The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Chun-Yu Liu,Tzu-Ting Huang,Pei-Yi Chu,Chun-Teng Huang,Chia-Han Lee,Wan-Lun Wang,Ka-Yi Lau,Wen-Chun Tsai,Tzu-I Chao,Jung-Chen Su,Ming-Huang Chen,Chung-Wai Shiau,Ling-Ming Tseng,Kuen-Feng Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

Antiproliferative and Antitumorigenic Activity of Toona sinensis Leaf Extracts in Lung Adenocarcinoma

Chih-Jen Yang,Yu-Jung Huang,Cheng-Yuan Wang,Chuan-Sheng Wang,Pei-Hui Wang,Jen-Yu Hung,Tung-Heng Wang,Hseng-Kuang Hsu,Hurng-Wern Huang,S.P. Anand Kumar,Ming-Shyan Huang,Ching-Feng Weng 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.1

Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G1 peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G1 arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti–lung cancer drug.

Photocatalytic study of Zinc Oxide with bismuth doping prepared by spray pyrolysis

Lin, Tzu-Yang,Hsu, Yu-Ting,Lan, Wen-How,Huang, Chien-Jung,Chen, Lung-Chien,Huang, Yu-Hsuan,Lin, Jia-Ching,Chang, Kuo-Jen,Lin, Wen-Jen,Huang, Kai-Feng Techno-Press 2015 Advances in nano research Vol.3 No.3

The unintentionally doped and bismuth (Bi) doped zinc oxide (ZnO) films were prepared by spray pyrolysis at $450^{\circ}C$ with zinc acetate and bismuth nitrate precursor. The n-type conduction with concentration $6.13{\times}10^{16}cm^{-3}$ can be observed for the unintentionally doped ZnO. With the increasing of bismuth nitrate concentration in precursor, the p-type conduction can be observed. The p-type concentration $4.44{\times}10^{17}cm^{-3}$ can be achieved for the film with the Bi/Zn atomic ratio 5% in the precursor. The photoluminescence spectroscopy with HeCd laser light source was studied for films with different Bi doping. The photocatalytic activity for the unintentionally doped and Bi-doped ZnO films was studied through the photodegradation of Congo red under UV light illumination. The effects of different Bi contents on photocatalytic activity are studied and discussed. Results show that appropriate Bi doping in ZnO can increase photocatalytic activity.

Analysis of Pickup Signals in the Time Domain and the Frequency Domain for the Beam Position Monitor at the Pohang Light Source

Jung Yun Huang,In Ha Yu,Myung Hwan Chun,Sung Chul Kim,Woon Ha Hwang 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.48 No.4

With a simple equivalent circuit model, we obtained an analytical equation for the electrical signal and its spectrum induced by a relativistic electron bunch on a pickup electrode of the beam position monitoring system. Useful formulae are derived to estimate beam position monitor parameters, such as V(fBPM) = 70 mV and the coupling impedance Zb = 0.5 , for the Pohang Light Source.

중·한 교육 현황 및 개혁 동향의 비교

황현옥,정홍섭 新羅大學校 2003 論文集 Vol.52 No.-

There are a lot of similarities between China and Korea in their cultural and historical background. Both countries have adopted the 6:3:3:4 pattern for their elementary school, junior high school, senior high school and college education. Their difference lies in the fact that most schools in China are public schools but the schools in Korea are both private and public ones. Korea is superior to China in teachers' quality, teaching facilities and ratio of high school students who can enter colleges and universities. But Korea is not as good as China in the quality of higher education owing to its over-reliance on private school education and students' tuition fees. In recent years both China and Korea have made great efforts in reformation of education. For example, they have given more financial support to education, changed their college entrance examination from purely written examination to comprehensive evaluation, and decentralized their control over education. But China falls behind Korea in financial support, reform of teaching methodology and introduction of market economy into education. At present, China is trying to put the idea of market economy into the development of private schools and the decision on the amount of tuition fees. Korean government, on the other hand, is giving more support to its private schools. This paper holds that China should learn from Korea in private school management, teachers' training and occupational education whereas Korea should learn from China in improving the quality of tertiary education.

Risk Assessment of Low-Level Cadmium and Arsenic on the Kidney

Huang, Mingai,Choi, Seong-Jin,Kim, Dong-Won,Kim, Na-Young,Park, Choong-Hee,Yu, Seung-Do,Kim, Dae-Seon,Park, Kyung-Su,Song, Jae-Seok,Kim, Heon,Choi, Byung-Sun,Yu, Il-Je,Park, Jung-Duck Informa UK (TaylorFrancis) 2009 Journal of toxicology and environmental health. Pa Vol.72 No.21

<P>Cadmium (Cd) and arsenic (As) are widely distributed in the environment and are known human carcinogens. Several studies reported that chronic exposure to Cd and As produced renal injuries in humans. As one of the mechanisms, oxidative stress was suggested to play a role in the early process of Cd- and/or As-induced tubular damage in the kidney. This study was performed to evaluate the significance of urinary biomarkers, role of oxidative stress, and effect of coexposure to environmental low-level exposure to Cd and/or As in the general population. Urine samples were collected from 290 adults (86 males and 204 females). Urinary concentrations of Cd and As were measured, and kidney biomarkers of toxicity such as ss(2)-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) activity determined in urine. Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured as oxidative stress indices. The mean concentration of Cd was 1.21 mug/L, 0.84 mug/g creatinine, and As was 5.7 mug/L, 3.95 mug/g creatinine in urine. NAG, MDA, and 8-OHdG were positively correlated with both Cd and As in urine. Positive correlations were also observed between NAG and oxidative indices. The effects of coexposure to Cd and As on biomarkers are more pronounced than for exposure to each metal alone. These findings suggest that chronic exposure to low levels of Cd and/or As might produce tubular damage in the kidney through oxidative stress in humans.</P>

An Economic-Statistical Design of Moving Average Control Charts

Yu, Fong-Jung,Chin, Hsiang,Huang, Hsiao Wei The Korean Society for Quality Management 2006 The Asian Journal on Quality Vol.7 No.3

Control charts are important tools of statistical quality control. In 1956, Duncan first proposed the economic design of $\bar{x}-control$ charts to control normal process means and insure that the economic design control chart actually has a lower cost, compared with a Shewhart control chart. An moving average (MA) control chart is more effective than a Shewhart control chart in detecting small process shifts and is considered by some to be simpler to implement than the CUSUM. An economic design of MA control chart has also been proposed in 2005. The weaknesses to only the economic design are poor statistics because it dose not consider type I or type II errors and average time to signal when selecting design parameters for control chart. This paper provides a construction of an economic-statistical model to determine the optimal parameters of an MA control chart to improve economic design. A numerical example is employed to demonstrate the model's working and its sensitivity analysis is also provided.

Reducing Body Fat with platycodon grandiflorum Using lactobacillus rhamnosus HK-9 Fermentation on C57BL/6 Mice

Yu-Hua Huang,Da-Woon Jung,Sun-Hyuk Im,Jeong Eun Ban,Yoon-Hee Choi,Il-Jun Kang 한국식품영양과학회 2015 한국식품영양과학회 학술대회발표집 Vol.2015 No.8

Mesenchymal Stem Cell Secreted-Extracellular Vesicles are Involved in Chondrocyte Production and Reduce Adipogenesis during Stem Cell Differentiation

Tsai Yu-Chen,Cheng Tai-Shan,Liao Hsiu-Jung,Chuang Ming-Hsi,Chen Hui-Ting,Chen Chun-Hung,Zhang Kai-Ling,Chang Chih-Hung,Lin Po-Cheng,Huang Chi-Ying F. 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.6

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. CONCLUSION: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.

이온화 에너지를 조사한 수입 오렌지의 유전독성학적 안전성 평가

황옥화(Yu-Hua Huang),정다운(Da-Woon Jung),강일준(Il-Jun Kang) 한국식품영양과학회 2014 한국식품영양과학회지 Vol.43 No.6

본 연구에서는 방사선 조사 오렌지의 수입 가능성이 높아짐에 따라 이들의 안전성을 검토할 목적으로 0.5, 1 kGy 감마선 조사 수입 오렌지의 복귀돌연변이 시험, 소핵 및 염색체 이상시험의 유전독성학적 안전성 평가를 수행하였다. S.Typhimurium TA98, TA100, TA1535 및 TA1537에 대한 감마선 조사 수입 오렌지(0.5, 1 kGy)의 복귀변이 집락수를 조사한 결과, 대사활성계 도입 및 부재 시 0.625~10 mg/plate의 범위에서 복귀변이 집락수의 농도 의존적인 증가 혹은 감소를 보이지 않았다. 포유류 배양세포를 이용한 염색체이상시험에서 0.5, 1 kGy 감마선 조사 수입 오렌지는 1.25~10 mg/mL의 시험적용 용량에서 염색체이상 유발능이 5% 미만이어서 염색체이상을 유발하지 않는 것으로 나타났다. 설치류 망상적혈구를 이용한 소핵형성 시험을 수행한 결과, 시험적용 용량인 250~2,000 mg/kg의 범위에서 0.5, 1 kGy 감마선 조사 수입 오렌지는 소핵을 가진 망상적혈구의 출현율이 음성대조군과 유의한 차이를 나타내지 않아 소핵을 유발하지 않음을 확인하였다. 이상의 결과, 0.5, 1 kGy 감마선 조사 수입 오렌지는 본 시험조건에서 유전독성이 없는 것으로 나타났다. This study was carried out to evaluate the genotoxicity of imported oranges irradiated with ionizing energy (0.5 and 1 kGy). In bacterial reversion assays with Salmonella Typhimurium TA98, TA100, TA1535, and TA1537, imported oranges irradiated with ionizing energy (0.5 and 1 kGy) showed no significant increase in the number of revertant colonies in both the absence and presence of the S9 metabolic activation system. In chromosomal aberration tests with Chinese hamster ovary (CHO) cells, imported oranges irradiated with ionizing energy (0.5 and 1 kGy) showed no increase in the frequency of chromosomal aberrations. In in vivo mouse micronucleus assay, imported oranges irradiated with ionizing energy (0.5 and 1 kGy) showed no increase in the frequency of polychromatic erythrocytes with micronucleus. These results indicate that imported oranges irradiated with ionizing energy (0.5 and 1 kGy) showed no genotoxic effects under these experimental conditions.