• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3103-3107
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• 2012

Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a critical role in tumorigenesis and drug-resistance. It is known that phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell fates, such as proliferation, cell cycling, survival and apoptosis. Whether and how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which are involved in the mitochondrial apoptosis pathway. Therefore, our results indicate PI3K inhibitors may represent a potential strategy for managing human osteosarcoma via affecting CSCs.

• Tuberculosis and Respiratory Diseases
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• v.76 no.2
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• pp.66-74
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• 2014

Background: The increasing number of outpatients with multidrug-resistant (MDR) pathogens has led to a new category of pneumonia, termed healthcare-associated pneumonia (HCAP). We determined the differences in etiology and outcomes between patients with HCAP and those with community-acquired pneumonia (CAP) to clarify the risk factors for HCAP mortality. Methods: A retrospective study comparing patients with HCAP and CAP at Jeju National University Hospital. The primary outcome was 30-day mortality. Results: A total of 483 patients (208 patients HCAP, 275 patients with CAP) were evaluated. Patients with HCAP were older than those with CAP (median, 74 years; interquartile range [IQR], 65-81 vs. median, 69 years; IQR, 52-78; p<0.0001). Streptococcus pneumoniae was the major pathogen in both groups, and MDR pathogens were isolated more frequently from patients with HCAP than with CAP (18.8% vs. 4.9%, p<0.0001). Initial pneumonia severity was greater in patients with HCAP than with CAP. The total 30-day mortality rate was 9.9% and was higher in patients with HCAP based on univariate analysis (16.3% vs. 5.1%; odds ratio (OR), 3.64; 95% confidence interval (CI), 1.90-6.99; p<0.0001). After adjusting for age, sex, comorbidities, and initial severity, the association between HCAP and 30-day mortality became non-significant (OR, 1.98; 95% CI, 0.94-4.18; p=0.167). Conclusion: HCAP was a common cause of hospital admissions and was associated with a high mortality rate. This increased mortality was related primarily to age and initial clinical vital signs, rather than combination antibiotic therapy or type of pneumonia.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3447-3450
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• 2015

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1154-1166
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• 1998

Background : In the management of patients whose primary chemotherapy has failed, careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The purpose of present study is establishment of retreatment regimen for pulmonary tuberculosis. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Masan Tuberculosis Hospital. Methods : Retrospective cohort study was made of 104 drug-resistant pulmonary tuberculosis patients who were treated by five regimens between Jan. 1994 and Nov. 1996. All the patients taken medicine for second anti-tuberculosis regimens for the first time. We separated the patients by three groups(Group I ; OFX+PTA+CS+PAS+Aminoglycoside, Group II : PZA+PTA+CS+PAS+Aminoglycoside, Group III : PZA+OFX+PTA+PAS+Aminoglycoside). Results : The age distribution was most frequent in fourth decade(36patients, 34.6%) and the mean age was 42.6 year. The sex distribution was more frequent in the males(81 patients, 85.7%). There was 31 patients(29.8%) with combined diseaes, 18 patients with complication and 24 patients(27.9%) with family history. Primary chemotherapy regimens were HERZ(S or K) in 48 patients (46.2%), HER(S or K) in 41 patients(39.4%) and others in 15 patients(14.4%). Result of drug sensitivity test showed that the resistance to INH and RFP is in 68 patients(65.4%), RFP is 12 patients(11.5%), INH is in 3 patients(2.9%) and all sensitive to INH and RFP is 3 patients(2.9%). The clinical symptoms on admission were coughing(89.4%), sputum(69.2%), dyspnea on exertion(37.5%), weight loss(33.7%) blood tinged sputum(15.4%) and others. The extent of disease on the radiograph was far-advanced in 73 patients(70.2%), moderate in 28 patients(26.9%) and minimal in 3 patients(2.9%). The side effects for drugs were gastrointestinal troubles in 31 patients(29.8%), arthralgia in 22 patients(21.2%), skin rash in 12 patients(11.5%) and others. The negative conversion rate on sputum AFB smear was 85.6%(87.5% in Group I, 80.0% in Group II and 90.5% in Group III). The average negative conversion time on sputum was 4 month(4.0 month in Group I, 4.6 month in Group II and 3.0 month in Group III). Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and combination of PZA and OFX can be use effectively substituting for CS.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.86-86
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• 2003

Research has been in progress for more than a decade to production of useful proteins by genetic modification in cattle. However, the levels of protein production in transgenic cattle have been reported very low. To enhance protein production in transgenic animal, we tried homologous recombination to donor cells for production of transgenic clone cattle through nuclear transfer procedure. Thus, we constructed the two targeting vectors of human thrombopoietin (TPO) at bovine $\beta$-casein locus using homologous recombination with 13.6 kb and 9.6 kb homology. In two targeting vectors, positive selection was through the neomycin resistance gene and negative selection was by the diphtheria toxin (DT). Gene targeting was attempted in bovine embryonic fibroblasts (bEF) and bovine ear skin fibroblasts (bESF). To determine the most appropriate concentration of neomycin for bEF and bESF, G4l8 resistance was confirmed by culturing the cells in various concentrations of the drug and both of the cells were optimally selected at $900 \mu g/ml$ of neomycin. The transfected bEF and bESF by the targeting vectors were colonized efficiently at the ratio of DNA to transfection reagent such as $4 \mu g$:2 ${mu}ell$ and $1 \mu g$:$2 \mu l$. Comparing number of healthy clones from passage 4 to passage 8, bESF (17%) persist in culture for much longer than bEF (6%). The two gene-targeted bESF clones of 30 random-integrated clones with 9.6 kb homology length were confirmed, however, nothing was out of 72 random integration clones with 13.6 kb homology length, The DT also worked more efficiently in clones transfected with the vector of 9.6 kb homology length. Our data suggests that the choice of donor cell for long culture period should be considered to obtain targeted cell clone, and the gene-targeting frequency and the DT working efficiency are dependent on the length of target homology.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.155-164
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• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Clinical and Experimental Pediatrics
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• v.49 no.7
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• pp.777-783
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• 2006

Purpose : Urinary tract infection(UTI) is one of the most frequent infections in children. E. coli is the most frequent etiological micropathogen in pediatric community UTI, and E. coli has developed resistance to many antibiotics, highlighting the need for regular surveys of this organism resistant patterns in the community. The aim of this study was to determine the oral antibiotic susceptibility patterns of E. coli, isolated from pediatric patients with uncomplicated community acquired UTI. Methods : E. coli isolates, obtained from pediatric patients with uncomplicated community acquired UTI between October in 2004 to September in 2005. And minimal inhibitory concentrations(MICs) of oral aminopenicillins and beta-lactamase inhibnitors(ampicillin, amoxacillin, ampicillin-sulbactam), oral cephalosporins(cefaclor, cefixime) and sulfa drug(trimethoprime-sulfamethoxazole) were performed according to the National Committee for Clinical Laboratory Standards(NCCLS) guide line. Results : Total 211 organisms were isolated from pediatric out-patients with community UTI. E. coli was the most common organism(89 percent), followed by E. fecalis, Proteus species, S. aureus, M. morganii, and P. aeruginosa. The resistant rates of aminopenicillins and beta-lactamase inhibitors, cefaclor and sulfa drug to E. coli were very high. But, the resistant rate of cefixime was markedly low, and ESBL strains were isolated with small rates. Conclusion : Our study results suggest that aminopenicillins, cefaclor and sulfa drug may not be useful as first line empirical antibiotics to treat pediatric patients with community UTI in Korea. But, 3rd generation cephalosporin such as cefixime can be used as effective second line antibiotics after primary treatment failure, also may be useful as an empirical first line antibiotic. Finally, we conclude that a continuous surveillance study to monitor susceptibility patterns of E. coli in community UTI will be needed for the standard guide lines of empirical oral antibiotic treatment.

• Journal of Life Science
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• v.30 no.9
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• pp.772-782
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• 2020

Skeletal muscle differentiation or myogenesis is important to maintain muscle mass and metabolic homeostasis. Muscle-specific microRNAs (miRNAs) are known to play a critical role in skeletal myogenic differentiation. In this study, we examined the expression profiling of miRNAs during myogenic differentiation in rat L6 myoblasts using rat miRNA microarrays. We identified the upregulated expression of miR-128 as well as several well-known myogenic miRNAs, including miR-1, miR-133b, and miR-206. We additionally confirmed the increased expression of miR-128 observed on microarray through quantitative real-time PCR (qRT-PCR), which showed similarly upregulated expression of both primary miR-128 and mature miR-128, consistent with the microarray findings. Furthermore, transfection of miR-128 into rat L6 myoblasts induced gene expression of myogenic markers such as muscle creatine kinase (MCK), myogenin, and myosin heavy chain (MHC). Protein expression of MHC was increased as well. Inhibition of miR-128 by inhibitory peptide nucleic acids (PNAs) blocked the expression of those myogenic markers. In addition, the transfection of miR-128 into rat L6 myoblasts enhanced the phosphorylation of Erk and Akt proteins stimulated by insulin, while simultaneously reversing the inhibited phosphorylation of Erk and Akt due to insulin resistance. These findings suggest that miR-128 may play important roles in myogenic differentiation and insulin signaling.

• Parasites, Hosts and Diseases
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• v.27 no.2
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• pp.79-86
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• 1989

A pathogenic free-living amoeba, Naegleria fowleri, causes primary amoebic meningoencephalitis to human and experimental animals. This infection is rare, but the mortality is very high. Nowadays, drug treatment or active immunization of human or mice are being tried with partial effectiveness. This study shows passive immunization effect by transfer of immunized spleen cells, serum, or milk from immunized mother in mouse experimental model. Young BALB/c mice were immunized intraperitoneally with $2~3{\times}10^{6}$ trophozoites of N. fowleri, and spleen cells and sera were collected for injection to recipient mice. There were seven transfer groups, i.e., immunized mouse serum, spleen cells, serum and spleen cells, normal mouse serum, spleen cells, serum and spleen cells, and control group. Three days later, BALB/c mice were inoculated with $1{\times}10^{4}$ trophozoites of N. fowleri intranasally. After infection, decreased mortality ana prolonged survival time of mice were noted in immunized Bloops compared with non.immuniBed control group. The groups Injected with immunized spleen cells or normal serum shewed lower moltality than that of controls bult showed no changes of Serum IgG level. The groups injected with immunized serum or normal spleen cells showed increased serum IgG level after immunization but hundred percent mortality was observed. Mother mice were ifnfnunised increperitqneeliy with $2~3{\times}10^{6}$ trephozoites of N. fowleri at the end of pregnancy and weaning Period. Soon after the delivery, Jitters born of non-immunszed mother were matched with immunized mother for feeding immune milk. After three weeks, the litters were infected with $1{\times}10^{4}$ trophozeites of N. fowleri or sacrificed for serum collection to measure the IgG levels. The results show that anti-JV. fowleri IgG from mother was transferred to litter through milk but this IgG did not inauence the mortality or survival time of the infected mice.

• Applied Microscopy
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• v.33 no.4
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• pp.261-266
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• 2003

The growth patterns of primary culture of bovine brain microvessel endothelial cells (BBMECs) were studied using electron microscopy when grown on $3.0{\mu}m$ and $0.4{\mu}m$ pore Transwell. The capillary fragments and isolated endothelial cells grew on collagen coated culture plate and Transwell membrane. The BBMECs grew only on the upper surface of membrane of $0.4{\mu}m$. But BBMECs on $3.0{\mu}m$ pore membrane migrated through the pore and grew on the opposite side of the membrane. In summary, BBMECs isolated by enzyme digestion could migrate through $3.0{\mu}m$ pore membrane but not through $0.4{\mu}m$ pore membrane. So $0.4{\mu}m$ pore membrane instead of $3{\mu}m$ pore membrane should be used for drug transport experiment or transendothelial electrical resistance measurement.