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.

Deficiency or activation of peroxisome proliferator-activated receptor ⍺ reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

Wen-Ting Hsiao,Hui-Min Su,Kuan-Pin Su,Szu-Han Chen,Hai-Ping Wu,Yi-Ling You,Ru-Huei Fu,Pei-Min Chao 한국영양학회 2019 Nutrition Research and Practice Vol.13 No.4

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPARα homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPARα agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: PPARα ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPARα activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by PPARα. Either PPARα deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Deterrence or Numbness? Insights into the Psychological Effects of the Encirclement Patrols Conducted by People’s Liberation Army Vessels and Aircraft around Taiwan

Yi-Ming Yu,Wen-Cheng Fu,Li-Wei Lin,Chien-An Ke 한국국방연구원 2020 The Korean Journal of Defense Analysis Vol.32 No.1

This study investigated the psychological effects of the long-term military intimidation imposed by the People’s Liberation Army (PLA) on the Taiwanese public. Online texts dating between 2016 and 2018 were mined and Russell’s (1980) semantic analysis was used to analyze the online discussions among the Taiwanese public regarding the PLA vessels and aircraft patrolling around Taiwan. The results showed that the PLA’s long-term encirclement patrols have generated numbness among the Taiwanese public. With regard to the Taiwanese government’s policy of disclosing information about such military encirclement patrols, the effects of proliferating this information were not significant, but have led to an increased sense of fear among the public. These ndings suggest that the effects of the PLA’s encirclement patrols around Taiwan are not determined by the PLA, but by the Taiwanese government’s policies regarding the disclosure of relevant information on encirclement patrols.

Genomic Screening for Targets Regulated by Berberine in Breast Cancer Cells

Wen, Chun-Jie,Wu, Lan-Xiang,Fu, Li-Juan,Yu, Jing,Zhang, Yi-Wen,Zhang, Xue,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

Wen, Chun-Jie,Wu, Lan-Xiang,Fu, Li-Juan,Shen, Dong-Ya,Zhang, Xue,Zhang, Yi-Wen,Yu, Jing,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. $17{\beta}$-estradiol ($E_2$), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH $E_2$) and 4-hydroxyestradiol ($4-OH\;E_2$) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that $2-OH\;E_2$ has putative protective effects, while $4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of $2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of $E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect $E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.

Development of Novel Pineapple Peel Juice Through Lactic Acid Fermentation for Enhancing Antioxidant Capacity and Stability

( Wen Fu Wu ),( Yi Ching Liu ),( Hsin Yun Chang ),( Chen Wei Huang ),( Ying Chen Lu ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Pineapples are tropical fruit that are rich in vitamins, enzymes and fibers with many health benefits not only in pulps but also peels. However, the peels of pineapples are normally removed and dropped. The pulps and peels of four pineapple cultivars, Milk, Honey Fragrance, Smooth Cayenne and Golden Diamond pineapples, were juiced, filtered and analyzed, and the Golden Diamond pineapple was found to have highest antioxidant capacity. The pulp and peel juices of Golden Diamond pineapple were inoculated with Enterococcus faecium LYC91 and various concentration calcium carbonate to ferment at 37°C for 24 hours follow by bacterial and antioxidant capacity analysis. The results indicated that the fermented pineapple peel juice with calcium carbonate had highest bacterial number, total polyphenol content, DPPH radical scavenging ability, Fe2 + chelating ability and reducing power activity than pulp juice and unfermented pineapple juice. The viable bacterial number of fermented pineapple pulp and peel juices with calcium carbonate remain 8.0 log CFU/mL after stored at 4°C for 1 month. The freeze-dried powder of the fermented pineapple pulp and peel juices with calcium carbonate retained the viable cell number of 9.0 log CFU/g after stored at 4°C for three months. These results showed that the fermented pineapple pulp and peel juices with calcium carbonate were novel pineapple lactic acid fermented drinks with growth potential.

A novel M2e-multiple antigenic peptide providing heterologous protection in mice

Feng Wen,Ji-Hong Ma,Hai Yu,Fu-Ru Yang,Meng Huang,Yan-Jun Zhou,Ze-Jun Li,Xiu-Hui Wang,Guo-Xin Li,Yi-Feng Jiang,Wu Tong,Guangzhi Tong 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.1

Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.

Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

Hsiao, Wen-Ting,Su, Hui-Min,Su, Kuan-Pin,Chen, Szu-Han,Wu, Hai-Ping,You, Yi-Ling,Fu, Ru-Huei,Chao, Pei-Min The Korean Nutrition Society 2019 Nutrition Research and Practice Vol.13 No.4

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Triterpenoids and Diarylheptainoids from Alnus hirsuta Inhibit HIF-1 in AGS Cells

Jin, Wen-Yi,Cai, Xing-Fu,Na, Min-Kyun,Lee, Jung-Joon,Bae, Ki-Hwan 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.4

Bioassay-guided fractionation and purification of the EtOAc soluble fraction from the MeOH extract of the stem bark of Alnus hirsuta (Betulaceae), using an in vitro HIF-1 assay, led to the isolation of four triterpenoids (1-4) and six diarylheptanoids (5-10). Their structures were deter-mined by comparison with the physicochemical and spectroscopic data in the literature. These compounds were investigated for their effects on the hypoxia-induced HlF-1 activation using an HIF-1 a mediated reporter gene assay in AGS cells. Among them, two diarylheptanoids, 2-oxatrycyclo[13.2.2.13,7]eicosa-3,5,7(20),15,17,18-hexaen-10-16-diol (6) and 2-oxatrycyclo[13.2.2.13,7]eicosa-3,5,7-(20),15,17,18-hexaen-10-one (7), inhibited HIF-1 activation dose-dependently with IC$_{50}$ values of 11.2 ${\mu}$M and 12.3 ${\mu}$M, respectively. These two compounds had no significant cytotoxicity to the AGS cells at the effective concentration for the inhibition of HIF-1 activation.

Drinking Deep Seawater Decreases Serum Total and Low-Density Lipoprotein–Cholesterol in Hypercholesterolemic Subjects

Zhao-Yang Fu,Feili Lo Yang,Hsin-Wen Hsu,Yi-Fa Lu 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.6

Drinking deep seawater (DSW) with high levels of magnesium (Mg) decreased serum lipids in animal studies. Therefore the effects of drinking DSW on blood lipids and its antioxidant capacity in hypercholesterolemic subjects were investigated. DSW was first prepared by a process of filtration and reverse osmosis, and then the concentrated DSW with high levels of Mg was diluted as drinking DSW. Forty-two hypercholesterolemic volunteers were randomly divided into three groups: reverse osmotic (RO) water, DSW (Mg: 395 mg/L, hardness 1410 ppm), and magnesium-chloride fortified (MCF)water (Mg: 386 mg/L, hardness 1430 ppm). The subjects drank 1050mL of water daily for 6 weeks, and blood samples were collected and analyzed on weeks 0, 3, and 6. Drinking DSW caused a decrease in blood total cholesterol levels and this effect was progressively enhanced with time. Serum low-density lipoprotein–cholesterol (LDL-C) was also decreased by DSW. Further, total cholesterol levels of subjects in the DSW group were significantly lower than those in the MCF water or RO water groups. Compared with week 0, the DSW group had higher blood Mg level on weeks 3 and 6, but the Mg levels were within the normal range in all three groups. DSW consumption also lowered thiobarbituric acid-reactive substances (TBARS)values in serum. In conclusion, DSW was apparently effective in reducing blood total cholesterol and LDL-C, and also in decreasing lipid peroxidation in hypercholesterolemic subjects.