Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Anti-Melanogenic Effect from Submerged Mycelial Cultures of Ganoderma weberianum

( Ying-jang Lai ),( Kai-di Hsu ),( Tzu-jung Huang ),( Chang-wei Hsieh ),( Yu-hin Chan ),( Kuan-chen Cheng ) 한국균학회 2019 Mycobiology Vol.47 No.1

Compounds from Lingzhi has been demonstrated the ability for inhibiting tyrosinase (a key enzyme in melanogenesis) activity. In this study, we investigated the anti-melanogenic activity from the submerged mycelial culture of Ganoderma weberianum and elucidated the skin lightening mechanism by B16-F10 murine melanoma cells. From the cellular context, several fractionated mycelium samples exhibited anti-melanogenic activity by reducing more than 40% extracellular melanin content of B16-F10 melanoma cells. In particular, the fractionated chloroform extract (CF-F3) inhibited both secreted and intracellular melanin with the lowest dosage (25ppm). Further analysis demonstrated that CF-F3 inhibited cellular tyrosinase activity without altering its protein expression. Taken together, our study has demonstrated that the chemical extracts from submerged mycelial culture of G. weberianum have the potential to serve as an alternative anti-melanogenic agent.

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.

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 Antiproliferation Activity of Ganoderma formosanum Extracts on Prostate Cancer Cells

( Cheng-yen Chiang ),( Kai-di Hsu ),( Yen-yi Lin ),( Chang-wei Hsieh ),( Jui-ming Liu ),( Tze-ying Lu ),( Kuan-chen Cheng ) 한국균학회 2020 Mycobiology Vol.48 No.3

Androgen-independent prostate cancer accounts for mortality in the world. In this study, various extracts of a medical fungus dubbed Ganoderma formosanum were screened for inhibition of DU145 cells, an androgen-independent prostate cancer cell line. Results demonstrated that both hexane (GF-EH) and butanol (GF-EB) fraction of G. formosanum ethanol extract inhibited DU145 cell viability in a dose-dependent manner. GF-EH induced cell-cycle arrest in G1 phase of DU145 cells via downregulation of cyclin E2 protein expression. In addition, GF-EB triggered extrinsic apoptosis of DU145 cells by activating caspase 3 gene expression resulting in programed cell death. Above all, both GF-EH and GF-EB show lower toxicity to normal human fibroblast cell line compared to DU145 cell, implying that they possess specific drug action on cancer cells. This study provides a molecular basis of G. formosanum extract as a potential ingredient for treatment of androgen-independent prostate cancer.

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.

해저지진계 운영을 통한 영덕 앞바다 미소지진 분석

한민희(Minhui Han),김광희(Kwang-Hee Kim),박순천(Sun-Cheon Park),Pei-ying Lin,Po-Chi Chen,Hsu-Kuang Chang,Jia-pu Jang,Ban-Yuan Kuo 대한지질학회 2016 대한지질학회 학술대회 Vol.2016 No.10

Negative effects on medical students’ scores for clinical performance during the COVID-19 pandemic in Taiwan: a comparative study

Eunice Jia-Shiow Yuan,Shiau-Shian Huang,Chia-An Hsu,Jiing-Feng Lirng,Tzu-Hao Li,Chia-Chang Huang,Ying-Ying Yang,Chung-Pin Li,Chen-Huan Chen 한국보건의료인국가시험원 2023 보건의료교육평가 Vol.20 No.-

Purpose Coronavirus disease 2019 (COVID-19) has heavily impacted medical clinical education in Taiwan. Medical curricula have been altered to minimize exposure and limit transmission. This study investigated the effect of COVID-19 on Taiwanese medical students’ clinical performance using online standardized evaluation systems and explored the factors influencing medical education during the pandemic. Methods Medical students were scored from 0 to 100 based on their clinical performance from 1/1/2018 to 6/31/2021. The students were placed into pre-COVID-19 (before 2/1/2020) and midst-COVID-19 (on and after 2/1/2020) groups. Each group was further categorized into COVID-19-affected specialties (pulmonary, infectious, and emergency medicine) and other specialties. Generalized estimating equations (GEEs) were used to compare and examine the effects of relevant variables on student performance. Results In total, 16,944 clinical scores were obtained for COVID-19-affected specialties and other specialties. For the COVID-19-affected specialties, the midst-COVID-19 score (88.51–3.52) was significantly lower than the pre-COVID-19 score (90.14–3.55) (P<0.0001). For the other specialties, the midst-COVID-19 score (88.32–3.68) was also significantly lower than the pre-COVID-19 score (90.06–3.58) (P<0.0001). There were 1,322 students (837 males and 485 females). Male students had significantly lower scores than female students (89.33–3.68 vs. 89.99–3.66, P=0.0017). GEE analysis revealed that the COVID-19 pandemic (unstandardized beta coefficient=-1.99, standard error [SE]=0.13, P<0.0001), COVID-19-affected specialties (B=0.26, SE=0.11, P=0.0184), female students (B=1.10, SE=0.20, P<0.0001), and female attending physicians (B=-0.19, SE=0.08, P=0.0145) were independently associated with students’ scores. Conclusion COVID-19 negatively impacted medical students' clinical performance, regardless of their specialty. Female students outperformed male students, irrespective of the pandemic.

Core prescription pattern of Chinese herbal medicine for depressive disorders in Taiwan: a nationwide population-based study

Diem Ngoc Hong Tran,I-Hsuan Hwang,Fun-Jou Chen,Yuan-Pu Tseng,Ching-Mao Chang,Shih-Jen Tsai,Jen-Lin Yang,Ta-Peng Wu,Chung-Hua Hsu,Fang-Pey Chen,Yen-Ying Kung 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.3

Background: Depressive disorders (DD) affect not only mood and behavior but also various physical functions. Traditional Chinese medicine (TCM) has been shown to have some benefits in treating DD. However, one formula or one single herb might be not show high efficacy when used to treat depression. Thus, this study aimed to examine the core prescription pattern of Chinese herbal medicine (CHM) among patients with DD in Taiwan as a reference for related research and clinical applications. Methods: All patients, who had been diagnosed with major depressive disorder or minor depression or dysthymia without any other baseline diseases and had at least one CHM outpatient clinical visit from 2002 to 2011, were extracted from three randomly sampled cohorts, namely the 2000, 2005 and 2010 cohorts of the National Health Insurance Research Database (NHIRD) of Taiwan. The collected data was analyzed to explore the patterns of herbal products. Results: There were 197,146 patients with a diagnosis of DD and of these 1806 subjects had only a diagnosis of DD and utilized CHM. The most common formula was Gan-Mai-Da-Zao-Tang (12.19%), while Suan-Zao-Ren (3.99%) was the most commonly prescribed single herb. The core pattern of prescriptions consisted of a combination of Gan-Mai-Da-Zao-Tang, Jia-Wei-Xiao-Yao-San, Chai-Hu-Jia-Long-Gu-Mu-Li-Tang, He-Huan-Pi, Yuan-Zhi and Shi-Chang-Pu. Conclusions: This study describes the CHM core prescription pattern used to treat patients in Taiwan with DD and it is a potential candidate for study in future pharmacological or clinical trials targeting DD.

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.