114 results on '"Kuan-Ting Kuo"'
Search Results
2. Supplementary Data from DNA Copy Numbers Profiles in Affinity-Purified Ovarian Clear Cell Carcinoma
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Tian-Li Wang, Ie-Ming Shih, Robert J. Kurman, M. Joe Ma, Ruth Glas, Yue Wang, Kentaro Nakayama, Yuanjian Feng, Xu Chen, Tsui-Lien Mao, and Kuan-Ting Kuo
- Abstract
Supplementary Data from DNA Copy Numbers Profiles in Affinity-Purified Ovarian Clear Cell Carcinoma
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- 2023
3. Supplementary Figures, Tables and Methods from Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-Grade and High-Grade Carcinomas
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Tian-Li Wang, Ie-Ming Shih, Robert J. Kurman, Yue Wang, Natini Jinawath, Xu Chen, Tsui-Lien Mao, Yuanjian Feng, Bin Guan, and Kuan-Ting Kuo
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Supplementary Figures, Tables and Methods from Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-Grade and High-Grade Carcinomas
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- 2023
4. Data from Analysis of DNA Copy Number Alterations in Ovarian Serous Tumors Identifies New Molecular Genetic Changes in Low-Grade and High-Grade Carcinomas
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Tian-Li Wang, Ie-Ming Shih, Robert J. Kurman, Yue Wang, Natini Jinawath, Xu Chen, Tsui-Lien Mao, Yuanjian Feng, Bin Guan, and Kuan-Ting Kuo
- Abstract
Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, is thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations, whereas low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain unknown. In addition, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG, and HG tumors using high-density 250K single nucleotide polymorphism arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions, including homozygous deletions, were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4%, and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except for the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profile in HG serous carcinomas, which can serve as a molecular foundation to study tumor suppressors in ovarian cancer. [Cancer Res 2009;69(9):4036–42]
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- 2023
5. Clinical factors associated with prognosis in low-grade serous ovarian carcinoma: experiences at two large academic institutions in Korea and Taiwan
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Jun-Hyeok Kang, Wen-Fang Cheng, Yoo-Young Lee, Yen-Ling Lai, Hyun Soo Kim, Kuan-Ting Kuo, and Yu-Li Chen
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Multivariate analysis ,Neoplasm, Residual ,medicine.medical_treatment ,Taiwan ,lcsh:Medicine ,Disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Ovarian carcinoma ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Republic of Korea ,Medicine ,Humans ,In patient ,Stage (cooking) ,lcsh:Science ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Ovarian Neoplasms ,Chemotherapy ,Academic Medical Centers ,Multidisciplinary ,business.industry ,lcsh:R ,Cytoreduction Surgical Procedures ,Middle Aged ,Prognosis ,Progression-Free Survival ,Cystadenocarcinoma, Serous ,Survival Rate ,Serous fluid ,030104 developmental biology ,Risk factors ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Ovarian Serous Carcinoma ,Female ,lcsh:Q ,business - Abstract
Low-grade ovarian serous carcinoma (LGSOC) has clinical features different from high-grade serous ovarian carcinoma (HGSOC) accounting for the majority of epithelial ovarian cancer. Because of its rarity, previous studies have only focused on the high-grade disease without considering the differences between the two subtypes. This study aimed to evaluate the effect of the clinical prognostic factors known for HGSOC on survival in patients with LGSOC. Based on the Federation of Gynecology and Obstetrics (FIGO) stage, progression-free survival (PFS) was markedly decreased in advanced disease compared with early disease. For stage I, patients with stage IC had poorer survival than those with stage IA and IB regardless of the number of cycles of adjuvant chemotherapy. For advanced disease, no gross residual disease after primary cytoreductive surgery was significantly associated with longer PFS when compared with gross residual disease. In multivariate analysis for PFS and overall survival (OS), age, preoperative CA-125, time interval from surgery to chemotherapy, and the number of cycles of adjuvant chemotherapy were not associated with prognosis. Complete cytoreduction was the only independent prognostic factor for PFS (HR 2.45, p = 0.045). Our study revealed that the known prognostic factors in HGSOC did not show any effect on the survival in LGSOC except for FIGO stage and complete cytoreduction.
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- 2020
6. An experimental model for ovarian cancer: propagation of ovarian cancer initiating cells and generation of ovarian cancer organoids
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Yu-An Chen, Chen-Yu Lu, Wen-Fang Cheng, Kuan-Ting Kuo, Chen-Wei Yu, Hon-Nerng Ho, Hsin-Fu Chen, and Szu-Hua Pan
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Organoids ,Ovarian Neoplasms ,Cancer Research ,Oncology ,Cell Line, Tumor ,Genetics ,Animals ,Humans ,Apoptosis ,Female ,Carcinoma, Ovarian Epithelial ,Models, Theoretical - Abstract
Background Ovarian cancer (OC) is the most lethal gynecological cancer due to the recurrence of drug-resistance. Cancer initiating cells (CICs) are proposed to be responsible for the aggressiveness of OC. The rarity and difficulty of in vitro long-term cultivation of CICs challenge the development of CIC-targeting therapeutics. Reprogramming cancer cells into induced cancer initiating cell (iCICs) could be an approach to solve these. Several inducible CICs have been acquired by activating the expression of stemness genes in different cancer cells. However, few reports have demonstrated the feasibility in OC. Methods Patients with primary OC receiving surgery were enrolled. Tumor tissue were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunohistochemistry (IHC) staining to investigate the association of stemness markers with overall survival (OS). An high-grade serous ovarian cancer (HGSOC) cell line, OVCAR-3 was reprogrammed by transducing Yamanaka four factors OCT4, SOX2, KLF4 and MYC (OSKM) to establish an iOCIC model, iOVCAR-3-OSKM. CIC characteristics of iOVCAR-3-OSKM were evaluated by RT-PCR, sphere formation assay and animal experiments. Drug-resistance and migration ability were accessed by dye-efflux activity assay, MTT assay and migration assay. Gene profile was presented through RNA-sequencing. Lineage differentiation ability and organoid culture were determined by in vitro differentiation assays. Results In OC patients, the co-expression of multiple stem-related transcription factors (OCT4, SOX2, and NANOG) was associated with worse OS. iOVCAR-3-OSKM cells generated by reprogramming successfully exhibited stemness characteristics with strong sphere-forming and tumorigenesis ability. iOVCAR-3-OSKM cells also showed malignant potential with higher drug resistance to chemodrug, Paclitaxel (PTX) and migration ability. iOVCAR-3-OSKM was maintainable and expandable on feeder-dependent culture condition, it also preserved ovarian lineage differentiation abilities, which could well differentiate into OC cells with CK-7 and CA125 expressions and develop into an organoid mimic poor prognostic OC histological feature. Conclusions The establishment of iOVCAR-3-OSKM not only allows us to fill the gap in the information on induced CICs in OC but also provides a potential strategy to develop personalized CICs and organoid models for treating OC in the near future.
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- 2022
7. Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer
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Kuan-Ting Kuo, Feng-Yi Ke, Yu-Chyi Hwang, Han-Chung Wu, Wan-Yu Chen, and Ming-Chieh Lin
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0301 basic medicine ,Cancer Research ,endocrine system diseases ,Integrin alpha3 ,Apoptosis ,Carboplatin ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Basic and Clinical Immunology ,Ovarian carcinoma ,Tumor Cells, Cultured ,Ovarian Neoplasms ,Mice, Inbred BALB C ,biology ,Antibodies, Monoclonal ,General Medicine ,Prognosis ,female genital diseases and pregnancy complications ,ovarian cancer ,Oncology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Original Article ,Female ,Antibody ,Cyclin-Dependent Kinase Inhibitor p21 ,Paclitaxel ,medicine.drug_class ,Monoclonal antibody ,Cell Line ,03 medical and health sciences ,laminin ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,cell apoptosis ,integrin α3 ,business.industry ,focal adhesion kinase ,Carcinoma ,medicine.disease ,HCT116 Cells ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Tumor progression ,monoclonal antibody ,Cancer cell ,biology.protein ,Cancer research ,Neoplasm Recurrence, Local ,Tumor Suppressor Protein p53 ,Ovarian cancer ,business - Abstract
Ovarian cancer has a high recurrence rate after platinum‐based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer‐specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV‐3, and generated hybridoma clones. Several rounds of screening yielded 30 monoclonal antibodies (mAbs) with no cross‐reactivity to normal cells. Among these mAbs, OV‐Ab 30‐7 was found to target integrin α3 and upregulate p53 and p21, while stimulating the apoptosis of cancer cells. We further found that binding of integrin α3 by OV‐Ab 30‐7 impaired laminin‐induced focal adhesion kinase phosphorylation. The mAb alone or in combination with carboplatin and paclitaxel inhibited tumor progression and prolonged survival of tumor‐bearing mice. Moreover, immunohistochemical staining of ovarian patient specimens revealed higher levels of integrin α3 in cancer cells compared with normal cells. By querying online clinical databases, we found that elevated ITGA3 expression in ovarian cancer is associated with poor prognosis. Taken together, our data suggest that the novel mAb, OV‐Ab 30‐7, may be considered as a potential therapeutic for ovarian cancer., The novel mAb, OV‐Ab 30‐7, can induce ovarian cancer cell apoptosis, and blockage integrin‐laminin signaling, and may be considered as a potential therapeutic for ovarian cancer.
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- 2020
8. 29‐2: Invited Paper: Mechanics of Bendable Glass Substrates
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Timothy Michael Gross, Toshihiko Ono, Kuan-Ting Kuo, Lezzi Peter Joseph, and Coble Claire Renata
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Thin glass ,Puncture resistance ,Materials science ,Composite material - Published
- 2020
9. 23‐2: Distinguished Paper: Wrap‐around Electrodes for MicroLED Tiled Displays
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Haregewine Tadesse, Tetyana Buchholz, Sean M. Garner, Kuan Ting Kuo, David A. Pastel, Jamie Curtis, Rajesh Vaddi, Sijan Khan, and Richard Curwood Peterson
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Thesaurus (information retrieval) ,Computer science ,Computer graphics (images) ,MicroLED ,Wrap around - Published
- 2020
10. Wrap‐around electrodes for microLED tiled displays
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Haregewine Tadesse, Sijan Khan, Rajesh Vaddi, Richard Curwood Peterson, Jamie Curtis, David A. Pastel, Tetyana Buchholz, Sean M. Garner, and Kuan Ting Kuo
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Materials science ,business.industry ,Electrode ,Wrap around ,MicroLED ,Optoelectronics ,Electrical and Electronic Engineering ,business ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Published
- 2020
11. Frequent CTNNB1 or PIK3CA Mutations Occurred in Endometrial Endometrioid Adenocarcinoma With High Levels of Microsatellite Instability and Loss of MSH2/MSH6 Expression
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Ming-Chieh Lin, Hsien-Neng Huang, Tsui-Lien Mao, Chun-Wei Kuo, and Kuan-Ting Kuo
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Adult ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Histology ,Class I Phosphatidylinositol 3-Kinases ,Biology ,MLH1 ,medicine.disease_cause ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,medicine ,PMS2 ,Humans ,neoplasms ,beta Catenin ,Aged ,Aged, 80 and over ,Mutation ,nutritional and metabolic diseases ,Microsatellite instability ,Middle Aged ,medicine.disease ,digestive system diseases ,Endometrial Neoplasms ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MSH6 ,Medical Laboratory Technology ,MutS Homolog 2 Protein ,030104 developmental biology ,MSH2 ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Microsatellite Instability ,DNA mismatch repair ,KRAS ,Carcinoma, Endometrioid - Abstract
Background DNA mismatch repair (MMR) proteins form 2 heterodimers-MutSα formed by MSH2 and MSH6, and MutLα by MLH1 and PMS2. In endometrial endometrioid adenocarcinomas, cases with MMR protein defect also usually harbor other recurrent genetic mutations of the neoplasm. However, it remains unknown whether defects of the 2 functionally different heterodimers are linked to mutations in different genes. We aimed to study the MMR protein expression, microsatellite instability (MSI), and other common genetic mutations of endometrial endometrioid adenocarcinoma. Materials and methods We investigated the MSI status of 107 endometrial endometrioid adenocarcinoma patients. MMR protein expression, and mutation of KRAS, CTNNB1, and PIK3CA were also evaluated by immunohistochemistry and sequencing. Results An overall 34.6% (37/107) of endometrial endometrioid adenocarcinomas were MSI-H. All MSI-H tumors exhibited loss of MMR protein expression (loss of MLH1, PMS2, MSH6, and MSH2 was noted in 22, 25, 12, and 7 cases, respectively). CTNNB1, PIK3CA, and KRAS mutation were present in 9, 7, and 7 MSI-H tumors. Compared with patients with loss of PMS2 and/or MLH1 expression, patients with loss of MSH6 and/or MSH2 expression were associated with higher frequencies of CTNNB1 mutation (P=0.036) and PIK3CA mutation (P=0.025). Conclusions In MSI-H endometrial endometrioid adenocarcinomas, different types of MMR protein deficiency indicate different molecular genetic alterations.
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- 2020
12. Effects of convection-SST interactions on the South China Sea summer monsoon onset in a multiscale modeling framework model
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Kuan-Ting Kuo, Chien-Ming Wu, and Wei-Ting Chen
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Convection ,lcsh:Geology ,Atmospheric Science ,South china ,Climatology ,lcsh:QE1-996.5 ,Earth and Planetary Sciences (miscellaneous) ,lcsh:G1-922 ,Oceanography ,Monsoon ,Multiscale modeling ,Geology ,lcsh:Geography (General) - Abstract
The present study explores the effects of convection-SST interactions on the onset of the South China Sea Summer Monsoon simulated by the superparameterized Community Atmosphere Model (SPCAM). The SPCAM is a global multi-scale modeling framework that embeds a 2-D cloud-resolving model in each grid column to replace the conventional convective parameterization. Two experiments are performed: CTRL uses prescribed sea surface temperature climatology, and CPL is coupled to a slab ocean model (SOM). The bias of excessive seasonal mean precipitation over Asia during boreal summer in CTRL is reduced in CPL. In the South China Sea, the seasonal evolution of precipitation and 850 hPa winds is more realistic in the coupled simulation. During the pre-onset stage, the mean pattern of synoptic flow and precipitation, as well as the land-ocean diurnal cycle contrast is also improved in CPL. The coupling to SOM does not change the sensitivity of precipitation to column moisture in the SPCAM. The improvements in CPL can be partly attributed to the lower SST in response to air-sea interactions, and also partly to the suppression of heavy precipitation under high SST regime likely associated with a different atmospheric meridional circulation. Our current results demonstrated that the SPCAM coupled with SOM could be a potential tool to study the interactions among convection, SST, and large-scale atmospheric circulation from seasonal to sub-seasonal time scales.
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- 2020
13. Convective Transition Statistics over Tropical Oceans for Climate Model Diagnostics: GCM Evaluation
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J. David Neelin, Y. H. Kuo, Andrew Gettelman, Leo J. Donner, Kathleen A. Schiro, Wei-Ting Chen, Eric D. Maloney, Xianan Jiang, Chien-Ming Wu, Kuan-Ting Kuo, Charles J. Seman, Yi Ming, Carlos R. Mechoso, Chih-Chieh Chen, and Ming Zhao
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Convection ,Atmospheric Science ,010504 meteorology & atmospheric sciences ,GCM transcription factors ,Madden–Julian oscillation ,Entrainment (meteorology) ,010502 geochemistry & geophysics ,01 natural sciences ,Convective parameterization ,Atmosphere ,Statistics ,Environmental science ,Climate model ,Precipitation ,0105 earth and related environmental sciences - Abstract
To assess deep convective parameterizations in a variety of GCMs and examine the fast-time-scale convective transition, a set of statistics characterizing the pickup of precipitation as a function of column water vapor (CWV), PDFs and joint PDFs of CWV and precipitation, and the dependence of the moisture–precipitation relation on tropospheric temperature is evaluated using the hourly output of two versions of the GFDL Atmospheric Model, version 4 (AM4), NCAR CAM5 and superparameterized CAM (SPCAM). The 6-hourly output from the MJO Task Force (MJOTF)/GEWEX Atmospheric System Study (GASS) project is also analyzed. Contrasting statistics produced from individual models that primarily differ in representations of moist convection suggest that convective transition statistics can substantially distinguish differences in convective representation and its interaction with the large-scale flow, while models that differ only in spatial–temporal resolution, microphysics, or ocean–atmosphere coupling result in similar statistics. Most of the models simulate some version of the observed sharp increase in precipitation as CWV exceeds a critical value, as well as that convective onset occurs at higher CWV but at lower column RH as temperature increases. While some models quantitatively capture these observed features and associated probability distributions, considerable intermodel spread and departures from observations in various aspects of the precipitation–CWV relationship are noted. For instance, in many of the models, the transition from the low-CWV, nonprecipitating regime to the moist regime for CWV around and above critical is less abrupt than in observations. Additionally, some models overproduce drizzle at low CWV, and some require CWV higher than observed for strong precipitation. For many of the models, it is particularly challenging to simulate the probability distributions of CWV at high temperature.
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- 2020
14. A DNA Damage Response Gene Panel for Different Histologic Types of Epithelial Ovarian Carcinomas and Their Outcomes
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Po-Han Lin, Wen-Fang Cheng, Yi-Jou Tai, Chia-Yi Lee, Chi-An Chen, Kuan-Ting Kuo, Tzu-Pin Lu, Chia Ying Wu, Hung Shen, Heng-Cheng Hsu, and Ying-Cheng Chiang
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Genome instability ,epithelial ovarian cancer ,endocrine system diseases ,Serous carcinoma ,QH301-705.5 ,Medicine (miscellaneous) ,Gene mutation ,medicine.disease_cause ,DNA damage response ,General Biochemistry, Genetics and Molecular Biology ,Article ,Germline mutation ,Carcinoma ,Medicine ,somatic mutation ,Biology (General) ,Mutation ,clear cell carcinoma ,business.industry ,medicine.disease ,female genital diseases and pregnancy complications ,body regions ,Serous fluid ,Clear cell carcinoma ,Cancer research ,business - Abstract
DNA damage response (DDR) is important for maintaining genomic integrity of the cell. Aberrant DDR pathways lead to accumulation of DNA damage, genomic instability and malignant transformations. Gene mutations have been proven to be associated with epithelial ovarian cancer, and the majority of the literature has focused on BRCA. In this study, we investigated the somatic mutation of DNA damage response genes in epithelial ovarian cancer patients using a multiple-gene panel with next-generation sequencing. In all, 69 serous, 39 endometrioid and 64 clear cell carcinoma patients were enrolled. Serous carcinoma patients (69.6%) had higher percentages of DDR gene mutations compared with patients with endometrioid (33.3%) and clear cell carcinoma (26.6%) (p <, 0.001, chi-squared test). The percentages of DDR gene mutations in patients with recurrence (53.9 vs. 32.9% p = 0.006, chi-squared test) or cancer-related death (59.2 vs. 34.4% p = 0.001, chi-squared test) were higher than those without recurrence or living patients. In endometrioid carcinoma, patients with ≥2 DDR gene mutations had shorter PFS (p = 0.0035, log-rank test) and OS (p = 0.015, log-rank test) than those with one mutation or none. In clear cell carcinoma, patients with ≥2 DDR gene mutations had significantly shorter PFS (p = 0.0056, log-rank test) and OS (p = 0.0046, log-rank test) than those with 1 DDR mutation or none. In the EOC patients, somatic DDR gene mutations were associated with advanced-stage tumor recurrence and tumor-related death. Type I EOC patients with DDR mutations had an unfavorable prognosis, especially for clear cell carcinoma.
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- 2021
15. Prediction of Human Intention in Vehicles, Pedestrians and Bicyclists Interactions
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Rosa H. M. Chan, Chi-Sheng Shih, Kuan-Ting Kuo, Tsung-Yu Chen, Hsiang-Jui Lin, and Qi Liu
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Human–computer interaction ,Computer science ,SAFER ,Advanced driver ,Road user - Abstract
Predicting human intention in vehicles, pedestrians and bicyclists interactions can help autonomous vehicles and human drivers to plan their routes in a safer manner and better optimise the use of road space. Several studies have studied human intention when interacting with other agents at crossroads using handcrafted features, motif analyses, and machine learning approaches. Yet, many of them are limited in accuracy due to relatively insufficient consideration of surrounding agents and limited observations (occlusions and inaccurate estimation of pose and location) confined by camera angles. This study utilised a multi-branch Gated Recurrent Unit encoder-decoder (MBGED) model to predict the intention of pedestrians and bicyclists when contenting with vehicles at intersections by analysing the properties of directly and indirectly involved road agents. This study identified decisive factors of human intention and constructed an encoder-decoder architecture based on those factors. The network was trained, validated, and tested on unsignalised and uncontrolled intersections. The system predicted the intention of vulnerable road users with 96% accuracy, 91% precision, and 93% recall at 2 seconds before the intersections happen, which could provide a reliable reference for autonomous vehicle navigation and advanced driver assistant systems.
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- 2021
16. High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia
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Ann-Lii Cheng, Kuan-Ting Kuo, Jean Paul Thiery, Eric Y. Chuang, Chiun-Sheng Huang, I-Chun Chen, Yen-Shen Lu, Tzu-Pin Lu, Ko-Yun Lo, Ruby Yun-Ju Huang, Chen Cy, and Ching-Hung Lin
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Estrogen receptor ,Article ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Immune system ,Internal medicine ,Cancer genomics ,medicine ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,East Asia ,Copy-number variation ,RC254-282 ,Tumor microenvironment ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,business - Abstract
In East Asia, the breast cancer incidence rate among women aged APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related– and GE–related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOA1, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumor-infiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged
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- 2021
17. Factors Influencing the Discordancy Between Intraoperative Frozen Sections and Final Paraffin Pathologies in Ovarian Tumors
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Hung Shen, Heng-Cheng Hsu, Yi-Jou Tai, Kuan-Ting Kuo, Chia-Ying Wu, Yen-Ling Lai, Ying-Cheng Chiang, Yu-Li Chen, and Wen-Fang Cheng
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Cancer Research ,medicine.medical_specialty ,Gastroenterology ,paraffin pathology ,03 medical and health sciences ,Ovarian tumor ,0302 clinical medicine ,Internal medicine ,Ascites ,medicine ,Sampling (medicine) ,discordancy of diagnosis ,RC254-282 ,Original Research ,Frozen section procedure ,030219 obstetrics & reproductive medicine ,business.industry ,Medical record ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,intraoperative frozen pathology ,medicine.disease ,Menopause ,ovarian cancer ,Oncology ,030220 oncology & carcinogenesis ,ovarian tumor ,Mann–Whitney U test ,medicine.symptom ,Ovarian cancer ,business - Abstract
AimTo retrospectively investigate the pre-operative clinical factors and ultrasonographic features that influence the accuracy of the intraoperative frozen section (IFS) of ovarian tumors.Patients and methodsWomen with ovarian tumors that underwent IFS in one tertiary medical center were recruited from January 2010 to December 2018. Demographic and clinical data of these women were retrieved from medical records in the hospital’s centralized database.ResultsA total of 903 ovarian tumors were enrolled, including 237 (26.2%) benign, 150 (16.6%) borderline tumor, and 516 (57.2%) malignant. The overall accuracy of IFS among all specimens was 89.9%. The sensitivities of IFS in diagnosing borderline tumors (82.0%) and malignant tumors (88.2%) were lower than in diagnosing benign tumors (98.7%, p vs. 51.5 ± 11.8 years, p = 0.013, Mann–Whitney U test), and higher percentage of early-stage disease (85.2% vs. 65.1%, p = 0.001, chi-square test) and mucinous (39.3% vs. 3.3%) and endometrioid histologic types (34.4% vs. 20.2%) than the concordant group (all by chi-square test). Menopause (OR 0.34, 95% CI 0.15–0.76, p = 0.009), multicystic tumor in ultrasound (OR 2.14, 95% CI 1.14–4.01, p = 0.018), and ascites existence (OR 0.33, 95% CI 0.14–0.82, p = 0.016) were factors related to the discordant IFS by multivariate analysis.ConclusionsIFS has good accuracy in the diagnosis of ovarian tumors. We recommend more frozen tissue sampling for sonographic multicystic tumors in premenopausal women to improve the accuracy of IFS.
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- 2021
18. Seroprevalence Surveys for Anti-SARS-CoV-2 Antibody in Different Populations in Taiwan With Low Incidence of COVID-19 in 2020 and Severe Outbreaks of SARS in 2003
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Wen-Pin Tseng, Jhong-Lin Wu, Chen-Chi Wu, Kuan-Ting Kuo, Chien-Hao Lin, Ming-Yi Chung, Ya-Fan Lee, Bey-Jing Yang, Chien-Hua Huang, Shey-Ying Chen, Chong-Jen Yu, Shyr-Chyr Chen, and Po-Ren Hsueh
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,cross-reactivity ,Cross-sectional study ,030106 microbiology ,Immunology ,Taiwan ,Cross Reactions ,Antibodies, Viral ,Severe Acute Respiratory Syndrome ,Disease Outbreaks ,03 medical and health sciences ,0302 clinical medicine ,Seroepidemiologic Studies ,Internal medicine ,Epidemiology ,Pandemic ,medicine ,Seroprevalence ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,skin and connective tissue diseases ,Original Research ,SARS ,seroprevalence ,Transmission (medicine) ,business.industry ,SARS-CoV-2 ,Incidence (epidemiology) ,Incidence ,fungi ,Outbreak ,COVID-19 ,RC581-607 ,Middle Aged ,body regions ,Cross-Sectional Studies ,Immunoglobulin G ,Female ,Immunologic diseases. Allergy ,business - Abstract
Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti−SARS−CoV−2 total and IgG antibodies in all participants were determined by Roche Elecsys® Anti−SARS−CoV−2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN recomLine SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.
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- 2021
19. Clinicopathologic Characterization of GREB1-rearranged Uterine Sarcomas With Variable Sex-Cord Differentiation
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Yun Ru Liu, Yi Jia Lin, Kuan-Ting Kuo, Stephen Yip, Tzu-Pin Lu, Cheng-Han Lee, Yu-Chien Kao, Tom Wei-Wu Chen, Chia Ying Chu, Yung Chuan Chung, Shih Chen Yu, Jen-Chieh Lee, Yi-Wen Hsiao, Wan Ru Lee, Tsung Han Hsieh, Amy Lum, Hsuan-Ying Huang, Cher-Wei Liang, and Yung-Ming Jeng
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0301 basic medicine ,Receptors, Steroid ,Pathology ,Cellular differentiation ,Fusion gene ,Nuclear Receptor Coactivator 2 ,Nuclear Receptor Coactivator 1 ,0302 clinical medicine ,In Situ Hybridization, Fluorescence ,Gene Rearrangement ,Ovarian Neoplasms ,Receptors, Thyroid Hormone ,Myometrium ,Cell Differentiation ,Sarcoma ,Karyotype ,Middle Aged ,Prognosis ,Neoplasm Proteins ,Tumor Burden ,DNA-Binding Proteins ,Phenotype ,030220 oncology & carcinogenesis ,Uterine Neoplasms ,Female ,Gene Fusion ,Anatomy ,Calretinin ,medicine.medical_specialty ,Taiwan ,Mitosis ,Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,Proto-Oncogene Proteins ,Biomarkers, Tumor ,medicine ,Humans ,Sex Cord-Gonadal Stromal Tumors ,Genetic Predisposition to Disease ,Aged ,Uterine sarcoma ,Sequence Analysis, RNA ,Mesenchymal stem cell ,Gene rearrangement ,medicine.disease ,Repressor Proteins ,030104 developmental biology ,Karyotyping ,Surgery - Abstract
Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5'-ESR1/GREB1 and 3'-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, α-inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.
- Published
- 2019
20. Mosaic paternal haploidy in a patient with pancreatoblastoma and Beckwith-Wiedemann spectrum
- Author
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Kuan-Ting Kuo, Mu-Zon Wu, Wen-Yu Tsai, Yi-Ching Tung, Yung-Li Yang, Cheng-Ting Lee, Yi-Ning Su, Wuh-Liang Hwu, Ni-Chung Lee, Jin-Chung Shih, Yiin-Jeng Jong, Huey-Ling Chen, Shih-Yao Liu, Ming Chen, and Wen-Hsi Lin
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Beckwith-Wiedemann Syndrome ,Genotype ,Placenta ,Beckwith–Wiedemann syndrome ,Pancreatoblastoma ,Haploidy ,030105 genetics & heredity ,Biology ,Polymorphism, Single Nucleotide ,Placental Mesenchymal Dysplasia ,Mesoderm ,03 medical and health sciences ,Pregnancy ,Pancreatic cancer ,Genetics ,medicine ,Humans ,Allele ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,medicine.diagnostic_test ,Mosaicism ,Chromosomes, Human, Pair 11 ,Haplotype ,Infant, Newborn ,Infant ,DNA Methylation ,Uniparental Disomy ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Chromosomes, Human, Pair 2 ,Paternal Inheritance ,Female ,Pancreas ,Fluorescence in situ hybridization - Abstract
Pancreatoblastoma is a rare type of pancreatic cancer in children. Here, we describe a case in which Beckwith-Wiedemann syndrome (BWS) was first suspected because of placental mesenchymal dysplasia. Although the baby did not show the stigmata characteristic of BWS or abnormal peripheral blood methylation, she developed a massive pancreatoblastoma 2 months later. She survived after partial excision of the tumor and chemotherapy. The methylation pattern of the pancreatoblastoma tissue was typical of BWS. Single nucleotide polymorphism (SNP) array analyzes revealed that the pancreatoblastoma tissue had genome-wide loss of maternal alleles. Peripheral blood and nontumor pancreatic tissue showed normal biparental genomic contribution. Interphase fluorescence in situ hybridization analysis with centromeric probes for chromosomes 2 and 11 revealed haploid pancreatoblastoma cells, whereas the placental mesenchymal dysplasia tissue and nontumor pancreas tissue showed diploidy. SNP genotype analysis suggested the presence of mosaicism with the pancreatoblastoma tissue having a different paternal haplotype than that of the peripheral blood and nontumor pancreatic tissue. We report for the first time mosaic paternal haploidy associated with pancreatoblastoma. Babies with placental mesenchymal dysplasia, even those without a definitive diagnosis of BWS, need to be closely followed for the occurrence of embryonic tumors.
- Published
- 2019
21. The Precipitation Hotspots of Afternoon Thunderstorms over the Taipei Basin: Idealized Numerical Simulations
- Author
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Chien-Ming Wu and Kuan-Ting Kuo
- Subjects
Atmospheric Science ,Deep convection ,Sea breeze ,Climatology ,Thunderstorm ,Environmental science ,Precipitation ,Structural basin - Published
- 2019
22. Outbreak of Microsporidial Keratoconjunctivitis Associated With Water Contamination in Swimming Pools in Taiwan
- Author
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Pei-Chun Lin, Po-Ren Hsueh, I-Jong Wang, Wen-Yi Wang, Kuan-Ting Kuo, Fung-Rong Hu, Tai-Fen Lee, and Hsiao-Sang Chu
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,Keratoconjunctivitis ,Taiwan ,Levofloxacin ,Microsporidiosis ,Betamethasone ,Polymerase Chain Reaction ,Stain ,Disease Outbreaks ,law.invention ,03 medical and health sciences ,Swimming Pools ,0302 clinical medicine ,law ,RNA, Ribosomal, 16S ,medicine ,Humans ,Glucocorticoids ,Retrospective Studies ,business.industry ,Outbreak ,Eye infection ,medicine.disease ,Anti-Bacterial Agents ,Drug Combinations ,Ophthalmology ,030104 developmental biology ,Gram staining ,Microsporidia ,030221 ophthalmology & optometry ,Female ,Ophthalmic Solutions ,Water Microbiology ,business ,Eye Infections, Fungal ,medicine.drug - Abstract
Purpose To report an outbreak of microsporidial keratoconjunctivitis resulting from a swimming pool in Taiwan. Design Retrospective case series. Methods The records of 13 teenagers (15 eyes) contracting microsporidial keratoconjunctivitis after swimming in a local swimming pool were reviewed. Corneal scrapings were collected in all eyes at a tertiary referred hospital in June 2017. Gram stain, modified Kinyoun acid-fast stain, polymerase chain reaction (PCR), and gene analysis of the microsporidian 16S ribosomal RNA (rRNA) were examined in all 15 cases. Results Symptoms occurred 1–12 days after the water contact. At presentation, all eyes showed nonpurulent conjunctivitis and small, plaque-like epithelial lesions peripherally (n = 6), centrally (n = 3), both peripherally and centrally (n = 5), or centrally with superficial punctate keratopathy (n = 1). During the follow-up period, 10 eyes developed central superficial punctate keratopathy (n = 6) or subepithelial haze or infiltrates, which were distributed centrally (n = 2) or peripherally (n = 3), following development of plaque-like epithelial lesions. The results of Gram stain and modified Kinyoun's acid-fast stain were confirmatory in 10 cases (67%). All 15 cases yielded positive PCR results and were all identified to be Vittaforma corneae. All followed-up eyes healed without sequelae using topical levofloxacin and betamethasone eye drops. Conclusions Microsporidial keratoconjunctivitis can develop from contact with swimming pool water. The clinical course initially manifested as rapidly resolving conjunctivitis and peripheral plaque-like epithelial lesions, followed by paracentral or central plaque-like epithelial lesions, which evolved into subepithelial haze or infiltrates.
- Published
- 2018
23. Comprehensive screening forMED12mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours
- Author
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Chen Hui Lee, Yu-Chien Kao, Ming Chieh Lin, Kuan-Ting Kuo, Hsuan-Ying Huang, Cheng-Han Lee, Jen-Chieh Lee, Chang Tsu Yuan, and Wen Chih Huang
- Subjects
Adult ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Histology ,Genotype ,Genital Neoplasms, Female ,DNA Mutational Analysis ,Laser Capture Microdissection ,Biology ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,MED12 ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,medicine ,Humans ,Adenomyosis ,Nuclear atypia ,YWHAE ,In Situ Hybridization, Fluorescence ,Aged ,Mediator Complex ,Splice site mutation ,Endometrial stromal sarcoma ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Adenosarcoma ,Cancer research ,Female ,Neoplasms, Connective and Soft Tissue - Abstract
Aims MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED12 mutations in uncommon gynaecological mesenchymal tumours. Methods and results Sixty-eight uncommon gynaecological mesenchymal tumours were genotyped for MED12 exon 2, including 27 Mullerian adenosarcomas (including three tentatively diagnosed as ‘variant adenosarcomas’), six cellular angiofibromas, six aggressive angiomyxomas, five angiomyofibroblastomas, five superficial myofibroblastomas, five atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, and fluorescence in-situ hybridization (FISH) for JAZF1, PHF1 and YWHAE rearrangement, were performed on selected cases. The three ‘variant adenosarcomas’ harboured MED12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF1–SUZ12 or JAZF1–PHF1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild-type. The three MED12-mutated ‘variant adenosarcomas’ showed distinctive morphological features, including ‘fibromyomatous’ cytomorphology, a close association with adenomyosis, clustered thick-walled vessels, focal conspicuous hyalinization, and intralymphovascular tumour growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes-like architecture, were inconspicuous. All three cases showed immunoreactivity for desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course. Conclusions These MED12-mutated adenosarcoma-like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.
- Published
- 2017
24. Electrophysiological parameters that contribute to the pathogenesis of familial amyloid polyneuropathy caused by transthyretin mutations
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Hsing-Jung Lai, Ming-Jen Lee, Wan-Ting Lai, Kuan-Ting Kuo, and Lu Jin
- Subjects
Genetically modified mouse ,medicine.medical_specialty ,Amyloid ,Transgene ,Mice, Transgenic ,Hindlimb ,Pathogenesis ,03 medical and health sciences ,Myelin ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,Prealbumin ,030212 general & internal medicine ,Amyloid Neuropathies, Familial ,biology ,Chemistry ,Sodium channel ,Axons ,Transthyretin ,Endocrinology ,Rheobase ,medicine.anatomical_structure ,Neurology ,Mutation ,biology.protein ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
Familial amyloid polyneuropathy (FAP) is a rare, hereditary peripheral neuropathy commonly caused by mutations in human transthyretin (TTR) gene. Clinically, FAP caused by TTR mutations (TTR-FAP) involves both large and small nerve fibers. Details of early electrophysiological features in TTR-FAP remain unclear. To address this issue, we evaluated nerve excitability (NET) results in motor axons of control mice and two transgenic mouse models carrying V30M (TTRV30M) or A97S (TTRA97S) mutations that simulate clinical features of TTR-FAP. Transgenic TTRV30M and TTRA97S mice demonstrated significant increases in latency in hindlimb withdraw tests, as well as, poor rotarod test performance, compared to TTRORF mice. NET evaluation showed reduced S2 accommodation, and increased TEdundershoot during threshold electrotonus (TE) in motor axons of both TTRV30M and TTRA97S mice, indicating that axonal membranes were in a depolarized state. Decreased rheobase combined with increased refractoriness in the transgenic mice suggested that there were reduced sodium currents. Further immunohistochemical study of the sciatic nerves revealed the significantly decrease of voltage-gated sodium channel expression in the transgenic mice. Moreover, superexcitability during the recovery cycle is significantly increased in transgenic mice compared with control mice, which is attributed to increased internodal capacitance. Finally, the electron microscopy demonstrated the reduced g-ratio in TTRA97S mice may correlate with an atrophic change of axons and/or increase of myelin thickness. In summary, we evaluated NET results in transgenic mice which modeled the clinical features presented in TTR-FAP patients. Reduced sodium channel expression and increased internodal capacitance are factors contributing to the electrophysiological changes in TTR-FAP.
- Published
- 2019
25. IgG4-related Ophthalmic Disease in Idiopathic Sclerosing and Non-Sclerosing Orbital Inflammation: A 25-Year Experience
- Author
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Chia-Ying Tsai, Yi-Hsuan Wei, Kenneth Chang, Shu-Lang Liao, Kuan-Ting Kuo, Anny M. S. Cheng, and Hsiao-Ching Chang
- Subjects
medicine.medical_specialty ,genetic structures ,Treatment outcome ,Inflammation ,Autoimmune Diseases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Orbital Pseudotumor ,parasitic diseases ,medicine ,Humans ,Orbital Myositis ,Retrospective Studies ,integumentary system ,business.industry ,fungi ,Idiopathic orbital inflammation ,Dermatology ,Immunohistochemistry ,Sensory Systems ,Ophthalmology ,Immunoglobulin G ,030221 ophthalmology & optometry ,sense organs ,Ophthalmic disease ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Follow-Up Studies ,Forecasting - Abstract
Purpose: To determine the prevalence, clinical manifestations, and treatment outcomes of IgG4-related ophthalmic disease (IgG4-ROD) in previously diagnosed idiopathic orbital inflammation (IOI).Mat...
- Published
- 2019
26. Developing a Prognostic Gene Panel of Epithelial Ovarian Cancer Patients by a Machine Learning Model
- Author
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Kuan-Ting Kuo, Chen Cy, Ming-Cheng Chang, Chi-An Chen, Wen-Fang Cheng, Yu Hao Hu, Hsiu-Ping Lin, Ying-Cheng Chiang, and Tzu-Pin Lu
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Microarray ,medicine.medical_treatment ,chemotherapy ,lcsh:RC254-282 ,Article ,predictive model ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cancer genome ,Gene panel ,medicine ,Epithelial ovarian cancer ,Chemotherapy ,Tumor size ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Clinical trial ,030104 developmental biology ,ovarian cancer ,machine learning ,030220 oncology & carcinogenesis ,business ,Ovarian cancer ,microarray - Abstract
Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436&ndash, 0.952, p = 0.027) and residual tumor size <, 1 cm (HR: 0.312, 95% CI: 0.170&ndash, 0.573, p <, 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334&ndash, 0.783, p = 0.002) and residual tumor size <, 1 cm (HR: 0.252, 95% CI: 0.128&ndash, 0.496, p <, 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.
- Published
- 2019
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27. Clear Cell Carcinoma of the Abdominal Wall as a Rare Complication of General Obstetric and Gynecologic Surgeries: 15 Years of Experience at a Large Academic Institution
- Author
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Chi-An Chen, Heng-Cheng Hsu, Wen-Fang Cheng, Kuan-Ting Kuo, Yu-Li Chen, and Yen-Ling Lai
- Subjects
endometriosis ,Adult ,medicine.medical_specialty ,malignant transformation ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Obstetric Surgical Procedures ,Taiwan ,lcsh:Medicine ,Palpation ,Article ,Abdominal wall ,Hospitals, University ,03 medical and health sciences ,0302 clinical medicine ,Gynecologic Surgical Procedures ,Pregnancy ,inguinal lymph node ,Medicine ,Humans ,Aged ,clear cell carcinoma ,030219 obstetrics & reproductive medicine ,Hysterectomy ,medicine.diagnostic_test ,cesarean section ,business.industry ,Medical record ,lcsh:R ,Abdominal Wall ,Public Health, Environmental and Occupational Health ,Middle Aged ,Surgery ,Radiation therapy ,Dissection ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Clear cell carcinoma ,Female ,business ,Complication ,Adenocarcinoma, Clear Cell - Abstract
The objective of this article was to report the clinicopathological characteristics, treatment modalities, and outcomes of patients with clear cell carcinoma (CCC) of the abdominal wall. Medical records of six patients diagnosed with CCC of the abdominal wall between May 2003 and May 2018 at the National Taiwan University Hospital were reviewed. All patients had prior obstetric or gynecologic surgeries. The primary clinical presentation was enlarging abdominal masses at previous surgical scars. Four patients underwent initial/primary surgeries with/without adjuvant chemotherapy. One patient received neoadjuvant chemotherapy followed by surgical intervention and adjuvant chemotherapy, the other received chemotherapy and sequential radiotherapy without any surgical intervention. Two of four patients undergoing initial/primary surgeries had disease recurrence and the remaining two cases without initial surgery experienced disease progression during primary treatment. Inguinal lymph nodes were the most frequent sites of recurrence. In conclusion, previous obstetric or gynecologic surgery can be a risk factor for CCC of the abdominal wall. Complete resection of abdominal wall tumor and suspected intra-abdominal lesions with hysterectomy and bilateral inguinal lymph nodes dissection may be the primary treatment. Adjuvant chemotherapy would be considered for potential benefits. For patients without bilateral inguinal lymph nodes dissection, careful inguinal lymph node palpation during postoperative surveillance is necessary. More cases are still needed to elucidate the clinical management of this disease.
- Published
- 2019
28. Differences in the association between glycemia and uric acid levels in diabetic and non-diabetic populations
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Feng Hwa Lu, Chih Jen Chang, I-Hsuan Wu, Kuan-Ting Kuo, Yi Ching Yang, Yin Fan Chang, and Jin Shang Wu
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Population ,Taiwan ,030209 endocrinology & metabolism ,Blood Pressure ,030204 cardiovascular system & hematology ,Body Mass Index ,Impaired glucose tolerance ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Sex Factors ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hyperuricemia ,education ,Life Style ,Glycemic ,Aged ,education.field_of_study ,business.industry ,nutritional and metabolic diseases ,Fasting ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Impaired fasting glucose ,Uric Acid ,chemistry ,Diabetes Mellitus, Type 2 ,Uric acid ,Female ,business ,Non diabetic - Abstract
Aims Our study aimed to investigate the influence of different glycemic statuses and their fasting plasma glucose/2-hour post-load glucose on uric acid level. Methods A total of 14,787 subjects were recruited after excluding subjects with medication for hyperuricemia or diabetes. Fasting plasma glucose (FPG), 2-hour post-load glucose (2hPG), and uric acid (UA) were measured. Then, subjects were divided into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes. Results After adjustment for clinical variables, in NGT group, there was no significant relationship found between UA level and FPG. However, there was a positive association between UA level and 2hPG (β = 0.003, 95% CI: 0.002~0.004). A similar trend was also observed between UA level and 2hPG in IFG group (β = 0.004, 95% CI: 0.000~0.009) and IGT group (β = 0.005, 95% CI: 0.002~0.008), but relationship between UA level and FPG remained insignificant. In diabetes group, UA level was negatively associated with both FPG (β = −0.008, 95% CI: −0.010 ~ −0.007) and 2hPG (β = −0.005, 95% CI: −0.006 ~−0.003). Conclusions In non-diabetic individuals, UA level increased with 2hPG, but not with FPG, and UA level was inversely associated with both FPG and 2hPG in diabetic population.
- Published
- 2019
29. Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup
- Author
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Alexandra Lauria, Tzu-Pin Lu, Ming-Chieh Lin, Hsuan-Ying Huang, Chin-Yao Lin, Jen-Chieh Lee, Ying-Cheng Chiang, Chun A. Changou, Hsien-Neng Huang, Cher-Wei Liang, Kuan-Ting Kuo, and Ben Davidson
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,DNA Copy Number Variations ,Gene Dosage ,Copy number analysis ,Biology ,Molecular Inversion Probe ,Chromosome Painting ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,CDKN2A ,Chromosome instability ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Mullerian Ducts ,Chromosome 12 ,Aged ,Chromothripsis ,Paraffin Embedding ,Adenosarcoma ,Cytogenetics ,Middle Aged ,Immunohistochemistry ,Phenotype ,030104 developmental biology ,030220 oncology & carcinogenesis ,Uterine Neoplasms ,Female ,Genome-Wide Association Study - Abstract
Müllerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin tissue. In conclusion, we identified frequent chromosome 12q amplifications, including loci containing potential pharmacological targets. Global chromosomal instability and chromothripsis were more frequent in cases with sarcomatous overgrowth. To our knowledge, this is the first time that evidence of chromothripsis has been demonstrated in paraffin-embedded clinical tissues and in adenosarcomas.
- Published
- 2016
30. Urorectal septum malformation sequence-Fetal series with the description of a new 'intermediate' variant. Time to refine the terminology?
- Author
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Jin-Chung Shih, Yi-Ping Li, Kuan-Ying Huang, Kuan-Ting Kuo, Ming Chen, and Ching-Uen Yu
- Subjects
0301 basic medicine ,Fetus ,Series (mathematics) ,business.industry ,Malformation sequence ,Anatomy ,Terminology ,03 medical and health sciences ,Urorectal septum ,030104 developmental biology ,Genetics ,Medicine ,Ultrasonography ,business ,Genetics (clinical) - Published
- 2016
31. Spectro-Temporal Neural Factorization for Speech Dereverberation
- Author
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Jen-Tzung Chien and Kuan Ting Kuo
- Subjects
Recurrent neural network ,Factorization ,Artificial neural network ,business.industry ,Computer science ,Feature extraction ,Bilinear interpolation ,Pattern recognition ,Artificial intelligence ,Affine transformation ,business ,Backpropagation ,Matrix decomposition - Abstract
This study presents a spectro-temporal neural factorization (STNF) for speech dereverberation. Traditionally, a contextual window of spectro-temporal reverberant speech was unfolded into a one-way vector which was fed into a neural network to estimate the spectra of source speech at each time frame. Model parameters were trained by using the vectorized error backpropagation algorithm. System performance is constrained because contextual correlations and common factors in frequency and time horizons are disregarded. To compensate this weakness, a spectro-temporal factorization is incorporated to preserve the structural information in neural network training based on bi-factorized error backpropagation where the spectral and temporal factor matrices are estimated. Affine transformation in one-way neural network is generalized to the bilinear decomposition in bi-factorized neural network. The spectro-temporal features are extracted and forwarded to fully-connected layers for regression outputs. Such a STNF is further improved by merging with long short-term memory layer to capture the temporal features. Experiments results on 2014 REVERB Challenge demonstrate the meaningfulness of the factorized features and the merit of integrating these features for speech dereverberation.
- Published
- 2018
32. Long-term outcomes of surgical treatment for intravascular leiomyomatosis
- Author
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Chi-An Chen, Shoei-Shen Wang, Yih-Sharng Chen, Hsiao-En Tsai, Hsi-Yu Yu, Kuan-Ting Kuo, and Nai-Hsin Chi
- Subjects
Adult ,medicine.medical_specialty ,Lung Neoplasms ,Pleural effusion ,Femoral vein ,Taiwan ,Vena Cava, Inferior ,030204 cardiovascular system & hematology ,Malignancy ,Inferior vena cava ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Gynecologic Surgical Procedures ,Leiomyomatosis ,medicine ,Humans ,lcsh:R5-920 ,Cardiopulmonary Bypass ,business.industry ,General Medicine ,Pelvic cavity ,Middle Aged ,medicine.disease ,Thrombosis ,Magnetic Resonance Imaging ,Surgery ,medicine.anatomical_structure ,Treatment Outcome ,medicine.vein ,030220 oncology & carcinogenesis ,Concomitant ,Uterine Neoplasms ,Female ,Renal vein ,Neoplasm Recurrence, Local ,business ,lcsh:Medicine (General) ,Tomography, X-Ray Computed - Abstract
Background: Intravascular leiomyomatosis (IVL) is relatively rare. The optimal surgical method and long-term outcomes are not completely understood. Methods: Medical records between 2007 and 2017 in our hospital were analyzed to identify IVL cases with surgical intervention. Their medical records, operative details, and follow-up were collected by chart review and telephone communication. Results: Eight patients with IVL were included in the study, accounting for 0.26% of all uterine leiomyoma cases. Primary IVL was confined to pelvic cavity in three patients, extended to the inferior vena cava (IVC) below renal vein in one, reached IVC and right atrium in three, and reached main pulmonary artery in one. One-stage operation was performed for seven patients. Cardiopulmonary bypass was done in four patients, and aortic cross-clamp and temporary circulatory arrest was performed in two patients. None of the four patients with intrapulmonary tumors received concomitant pulmonary tumor resection. There was no operative mortality and four morbidities, including ureter injury (2), bladder injury (1), and femoral vein thrombosis (1). During follow-up, two patients exhibited local recurrence of the tumor in the pelvis, and one patient had rapidly growing intrapulmonary tumor three months post-operatively. Intrapulmonary tumors in the other three patients remained stationary at 6, 84, and 120 months post-operatively. Conclusion: One-stage operation to completely remove IVL is feasible and with good long-term outcomes, which is recommended if the patient can tolerate the operation. Concomitant intrapulmonary tumors can be followed up watchfully except when associated with pleural effusion or the pathology indicating trend of increasing malignancy. Keywords: Intravascular leiomyomatosis, Intracardiac leiomyomatosis, Cardiac tumor, Surgery, Cardiopulmonary bypass, Follow-up
- Published
- 2018
33. Combined squamous cell carcinoma and Merkel cell carcinoma of the vulva: Role of human papillomavirus and Merkel cell polyomavirus
- Author
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Jau-Yu Liau, Chien-Heng Chen, Yih-Yiing Wu, Kuan-Ting Kuo, and Cher-Wei Liang
- Subjects
squamous cell carcinoma ,SCC - Squamous cell carcinoma ,Pathology ,medicine.medical_specialty ,MCC, Merkel cell carcinoma ,Cell ,Merkel cell polyomavirus ,Case Report ,HPV, human papillomavirus ,Dermatology ,SCC, squamous cell carcinoma ,Vulva ,PCR, polymerase chain reaction ,Merkel cell carcinoma ,medicine ,Basal cell ,Human papillomavirus ,human papillomavirus ,biology ,business.industry ,vulva ,biology.organism_classification ,medicine.disease ,medicine.anatomical_structure ,MCV, Merkel cell polyomavirus ,business ,Cutaneous malignancy - Abstract
Merkel cell carcinoma (MCC), an uncommon and highly aggressive cutaneous malignancy, usually occurs on the sun-damaged skin of the elderly and is characterized by coexpression of neuroendocrine markers and CK20, a discriminant from other types of visceral neuroendocrine neoplasias. Since the discovery of Merkel cell polyomavirus (MCV), many researchers have confirmed its presence in about 80% of cutaneous MCCs.1 Although some cutaneous MCCs were reported to be associated with squamous cell carcinomas (SCCs), such combined cases accounted for only a minor portion and the viral status appeared to be different from pure MCC.1, 2, 3, 4 Rarely, primary MCCs occur on the female vulva,5 with or without combined SCCs,6, 7 the latter is often human papillomavirus (HPV) related.
- Published
- 2015
34. New Aspects of RpoE in Uropathogenic Proteus mirabilis
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Ming Che Liu, Shwu-Jen Liaw, Hsiung-Fei Chien, Kuan-Ting Kuo, and Yi-Lin Tsai
- Subjects
Lipopolysaccharides ,Immunology ,Fimbria ,Swarming motility ,Virulence ,Sigma Factor ,Biology ,Microbiology ,Recombinases ,Mice ,Sigma factor ,medicine ,Animals ,Humans ,Urea ,Promoter Regions, Genetic ,Proteus mirabilis ,Polymyxin B ,Regulation of gene expression ,Interleukin-8 ,Wild type ,Epithelial Cells ,Gene Expression Regulation, Bacterial ,Bacterial Infections ,biology.organism_classification ,Mice, Inbred C57BL ,Infectious Diseases ,Fimbriae, Bacterial ,Mutation ,Urinary Tract Infections ,Female ,Parasitology ,Urothelium ,Proteus Infections ,medicine.drug - Abstract
Proteus mirabilis is a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms for P. mirabilis to establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulating mrpI , a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted from rpoE mutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness of P. mirabilis in the host, including the avoidance of immune attacks. Accordingly, rpoE mutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and the rpoE mutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression of rpoE by the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness of P. mirabilis , to build up a UTI.
- Published
- 2015
35. Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation
- Author
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Kuan-Ting Kuo, Chi-An Chen, Ming-Chieh Lin, Ying-Cheng Chiang, Hsien-Neng Huang, and Wen-Fang Cheng
- Subjects
Pathology ,medicine.medical_specialty ,endocrine system diseases ,ARID1A ,Class I Phosphatidylinositol 3-Kinases ,DNA Mutational Analysis ,Molecular Sequence Data ,Kaplan-Meier Estimate ,Biology ,medicine.disease_cause ,Pathology and Forensic Medicine ,Phosphatidylinositol 3-Kinases ,medicine ,Humans ,Telomerase reverse transcriptase ,Promoter Regions, Genetic ,Telomerase ,Aged ,Proportional Hazards Models ,Ovarian Neoplasms ,Mutation ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Nuclear Proteins ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Endometrial Neoplasms ,DNA-Binding Proteins ,Clear cell carcinoma ,Adenocarcinoma ,Female ,Carcinogenesis ,Clear cell ,Adenocarcinoma, Clear Cell ,Transcription Factors - Abstract
Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.
- Published
- 2015
36. Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations
- Author
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Ying-Cheng Chiang, Wen-Chih Huang, Kuan-Ting Kuo, Hsien-Neng Huang, Hsin Ying Huang, and Ching-Hung Lin
- Subjects
Chromosomes, Human, Pair 20 ,Locus (genetics) ,Biology ,Pathology and Forensic Medicine ,Phosphatidylinositol 3-Kinases ,Germline mutation ,Gene expression ,medicine ,Humans ,PTEN ,Tensin ,Phosphorylation ,PI3K/AKT/mTOR pathway ,Ovarian Neoplasms ,medicine.diagnostic_test ,Gene Amplification ,PTEN Phosphohydrolase ,Middle Aged ,Cadherins ,Prognosis ,Molecular biology ,Clear cell carcinoma ,biology.protein ,Cancer research ,Female ,Proto-Oncogene Proteins c-akt ,Adenocarcinoma, Clear Cell ,Signal Transduction ,Fluorescence in situ hybridization - Abstract
This study aims to evaluate the relationships between chromosome 20q13.2 zinc finger protein 217 (ZNF217) locus amplification, ZNF217 expression, E-cadherin expression, and PI3K-Akt pathway alterations (activating PIK3CA mutations or loss of phosphatase and tensin homolog [PTEN] expression), and whether these molecular alterations can predict the clinical survival data in ovarian clear cell carcinoma (OCCC) patients. Samples and clinical data of 72 OCCC patients were collected. Chromosome 20q13.2 ZNF217 locus amplification was detected by fluorescence in situ hybridization. ZNF217, E-cadherin and PTEN expression were assessed using immunohistochemical stain. PIK3CA mutation was identified by PCR-amplified gene sequencing. Cox proportional hazard regression model was used to estimate the adjusted hazard ratios of survival. Chromosome 20q13.2 ZNF217 locus amplification was detected in 31% (22/72) of cases, and ZNF217 expression was increased in 40% (27/68) of cases. E-cadherin and PTEN expressions were decreased or lost in 44% (32/72) and 14% (10/72) of cases, respectively. Activating PIK3CA mutations were present in 35% (25/72) of cases. Thirty-three OCCC patients (46%) showed activating PI3K-Akt pathway alterations. Chromosome 20q13.2 ZNF217 locus amplification was significantly associated with decreased E-cadherin expression (P = .001). In contrast, ZNF217 expression was not related to ZNF217 amplification or E-cadherin expression. In OCCC patients with activating PI3k-Akt pathway, decreased E-cadherin expression (P = .033) and advanced Federation of Gynecology and Obstetrics stage (P = .014) predicted shorter overall survival. Two conclusions were raised in our study. First, ZNF217 plays a role in down-regulating E-cadherin expression and is a potential therapeutic target for OCCC patients. Second, E-cadherin expression is a prognostic marker for OCCC patients with activating PI3K-Akt pathway.
- Published
- 2014
37. 68-4: Demonstration of the Novel Ultra-Slim Flexible Glass as Substrate with Metal Meshed Antenna
- Author
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Sean M. Garner, Hung-Yi Lin, Kuan Ting Kuo, Jen-Chieh Lin, Kai-Jiun Wang, Hoang Yan Lin, Yi-Jiun Chen, Yu-Ming Wang, Kao-Der Chang, Chia-Ying Tseng, and Scott Pollard
- Subjects
0301 basic medicine ,Materials science ,business.industry ,02 engineering and technology ,Substrate (printing) ,021001 nanoscience & nanotechnology ,Metal ,03 medical and health sciences ,Laser linewidth ,030104 developmental biology ,visual_art ,Return loss ,visual_art.visual_art_medium ,Optoelectronics ,Antenna (radio) ,0210 nano-technology ,business - Abstract
The ultra-slim flexible glass is demonstrated as the substrate with metal meshed antenna for developing thinner, lighter and fulltransparent smart devices. The linewidth and spacing of the meshed grids are 3 µm and 200–300 µm. The return loss of the mesh antenna has good performance (
- Published
- 2016
38. Variational Recurrent Neural Networks for Speech Separation
- Author
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Kuan Ting Kuo and Jen-Tzung Chien
- Subjects
030507 speech-language pathology & audiology ,03 medical and health sciences ,Recurrent neural network ,Computer science ,Time delay neural network ,Speech recognition ,Separation (statistics) ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,02 engineering and technology ,0305 other medical science ,Variational learning - Published
- 2017
39. Epithelioid Trophoblastic Tumor Around an Abdominal Cesarean Scar: A Pathologic and Molecular Genetic Analysis
- Author
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Chiun Hsu, Kuan-Ting Kuo, Tzu-Pin Lu, Li Hui Tseng, and Emily Han-Chung Hsiue
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Genotype ,Pathology and Forensic Medicine ,Lesion ,Abdominal wall ,03 medical and health sciences ,Cicatrix ,0302 clinical medicine ,Pregnancy ,Trophoblastic neoplasm ,Medicine ,Humans ,Epithelioid Trophoblastic Tumor ,Gestational Trophoblastic Disease ,Genotyping ,Peritoneal Neoplasms ,business.industry ,Cesarean Section ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Molecular analysis ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,business ,Microsatellite Repeats - Abstract
Epithelioid trophoblastic tumor (ETT) is a rare chemoresistant gestational trophoblastic neoplasm that typically presents as an intrauterine lesion. To our knowledge, no isolated abdominal wall ETT around a Cesarean scar has been reported. Here we describe a 54-yr-old woman with a complex obstetric history who presented with a solitary abdominal wall tumor adjacent to the abdominal Cesarean section scar. The tumor demonstrated typical morphologic and immunophenotypic features of ETT. The gestational origin of the tumor was confirmed by microsatellite genotyping. The tumor enlarged despite the patient undergoing multiagent chemotherapy. Whole-exome sequencing was performed to explore the mechanisms underlying chemoresistance. The ATP-binding cassette subfamily B member 1 (ABCB1) 3435CC genotype, and a putative deleterious x-ray cross-complementing group 4 (XRCC4) Ala73Pro mutations were found. In conclusion, ETT may present as a solitary abdominal wall lesion and microsatellite genotyping could facilitate the determination of its gestational origin. More studies are required to provide mechanistic insights into the chemoresistance of ETT.
- Published
- 2017
40. Cervical Papanicolaou Smears in Hematopoietic Stem Cell Transplant Recipients: High Prevalence of Therapy-Related Atypia during the Acute Phase
- Author
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Kuan-Ting Kuo, Shan-Chi Yu, Jih-Luh Tang, Yi-Hsuan Lee, Ming Yao, Bor-Sheng Ko, Chi-Cheng Li, Chien-Ting Lin, Tsui-Lien Mao, Jia-Hau Liu, and Huai-Hsuan Huang
- Subjects
Adult ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Papanicolaou stain ,Uterine Cervical Neoplasms ,chemical and pharmacologic phenomena ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Cytology ,Atypia ,medicine ,Humans ,030212 general & internal medicine ,Autografts ,Cervix ,Busulfan ,Aged ,Retrospective Studies ,Cervical cancer ,Gynecology ,Vaginal Smears ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematopoietic stem cell ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,medicine.disease ,Allografts ,Hematologic Diseases ,Survival Rate ,surgical procedures, operative ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Stem cell ,business ,therapeutics ,Papanicolaou Test - Abstract
Hematopoietic stem cell transplant (HSCT) recipients have a higher risk of cervical cancer. Papanicolaou (Pap) smear is the standard tool for screening cervical cancer, but there is limited research about the cervical cytology in HSCT recipients. Here, we retrospectively included adult female patients who underwent allogeneic or autologous HSCT at National Taiwan University Hospital during 2009 to 2015 and reviewed their Pap smears before and after HSCT. There were 248 allogeneic and 131 autologous HSCT recipients in our study. In allogeneic HSCT recipients, 38.7% (96 of 248) had pre-HSCT Pap smears and 17.1% (44 of 248) had post-HSCT Pap smears. In the autologous HSCT recipients, 35.1% (46 of 131) had pre-HSCT Pap smears and 13.7% (18 of 131) had post-HSCT Pap smears. Compared with allogeneic HSCT recipients without post-HSCT Pap smears, more recipients with post-HSCT Pap smears received bone marrow-derived stem cells (18.2% versus 4.9% respectively; P = .0077) and had longer overall survival (median overall survival, not reached versus 22.1 months; P .0001). The abnormal rates of post-HSCT Pap smear were 13% (6 of 44) and 11% (2 of 18) in allogeneic and autologous recipients respectively, higher than in the general Taiwanese population (1.22%). Infections were rare in post-HSCT Pap smears. Of note, 11% (5 of 44) of post-HSCT Pap smears from allogeneic recipients showed therapy-related atypia, manifesting as enlarged hyperchromatic nuclei, vacuolated cytoplasm, and occasional tadpole-like cells. These atypical cytological features mimic precancerous lesions, but cervical biopsies and human papilloma virus tests were negative. The atypical cytological features resolved spontaneously in the subsequent follow-up Pap smears. On average, Pap smears with therapy-related atypia were sampled at day +77, significantly earlier than those without therapy-related atypia (P = .016). Therapy-related atypia was more frequent in post-HSCT Pap smears sampled within 100 days after HSCT (before day +100, 4 of 5, 80%, versus after day +100, 1 of 39, 2.56%; P = .0002). The strong temporal relationship suggests these atypical cytological changes resulted from conditioning regimen, most likely busulfan-containing chemotherapy. No therapy-related atypia were observed after total body irradiation or nonbusulfan-containing chemotherapy. In conclusion, therapy-related atypia was common in post-HSCT Pap smears sampled within 100 days after HSCT. Clinical information is critical for correct cytological diagnosis.
- Published
- 2017
41. Frequent activating <scp>HRAS</scp> mutations in trichilemmoma
- Author
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J.‐Y. Jhuang, Mei-Ling Cheng, W.‐C. Huang, Jia-Huei Tsai, Jau-Yu Liau, Yung-Ming Jeng, Kuan-Ting Kuo, and Hsien-Yi Chiu
- Subjects
Neuroblastoma RAS viral oncogene homolog ,Skin Neoplasms ,Genotype ,Class I Phosphatidylinositol 3-Kinases ,Dermatology ,Biology ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,Phosphatidylinositol 3-Kinases ,Exon ,Mutation Rate ,medicine ,Humans ,Receptor, Fibroblast Growth Factor, Type 3 ,HRAS ,Gene ,Neoplasms, Basal Cell ,Genetics ,Mutation ,Trichilemmoma ,Exons ,Cowden syndrome ,medicine.disease ,Genes, ras ,Cancer research ,KRAS ,Hair Diseases ,Hair Follicle - Abstract
Summary Background Trichilemmoma is a benign follicular epithelial tumour exhibiting outer root sheath differentiation. It is associated with Cowden syndrome and naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly understood. Recently, NS was found to be caused by postzygotic HRAS or KRAS mutations. Objectives We sought to determine whether NS-related and NS-unrelated trichilemmomas harbour RAS mutations. Methods Formalin-fixed and paraffin-embedded blocks of 12 NS-related and 15 NS-unrelated trichilemmomas from 26 individuals were retrieved and analysed to determine the presence of mutations in exons 1 and 2 of the HRAS, KRAS and NRAS genes by polymerase chain reaction and direct sequencing. Mutational hotspots of the FGFR3 and PIK3CA genes were also analysed for NS-unrelated cases. Results Among the 27 cases, mutually exclusive HRAS c.37G>C and c.182A>G mutations were observed in 17 and three tumours, respectively. Of the 12 NS-related tumours, 11 (92%) harboured the HRAS c.37G>C substitution. Of the 15 sporadic tumours, nine (60%) harboured HRAS mutations, including six c.37G>C and three c.182A>G. An HRAS c.182A>G mutation was observed only in sporadic tumours. No mutations were observed in the other genes that were tested. Conclusions The high frequency of HRAS activating mutations, including the c.182A>G substitution, which was rather rare in NS, suggests that most trichilemmomas are authentic neoplasms.
- Published
- 2014
42. Anterior amorphous corneal opacity and corneal thinning
- Author
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Po-Ting Yeh, Yu-Chih Hou, Fung-Rong Hu, and Kuan-Ting Kuo
- Subjects
Effects of long-term contact lens wear on the cornea ,medicine.medical_specialty ,corneal dystrophy ,Visual acuity ,genetic structures ,Corneal dystrophy ,law.invention ,law ,Ophthalmology ,stromalysis ,Medicine ,Dioptre ,Keratometer ,business.industry ,corneal degeneration ,Dystrophy ,Histology ,Anatomy ,medicine.disease ,eye diseases ,Amorphous solid ,amorphous corneal opacity ,corneal thinning ,sense organs ,medicine.symptom ,business - Abstract
Purpose To present the clinical features of four cases with bilateral anterior amorphous corneal opacity. Methods A retrospective study in four patients with bilateral anterior amorphous corneal opacity was conducted. Examinations included visual acuity, keratometry, slit-lamp biomicroscopy, confocal microscopy, anterior segment optical coherence topography, and histology. Results Three female and one male patients (mean age, 52.3 ± 8.9 years) showed bilaterally oval, amorphous sheetlike corneal opacities with central depression and thinning. Superior limbal opacities were observed in two of these patients. The best-corrected visual acuity ranged from 20/50 to 20/400, and the mean of the keratometry was 39.81 ± 3.97 D (diopters). They had mild dry eyes. The anterior segment optical coherence topography demonstrated hyporeflective abnormalities in the anterior depressed stroma in these four patients. Confocal microscopy revealed large round cells at the epithelial layer in one patient, and amorphous opacities with some strand-shaped opacities in the anterior stroma in all four patients. The mean of the corneal endothelial cells density in the eight eyes was 1521 ± 402 cells/mm2. Central corneal stromalysis occurred in three patients, and descemetocele developed in two eyes. One patient received penetrating keratoplasty and two underwent lamellar keratoplasty. The histology of the corneal specimen revealed edematous basal epithelial cells, focal collagen disorganization in the thin stroma, and wartlike excrescences in a thickened Descemet's membrane. Conclusion Anterior amorphous corneal opacity is a rare keratopathy and may be one kind of rare corneal degeneration or dystrophy. Corneal stromalysis may occur in hyporefrective amorphous opacities and progress to descemetocele.
- Published
- 2014
43. Primary primitive neuroectodermal tumor of the ovary
- Author
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Ling-Hui Chu, Kuan-Ting Kuo, Wen-Chun Chang, and Bor-Ching Sheu
- Subjects
Ovarian Neoplasms ,medicine.medical_specialty ,Adolescent ,business.industry ,MEDLINE ,Obstetrics and Gynecology ,University hospital ,medicine.disease ,lcsh:Gynecology and obstetrics ,humanities ,Rare Diseases ,Obstetrics and gynaecology ,Family medicine ,Primitive neuroectodermal tumor ,Obstetrics and Gynaecology ,Medicine ,Humans ,Neuroectodermal Tumors, Primitive ,Female ,business ,lcsh:RG1-991 - Abstract
a Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan b Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan c Centre for Optoelectronic Biomedicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Published
- 2014
44. Extraocular well-differentiated sebaceous tumors with overlying cutaneous horns: four tumors in three patients
- Author
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Shu-Lang Liao, Jie-Yang Jhuang, Kuan-Ting Kuo, Hsiao-Ching Chang, Jau-Yu Liau, and Jia-Huei Tsai
- Subjects
Pathology ,medicine.medical_specialty ,Histology ,Holocrine ,H&E stain ,Dermatology ,Biology ,medicine.disease ,Pathology and Forensic Medicine ,MSH6 ,Muir–Torre syndrome ,MSH2 ,Cutaneous horn ,medicine ,PMS2 ,Sebaceous carcinoma - Abstract
Background Sebaceous tumors are adnexal neoplasms showing sebocytic differentiation. They range from benign to malignant and are associated with Muir-Torre syndrome (MTS). Several clinical and histopathological features associated with MTS have been described. Sebaceous tumors with an overlying cutaneous horn are extremely rare. Methods Hematoxylin and eosin-stained slides were retrospectively reviewed to identify sebaceous tumors with marked hyperkeratosis, a condition that is often associated with cutaneous horns. Clinical correlation and mismatch repair protein immunohistochemical studies were then conducted. Results Four tumors from three patients were identified in our archive. Three were classified as sebaceous adenomas, and the fourth was considered as a borderline sebaceous tumor favoring well-differentiated sebaceous carcinoma. All cases showed loss of expression of mismatch repair proteins (three tumors from two patients exhibited lost expression of MSH2 and MSH6, and the fourth exhibited lost expression of MLH1 and PMS2). Additionally, one patient presented characteristic clinical manifestations of MTS, including multiple sebaceous adenomas and visceral carcinomas. Conclusions We suggest that extraocular well-differentiated sebaceous neoplasms with overlying cutaneous horns may be an indication of underlying mismatch repair protein deficiency and potential MTS. This distinctive morphology might be an exaggerated combination of other features associated with MTS, i.e. keratoacanthoma-like architecture and extensive holocrine secretion.
- Published
- 2014
45. TERTpromoter mutation is uncommon in acral lentiginous melanoma
- Author
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Kuan-Ting Kuo, Jau-Yu Liau, Yung-Ming Jeng, Cher-Wei Liang, Chia-Yu Chu, and Jia-Huei Tsai
- Subjects
Pathology ,medicine.medical_specialty ,Telomerase ,Histology ,integumentary system ,Transition (genetics) ,Melanoma ,Promoter ,Dermatology ,Biology ,medicine.disease ,Acral lentiginous melanoma ,Reverse transcriptase ,Pathology and Forensic Medicine ,Pathogenesis ,medicine ,Cancer research ,skin and connective tissue diseases ,neoplasms ,Gene - Abstract
Background Melanoma is a heterogeneous group of diseases with distinct sets of genetic changes. Recurrent and mutually exclusive C>T or CC>TT transition mutations were identified in the promoter region of the reverse transcriptase catalytic subunit of the telomerase gene (TERT) in melanoma recently, and it was suggested that they enhanced the expression of TERT gene and played important roles in the melanoma pathogenesis. These mono or di-nucleotide transitions were ultraviolet (UV)-signature mutations. Methods In this study, polymerase chain reaction and direct sequencing of TERT promoter using formalin-fixed and paraffin-embedded tissue was performed to investigate whether these UV-signature mutations were also present in acral lentiginous melanoma. Results TERT promoter mutation was identified in only 2 of the 32 cases (6%) of acral lentiginous melanomas while it was identified in 3 of the 9 cases (33%) of non-acral cutaneous melanomas. The difference was statistically significant (p = 0.028). Conclusions The rarity of TERT promoter mutation in the acral lentiginous melanoma was consistent with the supposed role of UV light in the melanoma pathogenesis and also corroborated the view that acral lentiginous melanomas have a different pathogenesis with the melanomas from sun-exposed sites.
- Published
- 2014
46. Loss of ARID1A Expression Correlates With Stages of Tumor Progression in Uterine Endometrioid Carcinoma
- Author
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Tsui Lien Mao, Kuan-Ting Kuo, Ie Ming Shih, Ayse Ayhan, Laura Ardighieri, Chen Hsuan Wu, and Tian Li Wang
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Time Factors ,endocrine system diseases ,ARID1A ,Biopsy ,Down-Regulation ,Biology ,Endometrium ,Article ,Atypical hyperplasia ,Pathology and Forensic Medicine ,Predictive Value of Tests ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,Uterine Neoplasm ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Nuclear Proteins ,Middle Aged ,medicine.disease ,Immunohistochemistry ,female genital diseases and pregnancy complications ,DNA-Binding Proteins ,medicine.anatomical_structure ,Tumor progression ,Case-Control Studies ,Uterine Neoplasms ,Clear cell carcinoma ,Disease Progression ,Cancer research ,Female ,Surgery ,Neoplasm Grading ,Anatomy ,Carcinoma, Endometrioid ,Transcription Factors - Abstract
ARID1A is a recently identified tumor suppressor that functions in chromatin remodeling. Inactivating mutations of ARID1A and loss of its expression most frequently occur in ovarian clear cell carcinoma, ovarian endometrioid carcinoma, and uterine endometrioid carcinoma. In this study, we performed a detailed immunostaining analysis of ARID1A in 246 cases including benign endometrium and endometrioid carcinoma at different stages of progression. Special attention was paid to recording intratumoral heterogeneity of clonal loss of ARID1A immunoreactivity. All normal endometria (n= 51) and endometrial polyps (n= 14) retained ARID1A expression. Among complex atypical hyperplasia (n= 38), 16% exhibited clonal loss of ARID1A, but none showed complete loss. Among low-grade endometrioid carcinomas (n= 88), 25% exhibited complete loss and 24% exhibited clonal loss. In contrast, 44% of high-grade endometrioid carcinomas (n= 55) showed complete loss of ARID1A and 9% exhibited clonal loss. We found that 19 high-grade carcinomas also contained concurrent low-grade carcinomas. In the high-grade areas, 63% exhibited complete loss and 11% exhibited clonal loss, whereas in the low-grade areas, 37% exhibited complete loss and 42% clonal loss. In 5 of these 19 cases, progressive loss of ARID1A from retention or clonal loss to complete loss was observed between the low-grade and high-grade areas. Overall, the percentage of complete ARID1A loss increased from 0% in complex atypical hyperplasia, to 25% in low-grade endometrioid carcinoma, to 44% in high-grade endometrioid carcinoma. These findings suggest that loss of ARID1A expression, presumably due to mutation, plays an important role in tumor progression of uterine endometrioid carcinoma.
- Published
- 2013
47. Dedifferentiated liposarcoma with homologous lipoblastic differentiation: expanding the spectrum to include low-grade tumours
- Author
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Jau-Yu Liau, Jen-Chieh Lee, Cher-Wei Liang, Hsuan-Ying Huang, Chen-Tu Wu, and Kuan-Ting Kuo
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Histology ,Soft Tissue Neoplasms ,Liposarcoma ,Biology ,Pleomorphic Liposarcoma ,Pathology and Forensic Medicine ,Lipoblast ,Metastasis ,medicine ,Humans ,neoplasms ,In Situ Hybridization, Fluorescence ,Aged ,Gene Amplification ,Proto-Oncogene Proteins c-mdm2 ,DNA, Neoplasm ,General Medicine ,Middle Aged ,medicine.disease ,Cell Transformation, Neoplastic ,Adipose Tissue ,Immunohistochemistry ,Female ,Sarcoma ,Spindle cell sarcoma - Abstract
Aims Dedifferentiated liposarcoma (DDLPS) is traditionally defined as a non-lipogenic high-grade sarcoma arising from a well-differentiated liposarcoma that confers metastatic potential. Recently, DDLPSs with lipoblastic differentiation, i.e. morphologically lipogenic DDLPSs, were reported. Because of the lipoblastic differentiation, these tumours caused confusion, and were reported under different names. However, cytogenetic and molecular studies have revealed their DDLPS nature. So far, the cases reported have been high-grade pleomorphic liposarcoma-like tumours. In this study we have collected another series that contains low-grade tumours, and expand the histological spectrum. Methods and results Eighteen cases of DDLPS with lipoblastic differentiation from various anatomical locations were analysed by routine histology, immunohistochemistry, and MDM2 fluorescence in-situ hybridization. Two main histological patterns were seen: one featured a spindle cell sarcoma containing lipoblasts with variable nuclear pleomorphism, and the other a pleomorphic liposarcoma-like tumour including the epithelioid variant. Two cases showed low nuclear grade and lipogenic activity in the metastatic foci. CDK4, MDM2 and p16INK4a overexpression was seen in all except one case. MDM2 amplification was found in all 16 cases tested. Conclusions We have expanded the spectrum of this variant of DDLPS to include low-grade tumours, in which a careful search for increased mitotic activity is essential. Like conventional DDLPS, these tumours are capable of metastasis.
- Published
- 2013
48. Clinical significance of ESR1 gene copy number changes in breast cancer as measured by fluorescence in situ hybridisation
- Author
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Kuan-Ting Kuo, Chieh Lan, Jacqueline Ming Liu, Chung-Chieh Wang, Chiun-Sheng Huang, Yen-Shen Lu, Ann-Lii Cheng, Lee Wj, Ching-Hung Lin, and Dwan-Ying Chang
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Time Factors ,DNA Copy Number Variations ,Gene Dosage ,Breast Neoplasms ,Kaplan-Meier Estimate ,Biology ,Real-Time Polymerase Chain Reaction ,Gene dosage ,Disease-Free Survival ,Pathology and Forensic Medicine ,Breast cancer ,Predictive Value of Tests ,Gene duplication ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,In Situ Hybridization, Fluorescence ,Proportional Hazards Models ,Chi-Square Distribution ,medicine.diagnostic_test ,Age Factors ,Estrogen Receptor alpha ,Gene Amplification ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Repressor Proteins ,body regions ,Phenotype ,Real-time polymerase chain reaction ,Multivariate Analysis ,Cancer research ,Female ,Breast disease ,Fluorescence in situ hybridization - Abstract
AimsThe ESR1 gene encodes for oestrogen receptor (ER) α, which plays a crucial role in mammary carcinogenesis and clinical outcome in patients with breast cancer. However, the clinical significance of the ESR1 gene copy number change for breast cancer has not been clarified.MethodsESR1 gene copy number was determined by fluorescence in situ hybridisation (FISH) on tissue sections. A minimum of 20 tumour cells were counted per section, and a FISH ratio of ESR1 gene to CEP6 ≥2.0 was considered ESR1 amplification. A ratio >1.2 but ESR1 gain. The ESR1 copy number was further measured by quantitative real-time PCR (Q-PCR) with ASXL2 as a reference.ResultsFISH revealed ESR1 amplification in six cases (4.0%) and ESR1 gain in 13 cases (8.7%) from a total of 150 cases. ESR1 gain and amplification were more common in older patients (pESR1 copy number (pESR1 amplification was associated with a shorter disease-free survival (HR=5.56, p=0.03) and a shorter overall survival (HR=5.11, p=0.04).ConclusionsIn general, the frequency of ESR1 amplification in breast cancer is low when measured by FISH in large sections. ESR1 gain and amplification in breast cancer may be associated with older age and poorer outcomes.
- Published
- 2012
49. Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers
- Author
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Ching-Chung Chang, Kuan-Ting Kuo, Pei-Lung Chen, Kuen-Yuan Chen, Chia-Chi Lin, Jin-Ying Lu, and Wern-Cherng Cheng
- Subjects
0301 basic medicine ,Male ,medicine.medical_treatment ,Population ,DNA Mutational Analysis ,Taiwan ,PDGFRA ,MLH1 ,medicine.disease_cause ,Targeted therapy ,Iodine Radioisotopes ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Thyroid Neoplasms ,education ,Thyroid cancer ,Aged ,Aged, 80 and over ,education.field_of_study ,Mutation ,lcsh:R5-920 ,business.industry ,Thyroid ,Carcinoma ,High-Throughput Nucleotide Sequencing ,General Medicine ,Ion semiconductor sequencing ,Middle Aged ,medicine.disease ,Death ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Female ,business ,lcsh:Medicine (General) - Abstract
Background/Purpose: Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumor's genetic information. Methods: We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing. Results: We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers. Conclusion: The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers. Keywords: Fatal thyroid cancer, Genetics, MET, MLH1, PDGFRA
- Published
- 2016
50. Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer
- Author
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I-Chun Chen, Ming-Yang Wang, Kuei-Pin Chung, Tsu-Hsin Hsueh, Kuan-Ting Kuo, Yuan-Ching Chang, Chiun-Sheng Huang, Pei-Fang Wu, Ching-Hung Lin, Ann-Lii Cheng, Chen-Yang Shen, Tzu-Pin Lu, Wen-Hung Kuo, and Yen-Shen Lu
- Subjects
Adult ,0301 basic medicine ,Oncology ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Receptor, ErbB-2 ,Population ,Estrogen receptor ,CA 15-3 ,Breast Neoplasms ,Protein Serine-Threonine Kinases ,medicine.disease_cause ,Disease-Free Survival ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,AMP-Activated Protein Kinase Kinases ,Internal medicine ,Gene expression ,medicine ,Humans ,skin and connective tissue diseases ,education ,Aged ,Neoplasm Staging ,Regulation of gene expression ,education.field_of_study ,Multidisciplinary ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,Neoplasm Recurrence, Local ,Carcinogenesis ,business - Abstract
Liver kinase B1 (LKB1) is a tumor suppressor, and its loss might lead to activation of the mammalian target of rapamycin (mTOR) and tumorigenesis. This study aimed to determine the clinical relevance of LKB1 gene and protein expression in breast cancer patients. LKB1 protein expression was evaluated using immunohistochemistry in tumors from early breast cancer patients in two Taiwanese medical centers. Data on LKB1 gene expression were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data set. The correlations between LKB1 expression, clinicopathologic factors, and patient outcome were analyzed. LKB1 expression was significantly associated with estrogen receptor (ER) expression in 2 of the 4 cohorts, but not with other clinicopathologic factors. LKB1 expression was not a predictor for relapse-free survival, overall survival (OS), or breast cancer-specific survival. In a subgroup analysis of the two Taiwanese cohorts, high LKB1 protein expression was predictive of high OS in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients (P = 0.013). Our study results indicate that LKB1 expression is not prognostic in the whole population of breast cancer patients, but it is a potential predictor of OS in the subset of HER2-positive patients
- Published
- 2016
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