Research Progress in Applying Proteomics Technology to Explore Early Diagnosis Biomarkers of Breast Cancer, Lung Cancer and Ovarian Cancer

Luo, Lu,Dong, Li-You,Yan, Qi-Gui,Cao, San-Jie,Wen, Xin-Tian,Huang, Yong,Huang, Xiao-Bo,Wu, Rui,Ma, Xiao-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

According to the China tumor registry 2013 annual report, breast cancer, lung cancer, and ovarian cancer are three common cancers in China nowadays, with high mortality due to the absence of early diagnosis technology. However, proteomics has been widespreadly implanted into every field of life science and medicine as an important part of post-genomics era research. The development of theory and technology in proteomics has provided new ideas and research fields for cancer research. Proteomics can be used not only for elucidating the mechanisms of carcinogenesis focussing on whole proteins of the tissue or cell, but also seeking the biomarkers for diagnosis and therapy of cancer. In this review, we introduce proteomics principles, covering current technology used in exploring early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer.

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

Fu, Si-Rui,Zhang, Ying-Qiang,Li, Yong,Hu, Bao-Shan,He, Xu,Huang, Jian-Wen,Zhan, Mei-Xiao,Lu, Li-Gong,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials and Methods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.

Regulatory Mechanisms of Annexin-Induced Chemotherapy Resistance in Cisplatin Resistant Lung Adenocarcinoma

Wang, Chao,Xiao, Qian,Li, Yu-Wen,Zhao, Chao,Jia, Na,Li, Rui-Li,Cao, Shan-Shan,Cui, Jia,Wang, Lu,Wu, Yin,Wen, Ai-Dong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic.

Gene Microarray Assessment of Multiple Genes and Signal Pathways Involved in Androgen-dependent Prostate Cancer Becoming Androgen Independent

Liu, Jun-Bao,Dai, Chun-Mei,Su, Xiao-Yun,Cao, Lu,Qin, Rui,Kong, Qing-Bo Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

Whole-process Bond Characteristics of FRP-to-concrete Joint under Pressure

Lei Gao,Feng Zhang,Jia-qi Liu,Xiao-rui Lu 대한토목학회 2018 KSCE JOURNAL OF CIVIL ENGINEERING Vol.22 No.12

Lateral anchoring can effectively inhibit the premature debonding of FRP (Fiber-Reinforced Polymer) plate bonds to concrete. To effectively improve the efficiency of reinforcement, the bond characteristics of FRP-to-concrete joints under pressure through the entire debonding process were analyzed via a theoretical model, experimental evaluation, and parameter studies. The results show that the load-slip behavior of a bonded joint features an elastic stage, an elastic-softening stage, an elastic-softening-residual stage, a softening-residual stage and a residual stage. Moreover, the trilinear bond-slip model reveals changes in interface bonding properties under pressure. The experimental analysis of the load-slip relationship and bond stress distribution prove the accuracy of the theoretical model. Both load capacity and slip increase with increasing bond length or lateral pressure, while increasing the plate stiffness results in an increased load capacity and a reduction in ductility.

Heavy concrete shielding properties for carbon therapy

Jin-Long Wang,Jiade J Lu,Da-Jun Ding,Wen-Hua Jiang,Ya-Dong Li,Rui Qiu,Hui Zhang,Xiao-Zhong Wang,Huo-Sheng Ruan,Yan-Bing Teng,Xiao-Guang Wu,Yun Zheng,Zi-Hao Zhao,Kai-Zhong Liao,Huan-Cheng Mai,Xiao-Dong Korean Nuclear Society 2023 Nuclear Engineering and Technology Vol.55 No.6

As medical facilities are usually built at urban areas, special concrete aggregates and evaluation methods are needed to optimize the design of concrete walls by balancing density, thickness, material composition, cost, and other factors. Carbon treatment rooms require a high radiation shielding requirement, as the neutron yield from carbon therapy is much higher than the neutron yield of protons. In this case study, the maximum carbon energy is 430 MeV/u and the maximum current is 0.27 nA from a hybrid particle therapy system. Hospital or facility construction should consider this requirement to design a special heavy concrete. In this work, magnetite is adopted as the major aggregate. Density is determined mainly by the major aggregate content of magnetite, and a heavy concrete test block was constructed for structural tests. The compressive strength is 35.7 MPa. The density ranges from 3.65 g/cm³ to 4.14 g/cm³, and the iron mass content ranges from 53.78% to 60.38% from the 12 cored sample measurements. It was found that there is a linear relationship between density and iron content, and mixing impurities should be the major reason leading to the nonuniform element and density distribution. The effect of this nonuniformity on radiation shielding properties for a carbon treatment room is investigated by three groups of Monte Carlo simulations. Higher density dominates to reduce shielding thickness. However, a higher content of high-Z elements will weaken the shielding strength, especially at a lower dose rate threshold and vice versa. The weakened side effect of a high iron content on the shielding property is obvious at 2.5 µSv=h. Therefore, we should not blindly pursue high Z content in engineering. If the thickness is constrained to 2 m, then the density can be reduced to 3.3 g/cm³, which will save cost by reducing the magnetite composition with 50.44% iron content. If a higher density of 3.9 g/cm³ with 57.65% iron content is selected for construction, then the thickness of the wall can be reduced to 174.2 cm, which will save space for equipment installation.

Radiosensitivity Enhancement by Arsenic Trioxide in Conjunction with Hyperthermia in the EC-1 Esophageal Carcinoma Cell Line

Cui, Yan-Hui,Liang, Hai-Jun,Zhang, Qing-Qin,Li, Si-Qing,Li, Xiao-Rui,Huo, Xiao-Qing,Yang, Qing-Hui,Li, Wei-Wei,Gu, Jian-Fa,Hua, Qin-Liang,Lu, Ping,Miao, Zhan-Hui Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Objective: To explore the effect on radiosensitivity of arsenic trioxide ($As_20_3$) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of $As_20_3$ was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of $IC_{50}$ value and choice of 20% of the $IC_{50}$ as the experimental drug concentration. Blank control, $As_20_3$, hyperthermia, radiotherapy group, $As_20_3$ + hyperthermia, $As_20_3$ + radiotherapy, hyperthermia + radiotherapy and $As_20_3$ + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: $As_20_3$ exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an $IC_{50}$ of 18.7 ${\mu}mol/L$. After joint therapy of $As_20_3$ + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the $G_2$/M phase, and as the ratio of cells in $G_0/G_1$ and S phases decreased, cell death became more pronounced. Conclusion: $As_20_3$ and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, $As_20_3$ and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

Identification of drug target candidates of the swine pathogen Actinobacillus pleuropneumoniae by construction of protein–protein interaction network

Siqi Li,Zhipeng Su,Chengjun Zhang,Zhuofei Xu,Xiaoping Chang,Jiawen Zhu,Ran Xiao,Lu Li,Rui Zhou 한국유전학회 2018 Genes & Genomics Vol.40 No.8

Porcine pleuropneumonia caused by Actinobacillus pleuropneumoniae has led to severe economic losses in the pig industry worldwide. A. pleuropneumoniae displays various levels of antimicrobial resistance, leading to the dire need to identify new drug targets. Protein–protein interaction (PPI) network can aid the identification of drug targets by discovering essential proteins during the life of bacteria. The aim of this study is to identify drug target candidates of A. pleuropneumoniae from essential proteins in PPI network. The homologous protein mapping method (HPM) was utilized to construct A. pleuropneumoniae PPI network. Afterwards, the subnetwork centered with H-NS was selected to verify the PPI network using bacterial two-hybrid assays. Drug target candidates were identified from the hub proteins by analyzing the topology of the network using interaction degree and homologous comparison with the pig proteome. An A. pleuropneumoniae PPI network containing 2737 non-redundant interaction pairs among 533 proteins was constructed. These proteins were distributed in 21 COG functional categories and 28 KEGG metabolic pathways. The A. pleuropneumoniae PPI network was scale free and the similar topological tendencies were found when compared with other bacteria PPI network. Furthermore, 56.3% of the H-NS subnetwork interactions were validated. 57 highly connected proteins (hub proteins) were identified from the A. pleuropneumoniae PPI network. Finally, 9 potential drug targets were identified from the hub proteins, with no homologs in swine. This study provides drug target candidates, which are promising for further investigations to explore lead compounds against A. pleuropneumoniae.