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08 December 2017, Volume 44 Issue 12 Previous Issue    Next Issue

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Immune sensitization effect of tiopronin on IL-2 immunotherapy of human leukemia cells transplanted in nude mice Xiao Huaping, Xie Hui, Luo Chunyang, Li Qing, Fang Yujiang 2017, 44 (12):  881-885.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.001 Abstract ( 422 )   PDF (1329KB) ( 699 )   Save ObjectiveTo investigate the effects and its possible mechanisms of tiopronin (TIP) on interleukin-2 (IL-2) immunotherapy of human leukemia KG-1 cells transplanted in nude mice. MethodsKG-1 cells (1×107/ml) in logarithmic growth phase were injected subcutaneously into the groin of the left hind leg of the 45 5-week-old nude mice. When the subcutaneous tumor diameter was about 8 mm, nude mice were randomly divided into three groups (n=15): Control group (intraperitoneal injection of phosphate buffer), IL-2 group (hypodermic injection of IL-2), IL-2+TIP group (hypodermic injection of IL-2 and intraperitoneal injection of TIP). The therapeutic effect of TIP combined with IL-2 on human leukemia KG-1 cells transplanted in nude mice was observed. The number of nature killer (NK) cells in peripheral blood of nude mice was detected by flow cytometry. Nitrate reductase assay was used to detect reactive nitric metabolite (RNM) levels in peripheral blood of nude mice. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-β (TNF-β) and interferon-γ (IFN-γ) in peripheral blood of nude mice. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay was used to analyze apoptosis. ResultsBoth IL2 and IL2+TIP could inhibit the growth of transplanted tumor. Compared with IL-2 group ［(54.32±4.32)%］, the tumor inhibition rate of IL-2+TIP group was (90.15±3.75)%, and its inhibition of tumor growth was more obvious (t=11.893, P＜0.001). The tumor weights of Control group, IL-2 group and IL-2+TIP group were (0.95±0.05)g, (0.58±0.03)g and (0.27±0.07)g, and there was statistically significant difference among the three groups (F=52.716, P<0.001). Compared with IL-2 group, the tumor weight of IL-2+TIP group was significantly reduced (P=0.008). The number of NK cells in IL-2+TIP group was (0.658±0.157)/L, which was significantly higher than (0.452±0.124)/L of IL-2 group (P=0.021). The concentration of RNM in IL-2+TIP group was (42.92±4.68)μmol/ml, which was significantly lower than (163.38±5.49)μmol/ml in IL-2 group (P=0.007).The concentrations of TNF-β and IFNγ in IL-2+TIP group were (247.68±8.24)pg/ml and (185.61±7.58)pg/ml, which were significantly higher than (97.48±7.28)pg/ml (P=0.021) and (70.62±8.47)pg/ml (P=0.015) in IL-2 group. The apoptotic rate of tumor cells in IL-2+TIP group was (47.38±4.25)%, which was significantly higher than (21.41±2.79)% in IL-2 group (P＜0.001). ConclusionTIP can increase the sensitivity of leukemia cells to IL-2 immunotherapy by removing RNM, promoting NK cells activity and increasing NK cells-induced tumor cell apoptosis. Related Articles | Metrics

Expression and significance of long non-coding RNA RP11629B11.4 in triple negative breast cancer patients Pan Haixia, Liang Liang, Ren Gang, Bai Yifeng 2017, 44 (12):  886-891.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.002 Abstract ( 391 )   PDF (988KB) ( 611 )   Save ObjectiveTo investigate the expression and clinical significance of long non-coding RNA (lncRNA) RP11629B11.4 in triple negative breast cancer (TNBC) patients. MethodsThe expression of lncRNA RP11629B11.4 was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) in TNBC tissues （n=45） and non triple negative breast cancer (N-TNBC， n=89) to analyze the relationship between the expression of lncRNA RP11-629B11.4 and the prognosis of patients. ResultsThe expression of lncRNA RP11-629B11.4 in TNBC tissues was 7.805±0.538, significantly higher than that in N-TNBC tissues (1.637±0.409, t=21.460, P＜0.001). The expression of lncRNA RP11-629B11.4 in the TNBC patients was related with histological grade (χ2=7.540, P=0.040), clinical stage (χ2=9.858, P=0.007), lymph node metastasis (χ2=4.388, P=0.036) and Ki-67 expression (χ2=7.872, P=0.005). In the N-TNBC group, there was no significant correlation between the expression of lncRNA RP11-629B11.4 and clinicopathological characteristics (all P＞0.050). The progression free survival time of TNBC patients with higher expression of lncRNA RP11-629B11.4 was (15.90±2.76) months, shorter than that of patients with lower expression (26.62±3.80) months, with a statistically significant difference (χ2=49.750, P＜0.001). The overall survival time of TNBC patients with lower expression of lncRNA RP11-629B11.4 was (38.84±3.55) months, significantly longer than that of patients with higher expression ［(24.69±3.50) months］, with a statistically significant difference (χ2=50.730, P＜0.001). Cox regression model analysis showed that lymph node metastasis (HR=1.980, P=0.019), the expression of lncRNA RP11-629B11.4 (HR=4.030, P＜0.001)clinical stage (HR=2.670, P=0.008) and were independent prognostic factors in patients with TNBC. ConclusionThe lncRNA RP11629B11.4 is over-expressed in TNBC. lncRNA RP11-629B11.4 may be involved in the regulation of TNBC, and it may be used as a potential target for evaluating the prognosis of TNBC. Related Articles | Metrics

Relationships of ductal carcinoma in situ calcification feature and ER, PR and HER2 expression Cui Haixiong, Li Fei, He Lei 2017, 44 (12):  892-896.  doi: 10.3760/cma.j.issn.1673422X.2017.12.003 Abstract ( 877 )   PDF (937KB) ( 978 )   Save ObjectiveTo discuss the relationships of ductal carcinoma in situ calcification feature and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) expression. MethodsThe mammary gland molybdenum target Xray results of 226 patients with ductal carcinoma in situ were retrospectively analyzed in our hospital during January 2013 to December 2016. All patients were divided into calcification group (n=110) and no calcium group (n=116). Immunohistochemical method was used to detect the expressions of ER, PR and HER2, and their relationships with calcification feature were analyzed. ResultsThe positive expression rates of ER and PR in calcification group were 72.73% and 54.55%, significantly higher than those in no calcium group (39.66% and 38.79%; χ2=25.033, P＜0.001; χ2=5.632, P=0.036). The positive expression rate of HER2 in calcification group was 45.45%, significantly lower than that of the no calcium group (82.76%, χ2=34.358, P＜0.001). According to the single factor analysis, the calcified form (χ2=31.098, P＜0.001; χ2=24.117, P=0.003), distribution (χ2=30.272, P＜0.001; χ2=11.811, P=0.008), number (χ2=15.533, P＜0.001; χ2=7.875, P=0.019) and concomitant situation (χ2=27.915, P＜0.001; χ2=7.229, P=0.027) were associated with ER and PR expressions, and the calcified distribution (χ2=8.068, P=0.035), number (χ2=60.768, P＜0.001) and concomitant situation (χ2=24.915, P＜0.001) were associated with HER2 expression. Logistic regression analysis shows that the small polymorphic form, cluster distribution, number＞30, with mass were the independent prediction factors of ER, PR and HER2 expressions (all P＜0.001). ConclusionThe mammary gland molybdenum target calcification features of ductal carcinoma in situ are associated with ER, PR and HER2 expressions, the small polymorphic form, cluster distribution, number＞30, with mass can be used as important reference indexes to preliminarily predict biological therapy and expressions of prognostic factors. Related Articles | Metrics

Clinical study of raltitrexed plus oxaliplatin compared with S1 in treating the patients with advanced primary liver cancer Lin Deshuai*, Shen Yongqi, Han Chaowen, Huang Jun, Chen Chaoting, Si Tao, Wang Zhixiang, Xie Huadong, Kong Xiangying 2017, 44 (12):  897-901.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.004 Abstract ( 1169 )   PDF (1154KB) ( 928 )   Save ObjectiveTo evaluate the therapeutic efficacy and adverse reactions of raltitrexed plus oxaliplatin (RALOX project) and S1 in patients with advanced primary liver cancer. MethodsSeventy-one patients with advanced primary liver cancer admitted to 6 cancer centers from July 2013 to July 2015 were divided into 2 groups according to the wishes of the patients and their families: RALOX group (34 patients) and S1 group (37 patients). The therapeutic efficacy such as objective remission rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression free survival (mPFS), one year survival rate (SR), and adverse reactions in these patients were evaluated. ResultsThirty-one patients could be evaluated in RALOX group, and 6 patients obtained partial response (PR), 10 stable disease (SD) and 15 progressive disease (PD). Thirty-three patients could be evaluated in S1 group, and 3 patients obtained PR, 8 patients SD and 22 PD. The ORR, DCR, and one year SR were 19.4% vs. 9.1%, 51.6% vs. 33.3%, and 22.6% vs. 12.1% respectively, and there were no statistically significant differences in the two groups (χ2=1.393, P=0.238; χ2=2.190, P=0.139; χ2=1.229, P=0.268). The mOS and mPFS were 7.2 months vs. 6.1 months and 3.4 months vs. 2.8 months, and there were statistically significant differences in the two groups (χ2=6.433, P=0.011; χ2=4.078, P=0.043). There was more serious peripheral nerve toxicity (29.0% vs. 3.0%, χ2=6.344, P=0.012) and lighter hand-foot syndrome (9.7% vs. 30.3%, χ2=4.201, P=0.040) in RALOX group than S1 group. But the incidences of other adverse effects were similar in the two groups. ConclusionRALOX project is safe and effective to the patients with advanced primary liver cancer. Compare with S1 project, RALOX project has better curative effects and the majority of adverse reactions are tolerable. The patients have good condition control and survival benefit. Related Articles | Metrics

Expression and its clinical significance of AIB1 protein in the tissues of ovarian carcinoma Li Ling, Qin Li, Jiao Shuhong, Hao Chongli, Wang Wei, Zhang Fen, Zhang Kaiguo 2017, 44 (12):  902-906.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.005 Abstract ( 482 )   PDF (1136KB) ( 642 )   Save ObjectiveTo study the expression of amplified in breast cancer 1 (AIB1) protein in the tissues of ovarian carcinoma and its relationship with clinicopathological factors, and to analyze the predictive value of AIB1 in clinical prognosis of patients with ovarian carcinoma. MethodsImmunohistochemistry was used to detect the expression of AIB1 protein in the tissues of 112 patients with ovarian carcinoma, and compare the AIB1 protein expression levels of patients with various clinicopathological features. The survival analysis was conducted by Kaplan-Meier method. The multivariate analysis was performed to explore the relationship between the expression of AIB1 protein and clinical prognosis of the patients with ovarian carcinoma. ResultsThe positive expression rate of AIB1 protein in the tissues of ovarian carcinoma was 67.9% (76/112). The positive expression rate of AIB1 protein was associated with the degree of the tumor differentiation (χ2=32.483, P＜0.001) and the International Federation of Gynecology and Obstetrics (FIGO) staging (χ2=14.324, P＜0.001), but not with the age (χ2=0.001, P=0.989) or pathological type (χ2=0.106, P=0.745). Compared with the patients with the higher expression of AIB1, the median disease-free survival of patients with the lower expression of AIB1 was longer (48.7 months vs. 36.7 months, χ2=3.026, P=0.022), and there was also extended trend in the median overall survival (60.2 months vs. 43.6 months, χ2=0.916, P=0.055). The multivariate survival analysis showed that FIGO staging (RR=3.396, P=0.021) and AIB1 expression status (RR=1.407, P=0.049) were independent prognostic factors affecting the survival of patients. ConclusionThe overexpression of AIB1 protein is correlated with the degree of differentiation and FIGO staging. Patients with a high expression of AIB1 have poor predicted prognosis. The expression of AIB1 protein can be considered as one of the prognostic indicators in the patients with ovarian carcinoma. Related Articles | Metrics

Application of improved 13-core prostate biopsy in the diagnosis of prostate cancer Shen Junlong, Liu Quanhai, Liu Li, Nan Shuliang, Cheng Yongyi, Zhou Jiancheng. 2017, 44 (12):  907-910.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.006 Abstract ( 499 )   PDF (712KB) ( 700 )   Save ObjectiveTo investigate the clinical value of transrectal ultrasound-guided improved 13-core prostate biopsy in the detection of prostate cancer. MethodsRetrospective analysis was conducted in the clinical data of 82 clinically suspected prostate cancer patients in Shaanxi Provincial People′s Hospital from October 2015 to October 2016. All patients were undergone transrectal ultrasound-guided improved 13-core prostate biopsy and surgical treatment, and the prostate biopsy results were compared with the postoperative pathological results. The accuracy of the improved 13-core prostate biopsy and the standard 6-core prostate biopsy was compared. The complications of improved 13-core prostate biopsy were also discussed. ResultsThe diagnostic results of prostate biopsy included prostate cancer in 26 patients and benign prostatic hyperplasia (BPH) in 54 patients. The diagnostic results of 80 patients are consistent with postoperative pathological examination. Two patients were diagnosed as BPH by biopsy, but confirmed to be prostate cancer by postoperative pathological examination. The accuracy of the improved 13-core prostate biopsy and the standard 6-core prostate biopsy were 97.6% (80/82) and 84.1% (69/82) respectively, and the difference showed statistical significance (P=0.023). No severe complications were found in patients who underwent transrectal ultrasound improved 13-core prostate biopsy. ConclusionTransrectal ultrasound guided improved 13-core prostate biopsy can increase the detection rate significantly. It is safe and efficacious, and can be widely used in clinic. Related Articles | Metrics

Role of long non-coding RNA urothelial carcinoma associated antigen 1 as a competing endogenous RNA in the regulation of the initiation and progression of tumor Gu Shuming, Xu Min. 2017, 44 (12):  911-913.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.007 Abstract ( 330 )   PDF (671KB) ( 655 )   Save Long non-coding RNA urothelial carcinoma associated antigen 1 (UCA1) is highly expressed in multiple types of tumors, such as bladder cancer, breast cancer, colorectal cancer and so on. Recent studies show that UCA1 can interact with the microRNAs as a competing endogenous RNA (ceRNA), to indirectly regulate the expression of target genes, and then participates in the regulation of the initiation and progression of tumor. Therefore, using the mechanism of ceRNA to intervene the expression of UCA1 will provide new ideas for tumor treatment. Related Articles | Metrics

Interferon alpha-inducible protein 27 and tumor Liu Honglu, Liu Xin, Chen Yan, Li Ping, Wang Xicai 2017, 44 (12):  914-917.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.008 Abstract ( 687 )   PDF (681KB) ( 817 )   Save Interferon alpha-inducible protein 27 (IFI27) is a newly discovered protein that participates in biological functions such as apoptosis, cell autophagy, oncolytic and immunoregulation. It also plays a major role in promoting tumor development, such as in breast cancer, ovarian cancer, liver cancer, squamous cell carcinoma and so on. Besides, studies have shown that IFI27 can interact with signal transducer and activator of transcription 1, microRNAs, interferon regulatory factor 4 and other genes, which promotes the development of tumors. Therefore, IFI27 is expected to be a marker for the occurrence and development of tumors, providing a new target for cancer therapy. Related Articles | Metrics

Epigenetic regulation of epithelial-mesenchymal transition Li Wenqing, Hou Jinsong 2017, 44 (12):  918-921.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.009 Abstract ( 518 )   PDF (680KB) ( 661 )   Save The hallmark of epithelial-mesenchymal transition (EMT) is the loss of E-cadherin. The downregulation of E-cadherin can be mediated by its transcriptional repression through the binding of EMT transcription factors to the E-cadherin promoter. Epigenetic mechanisms including DNA methylation, histone code and microRNAs are involved in the regulation of EMT-related genes. Studies have shown that EMT transcription factors can cooperate with several epigenetic modifiers to participate in the expression of E-cadherin. Targeting epigenetic regulation of EMT represents a new promising therapeutic direction. Related Articles | Metrics

Mechanism, detection and clinical implication of tumor heterogeneity Yang Qifan, Liu Yangyang, Zeng Yulan, Liu Yuting, Liu Li 2017, 44 (12):  922-925.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.010 Abstract ( 1300 )   PDF (676KB) ( 1858 )   Save In recent years, with the rapid development of the Next Generation Sequencing, the tumor heterogeneity has attracted widespread attention. It has been clear that heterogeneity in the same patient includes inter-tumor heterogeneity and intra-tumor heterogeneity. The former exists between different tumor lesions, such as primary tumor and metastatic tumor, and the latter occurs in different cancer cells. Tumor heterogeneity represents the ongoing challenge in the field of cancer treatment and brings great difficulty for the precision medicine. Therefore, it is possible to achieve accurate diagnosis and therapy for tumor patients by detecting the subclone of tumors and adjusting the treatment plan in time. Related Articles | Metrics

Na+-K+-2Cl- cotransporter 1 and glioma Ma Haiwen, Yu Shengping, Yang Xuejun. 2017, 44 (12):  926-928.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.011 Abstract ( 516 )   PDF (671KB) ( 555 )   Save Na+-K+-2Cl- cotransporter 1 (NKCC1) is highly expressed in malignant gliomas, which is closely related to the degree of malignancy. NKCC1 protein has a vital function in the volume regulation of glioma cells. NKCC1 allows glioma cells to transform its volume freely, migrating through the narrow extracellular space to achieve distant metastases. There is also close relationship between NKCC1 and tumor cytoskeleton regulation. In addition, NKCC1 is closely associated with cell cycle, nerve activity and other biological functions. In conclusion, NKCC1 plays an important role in gliomas. Related Articles | Metrics

Treatment protocols of local-regional recurrence after breast cancer surgery Chen Dalei, Shen Yanyan, Lin Chuanqi, Wang Xiaohui, Shi Hao, Guo Guilong 2017, 44 (12):  929-932.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.012 Abstract ( 571 )   PDF (677KB) ( 606 )   Save Despite the deepening of research on breast cancer, improving of treatment techniques, there are still many patients will appear local-regional recurrence after surgery. For patients with local recu-rrence after radical mastectomy, according to whether the postoperative radiotherapy performed, prognosis and treatment protocols are absolutely different. As for patients with local recurrence after breast-conserving surgery, more and more studies have shown that lumpectomy (secondary breast conserving surgery) combined with brachytherapy can achieve a similar effect with radical surgery in recent years, so it is a worth considering treatment protocol. Related Articles | Metrics

Combinational immunological checkpoint inhibitors for non-small cell lung cancer Yuan Yingli, Ma Kewei. 2017, 44 (12):  933-936.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.013 Abstract ( 330 )   PDF (678KB) ( 796 )   Save Immunological checkpoint inhibitors have become one of the major treatment options for patients with advanced non-small cell lung cancer (NSCLC). Despite patients with NSCLC show the superiority of standard chemotherapy in different disease settings, the response rate is still low in patients with high macromolecule selection for chemotherapy tolerance and gene mutation. This is related to the complexity and dyna-mics of known limited biomarkers and tumor microenvironment. Different methods of tumor cells to evade the immune system used to lay the foundation for the new combination strategy. Combination therapy not only improves the efficacy of treatment, but also makes the objective response rate improved significantly. Related Articles | Metrics

Research progress of long noncoding RNA in gastric cancer Zhang Guohua, Zhang Wenbo, Jiang Pengcheng 2017, 44 (12):  937-939.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.014 Abstract ( 369 )   PDF (672KB) ( 678 )   Save Long noncoding RNA (lncRNA) can extensively participate in the pathogenesis, proliferation, invasion and metastasis, apoptosis, angiogenesis, immunization, and drug resistance of gastric cancer through various mechanisms, including epigenetic regulation, variable splicing and competitive endogenous RNA. In addition, lncRNA has broad prospects in the diagnosis, targeted therapy and prognosis of gastric cancer. Related Articles | Metrics

Role and mechanism of macrophages modulating the liver microenvironment in digestive tract malignancies liver metastasis Xiao Hua, Liu Wu. 2017, 44 (12):  940-943.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.015 Abstract ( 542 )   PDF (679KB) ( 1085 )   Save Macrophagses are important components of the liver microenvironment, and play an essential role in the occurrence and development of liver metastasis of digestive system malignancies. Macrophages and liver sinusoidal endothelial cells constitute the first defense line of the liver, which can rapidly recognize and arrest the circulating tumor cells invading into the liver sinusoidal, by phagocytosis or promoting their apoptosis, thus play a cytotoxic effect to inhibit the occurrence of liver metastases. On the other hand, macrophages can combine to the circulating tumor cells and be activated. As a result, hepatocyte growth factor and other cytokines were released, which significantly promoted the proliferation of tumors cells, and thus promoting liver metastases. It may provide a new idea in preventing and treating liver metastasis of digestive system malignancies by targeting macrophages during tumor immunotherapy Related Articles | Metrics

Sensitivity prediction of preoperative chemoradiotherapy in patients with rectal cancer and the clinical application Yan Xueqi, Zhou Jundong, Wu Jinchang 2017, 44 (12):  944-947.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.016 Abstract ( 498 )   PDF (681KB) ( 647 )   Save Some of the patients with rectal cancer are less sensitive to preoperative concurrent chemoradiotherapy (CCRT). Patients who are resistant to CCRT have a poor local tumor control and CCRT may also increase adverse reactions. The sensitivity of rectal cancer patients to CCRT can be predicted by magnetic resonance imaging (MRI), positron emission tomography, serum carcinoembryonic antigen, molecular biomarkers and gene expression profiling before treatment. According to the predicted results, the clinicians are instructed to choose individualized treatment for the patients so that the therapeutic effects of rectal cancer are further improved. Related Articles | Metrics

Autophagy and multidrug resistance Zhu Cong, Jia Xiuhong 2017, 44 (12):  948-950.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.017 Abstract ( 422 )   PDF (672KB) ( 775 )   Save Multidrug resistance （MDR） is the main reason for the failure of leukemia chemotherapy. Autophagy plays an important role in the regulation of MDR. On one hand, as a mechanism of programmed cell death, autophagy can directly induce the death of MDR cells. On the other hand, protective autophagy induced by different signaling pathways and factors such as Hedgehog (Hh) signaling pathway and p53 can promote the survival of MDR cells. Therefore, autophagy agonist or autophagy inhibitors combined with chemotherapeutics will be a new strategy for the treatment of leukemia. Related Articles | Metrics

Progress of research on the minimally invasive treatment of bone metastases Yang Yumei, Chen Jibing, Du Duanming 2017, 44 (12):  951-955.  doi: 10.3760/cma.j.issn.1673-422X.2017.12.018 Abstract ( 444 )   PDF (689KB) ( 527 )   Save In recent years, minimally invasive techniques, such as percutaneous cementoplasty, percutaneous cryoablation, magnetic-resonance-guided focused ultrasound surgery, radiofrequency ablation, microwave ablation, radioactive particle implantation, transcatheter arterial embolization and irreversible electroporation et al, play more and more important roles in the treatments of bone metastasis. Compare with traditional therapies like radiotherapy, drugs and surgery, the better efficacy and security of minimally invasive techniques have been demonstrated by voluminous animal experiments and clinical trials. However, the clinical application of minimally invasive techniques have still some controversial issues. Related Articles | Metrics