miR-340 Reverses Cisplatin Resistance of Hepatocellular Carcinoma Cell Lines by Targeting Nrf2-dependent Antioxidant Pathway

Shi, Liang,Chen, Zhan-Guo,Wu, Li-li,Zheng, Jian-Jian,Yang, Jian-Rong,Chen, Xiao-Fei,Chen, Zeng-Qiang,Liu, Cun-Li,Chi, Sheng-Ying,Zheng, Jia-Ying,Huang, Hai-Xia,Lin, Xiang-Yang,Zheng, Fang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

Upregulation of STK15 in Esophageal Squamous Cell Carcinomas in a Mongolian Population

Chen, Guang-Lie,Hou, Gai-Ling,Sun, Fei,Jiang, Hong-Li,Xue, Jin-Feng,Li, Xiu-Shen,Xu, En-Hui,Gao, Wei-Shi,Cao, Jian-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: The STK15 gene located on chromosome 20q13.2 encodes a centrosome-associated kinase critical for regulated chromosome segregation and cytokinesis. Recent studies have demonstrated STK15 to be significantly associated with many tumors, with aberrant expression obseved in many human malignancies. The purpose of this study was to investigate expression of STK15 in esophageal squamous cell carcinomas (ESCCs) in a Mongolian population. Methods: Two non-synonymous single nucleotide polymorphisms in the coding region of STK15, rs2273535 (Phe31Ile) and rs1047972 (Val57Ile) were assessed in 380 ESCC patients and 380 healthy controls. We also detected STK15 mRNA expression in 39 esophageal squamous cell carcinomas and corresponding adjacent tissues by real time PCR. Results: rs2273535 showed a significant association with ESCC in our Mongolian population (rs227353, P allele = 0.0447, OR (95%CI) = 1.259 (1.005~1.578)). Real time PCR analysis of ESCC tissues showed that expression of STK15 mRNA in cancer tissues was higher than in normal tissues (p = 0.013). Conclusions: Our study showed that functional SNPs in the STK15 gene are associated with ESCC in a Mongolian population and up-regulation of STK15 mRNAoccurs in ESCC tumors compared adjacent normal tissues. STK15 may thus have an important role in the prognosis of ESCC and be a potential therapeutic target.

Overexpression of Astrocyte Elevated Gene-1 (AEG-1) in Cervical Cancer and its Correlation with Angiogenesis

Yu, Jian-Qin,Zhou, Qing,Zhu, Hua,Zheng, Fei-Yun,Chen, Zhi-Wen Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Objectives: To explore the expression of astrocyte elevated gene-1 (AEG-1) in cervical cancer and analyze its correlation with microvascular density (MVD), nuclear factor kappaB (NF-kB p65) and vascular endothelial growth factor (VEGF). Materials and Methods: Immunohistochemical MaxVision method was adopted to detect the expression level of AEG-1, NF-kB p65 and VEGF in 45 samples of invading cervical cancer and 12 samples of cervicitis from The First Affiliated Hospital of Wenzhou Medical University. Tumor microvascular endothelial marker CD34 combined with Weidner was used to determine the MVD in cervical cancer tissue. The positive expression and staining conditions of AEG-1, NF-kB p65 and VEGF in cervical cancer tissues were observed under a light microscope. Correlations between expression of AEG-1 protein and those of NF-Kb p65 and VEGF, as well as MVD, were analyzed using Pearson correlation. Results: The expression levels of AEG-1 were $0.186{\pm}0.043$ in cervical cancer and $0.051{\pm}0.002$ in chronic cervicitis (p<0.01). Moreover, expression of AEG-1 was related to vascular invasion and lymphatic metastasis of cervical cancer (p<0.01), but not with age of the patients, differentiation degree, tumour size, pathological type and parametrial infiltration (p>0.05). Pearson correlation analysis showed that the expression of AEG-1 was linked with NF-kB p65 (r=0.501, p=0.000), VEGF (r=0.718, p=0.000) as well as MVD in cervical cancer tissue (r=0.815, p=0.000). Conclusions: AEG-1 is highly expressed in cervical cancer and promotes angiogenesis, which might be related to the fact that AEG-1 activating the signal pathway of NF-kB could up-regulate the level of VEGF expression.

Key challenges, recent advances and future perspectives of rechargeable lithium-sulfur batteries

Ze-Chen Lv,Peng-Fei Wang,Jian-Cang Wang,Shu-Hui Tian,Ting-Feng Yi 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.124 No.-

Lithium-sulfur (Li-S) battery, which releases energy by coupling high abundant sulfur with lithium metal,is considered as a potential substitute for the current lithium-ion battery. Thanks to the lightweight andmulti-electron reaction of sulfur cathode, the Li-S battery can achieve a high theoretical specific capacityof 1675 mAh g1 and specific energy of 2600 Wh kg1. However, some key scientific issues limit its practicalapplication, such as the ‘‘shuttle effect” of lithium polysulfides, large volume change, poor conductivityof sulfur and its solid-state products, and self-discharge phenomenon. Of these, the ‘‘shuttle effect”is recognized as the most critical challenge affecting on electrochemical performance. Hence, this reviewfirst systematically introduces the development of Li-S batteries and the corresponding ‘‘shuttle effect”. Then, the latest work on anode, cathode, separator and electrolyte are summarized. Finally, some promisingviews on the future research direction of this battery system are put forward.

Genetic variations in the bitter taste receptor gene TAS2R38 are related to cigarette smoking behavior in Han Chinese smokers

Qi Fei-Yan,Zhu Zhou-Hai,Li Meng,Guan Ying,Peng Qi-Yuan,Lu She-Ming,Liu Zhi-Hua,Wang Ming-Feng,Miao Ming-Ming,Chen Zhang-Yu,Li Xue-Mei,Bai Jie,Yao Jian-Hua 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear. Objective: This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population. Methods: The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293. Results: Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X2 = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X2 = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells. Conclusion: Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers.

Risk Factors, Patterns, and Outcomes of Late Recurrence after Liver Resection for Patients with Hepatocellular Carcinoma (Analysis of a Multicenter Cohort over 15 Years)

( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Hao Xing ),( Jun Han ),( Zhen-li Li ),( Han Wu ),( Han Zhang ),( Jian-hong Zhong ),( Yi- Sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Late recurrence (> 2 years) after liver resection of hepatocellular carcinoma (HCC) is usually considered as multi-centric tumors or de novo cancer formation. We aimed to investigate risk factors, patterns and outcomes of late recurrence after HCC resection. Methods: From a multicenter database from 2001 to 2015, 734 patients who were alive and recurrence-free at 2 years after curative resection of initial HCC were enrolled into this retrospective study. Univariate and multivariate Cox-regression analysis were used to identify independent risk factors of late recurrence. Patterns, treatments and outcomes of late recurrence were investigated and analyzed. Results: During a median follow-up of 78.0 months after surgery, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that cirrhosis, macroscopic vascular invasion, satellites, and tumor size > 5cm were independent risk factors of late recurrence. Among them, 273 (90.1%) were sole intrahepatic recurrence, 30 (9.9%) were concurrent intrahepatic and extrahepatic recurrence, and none of them was sole extrahepatic recurrence; 165 (54.4%) patients received curative treatments for recurrent HCC, including re-resection, transplantation and local ablation. Multivariate analysis showed regular postoperative surveillance and receiving curative treatments were two independent protective factors of prolonging survival for those patients with late recurrence. Conclusions: Late recurrence is correlated with cirrhosis and certain tumor-related characteristics of initial HCC. The patterns of late recurrence suggest that postoperative surveillance after 2 years of surgery could be adjusted and more targeted. Regular postoperative surveillance improves the probability to receive curative treatments again, yielding to better outcomes for patients with late recurrence.

A Color-Reaction-Based Biochip Detection Assay for RIF and INH Resistance of Clinical Mycobacterial Specimens

( Wen Fei Xue ),( Jing Fu Peng ),( Xiao Li Yu ),( Shu Lin Zhang ),( Boping Zhou ),( Dan Qing Jiang ),( Jian Bo Chen ),( Bing Bing Ding ),( Bin Zhu ),( Yao Li ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.1

The widespread occurrence of drug-resistant Mycobacterium tuberculosis places importance on the detection of TB (tuberculosis) drug susceptibility. Conventional drug susceptibility testing (DST) is a lengthy process. We developed a rapid enzymatic color-reaction-based biochip assay. The process included asymmetric multiplex PCR/templex PCR, biochip hybridization, and an enzymatic color reaction, with specific software for data operating. Templex PCR (tem- PCR) was applied to avoid interference between different primers in conventional multiplex- PCR. We applied this assay to 276 clinical specimens (including 27 sputum, 4 alveolar lavage fluid, 2 pleural effusion, and 243 culture isolate specimens; 40 of the 276 were non-tuberculosis mycobacteria specimens and 236 were M. tuberculosis specimens). The testing process took 4.5 h. A sensitivity of 50 copies per PCR was achieved, while the sensitivity was 500 copies per PCR when tem-PCR was used. Allele sequences could be detected in mixed samples at aproportion of 10%. Detection results showed a concordance rate of 97.46% (230/236) in rifampicin resistance detection (sensitivity 95.40%, specificity 98.66%) and 96.19% (227/236) in isoniazid (sensitivity 93.59%, specificity 97.47%) detection with those of DST assay. Concordance rates of testing results for sputum, alveolar lavage fluid, and pleural effusion specimens were 100%. The assay provides a potential choice for TB diagnosis and treatment.

The characteristics of genistin-induced inhibitory effects on intestinal motility

Yong-jian Xiong,Da-peng Chen,Bo-chao Lv,Fang-fei Liu,Li Wang,Yuan Lin 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.3

Genistin belongs to isoflavones. Based on thefacts that genistin exerts inhibitory effects on the contractilityof vascular smooth muscle,the present study wasdesigned to characterize the effects of genistin on intestinalcontractility and evaluate its potential clinical implication. Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, andin vivo assays were used in the study. The results indicatedthat genistin (5–80 lmol/L) inhibited the contraction of IJSin a dose-dependent manner and inhibited the increasedcontractilityof IJS induced by acetylcholine (ACh), histamine,high Ca2?, and erythromycin, respectively. Theinhibitory effects of genistin were correlated with thestimulation of alpha adrenergic and beta adrenergicreceptors since these inhibitory effects were significantlyblocked in the presence of phentolamine and propranololrespectively. No further inhibitory effects of genistin wereobserved in the presence of verapamil or in Ca2?-freecondition, indicating genistin-induced inhibitory effects areCa2?-dependent. Genistin decreased myosin light chainkinase (MLCK) protein contents and MLCK mRNAexpression in IJS, and inhibited both phosphorylation andMg2?-ATPase activity of purified myosin, implicating thatthe decrease of MLCK contents and inhibition of MLCKactivity are involved in the genistin-induced inhibitoryeffects. The study suggests the potential clinical implicationsof genistin in relieving intestinal hypercontractility.

Phase II Clinical Study on the GEMOX Regimen as Second-line Therapy for Advanced Ovarian Cancer

Yuan, Shao-Fei,Zhang, Lian-Ping,Zhu, Lin-Jia,Chen, Wen-Jun,Zheng, Wei-E,Xiong, Jian-Ping Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Aim: To investigate the effectiveness and adverse effects of gemcitabine by fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as second-line therapy for advanced ovarian cancer. Methods: 64 patients with advanced ovarian cancer were divided into an experimental group (44 cases) and a control group (20 cases). The experimental group was treated with continuous intravenous infusion of gemcitabine at 1000 $mg/m^2$ with a fixed-dose rate of 10 $mg/m^2/min$, on days 1 and 8 and oxaliplatin at 100 $mg/m^2$ on day 1, IVGTT, repeated every 3 weeks. The control group was treated with intravenous infusion of gemcitabine at 1000 $mg/m^2$ within 30 min on days 1 and and oxaliplatin at 100 $mg/m^2$ on day 1, IVGTT, again repeated every 3 weeks. CT scans or MRI were used for review every 1-2 cycles. Results: The effective rate in the experimental group was significantly high than control group (43.2% vs 35.0%; P < 0.05), with no obvious difference of hematologic or non-hematologic toxicity between the two groups (P > 0.05). Conclusion: GEMOX regimen is very effective to treat advanced ovarian cancer, with low toxicity, good tolerance and improved life quality in patients.

Effects of Monoclonal Antibodies against Human Stathmin Combined with Paclitaxel on Proliferation of the QG-56 Human Lung Carcinoma Cell Line

Yuan, Shao-Fei,Chen, Wen-Jun,Zhu, Lin-Jia,Zheng, Wei-E.,Chen, Hua,Xiong, Jian-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Objective: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. Methods: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. Results: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). Conclusions: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together. The observed synergistic effects may have important implications for clinical application.