• Journal of Life Science
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• v.19 no.8
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• pp.1073-1080
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• 2009

A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

• Journal of Life Science
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• v.21 no.9
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• pp.1234-1243
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• 2011

Liriope platyphylla has been used in oriental medicine as an effective medical plant to improve symptoms of cough, sputum production, neurodegenerative disorders, obesity and diabetes for long time. In order to investigate the effects of novel extracts on nerve growth factors (NGF)-stimulated neuritic outgrowth, the alteration of NGF expression and NGF receptor signaling pathway were detected in neuroblastoma cells and C57BL/6 mice. Of a total of 13 novel extracts, 4 extracts (LP-E, LP-M, LP-M50, LP2E17PJ) showed high viability on MTT assay. Also, all of these extracts induced NGF secretion and NGF mRNA expression in neuroblastoma cells. However, the NGF-induced neuritic outgrowth from PC12 cells was only stimulated by LP-E, LP-M and LP-M50. Furthermore, we selected LP-M as a best candidate, based on method and amounts of extraction, in order to verify its effect in mice. C57BL/6 mice were treated with 50 mg/kg of LP-M for 2 weeks and the effects on NGF regulation were analyzed with various methods. The expression of NGF mRNA was significantly increased in LP-M treated mice compared to vehicle treated mice. Also, the signaling pathway of p75NTR was inhibited in the cortex by LP-M treatment, with no change in the hippocampus of brain. However, the signaling pathway of TrkA was dramatically activated in only hippocampus via LP-M treatment. Therefore, these results suggest that the novel four extracts of L. platyphylla may contribute to the regulation of NGF expression and secretion in neuronal cells. LP-M was especially considered to be an excellent candidate for a neurodegenerative disease-therapeutic drug.

• Journal of Korean Neurosurgical Society
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• v.64 no.6
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• pp.983-994
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• 2021

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

• Journal of Life Science
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• v.33 no.9
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• pp.713-723
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• 2023

Lung cancer is a type of cancer that has the highest mortality rate. It is mainly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Chemotherapy is used to treat lung cancer, but long-term treatment causes side effects and drug resistances. Curcumin is a bright yellow polyphenol extracted from the root of turmeric. It has biological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory effects. In this study, we observed differential cell death in human lung cancer cells. Based on the results, curcumin at 10, 30, and 50 μM exhibited a dose-dependent inhibition on the cell survival of several lung cancer cells, with minor differential phenotypes. In addition, apoptosis, autophagy, and reactive oxygen species (ROS) regeneration were observed through flow cytometry. Curcumin dose-dependently increased these phenotypes in A549 (NSCLC) and DMS53 (SCLC), which were restored by corresponding inhibitors. Western blotting was performed to measure the level of expression of apoptosis- and autophagy-related proteins. The results indicate that Bax, PARP, pro-caspase-3, and Bcl-2 were dose-dependently regulated by curcumin, with seemingly higher Bax/Bcl-2 ratios in DMS53. In addition, autophagic proteins, p-AKT, p62, and LC3B, were dose-dependently regulated by curcumin. ROS inhibition by diphenyleneiodonium reduced the induction of apoptosis and autophagy generated by curcumin. Taken together, it is suggested that curcumin induces apoptosis and autophagy via ROS generation, leading to cell death, with minor differences between human lung cancer cells.

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.337-345
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• 1995

To evaluate the pathogenicity and immunogenicity of Eimeria tenella to the chicken treated with dexamethasone(DEX) and testosterone propionate (TES), we administered 0.1ml/chicken of dexamethasone and 40mg/chicken of testosterone propionate at 1-, 2-, and 7-days old, respectively. We also immunized with ND oil-emulsion vaccine at 2 weeks old. After that, we immunized and challenged with 100 and $1{\times}10^5$ oocysts/chicken of E tenella at 2 and 4 weeks old, respectively. And then we investigated the HI titers for ND virus, survival rate, body weight gain, lesion score and the weight of the bursa of Fabricius and thymus. The titers for ND virus in the groups treated with TES were higher than those in the groups treated with DEX and CON during 3 to 6 weeks. After challenge, the survival rate of testosterone propionate treated-challenged(TES-CHA) and TES-immunized and challenged(TES-V&C) groups were 61.5 and 83.3% and those of the other groups were all 100%. At 1 week after challenge, the lesion scores of TES-CHA group(4.0) was the highest of all experimental groups. Those of DEX and controlchallenged( CON-CHA) groups were 2.8, and those of all V&C groups were 2.4. During 1 and 2 weeks after immunization, the body weight gains of TES groups were severe low(61.6-82.2g and 189.6-260.4g). During 1 and 2 weeks after challenge, the body weight gains of all CHA groups were lower than those of not challenged groups. But, those of all V AC groups were not different from those of not immunized groups. At 4- and 6-weeks old, the weight of the bursa of Fabricius and thymus in the chicken of all TES groups were lower than those of all control (CON) and DEX groups. Therefore, testosterone propionate acted as immunosuppressive drug. Also, it was thought that the chicken affected a little humoral immunity to E tenella.

• Research in Community and Public Health Nursing
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• v.7 no.1
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• pp.69-79
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• 1996

To investigate the factors related with the compliance and the treatment of the patients with pulmonary tuberculosis in urban and suburb area, we followed up all the 755 registered patients(at urban Public Health Office 544, at suburb 210) as follow from January 1,1992 to December 31, 1993. We describe the general characteristics and the characteristics related with the disease of the patients according to the area as follow. 150 patients(27.5%) were at their age of 20 to 29 years in the urban area, whereas 45 patients (21.4%) were 60 to 69 years and another 45 patients(21.4%) were 70 to 79 years in the suburb area. According to the first chest X -ray examination, 54.5% of all cases were proved to be mild in the urban area. But in the suburb area, moderate cases (44.3%) were more than mild cases(p<0.01). Follow-up X-ray's were performed more properly(p<0.05) in the urban area(94.3%) than in the suburb area(90.0%). Most cases were found in the chest X -ray examination performed by Public Health Office (p<0.01) : payable chest X-ray in the urban area (56.7%) and free chest X-ray in the suburb area(35.2%). More patients were cured in the urban area(90.8%) than in the suburb area(87.1%). The presence of supporting family member were significantly higher(p<0.05) in the urban area(79.1%) than in the suburb area(88.1%). In the analysis of the treatment efficacy, more cure ate were found in the patients cytologically confirmed to be culture (+). In the urban area, 201 culture (+) patients (93.5%) 294 culture (-) patients (89.1%) were cured. In the suburb area, 99 culture (+) patients(91.7%) and 84 culture (-) patients(82.4%) were cured. Age, the presence of supporting family member, and the socioeconomic status of the patient had significant association with the prescription compliance related with the general characteristics of the patients. Whereas, X-ray finding and AFB culture finding were the significant factors associated with the prescription compliance related with pulmonary tuberculosis (p<0.05). The cumulative compliance in the survival analysis was 92.5% in the urban area and 88.1% in suburb area, at sixth month of follow-up. Failure rate for regular drug receipt was highest at second month in the urban area(3.75%) and at fourth month in the suburb area(4.15%). In logistic regression of the factors related with the tratment result, first X-ray examination and prescription compliance were significantly associated in the urban area(p<0.05). However, there is no factor significantly associated with the treatment result in the suburb area. It could be explained by too small size of the sample. In logistic regression of the factors related with the prescription compliance, first chest X-ray, sputum culture outcome and the presence of supporting family member were significant variables in the urban area(p<0.05). Most patients with family member were proved to be compliant with the prescription. This shows that it is important for the patients with long-lasting ilnesses to have supporting family member. Therefore, to improve prescription compliance we should strengthen the health education before the initiation of treatment and take special interest in the patients without supporting family member.