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( Ming-lung Yu ),( Ming-lun Yeh ),( Chi-yi Chen ),( Pin-nan Cheng ),( Ming-jong Bair ),( Jyh-jou Chen ),( Ching-chu Lo ),( Chi-ming Tai ),( Ching-yang Tsai ),( Kuo-chih Tseng ),( Chien-hung Chen ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Insufficient data regarding the treatment strategy for partial response to nucleot(s)ide analogue (NUC) raised the aim of investigating tenofovir alafenamide (TAF) switching for chronic hepatitis B (CHB) patients with advanced fibrosis and partial response to other NUCs. Methods: CHB patients with advanced fibrosis (stage 3 or 4) and under NUC (except TAF) therapy with detectable hepatitis B virus (HBV) DNA for >52 weeks are enrolled to TAF 25 mg/day for 96 weeks. The objectives are viral suppression, alanine aminotransferase (ALT) normalization and safety. Results: From Feb. 2019, 34 patients, including 21 (61.8%) with entecavir, 10 (29.4%) TDF and 3 (8.8%) lamivudine or adefovir, were enrolled (15 [44.1%] male, median 53 years). The fibroscan demonstrated a mean of 10.5 kPa (7 [20.6%] cirrhotic). Sixteen (47.1%) patients were HBV e antigen positive, seven (20.6%) had YMDD mutation. The median HBV DNA level declined from 68.5 IU/mL at enrollment to 27.0 IU/mL at 4<sup>th</sup> week, and undetectable at 12<sup>th</sup>, 24<sup>th</sup>, 36<sup>th</sup> week, respectively, after TAF switching, with undetectable HBV DNA in 14/34 (41.2%), 17/33 (51.5%), 15/25 (60.0%), and 9/15 (60.0%) patients and rate of ALT normalization (≤40 U/L) of 85.3%, 85.3%, 84.8%, 92.0%, and 80.0%, respectively, after TAF switching. (figure 1) Two patients experienced transient virological breakthrough and another one developed at the final time follow up. Serum creatinine and eGFR levels were stable after TAF switching (figure 1). Two patients early terminated including one at 12<sup>th</sup> week due to personal reason, and another one accidently died at 20<sup>th</sup> week due to acute heart attack. Others suffered only mild degrees of adverse events which were considered unrelated to treatment. Conclusions: The preliminary results demonstrated the TAF switching is effective and safe in viral suppression for CHB patients with advanced fibrosis and partial virologic responses to other NUCs.
Chien-Liang Liu,Ming-Jen Chen,Jiunn-Chang Lin,Chi-Hsin Lin,Wen-Chien Huang,Shih-Ping Cheng,Shan-Na Chen,Yuan-Ching Chang 한국유방암학회 2019 Journal of breast cancer Vol.22 No.2
Purpose: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. Methods: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. Results: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. Conclusion: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.
( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
( Ching Chi Lee ),( Ming Yuan Hong ),( Wen Chien Ko ) 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: Bacteremia, a indicative of a severe bacterial infection, has been associated with varied mortality rate, up to 37% in cirrhotic patients. This study was to investigate the clinical characteristics of community-onset bacteremia in cirrhotic adults and the clinical impact of appropriate empirical antibiotics on their outcome. Methods: Cirrhotic adults with community-onset bacteremia visiting the ED from January 2005 to December 2009 were identifi ed retrospectively. Demographic characteristics, severity, pathogens, port of entry, antibiotic therapy and clinical outcome were collected form the chart record. The susceptibility were determined by the broth microdilution method. Results: Of a total 246 episodes in cirrhotic patients, the mean age was 62.7 years, and 167 patients (67.9%) were male. The major resource of bacteremia included intra-abdominal infections (112 patients, 45.5%), primary bacteremia (43, 17.5%), urinary tract infection (39, 15.9%) and soft-tissue infection (22, 8.9%).Of a total 258 bacteremia-causing microorganisms, Enterobactericaeae and Gram-negative isolates account for 72.1% (186 isolates) and 76% (196), respectively; Escherichia coli (82 isolate, 31.8%) and Klebsiella species (61, 23.6%) were the most frequently encountered microorganisms. The in vitro susceptibility rate of each drug for Gram-negative and total isolates were demonstrated in Table 1. In multivariate analyses, the following variables were associated independently with 28-day mortality: the length of delayed appropriateness >72 hours (odds ratio [OR], 4.29; P=0.003); high serum creatinine (>1.5 mg/dL; OR, 3.12 ; P=0.005) in the ED; severe sepsis (OR, 3.61; P=0.01); high Piitt score(= 4; OR, 2.66 ; P=0.04); pneumonia (OR, 5.44; P=0.02); and diabetes (OR, 3.54; P=0.004). Conclusions: For cirrhotic adults with community-onset bacteremia in the ED, the clinical characteristics of bacteremia was demonstrated. In practice, their outcomes were superior following treatment with appropriate antibiotics compared to treatment with inappropriate antibiotics empirical.
( Ching-chih Lin ),( Ta-wei Liu ),( Ming-lun Yeh ),( Yi-shan Tsai ),( Pei-chien Tsai ),( Chung-feng Huang ),( Jee-fu Huang ),( Wan-long Chuang ),( Chia-yen Dai ),( Ming-lung Yu ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2
Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II-IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC. (Clin Mol Hepatol 2021;27:313-328)
Predictors of Positive Bone Metastasis in Newly Diagnosed Prostate Cancer Patients
Chien, Tsu-Ming,Lu, Yen-Man,Geng, Jiun-Hung,Huang, Tsung-Yi,Ke, Hung-Lung,Huang, Chun-Nung,Li, Ching-Chia,Chou, Yii-Her,Wu, Wen-Jeng,Huang, Shu-Pin Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3
Background: The prevalence of prostate cancer (PCa) has been increasing in recent years. Treatment strategies are largely based on the results of bone scan screening. Therefore, our aim was to investigate predictors of positive bone metastasis in newly diagnosed PCa patients. Materials and Methods: After extensive review, 336 consecutive patients newly diagnosed with PCa between April 2010 and November 2013 at our institution were enlisted in the study. Patients were divided into two groups according to bone scan results. Univariate analyses (Chi-square test for discrete variables and independent t-test for continuous variables) were applied to determine the potentially significant risk factors associated with distant bone metastasis. Binary logistic regression analyses were used to further investigate the influence of these factors on bone metastasis. Results: The patient mean age was $71.9{\pm}8.6years$ (range: 48 to 94 years). The mean prostate specific antigen (PSA) level and biopsy Gleason score were $260.2{\pm}1107.8ng/mL$ and $7.4{\pm}1.5$, respectively. The body mass index (BMI) for the series was $24.5{\pm}3.4kg/m^2$. Sixty-four patients (19.0%) had a positive bone scan result. Patients with positive bone scan results had a significantly lower BMI ($23.3{\pm}3.5$ vs. $24.8{\pm}3.3$; p=0.003), a higher Gleason score ($8.5{\pm}1.1$ vs. $7.1{\pm}1.5$; p < 0.001), and a higher PSA level ($1071.3{\pm}2337.1$ vs. $69.4{\pm}235.5$; p < 0.001) than those without bone metastasis. Multivariate logistic regression analysis employing the above independent predictors demonstrated that a Gleason score of ${\geq}7$, clinical stage ${\geq}T3$, $BMI{\leq}22kg/m^2$, and an initial PSA level of ${\geq}20ng/mL$ were all independent predictors of bone metastasis. Conclusions: A bone scan might be necessary in newly diagnosed PCa patients with any of the following criteria: clinical stage T3 or higher, a Gleason score of 7 or higher, BMI equal to or less than 22, and a PSA level of 20 or higher.
( Ching Fu Huang ),( Wei Ming Wang ),( Chien Ping Chiang ) 대한피부과학회 2011 Annals of Dermatology Vol.23 No.3s
Juvenile systemic lupus erythematosus (JSLE) is an autoimmune- mediated multiorgan disease. The cutaneous manifestation is one of the most common initial presentations in JSLE. A typical lesion is a facial malar rash, but a patient may sometimes present with nonclassical lesions. Herein, we report two cases of JSLE with similar persistent scaly ear rashes as the heralding cutaneous symptom preceding systemic symptoms. Identifying this atypical and underestimated cutaneous rash in juvenile patients might help the clinician make the correct diagnosis and provide earlier intervention, which may help prevent disease progression. (Ann Dermatol 23(S3) S333~S337, 2011)
Scaly Ear Rash as the Herald of a Young Girl with Juvenile Systemic Lupus Erythematosus
Ching-Fu Huang,Wei-Ming Wang,Chien-Ping Chiang 대한피부과학회 2011 Annals of Dermatology Vol.23 No.-
Juvenile systemic lupus erythematosus (JSLE) is an autoimmune-mediated multiorgan disease. The cutaneous manifestation is one of the most common initial presentations in JSLE. A typical lesion is a facial malar rash, but a patient may sometimes present with nonclassical lesions. Herein, we report two cases of JSLE with similar persistent scaly ear rashes as the heralding cutaneous symptom preceding systemic symptoms. Identifying this atypical and underestimated cutaneous rash in juvenile patients might help the clinician make the correct diagnosis and provide earlier intervention, which may help prevent disease progression. (Ann Dermatol 23(S3) S333∼S337, 2011)
Real-World Effectiveness and Safety of SOF/LDV for Pa-tients with Chronic Hepatitis C in Taiwan
( Ching-chu Lo ),( Pin-nan Cheng ),( Chi-yi Chen ),( Chung-feng Huang ),( Hsing-tao Kuo ),( Kuo-chih Tseng ),( Yi-hsiang Huang ),( Chi-ming Tai ),( Cheng-yuan Peng ),( Ming-jong Bair ),( Chien-hung Ch 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1