Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group

Yu-Li Chen,Kung-Liahng Wang,Min-Yu Chen,Mu-Hsien Yu,Chen-Hsuan Wu,Yu-Min Ke,Yi-Jen Chen,Yin-Yi Chang,Keng-Fu Hsu,Ming-Shyen Yen 대한부인종양학회 2013 Journal of Gynecologic Oncology Vol.24 No.1

Objective: To evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissuediagnosed endometrial hyperplasia. Methods: Between January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated. Results: Age ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors. Conclusion: Coexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.

The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings

Cheng-Chang Chang,Hui-Chen Wang,Yu-Ping Liao,Yu-Chih Chen,Yu-Chun Weng,Mu-Hsien Yu,Hung-Cheng Lai 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.1

Objective: We hypothesized that DNA methylation of development-related genes may occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in cervical scrapings. Methods: We tested methylation status by quantitative methylation-specific polymerase chain reaction for 14 genes in DNA pools of endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary, were verified in training set using cervical scrapings of 10 EC/10 OC patients and 10 controls, and further validated in the testing set using independent cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff values of methylation index (M-index) from cervical scrapings to distinguish between cancer patients and control. Sensitivity/specificity of DNA methylation biomarkers in detecting EC and OC was calculated. Results: Of 14 genes, 4 (PTGDR, HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is significantly higher that than in controls (2.85; p<0.001 and p=0.480, respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%–90% and 69%–75% for detection of EC, and 61% and 62%–69% for the detection of OC. Conclusion: The findings demonstrate the potential of EC/OC detection through testing for DNA methylation in cervical scrapings.

The EGF/hnRNP Q1 axis is involved in tumorigenesis via the regulation of cell cycle-related genes

Yu-Chu Wang,Kung-Chao Chang,Bo-Wen Lin,Jenq-Chang Lee,Chien-Hsien Lai,Li-Jyuan Lin,Yun Yen,Chang-Shen Lin,Shiang-Jie Yang,Peng-Chan Lin,Chung-Ta Lee,Liang-Yi Hung 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been implicated in many posttranscriptional processes, including RNA metabolism and mRNA splicing and translation. However, the role of hnRNP Q1 in tumorigenesis remains unclear. We previously performed RNA immunoprecipitation (RIP)-seq analysis to identify hnRNP Q1-interacting mRNAs and found that hnRNP Q1 targets a group of genes that are involved in mitotic regulation, including Aurora-A. Here, we demonstrate that altering the hnRNP Q1 level influences the expression of the Aurora-A protein, but not its mRNA. Stimulation with epidermal growth factor (EGF) enhances both binding between hnRNP Q1 and Aurora-A mRNA as well as the efficacy of the hnRNP Q1-induced translation of Aurora-A mRNA. The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways. In addition, we show that hnRNP Q1 up-regulates the translation of a group of spindle assembly checkpoint (SAC) genes. hnRNP Q1 overexpression is positively correlated with the levels of Aurora-A and the SAC genes in human colorectal cancer tissues. In summary, our data suggest that hnRNP Q1 plays an important role in regulating the expression of a group of cell cycle-related genes. Therefore, it may contribute to tumorigenesis by up-regulating the translation of these genes in colorectal cancer.

Exendin-4 improves resistance to Listeria monocytogenes infection in diabetic db/db mice

Hsien Yueh Liu,Chih-Yao Chung,Wen-Chin Yang,Chih-Lung Liang,Chi-Young Wang,Chih-Yu Chang,Cicero Lee-Tian Chang 대한수의학회 2012 Journal of Veterinary Science Vol.13 No.3

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.

Evaluation of Ride Comfort for Active Suspension System Based on Selftuning Fuzzy Sliding Mode Control

Chun-Yu Hsiao,Yu-Hsien Wang 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.4

This paper describes the application of a self-tuning fuzzy sliding mode controller (STFSMC) to design the control signal of an electro-hydraulic actuator under standard road excitation based on ISO 8608. The proposed damper was designed to achieve effective vibration isolation with an actuator force. The proposed damper was incorporated into a quarter-car system through experiments for the subsequent dynamic analysis of the suspension system. A single-input single-output (SISO) fuzzy inference was strategically used to regulate the slope of a sliding surface. In addition, the fuzzy control methodology was applied to achieve self-tuning online output of the scale factor of the fuzzy sliding mode controller. The comfortable riding time and ride comfort level were also evaluated based on ISO 2631-1. Experimental results revealed that the proposed controller demonstrated evident improvements in vehicle vibration suppression and the ride quality in comparison with passive and fuzzy logic controller control systems.

Comparison of the Infant and Adult Adipose-Derived Mesenchymal Stem Cells in Proliferation, Senescence, Anti-oxidative Ability and Differentiation Potential

Wu Szu-Hsien,Yu Jin-Huei,Liao Yu-Ting,Liu Kuo-Hao,Chiang En-Rung,Chang Ming-Chau,Wang Jung-pan 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.3

BACKGROUND: Infant adipose-derived mesenchymal stem cells (ADSCs) collected from excised polydactyly fat tissue, which was surgical waste, could be cultured and expanded in vitro in this study. In addition, the collecting process would not cause pain in the host. In this study, the proliferation, reduction of senescence, anti-oxidative ability, and differentiation potential in the infant ADSCs were compared with those in the adult ADSCs harvested from thigh liposuction to determine the availability of infant ADSCs. METHODS: Proliferation was determined by detecting the fold changes in cell numbers and doubling time periods. Senescence was analyzed by investigating the age-related gene expression levels and the replicative stress. The superoxide dismutase (SOD) gene expression, adipogenic, neurogenic, osteogenic, and tenogenic differentiation were compared by RTqPCR. The chondrogenic differentiation efficiency was also determined using RT-qPCR and immunohistochemical staining. RESULTS: The proliferation, SOD (SOD1, SOD2 and SOD3) gene expression, the stemness-related gene (c-MYC) and telomerase reverse transcriptase of the infant ADSCs at early passages were enhanced compared with those of the adults’. Cellular senescence related genes, including p16, p21 and p53, and replicative stress were reduced in the infant ADSCs. The adipogenic genes (PPARc and LPL) and neurogenic genes (MAP2 and NEFH) of the infant ADSC differentiated cells were significantly higher than those of the adults’ while the expression of the osteogenic genes (OCN and RUNX) and tenogenic genes (TNC and COL3A1) of both demonstrated opposite results. The chondrogenic markers (SOX9, COL2 and COL10) were enhanced in the infant ADSC differentiated chondrogenic pellets, and the expression levels of SODs were decreased during the differentiation process. CONCLUSION: Cultured infant ADSCs demonstrate less cellular senescence and replicative stress, higher proliferation rates, better antioxidant defense activity, and higher potential of chondrogenic, adipogenic and neurogenic differentiation.

Malignant transformation of ovarian mature cystic teratoma into squamous cell carcinoma: a Taiwanese Gynecologic Oncology Group (TGOG) study

An Jen Chiang,Min-Yu Chen,Chia-Sui Weng,Hao Lin,Chien-Hsing Lu,Peng-Hui Wang,Yu-Fang Huang,Ying-Cheng Chiang,Mu-Hsien Yu,Chih-Long Chang 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5

Objective: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT)to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiplemedical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, andprognostic factors of this disease and reviewed related literature. Methods: Pathological reports of 16,001 patients with primary ovarian cancer who weretreated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients withMT of MCT to SCC were identified. Results: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age ofpatients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40cm). We analyzed the patients in our study and those in the literature and determined thatearly identification and complete surgical resection of the tumor are essential for long-termsurvival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be usedto treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTsare suitable indicators predicting the risk of MT of MCT to SCC. Conclusion: Similar to general epithelial ovarian cancers, the early detection of MT of MCTto SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should beevaluated to exclude potential MT to SCC.

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

Po-Wei Lee,Tzu-Yun Wang,Yun-Hsuan Chang,Sheng-Yu Lee,Shiou-Lan Chen,Ze-Cheng Wang,Po See Chen,Chun-Hsien Chu,San-Yuan Huang,Nian-Sheng Tzeng,I Hui Lee,Kao Chin Chen,Yen Kuang Yang,Jau-Shyong Hong,Ru-B 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2+*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype. Conclusion: OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

Clinical Features and Computed Tomography Characteristics of Non-Klebsiella pneumoniae Liver Abscesses in Elderly (>65 Years) and Nonelderly Patients

Chih-Weim Hsiang,Wei-Chou Chang,Chang-Hsien Liu,Hsiu-Lung Fan,Kai-Hsiung Ko,Chih-Yung Yu,Hong-Hau Wang,Wen-I Liao,Hsian-He Hsu 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.2

Purpose: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. Materials and Methods: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and dividedinto two age groups: elderly (age ≥65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. Results: Elderly patients with non-KPLA were associatedwith a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were relatedto the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. Conclusion:In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.