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.

Liver Cancer Mortality Characteristics and Trends in China from 1991 to 2012

Fang, Jia-Ying,Wu, Ku-Sheng,Zeng, Yang,Tang, Wen-Rui,Du, Pei-Ling,Xu, Zhen-Xi,Xu, Xiao-Ling,Luo, Jia-Yi,Lin, Kun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Purpose: To investigate the distribution of liver cancer mortality as well as its developing trend from 1991 to 2012, forecast the future five-year trend, and provide a basis for the comprehensive prevention and management. Materials and Methods: Mortality data for liver cancer in China from 1991 to 2012 were used to describe characteristics and distribution of liver cancer mortality. Trend surface analysis was used to study the geographical distribution of liver cancer mortality. Curve estimation, time series modeling, gray modeling (GM) and joinpoint regression were used to predict and forecast future trends. Results: The mortality rate of liver cancer has constantly increased in China since 1991. Rates in rural areas are higher than in urban areas, and in males are higher than in females. In addition, our data predicted that the trend will continue to increase in the next 5 years. The age-specific mortality of liver cancer increases with age and peaks in the group of 80-84 years old. Geographical analysis showed the liver mortality rate was higher in the southeast provinces, such as Jiangsu, Zhejiang and Guangdong, and southwest regions like Guangxi Province. Conclusions: The standardized mortality rate of liver cancer in China has consistently increased from 1991 to 2012, and the upward trend is predicted to continue in the future. Much better prevention and management of liver cancer is needed in high mortality areas (the southwestern and southeastern parts of China) and high mortality age groups (80- to 84-year-olds), especially in rural areas.

The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Qian, Ying-Ying,Liu, Xin-You,Pei, Dong,Xu, Jia-Li,Shen, Hua,Chen, Xiao-Feng,Liu, Yi-Qian,Shen, Li-Zong,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

Colorectal Cancer Mortality Characteristics and Predictions in China, 1991-2011

Fang, Jia-Ying,Dong, Hong-Li,Sang, Xue-Jin,Xie, Bin,Wu, Ku-Sheng,Du, Pei-Ling,Xu, Zhen-Xi,Jia, Xiao-Yue,Lin, Kun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Background: To identify the epidemiological characteristics of colorectal cancer mortality in China during the period of 1991-2011, and forecast the future five-year trend. Materials and Methods: Mortality data for colorectal cancer in China from 1991 to 2011 was used to describe epidemiological characteristics in terms of age group, gender, and rural/urban residence. Trend surface analysis was performed to analyze the geographical distribution of colorectal cancer. Four models including curve estimation, time series modeling, gray modeling and joinpoint regression were applied to forecast the trends for the future five years. Results: Since 1991 the colorectal cancer mortality rate increased yearly, and our results showed that the trend would continue to increase in the ensuing 5 years. The mortality rate in males was higher than that of females and the rate in urban areas was higher than in rural areas. The mortality rate was relatively low for individuals less than 60 years of age, but increased dramatically afterwards. People living in the northeastern China provinces or in eastern China had a higher mortality rate for colorectal cancer than those living in middle or western China provinces. Conclusions: The steadily increasing mortality of colorectal cancer in China will become a substantial public health burden in the foreseeable future. For this increasing trend to be controlled, further efforts should concentrate on educating the general public to increase prevention and early detection by screening. More effective prevention and management strategies are needed in higher mortality areas (Eastern parts of China) and high-risk populations (60+ years old).

Metabolic dynamics across prolonged diapause development in larvae of the sawfly, Cephalcia chuxiongica (Hymenoptera: Pamphiliidae)

Xu Rong,Chen Yu-Hui,Xia Ju-Fei,Zeng Ting-Xiao,Li Yong-He,Zhu Jia-Ying 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.2

Nutrient metabolism is crucial for the survival of insects through the diapause. However, little is known about the metabolic mechanism of prolonged diapause. The sawfly, Cephalcia chuxiongica (Hymenoptera: Pamphilii�dae), is a notorious defoliator of pine trees in southwest China. One of the distinguishing biological character�istics of this pest is the prolonged diapause of about 1.5 years. In this study, the body lipid, carbohydrate (total body sugar, glycogen, trehalose, and glucose), protein, and glycerol contents were measured in diapausing larvae of C. chuxiongica. The results showed that the changes of biochemical composition in C. chuxiongica are asso�ciated with the diapause initiation, maintenance, and termination phases. During the initiation phase, trehalose, glucose, and glycerol increased significantly, but glycogen decreased sharply. In general, the lipid, carbohydrate, and glycerol levels decreased gradually across the maintenance phase. At termination phase, the contents of glycogen and lipid persistently decreased, while an increase of trehalose, glucose, and glycerol contents were detected. The protein level was significantly higher at maintenance phase than at initiation and termination phases. It was also found that elevation of trehalose, glucose, and glycerol contents occurred in winter. These implies that the metabolites with altered levels in diapausing larvae of C. chuxiongica are responsible for maintaining a prolonged development and overwintering.

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

Xu, Chao-Yang,Jiang, Zhi-Nong,Zhou, Ying,Li, Jia-Jia,Huang, Li-Ming Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Mortality Characteristic and Prediction of Nasopharyngeal Carcinoma in China from 1991 to 2013

Xu, Zhen-Xi,Lin, Zhi-Xiong,Fang, Jia-Ying,Wu, Ku-Sheng,Du, Pei-Ling,Zeng, Yang,Tang, Wen-Rui,Xu, Xiao-Ling,Lin, Kun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: To analyze the mortality distribution of nasopharyngeal carcinoma in China from 1991 to 2013, to predict the mortality in the ensuing five years, and to provide evidence for prevention and treatment of nasopharyngeal carcinoma. Materials and Methods: Mortality data for Nasopharyngeal Carcinoma in China from 1991 to 2013 were used to describe its epidemiological characteristics, such as the change of the standardized mortality rate, sex and age differences, urban-rural differences. Trend-surface analysis was used to study the geographical distribution of the mortality. Curve estimation, time series, gray modeling, and joinpoint regression were used to predict the mortality for the ensuing five years in the future. Results: In China, the standardized mortality rate of Nasopharyngeal Carcinoma increased with time from 1996, reaching the peak values of $1.45/10^5$ at the year of 2002, and decreased gradually afterwards. With males being 1.51 times higher than females, and the city had a higher rate than the rural during the past two decades. The mortality rate increased from age 40. Geographical analysis showed the mortality rate increased from middle to southern China. Conclusions: The standardized mortality rate of Nasopharyngeal Carcinoma is falling. The regional disease control for Nasopharyngeal Carcinoma should be focused on Guangdong province of China, and the key targets for prevention and treatment are rural men, especially after the age of 40. The mortality of Nasopharyngeal Carcinoma will decrease in the next five years.

In situ deposition of flower-like ZnO on silk fibroin fibers

Xu, Jia,Su, Huilan,Han, Jie,Chen, Ying,Song, Weiqiang,Gu, Yu,Moon, Won-Jin,Zhang, Di Springer-Verlag 2012 APPLIED PHYSICS A MATERIALS SCIENCE AND PROCESSING Vol.108 No.1

Neuroprotective Effects of Spinosin on Recovery of Learning and Memory in a Mouse Model of Alzheimer’s Disease

Fanxing Xu,Bosai He,Feng Xiao,Tingxu Yan,Kaishun Bi,Ying Jia,Zhenzhong Wang 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer’s disease (AD) induced by Aβ1-42 and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 μg/kg/day), the cognitive impairment of mice induced by Aβ1-42 was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aβ1-42 accumulation in hippocampus. Aβ1-42 induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.

Schisantherin B Improves the Pathological Manifestations of Mice Caused by Behavior Desperation in Different Ages-Depression with Cognitive Impairment

Mengjie Xu,Feng Xiao,Mengshi Wang,Tingxu Yan,Huilin Yang,Bo Wu,Kaishun Bi,Ying Jia 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.2

Depression is a major mood disorder. Abnormal expression of glial glutamate transporter-1 (GLT-1) is associated with depression. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on depressive mice induced by forced swimming test (FST). Additionally, we also assessed the impairment of FST on cognitive function in mice with different ages. FST and open field test (OFT) were used for assessing depressive symptoms, and Y-maze was used for evaluating cognition processes. Our study showed that STB acting as an antidepressant, which increased GLT-1 levels by promoting PI3K/AKT/mTOR pathway. Although the damage is reversible, short-term learning and memory impairment caused by FST test is more serious in the aged mice, and STB also exerts cognition improvement ability in the meanwhile. Our findings suggested that STB might be a promising therapeutic agent of depression by regulating the GLT-1 restoration as well as activating PI3K/AKT/mTOR pathway.