Metastasis associated genomic aberrations in stage II rectal cancer

Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

Clinical Observation of Three Dimensional Conformal Radiotherapy with Tamoxifen in Treatment of Postoperative Malignant Glioma

Zhou, Shao-Bing,Liu, Yang-Chen,Yin, Xiao-Xiang,Ding, Wen-Xiu,Guo, Xin-Wei,Gu, Liang,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Objective: To evaluate the efficacy and adverse effects of three dimensional conformal radiotherapy (3D-CRT) with tamoxifen in treating patients with postoperative malignant glioma. Patients and Methods: 60 patients of postoperative malignant glioma were randomly assigned into two groups, 30 patients were treated with 3D-CRT plus tamoxifen (treatment group), and the other 30 patients with 3D-CRT plus temozolomide (control group). All patients were radiated by 6MV X-ray, 2.0Gy per fraction, once daily, with a total dose (DT) of 56~60Gy. Tamoxifen was delivered at $60mg/m^2/d$, temozolomide was given at $75mg/m^2/d$. All patients were treated with concurrent radiotherapy. Results: One, 2, 3 year survival rates of treatment and control group were 63.3%, 30.0%, 23.0% and 70.0%, 33.3%, 26.7%, respectively (${\chi}^2=0.01$, 0.23, 0.09, P>0.05). The rate of thromboembolism in treatment group was 6.7%. Conclusion: Therapeutic efficacy of two groups was similar, but it was more cost-effective in treatment group, and toxicity did not increase.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

A new phenylethanoid glycoside with antioxidant and anti-HBV activity from Tarphochlamys affinis

Zhou, Xian-Li,Wen, Qing-Wei,Lin, Xing,Zhang, Shi-Jun,Li, Ying-Xin,Guo, You-Jia,Huang, Ren-Bin 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5

A new phenylethanoid glycoside, named taraffinisoside A (1), together with five known glycosides were isolated from the stems and leaves of Tarphochlamys affinis. The structure of taraffinisoside A was identified on the basis of detailed spectral analysis. Compounds 1-4 and 6 showed potent antioxidant activities with $IC_{50}$ values of 10.36, 19.73, 43.95, 15.30 and $46.04{\mu}M$ by 1,1-diphenyl-2-picryhydrazyl radical-scavenging assay. Compounds 1, 2 and 4 showed anti-HBV activities, with $IC_{50}$ values of 0.50, 0.72 and 0.26 mM for HBsAg and 0.93, 0.42 and 0.07 mM for HBeAg, respectively.

RNA binding protein QKI contributes to WT1 mRNA and suppresses apoptosis in ST cells

Xin Liu,Jia Guo,Mengjiao Zhou,Yuwei Yang,Mengdi Liang,Chunyan Bai,Zhihui Zhao,Boxing Sun 한국유전학회 2017 Genes & Genomics Vol.39 No.9

The RNA binding protein quaking (QKI), a key member of the STAR family, as an upstream gene could involve in much process including cell proliferation, apoptosis, differentiation and so on. However, the roles of QKI in germ cell, especially in swine testis (ST) cells, was not clear currently. And apoptosis plays important roles in the growth and development. The purpose of the present study was to clarify the relationship between QKI and apoptosis in ST cells. Firstly, our results showed that pEF1α- QKI and shQKI3 have clear effects on expression levels of QKI. Secondly, we established that QKI directly binds to WT1 3′UTR by binding with QRE-1 (2046–2052 bp, ACT AAC ) only. Furthermore, QKI overexpression significantly increased the expression levels of WT1 and Bcl-2. QKI also has the effect on delaying the degradation of WT1 mRNA. In addition, we verified that QKI had a significantly suppressed apoptosis in ST cells. Finally, pBI-WT1 could make up for shQKI3-induced decrease in WT1, Bcl-2 mRNA levels and suppress apoptosis in ST cells. The results demonstrated that QKI was an important regulatory factor that affects apoptosis by targeting WT1 gene.

Preparation, characterization and scale performance of scale inhibitor copolymer modification with chitosan

Xiaorui Guo,Ke Dong,Xin Zhou,Jing Qi,Yang Zhou,Dongya Yang,Fengxian Qiu 한국공업화학회 2012 Journal of Industrial and Engineering Chemistry Vol.18 No.6

A scale inhibitor copolymer modification with chitosan was prepared from maleic anhydride, styrene sulfonic sodium, acrylic amide and chitosan. The conditions of preparing scale inhibitor were optimized. The chemical structure and thermal property were investigated. Using the static experiment method, the influences of copolymer concentration, temperature time, Ca2+ concentration, HCO3 concentration of the system on the inhibition efficiency were investigated. The experimental results showed that the polymer was excellent calcium carbonate scale inhibition and the resistance rate of calcium carbonate scale up to 95.62%, and could be used in the system of high temperature and high hardness water.

Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Yan Zhou,Xin’an Wu,Guo-Qiang Zhang,Zhi Rao,Yang Yang,Qian Zhou,Hongyan Qin,Yuhui Wei 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.7

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX - SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX - SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and -22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX - SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX? empty SLN) and VLX solution with Verapamil (VLX ? Ver), respectively. Furthermore, the protein mass of P-gp in VLX - SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.

Telomere-Mitochondrion Links Contribute to Induction of Senescence in MCF-7 Cells after Carbon-Ion Irradiation

Miao, Guo-Ying,Zhou, Xin,Zhang, Xin,Xie, Yi,Sun, Chao,Liu, Yang,Gan, Lu,Zhang, Hong Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

The effects of carbon-ion irradiation on cancer cell telomere function have not been comprehensively studied. In our previous report cancer cells with telomere dysfunction were more sensitive to carbon-ion irradiation, but the underlying mechanisms remained unclear. Here we found that telomerase activity was suppressed by carbon-ion irradiation via hTERT down-regulation. Inhibition of telomere activity by MST-312 further increased cancer cell radiosensitivity to carbon-ion radiation. hTERT suppression caused by either carbon-ion irradiation or MST-312 impaired mitochondrial function, as indicated by decreased membrane potential, mtDNA copy number, mitochondrial mass, total ATP levels and elevated reactive oxygen species (ROS). PGC-$1{\alpha}$ expression was repressed after carbion-ion irradiation, and hTERT inhibition by MST-312 could further exacerbate this effect. Lowering the mitochondrial ROS level by MitoTEMPO could partially counteract the induction of cellular senescence induced by carbon-ion radiation and MST-312 incubation. Taken together, the current data suggest that telomere-mitochondrion links play a role in the induction of senescence in MCF-7 cells after carbon-ion irradiation.

The Data Processing Method for Small Samples and Multi-variates Series in GPS Deformation Monitoring

Liu Guo-lin,Zheng Wen-Hua,Wang Xin-zhou,Zhang Lian-Peng 한국항해항만학회 2006 한국항해항만학회 학술대회논문집 Vol.1 No.-

Time series analysis is a frequently effective method of constructing model and prediction in data processing of deformation monitoring. The monitoring data sample must to be as more as possible and time intervals are equal roughly so as to construct time series model accurately and achieve reliable prediction. But in the project practice of GPS deformation monitoring, the monitoring data sample can’t be obtained too much and time intervals are not equal because of being restricted by all kinds of factors, and it contains many variates in the deformation model moreover. It is very important to study the data processing method for small samples and multi-variates time series in GPS deformation monitoring. A new method of establishing small samples and multi-variates deformation model and prediction model are put forward so as to resolve contradiction of small samples and multi-variates encountered in constructing deformation model and improve formerly data processing method of deformation monitoring. Based on the system theory, a deformation body is regarded as a whole organism; a time-dependence linear system model and a time-dependence bilinear system model are established. The dynamic parameters estimation is derived by means of prediction fit and least information distribution criteria. The final example demonstrates the validity and practice of this method.

Synergistic Penetration of Ethosomes and Lipophilic Prodrug on the Transdermal Delivery of Acyclovir

Yan Zhou,Yu-Hui Wei,Guo-Qiang Zhang,Xin-An Wu 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.4

The aim of this study was to investigate the lipophilic prodrug as a means of promoting acyclovir (ACV) that exhibited biphasic insolubility into the ethosomes for optimum skin delivery. Acyclovir Palmitate (ACV-C16) was synthesized as the lipophilic prodrug of ACV. The ethosomal system and the liposomal system bearing ACV or ACV-C16 were prepared, respectively. The systems were characterized for shape, zeta potential value, particle size, and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy were used for the percutaneous absorption studies. The results showed that the entrapment efficiency of ACV-C16ethosomes (87.75%) were much higher than that of ACV ethosomes (39.13%). The quantity of drug in the skin from ACV-C16 ethosomes at the end of the 24 h transdermal experiment (622.89 μg/cm2) was 5.30 and 3.43 times higher than that from ACV-C16 hydroalcoholic solution and ACV ethosomes, respectively. This study indicated that the binary combination of the lipophilic prodrug ACV-C16 and the ethosomes synergistically enhanced ACV absorption into the skin.