Wen-Lin Hsu
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Previous Organizations / Institutes
The organizations / institutes from the scholar's other articles in the past ten years
Wen-Lin Hsu has a total of 47 co-authors. Here are the top co-authors by number of shared publications:
- Dai-Wei Liu
Cancer Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
3 shared publications - Ren-Jun Hsu
Cancer Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
3 shared publications - Ching-Feng Weng
Department of Physiology, School of Basic Medical Sciences, Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen 361023, China
2 shared publications - Hui-Chun Chung
Department of Nursing, Hualien Tzu Chi Hospital, Hualien 970, Taiwan
2 shared publications - Li-Hsuen Chen
Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan
2 shared publications Ren-Jun Hsu
Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Radiat Oncol, 707,Sect 3,Chung Yang Rd, Hualien, Taiwan
2 shared publications
Latest Publications
- Open Access
Aspirin and Primary Cancer Risk Reduction in Ischemic Cardiac or Cerebrovascular Disease Survivors: A Nationwide Population-Based Propensity-Matched Cohort Study
Ischemic cardiac or cerebrovascular disease (ICCD) survivors represent a subpopulation with a high cancer risk. Antiplatelet medications, such as aspirin, remain a fundamental therapy for the secondary prevention of ischemic attack in these patients. We conducted a population-based cohort study to investigate the association of long-term low-dose aspirin use with the risk of primary cancer in ICCD survivors. Patients aged ≥20 years with newly diagnosed ICCD (n = 98,519) between January 2000 and December 2013 were identified from the Taiwan National Health Insurance Research Database. The aspirin user and nonuser groups (each n = 24,030) were propensity-matched (1:1) for age, sex, comorbidities, prior medications, ICCD diagnosis year, and year of index dates. The incidence rate of primary cancer was significantly lower in the user group (6.49/1000 person-years) than in the nonuser group (14.04/1000 person-years). Multivariate Cox regression analysis indicated that aspirin use was an independent factor associated with a reduced risk of primary cancer (aHR (95% confidence interval) = 0.42 (0.38–0.45)) after adjustment. Kaplan–Meier curve analysis revealed that the cumulative incidence rate of primary cancer was significantly lower (p < 0.0001) in the user group than in the nonuser group over the 14-year follow-up period. Subgroup analyses demonstrated that this anticancer effect increased with duration of treatment and with similar estimates in women and men. In addition, aspirin use was associated with a reduced risk for seven out of the ten most common cancers in Taiwan. These findings suggest the anticancer effect of aspirin in ICCD survivors and provide information for assessing the benefit-to-risk profile of aspirin as an antiplatelet medication in these patients.
Open AccessAspirin and Primary Cancer Risk Reduction in Ischemic Cardiac or Cerebrovascular Disease Survivors: A Nationwide Population-Based Propensity-Matched Cohort Study
Ischemic cardiac or cerebrovascular disease (ICCD) survivors represent a subpopulation with a high cancer risk. Antiplatelet medications, such as aspirin, remain a fundamental therapy for the secondary prevention of ischemic attack in these patients. We conducted a population-based cohort study to investigate the association of long-term low-dose aspirin use with the risk of primary cancer in ICCD survivors. Patients aged ≥20 years with newly diagnosed ICCD (n = 98,519) between January 2000 and December 2013 were identified from the Taiwan National Health Insurance Research Database. The aspirin user and nonuser groups (each n = 24,030) were propensity-matched (1:1) for age, sex, comorbidities, prior medications, ICCD diagnosis year, and year of index dates. The incidence rate of primary cancer was significantly lower in the user group (6.49/1000 person-years) than in the nonuser group (14.04/1000 person-years). Multivariate Cox regression analysis indicated that aspirin use was an independent factor associated with a reduced risk of primary cancer (aHR (95% confidence interval) = 0.42 (0.38–0.45)) after adjustment. Kaplan–Meier curve analysis revealed that the cumulative incidence rate of primary cancer was significantly lower (p < 0.0001) in the user group than in the nonuser group over the 14-year follow-up period. Subgroup analyses demonstrated that this anticancer effect increased with duration of treatment and with similar estimates in women and men. In addition, aspirin use was associated with a reduced risk for seven out of the ten most common cancers in Taiwan. These findings suggest the anticancer effect of aspirin in ICCD survivors and provide information for assessing the benefit-to-risk profile of aspirin as an antiplatelet medication in these patients.
- Open Access
- 11 November 2022
- Published by MDPI AG in Diagnostics
- Vol. 12 (11) , 2765
Fully Convolutional Network for the Semantic Segmentation of Medical Images: A Survey
There have been major developments in deep learning in computer vision since the 2010s. Deep learning has contributed to a wealth of data in medical image processing, and semantic segmentation is a salient technique in this field. This study retrospectively reviews recent studies on the application of deep learning for segmentation tasks in medical imaging and proposes potential directions for future development, including model development, data augmentation processing, and dataset creation. The strengths and deficiencies of studies on models and data augmentation, as well as their application to medical image segmentation, were analyzed. Fully convolutional network developments have led to the creation of the U-Net and its derivatives. Another noteworthy image segmentation model is DeepLab. Regarding data augmentation, due to the low data volume of medical images, most studies focus on means to increase the wealth of medical image data. Generative adversarial networks (GAN) increase data volume via deep learning. Despite the increasing types of medical image datasets, there is still a deficiency of datasets on specific problems, which should be improved moving forward. Considering the wealth of ongoing research on the application of deep learning processing to medical image segmentation, the data volume and practical clinical application problems must be addressed to ensure that the results are properly applied.
- 11 November 2022
- Published by MDPI AG in Diagnostics
- Vol. 12 (11) , 2765
Open AccessFully Convolutional Network for the Semantic Segmentation of Medical Images: A Survey
There have been major developments in deep learning in computer vision since the 2010s. Deep learning has contributed to a wealth of data in medical image processing, and semantic segmentation is a salient technique in this field. This study retrospectively reviews recent studies on the application of deep learning for segmentation tasks in medical imaging and proposes potential directions for future development, including model development, data augmentation processing, and dataset creation. The strengths and deficiencies of studies on models and data augmentation, as well as their application to medical image segmentation, were analyzed. Fully convolutional network developments have led to the creation of the U-Net and its derivatives. Another noteworthy image segmentation model is DeepLab. Regarding data augmentation, due to the low data volume of medical images, most studies focus on means to increase the wealth of medical image data. Generative adversarial networks (GAN) increase data volume via deep learning. Despite the increasing types of medical image datasets, there is still a deficiency of datasets on specific problems, which should be improved moving forward. Considering the wealth of ongoing research on the application of deep learning processing to medical image segmentation, the data volume and practical clinical application problems must be addressed to ensure that the results are properly applied.
- Open Access
- 1 November 2021
- Published by Wiley in Cancer Medicine
- Vol. 10 (22) , 8162-8171
Association between Helicobacter pylori infection and mortality risk in prostate cancer patients receiving androgen deprivation therapy: A real-world evidence study
Purpose Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer and may affect androgen activity in men. The association between H. pylori and androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) remains unclear. Methods This retrospective cohort study linked National Health Insurance (NHI) data to Taiwan Cancer Registry (TCR) and Taiwan Death Registry (TDR) between 1995 and 2016. PCa patients who received ADT were classified into H. pylori infection and non-H. pylori infection groups. The outcomes were overall mortality, prostate cancer-specific mortality, and castration-resistant prostate cancer (CRPC). Propensity score matching was adopted for the primary analysis and inverse probability of treatment weighting (IPTW) was used for the sensitivity analysis. Results Of the 62,014 selected PCa patients, 23,701 received ADT, of whom 3516 had H. pylori infections and 20,185 did not. After matching, there were 3022 patients in the H. pylori infection group and 6044 patients in the non-H. pylori infection group. The mean follow-up period for the matched cohort was 4.8 years. Compared to the non-H. pylori group, the H. pylori group was significantly associated with decreased risks of all-cause mortality (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.84-0.96) and prostate cancer-specific mortality (HR 0.88; 95% CI 0.81-0.95) in the matched analysis. Conclusions H. pylori infection was associated with a reduced risk of mortality in PCa patients receiving ADT.
- 1 November 2021
- Published by Wiley in Cancer Medicine
- Vol. 10 (22) , 8162-8171
Open AccessAssociation between Helicobacter pylori infection and mortality risk in prostate cancer patients receiving androgen deprivation therapy: A real-world evidence study
Purpose Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer and may affect androgen activity in men. The association between H. pylori and androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) remains unclear. Methods This retrospective cohort study linked National Health Insurance (NHI) data to Taiwan Cancer Registry (TCR) and Taiwan Death Registry (TDR) between 1995 and 2016. PCa patients who received ADT were classified into H. pylori infection and non-H. pylori infection groups. The outcomes were overall mortality, prostate cancer-specific mortality, and castration-resistant prostate cancer (CRPC). Propensity score matching was adopted for the primary analysis and inverse probability of treatment weighting (IPTW) was used for the sensitivity analysis. Results Of the 62,014 selected PCa patients, 23,701 received ADT, of whom 3516 had H. pylori infections and 20,185 did not. After matching, there were 3022 patients in the H. pylori infection group and 6044 patients in the non-H. pylori infection group. The mean follow-up period for the matched cohort was 4.8 years. Compared to the non-H. pylori group, the H. pylori group was significantly associated with decreased risks of all-cause mortality (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.84-0.96) and prostate cancer-specific mortality (HR 0.88; 95% CI 0.81-0.95) in the matched analysis. Conclusions H. pylori infection was associated with a reduced risk of mortality in PCa patients receiving ADT.
- Open Access
- 21 July 2021
- Published by MDPI AG in International Journal of Environmental Research and Public Health
- Vol. 18 (15) , 7750
Development and Validation of Nurses’ Well-Being and Caring Nurse–Patient Interaction Model: A Psychometric Study
Nurses’ care nurse–patient interaction (CNPI) competence is critical for improving nursing care quality. The focus is the psychological quality of nurses, which may be derived from their sense of well-being. The purpose of this study was to develop a conceptual model of nurses’ well-being and their CNPI competence. A cross-sectional survey was conducted with a total of 212 valid questionnaires obtained from a medical center. Structural equation modeling analysis was performed to validate the conceptual model. The results demonstrated the positive correlation between two constructs of nurses’ well-being (“contentment” and “joyfulness”) and CNPI competence. A positive correlation between nurses’ CNPI competence and their health-promoting lifestyle and work environment satisfaction was supported. Among the constructs of CNPI competence, “respect patients’ life experience” was the most correlated with their well-being, health-promoting lifestyle, and work environment satisfaction. The constructs of these three scales, which showed a middle correlation with CNPI competence, are psychological constructs rather than material constructs. When nurses have a greater sense of well-being, a positive attitude towards life, and feel supported and respected in their work environment, their CNPI competence increases. The findings of this study provide important insights and can serve as empirical evidence for nursing managers to enhance nurses’ CNPI competence.
- 21 July 2021
- Published by MDPI AG in International Journal of Environmental Research and Public Health
- Vol. 18 (15) , 7750
Open AccessDevelopment and Validation of Nurses’ Well-Being and Caring Nurse–Patient Interaction Model: A Psychometric Study
Nurses’ care nurse–patient interaction (CNPI) competence is critical for improving nursing care quality. The focus is the psychological quality of nurses, which may be derived from their sense of well-being. The purpose of this study was to develop a conceptual model of nurses’ well-being and their CNPI competence. A cross-sectional survey was conducted with a total of 212 valid questionnaires obtained from a medical center. Structural equation modeling analysis was performed to validate the conceptual model. The results demonstrated the positive correlation between two constructs of nurses’ well-being (“contentment” and “joyfulness”) and CNPI competence. A positive correlation between nurses’ CNPI competence and their health-promoting lifestyle and work environment satisfaction was supported. Among the constructs of CNPI competence, “respect patients’ life experience” was the most correlated with their well-being, health-promoting lifestyle, and work environment satisfaction. The constructs of these three scales, which showed a middle correlation with CNPI competence, are psychological constructs rather than material constructs. When nurses have a greater sense of well-being, a positive attitude towards life, and feel supported and respected in their work environment, their CNPI competence increases. The findings of this study provide important insights and can serve as empirical evidence for nursing managers to enhance nurses’ CNPI competence.
- Open Access
- 1 January 2021
- Published by Medknow in Tzu Chi Medical Journal
- Vol. 33 (1) , 55-60
Androgen deprivation therapy and the risk of subsequent keratitis
Objectives: The objective of the study was to determine the risk of subsequent keratitis in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT). Materials and Methods: Three thousand three hundred and nine patients with PCa were identified using data from Taiwan’s National Health Insurance Research Database for 2001 through 2013. Among those patients, 856 treated with ADT comprised the study group, while 856 non-ADT-treated patients matched with 1:1 propensity-score-matched analysis comprised the control group. The demographic characteristics and comorbidities of all the patients were analyzed, and Cox proportional hazards regression was utilized to determine the hazard ratios (HRs) for subsequent keratitis. Results: A total of 157 (9.2%) patients had newly diagnosed keratitis. Compared to the non-ADT-treated patients, the ADT-treated patients had a reduced risk of subsequent keratitis, with an adjusted HR of 0.38 (95% confidence interval: 0.27–0.55; P < 0.001). Conclusion: ADT treatment apparently decreased the risk of subsequent keratitis in the investigated PCa patients, but the clinical significance of this finding should be further assessed in additional studies.
- 1 January 2021
- Published by Medknow in Tzu Chi Medical Journal
- Vol. 33 (1) , 55-60
Open AccessAndrogen deprivation therapy and the risk of subsequent keratitis
Objectives: The objective of the study was to determine the risk of subsequent keratitis in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT). Materials and Methods: Three thousand three hundred and nine patients with PCa were identified using data from Taiwan’s National Health Insurance Research Database for 2001 through 2013. Among those patients, 856 treated with ADT comprised the study group, while 856 non-ADT-treated patients matched with 1:1 propensity-score-matched analysis comprised the control group. The demographic characteristics and comorbidities of all the patients were analyzed, and Cox proportional hazards regression was utilized to determine the hazard ratios (HRs) for subsequent keratitis. Results: A total of 157 (9.2%) patients had newly diagnosed keratitis. Compared to the non-ADT-treated patients, the ADT-treated patients had a reduced risk of subsequent keratitis, with an adjusted HR of 0.38 (95% confidence interval: 0.27–0.55; P < 0.001). Conclusion: ADT treatment apparently decreased the risk of subsequent keratitis in the investigated PCa patients, but the clinical significance of this finding should be further assessed in additional studies.
- Open Access
- 20 May 2020
- Published by MDPI AG in International Journal of Environmental Research and Public Health
- Vol. 17 (10) , 3582
Nurses’ Well-Being, Health-Promoting Lifestyle and Work Environment Satisfaction Correlation: A Psychometric Study for Development of Nursing Health and Job Satisfaction Model and Scale
Although promoting healthy work environments to enhance staff members’ health and well-being is a growing trend, no empirical studies on such a model have been conducted in the nursing management field. The purpose of this study was to develop and validate measurement scales and a conceptual model of nurses’ well-being, health-promoting lifestyle, and work environment satisfaction (WHS). A cross-sectional survey was conducted to develop a WHS model and Nursing Health and Job Satisfaction (NHJS) scale. A total of 672 questionnaires were obtained from registered nurses by stratified random sampling for validation analysis. The percentage of total variance explained greater than 92.6%, suggesting a good ability of the scales to explain the variability in participants’ responses. The hypotheses of positive correlations among nurses’ health-promoting lifestyle, well-being, and work environment satisfaction were supported. The WHS model demonstrates the positive correlation with correlation coefficients of 0.57–0.86 among nurses’ health-promoting lifestyle, well-being, and work environment satisfaction. Nurses’ attitudes play a key role in promoting a healthy lifestyle. The most important work environment satisfaction variable for improved sense of well-being is respect from other medical staff. The findings can serve as an instrument for hospital nursing administrators to accurately assess and enhance nurses’ retention rate and health.
- 20 May 2020
- Published by MDPI AG in International Journal of Environmental Research and Public Health
- Vol. 17 (10) , 3582
Open AccessNurses’ Well-Being, Health-Promoting Lifestyle and Work Environment Satisfaction Correlation: A Psychometric Study for Development of Nursing Health and Job Satisfaction Model and Scale
Although promoting healthy work environments to enhance staff members’ health and well-being is a growing trend, no empirical studies on such a model have been conducted in the nursing management field. The purpose of this study was to develop and validate measurement scales and a conceptual model of nurses’ well-being, health-promoting lifestyle, and work environment satisfaction (WHS). A cross-sectional survey was conducted to develop a WHS model and Nursing Health and Job Satisfaction (NHJS) scale. A total of 672 questionnaires were obtained from registered nurses by stratified random sampling for validation analysis. The percentage of total variance explained greater than 92.6%, suggesting a good ability of the scales to explain the variability in participants’ responses. The hypotheses of positive correlations among nurses’ health-promoting lifestyle, well-being, and work environment satisfaction were supported. The WHS model demonstrates the positive correlation with correlation coefficients of 0.57–0.86 among nurses’ health-promoting lifestyle, well-being, and work environment satisfaction. Nurses’ attitudes play a key role in promoting a healthy lifestyle. The most important work environment satisfaction variable for improved sense of well-being is respect from other medical staff. The findings can serve as an instrument for hospital nursing administrators to accurately assess and enhance nurses’ retention rate and health.
- Open Access
- 1 May 2019
- Published by Wolters Kluwer Health in Medicine
- Vol. 98 (21) , e15363
The association between epididymo-orchitis and prostate cancer
To determine whether epididymo-orchitis, a common infectious disease among men, is associated with subsequent prostate cancer (PCa) via a nationwide cohort study. This nationwide population-based study of patients treated from 2001 to 2013 included a total of 4991 patients with epididymo-orchitis as the study group and 19,922 matched patients without epididymo-orchitis as a control group. We tracked the patients in both groups for a 5-year period to identify any new cases of PCa. Cox proportional hazards regressions were performed to calculate the hazard ratio (HR) of PCa during this 5-year follow-up period. Of the 24,913 patients in the study, 235 (0.9%) were newly diagnosed with PCa during the 5-year follow-up period; 77 (1.5%) of those were from the epididymo-orchitis group and 158 (0.8%) were from the control group. Compared to the patients without epididymo-orchitis, the adjusted HR for PCa for the patients with epididymo-orchitis was 1.56 (95% confidence interval [CI]: 1.18–2.06) during the 5-year follow-up period. Ages of more than 70 years, higher incomes, hypertension, and hyperlipidemia were more strongly associated with PCa in the study group than in the control group. The results were associated with a 56% increased risk for PCa among patients with epididymo-orchitis. Epididymo-orchitis may play an etiological role in the development of PCa in Asian populations. Further studies are warranted, however, to investigate the relationship between epididymo-orchitis and PCa.
- 1 May 2019
- Published by Wolters Kluwer Health in Medicine
- Vol. 98 (21) , e15363
Open AccessThe association between epididymo-orchitis and prostate cancer
To determine whether epididymo-orchitis, a common infectious disease among men, is associated with subsequent prostate cancer (PCa) via a nationwide cohort study. This nationwide population-based study of patients treated from 2001 to 2013 included a total of 4991 patients with epididymo-orchitis as the study group and 19,922 matched patients without epididymo-orchitis as a control group. We tracked the patients in both groups for a 5-year period to identify any new cases of PCa. Cox proportional hazards regressions were performed to calculate the hazard ratio (HR) of PCa during this 5-year follow-up period. Of the 24,913 patients in the study, 235 (0.9%) were newly diagnosed with PCa during the 5-year follow-up period; 77 (1.5%) of those were from the epididymo-orchitis group and 158 (0.8%) were from the control group. Compared to the patients without epididymo-orchitis, the adjusted HR for PCa for the patients with epididymo-orchitis was 1.56 (95% confidence interval [CI]: 1.18–2.06) during the 5-year follow-up period. Ages of more than 70 years, higher incomes, hypertension, and hyperlipidemia were more strongly associated with PCa in the study group than in the control group. The results were associated with a 56% increased risk for PCa among patients with epididymo-orchitis. Epididymo-orchitis may play an etiological role in the development of PCa in Asian populations. Further studies are warranted, however, to investigate the relationship between epididymo-orchitis and PCa.
- 1 April 2017
- Published by Oxford University Press (OUP) in Dentomaxillofacial Radiology
- Vol. 46 (4) , 20160395
Investigation of an optimized scanning protocol for the dentomaxillofacial region using 320-slice multidetector computed tomography
To propose an imaging protocol that provides satisfactory image quality for oral examination while minimizing radiation dosage using 320-slice multidetector CT (MDCT). An anthropomorphic head phantom was scanned using 320 MDCT with protocols combining different scanning modes: volume scanning (whole or local) vs helical scanning (80- or 64-slice detectors); tube voltage settings (80 kVp, 120 kVp and 135 kVp); and tube current settings (60 mA, 80 mA, 100 mA and 120 mA). A total of six anatomical bone structures and three anatomical soft-tissue structures were assessed using quantitative and qualitative analysis in the three orthographic planes (axial, sagittal and coronal). A figure of merit (FOM) was used to determine the optimal imaging protocol in terms of tube voltage, tube current and scanning mode. The 80-kVp setting had the worst quantitative and qualitative results (both p < 0.001) compared with the 135-kVp and 120-kVp settings, especially for soft-tissue structures. A significant difference was noted for the scores obtained using a tube current between 120 mA and 60 mA by quantitative analysis, but not by qualitative analysis. Volume scans using either whole or local modes had a significantly higher FOM than helical scanning of 80 or 64 slices. In 320 MDCT, a protocol using 135 kVp, 80 mA and the volume-scanning mode (whole or local) offers adequate visualization of both soft-tissue and bone structures while keeping the radiation dose as low as possible. This may therefore be considered a first choice among a wide selection of scanning protocols for dentomaxillofacial CT.
- 1 April 2017
- Published by Oxford University Press (OUP) in Dentomaxillofacial Radiology
- Vol. 46 (4) , 20160395
Investigation of an optimized scanning protocol for the dentomaxillofacial region using 320-slice multidetector computed tomography
To propose an imaging protocol that provides satisfactory image quality for oral examination while minimizing radiation dosage using 320-slice multidetector CT (MDCT). An anthropomorphic head phantom was scanned using 320 MDCT with protocols combining different scanning modes: volume scanning (whole or local) vs helical scanning (80- or 64-slice detectors); tube voltage settings (80 kVp, 120 kVp and 135 kVp); and tube current settings (60 mA, 80 mA, 100 mA and 120 mA). A total of six anatomical bone structures and three anatomical soft-tissue structures were assessed using quantitative and qualitative analysis in the three orthographic planes (axial, sagittal and coronal). A figure of merit (FOM) was used to determine the optimal imaging protocol in terms of tube voltage, tube current and scanning mode. The 80-kVp setting had the worst quantitative and qualitative results (both p < 0.001) compared with the 135-kVp and 120-kVp settings, especially for soft-tissue structures. A significant difference was noted for the scores obtained using a tube current between 120 mA and 60 mA by quantitative analysis, but not by qualitative analysis. Volume scans using either whole or local modes had a significantly higher FOM than helical scanning of 80 or 64 slices. In 320 MDCT, a protocol using 135 kVp, 80 mA and the volume-scanning mode (whole or local) offers adequate visualization of both soft-tissue and bone structures while keeping the radiation dose as low as possible. This may therefore be considered a first choice among a wide selection of scanning protocols for dentomaxillofacial CT.
- Open Access
- 8 July 2016
- Published by Springer Nature in BMC Cancer
- Vol. 16 (1) , 431
Involvement of DNMT 3B promotes epithelial-mesenchymal transition and gene expression profile of invasive head and neck squamous cell carcinomas cell lines
The 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile. Invasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 μm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array. DNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5′ region of E-cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion. DNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation.
- 8 July 2016
- Published by Springer Nature in BMC Cancer
- Vol. 16 (1) , 431
Open AccessInvolvement of DNMT 3B promotes epithelial-mesenchymal transition and gene expression profile of invasive head and neck squamous cell carcinomas cell lines
The 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile. Invasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 μm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array. DNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5′ region of E-cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion. DNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation.
- Open Access
- 17 July 2015
- Published by MDPI AG in Marine Drugs
- Vol. 13 (7) , 4436-4451
Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia
Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1) plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF) is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF) secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24) cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.
- 17 July 2015
- Published by MDPI AG in Marine Drugs
- Vol. 13 (7) , 4436-4451
Open AccessLow Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia
Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1) plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF) is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF) secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24) cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.