• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.255-260
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• 2012

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

• Tuberculosis and Respiratory Diseases
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• v.74 no.3
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• pp.129-133
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• 2013

The presence of epidermal growth factor receptor (EGFR ) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2879-2883
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• 2013

Objective: To investigate differences in mutations of epidermal growth factor receptor (EGFR) gene and relationships with clinicopathological features in patients with non-small cell lung cancer (NSCLC) between Uygur and Han ethnic groups. Methods: The Scorpions amplification refractory mutation system (Scorpions ARMS) was used to measure mutations in exons 18, 19, 20 and 21 of the EGFR gene in paraffin-embedded tumor tissue from NSCLC cases, and statistical analysis was performed to investigate links with clinicopathological features in different histological types of NSCLC. Results: Results from ARMS testing showed EGFR mutations in tumor tissues from six (6) of 50 NSCLC patients of Uygur ethnic group, with a positive rate of 12.0%; four of them (4) had exon 19 deletion in EGFR, and two (2) had L858R point mutation in exon 21 of EGFR. Statistically significant difference was noted in EGFR genetic mutation between adenocarcinoma and non-adenocarcinoma (P < 0.05), but no differences with gender, age group, smoking status, or stage (P > 0.05). EGFR mutations were detected in tumor tissues from 27 of 49 NSCLC patients of Han ethnic group, with a positive rate of 55.1%; 19 of them had exon 19 deletions, seven (7) had L858R point mutations in exon 21 of EGFR and one (1) had mutations in both exon 18 G719X and exon 20 T790M of EGFR. Statistically significant differences were noted in EGFR genetic mutations between genders and between adenocarcinoma and non-adenocarcinoma (P<0.05), but not with age group, smoking status, or stage (P > 0.05). Conclusion: Statistically significant differences were noted in the positive rates of EGFR genetic mutations in NSCLC patients between Uygur and Han ethnic groups, with lower positive rates for the Uygur cases.

• International Journal of Oncology
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• v.55 no.1
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• pp.320-330
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• 2019

The aim of this study was to investigate the underlying mechanisms responsible for the anticancer effects of lupeol on human non-small cell lung cancer (NSCLC). MTT assay and Trypan blue exclusion assay were used to evaluate the cell viability. DAPI staining and flow cytometric analysis were used to detect apoptosis. Molecular docking and western blot analysis were performed to determine the target of lupeol. We found that lupeol suppressed the proliferation and colony formation of NSCLC cells in a dose-dependent manner. In addition, lupeol increased chromatin condensation, poly(ADP-ribose) polymerase (PARP) cleavage, sub-G1 cell populations, and the proportion of Annexin V-positive cells, indicating that lupeol triggered the apoptosis of NSCLC cells. Notably, lupeol inhibited the phosphorylation of epithelial growth factor receptor (EGFR). A docking experiment revealed that lupeol directly bound to the tyrosine kinase domain of EGFR. We observed that the signal transducer and activator of transcription 3 (STAT3), a downstream molecule of EGFR, was also dephosphorylated by lupeol. Lupeol suppressed the nuclear translocation and transcriptional activity of STAT3 and downregulated the expression of STAT3 target genes. The constitutive activation of STAT3 by STAT3 Y705D overexpression suppressed lupeol-induced apoptosis, demonstrating that the inhibition of STAT3 activity contributed to the induction of apoptosis. The anticancer effects of lupeol were consistently observed in EGFR tyrosine kinase inhibitor (TKI)-resistant H1975 cells (EGFR L858R/T790M). Taken together, the findings of this study suggest that lupeol may be used, not only for EGFR TKI-naïve NSCLC, but also for advanced NSCLC with acquired resistance to EGFR TKIs.

• Journal of The Korean Society of Integrative Medicine
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• v.12 no.3
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• pp.189-199
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• 2024

Purpose : This study aimed to investigate the test-retest reliability, minimal detectable change (MDC), and the effect of turning direction on the time and number of steps taken during the 180 ° turn test in subacute stroke patients. Additionally, it examined the concurrent validity of the 180 ° turn test. Methods : The study included 28 subacute stroke patients. The test-retest reliability of the 180 ° turn test according to the direction of rotation (paretic and non-paretic sides) by comparing the consistency between the initial assessment and a reassessment conducted 7 days later. Concurrent validity was examined by assessing the correlation of the 180 ° turn test with the Fugl-Meyer assessment of lower extremity (FMA-L/E), Berg balance scale (BBS), 10-meter walk test (10 mWT), and timed up and go test (TUG). Results : The ICC for the time taken to turn 180 ° to the affected and unaffected sides were 0.971 and 0.918, respectively, indicating excellent reliability. The ICC for the number of steps were 0.944 and 0.932, respectively. The MDC for the time taken were 0.33 seconds (affected side) and 0.67 seconds (unaffected side). The MDC for the number of steps were 0.49 (affected side) and 0.63 (unaffected side). The paired t-test showed the limited community ambulator group took significantly longer to turn to the unaffected side (p<.048). Significant correlations were found between the 180 ° turn test and FMA-L/E (r= -0.395 to -0.416), BBS (r= -0.622 to -0.684), 10 mWT (r= 0.720 to 0.730), and TUG (r= 0.684 to 0.790) (p<.05 to .01). Conclusion : The 180 ° turn test demonstrated excellent test-retest reliability and high validity when correlated with other functional measures in subacute stroke patients. MDC values indicated high reliability. Faster walking speeds (≥0.95 m/s) were unaffected by turning direction, while slower speeds (<0.58 m/s) showed significant effects. The 180 ° turn test is a simple, sensitive, and reliable tool for evaluating turning ability in subacute stroke patients.

• Journal of The Korean Society of Grassland and Forage Science
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• v.36 no.4
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• pp.387-392
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• 2016

This study was conducted to ameliorate the productive performance of Hanwoo cow using hill pasture grazing system. Twenty seven animals aged 9 were designed to divide with 3 groups which were Control (restricted concentrate and hay for 5 months), T1 (restricted concentrate and pasture grazing ad libitum for 5 months) and T2 (restricted concentrate, 30 g/head of mineral nutrients and pasture grazing ad libitum for 5 months). Average daily gains increased higher in the order of T2, Control and T1. The conception rate of Control, T1 and T2 after artificial insemination during post-grazing period were 88.9%, 100%, 100%, respectively. In conclusion, the results indicated that hill pasture grazing system might enhance not only the productive performance of Hanwoo cow but also profit for conventional feeding system.

• Journal of the Korean Society of Marine Environment & Safety
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• v.19 no.5
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• pp.467-475
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• 2013

In order to seize quantitative materials as part of studies on measures for oil pollution prevention and control, the statistics of oil pollution incidents in Korean coastal waters for 10 years from 2003 to 2012 were analyzed with relation to the number of oil spills and the volume of oil spilt according to causes, sources and sea areas of spills. Total number and total volume of oil spills for 10 years were found to be 2,833 cases and 17,877 kL, respectively. 50.4 %(1,429 cases) of total number of oil spills were caused by negligence, although oil spillage due to negligence was 294 kL(1.7 %). While oil spillage caused by marine accidents was 17,400 kL(97.3 %), marine accidents accounted for 27.9 %(790 cases) of total number of oil spills. While negligence had a great influence on the number of oil spills, marine accidents had a huge impact on the amount of oil spilt. Fishing boats accounted for 42.7 %(1,210 cases) of the number of oil spills, and although oil tankers accounted for 9.2 %(261 cases) of the number of oil spills, oil spillage from oil tankers was 15,488kL(86.7 %). It means that oil tankers such as VLCC or ULCC may be the main sources of major oil spills and a few very large spills are responsible for a high percentage of the amount of oil spilt. While the number of oil spill incidents was closely related to the accidents of fishing boats, the volume of oil spilt was greatly affected by the major oil spill incidents of oil tankers such as M/T Hebei Spirit. The number and volume of oil spills were shown to be 1,613 cases(56.9 %) and 3,804 kL(21.3 %) in South Sea, 700 cases(24.7 %) and 13,501 kL(75.5 %) in West Sea, and 520 cases(18.2 %) and 572 kL(3.2 %) in East Sea of Korea, respectively. The highest number of oil spills was found in South Sea and the most volume of oil spilt was shown in West Sea of Korea for 10 years.