Alantolactone selectively suppresses STAT3 activation and exhibits potent anticancer activity in MDA-MB-231 cells

Chun, Jaemoo,Li, Rui-Juan,Cheng, Mao-Sheng,Kim, Yeong Shik Elsevier 2015 Cancer letters Vol.357 No.1

<P><B>Abstract</B></P> <P>The important goal of cancer drug discovery is to develop therapeutic agents that are effective, safe, and affordable. In the present study, we demonstrated that alantolactone, which is a sesquiterpene lactone, has potential activity against triple-negative breast cancer MDA-MB-231 cells by suppressing the signal transducer and activator of transcription 3 (STAT3) signaling pathway. Alantolactone effectively suppressed both constitutive and inducible STAT3 activation at tyrosine 705. Alantolactone decreased STAT3 translocation to the nucleus, its DNA-binding, and STAT3 target gene expression. Alantolactone significantly inhibits STAT3 activation with a marginal effect on MAPKs and on NF-κB transcription; however, this effect is not mediated by inhibiting STAT3 upstream kinases. Although SHP-1, SHP-2, and PTEN, which are protein tyrosine phosphatases (PTPs), were not affected by alantolactone, the treatment with a PTP inhibitor reversed the alantolactone-induced suppression of STAT3 activation, indicating that PTP plays an important role in the action of alantolactone. Finally, alantolactone treatment resulted in the inhibition of migration, invasion, adhesion, and colony formation. The <I>in vivo</I> administration of alantolactone inhibited the growth of human breast xenograft tumors. These results provide preclinical evidence to continue the development of alantolactone as a STAT3 inhibitor and as a potential therapeutic agent against breast cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> STAT3 is a transcription factor that is a potent regulator of tumorigenesis. </LI> <LI> Alantolactone suppresses constitutive and inducible STAT3 tyrosine phosphorylation. </LI> <LI> Alantolactone inhibits NF-κB translocation to the nucleus. </LI> <LI> Alantolactone inhibits cell migration, invasion, adhesion, and colony formation. </LI> <LI> Alantolactone inhibits the tumor growth of MDA-MB-231 xenografts in mice. </LI> </UL> </P>

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Beam position measurement system at HIRFL-CSRm

Li Min,Xiao Guoqing,Mao Ruishi,Zhao Tiecheng,Yuan Youjin,Li Weilong,Zhou Kai,Kang Xincai,Li Peng,Li Juan 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.4

Beam position measurement system can not only provide the beam position monitoring, but also be used for global orbit correction to reduce beam loss risk and maximize acceptance. The Beam Position Monitors (BPM) are installed along the synchrotron to acquire beam position with the front-end electronics and data acquisition system (DAQ). To realize high precision orbit measurement in the main heavy ion synchrotron and cooling storage ring of heavy-ion research facility in Lanzhou (HIRFL-CSRm), a series of alignment and calibration work has been implemented on the BPM and its DAQ system. This paper analyzed the tests performed in the laboratory as well as with beam based on the developed algorithms and hardware. Several filtering algorithms were designed and implemented on the acquired BPM raw data, then the beam position and resolution were calculated and analyzed. The results show that the position precision was significantly improved from more than 100 μm to about 50 μm by implementing the new designed filtering algorithm. According to the analyzation of the measurement results and upcoming physical requirements, further upgrade scheme for the BPM DAQ system of CSRm based on field programmable gate array (FPGA) technology was proposed and discussed.

A Genetic Variant in MiR-146a Modifies Digestive System Cancer Risk: a Meta-analysis

Li, Ying-Jun,Zhang, Zhen-Yu,Mao, Ying-Ying,Jin, Ming-Juan,Jing, Fang-Yuan,Ye, Zhen-Hua,Chen, Kun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83-0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations.

rs12904 Polymorphism in the 3'UTR of EFNA1 is Associated with Colorectal Cancer Susceptibility in a Chinese Population

Mao, Ying-Ying,Jing, Fang-Yuan,Jin, Ming-Juan,Li, Ying-Jun,Ding, Ye,Guo, Jing,Wang, Fen-Juan,Jiang, Long-Fang,Chen, Kun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR)=0.469, 95% confidence interval (CI): 0.225-0.977, and P=0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings.

Genetic diversity and spread of Lissorhoptrus oryzophilus (Coleoptera: Curculionidae) in China, based on amplified fragment length polymorphism

Shang-Wei Li,Fang-Chao Wei,Juan Du,Mao-Fa Yang 한국응용곤충학회 2017 Journal of Asia-Pacific Entomology Vol.20 No.3

The rice water weevil (RWW), Lissorhoptrus oryzophilus Kuschel, is one of the most destructive pests causing heavy rice yield loss worldwide. In the present study, amplified fragment length polymorphism (AFLP) was used to analyze the genetic differentiation and transmission routes of 26 RWW geographical populations from Guizhou and 6 other provinces in China. The genetic distance between the 26 populations ranged from 0 to 0.693; the genetic distance between Guizhou and 6 other provinces populations varied from 0.043 to 0.693, with an average of 0.382. There was higher genetic variation among the populations from Guizhou and 6 other provinces compared with populations within Guizhou. The Mantel test showed no correlation between the genetic and geographical distances of the 26 populations. According to genetic distance, clustering, and time that RWW was found in these regions, we deduced that the pest entered Guizhou and spread in this province most likely via three routes: (1) from Hebei to Zunyi and southward to the south-central regions; (2) from Sichuan to Bijie and eastward to the central regions; and (3) from Yunnan through Anshun to the central regions and Qiandongnan prefecture. RWW spread in a natural manner, including flight, crawling, swimming, and by human-associated mechanisms, comprising dissemination through paddies and hay and hitchhiking on human transportations.

Mortality of Urinary Tract Cancer in Inner Mongolia 2008-2012

Xin, Ke-Peng,Du, Mao-Lin,Li, Zhi-Jun,Li, Yun,Li, Wuyuntana,Su, Xiong,Sun, Juan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

The aim of this study was to determine the mortality rate and burden of urinary tract cancers among residents of Inner Mongolia. We analyzed mortality data reported by the Death Registry System from 2008 to 2012. The rate of mortality due to urinary tract cancer was 2.04 per 100,000 person-years for the total population, 2.91 for men, and 1.11 for women. Therefore, the mortality rate for men was 2.62-fold the mortality rate for women, constituting a statistically significant difference (p<0.001). Over the period 2008 through 2012, the total potential years of life lost was 1388.1 person-years for men and 777.1 person-years for women, and the average years of life lost were 7.71 years per male decedent and 12.0 years per female decedent. Mortality due to urinary tract cancers is substantially greater among the elderly population. Further, the mortality rate associated with urinary tract cancers is greater for elderly men than it is for elderly women. Therefore, in Inner Mongolia, urinary tract cancers appear to pose a greater mortality risk for men than they do for women.

Analysis of the Relationship between Breaking Stress and Whiteness in a New Hair Bleaching Method

Wei Wang,Qing-hui Mao,Yu Zhang,Jian-gang Qu,Zhi-jie Liang,Jia Yu,Lin-juan Zheng,Li Zhang 한국섬유공학회 2020 Fibers and polymers Vol.21 No.12

In order to investigate the relationship between breaking stress and whiteness in a bleaching treatment withlaccase, hair samples from three biogeographically distinct populations were characterized by various chemical and physicaltechniques. Factors affecting whiteness and breaking stress were investigated by attenuated total reflection infraredspectroscopy, atomic absorption spectroscopy, X-ray diffraction and scanning electron microscopy. The results reveal thatwhiteness and breaking stress after bleaching are primarily influenced by the diversity of concentration of metal ions andfunctional groups in the hair. The hair samples with lower content of metal ions obtain better whiteness and higher stressretention. The presence of OH functional group increases the final whiteness of the hair sample, while lack of that not onlydecreases the whiteness but also leads to more stress loss. In addition, the presence of the C=C functional group alsodecreases the whiteness.

Synthesis, Crystal Structure and Characterization of Cu(II) and Cd(II) Coordination Compounds Based on Ligand 2-(3-(Pyridin-2-yl)-1H-pyrazol-1-yl)acetic Acid

Ya-Jun Zhang,Cui-Juan Wang,Kai-Li Mao,Xiao-Lei Liu,Shuai Huang,Yan Tong,Xian-Li Zhou 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.7

Two novel coordination compounds [Cu2(pypya)3(H2O)2]·Cl·(H2O)5 (1) and {[Cd(pypya)(ta)1/2]·H2O}n (2) (Hpypya=2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid, H2ta=terephthalic acid) were synthesized and characterized by single X-ray diffraction. Structure determination reveals that complex 1 and complex 2 crystallize in the triclinic system, with the P-1 space group. The asymmetric unit of 1 contains two Cu(II) ions, and their coordination modes are different. These units of complex 1 are linked together via hydrogen bonds and π-π interactions, and the 3D structure of complex 1 was formed. Complex 2, a mononuclear Cd(II) coordination compound, has a 2D structure which was constructed via coordination bonds. TGA and fluorescence spectra analysis of complex 1 and complex 2 have also been studied. In addition, the geometry parameters of complex 1 have been optimized with the B3LYP method of density functional theory (DFT) to explain its coordination behavior. The electronic properties of the complex 1 and ligand Hpypya have been investigated based on the nature bond orbital (NBO) analysis at the B3LYP level of theory. The result verifies that the synergistic effect have occurred in the compound.

Distinctive Endophytic Fungal Assemblage in Stems of Wild Rice (Oryza granulata) in China with Special Reference to Two Species of Muscodor (Xylariaceae)

Zhi-lin Yuan,Zhen-zhu Su,Li-juan Mao,Yang-qing Peng,Guan-mei Yang,Fu-cheng Lin,Chu-long Zhang 한국미생물학회 2011 The journal of microbiology Vol.49 No.1

Ecological niches in the rhizosphere and phyllosphere of grasses capable of sustaining endophytes have been extensively studied. In contrast, little information regarding the identity and functions of endophytic fungi in stems is available. In this study, we investigated the taxonomic affinities, diversity, and host specificities of culturable endophytes in stems of wild rice (Oryza granulata) in China. Seventy-four isolates were recovered. Low recovery rate (11.7%) indicated that there were relatively few sites for fungal infection. Identification using morphology, morphospecies sorting, and molecular techniques resulted in classification into 50 taxa, 36 of which were recovered only once. Nucleotide sequence similarity analysis indicated that 30% of the total taxa recovered were highly divergent from known species and thus may represent lineages new to science. Most of the taxa were classified as members of the classes Sordariomycetes or Dothideomycetes (mainly in Pleosporales). The presence of Arthrinium and Magnaporthaceae species, most often associated with poaceous plants, suggested a degree of host specificity. A polyphasic approach was employed to identify two Muscodor taxa based on (i) ITS and RPB2 phylogenies, (ii) volatile compounds produced, and (iii)an in vitro bioassay of antifungal activity. This to our knowledge is only the second report regarding the isolation of Muscodor spp. in China. Therefore, we hypothesize that wild plants represent a huge reservoir of unknown fungi. The prevalence, novelty, and species-specificity of unique isolates necessitate a reevaluation of their contribution to ecosystem function and fungal biodiversity.