured. However, since sequential addition of Bay K8644 in the presence of GS389 further increased the fluorescence but not muscle tension, this compound seems to have the effects to inhibit $Ca^{2+}$ channels and to decrease $Ca^{2+}$ sensitivity of contractile elements.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.11-16
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• 2000

Purpose :We peformed the retrospective analysis to find the outcome of external beam radiotherapy alone in advanced esophageal cancer patients. Methods and Materials : One hundred and six Patients treated with external beam radiotherapy alone between July 1990 and December 1996 were analyzed retrospectively. We limited the site of the lesions to the thoracic esophagus and cell type to the squamous cell carcinoma. Follow-up was completed in 100 patients (94$\%$) and ranged from 1 month to 92 months (median; 6 months). Results :The median age was 62 years old and male to female ratio was 104 2. Fifty-three percent was the middle thorax lesion and curative radiotherapy was peformed in 83$\%$. Mean tumor dose delivered with curative aim was 58.6 Gy (55$\~$70.8 Gy) and median duration of the radiation therapy was 53 days. The median survival of all patients was 6 months and )-year and 2-year overall survival rate was 27$\%$ and 12$\%$, respectively, Improvement of dysphagia was obtained in most patients except for 7 patients who underwent feeding gastrostomy. The complete response rate immediately after radiation therapy was 32$\%$ (34/106). The median survival and 2-year survival rate of the complete responder was 14 months and 30$\%$ respectively, while those of the nonresponder was 4 months and 0$\%$ respectively (p=0.000). The median survival and 2-year survival rate of the patients who could tolerate regular diet was 9 months and 16$\%$ while those of the patients who could not tolerate regular diet was 3 months and 0$\%$, respectively (p=0.004). The survival difference between the patients with S cm or less tumor length and those with more than 5 cm tumor length was marginally statistically significant (u=0,06). However, the survival difference according to the periesophageal invasion or mediastinal tyrnphadenopathy in the chest CT imaging study was not statistically significant in this study. In a multivariate analysis, the statistically significant covariates to the survival were complete response to radiotherapy, tumor length, and initial degree of dysphagia in a decreasing order. The complication was observed in 10 patients (9$\%$). Conclusion :The survival outcome for advanced esophageal cancer patients treated by external beam radiotherapy alone was very poor. In the treatment of these patients, the brachytherapy and chemotherapy should be added to improve the treatment outcome.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.133-139
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• 2009

Purpose: This study was designed to analyze the outcome and toxicity of thoracic radiation therapy (TRT) and chemotherapy for patients who suffer with limited-stage small-cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively studied 35 patients with LS-SCLC. TRT was administered once daily (1.8 to 2 Gy per fraction) and it was directed to the primary tumor for a total 50 to 66 Gy in 6 to 7 weeks. The patients received four cycles of etoposide plus cisplatin. TRT was begun on day 1 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. Results: The median progression-free survival time was 16.5 months (95% confidence interval [CI], 9.0 to 24.1 months) for the sequential arm, and 26.3 months (95% CI, 16.6 to 35.9 months) for the concurrent arm. The 2-year progression-free survival rate was 16.0 percent for the sequential arm and 50.0 percent for the concurrent arm (p=0.0950 by log-rank test). Leukopenia was more severe and more frequent in the concurrent arm than in the sequential arm. However, severe esophagitis was infrequent in both arms. The radiotherapy was interrupted more frequently in the concurrent arm than in the sequential arm due to hematologic toxicities (p=0.001). Conclusion: This study suggests that concurrent TRT with etoposide plus cisplatin is more effective for the treatment of LS-SCLC than sequential TRT. However, there is a significant increase in the risk of toxicities, and radiotherapy was frequently interrupted in the concurrent arm due to hematologic toxicities.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.17-23
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• 2008

Purpose: The best treatment for advanced esophageal cancer is chemoradiotherapy followed by surgery. In spite of the advance of multimodality therapy, most patients with esophageal cancer are treated with radiation therapy alone. This study reports the outcome of the use of conventional external beam radiotherapy alone for the treatment of esophageal cancer. Materials and Methods: Between January 1998 and December 2005, 30 patients with squamous cell carcinoma of the esophagus were treated with external beam radiotherapy using a total dose exceeding 40 Gy. Radiotherapy was delivered with a total dose of 44-60 Gy(median dose, 57.2 Gy) over $36{\sim}115$ days(median time, 45 days). Thirteen patients(43.3%) had a history of disorders such as diabetes, hypertension, tuberculosis, lye stricture, asthma, cerebral infarct, and cancers. Four patients metachronously had double primary cancers. The most common location of a tumor was the mid-thoracic portion of the esophagus(56.7%). Tumor lengths ranged from 2 cm to 11 cm, with a median length of 6 cm. For AJCC staging, stage III was the most common (63.3%). Five patients had metastases at diagnosis. Results: The median overall survival was 8.3 months. The survival rates at 1-year and 2-years were 33.3% and 18.7%, respectively. The complete response rate $1{\sim}3$ months after radiotherapy was 20%(6/30) and the partial response rate was 70%(21/30). Sixteen patients(53.3%) had an improved symptom of dysphagia. Significant prognostic factors were age, tumor length, stage, degree of dysphagia at the time of diagnosis and tumor response. Cox regression analysis revealed the aim of treatment, clinical tumor response and tumor length as independent prognostic factors for overall survival. Twenty-eight patients had local failure and another four patients had metastases. Three patients were detected with double primary cancers in this analysis. A complication of esophageal stricture was observed in three patients(10%), and radiation pneumonitis occurred in two patients(6.7%). Conclusion: The prognosis of esophageal cancer remains poor, in spite of advances in radiotherapy techniques. Radiotherapy is one of the main treatment modalities for the relief of dysphagia and treatment related complications are minimal. It is expected that the addition of chemotherapy or another systemic modality to radiotherapy will improve tumor control and increase the survival rate in advanced esophageal cancer.

• Journal of Veterinary Clinics
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• v.18 no.4
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• pp.315-323
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• 2001

Changes in somatosensory evoked potentials (SEPs) which accompanied by insertion of foreign body in spinal canal were evaluated with clinical signs and positive contrasted myelography in dogs. Foreign bodies occupied 20∼50% of spinal canal. Foreign bodies occupying about 50% of spinal canal were inserted into the animals of group II and III for 1 week and 2 days, respectively. Foreign bodies occupying about 20% of spinal canal were inserted into the animals of group IV, V, and for 1 week, 2 days, and 8 weeks, respectively. in group I (control group), sham operation (lateral laminectomy) was performed. Group III, IV and V did not severely affect on SEPs latencies and clinical signs. Group VI affects on SEPs latencies but not on clinical signs. After foreign body removal, SEPs latencies showed similar recovery patterns with clinical signs. However, group II induced severe abnormalities in SEPs latencies and clinical signs. In group III, IV and V, thoracic potentials (TN1) were abnormally recorded after foreign body insertion and firstly/normally recorded on the 6th 9.5th and 3.5th day after foreign body (removal following) insertion. In group VI, TN1 was abnormally recorded after foreign body insertion and firstly recorded on the 7.7th day and normally recorded on 34th day after foreign body insertion. In group I, TN1 was not recorded from the 3rd day after foreign body insertion and until the 8th week after foreign body removal. In group I, TN1 was firstly recorded on the 1st day after laminectomy.

• Journal of Society of Preventive Korean Medicine
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• v.9 no.2
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• pp.59-75
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• 2005

The experiments were undertaken to evaluate the effects of Bosaengtang in pregnant rats and fetuses. Female Sprague-Dawley rats were orally administered with Bosaengtang at the dose of 5mg/kg/day for 20 days. Pregnant rats were sacrificed at the 20th day of gestation, and observed internal and reproductive organs. Fetuses were randomly selected and fixed in 95% ethanol. Fetuses were stained with alcian blue and alizarin red S, and observed skeletal malformations. The results obtained were as follows : Bosaengtang administered group showed higher maternal body weight than the control group, but both groups showed increase in weight. Bosaengtang administered group showed lower than the control group, and higher liver and kidney weight than the control group, but the differences were minimal. There were no significant changes between the control and treated group in blood chemistry values and hematological values but all the groups were within in normal ranges. There were no significant changes in the number of corpus luteum, implantation, live fetus and implantation rate, delivery rate, late resorption rate, sex ratio, but Bosaengtang administered group showed higher early resorption rate than control group. comparing the control and Bosaengtang group, neonatal body weight and the number of fetuses were increased in Bosaengtang group. The fetuses of dams treated with Oriental medicine didn't showed external malformation. Vertebral and sternal variations were observed in Bosaengtang group, but the differences were not apparent compared to the control group. The number of ribs, cervical, thoracic and lumbar vertebrae were normal. The number of sacral was similar and the number of caudal was increased. Fetuses showed significant difference in the number of caudal vertebrae. (P<0.01) From these results, we can carefully conclude that Bosaengtang showed beneficial effects on maternal body weight, early resorption rate, number of live fetus. There were no significant changes in organ weight, hematoscopy, reproduction organs. External malformation wasn't visible. Skeletal variations were showed in vertebrae and sternum but compared to the control group, these variations weren't much different.

• Journal of Chest Surgery
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• v.26 no.6
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• pp.427-440
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• 1993

The paucity of donor hearts for transplantation can be remedied by distant heart procurement. Prolonging donor heart preservation is essential for successful clinical cardiac transplantation. Thirty-two isolated rat hearts were perfused with Krebs-Henseleit buffer solution for 15 minutes, arrested and preserved at 4 oC for 4 hours, and then reperfused for 25 minutes. The following three groups were prepared and hemodynamic changes, creatine kinase-MB isoenzyme levels and ultrastructural changes of the myocardium were analysed before and after cardiac arrest. ; Group I : the heart was arrested with the cardioplegic solution [Plegisol, potassium : 16 mM, sodium : 120 mM] and then stored in a solution with ionic compositions of the extracellular fluid [Hartman, potassium : 4 mM, sodium : 130 mM] ; Group II : the heart was arrested with the cardioplegic solution and stored in a solution with ionic compositions of the intracellular fluid [Modified Euro-Collins, potassium : 108 mM, sodium : 10 mM] ; Group III : the heart was arrested with the cardioplegic solution containing adenosine 20 uM, and then stored in a solution with ionic compositions of the intracellular fluid [Modified University of Wisconsin solution, potassium : 119 mM, sodium: 23 mM]. Left ventricular developed pressure at 20 minutes of the reperfusion was significantly higher in group III [64.3 $\pm$ 3.12 mmHg, p<0.01] and group II [58.3 $\pm$ 1.55 mmHg, p<0.05] as compared with group I [51.4$\pm$ 2.78 mmHg]. The time to induce cardiac arrest after infusion of cardioplegic solution with adenosine 20 uM [5.3 $\pm$ 0.30 second, p<0.005] was significantly shorter than without adenosine [10.6$\pm$ 0.55 second]. Coronary flow at 20 minutes of the reperfusion was augmented significantly in group III [9.6$\pm$ 0.50 ml/min, p<0.05, p<0.05] as compared with group I [8.0 $\pm$ 0.41 ml/min] and group II [8.1$\pm$ 0.51 ml/min]. Percentage recovery of left ventricular developed pressure at 20 minutes of the reperfusion was significantly higher in group III [94.6$\pm$ 2.51 %, p<0.005] as compared with group II and in group II [83.1 $\pm$ 1.22 %, p<0.005] as compared with group I [69.9 $\pm$ 1.73 %], and also percentage recovery of coronary flow at 20 minutes of the reperfusion was significantly higher in group III [82.3 $\pm$ 3.86 %, p<0.05] as compared with group II [71.4 $\pm$ 3.46 %] but there was no significant difference between group I and group II. Measured level of creatine kinase-MB isoenzyme at 15 minutes of the reperfusion was significantly lower in group III [1.23 $\pm$ 0.16 ng/ml, p<0.025] and group II [1.42$\pm$ 0.10 ng/ml, p<0.05] as compared with group I [1.79 0.14 ng/ml]. In the semiquantitative evaluation of the ultrastructural changes of the myocardium, mitochondrial score was lower in group III [0.7 $\pm$ 0.21] than in group I [3.1$\pm$ 0.28] and group II [1.7 $\pm$ 0.19], and also the other structural score was lower in group III [2.7$\pm$ 0.99] than in group I [7.9 $\pm$ 0.89] and group II [5.0 $\pm$ 1.22]. In conclusion, the solution with ionic compositions of the intracellular fluid is appropriate for prolonged cardiac preservation, and it appears to be better preserving method for distant procurement when the donor heart is rapidly arrested with cardioplegic solution containing adenosine 20 uM, and then stored with Modified University of Wisconsin solution.