Weight Loss Correlates with Macrophage Inhibitory Cytokine-1 Expression and Might Influence Outcome in Patients with Advanced Esophageal Squamous Cell Carcinoma

Lu, Zhi-Hao,Yang, Li,Yu, Jing-Wei,Lu, Ming,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Zhang, Xiao-Tian,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy:>5% weight loss group and ${\leq}5%$ weight loss group. Results: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss >5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) Conclusions: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients.

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Li, Qing-Qing,Lu, Zhi-Hao,Yang, Li,Lu, Ming,Zhang, Xiao-Tian,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Preparation and Characterization of Anti-GP73 Monoclonal Antibodies and Development of Double-antibody Sandwich ELISA

Li, Qi-Wen,Chen, Hong-Bing,Li, Zhi-Yang,Shen, Peng,Qu, Li-Li,Gong, Lai-Ling,Xu, Hong-Pan,Pang, Lu,Si, Jin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. Materials and Methods: Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. Results: showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). Conclusions: Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Lu, Feng-Bin,Chen, Da-Zhi,Chen, Lu,Hu, En-De,Wu, Jin-Lu,Li, Hui,Gong, Yue-Wen,Lin, Zhuo,Wang, Xiao-Dong,Li, Ji,Jin, Xiao-Ya,Xu, Lan-Man,Chen, Yong-Ping Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Effects of Supplementary Composts on Microbial Communities and Rice Productivity in Cold Water Paddy Fields

( Kai Zhi Xie ),( Pei Zhi Xu ),( Shao Hai Yang ),( Yu Sheng Lu ),( Rui Ping Jiang ),( Wen Jie Gu ),( Wen Ying Li ),( Li Li Sun ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.5

Cold water paddy field soils are relatively unproductive, but can be ameliorated by supplementing with inorganic fertilizer from animal waste-based composts. The yield of two rice cultivars was significantly raised by providing either chicken manure or cow dung-based compost. The application of these composts raised the soil pH as well as both the total nitrogen and ammonium nitrogen content, which improved the soil’s fertility and raised its nitrification potential. The composts had a measurable effect on the abundance of nitrogencycling- related soil microbes, as measured by estimating the copy number of various bacterial and archaeal genes using quantitative real-time PCR. The abundance of ammonia oxidizing archaea and bacteria was markedly encouraged by the application of chicken manure-based compost. Supplementation with the composts helped promote the availability of soil nitrogen in the cold water paddy field, thereby improving the soil’s productivity and increasing the yield of the rice crop.

Determination of Protein, Fat, Starch, and Amino Acids in Foxtail Millet [Setaria italica (L.) Beauv.] by Fourier Transform Near-Infrared Reflectance Spectroscopy

Xiu-Shi Yang,Li-Li Wang,Xian-Rong Zhou,Shaomin Shuang,Zhi-Hua Zhu,Nan Li,Yan Li,Fang Liu,San-Cai Liu,Ping Lu,Guixing Ren,Chuan Dong 한국식품과학회 2013 Food Science and Biotechnology Vol.22 No.6

Quantitative detection of protein, fat, starch,and amino acids in foxtail millet using Fourier transformnear-infrared spectroscopy (NIRS) was investigated. Foxtail millet samples (n=259) were analyzed using NIRS. Spectral data were linearized with data from chemicalanalyses. Calibration models were established using apartial least-squares (PLS) algorithm with cross-validation. Optimized models were tested using external validation setsamples with coefficients of determination in the externalvalidation (R2val) of >0.90. Residual predictive deviation(RPD) values were nearly equal to or >2.5 for crudeprotein, alanine, aspartic acid, glutamic acid, isoleucine,leucine, and serine. However, for glycine, histidine,phenylalanine, proline, threonine, tyrosine, and valine, theR2val values were >0.83 and RPD values were nearly equalto or >2.0. For crude fat, total starch, arginine, and lysine,the R2val values were >0.70 and RPD values were >1.5. NIRS is a rapid determination tool for foxtail milletbreeding, and for quality control.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Yong-Ping Chen,Feng-Bin Lu,Da-Zhi Chen,Lu Chen,En-De Hu,Jin-Lu Wu,Hui Li,Yue-Wen Gong,Zhuo Lin,Xiao-Dong Wang,Ji Li,Xiao-Ya Jin,Lan-Man Xu 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

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.

Feasibility and Efficacy of Concurrent Chemoradiotherapy in Elderly Patients with Esophageal Squamous Cell Carcinoma: a Respective Study of 116 Cases from a Single Institution

Li, Xue,Zhao, Lu-Jun,Liu, Ning-Bo,Zhang, Wen-Cheng,Pang, Qing-Song,Wang, Ping,Yuan, Zhi-Yong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

Background: To evaluate the safety and efficacy of combined chemoradiotherapy or radiotherapy alone in elderly patients with esophageal carcinoma to identify the best method of treatment. Materials and Methods: One hundred and sixteen patients with esophageal carcinoma aged 70 and older who received definitive radiotherapy or chemoradiotherapy entered the study. Overall survival (OS), disease-free survival (DFS) and treatment-related toxicities were assessed. Results: The median OS of the overall population was 17.9 months. For patients treated with cCRT, sCRT and radiotherapy alone, the median OS was 22.3 months, 18.0 months and 12.4 months respectively(P=0.044). Median OS for patients treated with radiotherapy dose ${\geq}60Gy$ and <60Gy was 20.2 months and 10.9 months respectively (p=0.017). By univariate analysis, Chemoradiotherapy (include cCRT and sCRT) and radiotherapy dose ${\geq}60Gy$ were found to achieve higher survival rates compared with radiotherapy alone and radiotherapy dose <60Gy (P=0.015, P=0.017). By multivariate analysis, chemoradiotherapy (HR=1.645, P=0.022) and radiotherapy dose ${\geq}60Gy$ (HR=1.642, P=0.025) were identified as independent prognostic factors of OS. Conclusions: Definitive concurrent chemoradiotherapy could be considered as a feasible and effective treatment in esophageal carcinoma patients aged 70 and older. Radiotherapy dose 60Gy is an effective treatment option compared with standard dose radiotherapy, while higher doses are not beneficial to improve survival.

Etch-pits of GaN Films with different etching methods

LU MIN,CHANG XIN,FANG HUI-ZHI,LI ZI-LAN,REN QIAN,YANG HUA,YANG JHI-ZIAN,ZHANG GUO-YI,ZHANG BEI 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.3

The etch stop process of SrBi2Ta2O9 (SBT) over CeO2 in Inductively Coupled Plasma Reactive Ion Etching (ICP-RIE) is reported in this paper. The etch stop of ferroelectric thin lm on a silicon surface without damage is important for the self-aligned gate structure process in the fabrication of the single-transistor-type ferroelectric random access memory. A high vertical etching angle is also necessary for high integration. We investigated the etch rate of SBT and of Si and CeO2 which were used as a buer layer to improve the interface between SBT and silicon, with various Ar/Cl2 gas mixtures, ICP powers and RF bias powers in ICP-RIE. The highest etching selectivity of SBT/CeO2 and SBT/Si was 6.8 and 0.3 respectively. The vertical angle of SBT was 82 degrees. SEM images and XPS surface analyses showed good etch stop characteristics of the buer layer without damage to the silicon surface.