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08 January 2019, Volume 46 Issue 1 Previous Issue    Next Issue

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Study of proliferation ability of tumor antigen-loaded DC-CIK cells and its killing effect on hepatocarcinoma cells HepG2 2019, 46 (1):  1-5.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.001 Abstract ( 597 )   PDF (733KB) ( 452 )   Save Objective  To observe the proliferation ability of cocultured dendritic cells (DCs) loaded with tumor antigen and cytokineinduced killer cells (CIKs) and its killing effect on hepatocarcinoma cells HepG2. Methods  The antigen of hepatocarcinoma cells HepG2 was prepared by repeated freezing and thawing of liquid nitrogen. Peripheral blood mononuclear cells (PBMNCs) were isolated from healthy donors by blood cell separator, then DCs and CIKs were induced. AgDCs were obtained by impinging DCs with tumor antigens. CIKs were divided into three groups: the first group was CIKs alone, the second group was mixed in the proportion of DCs∶CIKs=1∶5, and the third group was mixed in the proportion of Ag-DCs∶CIKs=1∶5. The three groups of cells were recorded as CIK group, DC-CIK group and Ag-DC-CIK group. The proliferation and cell phenotype of the three groups of cells were observed and the killing effects on hepatocarcinoma cells HepG2 were detected by methyl thiazolyl tetrazolium (MTT) assay. Results  The proliferation multiples of the three groups of cells were gradually increased with the prolongation of culture time, and the proliferation rates of Ag-DC-CIK on the 9th day (61.32±1.72), the 12th day (190.83±3.53) and the 15th day (399.09±5.60) were significantly higher than those of CIK group (22.47±2.07, 55.91±1.81, 83.20±2.34) and DC-CIK group (40.26±2.49, 125.03±4.16, 251.55±3.25), and the difference between the three group was statistically significant (F=185.78, P=0.033; F=297.35, P=0.018; F=455.37, P<0.001), in addition, the differences between each two groups were statistically significant (all P＜0.05). The cytotoxicity of Ag-DC-CIK to HepG2 cells at the effective target ratios of 5∶1 (31.71%±0.29%), 10∶1 (42.43%±1.86%) and 20∶1 (57.69%±1.11%) were significantly higher than those of CIK group (12.11%±1.14%, 21.30%±0.52%, 30.71%±1.26%) and DC-CIK group (20.06%±0.67%, 29.89%±1.37%, 39.11%±0.92%),   and the difference between the three group was statistically significant (F=159.64, P=0.037; F=199.36, P=0.025; F=302.08, P＜0.001), in addition, the differences between each two groups were statistically significant (all P＜0.05). On the 15th day of cell culture, the flow cytometry analysis showed that all the three groups were expressed CD3+CD8+, CD3+CD56+ double positive cells, the contents of CD3+CD8+、CD3+CD56+ double positive cells in the Ag-DC-CIK group (88.12%±1.24%, 61.35%±2.63%) were significantly higher than those in the CIK group (54.37%±3.08%, 18.22%±1.83%) and DC-CIK group (69.80%±1.46%, 39.51%±2.17%),  and the difference between the three group was statistically significant (F=414.32, P<0.001; F=378.60, P<0.001), in addition, the differences between each two groups were statistically significant (all P＜0.001). Conclusion  The proliferation ability and killing effect of Ag-DC-CIK that obtained from antigen pulsed DCs cocultured with CIKs are significantly higher than those of CIKs and DCCIKs. References | Related Articles | Metrics

Expressions of PTEN and E-cadherin in breast cancer tissues and their clinical significance Chen Yiming, Zhou Yi 2019, 46 (1):  6-10.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.002 Abstract ( 716 )   PDF (810KB) ( 470 )   Save Objective To investigate the expressions of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and epithelial cadherin (E-cadherin) in breast cancer tissues and explore their clinical significance. MethodsWe retrospectively analyzed the clinical data of 263 breast cancer patients admitted to the First Affiliated Hospital of Harbin Medical University from November 2012 to December 2014. The expressions of PTEN and E-cadherin were detected by immunohistochemistry. The relationship of protein expression with clinicopathological characteristics was analyzed by  χ2 test or Fisher exact test. Contingency correlation analysis was used to analyze the correlation between PTEN and E-cadherin, and KaplanMeier was used to evaluate the relationship between their expressions and patients′ survival. COX regression model was used to analyze risk factors. ResultsThe positive expression rates of PTEN and Ecadherin in breast cancer tissues were 68.4% (180/263) and 95.4% (251/263) respectively, lower than those in paratumor breast tissues 77.9% (205/263) and 98.5% (259/263), with statistically significant differences (χ2=6.056, P=0.014;  χ2=4.125, P=0.042). PTEN expression was associated with lymph node metastasis (χ2=8.443, P=0.015) and clinical stage (χ2=9.253, P=0.010). Ecadherin expression was not correlated with age, menopausal status, tumor maximum diameter, lymph node metastasis and clinical stage (all P>0.05). Contingency correlation analysis showed a positive correlation between PTEN and Ecadherin expressions in breast cancer tissues (C=0.125, P=0.041). Survival analysis showed that the 5 year tumorfree survival rate was 81.9% in the PTEN negative group, lower than 95.0% in the positive group (χ2=12.040, P=0.001). The 5year tumorfree survival rate in the E-cadherin negative group was 66.7%, lower than  92.0% in the positive group (χ2=13.313, P<0.001). COX multivariate analysis showed that negative expressions of PTEN and E-cadherin and lymph node metastasis were independent risk factors for the prognosis of breast cancer patients (HR=2.554, 95%CI: 1.0166.420, P=0.046; HR=3.573, 95%CI: 1.13611.239, P=0.029; HR=3.622, 95%CI: 2.0266.476, P＜0.001). Conclusion PTEN is related to Ecadherin expression and low expressions of both may be one of the mechanisms of breast cancer development, invasion and metastasis. Combined detection can be used as an indicator to determine the prognosis of breast cancer. References | Related Articles | Metrics

Analysis of gene detection status of EGFR mutation in 170 patients with advanced lung adenocarcinoma Hu Wei, Zhang Yu 2019, 46 (1):  11-16.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.003 Abstract ( 725 )   PDF (3919KB) ( 476 )   Save Objective To explore and analyze the actual use of different detection methods and samples in detection of epidermal growth factor receptor (EGFR) mutation in patients with advanced lung adenocarcinoma. Methods The clinical data of 170 patients with advanced lung adenocarcinoma receiving EGFR gene detection in Department of Respiratory Medicine of Nanjing Chest Hospital were collected and an analysis of initial result and continuous detection conditions was made. Results The EGFR sensitive mutation rate of the first detection in 170 patients was 49.4% (84/170). The detection rate of EGFR sensitive mutation in female patients was higher than that in male patients ［61.4% (43/70) vs. 41.0% (41/100); χ2=6.875, P=0.009］. The detection rate of EGFR sensitive mutation in patients aged 65 or older was lower than that in patients younger than 65 years old ［41.6% (47/113) vs. 64.9% (37/57); χ2=8.242, P=0.004］. The detection rate of EGFR sensitive mutation in smokers was lower than that in nonsmokers ［34.3% (24/70) vs. 60.0% (60/100); χ2=10.892, P=0.001］. A total of 60 patients were retested after disease progression, and the detection rate of T790M was 48.3% (29/60). The detection rate of EGFR sensitive mutation in the initial examination in 170 patients: tumor tissue (biopsy and pleural effusion cell wax block) for 50.8% (64/126), ctDNA (pleural effusion and peripheral blood) for 45.5% (20/44), with no significant difference (χ2=0.372, P=0.542); PCR method for 51.0% (77/151),  nextgeneratio sequencing (NGS) method for 36.8% (7/19), with no significant difference (χ2=1.352, P=0.245). The detection rate of T790M in 60 patients receiving drug resistance: PCR method for 51.9% (14/27), NGS method for 45.5% (15/33), with no significant difference (χ2=0.243, P=0.622). The use of tumor tissue was 74.1% (126/170) in the initial examination, and ctDNA accounted for 25.9% (44/170). The use of tumor tissue was 11.7% (7/60) in the second examination, and ctDNA accounted for 88.3% (53/60). The use of tumor tissue was 23.1% (3/13) in the third examination, and ctDNA accounted for 76.9% (10/13). The proportions of detection methods used for the 3 tests were as follows, the first test: PCR accounted for 88.8% (151/170), and NGS accounted for 11.2% (19/170); the second test: PCR accounted for 45.0% (27/60), and NGS accounted for 55.0% (33/60); the third test: NGS accounted for 100% (13/13). Conclusion For patients with advanced lung adenocarcinoma, making full use of different tumor specimens and ctDNA helps improving the detection rate of EGFR mutation, and reasonable use of PCR technology and NGS method can bring maximum benefits to patients. References | Related Articles | Metrics

Effects of Xiaoaiping injection assisted TP regimen on immune status, adverse reactions and quality of life in the treatment of advanced NSCLC Chen Yu, Li Qiang, Zhang Cong, Li Shijie 2019, 46 (1):  17-21.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.004 Abstract ( 584 )   PDF (3237KB) ( 337 )   Save Objective To explore the shortterm efficacy of Xiaoaiping injection assisted TP regimen (taxotere + paraplatin) in the treatment of advanced nonsmall cell lung cancer (NSCLC) and its effects on immune function, adverse reactions and quality of life. Methods Onehundred cases of patients with advanced NSCLC who were admitted to the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from October 2014 to October 2017 were selected as subjects, and they were randomly divided into Xiaoaiping group (n=55) and TP group (n=45) according to the random number table method. Patients in TP group were given TP regimen chemotherapy, and patients in Xiaoaiping group were added with Xiaoaiping injection on the basis of TP group. The shortterm efficacy and changes of immune function, adverse reactions and quality of life were observed in the two groups, and statistical comparison was performed. ResultsAfter treatment, the response rates of patients in Xiaoaiping group and TP group were 49.09% (27/55) and 28.89% (13/45) respectively, with a significant difference (χ2=4.209, P=0.040). After treatment, the disease control rates of patients in Xiaoaiping group and TP group were 83.64% (46/55) and 73.33% (33/45) respectively, with no significant difference (χ2=1.584, P=0.208). The CD4+ (40.98%±5.73% vs. 33.47%±5.06%), CD4+/CD8+ (1.53±0.34     vs. 1.25±0.26) and nature killer (NK) cells (19.59%±4.77% vs. 17.05%±4.12%) in Xiaoaiping group after treatment were significantly higher than those in TP group (t=6.869, P＜0.001; t=4.542, P＜0.001; t=5.609, P＜0.001). And there was no significant difference in CD8+ between the two groups (26.83%±5.21% vs. 26.58%±5.20%; t=0.239, P=0.812). The incidence rates of leucopenia (50.91% vs. 75.56%), thrombocytopenia (38.18% vs. 66.67%) and hemoglobin reduction (52.73% vs. 77.78%) in Xiaoaiping group were lower than those in TP group, with significant differences (χ2=6.381, P=0.012; χ2=8.306, P=0.005; χ2=6.741, P=0.009). There were no significant differences in the incidence rates of nausea and vomiting (32.73% vs. 48.89%), diarrhea constipation (45.45% vs. 60.00%)  and liver damage (7.27% vs. 13.33%) between the two groups (χ2=2.694, P=0.101; χ2=2.098, P=0.148; χ2=0.449, P=0.503). After treatment, the Karnofsky functional status scores of patients in Xiaoaiping group and TP group were 81.47±11.26 and 73.38±10.45  respectively, and the stability rates of quality of life improvement were 78.18% (43/55) and 57.78% (26/45) respectively, with significant differences (t=3.691, P＜0.001; χ2=4.817, P=0.028). Conclusion Xiaoaiping injection assisted TP regimen has a good shortterm efficacy on advanced NSCLC, which can effectively improve immune function, reduce adverse reactions and improve the quality of life. References | Related Articles | Metrics

Comparison of magnifying endoscopy combined with narrowband imaging and endoscopic ultrasonography for assessment of the invasion depth of early esophageal cancer Wu Dapeng, Sun Renhu, Li Yang, Han Shutang, Xiao Jun 2019, 46 (1):  22-26.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.005 Abstract ( 687 )   PDF (16240KB) ( 219 )   Save Objective To investigate the clinical utility of magnifying endoscopy combined with narrowband imaging (ME-NBI) and endoscopic ultrasonography (EUS) in predicting the depth of early esophageal cancer. Methods Sixtyeight patients with early esophageal cancer after gastroscopic and pathological diagnosis were enrolled in Jiangsu Provincal Hospital of Traditional Chinese Medicine from January 2017 to May 2018, ME-NBI and EUS were performed preoperatively to determine the depth of lesion infiltration respectively, the accuracies of the two methods were calculated by referring to the postoperative pathology, and the McNemar test and Kappa test were used for comparison. Results The lesion confined to shallow mucosa and submucosa superficial layer was confirmed in 57 patients by postoperative pathology, submucosa superficial below in 11 patients. Compared with that of histology, the ability of assessment of the invasion depth was moderately consistent with MENBI (McNemar test P=0.508; Kappa=0.560, P＜0.001), not with EUS (McNemar test P=0.019; Kappa=0.266, P=0.015). The accuracy for assessing invasion depth of early esophageal cancer was 86.8% (59/68) by MENBI, 72.1% (49/68) by EUS, respectively,  with statistically significant difference (McNemar test P=0.015; Kappa=0.258, P=0.026). Conclusion ME-NBI and EUS can help to determine the infiltration level of early esophageal cancer. The accuracy of MENBI is higher, which is of high value for the formulation of surgical plans for patients. References | Related Articles | Metrics

Effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B Zhang Wei, Su Fang, Wang Zishu 2019, 46 (1):  27-31.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.006 Abstract ( 566 )   PDF (3554KB) ( 290 )   Save Objective To observe the effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B. Methods The clinical data of 72 patients with advanced hepatocellular carcinoma associated with hepatitis B admitted to the First Affiliated Hospital of Bengbu Medical College from January 2015 to May 2017 were retrospectively analyzed. Among them, 37 patients were treated with apatinib once a day, as apatinib group; 35 patients were treated with FOLFOX4 (oxaliplatin+calcium folinate+5-fluorouracil) palliative chemotherapy, as FOLFOX4 group. The objective response rate (ORR), disease control rate (DCR), serum alpha fetal protein (AFP), improvement of clinical symptoms, Karnofsky functional status (KPS) score improvement rate, median progressionfree survival (PFS), median overall survival (OS), and the incidence of adverse reactions from both groups were contrastively analyzed. Results The ORR of apatinib group (27.03%, 10/37) was higher than that of FOLFOX4 group (17.14%, 6/35), and DCR (64.86%, 24/37) was also higher than that of FOLFOX4 group (48.57%, 17/35). However, there were no significant difference in ORR and DCR between the two groups (χ2=1.017, P=0.313; χ2=1.948, P=0.163). After 16 weeks of treatment, serum AFP of apatinib group ［(280±20) ng/ml］ was significantly lower than that in FOLFOX4 group ［(450±20) ng/ml, t=36.049，P＜0.001］. Improvement rate of KPS score (86.49%, 32/37) was significantly more than that of FOLFOX4 group (57.14%, 20/35; χ2=7.720, P=0.006). Improvement rate of clinical symptoms (72.97%, 27/37) was significantly more than that of FOLFOX4 group (42.86%, 15/35; χ2=6.712, P=0.010). The mean PFS of apatinib group was 6.2 months, which was significantly longer than that of FOLFOX4 group (2.8 months, χ2=4.815, P=0.028). The mean OS of apatinib group was 10.9 months, which was significantly longer than that of FOLFOX4 group (6.6 months, χ2=26.429, P＜0.001). In apatinib group, the main adverse reactions were hypertension, proteinuria and handfoot syndrome; and in FOLFOX4 group, the main adverse reactions were leukopenia, neurotoxicity and liver function damage. Moreover, the adverse reactions in both groups were mostly 1 or 2 grade，which could be relieved or improved through symptomatic treatment. Conclusion Apatinib is safe and effective in the treatment of advanced hepatocellular carcinoma associated with hepatitis B. It can significantly prolong the life of patients and improve the quality of life and the clinical symptoms of patients. References | Related Articles | Metrics

Comparison of the efficacy and safety of liposome doxorubicin and gemcitabine combined with oxaliplatin in the treatment of recurrent platinum resistant ovarian cancer Chu Chaonan, Huang Qi 2019, 46 (1):  32-35.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.007 Abstract ( 742 )   PDF (647KB) ( 561 )   Save Objective To evaluate and compare the efficacy and safety of liposome doxorubicin and gemcitabine combined with oxaliplatin in the treatment of recurrent platinumresistant ovarian cancer. Methods From January 1, 2015 to December 31, 2016, 80 patients from Hunan Cancer Hospital with recurrent platinumresistant ovarian cancer were divided into two groups by using random number table method, 40 cases in each group: group PLD was treated with liposome doxorubicin and group G/O was treated with gemcitabine combined with oxaliplatin. The therapeutic effects of the two groups were evaluated, the expressions of CA125 after treatment were compared and the occurrence of adverse reactions were observed. Results The objective response rate (ORR) and disease control rate (DCR) were respectively 27.5% (11/40) and 35.0% (14/40) in group PLD, and the ORR and DCR were respectively 22.5%（9/40） and 27.5%（11/40） in group G/O, and there was no significant difference between the two groups (χ2=0.27, P=0.61;  χ2=0.52, P=0.47). In PLD group and G/O group, the CA125 values of ORR patients were (61.27±28.11)U/ml and (78.29±34.26)U/ml respectively, with no significant difference (t=1.22, P=0.24), the CA125 values of non ORR patients were (530.07±77.15)U/ml and (551.00±78.78)U/ml respectively, with no significant difference (t=1.04, P=0.30). The main adverse reactions in group PLD were hand foot syndrome and myelosuppression. The main adverse reactions in group G/O were gastrointestinal reaction and myelosuppression. The incidence rates of leucocyte reduction (65.0% vs. 92.5%,  χ2=9.04, P=0.005), thrombopenia (15.0% vs. 52.5%,  χ2=12.58, P＜0.001), anemia (15.0% vs. 40.0%,  χ2=6.27, P=0.012), gastrointestinal reaction (17.5% vs. 60.0%,  χ2=15.22, P＜0.001) and neurotoxicity (5.0% vs. 30.0%,  χ2=8.66, P=0.006) in group PLD were lower than those in group G/O, with significant differences. Conclusion The efficacy of two chemotherapy regimens is similar in patients with recurrent platinumresistant ovarian cancer. Liposome doxorubicin has less adverse reactions than gemcitabine combined with oxaliplatin. References | Related Articles | Metrics

Branched chain amino acid transferase 1 and malignant tumors Lyu Tianxin, Zhang Binglei, Song Yongping 2019, 46 (1):  36-39.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.008 Abstract ( 714 )   PDF (643KB) ( 773 )   Save As a key enzyme that catalyzes the metabolism of branched chain amino acids, branched chain amino acid transferase 1 (BCAT1) is often involved in a variety of biosynthetic pathways. Reaserches show that BCAT1 is  highly expressed in many kinds of malignant tumors such as leukemia, glioma, nasopharyngeal carcinoma, gastric cancer and breast cancer, et al, suggesting a close relationship with the proliferation, invasion and metastasis of tumor cells. Thus, BCAT1  plays an important role in the genesis and progression of tumor, and may have the potential to be a new therapeutic target. References | Related Articles | Metrics

Research progress of anti PD-1/PD-L1 immunotherapy biomarkers Wang Huan, Jiang Haiping, Gao yuan, Xu Nong, Yu Xiongfei 2019, 46 (1):  40-44.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.009 Abstract ( 813 )   PDF (653KB) ( 872 )   Save Immunological checkpoint inhibitors of antiprogrammed cell death-1  and programmed cell death ligand-1 (PD-L1) have already demonstrated remarkable clinical efficacy for solid tumors, however, the effectiveness of single drug therapy in immunotherapy is not very high. Therefore, exploring the appropriate therapeutic predictive biomarkers so as to accurately identify the potential patients suitable for this therapy has become a research hotspot. Studies have shown that biomarkers such as PD-L1, tumor mutation burden and mismatch repair deficiency may be related to the efficacy of immunotherapy. Indepth analysis and exploration of these markers may provide a basis for determining those patients who are more likely to benefit from checkpoint inhibitor. References | Related Articles | Metrics

Clinical application of Apatinib in the treatment of malignancies Huang Hai, Bi Feng 2019, 46 (1):  45-48.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.010 Abstract ( 764 )   PDF (2982KB) ( 423 )   Save Apatinib is a kind of antiangiogenesis drug of small molecular tyrosine kinase inhibitor, which can strongly against tumor angiogenesis by inhibiting vascular endothelial growth factor receptor 2 with highly selectivity. Apatinib can block cell cycle and reverse drug resistance. Clinical studies have shown that Apatinib is effective for many malignant tumors, including non-small-cell lung cancer, breast cancer and gastric cancer, which has encouraging objective response rate and survival benefit. Apatinib also has good safety and tolerance. References | Related Articles | Metrics

Progress of radiotherapy combined with anti-PD-1/PD-L1 in tumor therapy 2019, 46 (1):  49-53.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.011 Abstract ( 717 )   PDF (653KB) ( 889 )   Save Radiotherapy is widely used in local treatment of tumors. It can not only directly kill tumor cells by damaging DNA, but also have a great impact on the immune system of the body. This effect is not only inhibited, but also more activated. Programmed death1 (PD1) and its ligand 1 (PDL1) antibody, as the most popular immune checkpoint inhibitor, can inhibit tumor growth by restoring and enhancing the immune killing function of T cells. With the deepening of the study, it is found that the combination of the two treatment of tumor, the curative effect is better than the single mode.  References | Related Articles | Metrics

Research progress of new antioxidants in urological neoplasms Song Jiarui, Zhang Bin, Yang Zhongwen, Xu Baocai, Wang Chao, Ma Ming 2019, 46 (1):  54-56.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.012 Abstract ( 399 )   PDF (638KB) ( 596 )   Save Antioxidants are important substances in the body against oxidative stress, which can maintain the balance of redox substances by reducing the content of reactive oxygen species in cells. Studies have shown that new antioxidants have significant inhibitory effects on the growth of urological neoplasms by inhibiting tumor cell proliferation, inducing apoptosis, disturbing angiogenesis and metastasis of tumor cells. Antioxidants are of great value in the prevention and treatment of urinary system tumors and are expected to become new antitumor drugs. References | Related Articles | Metrics

Research progress of circulating tumor DNA in ovrian cancer Yuan Qiuyue, Qiao Huimin, Zhang Shengmiao, Xia Baoguo, Bi Shuna, Chen Long 2019, 46 (1):  57-60.  doi: 10.3760/cma.j.issn.1673-422X.2019.01.013 Abstract ( 498 )   PDF (645KB) ( 700 )   Save With the continued development of molecular biology technologies, circulating tumor DNA (ctDNA) has shown certain value in the diagnosis and treatment of malignant tumors. The emergence of next generation sequencing technology makes ctDNA detection more accurate and rapid. ctDNA plays a certain role in the early diagnosis, disease monitoring, therapeutic evaluation and medication guide of ovarian cancer by virtue of its safety and noninvasiveness. The application of ctDNA detection is insufficient at present, but with the continuous development of sequencing technology, ctDNA will play increasingly important roles in the diagnosis, personalized treatment and prognosis evaluation of ovarian cancer. References | Related Articles | Metrics