Browsing by Author "Wang, Yen-Yun"

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DNA Repair Protein Rad51 Induces Tumor Growth and Metastasis in Esophageal Squamous Cell Carcinoma via a p38/Akt-Dependent Pathway
(2020-06-01)
Chiu, Wen-Chin
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Fang, Pen-Tzu
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Lee, Yi-Chen
;
Wang, Yen-Yun
;
Su, Yu-Han
Background Rad51 is a protein which plays a vital role in DNA double-strand break repair and maintenance of telomeres. However, the underlying mechanism for its action in esophageal squamous cell carcinoma (ESCC) remains unclear. Patients and Methods Eighty-seven patients with ESCC were enrolled in this study. Expression of Rad51 in ESCC was determined by immunohistochemistry and correlated with clinicopathological variables by Chi square test. The role of Rad51 in patient survival was determined by Kaplan-Meier estimates. The effects of Rad51 knockdown and overexpression on esophageal cancer growth, migration, and invasion were examined using TE8, CE81T, and KYSE70 cells. The mechanisms involved were also analyzed. Nude mice models were used for assessment of tumor growth. Results Rad51 staining was predominantly observed in ESCC patients. ESCC patients with high Rad51 expression had significantly decreased survival (P < 0.001) combined with increased tumor size (P = 0.034) and lymph node metastasis (P = 0.039). Rad51 overexpression promoted, while its knockdown attenuated, esophageal cancer cell viability through cell cycle entry and migration/invasion via epithelial-mesenchymal transition. Moreover, Rad51 overexpression increased colony formation in vitro and tumor growth in vivo. In addition, high Rad51 expression increased cancer progression through the p38/Akt/Snail signaling pathway. Conclusions This study indicates a new biological role for Rad51 in ESCC progression. Rad51 may serve as a potential prognostic biomarker and therapeutic target for ESCC patients.
Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury
(2019-04-04)
Lee, Yi-Chen
;
Lin, Chun-Yu
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Chen, Yen-Hsu
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Chiu, Wen-Chin
;
Wang, Yen-Yun
Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NF kappa B pathway, and increased the expression of pro-inflammatory cytokines, including IL1-beta, IL-6, and TNF-alpha in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NF kappa B pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.
MAL-PDT inhibits oral precancerous cells and lesions via autophagic cell death
(2019-04-01)
Wang, Yen-Yun
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Chen, Yuk-Kwan
;
Hu, Chu-Sung
;
Xiao, Ling-Yi
;
Huang, Wan-Ling
Background Oral cancer is a common cancer with a high mortality rate. While surgery is the most effective treatment for oral cancer, it frequently causes deformity and dysfunction in the orofacial region. In this study, methyl aminolevulinate photodynamic therapy (MAL-PDT) as a prevention tool against progression of precancerous lesion to oral cancer was explored. Methods For in vitro studies, we evaluated the effects of MAL-PDT on viability of DOK oral precancerous cells by XTT, cell morphology by TEM, and intracellular signaling pathways by flow cytometry, Western blotting, and immunofluorescence. For in vivo study, DMBA was used to induce oral precancerous lesions in hamsters followed by MAL-PDT treatment. We measured tumor size and body weight weekly. After sacrifice, buccal pouch lesions were processed for H&E stain and immunohistochemistry analysis. Results MAL-PDT induced autophagic cell death in DOK oral precancerous cells. The autophagy-related markers LC3II and p62/SQSTM1 and autophagosome formation in DOK cells were increased after MAL-PDT treatment. In vivo, MetvixA (R)-PDT treatment decreased tumor growth and enhanced LC3II expression in hamster buccal pouch tumors induced by DMBA. Conclusions Our in vitro and in vivo results suggest that MAL-PDT may provide an effective therapy for oral precancerous lesions through induction of autophagic cell death.
Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer
(2020-01-01)
Huang, Jyun-Yuan
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Wang, Yen-Yun
;
Lo, Steven
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Tseng, Ling-Ming
;
Chen, Dar-Ren
Adipose-derived stem cells (ADSCs) have been implicated in tumor growth and metastasis in breast cancer. ADSCs exhibit tumor tropism, and are of increasing clinical relevance due to the autologous fat grafting for breast reconstruction. Although we have previously shown that a high level of the adipocytokine visfatin in human breast cancer tissues correlated with tumor progression mediated by cAbl and STAT3, the effects of visfatin in the tumor microenvironment are unclear. To understand how visfatin modulates breast cancer within the tumor-stromal environment, we examined determinants of breast cancer progression using a visfatin-primed ADSCs-tumor co-culture model. ADSCs were isolated from tumor-free adipose tissue adjacent to breast tumors. ADSCs were treated with or without visfatin for 48 h and then collected for co-culture with breast cancer cell line MDA-MB-231 for 72 h in a transwell system. We found that the MDA-MB-231 cells co-cultured with visfatin-treated ADSCs (vADSCs) had higher levels of cell viability, anchorage independent growth, migration, invasion, and tumorsphere formation than that co-cultured with untreated ADSCs (uADSCs). Growth differentiation factor 15 (GDF15) upregulation was found in the co-culture conditioned medium, with GDF15 neutralizing antibody blocking the promoting effect on MDA-MB-231 in co-culture. In addition, a GDF15-induced AKT pathway was found in MDA-MB-231 and treatment with PI3K/AKT inhibitor also reversed the promoting effect. In an orthotopic xenograft mouse model, MDA-MB-231 co-injected with vADSCs formed a larger tumor mass than with uADSCs. Positive correlations were noted between visfatin, GDF15, and phosphor-AKT expressions in human breast cancer specimens. In conclusion, visfatin activated GDF15-AKT pathway mediated via ADSCs to facilitate breast cancer progression.