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Arginine Signaling and Cancer Metabolism

Chia-Lin Chen, Sheng-Chieh Hsu, David K. Ann, Yun Yen, Hsing-Jien Kung
2021 Cancers  
Arginine is an amino acid critically involved in multiple cellular processes including the syntheses of nitric oxide and polyamines, and is a direct activator of mTOR, a nutrient-sensing kinase strongly implicated in carcinogenesis. Yet, it is also considered as a non- or semi-essential amino acid, due to normal cells' intrinsic ability to synthesize arginine from citrulline and aspartate via ASS1 (argininosuccinate synthase 1) and ASL (argininosuccinate lyase). As such, arginine can be used as
more » ... a dietary supplement and its depletion as a therapeutic strategy. Strikingly, in over 70% of tumors, ASS1 transcription is suppressed, rendering the cells addicted to external arginine, forming the basis of arginine-deprivation therapy. In this review, we will discuss arginine as a signaling metabolite, arginine's role in cancer metabolism, arginine as an epigenetic regulator, arginine as an immunomodulator, and arginine as a therapeutic target. We will also provide a comprehensive summary of ADI (arginine deiminase)-based arginine-deprivation preclinical studies and an update of clinical trials for ADI and arginase. The different cell killing mechanisms associated with various cancer types will also be described.
doi:10.3390/cancers13143541 fatcat:4v35oxki6bhwpbnukqokk3tr2i

Variable Neighborhood Search for Major League Baseball Scheduling Problem

Yun-Chia Liang, Yen-Yu Lin, Angela Hsiang-Ling Chen, Wei-Sheng Chen
2021 Sustainability  
Modern society pays more and more attention to leisure activities, and watching sports is one of the most popular activities for people. In professional leagues, sports scheduling plays a very critical role. To efficiently arrange a schedule while complying with the relevant rules in a sports league has become a challenge for schedule planners. This research uses Major League Baseball (MLB) of the year 2016 as a case study. The study proposed the Variable Neighborhood Search (VNS) algorithm
more » ... different coding structures to optimize the objective function—minimize the total travelling distance of all teams in the league. We have compared the algorithmic schedules with the 2016 and 2019 MLB regular-season schedules in the real-world case for its performance evaluation. The results have confirmed success in reducing the total travelling distances by 2.48% for 2016 and 6.02% in 2019 while lowering the standard deviation of total travelling distances by 7.06% for 2016.
doi:10.3390/su13074000 fatcat:4d5hfngif5b3ro6gqwxzzagbwy

The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders

Tzu-Yun Wang, Sheng-Yu Lee, Shiou-Lan Chen, Yi-Lun Chung, Chia-Ling Li, Yun-Hsuan Chang, Liang-Jen Wang, Po See Chen, Shih-Heng Chen, Chun-Hsien Chu, San-Yuan Huang, Nian-Sheng Tzeng (+7 others)
2016 International Journal of Neuropsychopharmacology  
doi:10.1093/ijnp/pyw012 pmid:26865313 pmcid:PMC5006191 fatcat:6nrbpth25bhoffxdldkvch7pna

Small blood stem cells for enhancing early osseointegration formation on dental implants: a human phase I safety study

Sheng-Wei Feng, Yi-Han Su, Yen-Kuang Lin, Yu-Chih Wu, Yen-Hua Huang, Fu-Hung Yang, Hsi-Jen Chiang, Yun Yen, Peter Da-Yen Wang
2021 Stem Cell Research & Therapy  
Yen-Kung Lin at TMU.  ... 
doi:10.1186/s13287-021-02461-z pmid:34215319 pmcid:PMC8254299 fatcat:dpud6bj52ngpthtlsorzakpune

Integrin β3 and LKB1 are independently involved in the inhibition of proliferation by lovastatin in human intrahepatic cholangiocarcinoma

Sheng-Huei Yang, Hung-Yun Lin, Chun A Changou, Chun-Han Chen, Yun-Ru Liu, Jinghan Wang, Xiaoqing Jiang, Frank Luh, Yun Yen
2015 OncoTarget  
Human intrahepatic cholangiocarcinomas are one of the most difficult cancers to treat. In our study, Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme- CoA (HMG-CoA) reductase inhibitor, demonstrated anticancer properties by inhibiting cancer cell proliferation, cell migration and cell adhesion. Lovastatin inhibited the expressions of transforming growth factor (TGF)-β1, cyclooxygenase (COX)-2, and intercellular adhesion molecule (ICAM)-1. Furthermore, lovastatin inhibited the expressions of
more » ... egrin β1 and integrin β3 but not integrin αv or integrin β5. While Lovastatin's inhibitory effects on TGFβ1, COX2, and ICAM-1 expression were independently controlled by the tumor suppressor LKB1, integrin β3 expression was not affected. Lovastatin's inhibitory effect on cell adhesion was associated with the decreased expression of integrin β3 and cell surface heterodimer integrin αvβ3. Quantitative real time PCR, fluorescent microscopy, and cell migration assays all confirmed that Lovastatin inhibits integrin αvβ3 downstream signaling including FAK activation, and β-catenin, vimentin, ZO-1, and β-actin. Overall, Lovastatin reduced tumor cell proliferation and migration by modifying the expression of genes involved in cell adhesion and other critical cellular processes. Our study highlights novel anti-cancer properties of Lovastatin and supports further exploration of statins in the context of cholangiocarcinoma therapy.
doi:10.18632/oncotarget.6238 pmid:26517522 pmcid:PMC4808004 fatcat:pzmlw3fut5gzhkv2pmxiny26yi

Cellular Neurothekeoma of the Upper Lip in an Infant

Hsin-Yen Pan, Sheng-Hong Tseng, Chia-Chi Weng, Yun Chen
2014 Pediatrics and Neonatology  
Cellular neurothekeoma is an uncommon benign skin neoplasm and also a variant of neurothekeoma. Cellular neurothekeomas usually occur in the skin of the upper trunk, head, or neck of children and young adults; however, they rarely occur in infants or involve the lip. A 6-monthold male infant was incidentally found to have a tumor in the upper lip. The tumor was elastic, nontender, and movable, and the overlying mucosa and skin were normal without discoloration. The tumor was excised from the
more » ... osal side of the upper lip, and a pathological examination revealed cellular neurothekeoma. Cellular neurothekeoma in the lip of an infant without overlying skin discoloration might delay the diagnosis and lead to wrong preoperative diagnosis. No similar case has been reported in the literature.
doi:10.1016/j.pedneo.2012.12.004 pmid:23597544 fatcat:j326givhzvdnlh3yc4t7oas7ca

Global dynamic home agent discovery on mobile IPv6

Yun-Sheng Yen, Chia-Chang Hsu, Han-Chieh Chao
2006 Wireless Communications and Mobile Computing  
Mobile IPv6 is a novel technology that supports mobile Internet communications. When a mobile node approaches another scalable domain, such as another ISP or mobile network company, serious problems occur such as registration delay and transmission latency owing to the binding update that the mobile node registers back to its original home agent. This work attempts to construct a scalable mobile IPv6 global network anycast by dynamically determining the nearest home agent to the current home
more » ... nt for registration and transmission. This scheme is called Global Dynamic Home Agent Discovery (GDHAD). This investigation also performed and evaluated an anycast simulation to find how to obtain the best performance.
doi:10.1002/wcm.414 fatcat:v3b2zc6m2zh6llxolc76ulr64u

Clerodane Diterpenoids from Callicarpa hypoleucophylla and Their Anti-Inflammatory Activity

Yu-Chi Lin, Jue-Jun Lin, Shu-Rong Chen, Tsong-Long Hwang, Shu-Yen Fang, Michal Korinek, Ching-Yeu Chen, Yun-Sheng Lin, Tung-Ying Wu, Ming-Hong Yen, Chih-Hsin Wang, Yuan-Bin Cheng
2020 Molecules  
Ming-Hong Yen. A voucher sample (specimen code: CH001) was deposited at the Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.  ... 
doi:10.3390/molecules25102288 pmid:32414033 pmcid:PMC7287842 fatcat:2pc6f5mbmzd23imehfye2kkixu

Brain activation for response inhibition under gaming cue distraction in internet gaming disorder

Gin-Chung Liu, Ju-Yu Yen, Chiao-Yun Chen, Cheng-Fang Yen, Cheng-Sheng Chen, Wei-Chen Lin, Chih-Hung Ko
2014 Kaohsiung Journal of Medical Sciences  
We evaluated neural substrates related to the loss of control in college students with internet gaming disorder (IGD). We hypothesized that deficit in response inhibition under gaming cue distraction was the possible mechanism for the loss of control internet use. Eleven cases of IGD and 11 controls performed Go/NoGo tasks with/without gaming distraction in the functional magnetic resonance imaging scanner. When the gaming picture was shown as background while individuals were performing
more » ... tasks, the IGD group committed more commission errors. The control group increased their brain activations more over the right dorsolateral prefrontal cortex (DLPFC) and superior parietal lobe under gaming cue distraction in comparison with the IGD group. Furthermore, brain activation of the right DLPFC and superior parietal lobe were negatively associated with performance of response inhibition among the IGD group. The results suggest that the function of response inhibition was impaired under gaming distraction among the IGD group, and individuals with IGD could not activate right
doi:10.1016/j.kjms.2013.08.005 pmid:24388058 fatcat:h5ntfiiix5cgpcpn3d7ezaygfq

Correlation between interleukin-6 levels and methadone maintenance therapy outcomes

Ru-Band Lu, Tzu-Yun Wang, Sheng-Yu Lee, Shiou-Lan Chen, Yun-Hsuan Chang, Po See Chen, Shih-Hsien Lin, Chun-Hsien Chu, San-Yuan Huang, Nian-Sheng Tzeng, I Hui Lee, Kao Chin Chen (+4 others)
2019 Drug and Alcohol Dependence  
Each patient was initially interviewed and diagnosed by a board certified psychiatrist (author Tzu-Yun Wang) and then were also screened by a research team member well trained in using the Diagnostic and  ... 
doi:10.1016/j.drugalcdep.2019.06.018 pmid:31513981 pmcid:PMC7077753 fatcat:jvexxxdtznhophgxo4tiovl5e4

A potential interaction between COMT and MTHFR genetic variants in Han Chinese patients with bipolar II disorder

Liang-Jen Wang, Sheng-Yu Lee, Shiou-Lan Chen, Yun-Hsuan Chang, Po See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Kao Chin Chen, I. Hui Lee, Tzu-Yun Wang, Yen Kuang Yang, Ru-Band Lu
2015 Scientific Reports  
Bipolar II disorder (BP-II), characterized by recurrent dysregulation of mood, is a serious and chronic psychiatric illness. However, BP-II is commonly under-recognized, even in psychiatric settings. Because dopaminergic disturbance is thought to be involved in the development of bipolar disorder (BPD), it seems essential to investigate dopamine-related genes like the catechol-O-methyltransferase (COMT) gene, which are involved in dopamine metabolism, and the methylenetetrahydrofolate reductase
more » ... (MTHFR) gene, which may affect COMT methylation and COMT function. The current study examined the association and interaction of the COMT Val158Met and MTHFR C677T variants with BP-II. Nine hundred seventy-eight participants were recruited: 531 with BP-II and 447 healthy controls. The genotypes of the COMT and MTHFR polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant interaction effect of the COMT Val158Met Val/Val genotype and the MTHFR C677T C/T 1 T/T genotype (P 5 0.039) for the protective effect on the odds of developing BP-II. Our findings support preliminary evidence that the COMT and MTHFR genes interact in BP-II, and they imply the connection of both dopaminergic pathways and methylation pathways in the pathogenesis of BP-II.
doi:10.1038/srep08813 pmid:25744938 pmcid:PMC4351536 fatcat:mdoihejwzjdwbktekakhbl63la

Lovastatin overcomes gefitinib resistance through TNF-α signaling in human cholangiocarcinomas with different LKB1 statuses in vitro and in vivo

Sheng-Huei Yang, Hung-Yun Lin, Vincent H.S. Chang, Chien-Chung Chen, Yun-Ru Liu, Jinghan Wang, Keqiang Zhang, Xiaoqing Jiang, Yun Yen
2015 OncoTarget  
Gefitinib resistance has been shown to complicate cancer therapy. Lovastatin is a proteasome inhibitor that enhances gefitinib-induced antiproliferation in nonsmall cell lung cancer. The objective of this study is to investigate the mechanism of lovastatin-induced antiproliferation in gefitinib-resistant human cholangiocarcinoma. Two gefitinib-resistant cholangiocarcinoma cell lines, SSP-25 and HuH-28, were used in this study to determine how to compensate gefitinib resistance. The combined
more » ... ct of these two drugs was examined using the MTT assay, qPCR, immunoblotting, flow cytometry, and in vivo xenograft. Results indicated that lovastatin enhanced TNFα-induced cell death in vitro. In addition, the combination of lovastatin with gefitinib enhanced accumulation of TNF-α. Furthermore, the treatment induced a synergistic cytotoxic effect and antiproliferation through apoptosis in SSP-25 cells and cell cycle arrest in HuH-28 cells. Reproductive results were also observed in in vivo xenografts. These observations suggest that the combination of gefitinib and lovastatin might have additive antiproliferative effects against gefitinib-resistant cholangiocarcinoma cells. Based on these observations, we concluded that the combination of gefitinib and lovastatin could be used to overcome gefitinib resistance in cholangiocarcinoma cells.
doi:10.18632/oncotarget.4408 pmid:26160843 pmcid:PMC4695157 fatcat:ma32ggecxnhsjmkjont6amqrgm

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism

Sheng-Yu Lee, Tzu-Yun Wang, Shiou-Lan Chen, Yun-Hsuan Chang, Po-See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, I. Hui Lee, Kao Chin Chen, Yen Kuang Yang, Yi-Hsin Yang (+2 others)
2016 Scientific Reports  
We explored the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment in bipolar disorder (BD). Symptom severity and plasma BDNF levels were assessed upon recruitment and during weeks 1, 2, 4, 8 and 12. QoL, the Wisconsin Card Sorting Test (WCST), and the Conners' Continuous Performance Test (CPT) were assessed at baseline and
more » ... . The BDNF Val66Met polymorphism was genotyped. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF. Five hundred forty-one BD patients were recruited and 65.6% of them completed the 12-week follow-up. Changes in plasma BDNF levels with factor 1 (WCST) were significantly negatively correlated (r = −0.25, p = 0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BP-I and the Val/Met genotype (r = −0.54, p = 0.008). We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD. Bipolar disorder (BD) is characterized by recurrent episodes of dysregulated moods 1,2 . With high heritability 3 , genetic factors had been regarded as an important etiology for BD. The most frequently seen subtypes of BD are bipolar I disorder (BP-I) and bipolar II disorder (BP-II). Being a chronic mental disorder, BD is increasingly regarded as a neurodegenerative disorder supported by imaging studies 4,5 . Brain-derived neurotrophic factor (BDNF) is an important protein for neuron development, growth and survival 6 . BDNF is robustly expressed
doi:10.1038/srep37950 pmid:27905499 pmcid:PMC5131343 fatcat:d4u2monxz5gfzibw7zyoqqjtqy

A genetic algorithm for energy-efficient based multicast routing on MANETs

Yun-Sheng Yen, Yi-Kung Chan, Han-Chieh Chao, Jong Hyuk Park
2008 Computer Communications  
Yen et al. / Computer Communications 31 (2008) 2632-2641  ... 
doi:10.1016/j.comcom.2007.10.033 fatcat:oa47cmim3jg57dxr6p23icxhqi

Epstein–Barr virus BRLF1 induces genomic instability and progressive malignancy in nasopharyngeal carcinoma cells

Sheng-Yen Huang, Chung-Chun Wu, Yu-Jhen Cheng, Sheng-Ping Chou, Yun-Jin Jiang, Kuo-Chang Chu, Ching-Hwa Tsai, Su-Fang Lin, Jen-Yang Chen
2017 OncoTarget  
doi:10.18632/oncotarget.20695 pmid:29108278 pmcid:PMC5668011 fatcat:bqt5gqlyijbkhhgudlmgb6fx4i
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