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25 April 2019, Volume 11 Issue 2 Previous Issue    Next Issue

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How far is tumor immunotherapy from the path of precision medicine ZHANG Xiaoyu , XIE Xiaodong 2019, 11 (2):  89-92.  doi: 10.3969/j.issn.1674-5671.2019.02.01 Abstract ( 777 )   PDF (1573KB) ( 198 )   Save Related Articles | Metrics

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Research progress and application of cancer epigenetic markers XIAO Ting, FU Junjiang 2019, 11 (2):  93-98.  doi: 10.3969/j.issn.1674-5671.2019.02.02 Abstract ( 458 )   PDF (1107KB) ( 429 )   Save Related Articles | Metrics

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Current status and research progress of exsome biomarker and liquid biopsy for cancer  LIN Yusheng, GAN Jinfeng, JIANG Yuchen, WANG Feihan, ZHANG Hao 2019, 11 (2):  99-103.  doi: 10.3969/j.issn.1674-5671.2019.02.03 Abstract ( 398 )   PDF (1125KB) ( 319 )   Save Related Articles | Metrics

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Expression of ACCα and its effect on cell growth in hepatocellular carcinoma LIANG Ning, WANG Qian, HUANG Qian, LI Renzhi, YANG Tao, YANG Yi, HUANG Xiaojun, HE Xianli 2019, 11 (2):  104-109.  doi: 10.3969/j.issn.1674-5671.2019.02.04 Abstract ( 388 )   PDF (5927KB) ( 254 )   Save Objective To investigate the expression of acetyl CoA carboxylase alpha（ACCα） in hepatocellular carcinoma（HCC） and its regulation in HCC cell growth. Methods The expression levels of ACCα at both mRNA and protein were examined in 30 cases of HCC and adjacent normal tissues by using real-time quantitative PCR（qRT-PCR） and Western blot analysis. Cell proliferation，cell cycle distribution and cell apoptosis were determined by using MTS assay and flow cytometry after ACCα was knocked-down by small interference RNA （siRNA）. Results The qRT-PCR and Western　blot showed that the expression of ACCα at mRNA and protein levels were significantly higher in HCC tissues than in adjacent normal tissues（3.26±0.81 vs1.88±0.64，P＝0.021；3.41±0.71 vs 1.74±0.54，P＝0.019）. Knockdown of ACCα significantly decreased cell proliferation（P<0.01） and suppressed cell cycle progression（P<0.05），while increased cell apoptosis （P<0.01）.Conclusions The expression of ACCα is significantly upregulated in HCC，which promoted the proliferation of HCC cells mainly by inducing cell cycle progression and suppressing cell apoptotic. ACCα may be used as a potential therapy target for the treatment of HCC. Related Articles | Metrics

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The preliminary study on ctDNA-driven gene mutation detected by cSMART and its effect on precise treatment of non-small cell lung cancer LI Fangying, E Ying, JING Mingxi, XU Junnan, SUN Tao 2019, 11 (2):  110-115.  doi: 10.3969/j.issn.1674-5671.2019.02.05 Abstract ( 375 )   PDF (3325KB) ( 249 )   Save Objective To investigate ctDNA-driven gene mutations in patients with non-small cell lung cancer（NSCLC） based on circulating single-molecule amplification and resequencing technology（cSMART） and guide its treatment. Methods Totals of 107 patients with NSCLC were enrolled from July 2016 to December 2018 at the Department of Oncology Medical in Liaoning Cancer Hospital. The mutations of 9 ctDNA-driven genes such as EGFR，ALK，KRAS，BRAF，PIK3CA，ERBB2，ROS1，RET and MET were detected by cSMART. After each 2-4 treatment courses，the patient's 9 ctDNA-driven genes mutation distributions were evaluated，and the patients were guided to medication based on the NCCN guidelines and 9 genes test results. A total of 57 patients with NSCLC who completed the survival information and completed the follow-up treatment were divided into the standard treatment group（n=39） and the non-standard treatment group （n=18） according to whether they followed the guidelines，and compared the therapeutic effects. Results Based on cSMART，78 cases were positive mutation and 28 cases were negative mutation. Among the 78 patients who drived gene mutations，27 patients had single gene mutation，24 patients had double gene mutations，11 patients had three gene mutations，5 patients had four gene mutations，and 5 patients had five gene mutations. 106 patients with non-small　cell lung cancer had a total of 186 mutations, including 26 without mutations and 160 mutations. Among 160 mutations，there were 61　EGFR mutations，11 ALK mutations（including ALK fusion and point mutation），54 TP53 mutations，26 KRAS mutations，5 PIK3CA mutations，1  BRAF mutation，1  MET mutation and 1 ERBB2 mutation. The median progression-free survival（mPFS） of patients receiving standard treatment was longer than that of patients receiving non-standard treatment（10.0 months vs 5.5 months χ2=6.420，P=0.011）. Conclusions It is simple and non-invasive based on cSMART assay ctDNA to identify non-small cell lung cancer drive gene mutations. EGFR and ALK are common driving mutations，and their targeted therapy are better. Related Articles | Metrics

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Expression of HOXC8 in hilar cholangiocarcinoma and its clinical significance XU Dongyun, WANG Juan, LI Ke, YU Guanzhen, YU Wenlong, XU Yongmao 2019, 11 (2):  116-120.  doi: 10.3969/j.issn.1674-5671.2019.02.06 Abstract ( 272 )   PDF (2396KB) ( 140 )   Save  Objective To investigate the expression of HOXC8 in human hilar cholangiocarcinoma and its effect on prognosis.Methods The expression levels of HOXC8 protein in 49 cases of hilar cholangiocarcinoma and corresponding adjacent tissues were detected by tissue microarray and immunohistochemistry. The relationship of the expression of HOXC8 protein，the clinico-pathological features and prognosis of patients with hilar cholangiocarcinoma was analyzed. Results The positive expression rate of HOXC8 protein in hilar cholangiocarcinoma tissues was significantly higher than that in adjacent normal tissues（57.1% vs 42.9%，P<0.001）. HOXC8 expression was correlated with tumor invasion，lymph node metastasis，and TNM stage（P<0.05）. Univariate survival analysis showed that patients with positive expression of HOXC8 had poor overall survival than those with negative HOXC8 expression patients（12 months vs 46 months，P<0.001）. Multivariate regression analysis showed that HOXC8 was an independent prognostic factor for patients with hilar cholangiocarcinoma（P=0.039）. Conclusions HOXC8 is highly expressed in hilar cholangiocarcinoma and is associated with poor prognosis. HOXC8 may be used as a prognostic marker and potential therapeutic target for patients with hilar cholangiocarcinoma. Related Articles | Metrics

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Effects of asiatic acid on proliferation and autophagy of human hepatoma SMMC-7721 cells SU Qi, WANG Xianzhe, LIANG Cong, LI Yuanyuan, HE Ping 2019, 11 (2):  121-125.  doi: 10.3969/j.issn.1674-5671.2019.02.07 Abstract ( 334 )   PDF (3641KB) ( 164 )   Save Objective To investigate the effects of asiatic acid（AA） on cell proliferation and autophagy of human hepatoma SMMC-7721 cells. Methods The human hepatoma SMMC-7721 cells were exposed to different concentrations of AA alone or combined with autophagy inhibitor 3-MA for 24 h，after that，the cell viability was examined by MTT method，the formation of autophagic vacuoles were detected by MDC staining，the expression of the autophagy-related proteins including LC3-Ⅰ，LC3-Ⅱ，p62，mTOR，p-mTOR，and p53 were detected by Western-blot. Results  MTT assay results showed that different concentrations of AA could inhibit the proliferation of human hepatocarcinoma SMMC-7721 cells in a concentration-dependent manner（F＝46.790，P＝0.006） with IC50= 37.313 μmon/L.When combined with autophagy inhibitor 3-MA，the cell proliferation inhibition rate （%） of AA to SMMC-7721 cells was significantly reduced compared with the group treated with 40 μmol/L AA alone［（22.000±3.391）% vs （46.400±9.099） %，P<0.001）］. AA increased the amount of autophagic vacuoles detected by MDC staining. Compared with the control group，40 μmol/L AA significantly down-regulated the protein expression level of LC3-I while up-regulated the protein expression of LC3-Ⅱ（1.744±0.108 vs 1.529±0.065，t=2.928，P=0.043；0.113±0.031  vs 0.380±0.036，t=-9.754，P<0.001），but down-regulated the p62 protein expression（0.522±0.024 vs 0.123±0.019，t=22.565，P<0.001）.　Besides，AA significantly reduced the protein expression level of p-mTOR（1.252±0.039 vs 0.353±0.028，t=30.775，P<0.001），but had no influence on the protein expression of mTOR and p53（1.713±0.111 vs 1.556±0.076，t=1.555，P=0.190；0.671±0.040 vs 0.726±0.055，t=-1.555，P=0.210）. Conclusions AA can inhibit the proliferation of human hepatoma SMMC-7721 cells，which may be related to the AA-inducted autophagy via the suppression of mTOR signaling pathway in a p53-indepandent manner. Related Articles | Metrics

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Effect of Hsa-miR-4282 on the growth of hepatoma cell line SMMC-7721 WANG Huifeng, CHEN Jie, LUO Tao, CHEN Miao, ZHAO Yuan, WANG Duo, LI Lequn 2019, 11 (2):  126-131.  doi: 10.3969/j.issn.1674-5671.2019.02.08 Abstract ( 358 )   PDF (8329KB) ( 81 )   Save Objective To investigate the expression of Hsa-miR-4282 in hepatocellular carcinoma cell line SMMC-7721 and its effect on cell growth. Methods The expression of Hsa-miR-4282 in human normal liver epithelial cell line HL-7702，human hepatoma cell lines MHCC97-H and SMMC-7721，20 cases of primary liver cancer tissues and their corresponding adjacent tissues were detected by quantitative real-time PCR. The SMMC-7721 cells were transfected with Hsa-miR-4282 mimics（up-regulation group） or Hsa-miR-4282 inhibitor（down-regulation group） by transient transfection method，and negative control group were set in the up-regulated group and the down-regulated group，respectively.After transfection，the cell proliferation ability was detected by MTT assay，the cell clone formation ability was detected by plate cloning assay，and the apoptosis ability was detected by flow cytometry. Results The expres-sion of Hsa-miR-4282 in liver cancer tissues，liver cancer cells MHCC97-H and liver cancer cells SMMC-7721 were lower than that in adjacent tissues and normal liver cells HL-7702 （P<0.05）.The MTT assay showed that the OD value of liver cancer SMMC-7721 cells up-regulated by Hsa-miR-4282 was lower than that of the negative control group，but the OD value of liver cancer SMMC-7721 cells down-regulated by Hsa-miR-4282 was higher than that of the control group.Plate cloning experiments showed that the number of cell clones in the down-regulated group was higher than that in the negative control group ［（240±7） vs （191±10），P=0.005）］，while the number of cell clones in the up-regulated group was lower than that in the control group ［（146±10） vs （193±12），P=0.013）］.The results of flow cytometry showed that the apoptosis rate of Hsa-miR-4282 up-regulated group was higher than that of the control group ［（23.89±1.89）% vs （16.6±1.14）%，P=0.009）］，while the rate in Hsa-miR-4282 down-regulated group was lower than that of the control group ［（14.98±0.46）% vs （17.79±0.73）%，P=0.010］. Conclusions  Up-regulation of Hsa-miR-4282 can inhibit the proliferation of liver cancer SMMC-7721 cells and promote cell apoptosis，which may be related to the pathogenesis of liver cancer. Related Articles | Metrics

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Differentiation and tumor-forming activity of oral squamous cell carcinoma stem cells selected by immunomagnetic beads LIAO Xianxiang, FANG Fang, YANG Lianghui, CHEN Guosheng, WANG Daiyou, PENG Jianbo, LIU Shiqi, MAI Huaming 2019, 11 (2):  131-137.  doi: 10.3969/j.issn.1674-5671.2019.02.09 Abstract ( 262 )   PDF (33808KB) ( 73 )   Save Objective To investigate the differentiation and tumor-forming aitivity of oral squamous cell carcinoma stem cells. Methods The CD133+ and CD44+ cells were isolated by immunomagnetic beads from oral squamous carcinoma cells，and the purity of sorted cells and cell cycle were identified by flow cytometry.The CD133+ cell growth curve was determined. The selected cells were induced to differentiate into osteoblasts and adipocytes.In vivo tumorigenesis experiments were carried out using primary squamous cells and CD44+，CD133+ cells. Results The purity of CD44+ cells and CD133+ cells that were isolated by immuno-magnetic beads were more than 94% detected by flow cytometry. Most of their cell cycle were in G0/G1 phase.CD133+ cells entered log phase on the 2nd day after inoculation，and the cell doubling time was 3.22 d.After induction，CD44+ and CD133+ cells were successfully differentiated into osteoblasts and adipocytes. On the 3rd day after subcutaneous injection，new tumors could be touched， the tumor volume in the CD133+ cell group was the greatest in three cells，and HE staining showed that it was consistent with the pathological manifestations of oral squamous cell carcinoma. Conclusion High-purity oral squamous cell carcinoma stem cells can be successfully sorted by immunomagnetic beads method.CD44+ and CD133+ cells have great multidirectional differentiation，but the tumorigenicity of CD133+ is greater. Related Articles | Metrics

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Analgesic effect of active ingredients of polygonum multiflorum on bone cancer pain in rats ZHANG Yi, HONG Xueqi, DUAN Tanyan, SHI Peng, YANG Min, HE Bingwen, LIN Fei 2019, 11 (2):  138-142.  doi: 10.3969/j.issn.1674-5671.2019.02.10 Abstract ( 283 )   PDF (2543KB) ( 193 )   Save Objective To explore the analgesic effect of active ingredients of polygonum multiflorum on bone cancer pain in rats. Methods Specific pathogen-free female Sprague-Dawley rats were randomly divided into 3 groups： blank control group（A group，n=6），modeled as sterile saline group（B group，n=6），and bone cancer pain group（C group，n=24）. Rats in B group were given sterile saline during establishment of model while those in C group were injected with breast cancer cells （walker256） at the upper part of the left hind leg to establish a model with bon cancer pain. Those rats in C group were randomly divided into C1，C2，C3 and C4 groups according to the species of drugs administered intragastrically（n=6）. After successful modeling 14 d，15 d and 16 d，rats in C1~C4 group were intragastrically administered with normal saline（2 mL），tetrahydroxystilbene glucoside（60 mg/mL，2 mL），emodin（60 mg/mL，2 mL） and catechin（60 mg/mL，2 mL） respectively. The pain threshold of left foot in each group was measured before each gavage，30 min after gavage，1h after gavage. Results From the 5th day of feeding in rats with cancer pain model，the mechanical pain threshold in C group was significantly decreased and sclerotin structure were obviously destructed compared with A and B groups（P<0.05），but there were no statistical difference observed on the pain threshold and sclerotin structure between A and B groups. Compared with C1，C3 and C4 group，the mechanical pain threshold at each time point in C2 group was significantly increased（P<0.05）. In the C2 group，pain threshold after 30 min and 1 h of gavage were both signifi-cantly increased than that before gavage（P<0.05）；but the pain threshold after 30 min and 1 h of gavage were similar（P>0.05）. Conclusion Polygonum multiflorum can effectively attenuate bone cancer pain in rats and its active ingredients was tetrahydrox-ystilbene glucoside.   Related Articles | Metrics

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Genomic analysis revealed new prognosis signature in hepatocellular carcinoma MAO Xinru, LIU Wenbin, CAO Guangwen 2019, 11 (2):  143-150.  doi: 10.3969/j.issn.1674-5671.2019.02.11 Abstract ( 460 )   PDF (49473KB) ( 108 )   Save Objective To explore the effects of tumor mutational burden（TMB） and the genetic aberrations in key signal pathway genes on survival prognosis of hepatocellular carcinoma（HCC）. Methods The whole exon sequencing data of 376  and 243 HCC patients were downloaded from the TCGA and schulze2015 cohort of cBioPortal，respectively. Whole genome sequencing data of 394 patients of JP and 250 patients of FR were obtained from ICGC. The relationship of TMB and genetic aberrations in key signal pathway genes and prognosis in HCC patients was analyzed by survival analysis. Results In the TCGA，JP，schulze2015 and FR cohorts，TMB after logarithmic transformation was correlated with age（P<0.001）.In schulze2015，TMB after logarithmic transformation was correlated with tumor size（r=0.204，P=0.002）. In TCGA，OS and DFS of HCC patients in the high TMB group were significantly lower than those in the low TMB group（P<0.001，P＝0.088）. The risk of death in HCC patients in the high TMB group was 2.156 times higher than that in the low TMB group（P<0.001）.There was no association between TMB and OS and DFS in both JP and FR. In TCGA，JP，and FR cohorts，it was found that the median DFS，OS of HCC patients with genetic aberrations in cell cycle control pathway genes were lower than those without variation（P<0.05），while the risk of recurrence and death of HCC patients with genetic aberrations in cell cycle control pathway genes were higher than those without variation（P<0.05）. Conclusion High TMB  and genetic aberrations in cell cycle control pathway genes were associated with poor prognosis in HCC patients. Related Articles | Metrics

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Association between RAD23B gene rs10759225 polymorphism and clinical outcomes of non-small cell lung cancer patients treated with platinum-based chemotherapy XIE Xiaonan, WEN Yiyong, LING Qiongying, HUANG Wenfeng, QIN Fanghui, WANG Hongxue, ZHOU Wenxian, LU Yongkui, XIE Yu'an, XIE Weimin 2019, 11 (2):  151-157.  doi: 10.3969/j.issn.1674-5671.2019.02.12 Abstract ( 335 )   PDF (2770KB) ( 162 )   Save Objective To investigate the relationship between the rs10759225 polymorphism of the RAD23B gene and clinical outcomes of platinum-based chemotherapy　as　first-line　treatment in patients with advanced non-small cell lung cancer（NSCLC）. Methods The clinical data and peripheral blood samples of 150 NSCLC patients receiving first-line treatment with platinum-based combination regimen were retrospectively analyzed.　The polymorphism of rs10759225 was genotyped by improved multiple ligase detection reaction（iMLDR） technology. Results The overall response rate（ORR） was 27.8%（43/150） of all group.Compared with G/G genotype carriers，A allele（included G/A genotype and A/A genotype） carriers had markedly higher response rate （ORadjusted =1.780，95%CI：1.110-2.884，P=0.042）.The median progression-free　survival（mPFS） of all patients was 5.6 months，and there was no significance of mPFS among difference genotype groups（P>0.05）.　Compared with G/G genotype （as a reference），A/A genotype increased the risk of grade Ⅲ/Ⅳ of leukopenia （ORadjusted=0.468，95%CI：0.204-0.711，P=0.008），and an allele was each associated with grade Ⅲ/Ⅳ of neutropenia （ORadjusted=0.502，95%CI：0.155-0.887，P=0.022） and grade ≥Ⅰ of thrombocytopenia（ORadjusted=0.494，95%CI：0.101-0.833，P=0.047），respectively.The risk of grade Ⅱ/Ⅲ anemia was significantly higher in patients with G/A genotype compared with G/G genotype carriers（OR校正=0.504，95%CI：0.213~0.890，P=0.047）.　Conclusions RAD23B gene rs10759225 polymorphism is associated with response rate and hematological toxicity of NSCLC patients treated with platinum-based chemotherapy，but there is no relationship between the polymorphism and the PFS of patients.Compared with G/G genotype carriers，A allele carriers may have better efficacy，and，as well as have a higher risk of myelosuppression. Related Articles | Metrics

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Analysis of GOLM1 gene expression in prostate cancer and its effect on prognosis based on data mining YU Zhanpeng, JIANG Yanqiong 2019, 11 (2):  158-162.  doi: 10.3969/j.issn.1674-5671.2019.02.13 Abstract ( 414 )   PDF (16347KB) ( 80 )   Save  Objective To investigate the expression of GOLM1 gene in prostate cancer and its clinical significance. Methods The Oncomine database was used to analyze the expression of GOLM1 gene in prostate cancer and normal prostate tissues. RNA-Seq data and clinical data downloaded from TCGA data，was analyzed the correlation between GOLM1 gene expression and clinicopathological features and prognosis. Results The analysis of Oncomine and TCGA databases showed that the expression of GOLM1 gene in prostate cancer tissues was significantly higher than that in normal prostate tissues（P<0.001）. By analyzing the clinical data in 547 patients，it was found that the expression level of GOLM1 gene was not significantly correlated with age，Clinical T stage，Pathological T stage，and Gleason score. Kaplan-Meier analysis found that low expression of GOLM1 gene patients with overall survival was significantly longer than those with high expression（HR=4.50，95%CI：3.77-5.37，P=0.038）. ROC curve analysis showed that the best cutoff point was 8.889，the sensitivity was 80.5%，the specificity was 80.8%，and the area under the ROC cwrve was 0.530（95%CI：0.813-0.912）. Conclusions The GOLM1 gene is highly expressed in prostate cancer tissues and its expression level is related to poor prognosis. GOLM1 mRNA can be used as a candidate prostate cancer marker. Related Articles | Metrics

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Meta-analysis of the efficacy of Kangfuxin liquid in the prevention and treatment of radiation esophagitis caused by radiotherapy for malignant tumors LU Jingyu, CHEN Ling, CHEN Dan, SHI Limei, LI Lirong 2019, 11 (2):  163-168.  doi: 10.3969/j.issn.1674-5671.2019.02.14 Abstract ( 399 )   PDF (2137KB) ( 186 )   Save Objective To evaluate the efficacy of Kangfuxin Liquid in radioactive esophagitis caused by radiotherapy for malignant tumors. Methods Medline，PubMed，CNKI，WanFang Date and VIP databases were searched to find clinical controlled trials of Kangfuxin liquid for prevention and treatment of radiation esophagitis caused by radiotherapy for malignant tumors from inception to December 2018. According to the inclusion and exclusion criteria，screened the literature，extracted data and evaluated the quality. Meta-analysis was performed by RevMan 5.0 software. Results A total of 6 literatures were included，involving 482 patients of whom，237 cases of Kangfuxin liquid（experimental group） and 245 cases of conventional comprehensive western medicine therapy or routine health education（control group）. Meta-analysis showed that there were no significant differences in the incidence of grade Ⅰ，grade Ⅲand above lesions between the experimental group and the control group（RR=1.36，95%CI：0.96-1.95，P=0.09；RR=0.22，95%CI：0.04-1.25，P=0.09）. However，the incidence of grade Ⅱ injury in the experimental group was lower than that in the control group，and the difference was statistically significant（RR=0.53，95%CI： 0.37-0.77，P=0.0006）. The toxicity score of radioactive esophagitis in the experimental group was also significantly lower than that in the control group（MD=-0.31， 95%CI：-0.47--0.16，P<0.0001）. Conclusion In the course of radiotherapy for malignant tumors，the Kangfuxin liquid can effectively reduce the incidence of grade Ⅱ injury of radiation esophagitis，but there is no obvious advantage in reducing the damage of grade Ⅰ，grade Ⅲ and above lesions. Related Articles | Metrics

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Advances in research of circulating tumor DNA detection in clinical diagnosis and treatment of colorectal cancer WANG Tian, YIN Chun, GUO Xu, XING Jinliang, XING Yanfang 2019, 11 (2):  168-171.  doi: 10.3969/j.issn.1674-5671.2019.02.15 Abstract ( 319 )   PDF (604KB) ( 194 )   Save Related Articles | Metrics

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Research progress of microRNAs regulation of tumor associated fibroblasts ZHENG Xuan, LIU Yankun, LI Yufeng, ZHANG Guangling 2019, 11 (2):  171-175.  doi: 10.3969/j.issn.1674-5671.2019.02.16 Abstract ( 334 )   PDF (765KB) ( 206 )   Save Related Articles | Metrics

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Advances in research of toll-like receptor 9 in tumor PANG Mimi, LI Yujia, WAN Shaogui, BAO Dengke 2019, 11 (2):  175-178.  doi: 10.3969/j.issn.1674-5671.2019.02.17 Abstract ( 376 )   PDF (650KB) ( 527 )   Save Related Articles | Metrics

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Progress in the study of circulating tumor markers in breast cancer recurrence and prognosis GUO Yuanwei, HU Zheng, LUO Weihao, HE Rongzhang, LI Jia, DUAN Lili, LIU Xiaojun, LUO Dixian 2019, 11 (2):  178-182.  doi: 10.3969/j.issn.1674-5671.2019.02.18 Abstract ( 317 )   PDF (717KB) ( 206 )   Save Related Articles | Metrics