The off-target activities of lapatinib : Achilles` shield or heel?

Wei-Chien Huang(黃偉謙) 한의병리학회 2015 대한동의병리학회 학술대회논문집 Vol.2015 No.10

Lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) kinase inhibitor, showed clinical benefits in advanced HER2-positive breast cancer patients. Because EGFR overexpression was frequently found in triple-negative breast cancers (TNBCs), the antitumor activity of lapatinib in such diseases was also tested. However, the results showed a worse event-free survival rate. Recently, our studies demonstrated that lapatinib facilitated axillary and lung metastases of triple-negative MDA-MB-231 breast cancer cells without affecting their viability, leading to worse survival in orthotopic xenograft mice. The lapatinib-increased motility was attributed by its off target effects on the downregulation of microRNA-7 and the subsequent overexpression of cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) through NF- B and Raf-1 activation respectively. Unexpectedly, lapatinib-induced NF- B activation and HDAC expression render TNBC cells more sensitive to proteasome inhibitor and HDAC inhibitor, showing potential partners for combination therapies with with lapatinib to benefit TNBC patients.

Characterization of Protein Arginine Methyltransferases in Porcine Brain

( Chien Jen Hung ),( Da Huang Chen ),( Yi Ting Shen ),( Yi Chen Li ),( Yi Wei Lin ),( Mingli Hsieh ),( Chuan Li ) 생화학분자생물학회 2007 BMB Reports Vol.40 No.5

Conjugation of mono-sulfobetaine to alkyne-PPX films via click reaction to reduce cell adhesion

Chien, Hsiu-Wen,Keng, Ming-Chun,Chen, Hsien-Yeh,Huang, Sheng-Tung,Tsai, Wei-Bor Techno-Press 2016 Biomaterials and biomedical engineering Vol.3 No.1

A surface resisting protein adsorption and cell adhesion is highly desirable for many biomedical applications such as diagnostic devices, biosensors and blood-contacting devices. In this study, a surface conjugated with sulfobetaine molecules was fabricated via the click reaction for the anti-fouling purpose. An alkyne-containing substrate (Alkyne-PPX) was generated by chemical vapor deposition of 4-ethynyl-[2,2]paracyclophane. Azide-ended mono-sulfobetaine molecules were synthesized and then conjugated on Alkyne-PPX via the click reaction. The protein adsorption from 10% serum was reduced by 57%, while the attachment of L929 cells was reduced by 83% onto the sulfobetaine-PPX surface compared to the protein adsorption and cell adhesion on Alkyne-PPX. In conclusion, we demonstrate that conjugation of mono-sulfobetaine molecules via the click chemistry is an effective way for reduction of non-specific protein adsorption and cell attachment.

Resource Management in 5G Mobile Networks: Survey and Challenges

Wei-Che Chien,Shih-Yun Huang,Chin-Feng Lai,Han-Chieh Chao 한국정보처리학회 2020 Journal of information processing systems Vol.16 No.4

With the rapid growth of network traffic, a large number of connected devices, and higher application services, the traditional network is facing several challenges. In addition to improving the current network architecture and hardware specifications, effective resource management means the development trend of 5G. Althoughmany existing potential technologies have been proposed to solve the some of 5G challenges, such as multipleinput multipleoutput (MIMO), softwaredefined networking (SDN), network functions virtualization (NFV), edge computing, millimeterwave, etc., research studies in 5G continue to enrich its function and move toward B5G mobile networks. In this paper, focusing on the resource allocation issues of 5G core networks and radio access networks, we address the latest technological developments and discuss the current challenges for resource management in 5G.

A Methodology to Build a Groutability Formula via a Heuristic Algorithm

Chien-Lin Huang,Jen-Chen Fan,Kuo-Wei Liao,Tsung-Hsun Lien 대한토목학회 2013 KSCE JOURNAL OF CIVIL ENGINEERING Vol.17 No.1

The goal of this study is to provide a methodology to develop a groutability (N) formula of sandy silt soils using microfine cement grouts in a permeation grouting. Because the Fines Content (FC) of the sandy silt soils studied is relatively high, and the size of the grouts used is significantly smaller than the Portland cement, the existing empirical formulas cannot deliver a promising prediction of N. Support Vector Machines (SVMs) is an alternative tool used to predict N. However, SVMs do not provide an explicit formula,which creates an obstacle for practical engineers. Thus, a heuristic algorithm (the Tabu search, TS) was used to build the prediction formula. A total of 240 in-situ data samples were analyzed to ensure the accuracy of the proposed formula. The format of the existing empirical formula was adopted in the proposed TS-based formula. Four parameters were considered in our TS models: the effective soil particle size (D10), the soil particle size (D15), the water-to-cement ratio (w/c) and the FC. The prediction accuracy of the TSbased formula was approximately 94.17%, indicating that the proposed formula is a suitable tool. Because the proposed formula has a similar format to that of formulas that are typically used, the proposed approach can be implemented readily in practical engineering settings. Note that the proposed formula was only verified by the collected data samples, the suitability of applying the built formula to other conditions needs more investigation.

Conjugation of mono-sulfobetaine to alkyne-PPX films via click reaction to reduce cell adhesion

Chien, Hsiu-Wen,Keng, Ming-Chun,Chen, Hsien-Yeh,Huang, Sheng-Tung,Tsai, Wei-Bor Techno-Press 2016 Biomaterials and Biomechanics in Bioengineering Vol.3 No.1

A surface resisting protein adsorption and cell adhesion is highly desirable for many biomedical applications such as diagnostic devices, biosensors and blood-contacting devices. In this study, a surface conjugated with sulfobetaine molecules was fabricated via the click reaction for the anti-fouling purpose. An alkyne-containing substrate (Alkyne-PPX) was generated by chemical vapor deposition of 4-ethynyl-[2,2]paracyclophane. Azide-ended mono-sulfobetaine molecules were synthesized and then conjugated on Alkyne-PPX via the click reaction. The protein adsorption from 10% serum was reduced by 57%, while the attachment of L929 cells was reduced by 83% onto the sulfobetaine-PPX surface compared to the protein adsorption and cell adhesion on Alkyne-PPX. In conclusion, we demonstrate that conjugation of mono-sulfobetaine molecules via the click chemistry is an effective way for reduction of non-specific protein adsorption and cell attachment.

Characterization of Protein Arginine Methyltransferases in Porcine Brain

Hung, Chien-Jen,Chen, Da-Huang,Shen, Yi-Ting,Li, Yi-Chen,Lin, Yi-Wei,Hsieh, Mingli,Li, Chuan Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.5

Protein arginine methylation is a posttranslational modification involved in various cellular functions including cell signaling, protein subcellular localization and transcriptional regulation. We analyze the protein arginine methyltransferases (PRMTs) that catalyze the formation of methylarginines in porcine brain. We fractionated the brain extracts and determined the PRMT activities as well as the distribution of different PRMT proteins in subcellular fractions of porcine brain. The majority of the type I methyltransferase activities that catalyze the formation of asymmetric dimethylarginines was in the cytosolic S3 fraction. High specific activity of the methyltransferase was detected in the S4 fraction (high-salt stripping of the ultracentrifugation precipitant P3 fraction), indicating that part of the PRMT was peripherally associated with membrane and ribosomal fractions. The amount and distribution of PRMT1 are consistent with the catalytic activity. The elution patterns from gel filtration and anion exchange chromatography also indicate that the type I activity in S3 and S4 are mostly from PRMT1. Our results suggest that part of the type I arginine methyltransferases in brains, mainly PRMT1, are sequestered in an inactive form as they associated with membranes or large subcellular complexes. Our biochemical analyses confirmed the complex distribution of different PRMTs and implicate their regulation and catalytic activities in brain.

Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in ApcMin/+ Mice: Relation to Metabolism and Gut Microbiota Composition

Yi-Wen Huang,Chien-Wei Lin,Pan Pan,Carla Elena Echeveste,Athena Dong,Kiyoko Oshima,Martha Yearsley,Jianhua Yu,Li-Shu Wang 대한암예방학회 2021 Journal of cancer prevention Vol.26 No.1

Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (ApcMin/+). Ffar2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, ApcMin/+, and ApcMin/+-Ffar2-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the ApcMin/+-Ffar2-/- mice compared to the ApcMin/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, longchain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that Ffar2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.

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)

Case Reports : 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.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)