Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells

Ying-ying Xu,Hai-ru Yu,Jia-yi Sun,Zhao Zhao,Shuang Li,Xin-feng Zhang,Zhi-xuan Liao,Ming-ke Cui,Juan Li,Chan Li,Qiang Zhang 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2

Purpose Although the interferon  (IFN) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. Materials and Methods PITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. Results PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFN signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFN-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFN-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. Conclusion These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

What Did They Mean by “Calculation Principles”?: Revisiting Argumentative Styles in Late Ming to Mid-Qing Chinese Mathematics

( Su Jim-hong ),( Ying Jia-ming ) 한국과학사학회 2016 한국과학사학회지 Vol.38 No.2

This article discusses the influence that two versions of the Elements had in Ming and Qing China as well as Chinese scholars` efforts to “integrate” (huitong 會通) Western and Chinese mathematics into a unified system in terms of argumentative styles in mathematics. Although much high praise was given to the axiomatic-de-ductive system of Euclid`s Elements, numerical arguments and problem-solving re-main important traits in the works of Chinese scholars. The compilation of the Shuli jingyun 數理精蘊 and the inclusion of another version of the Elements in it again prompted East Asian mathematicians to reflect more upon their methods of argu-mentation, and later scholars began to write texts whose arguments are more abstract than numerical. This paper presents examples taken from the works of several rep-resentative scholars from the late Ming to the mid-Qing periods to argue that their efforts of huitong produced argumentative styles that are a combination of both Chi-nese and Western approaches, and that there was a trend of moving from concrete calculations to general arguments in mathematical texts throughout the course of history. Finally, the authors conclude that what 17^th and 18^th century Chinese math-ematicians meant by “calculation principles” (suanli 算理) was never the kind of pure deduction in the Euclidean manner, but a combination of induction and deduc-tion, with the help of intuition, for the purpose of problem-solving.

High Expression of MICA in Human Kidney Cancer Tissue and Renal Cell Carcinoma Lines

Jia, Hong-Ying,Liu, Jun-Li,Zhou, Cheng-Jun,Kong, Feng,Yuan, Ming-Zhen,Sun, Wen-Dong,Wang, Jue,Liu, Ling,Zhao, Jing-Jie,Luan, Yun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

The overall incidence and mortality of renal cell carcinoma (RCC), the most common kidney cancer, are steadily increasing for reasons that are not fully explained. Our aim was to explore the expression of membrane MHC class I chain-related gene A (mMICA) in human RCC cell lines and tissue specimens, and to determine expression of soluble MICA (sMICA) in serum of patients with renal cell carcinoma, we used flow cytometry (FCM) and immunohistochemistry as well as an enzyme linked immunosorbent assay (ELISA). The results showed that percentage of mMICA expression was significantly increased in human kidney cancer tissues and RCC cell lines (786-O and Ketr-3) than that in healthy adults and human embryonic kidney 293 (HEK293) cell line individuality (P<0.05). sMICA content in healthy adults was negative, but in renal cancer patients was significantly elevated (P<0.05). Our research showed that high expression of MICA in human kidney cancer, this results show that MICA might serve as potential tumor-associated antigen (TAA) in RCC.

Regulation Roles of MICA and NKG2D in Human Renal Cancer Cells

Jia, Hong-Ying,Liu, Jun-Li,Yuan, Ming-Zhen,Zhou, Cheng-Jun,Sun, Wen-Dong,Zhao, Jing-Jie,Wang, Jue,Liu, Ling,Luan, Yun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Objective: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. Materials and Methods: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. Results: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies (P<0.05), and serum containing sMICA can obviously lower the function of NKG2D (P<0.05). Conclusions: The interaction of mMICA and NKG2D play important roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA may mediate tumor immune escape through down- regulated NKG2D expression.

Support Vector Machine Based on Type-2 Fuzzy Training Samples

Ming-hu Ha,Jia-ying Huang,Yang Yang,Chao Wang 대한산업공학회 2012 Industrial Engineeering & Management Systems Vol.11 No.1

In order to deal with the classification problems of type-2 fuzzy training samples on generalized credibility space. Firstly the type-2 fuzzy training samples are reduced to ordinary fuzzy samples by the mean reduction method. Secondly the definition of strong fuzzy linear separable data for type-2 fuzzy samples on generalized credibility space is introduced. Further, by utilizing fuzzy chance-constrained programming and classic support vector machine, a support vector machine based on type-2 fuzzy training samples and established on generalized credibility space is given. An example shows the efficiency of the support vector machine.

Professionals’ experiences and attitudes toward use of Traditional Chinese Medicine in hospice palliative inpatient care units: A multicenter survey in Taiwan

Yu-Jia Lin,Hsiao-Ting Chang,Ming-Hwai Lin,Ru-Yih Chen,Ping-Jen Chen,Wen-Yuan Lin,Jyh-Gang Hsieh,Ying-Wei Wang,Chung-Chieh Hu,Yi-Sheng Liou,Tai-Yuan Chiu,Chun-Yi Tu,Yi-Jen Wang,Bo-Ren Cheng,Tzeng-Ji Ch 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.2

Background: Medical staff may have difficulties in using conventional medicine to manage symptoms among terminally ill patients, including adverse effects of the treatment. Traditional Chinese medicine (TCM) is regarded as a complementary or alternative medicine, and has been increasingly used in the field of palliative medicine in recent years. This study aimed to investigate the experiences of and attitudes toward using TCM among palliative care professionals, and to provide preliminary information about its use in palliative care. Methods: This was a cross-sectional survey study conducted in eight inpatient hospice wards in Taiwan between December 2014 and February 2016. The questionnaire was self-administered, and was analyzed with descriptive statistics including Pearson’s Chi-square test and Fisher’s exact test. Results: A total of 251 palliative care professionals responded to the questionnaire, of whom 89.7% and 88.9% believed that the use of TCM could improve the physical symptoms and quality of life in terminally ill patients, respectively. Overall, 59.8%, of respondents suggested that TCM had rare side effects, and 58.2% were worried that TCM could affect the liver and kidney function of patients. In total, 89.7% and 88.0% of professionals agreed there were no suitable clinical practice guidelines and educational programs, respectively, for TCM use in palliative care. Conclusions: Most of the respondents agreed there was insufficient knowledge, skills-training, and continuing education on the use of TCM in terminally ill patients in Taiwan. These results show that to address patient safety considerations, guidelines about use of TCM in palliative care should be established.

Expression Profile and Potential Roles of EVA1A in Normal and Neoplastic Pancreatic Tissues

Tao, Ming,Shi, Xue-Ying,Yuan, Chun-Hui,Hu, Jia,Ma, Zhao-Lai,Jiang, Bin,Xiu, Dian-Rong,Chen, Ying-Yu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: EVA1A (eva-1 homolog A) is a novel gene that regulates programmed cell death through autophagy and apoptosis. Our objective was to investigate the expression profiles and potential role of EVA1A in normal and neoplastic human pancreatic tissues. Materials and Methods: The expression pattern of EVA1A in normal pancreatic tissue was examined by indirect immunofluorescence and confocal microscopy. Protein levels in paraffin-embedded specimens from normal and diseased pancreatic and matched non-tumor tissues were evaluated by immunohistochemistry. Results: EVA1A colocalized with glucagon but not with insulin, demonstrating production in islet alpha cells. Itwas strongly expressed in chronic pancreatitis, moderately or weakly expressed in the plasma membrane and cytoplasm in pancreatic acinar cell carcinoma, and absent in normal pancreatic acinar cells. Although the tissue architecture was deformed, EVA1A was absent in the alpha cells of pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, mucinous cystadenomas, solid papillary tumors and pancreatic neuroendocrine tumors. Conclusions: EVA1A protein is specifically expressed in islet alpha cells, suggesting it may play an important role in regulating alpha-cell function. The ectopic expression of EVA1A in pancreatic neoplasms may contribute to their pathogenesis and warrants further investigation.

New Safrole Oxide Derivatives: Synthesis and in vitro Antiproliferative Activities on A549 Human Lung Cancer Cells

Li-Ying Wang,Xiu-Hua Wang,Jia-Lian Tan,Shuai Xia,Heng-Zhi Sun,Jin-Wen Shi,Ming-Dong Jiang,Liang Fang,Hua Zuo,Gautam Dupati,장기완,신동수 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.11

A number of novel small molecules, safrole oxide derivatives 4a-c, 6a-c, 9a-h, were synthesized by the reaction of safrole oxide with anilines 3 and 5, or its alkyl allyl ether derivative 7 with alkyl bromide 8 in moderate yields. The antiproliferative effects of all the target molecules on A549 cell growth were investigated and it was found that the 14 novel compounds could suppress A549 lung cancer cell growth. Among them, compound 6b was the most effective compound in inhibiting the proliferation of A549 cells.

Substituent Effects of Accelerator on Nitroxide-Mediated Radical Polymerization

Jian-ying Huang,Jia-ming Zhuang,You-si Zou 한국고분자학회 2011 Macromolecular Research Vol.19 No.8

The acceleration effect of various agents on the rate of styrene bulk polymerization in 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) mediated polymerization was investigated, including dimethyl malonate (DMM), diethyl methyl malonate (DEMM), diethyl tert-butylmalonate (DEBM), diethyl diethylmalonate (DEDEM), 3-methyl-2,4-pentanedione (MPD), acetyl malononitrile (Ac-MN), and dimethyl malononitrile (DM-MN). Polymerization with the additive proceeded in a living manner, as indicated by keeping a low polydispersity and increasing the molecular weight with the reaction time and conversion. The structure of the styrene polymerization did not change in the presence of these additives. The monomer conversion efficiency was approximately 99% and maintained a relatively narrow polydispersity of 1.29 with the optimal [Ac-MN]/[TEMPO] molar ratios of 4 in 1.5 h. With the accelerator,dipole/dipole interactions led to a weakening of the C-ON bond and an acceleration of the reaction. There is a trend for a higher polymerization rate with more electron-withdrawing substituents.

MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN?

( Xing Ming Ye ),( Wen Dong Bai ),( Hua Yu Zhu ),( Xiao Zhang ),( Ying Chen ),( Lei Wang ),( An Gang Yang ),( Jing Zh Ao ),( Lin Tao Jia ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.5

HER2-overexpressing breast cancers are characterized byfrequent distant metastasis and often develop resistance aftershort-term effective treatment with the monoclonal antibodydrug, trastuzumab. Here, we found that the oncogenic miRNA,miR-221, inhibited apoptosis, induced trastuzumab resistanceand promoted metastasis of HER2-positive breast cancers. Thetumor suppressor PTEN was identified as a miR-221 target;overexpression of PTEN abrogated the aforementionedmiR-221-induced malignant phenotypes of the cells. Thesefindings indicate that miR-221 may promote trastuzumabresistance and metastasis of HER2-positive breast cancers bytargeting PTEN, suggesting its role as a potential biomarker forprogression and poor prognosis, and as a novel target fortrastuzumab-combined treatment of breast cancers.[BMB Reports 2014; 47(5): 268-273]