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08 January 2018, Volume 45 Issue 1 Previous Issue    Next Issue

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Effects of knockdown of Stat5 on invasion and epithelial mesenchymal transition of thyroid carcinoma TT cells Li Yan, Chen Qiongxia, Wang Xuming 2018, 45 (1):  1.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.001 Abstract ( 527 )   Save ObjectiveTo investigate the effects of knockdown of signal transducer and activator of transcription 5 (Stat5) on invasion and epithelial mesenchymal transition (EMT) of thyroid carcinoma TT cells. MethodsThyroid carcinoma TT cells were cultured and divided into Stat5small interfering RNA (siRNA) group and NCsiRNA group, transfected with Stat5 siRNA and negative control NCsiRNA respectively. After transfection, the numbers of invasive cells were determined by Transwell model and the expressions of matrix metalloproteinase (MMP) family genes, EMT marker genes, angiogenesis genes in the cells were determined by fluorescent quantitative PCR. ResultsThe numbers of invasive cells in Stat5siRNA group were significantly lower than those in NCsiRNA group (42.39±5.82 vs. 64.41±8.49, t＝-4.784, P=0.001; 51.23±6.38 vs. 78.54±9.52, t＝-5.329, P＜0.001; 60.35±8.35 vs. 98.42±11.25, t＝-6.076, P＜0.001) after the transfection of siRNA for 12 hours, 18 hours and 24 hours. Twentyfour hours after transfection of siRNA, the mRNA expressions of MMP1, MMP2, MMP9, MMP13, Ncadherin, Vimentin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin (Ang)1 and Ang2 in Stat5siRNA group were significantly lower than those in NCsiRNA group (0.42±0.07 vs. 1.03±0.15, t＝-8.240, P＜0.001; 0.35±0.06 vs. 1.01±0.13, t＝-10.307, P＜0.001; 0.29±0.05 vs. 1.05±0.18, t＝-9.097, P＜0.001; 0.54±0.08 vs. 0.98±0.12, t＝-6.822, P＜0.001; 0.38±0.06 vs. 1.04±0.18, t＝-7.778, P＜0.001; 0.29±0.04 vs. 1.06±0.12, t＝-12.612, P＜0.001; 0.36±0.07 vs. 1.06±0.14, t＝-10.000, P＜0.001; 0.43±0.08 vs. 0.97±0.12, t＝-8.372, P＜0.001; 0.25±0.03 vs. 1.03±0.12, t＝-14.100, P＜0.001; 0.19±0.03 vs. 0.99±0.13, t＝-13.408, P＜0.001). The mRNA expression of Ecadherin was significantly higher than that in NCsiRNA group (2.88±0.42 vs. 0.98±0.12, t＝9.726, P＜0.001). ConclusionKnockdown of Stat5 inhibits the invasion and EMT of thyroid carcinoma TT cells. References | Related Articles | Metrics

Effect of resveratrol on cisplatin chemotherapy sensitivity of ovarian cancer cells Li Yan 2018, 45 (1):  5.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.002 Abstract ( 720 )   PDF (862KB) ( 872 )   Save ObjectiveTo investigate the effect and mechanism of resveratrol on cisplatin chemotherapy sensitivity of human epithelial ovarian cancer SKOV3 cells. MethodsThe cultured in vitro human ovarian cancer SKOV3 cells in logarithmic growth phase were treated with resveratrol (20 μg/ml), cisplatin (40 μg/ml) and resveratrol (20 μg/ml) + cisplatin (20 μg/ml) respectively, and the blank group was set, n=10. After 48 hours, the cellular growth inhibition rate was calculated by methyl thiazolyl thiazolium (MTT), cell cycle and apoptosis rate were analyzed by flow cytometry, the expressions of Bax mRNA and Bcl2 mRNA were detected by reverse transcriptionpolymerase chain reaction (RTPCR), and the expression of cleaved Caspase3 protein was detected by Western blotting. ResultsThe cellular growth inhibition rate of SKOV3 cells in resveratrol + cisplatin group was significantly increased than that in cisplatin group ［(53.0±8.1)% vs. (37.5±6.5)%, P=0.017］, the proportion of G0G1 phase cells in resveratrol + cisplatin group was significantly higher than that in cisplatin group ［(61.2±3.4)% vs. (54.9±2.8)%, P=0.017］, the proportion of G2M phase cells in resveratrol + cisplatin group was significantly lower than that in cisplatin group ［(5.1±0.5)% vs. (8.6±0.9)%, P=0.008］, the apoptosis index in resveratrol + cisplatin group was significantly increased than that in cisplatin group ［(59.3±7.4)% vs. (43.6±6.0)%, P=0.015］, the ratio of Bax/Bcl2 in resveratrol + cisplatin group was significantly increased than that in cisplatin group (4.6±1.8 vs. 3.3±1.4, P=0.026), and the expression of cleaved Caspase3 protein in resveratrol + cisplatin group was significantly increased than that in cisplatin group (0.47±0.15 vs. 0.38±0.12, P=0.011). Compared with blank group, the G0G1 phase in cell cycle of resveratrol group was significantly increased ［(46.5±2.4)% vs. (37.8±1.9)%, P=0.023］, the expression of Bcl2 mRNA was significantly decreased ［(32.9±11.2) ×10-3 vs. (44.8±13.0)×10-3, P=0.028］, the ratio of Bax/Bcl2 was significantly increased (2.1±0.8 vs. 1.5±0.6, P=0.019), and the expression of cleaved Caspase3 protein was significantly increased (0.26±0.10 vs. 0.08±0.03, P＜0.001). ConclusionResveratrol can effectively enhance the effect on human epithelial ovarian cancer SKOV3 cells treated by cisplatin, which is perhaps related to its effects of blocking the cell cycle G0G1 and altering the expression of apoptosisrelated genes and proteins. References | Related Articles | Metrics

Comparison of EGFR mutation between supernatant and pellets of malignant pleural effusion from patients with advanced nonsmall cell lung cancer Li Hui*, Yan Shi, Liu Yan, Liu Ying, Ma Lixia, Liu Xianhong, Cheng Ying 2018, 45 (1):  10.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.003 Abstract ( 485 )   PDF (853KB) ( 954 )   Save ObjectiveTo compare the epidermal growth factor receptor (EGFR) mutation differences between supernatant and pellets of malignant pleural effusion (MPE) in advanced nonsmall cell lung cancer (NSCLC) patients and provide the evidence for clinical accurate detection. MethodsA total of 386 consecutive MPE specimens were collected in the study (202 in experimental group and 184 in validation group). Specimens in experimental group were divided into 4 groups depending on tumors cell concentration in the samples: zero cell (n=77), (15)×104/ml cells (n=43), (610)×104/ml cells (n=52) and >10×104/ml cells group (n=30). Amplification refractory mutation system (ARMS) was performed to detect EGFR gene mutation in supernatant and pellets of each individual case respectively, and the EGFR mutation positive rates were compared between the two groups. EGFR mutation test was carried out using either supernatant or pellets in validation group to verify the established method. ResultsIn the experimental group, the total EGFR mutation positive rate was 30.7% (62/202). In the zero cell group, EGFR mutation positive rate was higher in supernatant than that in pellets (37.6% vs. 33.8%). In the (15)×104/ml cells group and (610)×104/ml cells group, EGFR mutation positive rate was equal but not concordant between supernatant and pellets (25.6% and 21.1% respectively). In the >10×104/ml cells group, EGFR mutation positive rate was equal (33.3%) with 100% concordance between supernatant and pellets. In the validation group (n=184), EGFR mutation rate was 32.7% (36/110) in supernatant and 32.4% (24/74) in pellets, and there was no statistical significance (χ2=0.02, P=0.97). ConclusionTumor cell free MPE specimens from patients with advanced NSCLC are suitable for EGFR mutation test. Heterogeneity of MPE results in difference with respect to EGFR gene mutation status between cellfree supernatant and pellet. Pathological evaluation based on the quantity and quality of tumor cells in MPE patients prior to test and optional samples selection are necessary to increase EGFR mutation positive rate. References | Related Articles | Metrics

Expression of MFF and its biological effects in hepatocellular carcinoma Li Bo*, Zhang Jiansheng, Li Jiaqi, Yang Yi, Zhang Hongxin, Mou Jiao 2018, 45 (1):  16.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.004 Abstract ( 539 )   PDF (2162KB) ( 1190 )   Save ObjectiveTo evaluate the expression of mitochondrial fission factor (MFF) and its biological effects in the progression of hepatocellular carcinoma (HCC). Methods①Quantitative realtime PCR (qPCR), Western blotting and immunohistochemistry analysis were used to detect the expression levels of MFF in HCC tumor tissues and cell lines. ②The effect of MFF knockdown on proliferation of HCC cells was analyzed by methyl thiazolyl tetrazolium (MTT) and colony formation assays in siCtrl, siMFF#1, siMFF#2 groups. ③The effect of MFF knockdown on apoptosis of HCC cells was analyzed by apoptosis assay with Annexin ⅤFITC and PI. Results①The MFF expression was higher in tumor tissues compared with tumoradjacent normal tissues ［mRNA level M(QR): 0.292(0.443) vs. 0.235(0.333), Z=-4.166, P＜0.001; protein level M(QR): 5.414 (4.545) vs. 3.120 (3.955), Z=-3.961， P＜0.001)］. The MFF expression was higher in HCC cell lines compared with normal liver cell line. ②RNA interferencemediated knockdown of MFF inhibited proliferation of HCC cells (siCtrl vs. siMFF#1: 5.29±0.34 vs. 3.34±0.37, P=0.014; siCtrl vs. siMFF#2: 5.29±0.34 vs. 3.09±0.40, P=0.010). RNA interferencemediated knockdown of MFF inhibited colony formation of HCC cells (siCtrl vs. siMFF#1: 95.35±21.20 vs. 37.56±10.61, P=0.003; siCtrl vs. siMFF#2: 95.35±21.20 vs. 41.23±10.82, P=0.004). ③RNA interferencemediated knockdown of MFF induced apoptosis of HCC cells (siCtrl vs. siMFF#1: 9.56%±1.70% vs. 20.08%±2.03%, P＜0.001; siCtrl vs. siMFF#2: 9.56%±1.70% vs. 21.14%±1.38%, P＜0.001). ConclusionMFF is overexpressed in HCC, which accelerates cell proliferation and suppresses apoptosis, indicating that MFF can serve as a potential oncogene and drug target in HCC treatment. References | Related Articles | Metrics

Prognostic value analysis of TOP2A gene expression for bladder cancer Yuan Jiayi, He Hengjing, Bi Yaqiong, Guo Zixin, Xiao Yu, Li Sheng 2018, 45 (1):  22.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.005 Abstract ( 528 )   PDF (831KB) ( 859 )   Save ObjectiveTo investigate the relationship between DNA topoisomerase Ⅱα (TOP2A) gene expression and clinicopathological characteristics and its significance of prognostic evaluation for patients with bladder cancer. MethodsBladder cancer gene expression profile GSE13507 (n=165) and GSE31189 (n=52) were obtained. The expression profile and clinical information of patients with bladder cancer were retrospectively analyzed, and the survival analysis was made. Gene set enrichment analysis (GSEA) was conducted to explore the related pathways which were regulated by TOP2A. ResultsCompared with normal bladder tissues, TOP2A was upregulated in bladder cancer tissues (5.823±1.079 vs. 4.820±1.129), with a statistically significant difference (t=4.336, P＜0.001). The TOP2A gene expression in patients with bladder cancer was correlated with the age of patients (χ2=5.926, P=0.015), sex (χ2=6.046, P=0.014), T staging (χ2=19.484, P＜0.001), N staging (χ2=9.178, P=0.002), M staging (χ2=21.142, P＜0.001), tumor grade (χ2=47.005, P＜0.001), and progression (χ2=11.735, P=0.001), but it was not correlated with recurrence (χ2=0.808, P=0.369). Survival analysis showed that the specific survival rate in the 100 months of TOP2A gene high expression group and low expression group had a statistically significant difference (66.59% vs. 87.95%, χ2=15.820, P＜0.001). The median overall survival time of TOP2A gene high expression group and low expression group were 51.77 months and 134.97 months respectively, with a statistically significant difference (χ2=11.280, P=0.008). The results of GSEA indicated that TOP2A could regulate gene sets related with several pathways like MYCV1 signaling (P=0.035, FDR=0.132), MYCV2 signaling (P=0.012, FDR=0.058), E2F signaling (P<0.001, FDR=0.006) and G2M checkpoint (P=0.006, FDR=0.044). ConclusionThe TOP2A gene expression is closely related with clinicopathological characteristics of patients with bladder cancer. TOP2A may function as a potential marker of prognosis for patients with bladder cancer. References | Related Articles | Metrics

Diagnostic value of serum lipocalin 2 combined with prostatespecific antigen in prostate cancer Bi Sicheng*, Liu Hao, Zhang Peng, Li Zhe, Mai Tiejun, Zhu Zhizhen 2018, 45 (1):  27.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.006 Abstract ( 487 )   PDF (1016KB) ( 888 )   Save ObjectiveTo investigate the diagnostic value of lipocalin 2 (LCN2) combined with prostatespecific antigen (PSA) in prostate cancer (PCa). MethodsEnzymelinked immunosorbent assay (ELISA) was used to determine the levels of serum LCN2 in patients with PCa (PCa group, n=82), patients with benign prostatic hyperplasia (BPH group, n=40) and healthy subjects (NC group, n=30). The levels of serum PSA were measured by chemiluminescence. The diagnostic value of LCN2 combined with PSA in PCa was analyzed by the receiver operating characteristic (ROC) curve. The relationship between the level of LCN2 and clinical parameters in PCa patients was analyzed. ResultsThe levels of serum LCN2 in PCa group, BPH group and NC group were (88.97±40.83) pg/ml, (53.12±25.66) pg/ml, (13.34±4.86) pg/ml (F=61.306, P<0.001). The level of LCN2 in PCa group was significantly higher than that in BPH group and NC group (both P<0.001). The levels of serum PSA in PCa group, BPH group and NC group were (17.65±8.43) ng/ml, (11.27±3.56) ng/ml, (2.61±0.87) ng/ml (F=60.959, P<0.001). The level of serum PSA in PCa group was significantly higher than that in BPH group and NC group (both P<0.001). There was positive correlation between serum LCN2 and PSA levels (r=0.360, P＜0.001). The levels of serum LCN2 in PCa patients with different Gleason score, TNM stage and distant metastasis were significantly different (F=8.546, P＜0.001; t=3.421, P=0.001; t=3.622, P=0.010). The area under the curve (AUC) of serum LCN2 was 0.763 (95%CI: 0.6770.850, P＜0.001). The sensitivity and specificity of serum LCN2 were 62.2% and 85.0%. The AUC of PSA was 0.750 (95%CI: 0.6650.836, P＜0.001). The sensitivity and specificity of serum PSA were 51.2% and 87.5%. The AUC of LCN2 combined with PSA was 0.822 (95%CI: 0.7490.895, P＜0.001). ConclusionSerum LCN2 level in the patients with PCa is significantly higher, which participates in tumor invasion. LCN2 may be a potential serum marker for the diagnosis of PCa. Combined detection of LCN2 and PSA contributes to the early diagnosis of PCa. References | Related Articles | Metrics

Connexin 43 and tumors Wen Xiaorong*, Mo Hongmei, Guo Tao, Ding Mengting 2018, 45 (1):  32.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.007 Abstract ( 724 )   PDF (639KB) ( 792 )   Save Cell gap junction is a special protein channel. Gap junctionmediated exchange of information between cells is crucial for cell growth, differentiation and tissue homeostasis. Connexin 43 (Cx43) is one of the members of the gap junction protein family. In recent years, researches show that abnormal Cx43 gene expression leads to the cell gap junctional communication dysfunction, which is closely related to the occurrence, metastasis and prognosis of a variety of tumors. Cx43 is expected to become a new target for clinical diagnosis and treatment of tumors. References | Related Articles | Metrics

Application of fluorescence in the identification of circulating tumor cells Yu Huajie*, Han Lu, Ou Yang, Li Sheng, Gao Dehai 2018, 45 (1):  35.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.008 Abstract ( 468 )   PDF (648KB) ( 1062 )   Save There are many ways to identify circulating tumor cells in the current. Fluorescence has a wide range of applications in the identification of circulating tumor cells. The labeled cells can be observed and counted more intuitively by labeling the tumor cells with fluorescent group containing antibodies, probes and aptamers, and cytokine, CD45 and fluorescence in situ hybridization are widely used in the identification of various circulating tumor cell related tests. In recent years, people have explored the feasibility of using fluorescent probes to directly identify circulating tumor cells. With the development of biopsy probes and optical sectioning imaging technology of confocal microscopy, it is possible to directly identify circulating tumor cells with fluorescent probes in the future. References | Related Articles | Metrics

Molecular targeted therapy of nonsmall cell lung cancer Nan Zhaodi, Chen Shaoshui 2018, 45 (1):  39.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.009 Abstract ( 423 )   PDF (655KB) ( 1173 )   Save At present, the treatment of nonsmall cell lung cancer (NSCLC) has entered the era of targeted therapy, and small molecule tyrosine kinase inhibitors are typical representatives, which have clear molecular targets and remarkable effects. But many patients without mutations are not able to benefit from them. Vascular endothelial growth factor and immune targeted therapy have become the new focus of NSCLC treatment. Inhibitors such as programmed cell death1 and programmed cell deathligand 1 have shown great applied potential in a series of clinical trials of NSCLC. References | Related Articles | Metrics

Treatment of advanced or recurrent cervical cancer Li Dan*, Lou Hanmei 2018, 45 (1):  44.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.010 Abstract ( 467 )   PDF (658KB) ( 2003 )   Save The treatment of advanced or recurrent cervical cancer is difficult in clinic. Most of the patients have lost the opportunities for surgery or radiotherapy. Palliative treatment with chemotherapy is the main treatment. In recent years, the intensive studies on molecular targeted therapy and immunotherapy have provided a new treatment strategy for patients with advanced or recurrent cervical cancer, improving the efficacy and quality of life of patients. References | Related Articles | Metrics

Prognostic significance of peripheral blood absolute lymphocyte count in acute lymphoblastic leukemia Li Congchi*, Hou Lihong 2018, 45 (1):  49.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.011 Abstract ( 639 )   PDF (648KB) ( 992 )   Save The prognosis of acute lymphoblastic leukemia (ALL) is affected by multiple factors. As a simple and inexpensive prognostic indicator, the peripheral blood absolute lymphocyte count (ALC) is more and more concerned. Relevant studies show that ALC values of different time points during induction therapy and its ratio show important value in the assessment of ALL prognosis, which is expected to provide a basis for subsequent individualized treatment. References | Related Articles | Metrics

Application of circulating microRNAs in multiple myeloma Yuan Qing, Chen Shaoshui 2018, 45 (1):  53.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.012 Abstract ( 481 )   PDF (635KB) ( 681 )   Save Circulating microRNAs (miRNAs) are closely related to the occurrence and development of multiple myeloma (MM). miRNAs play a significant role in early prediction, disease diagnosis, prognosis evaluation, progress monitoring and assessment of drug resistance of MM. As important biologic tumor markers, miRNAs are expected to become new targets for the diagnosis and treatment of MM. References | Related Articles | Metrics

Detection and clinical application of minimal residual disease in multiple myeloma Liu Xiaolan, Guan Tao, Su Liping 2018, 45 (1):  56.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.013 Abstract ( 1007 )   PDF (638KB) ( 1624 )   Save Minimal residual disease (MRD) is a very important prognostic factor in multiple myeloma (MM). The major types of MRD tests include cellbased test (multiparameter flow cytometry) and molecular tests (including PCR and gene sequencing), and the various techniques have inherent advantages and limitations. In clinical application, MRD negative can significantly prolong progressionfree survival and overall survival of patients who receive hematopoietic stem cell transplantation and conventional chemotherapy. Moreover, the MRD status is of great significance to the selection of treatment options. References | Related Articles | Metrics

Biomarkers for malignant melanoma Wang Yanjun, Kang Xiaojing 2018, 45 (1):  59.  doi: 10.3760/cma.j.issn.1673-422X.2018.01.014 Abstract ( 1400 )   PDF (644KB) ( 1452 )   Save Malignant melanoma is one of the most aggressive cancers. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. Recently, with the further study of the pathogenesis of melanoma and the development of molecular biology techniques, some new biomarkers have been found to play an important role in melanoma. Several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Considerable efforts have been made to classify melanoma into distinct subtypes based on genetic mutations and gene expression profile offer important information on patients′ prognosis and individual treatment options. Epigenetic alterations can be used as a noninvasive diagnostic tool for melanoma and can be used as a new biomarker for predicting prognosis and predicting disease. And the discovery of biomarkers for melanoma provides a theoretical basis for early diagnosis, individualized treatment and prognosis. References | Related Articles | Metrics