30 results on '"Chia-Jung Liao"'
Search Results
2. Glyoxalase-I is a novel prognosis factor associated with gastric cancer progression.
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Wan-Li Cheng, Ming-Ming Tsai, Chung-Ying Tsai, Ya-Hui Huang, Cheng-Yi Chen, Hsiang-Cheng Chi, Yi-Hsin Tseng, Im-Wai Chao, Wei-Chi Lin, Sheng-Ming Wu, Ying Liang, Chia-Jung Liao, Yang-Hsiang Lin, I-Hsiao Chung, Wei-Jan Chen, Paul Y Lin, Chia-Siu Wang, and Kwang-Huei Lin
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Medicine ,Science - Abstract
Glyoxalase I (GLO1), a methylglyoxal detoxification enzyme, is implicated in the progression of human malignancies. The role of GLO1 in gastric cancer development or progression is currently unclear. The expression of GLO1 was determined in primary gastric cancer specimens using quantitative polymerase chain reaction, immunohistochemistry (IHC), and western blotting analyses. GLO1 expression was higher in gastric cancer tissues, compared with that in adjacent noncancerous tissues. Elevated expression of GLO1 was significantly associated with gastric wall invasion, lymph node metastasis, and pathological stage, suggesting a novel role of GLO1 in gastric cancer development and progression. The 5-year survival rate of the lower GLO1 expression groups was significantly greater than that of the higher expression groups (log rank P = 0.0373) in IHC experiments. Over-expression of GLO1 in gastric cancer cell lines increases cell proliferation, migration and invasiveness. Conversely, down-regulation of GLO1 with shRNA led to a marked reduction in the migration and invasion abilities. Our data strongly suggest that high expression of GLO1 in gastric cancer enhances the metastasis ability of tumor cells in vitro and in vivo, and support its efficacy as a potential marker for the detection and prognosis of gastric cancer.
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- 2012
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3. Circulating p16-Positive and p16-Negative Tumor Cells Serve as Independent Prognostic Indicators of Survival in Patients with Head and Neck Squamous Cell Carcinomas
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Hung-Ming Wang, Chia-Jung Liao, Li-Yu Lee, Jason Chia-Hsun Hsieh, Pei-Wei Huang, Chun-Ta Liao, Tyler Min-Hsien Wu, Cheng-Lung Hsu, Yung-Chia Kuo, Hsuan-Chih Kuo, Sanger Hung-Chi Lin, and Pei-Hung Chang
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Oncology ,medicine.medical_specialty ,Cell ,Medicine (miscellaneous) ,circulating tumor cells ,head and neck squamous cell carcinoma ,Article ,Circulating tumor cell ,Internal medicine ,medicine ,Liquid biopsy ,liquid biopsy ,business.industry ,Hazard ratio ,HPV genotyping ,medicine.disease ,Head and neck squamous-cell carcinoma ,Confidence interval ,medicine.anatomical_structure ,p16 expression ,Biomarker (medicine) ,biomarker ,Medicine ,business ,Chemoradiotherapy - Abstract
Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (>, 0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.
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- 2021
4. Utilization of optically induced dielectrophoresis in a microfluidic system for sorting and isolation of cells with varied degree of viability: Demonstration of the sorting and isolation of drug-treated cancer cells with various degrees of anti-cancer drug resistance gene expression
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Min-Hsien Wu, Po-Yu Chu, Chia-Jung Liao, Ping-Hei Chen, Hung-Ming Wang, Wen-Pin Chou, and Chia-Hsun Hsieh
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Drug ,media_common.quotation_subject ,Microfluidics ,Cell ,02 engineering and technology ,Drug resistance ,010402 general chemistry ,01 natural sciences ,Materials Chemistry ,medicine ,Viability assay ,Electrical and Electronic Engineering ,Instrumentation ,media_common ,Chemistry ,Metals and Alloys ,Sorting ,Dielectrophoresis ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Cell biology ,medicine.anatomical_structure ,Cancer cell ,0210 nano-technology - Abstract
The heterogeneity of the drug resistance of cancer cells in a tumor is regarded as an important cause of therapeutic resistance and thus treatment failure. An understanding of the heterogeneity of cancer cells in a tumor in terms of their anti-cancer drug resistance is of great value for clinical applications or fundamental studies. To achieve this goal, a combination of cell-based drug testing and optically induced dielectrophoresis (ODEP)-based cell manipulation for sorting, separation, and isolation of drug-treated cells with various degrees of cell viability is proposed. For the latter, the key working principle is based on the difference in the ODEP force generated on the cells with various degrees of viability. To test the proposed idea, an ODEP microfluidic system was designed and fabricated in which two types of ODEP-based cell manipulation schemes were tested. The results successfully demonstrated that the proof-of-concept and practical application schemes were capable of effectively sorting, separating, and isolating doxorubicin-treated Dx5 (i.e., cells with drug resistance) and MES-SA (i.e., cells without drug resistance) cells that exhibited various degrees of viability and levels of anti-cancer drug resistance gene (i.e., ABCB1) expression. Moreover, the results also demonstrated that the proposed technique was capable of sorting and separating cell of the same type (i.e., drug-treated Dx5 cells) but different degrees of viability and anti-cancer drug resistance gene expression levels. Overall, this study presents a technique that is able to effectively sort, separate, and isolate drug-treated cancer cells with phenotypic heterogeneity for subsequent clinical applications or fundamental studies.
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- 2019
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5. Optically-induced-dielectrophoresis (ODEP)-based cell manipulation in a microfluidic system for high-purity isolation of integral circulating tumor cell (CTC) clusters based on their size characteristics
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A-Ching Chao, Wen-Pin Chou, Hung-Ming Wang, Jyun-Huan Chang, Min-Hsien Wu, Tzu-Keng Chiu, Chia-Jung Liao, and Ping-Hei Chen
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0301 basic medicine ,Microfluidics ,Cell ,01 natural sciences ,03 medical and health sciences ,Circulating tumor cell ,Materials Chemistry ,medicine ,Cell isolation ,Isolation (database systems) ,Electrical and Electronic Engineering ,Instrumentation ,Chemistry ,010401 analytical chemistry ,Metals and Alloys ,Cancer ,Dielectrophoresis ,Condensed Matter Physics ,medicine.disease ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,030104 developmental biology ,medicine.anatomical_structure ,Cancer cell ,Biomedical engineering - Abstract
Circulating tumor cell (CTC) clusters play a more critical role in cancer metastasis than single CTCs. The study of CTC clusters might therefore provide more biologically meaningful information for a clear understanding of cancer metastasis. To achieve this goal, the isolation of high-purity, and integral CTC clusters from the blood samples of cancer patients is required. We herein propose to integrate optically-induced-dielectrophoresis (ODEP)-based cell manipulation with a microfluidic system for isolating cancer cell clusters based on their size characteristics. In this work, a two-step ODEP-based cell manipulation was designed. A dynamic square light image array was designed for the preliminary isolation of cancer cell clusters, followed by the utilization of another ODEP-based cell manipulation to refine the purity of the cancer cell clusters harvested in the first step. In this study, the optimal ODEP operating conditions for cell isolation process were experimentally determined. Moreover, the performance of cell isolation was experimentally evaluated for the isolation of CTC clusters with a cell purity and recovery rate of 91.5 ± 5.6%, and 70.5 ± 5.2%, respectively, without compromising the integrity of cancer cell clusters. Overall, this study presents a method and device capable of isolating high-purity and integral cancer cell clusters.
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- 2018
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6. Functional and Clinical Significance of Dysregulated microRNAs in Liver Cancer
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Hui-Chi Tang, Chia-Jung Liao, Kwang-Huei Lin, Cheng-Chih Chang, Cheng Yi Chen, Ya-Hui Huang, Po-Shuan Huang, and Chau-Ting Yeh
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Cancer Research ,microRNA ,business.industry ,Hepatitis C virus ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RNA ,Review ,medicine.disease ,Bioinformatics ,medicine.disease_cause ,clinical ,Biomarker (cell) ,liver cancer ,Oncology ,Drug development ,Clinical diagnosis ,medicine ,Clinical significance ,Liver cancer ,business ,RC254-282 - Abstract
Simple Summary Liver cancer has a high mortality rate. Here, we retrospectively discuss the current progress and dilemmas in the clinical research and treatment of liver cancer. We primarily focus on microRNAs because of their extremely high value in applications and research. We discuss whether microRNAs can be used for the development of better biomarkers and/or therapeutic drugs, and address the difficulties, requirements for improved diagnostic technologies, and side effects related to microRNA-based drugs. Abstract Liver cancer is the leading cause of cancer-related mortality in the world. This mainly reflects the lack of early diagnosis tools and effective treatment methods. MicroRNAs (miRNAs) are a class of non-transcribed RNAs, some of which play important regulatory roles in liver cancer. Here, we discuss microRNAs with key impacts on liver cancer, such as miR-122, miR-21, miR-214, and miR-199. These microRNAs participate in various physiological regulatory pathways of liver cancer cells, and their modulation can have non-negligible effects in the treatment of liver cancer. We discuss whether these microRNAs can be used for better clinical diagnosis and/or drug development. With the advent of novel technologies, fast, inexpensive, and non-invasive RNA-based biomarker research has become a new mainstream approach. However, the clinical application of microRNA-based markers has been limited by the high sequence similarity among them and the potential for off-target problems. Therefore, researchers particularly value microRNAs that are specific to or have special functions in liver cancer. These include miR-122, which is specifically expressed in the liver, and miR-34, which is necessary for the replication of the hepatitis C virus in liver cancer. Clinical treatment drugs have been developed based on miR-34 and miR-122 (MRX34 and Miravirsen, respectively), but their side effects have not yet been overcome. Future research is needed to address these weaknesses and establish a feasible microRNA-based treatment strategy for liver cancer.
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- 2021
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7. A low-sample-loss microfluidic system for the quantification of size-independent cellular electrical property—Its demonstration for the identification and characterization of circulating tumour cells (CTCs)
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Beiyuan Fan, Yang Zhao, Junbo Wang, Jian Chen, Chia-Jung Liao, Hsin-Yao Wang, Min-Hsien Wu, Ke Wang, Tzu-Keng Chiu, Chia-Hsun Hsieh, Deyong Chen, and Wen-Pin Chou
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Sample (material) ,Cell ,Microfluidics ,Nanotechnology ,02 engineering and technology ,01 natural sciences ,Single-cell analysis ,Materials Chemistry ,medicine ,Electrical and Electronic Engineering ,Instrumentation ,Microchannel ,Chemistry ,010401 analytical chemistry ,Metals and Alloys ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Characterization (materials science) ,Identification (information) ,medicine.anatomical_structure ,Cytoplasm ,0210 nano-technology ,Biomedical engineering - Abstract
The current approaches for the characterization of cellular electrical properties normally require a tested sample with high cell quantity, restricting their application in the cases in which the cell number in a sample is limited. To address this issue, this study presented a low-sample-loss microfluidic system capable of characterizing the size-independent electrical properties (e.g., specific membrane capacitance and cytoplasm conductivity) of single cells. In the design, a capillary tube was used to transfer cells directly into the entrance of a microfluidic constriction microchannel to possibly minimize cell sample loss. Results revealed that the microfluidic system was able to significantly reduce the sample loss phenomenon, by which the cell processing ratio could be raised from the original 0.2% to 49.3–60.0%. As a demonstration, moreover, the feasibility of using the proposed method for the identification of the EpCAM-positive CTCs after a CTC isolation process, and for the differentiation of the EpCAM-positive CTCs of three different (hepatic, oral and lung) cancer types were experimentally evaluated. Within the experimental conditions explored, our findings indicated that the proposed method was able to significantly identify the EpCAM-positive CTCs from the surrounding EpCAM-negative cells, as well as to differentiate the EpCAM-positive CTCs of the three different cancer types tested, based on their unique electrical properties of cells. As a whole, the proposed microfluidic system was found useful for the identification of CTCs after a conventional CTC isolation process. In addition to CTC identification, the proposed method might hold potential for the detection of a specific cell species in a cell suspension sample with limited cell quantity.
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- 2017
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8. Hazardous factors besides infection in hypoglycemia
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Yu-Jang Su, Yen‑Chun Lai, and Chia‑Jung Liao
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medicine.medical_specialty ,Cirrhosis ,General Neuroscience ,Mortality rate ,Urinary system ,030209 endocrinology & metabolism ,Articles ,General Medicine ,030204 cardiovascular system & hematology ,Biology ,Hypoglycemia ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Uremia ,03 medical and health sciences ,Pneumonia ,0302 clinical medicine ,Internal medicine ,Concomitant ,Immunology ,medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Stroke - Abstract
Hypoglycemia is one of the most common issues encountered in daily emergency practice. In addition to the treatment of hypoglycemia, certain other situations concomitant with hypoglycemia require further treatment. The aim of the present study was to compare demographic and clinical characteristics of infected [urinary tract infection (UTI), pneumonia or biliary tract infection (BTI)] vs. non-infected hypoglycemic patients to establish which hypoglycemic patients required further observation or hospitalization. This was a retrospective cross-sectional study of hypoglycemic (
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- 2017
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9. Predisposing factors for hypoglycaemia in the emergency department
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Chia-Jung Liao and Yu-Jang Su
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Blood Glucose ,Male ,Medicine (General) ,Cirrhosis ,Clinical Research Reports ,Comorbidity ,mortality rate ,Biochemistry ,Tertiary Care Centers ,Acute renal failure ,Liver disease ,0302 clinical medicine ,Risk Factors ,Medicine ,Stroke ,Aged, 80 and over ,Incidence ,Mortality rate ,General Medicine ,Middle Aged ,Prognosis ,Hospitalization ,Survival Rate ,Female ,Emergency Service, Hospital ,Adult ,medicine.medical_specialty ,liver cirrhosis ,Taiwan ,Vital signs ,030209 endocrinology & metabolism ,03 medical and health sciences ,R5-920 ,Internal medicine ,Diabetes mellitus ,Humans ,Aged ,Retrospective Studies ,business.industry ,Biochemistry (medical) ,030208 emergency & critical care medicine ,Cell Biology ,Emergency department ,Length of Stay ,medicine.disease ,Hypoglycemia ,infection ,business ,Complication ,Follow-Up Studies ,advanced age ,hypoglycaemia - Abstract
Objective Hypoglycaemia is a common complication of diabetes mellitus. Previous studies suggest that hypoglycaemic episodes may occur with other comorbidities, influencing the outcome of recovery. Recognising the predisposing factors for hypoglycaemic episodes in the emergency department is important. Therefore, we investigated the characteristics of and predisposing factors for hypoglycaemia in the emergency department. Methods Data from 186 patients were retrospectively collected from a medical centre in northern Taiwan. We divided the patients into the advanced-age group (132 patients) and the younger group (54 patients). Associated data collected for statistical analysis included vital signs on arrival, first measured blood glucose level, laboratory results, related comorbidities, length of hospital stay, and survival to discharge. Results Hypoglycaemia was more frequently observed in women in the advanced-age group than in the younger group. Tachycardia and elevated systolic blood pressure were less predominant in the advanced-age group than younger group. More patients in the advanced-age group had concurrent infection, and more patients in the younger group had liver dysfunction, elevated liver enzymes, liver cirrhosis, and concurrent stroke. Conclusions Closer attention should be paid to the possibility of infection in patients of advanced age. Liver disease and stroke need to be ruled out in younger patients.
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- 2019
10. Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression
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Chung-Ying Tsai, Yang Hsiang Lin, Sheng Ming Wu, Po Hao Feng, Wan-Li Cheng, Syuan Ling Lin, Wei Jan Chen, Chia Jung Liao, Kang Yun Lee, Hsiang Cheng Chi, Chau Ting Yeh, Kwang-Huei Lin, and Hsiao Chi Chuang
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0301 basic medicine ,Cancer Research ,Angiogenesis ,Cell growth ,Biology ,medicine.disease_cause ,medicine.disease ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,Oncology ,medicine ,Cancer research ,Centrosome duplication ,Signal transduction ,Carcinogenesis ,Liver cancer ,PI3K/AKT/mTOR pathway - Abstract
NEK2 (NIMA-related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC. However, the precise roles and mechanisms of NEK2 in liver cancer progression remain largely unknown. An earlier functional study revealed that NEK2 mediates drug resistance (cisplatin or lipo-doxorubicin) via expression of an ABCC10 transporter. Active angiogenesis and metastasis underlie the rapid recurrence and poor survival of HCC. Results from the current study showed that NEK2 mediates tumor growth, metastasis and angiogenesis in vivo. NEK2-mediated drug resistance was blocked by a specific PI3K or AKT inhibitor. Moreover, NEK2 mediated liver cancer cell migration via pAKT/NF-κB signaling and matrix metalloproteinase (MMP) activation. Angiogenesis was induced via the same signaling pathway and IL-8 stimulation. Our findings collectively indicate that NEK2 modulates hepatoma cell functions, including growth, drug resistance, metastasis and angiogenesis via downstream genes activation.
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- 2017
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11. Isolation of label-free and viable circulating tumour cells (CTCs) from blood samples of cancer patients through a two-step process: negative selection-type immunomagnetic beads and spheroid cell culture-based cell isolation
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Hung-Ming Wang, Chia-Jung Liao, Jyun-Huan Chang, Chia-Hsun Hsieh, Min-Hsien Wu, Tzu-Keng Chiu, Wen-Pin Chou, and A.-Ching Chao
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0301 basic medicine ,Chemistry ,General Chemical Engineering ,Cell ,Spheroid ,Cancer ,General Chemistry ,medicine.disease ,Isolation (microbiology) ,Molecular biology ,03 medical and health sciences ,Negative selection ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,medicine ,Cell isolation - Abstract
Isolation of high-purity, label-free, and viable circulating tumour cells (CTCs) from cancer patients is crucial for subsequent analyses. To address this issue, a two-step CTC isolation scheme was proposed, wherein a spheroid cell culture was used to further purify viable CTCs after conventional negative selection-based CTC isolation methods. Our results from a cancer cell line model revealed that the survival of leukocytes in spheroid cell cultures was significantly decreased with time, whereas OECM-1 cells maintained viability and proliferated. Therefore, such a cell culture operation was expected to increase cancer cell purity in the cell spheroids. This assumption was confirmed by our results, which showed that cancer cell purities were 10.6 to 80.3-fold increased after spheroid cell culture for 8 days. In the following clinical tests, CTC-related cells were observed in 6 of 13 blood samples. Furthermore, the average purity of CTC-related cells was 34.8 ± 14.0%. By utilizing a second-step spheroid cell culture operation, the purity of CTC-related cells was greatly improved when compared with that (less than 10%) achievable by conventional negative selection-based CTC isolation. Overall, this study proposed a two-step process for the isolation of high-purity, label-free, and viable CTCs.
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- 2017
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12. An Optically Induced Dielectrophoresis (ODEP)-Based Microfluidic System for the Isolation of High-Purity CD45
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Wen-Pin Chou, Chia-Hsun Hsieh, Yu-Xian Zhu, Min-Hsien Wu, Chia-Jung Liao, Hung-Ming Wang, Feng-Chun Hung, and Tzu-Keng Chiu
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lcsh:Mechanical engineering and machinery ,Microfluidics ,Population ,Cell ,02 engineering and technology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,cell isolation ,0302 clinical medicine ,Antigen ,Nucleated cell ,cancer metastasis ,medicine ,lcsh:TJ1-1570 ,microfluidic systems ,Electrical and Electronic Engineering ,education ,education.field_of_study ,Chemistry ,Mechanical Engineering ,Cancer ,Epithelial cell adhesion molecule ,Dielectrophoresis ,021001 nanoscience & nanotechnology ,medicine.disease ,optically induced dielectrophoresis (ODEP) ,medicine.anatomical_structure ,Control and Systems Engineering ,circulating tumour cells (CTCs) ,030220 oncology & carcinogenesis ,Cancer research ,0210 nano-technology - Abstract
Circulating tumour cells (CTCs) in blood circulation play an important role in cancer metastasis. CTCs are generally defined as the cells in circulating blood expressing the surface antigen EpCAM (epithelial cell adhesion molecule). Nevertheless, CTCs with a highly metastatic nature might undergo an epithelial-to-mesenchymal transition (EMT), after which their EpCAM expression is downregulated. In current CTC-related studies, however, these clinically important CTCs with high relevance to cancer metastasis could be missed due to the use of the conventional CTC isolation methodologies. To precisely explore the clinical significance of these cells (i.e., CD45neg/EpCAMneg cells), the high-purity isolation of these cells from blood samples is required. To achieve this isolation, the integration of fluorescence microscopic imaging and optically induced dielectrophoresis (ODEP)-based cell manipulation in a microfluidic system was proposed. In this study, an ODEP microfluidic system was developed. The optimal ODEP operating conditions and the performance of live CD45neg/EpCAMneg cell isolation were evaluated. The results demonstrated that the proposed system was capable of isolating live CD45neg/EpCAMneg cells with a purity as high as 100%, which is greater than the purity attainable using the existing techniques for similar tasks. As a demonstration case, the cancer-related gene expression of CD45neg/EpCAMneg cells isolated from the blood samples of healthy donors and cancer patients was successfully compared. The initial results indicate that the CD45neg/EpCAMneg nucleated cell population in the blood samples of cancer patients might contain cancer-related cells, particularly EMT-transformed CTCs, as suggested by the high detection rate of vimentin gene expression. Overall, this study presents an ODEP microfluidic system capable of simply and effectively isolating a specific, rare cell species from a cell mixture.
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- 2018
13. Hypoglycemia in Emergency Department
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Chia-Jung Liao and Yu-Jang Su
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medicine.medical_specialty ,Cirrhosis ,business.industry ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,General Medicine ,Emergency department ,Hypoglycemia ,Malignancy ,medicine.disease ,Mortality rate ,Uremia ,Acute renal failure ,Internal medicine ,Concomitant ,Liver cirrhosis ,medicine ,Etiology ,Infection ,Intensive care medicine ,business ,Stroke - Abstract
Objective To study the epidemiology, etiologies and prognostic factors of hypoglycemia. Methods A retrospective chart review of hypoglycemic cases from December, 2009 to February, 2012 was conducted to gather the following patient data: age, gender, vital signs at triage, white blood cell count, serum glucose, C-reactive protein, glutamic oxaloacetic transaminase, creatinine, sodium, potassium, past history of liver cirrhosis, uremia, concomitant infection, concomitant cancer/malignancy, length of stay, lack of recent meal, status of acute renal failure and concomitant stroke. A total of 186 cases were enrolled in our study. We analyzed the data using commercial statistics software (SPSS for Windows, version 11.0, SPSS Inc., Chicago, IL). We used the Student's t-test and χ2 test for the statistical analyses, and significance was set at a P value less than 0.05. Results Hypoglycemia is related to several co-morbidities. In total, 10.2% of the patients had liver cirrhosis and 7.0% had uremia. More than half (55.4%) were bacterial infection during hospitalization. Acute renal failure accounted for 26.3% of the hypoglycemic episodes. In addition to the etiology of infection, the lack of a recent meal accounted for 44.6% hypoglycemic episodes. A total of 2.2% of the cases resulted from an acute cerebrovascular accident. Approximately 8.6% were concomitant with malignancy. Conclusions When hypoglycemic patients present in the emergency department, physicians should pay attention to the presence of infection, malignancy, liver diseases (liver cirrhosis and biliary tract infection), and acute renal failure.
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- 2015
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14. The Integration of a Three-Dimensional Spheroid Cell Culture Operation in a Circulating Tumor Cell (CTC) Isolation and Purification Process: A Preliminary Study of the Clinical Significance and Prognostic Role of the CTCs Isolated from the Blood Samples of Head and Neck Cancer Patients
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Chia-Hsun Hsieh, Chia-Jung Liao, Wen-Pin Chou, Min-Hsien Wu, Feng-Chun Hung, and Hung-Ming Wang
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0301 basic medicine ,Cancer Research ,circulating tumor cells (CTCs) ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Negative selection ,0302 clinical medicine ,Circulating tumor cell ,Medicine ,Clinical significance ,business.industry ,Head and neck cancer ,Mesenchymal stem cell ,Spheroid ,spheroid cell culture ,cell isolation and purification ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Head and neck squamous-cell carcinoma ,030104 developmental biology ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,head and neck cancer ,prognosis ,business ,epithelial-to-mesenchymal transition (EMT) - Abstract
Conventional positive and negative selection-based circulating tumor cell (CTC) isolation methods might generally ignore metastasis-relevant CTCs that underwent epithelial-to- mesenchymal transition and suffer from a low CTC purity problem, respectively. To address these issues, we previously proposed a 2-step CTC isolation method integrating a negative selection CTC isolation and subsequent spheroid cell culture. In addition to its ability to isolate CTCs, more importantly, the spheroid cell culture used could serve as a cell culture model mimicking the process of new tumor tissue formation during cancer metastasis. Therefore, it is promising not only to selectively isolate metastasis-relevant CTCs but also to test the potential of cancer metastasis and thus the prognosis of disease. To explore these issues, experiments were performed. The key findings of this study demonstrated that the method was able to harvest both epithelial (E)- and mesenchymal (M)-type CTCs without selection bias. Moreover, both the M-type CTC count and the information obtained from the multidrug resistance-associated protein 2 (MRP2) and MRP5 gene expression analysis of the CTCs isolated via the 2-step CTC isolation method might be able to serve as prognostic factors for progression-free survival in head and neck squamous cell carcinoma.
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- 2019
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15. Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism
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Yang Hsiang Lin, Kwang-Huei Lin, Po-Yuan Ke, Yi Hsin Tseng, Sheng Ming Wu, Cheng Yi Chen, Chia Jung Liao, Chung-Ying Tsai, and Hsiang Cheng Chi
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Transcriptional Activation ,Thyroid Hormones ,medicine.medical_specialty ,Peptide Hormones ,Molecular Sequence Data ,Endosomes ,Biology ,Cell Line ,Thyroid hormone receptor beta ,Downregulation and upregulation ,Angiopoietin-Like Protein 8 ,Internal medicine ,Lipid droplet ,Lysosome ,Autophagy ,medicine ,Humans ,Molecular Biology ,Receptors, Thyroid Hormone ,Thyroid hormone receptor ,Base Sequence ,Lipid metabolism ,Cell Biology ,Lipid Metabolism ,Basic Research Paper ,Up-Regulation ,Cell biology ,Protein Transport ,Angiopoietin-like Proteins ,Endocrinology ,medicine.anatomical_structure ,Liver ,Gene Knockdown Techniques ,Vacuoles ,Triiodothyronine ,Lysosomes ,Hormone - Abstract
The thyroid hormone, T3, regulates cell growth, differentiation and development through binding to the nuclear thyroid hormone receptor (THR), a member of the steroid/TR superfamily of ligand-dependent transcriptional factors. T3 modulates lipid metabolism in liver, although the detailed molecular mechanisms are unclear at present. Here, by a microarray analysis, we identified a novel chromosome 19 open reading frame 80 (C19orf80) which was activated by T3. T3 stimulation led to upregulation of both mRNA and protein levels of C19orf80. Immunofluorescence analysis revealed a vesicle-like pattern of C19orf80 around lipid droplets or within the lysosome-associated compartment in cells. Furthermore, T3 treatment as well as C19orf80 overexpression specifically activated the autophagic response and lipid metabolism, as observed from lipidated LC3 (LC3-II) and levels of oxygen consumption rate, respectively. Reciprocally, knockdown of C19orf80 obstructed T3-activated autophagy and lipolysis. Moreover, treatment with autolysosome maturation inhibitors, ammonium chloride and chloroquine, not only suppressed the T3-activated autophagic process but also lipid metabolism. Our results collectively suggested that T3 regulates lipid metabolism through a C19orf80-activated autophagic process.
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- 2013
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16. Thyroid hormone receptors promote metastasis of human hepatoma cells via regulation of TRAIL
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Chia-Jung Liao, Yin-Cheng Huang, Yi-Hsin Tseng, Shen Liang Chen, C. Y. Chen, Sheng-Ming Wu, Chien-Yuh Yeh, Ming-Ming Tsai, I-Hsiao Chung, Kwang-Huei Lin, Hsiang-Cheng Chi, Wei Jan Chen, Chung-Ying Tsai, Yang Hsiang Lin, and Chen-Hsin Liao
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Transplantation, Heterologous ,bcl-X Protein ,Apoptosis ,Mice, SCID ,Biology ,medicine.disease_cause ,Metastasis ,TNF-Related Apoptosis-Inducing Ligand ,Mice ,Downregulation and upregulation ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Receptor ,Molecular Biology ,Original Paper ,Receptors, Thyroid Hormone ,Thyroid hormone receptor ,Liver Neoplasms ,Hep G2 Cells ,Cell Biology ,medicine.disease ,Up-Regulation ,Endocrinology ,Matrix Metalloproteinase 9 ,Tumor progression ,Matrix Metalloproteinase 7 ,Cancer cell ,Cancer research ,Matrix Metalloproteinase 2 ,Triiodothyronine ,Tumor necrosis factor alpha ,Carcinogenesis - Abstract
Although accumulating evidence has confirmed the important roles of thyroid hormone (T(3)) and its receptors (TRs) in tumor progression, the specific functions of TRs in carcinogenesis remain unclear. In the present study, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was directly upregulated by T(3) in TR-overexpressing hepatoma cell lines. TRAIL is an apoptotic inducer, but it can nonetheless trigger non-apoptotic signals favoring tumorigenesis in apoptosis-resistant cancer cells. We found that TR-overexpressing hepatoma cells treated with T(3) were apoptosis resistant, even when TRAIL was upregulated. This apoptotic resistance may be attributable to simultaneous upregulation of Bcl-xL by T(3), because (1) knockdown of T(3)-induced Bcl-xL expression suppressed T(3)-mediated protection against apoptosis, and (2) overexpression of Bcl-xL further protected hepatoma cells from TRAIL-induced apoptotic death, consequently leading to TRAIL-promoted metastasis of hepatoma cells. Moreover, T(3)-enhanced metastasis in vivo was repressed by the treatment of TRAIL-blocking antibody. Notably, TRAIL was highly expressed in a subset of hepatocellular carcinoma (HCC) patients, and this high-level expression was significantly correlated with that of TRs in these HCC tissues. Together, our findings provide evidence for the existence of a novel mechanistic link between increased TR and TRAIL levels in HCC. Thus, TRs induce TRAIL expression, and TRAIL thus synthesized acts in concert with simultaneously synthesized Bcl-xL to promote metastasis, but not apoptosis.
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- 2012
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17. Dickkopf 4 positively regulated by the thyroid hormone receptor suppresses cell invasion in human hepatoma cells
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Chen-Hsin Liao, Hsiang-Cheng Chi, I-Hsiao Chung, Chung-Ying Tsai, Cheng Yi Chen, Ming-Ming Tsai, Wei-Jan Chen, Kwang-Huei Lin, Yi-Hsin Tseng, Sheng-Ming Wu, Yang-Hsiang Lin, Chia-Jung Liao, Chau-Ting Yeh, Wan-Li Cheng, and Ya-Hui Huang
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Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Transplantation, Heterologous ,Down-Regulation ,Mice, Nude ,In Vitro Techniques ,Mice ,Cyclin D1 ,Cell Movement ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Receptor ,beta Catenin ,Aged ,Cell Proliferation ,Retrospective Studies ,Aged, 80 and over ,Receptors, Thyroid Hormone ,Thyroid hormone receptor ,Hepatology ,biology ,Cell growth ,Liver Neoplasms ,CD44 ,Wnt signaling pathway ,Transfection ,Middle Aged ,Wnt Proteins ,Endocrinology ,Tumor progression ,Disease Progression ,biology.protein ,Cancer research ,Intercellular Signaling Peptides and Proteins ,Female ,Signal Transduction - Abstract
Thyroid hormone (T3) mediates cellular growth, development, and differentiation by binding to the nuclear thyroid hormone receptor (TR). Recent studies suggest that long-term hypothyroidism is associated with human hepatocellular carcinoma (HCC) independent from other major HCC risk factors. Dickkopf (DKK) 4, a secreted protein, antagonizes the Wnt signal pathway. In this study, we demonstrate that T3 may play a suppressor role by inducing DKK4 expression in HCC cells at both the messenger RNA (mRNA) and protein levels. DKK4 was down-regulated in 67.5% of HCC cancerous tissues. The decrease in DKK4 levels was accompanied by a concomitant decrease in TR protein levels in the matched cancerous tissues in 31% of tissues compared by immunoblotting with the adjacent noncancerous tissues. Further, TR and DKK4 expression levels were positively correlated in both normal and cancerous specimens by tissue array analysis. In function assays, stable DKK4 transfected into J7 or HepG2 cells decreased cell invasion in vitro. Conversely, knocking down DKK4 restores cell invasiveness. DKK4-expressing J7 clones showed increased degradation of β-catenin, but down-regulation of CD44, cyclin D1, and c-Jun. To investigate the effect of DKK4 and TR on tumor growth in vivo, we established a xenograft of J7 cells in nude mice. J7-DKK4 and J7-TRα1 overexpressing mice, which displayed growth arrest, lower lung colony formation index, and smaller tumor size than in control mice, supporting an inhibitory role of DKK4 in tumor progression. Conclusion: Taken together, these data suggest that the TR/DKK4/Wnt/β-catenin cascade influences the proliferation and migration of hepatoma cells during the metastasis process and support a tumor suppressor role of the TR. (Hepatology 2012)
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- 2012
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18. Glucose-regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer
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Tzu I. Wu, Ting-Chang Chang, Ying Liang, Chia Siu Wang, Shih-Ming Jung, Kwang-Huei Lin, Chyong-Huey Lai, Chia Jung Liao, Ya-Hui Huang, and Ming Ming Tsai
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Adult ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Transplantation, Heterologous ,Cell ,Protein Disulfide-Isomerases ,Uterine Cervical Neoplasms ,Kaplan-Meier Estimate ,Adenocarcinoma ,Biology ,HeLa ,Carcinoma, Adenosquamous ,Mice ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Carcinoma ,Animals ,Humans ,Neoplasm Invasiveness ,Clinical significance ,RNA, Small Interfering ,Aged ,Cervical cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,biology.organism_classification ,Survival Analysis ,Transplantation ,medicine.anatomical_structure ,Oncology ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Cancer research ,Immunohistochemistry ,Female ,RNA Interference ,Neoplasm Transplantation ,HeLa Cells - Abstract
Human papilloma virus infection is critical but not sufficient to cause cervical cancer. Molecular markers of cervical carcinogenesis are essential. The aim of this study was to identify aberrantly expressed proteins in cervical cancer and determine their clinical significance. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used for screening candidate proteins. Immunoblotting and immunohistochemical (IHC) analyses were performed to confirm the results of 2-DE, and the clinical significance was estimated. Glucose-regulated protein 58 (Grp58) was overexpressed in 73% of cancers. The IHC staining showed that the Grp58 histoscore was significantly higher in patients with adenocarcinoma (AD) compared with squamous cell carcinoma (P < 0.05). Grp58 staining was intense in AD with a penetration depth greater than half of the cervical stroma (P = 0.033). High Grp58 expression was associated with low overall survival and recurrence-free survival (RFS) rates (P = 0.007 and P = 0.013, respectively). In multivariate analysis, high Grp58 expression (P = 0.042) and lymph node metastasis (P = 0.026) were determined as independent prognostic factors for RFS. Patients exhibiting both high Grp58 expression and lymph node metastasis displayed poorer outcomes than the other patient groups. In functional studies, knockdown of Grp58 in HeLa cells led to decreased cell invasiveness and inhibition of lung metastasis in a xenograft mouse model. In conclusion, Grp58 serves as a potent prognostic factor of cervical AD. Estimation of the Grp58 index in conjunction with the lymph node metastasis status might aid in predicting the prognosis of cervical AD.
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- 2011
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19. Overexpression of gelsolin in human cervical carcinoma and its clinicopathological significance
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Ming Hung Tsai, Chia Siu Wang, Chia Jung Liao, Kwang-Huei Lin, Ya-Hui Huang, Ming Ming Tsai, Tzu I. Wu, Chung Yuan Hsu, Chyong-Huey Lai, and Ting-Chang Chang
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Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Uterine Cervical Neoplasms ,Cell Growth Processes ,macromolecular substances ,medicine.disease_cause ,Cell Movement ,Biomarkers, Tumor ,medicine ,Humans ,Vimentin ,Cyclin D1 ,Epithelial–mesenchymal transition ,Survival rate ,Gelsolin ,Aged ,Neoplasm Staging ,Retrospective Studies ,Tumor marker ,Cervical cancer ,business.industry ,Gene Expression Profiling ,Obstetrics and Gynecology ,Middle Aged ,Cadherins ,Prognosis ,medicine.disease ,Fibronectins ,Up-Regulation ,Survival Rate ,Oncology ,Case-Control Studies ,Gene Knockdown Techniques ,Cancer cell ,Cancer research ,Matrix Metalloproteinase 2 ,Immunohistochemistry ,Female ,Carcinogenesis ,business ,HeLa Cells - Abstract
Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited.A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer.The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation.These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.
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- 2011
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20. Overexpression of lipocalin 2 in human cervical cancer enhances tumor invasion
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Jin-Yo Hu, Yang-Hsiang Lin, Kwang-Huei Lin, Tzu-I Wu, Chyong-Huey Lai, Chia-Jung Liao, I-Hsiao Chung, and Pei-ju Tai
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0301 basic medicine ,Adult ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,cervical cancer ,Uterine Cervical Neoplasms ,Mice, SCID ,Lipocalin ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Lipocalin-2 ,medicine ,Animals ,Humans ,metastasis ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Aged ,Cervical cancer ,Gene knockdown ,biology ,business.industry ,Middle Aged ,medicine.disease ,invasion ,Up-Regulation ,Fibronectin ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Heterografts ,Ectopic expression ,Female ,business ,lipocalin2 ,Research Paper - Abstract
Cervical carcinoma is the third-most common cause of cancer-related deaths in women worldwide. However, the molecular mechanisms underlying the metastasis of cervical cancer are still unclear. Oligonucleotide microarrays coupled with bioinformatics analysis show that cytoskeletal remodeling and epithelial-to- mesenchymal transition (EMT) are significant pathways in clinical specimens of cervical cancer. In accord with clinical observations demonstrating ectopic expression of lipocalin 2 (LCN2), an oncogenic protein associated with EMT, in malignant tumors, was significantly upregulated in cervical cancer and correlated with lymph node metastasis. Overexpression of LCN2 enhanced tumor cell migration and invasion both in vitro and in vivo. Conversely, knockdown or neutralization of LCN2 reduced tumor cell migration and invasion. LCN2-induced migration was stimulated by activation of the EMT-associated proteins, Snail, Twist, N-cadherin, fibronectin, and MMP-9. Our findings collectively support a potential role of LCN2 in cancer cell invasion through the EMT pathway and suggest that LCN2 could be effectively utilized as a lymph node metastasis marker in cervical cancer.
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- 2015
21. Thyroid hormone-mediated regulation of lipocalin 2 through the Met/FAK pathway in liver cancer
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I-Hsiao Chung, Cheng-Yi Chen, Yang-Hsiang Lin, Hsiang-Cheng Chi, Ya-Hui Huang, Pei-Ju Tai, Chia-Jung Liao, Chung-Ying Tsai, Syuan-Ling Lin, Meng-Han Wu, Ching-Ying Chen, and Kwang-Huei Lin
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Thyroid Hormones ,Blotting, Western ,Transplantation, Heterologous ,Mice, SCID ,Biology ,medicine.disease_cause ,Response Elements ,LCN2 ,Downregulation and upregulation ,Lipocalin-2 ,Cell Movement ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Met/FAK cascade ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Thyroid hormone receptor ,Triiodothyronine ,Receptors, Thyroid Hormone ,Reverse Transcriptase Polymerase Chain Reaction ,Thyroid ,Liver Neoplasms ,Cancer ,thyroid hormone receptor ,Hep G2 Cells ,Proto-Oncogene Proteins c-met ,medicine.disease ,Lipocalins ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,Focal Adhesion Kinase 1 ,Cancer research ,Liver cancer ,Carcinogenesis ,Hormone ,Acute-Phase Proteins ,Signal Transduction ,Research Paper - Abstract
// I-Hsiao Chung 1 , Cheng-Yi Chen 2 , Yang-Hsiang Lin 1 , Hsiang-Cheng Chi 1 , Ya-Hui Huang 3 , Pei-Ju Tai 1 , Chia-Jung Liao 1 , Chung-Ying Tsai 1 , Syuan-Ling Lin 1 , Meng-Han Wu 1 , Ching-Ying Chen 1 , Kwang-Huei Lin 1 1 Department of Biochemistry, School of Medicine, Chang-Gung University, Taoyuan, Taiwan 2 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 3 Liver Research Center, Department of Hepato-Gastroenterology, Chang-Gung Memorial Hospital, Linkou, Taoyuan, Taiwan Correspondence to: Kwang-Huei Lin, e-mail: khlin@mail.cgu.edu.tw Keywords: thyroid hormone receptor, LCN2, Met/FAK cascade Received: December 02, 2014 Accepted: March 25, 2015 Published: April 10, 2015 ABSTRACT The thyroid hormone, 3,3′,5-triiodo-L-thyronine (T 3 ), regulates cell growth, development and differentiation via interactions with thyroid hormone receptors (TR), but the mechanisms underlying T 3 -mediated modulation of cancer progression are currently unclear. Lipocalin 2 (LCN2), a tumor-associated protein, is overexpressed in a variety of cancer types. Oligonucleotide microarray, coupled with proteomic analysis, has revealed that LCN2 is positively regulated by T 3 /TR. However, the physiological role and pathway of T 3 -mediated regulation of LCN2 in hepatocellular carcinogenesis remain to be characterized. Upregulation of LCN2 after T 3 stimulation was observed in a time- and dose-dependent manner. Additionally, TRE on the LCN2 promoter was identified at positions -1444/-1427. Overexpression of LCN2 enhanced tumor cell migration and invasion, and conversely, its knockdown suppressed migration and invasion, both in vitro and in vivo . LCN2-induced migration occurred through activation of the Met/FAK cascade. LCN2 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively correlated with TRα levels. Both TRα and LCN2 showed similar expression patterns in relation to survival rate, tumor grade, tumor stage and vascular invasion. Our findings collectively support a potential role of T 3 /TR in cancer progression through regulation of LCN2 via the Met/FAK cascade. LCN2 may thus be effectively utilized as a novel marker and therapeutic target in HCC.
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- 2014
22. A novel small-form NEDD4 regulates cell invasiveness and apoptosis to promote tumor metastasis
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Yang-Hsiang Lin, Chung-Ying Tsai, Ya-Hui Huang, Yi-Hsin Tseng, Chia-Jung Liao, Sheng-Ming Wu, Hsiang-Cheng Chi, Ching-Ying Chen, Shiu-Feng Huang, Kwang-Huei Lin, I-Hsiao Chung, Chi-De Chen, and Syuan-Ling Lin
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Male ,Myeloid ,Carcinoma, Hepatocellular ,Nedd4 Ubiquitin Protein Ligases ,Ubiquitin-Protein Ligases ,Cell ,Mice, Nude ,Mice, SCID ,Biology ,Metastasis ,Mice ,Downregulation and upregulation ,sNEDD4 ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Protein Isoforms ,metastasis ,Neoplasm Invasiveness ,Mice, Inbred BALB C ,Hepatoma ,Endosomal Sorting Complexes Required for Transport ,Liver Neoplasms ,apoptosis ,medicine.disease ,Prognosis ,Molecular medicine ,Molecular biology ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Leukemia ,medicine.anatomical_structure ,Oncology ,Apoptosis ,Hepatocellular carcinoma ,Cancer research ,Research Paper - Abstract
// Chia-Jung Liao 1 , Hsiang-Cheng Chi 1 , Chung-Ying Tsai 1 , Chi-De Chen 2 , Sheng-Ming Wu 1 , Yi-Hsin Tseng 1 , Yang-Hsiang Lin 1 , I-Hsiao Chung 1 , Ching-Ying Chen 1 , Syuan-Ling Lin 1 , Shiu-Feng Huang 3 , Ya-Hui Huang 4 , Kwang-Huei Lin 1 1 Department of Biochemistry, Chang-Gung University, Taoyuan, Taiwan 333, Republic of China 2 Chang Gung Molecular Medicine Research Center, Chang-Gung University, Taoyuan, Taiwan 333, Republic of China 3 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan 350, Republic of China 4 Medical Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan 333, Republic of China Correspondence to: Kwang-Huei Lin, e-mail: khlin@mail.cgu.edu.tw Keywords: Hepatoma, prognosis, sNEDD4, metastasis, apoptosis Received: October 21, 2014 Accepted: February 09, 2015 Published: March 20, 2015 ABSTRACT Despite numerous investigations on metastasis, the determinants of metastatic processes remain unclear. We aimed to identify the metastasis-associated genes in hepatocellular carcinoma (HCC). Potent metastatic SK-hep-1 (SK) cells, designated ‘SKM’, were generated using Transwell assay followed by selection in a mouse model. Genes expressed differentially in SKM and SK cells were identified via microarray analyses. A small form of Neural precursor cell-expressed developmentally downregulated 4 (sNEDD4) was identified to be overexpressed in SKM cells, which was confirmed as a novel transcript using liquid chromatography-mass spectrometry. In clinical specimens, sNEDD4 was significantly overexpressed in tumors and serves as a poor prognostic factor for male patients with HCC ( P = 0.035). Upon subcutaneous introduction of sNEDD4-overexpressing SK cells into flanks of nude mice, tumors grew faster than those of the control group. Furthermore, sNEDD4-mediated promotion of tumor metastasis was demonstrated in the orthotopic mouse model. Overexpression of sNEDD4 increased the invasive ability of SK cells through upregulation of matrix metalloproteinase 9 and inhibited serum deprivation-induced apoptosis via upregulation of myeloid cell leukemia 1. In conclusion, sNEDD4 is a novel metastasis-associated gene, which prevents apoptosis under nutrient restriction conditions. The present findings clearly support the prognostic potential of sNEDD4 for HCC.
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- 2014
23. Glucose-regulated protein 58 modulates β-catenin protein stability in a cervical adenocarcinoma cell line
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Chuen Hsueh, Chyong-Huey Lai, Tzu I. Wu, Ya-Hui Huang, Shih-Ming Jung, Chia Jung Liao, Ting-Chang Chang, and Kwang-Huei Lin
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Pathology ,medicine.medical_specialty ,Cancer Research ,Beta-catenin ,Glucose-regulated protein ,Protein Disulfide-Isomerases ,Uterine Cervical Neoplasms ,Biology ,Adenocarcinoma ,HeLa ,Gene Knockdown Techniques ,medicine ,Genetics ,Humans ,Wnt Signaling Pathway ,beta Catenin ,Oligonucleotide Array Sequence Analysis ,Gene knockdown ,Protein Stability ,Wnt signaling pathway ,biology.organism_classification ,Gene Expression Regulation, Neoplastic ,Oncology ,Cell culture ,Catenin ,Cancer research ,biology.protein ,Female ,Lithium Chloride ,HeLa Cells ,Research Article - Abstract
Background Cervical cancer continues to threaten women’s health worldwide, and the incidence of cervical adenocarcinoma (AD) is rising in the developed countries. Previously, we showed that glucose-regulated protein 58 (Grp58) served as an independent factor predictive of poor prognosis of patients with cervical AD. However, the molecular mechanism underlying the involvement of Grp58 in cervical carcinogenesis is currently unknown. Methods DNA microarray and enrichment analysis were used to identify the pathways disrupted by knockdown of Grp58 expression. Results Among the pathway identified, the WNT signaling pathway was one of those that were significantly associated with knockdown of Grp58 expression in HeLa cells. Our experiments showed that β-catenin, a critical effector of WNT signaling, was stabilized thereby accumulated in stable Grp58 knockdown cells. Membrane localization of β-catenin was observed in Grp58 knockdown, but not control cells. Using a transwell assay, we found that accumulated β-catenin induced by Grp58 knockdown or lithium chloride treatment inhibited the migration ability of HeLa cells. Furthermore, an inverse expression pattern of Grp58 and β-catenin was observed in cervical tissues. Conclusions Our results demonstrate that β-catenin stability is negatively regulated by Grp58 in HeLa cells. Overexpression of Grp58 may be responsible for the loss of or decrease in membranous β-catenin expression in cervical AD. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-555) contains supplementary material, which is available to authorized users.
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- 2013
24. Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells
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Tzu-I Wu, Sheng-Ming Wu, Chia-Jung Liao, Kwang-Huei Lin, Hsiang-Cheng Chi, I-Hsiao Chung, Yang Hsiang Lin, Ming-Ming Tsai, Ya-Hui Huang, Crystal D. Lin, Yi-Hsin Tseng, Meng-Han Wu, Chung-Ying Tsai, and C. Y. Chen
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Cancer Research ,Thyroid Hormones ,Carcinoma, Hepatocellular ,Biology ,Response Elements ,Molecular oncology ,Hyperthyroidism ,Metastasis ,Growth factor receptor ,Cell Movement ,Cell Line, Tumor ,Tumor Virus ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Promoter Regions, Genetic ,Molecular Biology ,Thyroid hormone receptor ,Receptors, Thyroid Hormone ,Liver Neoplasms ,Cancer ,Cell cycle ,medicine.disease ,Molecular biology ,digestive system diseases ,Rats ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,MicroRNAs ,Cancer research ,Matrix Metalloproteinase 3 ,Proto-Oncogene Proteins c-akt ,Protein Binding ,Thyroid Hormone Receptors alpha - Abstract
MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.
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- 2013
25. Overexpression of ADP‐ribosylation factor 1 in human gastric carcinoma and its clinicopathological significance
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Chia-Siu Wang, Hsiang-Cheng Chi, Ming-Ming Tsai, Sheng-Ming Wu, Chung-Ying Tsai, Chia-Jung Liao, I-Hsiao Chung, Chi-De Chen, Cheng Yi Chen, Yi-Hsin Tseng, Ying Liang, Wan-Li Cheng, Yang-Hsiang Lin, Kwang-Huei Lin, Yi-Fen Cheng, and Paul Y. Lin
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Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lymphovascular invasion ,Pathological staging ,Biology ,Western blot ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Survival rate ,Aged ,Cell Proliferation ,Aged, 80 and over ,medicine.diagnostic_test ,Cell growth ,Correction ,Cancer ,General Medicine ,Original Articles ,Middle Aged ,Prognosis ,medicine.disease ,Oncology ,Lymphatic Metastasis ,Cancer research ,Biomarker (medicine) ,Immunohistochemistry ,ADP-Ribosylation Factor 1 ,Female - Abstract
Gastric cancer is the sixth leading cause of cancer‐related death in Taiwan, and the identification of related factors is essential to increase patient survival. ADP‐ribosylation factor 1 (ARF1) was initially identified using 2‐D electrophoresis combined with MALDI–time‐of‐flight mass spectrometry. ADP‐ribosylation factor 1 belongs to the Ras superfamily or GTP‐binding protein family and has been shown to enhance cell proliferation. In the current study, we evaluated the potential of ARF1 as a biomarker for gastric cancer detection. ADP‐ribosylation factor 1 mRNA was upregulated in tumor tissues (compared with adjacent non‐tumor tissues, n = 55) in approximately 67.2% of gastric cancer patients. Expression of ARF1 protein was additionally observed using Western blot and immunohistochemistry (IHC) analyses. The clinicopathological correlations of ARF1 were further evaluated. Elevated ARF1 expression was strongly correlated with lymph node metastasis (P = 0.008), serosal invasion (P = 0.046), lymphatic invasion (P = 0.035), and pathological staging (P = 0.010). Moreover, the 5‐year survival rate for the lower ARF1 expression group (n = 50; IHC score
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- 2012
26. Glyoxalase-I Is a Novel Prognosis Factor Associated with Gastric Cancer Progression
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Paul Y. Lin, Wei-Chi Lin, Chia-Siu Wang, Chung-Ying Tsai, Sheng-Ming Wu, Hsiang-Cheng Chi, Ming-Ming Tsai, Yang-Hsiang Lin, Im-Wai Chao, Wan-Li Cheng, Cheng Yi Chen, Ya-Hui Huang, Ying Liang, Wei-Jan Chen, Chia-Jung Liao, I-Hsiao Chung, Kwang-Huei Lin, and Yi-Hsin Tseng
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Multidisciplinary ,biology ,business.industry ,Science ,lcsh:R ,Cancer ,Correction ,lcsh:Medicine ,Bioinformatics ,medicine.disease ,Lactoylglutathione lyase ,biology.protein ,Medicine ,lcsh:Q ,business ,lcsh:Science - Abstract
A second corresponding author, Chia-Siu Wang, was not signified. The author Chia-Siu Wang can be contacted at wangcs@adm.cgmh.org.tw Also, there is an error in Figure 3. The correct Figure 3 can be seen here: [^]
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- 2012
27. Abstract 3855: Clinical implications of FADD copy number gain/amplification and high protein expression in areca-quid-associated oral cavity squamous cell carcinomas
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Chia-Jung Liao, Chun-Ta Liao, I-How Chen, Huei-Tzu Chien, Shiang-Fu Huang, Hung-Ming Wang, and Ling-Ling Hsieh
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Cancer Research ,biology ,Cancer ,medicine.disease ,Molecular biology ,Head and neck squamous-cell carcinoma ,Cyclin D1 ,Oncology ,Gene duplication ,biology.protein ,medicine ,FADD ,Copy-number variation ,Oral Cavity Squamous Cell Carcinoma ,Gene - Abstract
Gene amplification provides a means for overexpression of cell growth promoting genes driving tumor formation and progression. Indeed, cancer genomic analyses have indicated that gene amplification occurs somatically in certain regions of human cancer genome. Among them, amplification of the 11q13.3 is a frequent event in human cancers including head and neck squamous cell carcinoma. Our whole genome copy number alterations (CNAs) study also revealed amplification of 11q13.3 in oral cavity squamous cell carcinoma (OSCC) in Taiwan. This region contains at least 5 cancer-related genes including CCND1 and FADD. CCND1 amplification has been demonstrated as an oncogenic driver gene in breast, bladder, head and neck, liver and lung squamous cancer. FADD, an apoptotic effector, was previously identified as a novel cancer driver gene in laryngeal/pharyngeal cancer. It is warranting for further investigation to determine whether FADD amplification is also a cancer driver in other types of human cancer. Therefore, this study was designed to explore whether FADD is a cancer driver in Taiwanese OSCC based on CNAs, protein expression and their clinical implications. A total of 346 male OSCCs were examined for gene copy number using TaqMan CNV analysis and protein expression using immunohistochemistry. We found that the intensity of FADD protein expression was strongly correlated with gene copy number gain/amplification. Gene copy number gain/amplification and high protein expression was observed in 70 (20.23%) and 199 (57.51%) OSCCs, respectively. Both FADD gene copy number gain/amplification and high protein expression were significantly associated with lymph node metastasis (p Citation Format: Chia-Jung Liao, Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Ling-Ling Hsieh. Clinical implications of FADD copy number gain/amplification and high protein expression in areca-quid-associated oral cavity squamous cell carcinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3855. doi:10.1158/1538-7445.AM2015-3855
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- 2015
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28. Abstract 3290: Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma
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Chia-Jung Liao, Tzu-Hao Wang, Syuan-Ling Lin, and Kwang-Huei Lin
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Cervical cancer ,Cancer Research ,Gene knockdown ,biology ,business.industry ,Glucose-regulated protein ,Wnt signaling pathway ,Cancer ,medicine.disease ,biology.organism_classification ,medicine.disease_cause ,HeLa ,Oncology ,Catenin ,Immunology ,Cancer research ,biology.protein ,Medicine ,business ,Carcinogenesis - Abstract
Cervical cancer is still a serious problem threatening to women health worldwide. The incidence of cervical adenocarcinoma (AD) is rising in more developed countries. Previously we have identified that glucose-regulated protein 58 (Grp58) serves as a poor independent prognostic factor for cervical AD. The molecular mechanism underlying Grp58 involved cervical AD carcinogenesis is unknown. The DNA microarray and enrichment analysis were used to identify pathway maps perturbed by knockdown of Grp58 expression. The WNT singling map is one of the significant enriched pathways. The β-catenin, vital effector of WNT signaling, was stably accumulated in Grp58 knockdown stable cells. A membrane fashion of β-catenin was observed in Grp58 knockdown but not control cells. By using transwell assay, we have demonstrated that accumulation of β-catenin, which was induced by Grp58 knockdown or lithium chloride treatment, inhibited the migration ability of HeLa cell. Furthermore, an exclusive expression pattern of Grp58 and β-catenin was observed in cervix tissues. In sum, we have demonstrated that β-catenin stability is negatively regulated by Grp58. Overpression of Grp58 might result in lost or decreased of membranous β-catenin in cervical cancer to promote cancer progression. Citation Format: Chia-Jung Liao, Syuan-ling Lin, Tzu-Hao Wang, Kwang-Huei Lin. Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2014-3290
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- 2014
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29. Abstract 3807: ER-60 increases cell migration and serves as a prognostic marker of cervical cancer
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Kwang-Huei Lin, Yang-Hsiang Lin, and Chia-Jung Liao
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Cervical cancer ,Cancer Research ,Gene knockdown ,Severe combined immunodeficiency ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,CD44 ,Cell ,Cancer ,medicine.disease ,biology.organism_classification ,HeLa ,medicine.anatomical_structure ,Oncology ,medicine ,Cancer research ,biology.protein ,Immunohistochemistry ,business - Abstract
Cervical cancer is the second most common cancer in women worldwide. Human papilloma virus infection is the primary cause of cervical cancer, although it cannot cause cancer by itself. Molecular markers involved in cervical carcinogenesis are needed. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used to discover genes with exceptional expression from four paired cervical cancer tissues. Immunoblotting and immunohistochemical analysis with 52 paired specimens and 107 sections were used to confirm the results of 2-DE, and the clinical significance was estimated. The molecular functions of ER-60 were investigated in vitro and in vivo. We identified ER-60 was upregulated in 71.2% of cancerous tissues. ER-60 expression differed significantly between patients with different histological types and differentiation grades (P = 0.013 and 0.045, respectively). Patients with high ER-60 expression had a lower 5-year overall survival (OS) and recurrence-free survival (RFS) rate (P = 0.038 and 0.017, respectively). High ER-60 expression was an independent prognostic factor of poor RFS (P = 0.019). Knockdown of ER-60 expression in HeLa cell decreased cell motility. The lung metastasis was inhibited when introduced ER-60-knockdown cells into severe combined immunodeficiency mice. We observed accumulation of b-catenin and regulation of b-catenin downstream CD44 and S100A4 expression in ER-60-knockdown cell were responsible for this migration inhibition. Taken together, ER-60 overexpression is a potential prognostic factor of poor OS and an independent factor of poor RFS in cervical cancer. ER-60 may be involved in cervical cancer invasion by modulating b-catenin protein stability and signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3807. doi:10.1158/1538-7445.AM2011-3807
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- 2011
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30. Abstract 1740: Over-expression of gelsolin protein in human cervical carcinoma associate with cell migration in vitro and recurrence-free survival in vivo
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Chia-Jung Liao, Kwang-Huei Lin, Ting-Chang Chang, and Tzu-I Wu
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Cervical cancer ,Cancer Research ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Cancer ,medicine.disease ,biology.organism_classification ,Actin cytoskeleton ,HeLa ,medicine.anatomical_structure ,Oncology ,medicine ,biology.protein ,Cancer research ,Immunohistochemistry ,Antibody ,business ,Gelsolin ,Lymph node - Abstract
Introduction: The global yearly incidence and mortality of cervical cancer are 471,000 annual new cases and 233,000 deaths. Almost 80% cases occur in less developed countries, where it accounts for 15% of cancer in women. Cervical carcinoma ranks as the leading malignancy of genital tract malignancy in the developing countries. The recurrence indicate poor prognosis while the clinicopathological risk factors exist. In order to identify the potential molecular biomarker, proteomic analysis was performed and gesolin protein was selected. Materials and Methods: The plasma from normal healthy and cervical cancer, and tissue of cervical cancer plus adjacent normal tissue were collected for Western blotting assay, enzyme-linked immunosorbent assay (ELISA) or immunohistochemical stain (IHC). One hundred and twenty four patients with cervical cancers underwent surgical management were enrolled to evaluate IHC Histoscore of gesolin according to the multiply of immunoreactivity and involved percentage. The Transwell assay was conducted for cell migration analysis in HeLa cell line. The statistical analysis include independent t tests, Kaplan-Meier method using the log-rank test and the Cox proportional hazard model Receiver operating characteristics (ROC) curve analysis was used to determine cut-off points of the predictive parameters in univariate analysis. Results: The Western blot and ELISA assay both demonstrated the overexpression of plasma gelsolin in cases with cervical cancer rather than normal population, and with staged III/IV rather than stage I/II cases, In addition, gelsolin protein level also increased in conditional medium of cultured HeLa cell. Thus in vitro cell migration assay revealed decreased cell numbers while adding the gelsolin neutralizing antibody or small interference RNA compared with adding mock, non-specific antibody or Luciferase-shRNA. The other clinical parameters including stage, tumor size and lymph node status also put into consideration. The best cut-off point of gesolin Histosore to clarify the recurrence by ROC curve analysis is 115. The gelsolin Histosore (≤ 115 vs > 115, P= 0.018) and lymph node metastasis (no vs yes, P Conclusion: Overexpression of plasma and cytoplasmic gelsolin protein in cervical cancer promote cell migration by binding to actin cytoskeleton for rearrangement and cell motility. Among the clinicopathological parameters, the gelsolin overexpression and lymph node metastasis disclosed the recurrence-free survival impact by multivariate analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1740.
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- 2010
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