Browsing by Author "Lee, Jih-Chin"

Now showing 1 - 11 of 11

A site-moiety map and virtual screening approach for discovery of novel 5-LOX inhibitors
(2020-06-29)
Hsu, Kai-Cheng
;
HuangFu, Wei-Chun
;
Lin, Tony Eight
;
Chao, Min-Wu
;
Sung, Tzu-Ying
The immune system works in conjunction with inflammation. Excessive inflammation underlies various human diseases, such as asthma, diabetes and heart disease. Previous studies found that 5-lipoxygenase (5-LOX) plays a crucial role in metabolizing arachidonic acid into inflammatory mediators and is a potential therapeutic target. In this study, we performed an in silico approach to establish a site-moiety map (SiMMap) to screen for new 5-LOX inhibitors. The map is composed of several anchors that contain key residues, moiety preferences, and their interaction types (i.e., electrostatic (E), hydrogen-bonding (H), and van der Waals (V) interactions) within the catalytic site. In total, we identified one EH, one H, and five V anchors, within the 5-LOX catalytic site. Based on the SiMMap, three 5-LOX inhibitors (YS1, YS2, and YS3) were identified. An enzyme-based assay validated inhibitory activity of YS1, YS2, and YS3 against 5-LOX with an IC50 value of 2.7, 4.2, and 5.3 mu M, respectively. All three inhibitors significantly decrease LPS-induced TNF-alpha and IL-6 production, which suggests its potential use an anti-inflammatory agent. In addition, the identified 5-LOX inhibitors contain a novel scaffold. The discovery of these inhibitors presents an opportunity for designing specific anti-inflammatory drugs.
An Integrated Genomic Strategy to Identify CHRNB4 as a Diagnostic/Prognostic Biomarker for Targeted Therapy in Head and Neck Cancer
(2020-05-01)
Chuang, Yi-Hsuan
;
Lee, Chia-Hwa
;
Lin, Chun-Yu
;
Liu, Chia-Lin
;
Huang, Sing-Han
Although many studies have shown the association between smoking and the increased incidence and adverse prognosis of head and neck squamous cell carcinoma (HNSCC), the mechanisms and pharmaceutical targets involved remain unclear. Here, we integrated gene expression signatures, genetic alterations, and survival analyses to identify prognostic indicators and therapeutic targets for smoking HNSCC patients, and we discovered that the FDA-approved drug varenicline inhibits the target for cancer cell migration/invasion. We first identified 18 smoking-related and prognostic genes for HNSCC by using RNA-Seq and clinical follow-up data. One of these genes, CHRNB4 (neuronal acetylcholine receptor subunit beta-4), increased the risk of death by approximately threefold in CHRNB4-high expression smokers compared to CHRNB4-low expression smokers (log rank, p = 0.00042; hazard ratio, 2.82; 95% CI, 1.55-5.14), former smokers, and non-smokers. Furthermore, we examined the functional enrichment of co-regulated genes of CHRNB4 and its 246 frequently occurring copy number alterations (CNAs). We found that these genes were involved in promoting angiogenesis, resisting cell death, and sustaining proliferation, and contributed to much worse outcomes for CHRNB4-high patients. Finally, we performed CHRNB4 gene editing and drug inhibition assays, and the results validate these observations. In summary, our study suggests that CHRNB4 is a prognostic indicator for smoking HNSCC patients and provides a potential new therapeutic drug to prevent recurrence or distant metastasis.
Bilateral Nasolabial Cysts
(2019-02-01)
Lai, Wen-Sen
;
Lin, Yuan-Yung
;
Chu, Yueng-Hsiang
;
Lee, Jih-Chin
;
生物資訊及系統生物研究所
Clinical application of suction-tube-assisted septal submucosal dissection for endoscopic septoplasty
(2017-03)
Lai, Wen-Sen
;
Lin, Yuan-Yung
;
Shih, Cheng-Ping
;
Chen, Hsin-Chien
;
Yang, Pei-Lin
Endoscopic septoplasty has become the favored approach for the treatment of a deviated septum. Careful septal dissection results in less bleeding, clear endoscopic view, shortened operative time, and fewer postoperative complications. We describe our 5-year experience of using an 8 French Frazier suction tube for submucosal dissection compared with the traditional septoplasty. A total of 434 patients who underwent septoplasty were recruited. The patients in the study were divided into two Groups 1 and 2 based on the employed surgical techniques to treat deviated nasal septum: traditional septoplasty (Group 1: 105 patients) and suction-tube-assisted endoscopic septoplasty (Group 2: 329 patients). All the patients were followed up for a minimum of 6 months. No statistically significant differences could be traced between the groups in any demographic factor, regarding the gender, age, and the intraoperative and postoperative complications. A significantly shorter operative time was found in Group 2 (P < 0.001). The overall incidence of minor complications was 6.6% in Group 1 and 4.6% in Group 2. The suction-tube-assisted dissection technique is found to be a surgical alternative, effective with a significantly shorter operating time, and economical option in septal surgery.
Clinical assessment of diode laser-assisted endoscopic intrasphenoidal vidian neurectomy in the treatment of refractory rhinitis
(2017-12-01)
Lai, Wen-Sen
;
Cheng, Sheng-Yao
;
Lin, Yuan-Yung
;
Yang, Pei-Lin
;
Lin, Hung-Che
For chronic rhinitis that is refractory to medical therapy, surgical intervention such as endoscopic vidian neurectomy (VN) can be used to control the intractable symptoms. Lasers can contribute to minimizing the invasiveness of ENT surgery. The aim of this retrospective study is to compare in patients who underwent diode laser-assisted versus traditional VN in terms of operative time, surgical field, quality of life, and postoperative complications. All patients had refractory rhinitis with a poor treatment response to a 6-month trial of corticosteroid nasal sprays and underwent endoscopic VN between November 2006 and September 2015. They were non-randomly allocated into either a cold instrument group or a diode laser-assisted group. Vidian nerve was excised with a 940-nm continuous wave diode laser through a 600-mu m silica optical fiber, utilizing a contact mode with the power set at 5 W. A visual analog scale (VAS) was used to grade the severity of the rhinitis symptoms for quality of life assessment before the surgery and 6 months after. Of the 118 patients enrolled in the study, 75 patients underwent cold instrument VN and 43 patients underwent diode laser-assisted VN. Patients in the laser-assisted group had a significantly lower surgical field score and a lower postoperative bleeding rate than those in the cold instrument group. Changes in the VAS were significant in preoperative and postoperative nasal symptoms in each group. The application of diode lasers for vidian nerve transection showed a better surgical field and a lower incidence of postoperative hemorrhage. Recent advancements in laser application and endoscopic technique has made VN safer and more effective. We recommend this surgical approach as a reliable and effective treatment for patients with refractory rhinitis.
Diode Laser Assisted Minimal Invasive Sphenoidotomy for Endoscopic Transphenoidal Pituitary Surgery: Our Technique and Results
(2015-03-01)
Lee, Jih-Chin
;
Lai, Wen-Sen
;
Ju, Da-Tong
;
Chu, Yueng-Hsiang
;
Yang, Jinn-Moon
Background and ObjectiveDuring endoscopic sinus surgery (ESS), intra-operative bleeding can significantly compromise visualization of the surgical field. The diode laser that provides good hemostatic and vaporization effects and excellent photocoagulation has been successfully applied in endoscopic surgery with several advantages. The current retrospective study demonstrates the feasibility of diode laser-combined endoscopic sinus surgery on sphenoidotomy. Study Design/Materials and MethodsThe patients who went through endoscopic transphenoidal pituitary surgery were enrolled. During the operation, the quality of the surgical field was assessed and graded by the operating surgeon using the scale proposed by Boezaart. ResultsThe mean operation time was 37.8010.90 minutes. The mean score on the quality of surgical field was 1.95. A positive correlation between the lower surgical field quality score and the shorter surgical time was found with statistical significance (P<0.0001). No infections, hemorrhages, or other complications occurred intra- or post-operatively. ConclusionThe diode laser-assisted sphenoidotomy is a reliable and safe approach of pituitary gland surgery with minimal invasiveness. It is found that application of diode laser significantly improved quality of surgical field and shortened operation time. Lasers Surg. Med. 47:239-242, 2015. (c) 2015 Wiley Periodicals, Inc.
Gender Differences in the Association between Moderate Alcohol Consumption and Hearing Threshold Shifts
(2017-05-19)
Lin, Yuan-Yung
;
Chen, Hsin-Chien
;
Lai, Wen-Sen
;
Wu, Li-Wei
;
Wang, Chih-Hung
Hearing loss is a global public health problem with a high prevalence, significantly impairing communication and leading to a decrease in the quality of life. The association between moderate alcohol consumption (MAC) and hearing impairment has been addressed in several studies with inconsistent results. The intent of our study is to clarify the correlation between MAC and the hearing threshold and further investigate the interplay between MAC and the hearing threshold categorized by gender. The study included 4,075 participants aged 20-69 years from the 1999-2004 data of National Health and Nutrition Examination Survey (NHANES). The associations among MAC, gender differences, and high-frequency and low-frequency hearing thresholds were analyzed. We found that current female drinkers with MAC tended to have lower hearing thresholds. There is a significant protective effect of MAC on hearing threshold shifts in the US adult population, especially in females. Our research was the first study to further indicate that there is a gender difference in the association between MAC and hearing impairment. In accordance with our results, if people drink, they should consume moderate rather than higher amounts, especially in women, which may result in a reduced risk of hearing loss.
Management of different kinds of head and neck defects with the submental flap for reconstruction
(2015-12-01)
Tsai, Wan-Chun
;
Yang, Jinn-Moon
;
Liu, Shao-Cheng
;
Chu, Yueng-Hsiang
;
Lai, Wen-Sen
Head and neck surgeries often accompany with moderate-sized defects that require time-consuming reconstructions by free flaps. The submental flap is a versatile and time-effective option for reconstruction of orofacial defects providing acceptable cosmetic and functional results without requiring microsurgical techniques. A retrospective case series study of patients who underwent reconstruction with the submental flap between 2009 and 2013 was conducted. There were 36 patients (33 men and 3 women), with a mean age of 56.4 years, enrolled in this study. The primary lesion sites included oral cavity (24 patients), pharynx (8 patients), larynx (2 patients), neck (1 patient) as well as maxillary sinus (1 patient). All flaps were harvested as the myocutaneous flaps. All donor sites were closed primarily without the need of additional surgery. No complete loss of the flap was encountered and two cases developed marginal necrosis of the flap. The submental flap had a reliable pedicle and had minimal donor-site morbidity. It is an excellent flap option for patients with small- to medium-sized defects in head and neck region.
Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/beta-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts
(2020-01-01)
Chen, Jia-Hong
;
Wu, Alexander T. H.
;
Bamodu, Oluwaseun Adebayo
;
Yadav, Vijesh Kumar
;
Chao, Tsu-Yi
Oral squamous cell carcinoma (OSCC) is among the most commonly diagnosed malignancies in the world. Patients with OSCC often develop treatment resistance, resulting in a poor prognosis. Mounting evidence indicates that interactions between cancerous cells and other components of the tumor microenvironment (TME) determine their response to treatment. Herein, we examined the role of cancer stem cell-derived extracellular vesicles (CSC_EVs) generated from CAL27 and SCC-15 OSCC cells in the development of cisplatin (CDDP) resistance. We demonstrated that CSC_EVs enhance CDDP resistance, clonogenicity, and the tumorsphere formation potential of OSCC cells. Our bioinformatics analyses revealed that OSCC_EVs are enriched with microRNA (miR)-21-5p and are associated with increased metastasis, stemness, chemoresistance, and poor survival in patients with OSCC. Mechanistically, enhanced activity of CSC_EVs was positively correlated with upregulated beta-catenin, phosphatidylinositol-3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and transforming growth factor (TGF)-beta 1 messenger (m)RNA and protein expression levels. CSC_EVs also conferred a cancer-associated fibroblast (CAF) phenotype on normal gingival fibroblasts (NGFs), with the resultant CAFs enhancing the oncogenicity of OSCC cells. Interestingly, treatment with ovatodiolide (OV), the bioactive component of Anisomeles indica, suppressed OSCC tumorigenesis by reducing the cargo content of EVs derived from CSCs, suppressing self-renewal, and inhibiting the NGF-CAF transformation by disrupting EV-TME interactions. Moreover, by suppressing miR-21-5p, STAT3, and mTOR expressions in CSC_EVs, OV re-sensitized CSCs to CDDP and suppressed OSCC tumorigenesis. In vivo, treatment with OV alone or in combination with CDDP significantly reduced the tumor sphere-forming ability and decreased EV cargos containing mTOR, PI3K, STAT3, beta-catenin, and miR-21-5p. In summary, our findings provide further strong evidence of OV's therapeutic effect in OSCC.
The use of adjunctive traditional Chinese medicine therapy and survival outcome in patients with head and neck cancer: a nationwide population-based cohort study
(2015-12-01)
Lin, Hung-Che
;
Lin, Cheng-Li
;
Huang, Wen-Yen
;
Shangkuan, Wei-Chuan
;
Kang, Bor-Hwang
Background: Traditional Chinese medicine (TCM) is widely used in the treatment of patients with several types of cancer. However, no large-scale clinical studies have evaluated whether TCM is associated with better survival in patients with head and neck cancer (HNC). Methods: The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort study of patients with HNC between 2001 and 2011. The patients with HNC were separated into TCM users and non-users, and Cox regression models were applied to determine the association between the use of TCM and survival outcome. Results: The TCM and comparison cohorts comprised data for 2966 and 2670 patients, respectively. The mean age was 51.3 years in the TCM cohort and 51.7 years in the comparison cohort. Multivariate analysis demonstrated that the use of TCM was significantly associated with lower risk of all-cause mortality by 32% (adjusted hazard ratio, 0.68; 95% confidence interval, 0.62-0.75). Patients with longer TCM use had a lower mortality rate (P for trend<0.001). Conclusions: Our study showed that adjunctive therapy with TCM is associated with higher survival outcome. However, some limitations exist, such as the lack of information of cancer stage. In addition, causality cannot be assessed with this retrospective study. A randomized controlled trial to test the effect of adjunctive TCM therapy in HNC patients is needed.
Vascular anatomy is a determining factor of successful submental flap raising: a retrospective study of 70 clinical cases
(2017-09-19)
Lin, Hung-Che
;
Huan, Yuahn-Sieh
;
Chu, Yueng-Hsiang
;
Liu, Shao-Cheng
;
Shangkuan, Wei-Chuan
The vascular anatomy of submental flaps (SFs) represents a determining factor in successful SF raising. However, little attention has been focused on the venous return of SFs. Thus, the present study aimed to investigate SF venous return. This study enrolled patients who underwent SF reconstructive surgery in a tertiary referral center between November 2009 and October 2016. The drainage pathway of the SF venous return was routinely identified during the course of our operations to prevent damage during head and neck surgery. The venous return data of 70 patients were reviewed. The size of the flaps ranged from 15 to 84 cm(2), and total flap loss was not observed in the case series. All of the submental arteries originated from the facial artery; however, the submental veins of 70 patients returned to either the internal jugular vein (IJV, 72.9%) or the external jugular vein (EJV, 27.1%). Our data suggest that drainage of the submental vein into the EJV, which has been previously overlooked, should receive greater attention during SF surgeries. The results support mandatory preservation of the EJV and IJV and indicate that vascular anatomy is a determining factor for successful SF raising.