Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells

Chih-Ta Chen,Li-Zhu Liao,Ching-Hui Lu,Yung-Hsuan Huang,Yu-Kie Lin,Jung-Hsin Lin,Lu-Ping Chow 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Limited therapeutic options are available for advanced-stage hepatocellular carcinoma owing to its poor diagnosis. Drug resistance to sorafenib, the only available targeted agent, is commonly reported. The comprehensive elucidation of the mechanisms underlying sorafenib resistance may thus aid in the development of more efficacious therapeutic agents. To clarify the signaling changes contributing to resistance, we applied quantitative phosphoproteomics to analyze the differential phosphorylation changes between parental and sorafenib-resistant HuH-7 cells. Consequently, an average of ~1500 differential phosphoproteins were identified and quantified, among which 533 were significantly upregulated in resistant cells. Further bioinformatic integration via functional categorization annotation, pathway enrichment and interaction linkage analysis led to the discovery of alterations in pathways associated with cell adhesion and motility, cell survival and cell growth and the identification of a novel target, EphA2, in resistant HuH-7R cells. In vitro functional analysis indicated that the suppression of EphA2 function impairs cell proliferation and motility and, most importantly, overcomes sorafenib resistance. The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Binding analyses and in silico modeling revealed a ligand mimic lead compound, prazosin, that could abate the ligand-independent oncogenic activity of EphA2. Finally, data obtained from in vivo animal models verified that the simultaneous inhibition of EphA2 with sorafenib treatment can effectively overcome sorafenib resistance and extend the projected survival of resistant tumor-bearing mice. Thus our findings regarding the targeting of EphA2 may provide an effective approach for overcoming sorafenib resistance and may contribute to the management of advanced hepatocellular carcinoma.

Clinical Features and Computed Tomography Characteristics of Non-Klebsiella pneumoniae Liver Abscesses in Elderly (>65 Years) and Nonelderly Patients

Chih-Weim Hsiang,Wei-Chou Chang,Chang-Hsien Liu,Hsiu-Lung Fan,Kai-Hsiung Ko,Chih-Yung Yu,Hong-Hau Wang,Wen-I Liao,Hsian-He Hsu 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.2

Purpose: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. Materials and Methods: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and dividedinto two age groups: elderly (age ≥65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. Results: Elderly patients with non-KPLA were associatedwith a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were relatedto the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. Conclusion:In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.

The Impact of Health Promotion Activities on the Physiological, Psychological, and Social Functions of Inpatients With Chronic Mental Illness

Yu Li Lan,Lieh Yung Ping,Li Wen Su,Chien Chih Chen 대한신경정신의학회 2022 PSYCHIATRY INVESTIGATION Vol.19 No.3

Objective To explore the impact of the participation of patients with chronic mental illness in health promotion activities on their physical, psychological, and social functions.Methods This study included inpatient with chronic mental illness from a hospital in Eastern Taiwan. According to the experimental research design, the selected subjects were randomly divided into a health promotion group and a control group, with 60 people in each group. The health promotion team conducts health promotion activities twice a week, each for approximately 50 minutes, over the course of eight weeks (16 times in total). The measurement instrument adopts the Adult Mental Health Scale (AMHS) scale. Five experts and scholars in related fields are invited to conduct expert validity.Results Using independent sample t-tests to analyze the changes in the two groups after 8 weeks, the physical, psychological and social problems of the health promotion group were significantly improved compared with the control group.Conclusion Health promotion activities can alleviate the physical illness, anxiety, irritability, depression, and social distress of chronic hospitalized mental patients, and can also increase their positive and optimistic mood. It can provide chronic mental health care institutions to plan patients’ physical activities or exercises.

Using Multidetector-Row CT for the Diagnosis of Afferent Loop Syndrome Following Gastroenterostomy Reconstruction

Yu-Hsiu Juan,Wei-Chou Chang,Chih-Yung Yu,Hsian-He Hsu,Guo-Shu Huang,De-Chuan Chan,Chang-Hsien Liu,Ho-Jui Tung 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.4

Purpose: To assess the clinical manifestations and multidetector-row computed tomography (MDCT) findings of afferent loop syndrome (ALS) and to determine the role of MDCT on treatment decisions. Materials and Methods: From January 2004 to December 2008, 1,100 patients had undergone gastroenterostomy reconstruction in our institution. Of these, 22 (2%) patients were diagnosed as ALS after surgery that included Roux-en-Y gastroenterotomy (n=9), Billroth-II gastrojejunostomy (n=7), and Whipple’s operation (n=6). Clinical manifestations and MDCT features of these patients were recorded and statistically analyzed. The presumed etiologies of obstruction shown on the MDCT were correlated with clinical information and confirmed by surgery or endoscopic biopsy. Results: The most common clinical symptom was acute abdominal pain, presenting in 18 patients (82%). We found that a fluid-filled C-shaped afferent loop in combination with valvulae conniventes projecting into the lumen was the most common MDCT features of ALS. Malignant causes of ALS, such as local recurrence and carcinomatosis, are the most common etiologies of obstruction. These etiologies and associated complications can be predicted 100% by MDCT. Conclusion: Our results suggest that MDCT is a reliable modality for assessing the etiologies of ALS and guiding treatment decisions.

Scatternet Restructuring and Routing for Bluetooth Radio Systems

Chih-Yung Chang,Gwo-Jong Yu,Ching-Feng Lin,Tzu-Ting Wu 한국정보과학회 2002 한국정보과학회 학술발표논문집 Vol.2002 No.1

Alpinate Oxyphyllae Fructus Inhibits IGFII-Related Signaling Pathway to Attenuate Ang II-Induced Pathological Hypertrophy in H9c2 Cardiomyoblasts

Chuan-Te Tsai,Yung-Ming Chang,Shu-Luan Lin,Yueh-Sheng Chen,Yu-Lan Yeh,Viswanadha Vijaya Padma,Chin-Chuan Tsai,Ray-Jade Chen,Tsung-Jung Ho,Chih-Yang Huang 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.3

Angiotensin II (Ang II) is a very important cardiovascular disease inducer and may cause cardiac pathological hypertrophy and remodeling. We evaluated a Chinese traditional medicine, alpinate oxyphyllae fructus (AOF), for therapeutic efficacy for treating Ang II-induced cardiac hypertrophy. AOF has been used to treat patients with various symptoms accompanying hypertension and cerebrovascular disorders in Korea. We investigated its protective effect against Ang II-induced cytoskeletal change and hypertrophy in H9c2 cells. The results showed that treating cells with Ang II resulted in pathological hypertrophy, such as increased expression of transcription factors NFAT-3/p-NFAT-3, hypertrophic response genes (atrial natriuretic peptide [ANP] and b-type natriuretic peptide [BNP]), and Gαq down-stream effectors (PLCβ3 and calcineurin). Pretreatment with AOF (60–100 μg/mL) led to significantly reduced hypertrophy. We also found that AOF pretreatment significantly suppressed the cardiac remodeling proteins, metalloproteinase (MMP9 and MMP2), and plasminogen activator, induced by Ang II challenge. In conclusion, we provide evidence that AOF protects against Ang II-induced pathological hypertrophy by specifically inhibiting the insulin-like growth factor (IGF) II/IIR-related signaling pathway in H9c2 cells. AOF might be a candidate for cardiac hypertrophy and ventricular remodeling prevention in chronic cardiovascular diseases.

Perforated Sigmoid Colon Cancer within an Irreducible Inguinal Hernia: a Case Report

Kai-Hsiung Ko,Chih-Yung Yu,Chien-Chang Kao,Shih-Hung Tsai,Guo-Shu Huang,Wei-Chou Chang 대한영상의학회 2010 Korean Journal of Radiology Vol.11 No.2

A perforated sigmoid colon cancer within an inguinal hernia is extremely rare. This unexpected finding is usually discovered during surgery and causes an unavoidable septic evolution. Here, we describe the case of an 84-year-old man who presented with fever, abdominal distension, and a painful, enlarged, left scrotum. A CT showed a left, incarcerated, inguinal hernia containing a perforated sigmoid adenocarcinoma (which was confirmed by histopathology). The possibility of an irreducible inguinal hernia in association with perforated sigmoid colon cancer should be considered in the array of diagnoses. A pre-operative CT scan would be helpful in facilitating an accurate diagnosis.

Using Chlorophyll Fluorescence and Vegetation Indices to Predict the Timing of Nitrogen Demand in Pentas lanceolata

Chun-Wei Wu,Kuan-Hung Lin,Ming-Chih Lee,Yung-Liang Peng,Ting-Yi Chou,Yu-Sen Chang 한국원예학회 2015 원예과학기술지 Vol.33 No.6

The objective of this study was to predict the timing of nitrogen (N) demand through analyzing chlorophyll fluorescence (ChlF), soil-plant analysis development (SPAD), and normalized difference vegetation index (NDVI), which are positively correlated with foliar N concentration in star cluster (Pentas lanceolata). The plants were grown in potting soil under optimal conditions for 30 d, followed by weekly irrigation with five concentrations (0, 4, 8, 16, and 24 mM) of N for an additional 30 d. These five N application levels corresponded to leaf N concentrations of 2.62, 3.48, 4.00, 4.23, and 4.69%, respectively. We measured 13 morphological and physiological parameters, as well as the responses of these parameters to various N-fertilizer treatments. The general increases in Dickson’s quality index (DQI), above-ground dry weight (DW), total DW, flowering rate, △F/Fm’, and qP in response to t reatment with 0 to 8 mM N were similar to those of SPAD, NDVI, and Fv/Fm. Consistent and s trong correlations (R² = 0.60 to 0.85) were observed between leaf N concentration (%) and SPAD, NDVI, △F/Fm’, and above-ground DW. Validation of leaf S PAD, NDVI, and △F/Fm’ revealed that these vegetation indices are accurate predictors of leaf N concentration that can be used for non-destructive estimation of the proper timing for N-solution irrigation of P. lanceolata. Moreover, irrigation with 8 mM N-fertilizer i s recommended w hen leaf N concentration, SPAD, NVDI, and △F/Fm’ ratios are reduced from their saturation values of 4.00, 50.68, 0.64, and 0.137%, respectively.

Using Chlorophyll Fluorescence and Vegetation Indices to Predict the Timing of Nitrogen Demand in Pentas lanceolata

Wu, Chun-Wei,Lin, Kuan-Hung,Lee, Ming-Chih,Peng, Yung-Liang,Chou, Ting-Yi,Chang, Yu-Sen Korean Society of Horticultural Science 2015 원예과학기술지 Vol.33 No.6

The objective of this study was to predict the timing of nitrogen (N) demand through analyzing chlorophyll fluorescence (ChlF), soil-plant analysis development (SPAD), and normalized difference vegetation index (NDVI), which are positively correlated with foliar N concentration in star cluster (Pentas lanceolata). The plants were grown in potting soil under optimal conditions for 30 d, followed by weekly irrigation with five concentrations (0, 4, 8, 16, and 24 mM) of N for an additional 30 d. These five N application levels corresponded to leaf N concentrations of 2.62, 3.48, 4.00, 4.23, and 4.69%, respectively. We measured 13 morphological and physiological parameters, as well as the responses of these parameters to various N-fertilizer treatments. The general increases in Dickson's quality index (DQI), above-ground dry weight (DW), total DW, flowering rate, ${\Delta}F/Fm$', and qP in response to treatment with 0 to 8 mM N were similar to those of SPAD, NDVI, and Fv/Fm. Consistent and strong correlations ($R^2$= 0.60 to 0.85) were observed between leaf N concentration (%) and SPAD, NDVI, ${\Delta}F/Fm$', and above-ground DW. Validation of leaf S PAD, NDVI, and ${\Delta}F/Fm$' revealed that these vegetation indices are accurate predictors of leaf N concentration that can be used for non-destructive estimation of the proper timing for N-solution irrigation of P. lanceolata. Moreover, irrigation with 8 mM N-fertilizer i s recommended w hen leaf N concentration, SPAD, NVDI, and ${\Delta}F/Fm$' ratios are reduced from their saturation values of 4.00, 50.68, 0.64, and 0.137%, respectively.

Intra-Arterial Treatment in Patients with Acute Massive Gastrointestinal Bleeding after Endoscopic Failure: Comparisons between Positive versus Negative Contrast Extravasation Groups

Wei-Chou Chang,Chang-Hsien Liu,Hsian-He Hsu,Guo-Shu Huang,Ho-Jui Tung,Tsai-Yuan Hsieh,Shih-Hung Tsai,Chung-Bao Hsieh,Chih-Yung Yu 대한영상의학회 2011 Korean Journal of Radiology Vol.12 No.5

Objective: To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. Materials and Methods: From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Results: Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Conclusion: Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage. Objective: To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. Materials and Methods: From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Results: Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Conclusion: Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage.