Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study

Hung-Chun Fu,Jen-Ruei Chen,Min-Yu Chen,Keng-Fu Hsu,Wen-Fang Cheng,An Jen Chiang,Yu-Min Ke,Yu-Chieh Chen,Yin-Yi Chang,Chia-Yen Huang,Chieh-Yi Kang,Yuan-Yee Kan,Sheng-Mou Hsiao,Ming-Shyen Yen 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

Objective: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. Methods: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. Results: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR=7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI, 1.38–19.1) and DSS (HR=5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. Conclusion: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.

Nucleophosmin modulates the alleviation of atopic dermatitis caused by the marine-derived compound dihydroaustrasulfone alcohol

Han-Chun Hung,Chien-Wei Feng,Yen-You Lin,Chun-Hong Chen,Kuan-Hao Tsui,Wu-Fu Chen,Chieh-Yu Pa,Jyh-Horng Sheu,Chun-Sung Sung,Zhi-Hong Wen 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

Quantifying and Clustering Texture Traits in Flowers of Genus Sinningia

( Tzu-ting Hung ),( Hao-chun Hsu ),( Yan-fu Kuo ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

The flowers of genus Sinningia has a high degree of diversity in stripe and spot patterns. Delimiting these pattern as textural traits usually rely on horticulturalists’ judgment. However, the judgment by intuitive observation is subjective. This study aimed to quantify the stripe and spot pattern of genus Sinningia flowers automatically using machine vision and to cluster the textural traits using machine learning. The image of ventral petal was acquired using flatbed scanners. Two regions of interest (ROI), lobe region and tube region, were identified and were used for the feature quantification. The features of stripe and spot patterns were then quantified from the ROI using Gabor and Laplacian of Gaussian filters, respectively. The k-means clustering algorithm was next applied to the feature of patterns. The clusters were significantly associated with the textural traits.

Efficacy and Safety of 12 Weeks of Daclatasvir, Asunaprevir Plus Ribavirin for the Treatment of HCV Genotype 1b Infection without Baseline NS5A Resistance-Associated Variants (DARING)-Interim Report

( Ming-lung Yu ),( Chao-hung Hung ),( Yi-hsiang Huang ),( Cheng-yuan Peng ),( Chun-yen Lin ),( Pin-nan Cheng ),( Rong-nan Chien ),( Shih-jer Hsu ),( Chen-hua Liu ),( Jee-fu Huang ),( Chung-feng Huang 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The current study aims to elucidate the treatment efficacy (defined as undetectable HCV RNA throughout 12 weeks of post-treatment follow-up, SVR12) and safety DCV/ASV plus ribavirin for 12 weeks in HCV-1b patients without NS5A RAS. Methods: This is a single-arm, open-label phase 2 study. Seventy directly acting antivirals (DAA)-naïve HCV-1b patients without L31/Y93 RAS are planned to receive daclatasvir (60 mg/ day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks. After treatment they were followed up for 12 weeks. Results: As of 31 Oct 2017, 58 eligible patients are allocated to treatment, with a mean age of 59.3 years and female predominance (67.2%, 39/58). The mean HCV RNA was 5.87+0.77 log10 IU/mL; 23 patients (39.7 %) had significant hepatic fibrosis (>F2). In the modified intention-to-treat analysis, the rate of undetectable HCV at week 1, week 2, week 4, week 8 and endof- treatment was 25 % (14/56), 84.8 % (39/46), 100 % (46/46), 100 % (38/38) and 100 % (27/27), respectively. Undetectable HCV RNA were observed in all of the patients with HCV RNA assessable 4 weeks (SVR4, 18/18) and 12 weeks (SVR12, 12/12) post treatment. None of the 18 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. The most common adverse event was fatigue (78.3 %), followed by pruritus (65.2 %) and dizziness (52.2 %), of which were considered as ribavirin related. None of the participating subjects withdrew treatment or follow-up throughout the trial peroid. Three serious adverse events were reported which included urosepsis, appendicitis and left ureteral stone. All were unrelated to the investigating drugs. Conclusions: 12 weeks of DCV/ASV plus ribavirin was highly effective and safe in HCV-1b patients without NS5A RAS in the interim analysis. The satisfactory results would be anticipated in the full patient set.

Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus

Liu Wen-Chung,Wu Chih-Wei,Fu Mu-Hui,Tain You-Lin,Liang Chih-Kuang,Chen I-Chun,Hung Chun-Ying,Lee Yu-Chi,Wu Kay L.H. 한국뇌신경과학회 2022 Experimental Neurobiology Vol.31 No.5

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g-1•hour-1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2+-Beclin 1+ and SOX2+-S100β+ cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.