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 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.

The Beneficial Effects of Raffinee in Permanent Occulted Stroke Mice

Chun-Ching Chiu,Jer-Min Lin,Li-Yi Wu,Tsai-Ching Hsu,Bor-Show Tzang 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.12

Ischemic stroke is a major cause of disability and mortality globally. Although thrombolytic therapy is routinely adopted in cases of ischemic stroke, various alternative natural neuroprotectants are also used as effective adjuvant therapies to recover neurofunction following ischemic stroke. Raffinee, a natural fermented product with strong antioxidant and neuroprotective activities, has antiatherogenic effects in animals and has exhibited neuroprotective effects in a clinical trial by recovering motor and sensory function following spinal cord lesion. This study reveals the advantageous effects of Raffinee on PC12 cells by decreasing hypoxia-induced apoptosis in mice with permanent middle cerebral artery occlusion (pMCAO) by increasing the levels of neurotrophic factors such as S100β, reducing serum inflammatory factors such as matrix metalloproteinases (MMP)-9/MMP-2 ratio, tumor necrosis factor-α, and interleukin (IL)-6 level, and increasing IL-10 levels. Significantly reduced brain infarct volume along with a favorable survival ratio was observed for pMCAO mice that received Raffinee, suggesting a neuroprotective potential of Raffinee in cases of acute ischemic stroke by suppressing apoptosis.

Exploring Humanized Care in Emergency Department

Chun-Chang Lin,Hung-Jung Lin,Ching-Huey Chen,Co-Shi Chantal Chao 한국간호과학회 2009 한국간호과학회 학술대회 Vol.2009 No.10

Taurine Attenuates Hepatic Inflammation in Chronic Alcohol-Fed Rats Through Inhibition of TLR4/MyD88 Signaling

Chao-Jen Lin,Chun-Ching Chiu,Yi-Chen Chen,Mu-Lin Chen,Tsai-Ching Hsu,Bor-Show Tzang 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.12

Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc + taurine (Tau), and (4) Alc + silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

Shielding-benefit Evaluation of Electromagnetic Radiation and UV Radiation for Multifunctional Composite Polypropylene Woven Fabrics

Ting An Lin,Yu-Chun Chuang,Jan-Yi Lin,Mei-Chen Lin,Ching-Wen Lou,Keng Siang Sim,Jia-Horng Lin 한국섬유공학회 2020 Fibers and polymers Vol.21 No.10

People have increasingly rising health consciousness in recent years and researchers are thus devoted themselvesto develop multi-functional textile products. In this study, stainless steel (SS) filaments are used for electromagnetic shieldingeffectiveness (EMSE) while polypropylene (PP) filaments are used for ultraviolet resistance and good mechanical properties. Spinning and weaving continuous formation techniques are employed to produce wrapped yarns with SS and PP filaments,after which a weaving process is employed for the preparation of SS/PP woven fabrics. The woven fabrics are tested forEMSE and UV resistance, examining the effect of the lamination-layer numbers and lamination-layer angles. Test resultsshow that the optimal EMSE and UV resistance occur when SS/PP woven fabrics are laminated with two layers at 90 °. Notonly focus on the mechanical performance, the proposed woven fabrics with good EMSE, UV resistance, and a light weight,and are good candidate for a variety of application as required. The proposed UV resistance and EMSE woven fabricssignificantly increase the additional values of traditional textiles.

Enhancing antimicrobial activity of mastoparan-B by amino acid substitutions

Mars J. Yang,Wen-Yuh Lin,Chun-Hsien Lin,Ching-Lin Shyu,Roger F. Hou,Wu-Chun Tu 한국응용곤충학회 2013 Journal of Asia-Pacific Entomology Vol.16 No.4

This study evaluated antimicrobial and hemolytic activities of mastoparan-B (MP-B) isolated fromthe venomof the hornet, Vespa basalis, and its analogs after substituting certain amino acid (aa) residues.MP-B exhibited significantly different antimicrobial activities against bacteria species/strains tested, especially two Escherichia coli strains, Staphylococcus xylosus and Citrobacter koseri at low dosages, and was non-specific against certain Gram-positive and -negative bacteria. Our results indicated that hydrophobicitymodification by single aa substitution may enhance their antimicrobial activities. An aa substituted MP-B, viz., MP-B-1, inwhich Trp substituted for Leu3, became more effective than the original peptide at inhibiting or killing the bacterial species tested, especially Klebsiella pneumonia, Salmonella typhimurium, and Salmonella Cholerasuis, and even up to 8 timesmore effective in some cases. However, MP-B-2 was virtually similar to MP-B against each bacterial species assayed,while MP-B-3 reduced its effectiveness greatly compared to others. On the other hand, MP-B and its analogs were not effective against the beneficial probiotics and they were not hemolytic to erythrocytes at the dosages tested. Our results suggested that MP-B becomes more potent against specific pathogenic bacteria and safe to the probiotics after undergoing appropriate amino acid substitutions.

Can Elderly Patients with Severe Mitral Regurgitation Benefit from Trans-catheter Mitral Valve Repair?

Ching-Wei Lee,Shih-Hsien Sung,Wei-Ming Huang,Yi-Lin Tsai,Hsiang-Yao Chen,Chiao-Po Hsu,Chun-Che Shih,Kuo-Piao Chung 대한심장학회 2019 Korean Circulation Journal Vol.49 No.6

Background and ObjectivesAge is a traditional risk factor for open-heart surgery. The efficacy and safety of transcatheter edge-to-edge mitral valve repair, using MitraClip (Abbott Vascular), has been demonstrated in patients with severe mitral regurgitation (MR). Since octogenarians or older patients are usually deferred to receive open-heart surgery, the main interest of this study is to elucidate the procedural safety and long-term clinical impact of MitraClip in elderly patients. MethodsPatients with symptomatic severe MR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before, 1-month, 6-months, and 1 year after index procedure. ResultsA total of 46 consecutive patients receiving MitraClip procedure were enrolled. Nineteen patients (84.2±4.0 years) were over 80-year-old and 27 (73.4±11.1 years) were younger than 80. Compare to baseline, the significant reduction in MR severity was achieved after the procedure and sustained. All the patients benefited from significant improvement in New York Heart Association functional class. The 6-minute walk test (6MWT) increased from 259±114 to 319±92 meters (p=0.03) at 1 year. The overall 1-year survival rate was 80% in the elderly and 88% in those <80 years, p=0.590. Baseline 6MWT was a predictor for all-cause mortality (odds ratio, 0.99; 95% confidence interval, 0.982–0.999; p=0.026) after the MitraClip procedure. ConclusionsTrans-catheter edge-to-edge mitral valve repairs are safe and have positive clinical impact in subjects with severe MR, even in advanced age.

Grasping the Pseudo-Cleft in the Case of a Small, Severely Tethered Posterior Mitral Leaflet

Ching-Wei Lee,Shih-Hsien Sung,Ting-Yung Chang,I-Lin Tsai,Chih-Po Hsu,Chun-Che Shih 대한심장학회 2017 Korean Circulation Journal Vol.47 No.4

Cis-3-O-p-hydroxycinnamoyl Ursolic Acid Induced ROS-Dependent p53-Mediated Mitochondrial Apoptosis in Oral Cancer Cells

Ching-Ying Wang,Chen-Sheng Lin,Chun-Hung Hua,Yu-Jen Jou,Chi-Ren Liao,Yuan-Shiun Chang,Lei Wan,Su-Hua Huang,Mann-Jen Hour,Cheng-Wen Lin 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 μM and 17.8 μM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentrationdependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.

Modeling and Evaluating Inventory Replenishment for Short Life-cycle Products

Ching-Ho Wang,Shih-Wei Lin,Shuo-Yan Chou,Chun-Hsiang Tsai 대한산업공학회 2008 대한산업공학회지 Vol.34 No.4

Due to the rapid advancement of technologies, a growing number of innovative products with a short life-cycle have been introduced to the market. As the life-cycles of such products are shorter than those of durable goods, the demand variation during the life-cycle adds to the difficulty of inventory management. Traditional inventory planning models and techniques mostly deal with products that have long life-cycles. The assumptions on the demand pattern and subsequent solution approaches are generally, not suitable for dealing with products with short life-cycles. In this research, inventory replenishment problems based on the logistic demand model are formulated and solved to facilitate the management of products with short life-cycles. An extended Wagner-Whitin approach is used to determine the replenishment cycle, schedules and lot-sizes.