Inhibition of the NEDD8 Conjugation Pathway by shRNA to UBA3, the Subunit of the NEDD8-Activating Enzyme, Suppresses the Growth of Melanoma Cells

Cheng, Fang,Chen, Hao,Zhang, Lei,Ruo-Hong, Li,Liu, Yi,Sun, Jian-Fang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Neural precursor cell-expressed developmentally down-regulated 8 (NEDD8), a ubiquitin-like protein, mainly functions through covalent ligation to cullin proteins. Conjugation of NEDD8 with cullins can promote ubiquitination, which plays a critical role in the degradation of many proteins. UBA3 is the subunit of NEDD8-activating enzyme which is one of the keys for NEDD8 linkage to cullin proteins. Previous research showed NEDD8 conjugation to be up-regulated in highly proliferative cell lines. In the present study, up-regulated NEDD8 conjugation was observed in melanoma cell lines by Western blot analysis. After down-regulation with a RNAi to UBA3, proliferation of M14 was suppressed in vitro and in vivo. In conclusion, up-regulated NEDD8 conjugation may be involved in the development of melanoma. Interference in this pathway might offera promising method for melanoma therapy.

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study

Yi-Jou Tai,Yun-Yuan Chen,Huang-Cheng Hsu,Chun-Ju Chiang,San-Lin You,Chi-An Chen,Wen-Fang Cheng,Taiwan Cervical Cancer Control Task Force 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.4

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

The acrosswind response of the downwind prism in a twin-prism system with a staggered arrangement

Fang, Fuh-Min,Chung, Cheng-Yang,Li, Yi-Chao,Liu, Wen-Chin,Lei, Perng-Kwei Techno-Press 2013 Wind and Structures, An International Journal (WAS Vol.17 No.3

The flow interaction between two identical neighboring twin square prisms in a staggered arrangement in an open terrain was investigated experimentally. The downwind prism was mounted on a rigid-aeroelastic setup in an open-terrain boundary layer flow to measure its acrosswind root-mean-square responses and aerodynamic damping ratios. By varying the relative location of the upwind prism and the Scruton number associated with the downwind prism, the acrosswind aeroelastic behavior of the downwind prism was analyzed and compared to that of an isolated one. Results showed that the acrosswind root-mean-square response of the downwind prism could be either suppressed or enhanced by the wake flow produced by the neighboring upwind prism. Besides the assessment of the wake effect of the downwind prism, finally, regressed relationships were presented to describe the variation of the aerodynamic damping ratio so as to predict its acrosswind fluctuating response numerically.

Pathophysiological Mechanisms Underlying Unilateral Vocal Fold Paralysis in Female Patients: An Ultrasonographic Study

Yi-An Lu,Tuan-Jen Fang,Yu-Cheng Pei,Yun-Chen Tsai,Wan-Ni Lin 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

Objectives. Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal foldparalysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFPpatients to investigate the pathophysiologic mechanisms of UVFP. Methods. In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measuredusing B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode. Results. Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA)muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respec-tively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side,as observed through LEMG, correlated with the VF length during the resting phase (R =0.368, P =0.050) and CDVLvalues (R =0.627, P =0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlatedwith the normalized phonatory vocal length change (nPLC; R =0.621, P =0.041) on the paralyzed side. Conclusion. CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFPcases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The find-ings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngealnerve injury and offer valuable insights into the pathophysiology of UVFP.

Weekly topotecan chemotherapy in the treatment of recurrent ovarian cancer patients

( Wan Yi Huang ),( Wen Fang Cheng ),( Chang Yao Hsieh ),( Chi An Chen ) 대한산부인과학회 2007 대한산부인과학회 학술대회 Vol.93 No.-

Study on Cellar Behaviors on Different Nanostructures by Nanoporous Alumina Template

Chiung-Fang Huang,Yung-Kang Shen,Hsin-Chung Cheng,Yi Lin,Chih-Wei Wu 한국정밀공학회 2014 International Journal of Precision Engineering and Vol. No.

Nanoporous anodic aluminum oxide (AAO) templates are fabricated using an nodization method. The mean diameters of nanoporousanodic aluminum oxide templates are 100 nm and 200 nm by various processing parameters of the anodization method. A moldedplastic thin film nanostructure is fabricated by nanoimprinting using the AAO template as a mold insert. The surface properties ofthe molded plastic thin film are discussed using various nanoimprinting process parameters. Contact angles of the molded plastic thinfilm with the nanostructure exceed those without the nanostructure. The molded plastic thin films with a nanostructure and ahydrophobic surface are formed, and their contact angles exceed 90o. This study observes the behavior of osteoblast-like cells (MG63)cultured on nanostructure thin films, i.e., AAO, polylactic acid (PLA) and polycarbonate (PC). Cell growth behavior indicates thatthe AAO template with a 200 nm nanostructure is best. This study shows that cell adhesion and spreading are influenced by surfacetopography in the nanometer feature.

Chemopreventive and Chemotherapeutic Effect of Propolis and Its Constituents: A Mini-review

Hui-Fang Chiu,Yi-Chun Han,You-Cheng Shen,Oksana Golovinskaia,Kamesh Venkatakrishnan,Chin-Kun Wang 대한암예방학회 2020 Journal of cancer prevention Vol.25 No.2

Propolis is a bee wax rich in various phytocomponents and traditionally used to treat various ailments. Propolis is reported to possess an array of biological properties including anti-inflammatory, antioxidant, anti-cancer, and anti-diabetic as well as cardioprotective, hepatoprotective, renoprotective, and derma protective activities. A plethora of studies confirmed that propolis is effective against various types of cancer including head and neck, lung, liver, brain (glioma), pancreas, kidney, prostate, skin (melanoma), breast, oral, esophagus, gastric, colorectal, and bladder cancers. However, many researchers have demonstrated that propolis displays potent chemoprotective/chemopreventive or anti-cancer activity against only a few types of cancers like oral, gastrointestinal, dermal (melanoma), breast, and prostate cancers. Therefore, this mini-review only summarizes the chemopreventive/chemotherapeutic activities of propolis and its updated underlying mechanisms. Taken together, propolis displays potent chemoprotective or anti-cancer effect due to the presence of various phytocomponents which contribute to pro-apoptotic, cytotoxic, anti-proliferative (cell cycle arrest), anti-metastatic, anti-invasive, anti-angiogenic and anti-genotoxic or anti-mutagenic properties along with antioxidant, immunomodulatory, and anti-inflammatory functions. Hence, propolis could be used as an adjuvant for treating various cancers along with standard chemotherapeutic drugs. However, many large-scale clinical studies are needed to justify such applications.

TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome

Lanlan Fang,Yiran Li,Sijia Wang,Yuxi Li,Hsun-Ming Chang,Yuyin Yi,Yang-yang Sun,Avinash Thakur,Peter C. K. Leung,Jung-Chien Cheng,Ying-Pu Sun 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Ovarian hyperstimulation syndrome (OHSS) is one of the most serious and iatrogenic complications that can occur during in vitro fertilization treatment. Although the pathogenesis of OHSS is not fully understood, vascular endothelial growth factor (VEGF) has been recognized as an important mediator of the development of OHSS. Transforming growth factor-beta-1 (TGF-β1) is known to regulate various ovarian functions. However, whether VEGF can be regulated by TGF-β1 in human granulosa cells has not been determined. In addition, the role of TGF-β1 in the pathogenesis of OHSS remains unknown. In the present study, we demonstrate that TGF-β1 stimulates VEGF expression in and secretion from both immortalized human granulosa-lutein (hGL) cells and primary hGL cells. Our results demonstrate that the SMAD2/3, ERK1/2, and p38 MAPK signaling pathways are involved in TGF-β1-induced VEGF expression and secretion. Using a mouse OHSS model, we show that the expression levels of TGF-β1 and VEGF are increased in the ovaries of OHSS mice. Blocking TGF-β1 signaling inhibits the development of OHSS by attenuating VEGF expression. Moreover, clinical results reveal that the protein levels of TGF-β1 and VEGF are increased in the follicular fluid of patients with OHSS, and that the levels of these two proteins in the follicular fluid are positively correlated. The results of this study help to elucidate the mechanisms by which VEGF expression is regulated in hGL cells, which could lead to the development of alternative therapeutic approaches for treating OHSS.

Hypermethylation of TET1 Promoter Is a New Diagnosic Marker for Breast Cancer Metastasis

Sang, Yi,Cheng, Chun,Tang, Xiao-Feng,Zhang, Mei-Fang,Lv, Xiao-Bin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Breast cancer metastasis is a major cause of cancer-related death in women. However, markers for diagnosis of breast cancer metastasis are rare. Here, we reported that TET1, a tumor suppressor gene, was downregulated and hypermethylated in highly metastatic breast cancer cell lines. Moreover, silencing of TET1 in breast cancer cells increased the migration and spreading of breast cancer cells. In breast cancer clinical samples, TET1 expression was reduced in LN metastases compared with primary tissues. Besides, the methylation level of the TET1 promoter was increased significantly in LN metastases. Taken together, these findings indicate that promoter hypermethylation may contribute to the downregulation of TET1 and could be used as a promising marker for diagnosis in patients with breast cancer metastasis.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents

Ji Cheng Zhang,Jin Hua Wang,Jun Yi Liu,Qi Wei Guo,Jia Lin,Yi Lin Shen,Ke Xin Jia,Jia Jing Cai,Guo Ming Su,Ding Zhi Fang 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.11

Objective To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (<i>TNF-RII</i>) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents.Methods PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for <i>TNF-RII</i> rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods.Results G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD.Conclusion These results suggest reciprocal actions of <i>TNF-RII</i> rs1061622 with other factors on PTSD severity, interplays of <i>TNF-RII</i> rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of <i>TNF-RII</i> rs1061622 after experiencing traumatic events.