1.Induction of apoptosis in human Hep3B hepatoma cells by norcantharidin through a p53 independent pathway via TRAIL/DR5 signal transduction.
Chung-Hsin YEH ; Yu-Yen YANG ; Ya-Fang HUANG ; Kuan-Chih CHOW ; Ming-Feng CHEN
Chinese journal of integrative medicine 2012;18(9):676-682
OBJECTIVETo investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.
METHODSThe survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.
RESULTSNCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.
CONCLUSIONNCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.
Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Caspase 10 ; metabolism ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Humans ; Immunohistochemistry ; Liver Neoplasms ; enzymology ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Signal Transduction ; drug effects ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tumor Suppressor Protein p53 ; metabolism
2.Hyaluronan Induces a Mitochondrial Functional Switch in Fast-Proliferating Human Mesenchymal Stem Cells
Mairim Alexandra SOLIS ; Yau-Huei WEI ; Chiung-Hsin CHANG ; Chen-Hsiang YU ; Lynn L.H. HUANG
International Journal of Stem Cells 2020;13(1):151-162
Background and Objectives:
Hyaluronan preserves the proliferation and differentiation potential of mesenchymal stem cells. Supplementation of low-concentration hyaluronan (SHA) in stem cells culture medium increases its proliferative rate, whereas coated-surface hyaluronan (CHA) maintains cells in a slow-proliferating mode. We have previously demonstrated that in CHA, the metabolic proliferative state of stem cells was influenced by upregulating mitochondrial biogenesis and function. However, the effect of SHA on stem cells’ energetic status remains unknown. In this study, we demonstrate the effect that low-concentration SHA at 0.001 mg/ml (SHA0.001) and high-concentration SHA at 5 mg/ml (SHA5) exert on stem cells’ mitochondrial function compared with CHA and noncoated tissue culture surface (control).
Methods:
and Results: Fast-proliferating human placenta-derived mesenchymal stem cells (PDMSCs) cultured on SHA0.001 exhibited reduced mitochondrial mass, lower mitochondrial DNA copy number, and lower oxygen consumption rate compared with slow-proliferating PDMSCs cultured on CHA at 5.0 (CHA5) or 30 μg/cm2 (CHA30). The reduced mitochondrial biogenesis observed in SHA0.001 was accompanied by a 2-fold increased ATP content and lactate production, suggesting that hyaluronan-induced fast-proliferating PDMSCs may rely less on mitochondrial function as an energy source and induce a mitochondrial functional switch to glycolysis.
Conclusions
PDMSCs cultured on both CHA and SHA exhibited a reduction in reactive oxygen species levels. The results from this study clarify our understandings on the effect of hyaluronan on stem cells and provide important insights into the effect of distinct supplementation methods used during cell therapies.
3.The reliability of ultrasonographic measurements for testicular volume assessment: comparison of three common formulas with true testicular volume.
Ming-Li HSIEH ; Shih-Tsung HUANG ; Hsin-Chieh HUANG ; Yu CHEN ; Yu-Chao HSU
Asian Journal of Andrology 2009;11(2):261-265
The aim of this study was to determine the correlation of ultrasonographic estimates of testicular volume with true testicular volume and to compare the accuracy and precision of the three most commonly utilized formulas. A total of 15 patients underwent high-resolution ultrasonography (US) analysis for testicular volume before orchiectomy. Testicular volume was calculated using three common formulas: (1) length (L) x width (W) x height (H) x 0.52; (2) the empirical formula of Lambert: L x W x H x 0.71; and (3) L x W2 x 0.52. The actual volume of each removed testis was estimated directly by a water displacement method. Thus, four volume measurements were obtained for each of the 30 testes. The obtained data were analyzed by paired t-test and linear regression analysis. All three US formula measurements significantly underestimated the true testicular volume. The largest mean biases were observed with US formula 1, which underestimated the true volume by 3.3 mL (31%). US formula 2 had a smaller mean difference from the true volume, with an underestimation of only 0.6 mL (6%). Regression analysis showed that formulas 1 and 2 had better R2 values than formula 3. However, all three US formulas displayed a strong linear relationship with the true volume (R2= 0.872-0.977; P < 0.001). Among the commonly used US formulas, the empirical formula of Lambert (L x W x H x 0.71) provided better accuracy than the other two formulas evaluated, and better precision than formula 3. Therefore, the formula of Lambert is the optimal choice in clinical practice.
Aged
;
Aged, 80 and over
;
Humans
;
Male
;
Middle Aged
;
Organ Size
;
Reproducibility of Results
;
Testis
;
anatomy & histology
;
diagnostic imaging
;
Ultrasonography
;
methods
4.A retrospective analysis of 20-year data of the surgical management of ulcerative colitis patients in Taiwan: a study of Taiwan Society of Inflammatory Bowel Disease.
Chun Chi LIN ; Shu Chen WEI ; Been Ren LIN ; Wen Sy TSAI ; Jinn Shiun CHEN ; Tzu Chi HSU ; Wei Chen LIN ; Tien Yu HUANG ; Te Hsin CHAO ; Hung Hsin LIN ; Jau Min WONG ; Jen Kou LIN
Intestinal Research 2016;14(3):248-257
BACKGROUND/AIMS: With the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD. METHODS: A retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed. RESULTS: The data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively). CONCLUSIONS: In the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount.
Colectomy
;
Colitis, Ulcerative*
;
Cooperative Behavior
;
Diagnosis
;
Emergencies
;
Follow-Up Studies
;
Hemorrhage
;
Humans
;
Inflammatory Bowel Diseases*
;
Mortality
;
Prognosis
;
Retrospective Studies*
;
Sepsis
;
Taiwan*
;
Ulcer*
5.Comparative Analysis of Logistic Regression, Support Vector Machine and Artificial Neural Network for the Differential Diagnosis of Benign and Malignant Solid Breast Tumors by the Use of Three-Dimensional Power Doppler Imaging.
Shou Tung CHEN ; Yi Hsuan HSIAO ; Yu Len HUANG ; Shou Jen KUO ; Hsin Shun TSENG ; Hwa Koon WU ; Dar Ren CHEN
Korean Journal of Radiology 2009;10(5):464-471
OBJECTIVE: Logistic regression analysis (LRA), Support Vector Machine (SVM) and a neural network (NN) are commonly used statistical models in computer-aided diagnostic (CAD) systems for breast ultrasonography (US). The aim of this study was to clarify the diagnostic ability of the use of these statistical models for future applications of CAD systems, such as three-dimensional (3D) power Doppler imaging, vascularity evaluation and the differentiation of a solid mass. MATERIALS AND METHODS: A database that contained 3D power Doppler imaging pairs of non-harmonic and tissue harmonic images for 97 benign and 86 malignant solid tumors was utilized. The virtual organ computer-aided analysis-imaging program was used to analyze the stored volumes of the 183 solid breast tumors. LRA, an SVM and NN were employed in comparative analyses for the characterization of benign and malignant solid breast masses from the database. RESULTS: The values of area under receiver operating characteristic (ROC) curve, referred to as Az values for the use of non-harmonic 3D power Doppler US with LRA, SVM and NN were 0.9341, 0.9185 and 0.9086, respectively. The Az values for the use of harmonic 3D power Doppler US with LRA, SVM and NN were 0.9286, 0.8979 and 0.9009, respectively. The Az values of six ROC curves for the use of LRA, SVM and NN for non-harmonic or harmonic 3D power Doppler imaging were similar. CONCLUSION: The diagnostic performances of these three models (LRA, SVM and NN) are not different as demonstrated by ROC curve analysis. Depending on user emphasis for the use of ROC curve findings, the use of LRA appears to provide better sensitivity as compared to the other statistical models.
Adolescent
;
Adult
;
Aged
;
Aged, 80 and over
;
*Artificial Intelligence
;
Breast Neoplasms/*ultrasonography
;
Diagnosis, Computer-Assisted
;
Diagnosis, Differential
;
Female
;
Humans
;
Image Interpretation, Computer-Assisted
;
Imaging, Three-Dimensional/*statistics & numerical data
;
Logistic Models
;
Middle Aged
;
*Neural Networks (Computer)
;
Predictive Value of Tests
;
ROC Curve
;
Sensitivity and Specificity
;
Ultrasonography, Doppler/*statistics & numerical data
;
Ultrasonography, Mammary/*statistics & numerical data
6.Linking an Anxiety-Related Personality Trait to Cardiac Autonomic Regulation in Well-Defined Healthy Adults: Harm Avoidance and Resting Heart Rate Variability.
Lien Cheng KAO ; Yu Wen LIU ; Nian Sheng TZENG ; Terry B J KUO ; San Yuan HUANG ; Chuan Chia CHANG ; Hsin An CHANG
Psychiatry Investigation 2016;13(4):397-405
OBJECTIVE: Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. METHODS: We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05-0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. RESULTS: The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. CONCLUSION: This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD.
Adult*
;
Anxiety
;
Baroreflex
;
Cardiovascular Diseases
;
Depression
;
Healthy Volunteers
;
Heart Rate*
;
Heart*
;
Humans
7.Molecular Identification of Diphyllobothrium latum from a Pediatric Case in Taiwan.
Yu Chin AN ; Chia Cheng SUNG ; Chih Chien WANG ; Hsin Chung LIN ; Kuang Yao CHEN ; Fu Man KU ; Ruei Min CHEN ; Mei Li CHEN ; Kuo Yang HUANG
The Korean Journal of Parasitology 2017;55(4):425-428
Human diphyllobothriasis is a parasitic disease caused by ingestion of larvae (plerocercoids) in raw or undercooked fish and commonly found in temperate areas. Rare cases were reported in tropical or subtropical areas especially in children. The first documented case of pediatric diphyllobothriasis in Taiwan had been reported 11 years ago. Here, we report another 8-year-old girl case who presented with a live noodle-like worm hanging down from her anus, with no other detectable symptoms. We pulled the worm out and found the strobila being 260 cm in length. Examination of gravid proglottids showed that they were wider than their lengths, containing an ovoid cirrus sac in the anterior side and the rosette-shaped uterus. Eggs extracted from the uterus were ovoid and operculated. Diphyllobothrium latum was confirmed by molecular analysis of the mitochondrial DNA cytochrome c oxidase subunit 1 (cox1) gene. The girl was treated with a single oral dose of praziquantel, and no eggs or proglottids were observed from her stool in the subsequent 3 months. The reemergence of human diphyllobothriasis in non-endemic countries is probably due to prevalent habit of eating imported raw fish from endemic areas. This pediatric case raised our concern that human diphyllobothriasis is likely underestimated because of unremarkable symptoms.
Anal Canal
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Child
;
Diphyllobothriasis
;
Diphyllobothrium*
;
DNA, Mitochondrial
;
Eating
;
Eggs
;
Electron Transport Complex IV
;
Female
;
Humans
;
Larva
;
Ovum
;
Parasitic Diseases
;
Praziquantel
;
Taiwan*
;
Uterus
8.The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder.
Hui Ching HUANG ; Lawrence Shih Hsin WU ; Shun Chieh YU ; Bo Jian WU ; Ahai Chang LUA ; Shin Min LEE ; Chao Zong LIU
Psychiatry Investigation 2018;15(3):306-312
OBJECTIVE: The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. METHODS: The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. RESULTS: Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). CONCLUSION: The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.
Adolescent*
;
Alleles
;
Child*
;
Diagnosis
;
Diagnostic and Statistical Manual of Mental Disorders
;
Homozygote
;
Humans
;
Logistic Models
;
Methylphenidate*
;
Odds Ratio
;
Pharmacogenetics
;
Polymorphism, Single Nucleotide*
;
Receptors, Adrenergic, alpha-2*
;
Sequence Analysis, DNA
9.Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo
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
Biomolecules & Therapeutics 2021;29(5):551-561
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.
10.Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo
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
Biomolecules & Therapeutics 2021;29(5):551-561
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.