The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

The Applications of Smart Wearable Devices for Detecting Balance Function in Individuals at High Risk of Falls

Tsung-Hsun Hsieh,Chih-Wei Peng,Kai-Yun Chen,Ying-Zu Huang,Yi-Huang Lin,Wei-Zong Zhong,Chun-Yu Cheng,Ya-Ju Chang,Chih-Hsiu Cheng,Yu-Fen Chuang 한국재활복지공학회 2017 한국재활복지공학회 학술대회논문집 Vol.2017 No.11

The most ideal interval between blastocyst biopsy and vitrification applied in preimplantation genetic screening (PGS)

( Hui-ying Low ),( Hsiu-hui Chen ),( Chun-chia Huang ),( Tsung-hsien Lee ),( Chung-i Chen ),( Lii-sheng Huang ),( Maw-sheng Lee ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

Study Question: To evaluate the most ideal interval between blastocyst biopsy and vitrification in preimplantation genetic screening (PGS). Study Design, Size, Duration: This is a retrospective study and total 224 patients underwent the PGS from 2012 Dec. to 2015 Mar. All of patients underwent blastocyst vitrification after biopsy and 1~2 euploid blastocyst for transfer after warming. The primary outcome measures were the implantation and pregnancy rates per PGS-frozen embryo transfer cycle. Materials, Setting, Methods: The blastocyst grading including grade 4, 5 and 6 (according to Gardner grading system) on day 5 or day 6 were selected for trophectoderm biopsy. All blastocyst underwent vitrification immediately (interval: 0.5 hour) or 1 to 7 hours after biopsy. At the time of vitrification the grade of blastocyst expansion was also recorded. All patients were divided into two groups according to the grade of expanded (Group1: ≤1/2 expansion (n=41), Group2: ≥3/4 expansion (n=183)). Furthermore, combined two factors including the interval and morphology of blastocyst after biopsy, all patients were further divided into interval 1 (<3 hours and ≤1/2 expansion) and interval 2 (≥3 hours and ≥3/4 expansion). The morphologically best euploid blastocyst(s) (1~2 embryos) was/were selected first for transfer on the next cycle. Main Results: Assessment morphology of blastocyst after biopsy in different interval, at 0.5 hour after biopsy, 100% blastocyst was non-expansion; at 1 hour after biopsy, only 17% blastocyst was 3/4 expansion or all-expansion; at 3 hours after biopsy, 86% blastocyst was 3/4 expansion or all-expansion and after 5.5 hours, 100% blastocyst was all-expansion or hatching. All blastocysts were survival (100%, 359/359) after warming. The mean of embryo transfer number between all groups were no significantly difference. The implantation rate in Group2 (63.4%) was significantly higher than that in Group1 (46.9%, p=0.014). The pregnancy rates in Group4 (73.8%) was sig-nificantly higher than that in Group1 (51.2%, p=0.004). The implantation and pregnancy rates in the group of embryo ≥3/4 expansion combined with ≥3 hours after biopsy (63.6%, 178/280; 73.8%, 127/172) were significantly higher than that in the group of ≤1/2 expansion with <3 hour (45.6, 26/57; 50.0%, 18/36; p=0.0113 and p=0.0056, respectively). Conclusion: The most ideal interval between biopsy and vitrification was least 3 hours and ≥3/4 expansion of blastocyst after biopsy could improve the implantation and pregnancy rates for PGS.

Rock Slope Deformation at Collapse Influenced by Weak Plane Orientation

( Kuang-tsung Chang ),( Ying-chen Lee ) 대한지질공학회 2024 대한지질공학회 학술발표회논문집 Vol.2024 No.1

Improved high-k stacks with chemical oxide interfacial layer by DPN/ PNA treatment

Shuguang Li,Ying-Tsung Chen,Shoou-Jinn Chang 한국물리학회 2015 Current Applied Physics Vol.15 No.3

A decoupled plasma nitridation (DPN) with post nitridation annealing (PNA) treatment method was introduced to improve the performances of MOS devices with high-k (HK)-last/gate-last integration scheme and chemical oxide interface layer (IL). By introducing N to form HfSiON, it was found that DPN + PNA treatments could provide smaller equivalent oxide thickness (EOT) for both nMOS and pMOS devices. It was also found that we could achieve the best overall device performance for the HK-last/gatelast integration scheme with a chemical oxide IL by introducing nitrogen gas with low percentage content during DPN followed by high temperature PNA.

Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment

Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kuo-Hsuan Hsu,Yen-Hsiang Huang,Kang-Yi Su,Sung-Liang Yu,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. Materials and Methods Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription. Results A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease control rate were 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patients who received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome. Conclusion Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

Melatonin acts synergistically with pazopanib against renal cell carcinoma cells through p38 mitogen-activated protein kinase-mediated mitochondrial and autophagic apoptosis

( Chien-pin Lai ),( Yong-syuan Chen ),( Tsung-ho Ying ),( Cheng-yen Kao ),( Hui-ling Chiou ),( Shao-hsuan Kao ),( Yi-hsien Hsieh ) 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.4

Background: Mounting evidence indicates that melatonin has possible activity against different tumors. Pazopanib is an anticancer drug used to treat renal cell carcinoma (RCC). This study tested the anticancer activity of melatonin combined with pazopanib on RCC cells and explored the underlying mechanistic pathways of its action. Methods: The 786-O and A-498 human RCC cell lines were used as cell models. Cell viability and tumorigenesis were detected with the MTT and colony formation assays, respectively. Apoptosis and autophagy were assessed using TUNEL, annexin V/propidium iodide, and acridine orange staining with flow cytometry. The expression of cellular signaling proteins was investigated with western blotting. The in vivo growth of tumors derived from RCC cells was evaluated using a xenograft mouse model. Results: Together, melatonin and pazopanib reduced cell viability and colony formation and promoted the apoptosis of RCC cells. Furthermore, the combination of melatonin and pazopanib triggered more mitochondrial, caspase-mediated, and LC3-II-mediated autophagic apoptosis than melatonin or pazopanib alone. The combination also induced higher activation of the p38 mitogen-activated protein kinase (p38MAPK) in the promotion of autophagy and apoptosis by RCC cells than melatonin or pazopanib alone. Finally, tumor xenograft experiments confirmed that melatonin and pazopanib cooperatively inhibited RCC growth in vivo and predicted a possible interaction between melatonin/pazopanib and LC3-II. Conclusion: The combination of melatonin and pazopanib inhibits the growth of RCC cells by inducing p38MAPK-mediated mitochondrial and autophagic apoptosis. Therefore, melatonin might be a potential adjuvant that could act synergistically with pazopanib for RCC treatment.

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Chun-Shih Chin,Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kang-Yi Su,Sung-Liang Yu,Jeremy J.W. Chen,Gee-Chen Chang 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

Purpose The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients. PurposeThe aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.