Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; 25 microg/ml) and methotrexate (MTX; 50 microg/ml), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptasepolymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

Prospective Randomization Trial of G-CSF-Primed Induction Regimen versus Standard Regimen in Patients with AML / 전남의대학술지

The sensitization of leukemia cells with hematopoietic growth factors can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). Therefore, the current trial attempted to evaluate the efficacy of granulocyte colony-stimulating factor (G-CSF) priming in remission induction chemotherapy with an intensified dose of Ara-C for newly diagnosed AML. Patients with newly diagnosed AML were randomly assigned to receive idarubicin (12 mg/m2/24 hr, days 1-3) plus Ara-C (500 mg/m2/12 hr, days 4-8) with G-CSF (250 microg/m2/d, days 3-7) (IAG group) or standard idarubicin (12 mg/m2/24 hr, days 1-3) plus Ara-C (100 mg/m2/12 hr, days 1-7) without G-CSF (IA group). There were no significant differences in sex, age, subtype, or cytogenetic risk between the two groups. Complete remission was achieved in 15 patients (88.2%) from the IAG group and in 14 patients (82.4%) from the IA group (p=0.31). The median time to complete remission was 26 vs. 31 days (p=0.779) for the IA and IAG groups, respectively. The median time to neutrophil recovery (>1x10(9)/L) and platelet recovery (>20x10(9)/L) did not differ significantly between the two groups (26 vs. 26 days, p=0.338; 21 vs. 16 days, p=0.190, respectively). After a median follow-up of 682 days, the 3-year overall survival rate for the IA group was 64.7%, whereas that for the IAG group was 45.6% (p=0.984). No improved clinical outcomes were observed for the AML patients subjected to intensified remission induction with G-CSF priming when compared with standard induction chemotherapy.

Determination of Oxyclozanide in Beef and Milk using High-Performance Liquid Chromatography System with UV Detector / 한국실험동물학회지

This study was developed and validated for the determination of oxyclozanide residue concentrations in beef and commercial milk, using high-performance liquid chromatography system. Oxyclozanide was successfully separated on a reverse phase column (Xbridge-C18, 4.6x250 mm, 5 microm) with a mobile phase composed of acetonitrile and 0.1% phosphoric acid (60:40, v/v%). This analytical procedure involved a deproteinization process using acetonitrile for beef and 2% formic acid in acetonitrile for commercial milk, dehydration by adding sodium sulfate to the liquid analytical sample, and a defatting process using n-hexane; after these steps, the extract was exposed to a stream of nitrogen dryness. The final extracted sample was dissolved in the mobile phase and filtered using a 0.45 microm syringe filter. This method had good selectivity and recovery (70.70+/-7.90-110.79+/-14.95%) from the matrices. The LOQs ranged from 9.7 to 9.8 microg/kg for beef and commercial milk. The recoveries met the standards set by the CODEX guideline.

Prospective Randomization Trial of G-CSF-Primed Induction Regimen versus Standard Regimen in Patients with AML / 전남의대학술지

The sensitization of leukemia cells with hematopoietic growth factors can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). Therefore, the current trial attempted to evaluate the efficacy of granulocyte colony-stimulating factor (G-CSF) priming in remission induction chemotherapy with an intensified dose of Ara-C for newly diagnosed AML. Patients with newly diagnosed AML were randomly assigned to receive idarubicin (12 mg/m2/24 hr, days 1-3) plus Ara-C (500 mg/m2/12 hr, days 4-8) with G-CSF (250 microg/m2/d, days 3-7) (IAG group) or standard idarubicin (12 mg/m2/24 hr, days 1-3) plus Ara-C (100 mg/m2/12 hr, days 1-7) without G-CSF (IA group). There were no significant differences in sex, age, subtype, or cytogenetic risk between the two groups. Complete remission was achieved in 15 patients (88.2%) from the IAG group and in 14 patients (82.4%) from the IA group (p=0.31). The median time to complete remission was 26 vs. 31 days (p=0.779) for the IA and IAG groups, respectively. The median time to neutrophil recovery (>1x10(9)/L) and platelet recovery (>20x10(9)/L) did not differ significantly between the two groups (26 vs. 26 days, p=0.338; 21 vs. 16 days, p=0.190, respectively). After a median follow-up of 682 days, the 3-year overall survival rate for the IA group was 64.7%, whereas that for the IAG group was 45.6% (p=0.984). No improved clinical outcomes were observed for the AML patients subjected to intensified remission induction with G-CSF priming when compared with standard induction chemotherapy.

Pharmacokinetic and Toxicokinetic Studies of Potential Antifungal Compounds, KAF-200522 and KAF-200522 . HCl, in Animal Models / 한국실험동물학회지

Recent researches on clinically used triazole antifungal reagents are focused on their pharmacokinetic disadvantage which increases the probability of inducing adverse effects in patients. For this point, in the present laboratory, Chemon Inc., has investigated new antifungal reactive compounds, KAF-200522 and its chloride form, KAF-200522 . HCl, which has a modified triazole structure. Pharmacokinetic data were measured with LC-MS/MS in male mice which were orally treated with the above compounds at 10 mg/kg. Tmax and t1/2 of KAF-200522 . HCl were comparable to KAF-200522, but AUC and Cmax were 1.4 and 1.6 times higher than those of KAF-200522, respectively. In beagle dogs, AUC and Cmax of KAF-200522 . HCl were 2.7 and 1.4 times higher than those of KAF-200522, and t1/2 was 3.5 times higher than that of KAF-200522. Moreover, in beagle dogs, the oral bioavailability value of KAF-200522 . HCl was revealed as 31.0% to contrast to 6.2% of KAF-200522. In 1-week repeated oral treatment toxicity study of KAF-200522 in male rats, inhibition of body weight gain was observed in 120 mg/kg treatment group, and loss of body weight was observed in 600 mg/kg treatment group. In the toxicokinetic study of KAF-200522, no accumulation after the systemic exposure was observed. In conclusion, as to the new antifungal drug development, KAF-200522 . HCl was considered to be advantageous in pharmacokinetic characteristics compared to KAF-200522.

The Reliability and the Validity of Health Related QOL Measurement Method in Hemodialysis Patients / 대한신장학회지

PURPOSE: It is necessary to confirm of the reliability and the validity of health-related quality of life (HRQOL) methods, because there could be some difference according to the underlying diseases, languages and cultures. METHODS: To assess the reliability, we did the test-retest by using the WHO-QOL (Korean version) and the SF-36 (Korean version) in the maintain hemodialysis (HD) patients (N=57). And then, we measured the Cronbach coefficient in the domains of both HRQOL methods. To assess the validity, we compared the result of both HRQOL methods in HD group with control group (N=60). We analyzed the inter-relationship of the domains which keep identical meanings in both methods. RESULT: 1. The test-retest showed high correlation between two tests, except the two domains of SF- 36 which are the role limitation-physical activity (RP) domain and the role limitation-emotion (RE) domain. The Cronbach coefficients are range of 0.749-0.862 in the WHO-QOL, and 0.666-0.944 in the SF-36 (p<0.05). 2. We found that HRQOL of HD group was lower than that of control group except in the RP domain and the RE domain of SF-36. And there was the highest correlation between the domains which keep identical meaning of both HRQOL methods. CONCLUSION: The Korean WHO-QOL and SF-36 are reliable and valid to measure the QOL of ESRD patients except in the RP domain and the RE domain of SF-36. We expect these methods will be used easily in the evaluation of the HRQOL in HD patients.

Readability of Patient Information on Hypertension in Korea

BACKGINFORMAROUND: Patient education is an important component of family practice. Pamphlets and the websites have been one of the most common resources for patient education. Patient information has been assessed using criteria with marks allocated for its content, design, readability. Up to present there have been studies on content, design but not readability. The WHO identifies readability as an essential tool for people to increase control over their health. Therefore, patient information should be assessed readability. The objective of our study was to assess patient information leaflets and the websites on hypertension to determine the readability of information currently available to patients. METHODS: Ten leaflets were reviewed, five form the internet and five from other sources. A total of ten subjects were assessed for readability using 'grading system of vocabulary' presented by the Academy of Korea Education in 2002. RESULTS: In five leaflets, about 41.3% vocabularies were comprised of 1st and 2nd grade. The portion of vocabularies in higher grade than 4th was 35%. In the five websites, 41.3% vocabularies in 1st and 2nd grade were used. The mean reading level (calculated with weight) was 2.057 for the five leaflets and 2.050 for the five websites. These results indicated that the leaflets were easier to read than websites. But, both of them were not comprehensible to the majority of patients. CONCLUSION: All 10 patient information materials for hypertension were at higher readability level than high school level. As recommended levels of readability were lower than 2nd grade, educational materials need to be modified to meet the information needs for the people with low reading skills.

Readability of Patient Information on Hypertension in Korea

BACKGINFORMAROUND: Patient education is an important component of family practice. Pamphlets and the websites have been one of the most common resources for patient education. Patient information has been assessed using criteria with marks allocated for its content, design, readability. Up to present there have been studies on content, design but not readability. The WHO identifies readability as an essential tool for people to increase control over their health. Therefore, patient information should be assessed readability. The objective of our study was to assess patient information leaflets and the websites on hypertension to determine the readability of information currently available to patients. METHODS: Ten leaflets were reviewed, five form the internet and five from other sources. A total of ten subjects were assessed for readability using 'grading system of vocabulary' presented by the Academy of Korea Education in 2002. RESULTS: In five leaflets, about 41.3% vocabularies were comprised of 1st and 2nd grade. The portion of vocabularies in higher grade than 4th was 35%. In the five websites, 41.3% vocabularies in 1st and 2nd grade were used. The mean reading level (calculated with weight) was 2.057 for the five leaflets and 2.050 for the five websites. These results indicated that the leaflets were easier to read than websites. But, both of them were not comprehensible to the majority of patients. CONCLUSION: All 10 patient information materials for hypertension were at higher readability level than high school level. As recommended levels of readability were lower than 2nd grade, educational materials need to be modified to meet the information needs for the people with low reading skills.

Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats

The primary objective of this study was to compare thepharmacokinetics of a new anti-human immunodeficiencyvirus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethyl-benzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502)with its amino acid prodrug alanine amide of VP-0502(VP-0502AL), following intravenous and oral administrationsto rats. The plasma concentrations of both analytes wereanalyzed via high-performance liquid chromatographycoupled with photodiode-array detection (HPLC-DAD).When VP-0502 was intravenously administered at 20mg/kg, the analyte appeared in low levels with an AUC of 0.3microg.h/ml, and C0 of 0.2microg/ml in plasma. However, boththe prodrug VP-0502AL and its metabolite VP-0502 appearedat comparatively higher levels following intravenousinjection of VP-0502AL at the same dose. VP-0502AL'spharmacokinetic parameters were Vd: 4.6 l/kg; AUC:3microg.h/ml; t1/2: 0.5h; C0: 6microg/ml; CLtot: 7l/h/kg; andMRT: 0.6h. Following oral administration of VP-0502(100mg/kg), it was not detectable in plasma (<50ng/ml),while after the oral administration of VP-0502AL, VP-0502 was quantitatively detected as an active metabolite forthe first 7h, with a maximum plasma concentration(Cmax) of 0.8microg/ml, and an area under the concentration-time curve (AUC) of 2microg.h/ml. The oral pharmacokineticparameters of VP-0502AL were calculated to be: maximumconcentration time (tmax) 2.7h; Cmax 0.2microg/ml; eliminationhalf-life (t1/2): 0.8h; and AUC 0.5microg.h/ml. Overall thefindings indicate that VP-0502AL has a favorable pharmaco-kinetic profile as a prodrug with rapid transformationinto the active metabolite, and that the attachment of theamino acid alanine to VP-0502 is an effective approach toimprove its oral bioavailability. VP-0502AL is predictedto become a new highly bioavailable anti-AIDS drugcandidate and/or lead compound.

The Reliability and Validity of the Korean Translation of the Gambling Symptom Assessment Scale(KG-SAS) / 신경정신의학

OBJECTIVES: The purpose of this study was to test the reliability and validity of the Korean translation of Gambling Symptom Rating Scale (KG-SAS). METHODS: Using self-report sampling, we eventually included 231 subjects and analysed 70 subjects. These subjects were tested for KG-SAS and the Korean version of Barratt Impulsiveness Scale (BIS). RESULTS: In the reliability test, Cronbach's alpha coefficient was .913 which provided the evidence for the internal consistency. Content validity was assessed with factor analysis and two factors were extracted. Compared with the original scale, both scales embody the same theoretical conceptualization. To assess the validity of the KG-SAS, correlation coefficient was calculated between the KG-SAS and the Korean version of BIS. We got the result that there was a correlation between the KG-SAS and the Korean version of BIS (p<0.01). CONCLUSION: The results of the present study support that the KG-SAS is a reliable and valid scale for evaluating pathological gambling symptom assessment. Based on the results, this study suggests that KG-SAS would be a promising measurement to treat and study pathological gambling.

Cadaveric Study of Robotic Femoral Canal Preparation by Gauge Based Registration in Total Hip Arthroplasty / 대한정형외과연구학회지

PURPOSE: To propose a method providing an accurate femoral shaping for cementless total hip arthroplasty to maximize bone contact without femoral bone breakage and make secure correct position of the implant by eliminating the manual broach process MATERIALS AND METHODS: 5-cadaver specimens were tested with this system. A reamer-shaped registration gauge is inserted into the femoral canal. This gauge defines the position of the implant to be inserted. Then, the base frame is attached to the femur and the position of the gauge with respect to the base frame is measured. After removing the gauge, a mini robot is mounted on the frame and shapes the femoral canal. After the milling operation, model implant is inserted and its position and gap are measured. RESULTS: Anteversion angle error was 0.9degrees(S.D.1.7) and Varus/Valgus alignment error was 1.1degrees(S.D.1.5). 95%(S.D. 3.2) of contact surface had less than 0.3mm gap error. CONCLUSIONS: Proposed THA surgery system increased the accuracy of stem position and fitness compared with manual operation. Our mini robot THA surgery provides most of the benefits RobodocR does while operating procedure is much more simplified and economic.

Geriatrics Clinic in the primary care practice

No abstract available.

A multicenter trial on the effectiveness of transdermal nicotine patch in smoking cessation

No abstract available.