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08 July 2018, Volume 45 Issue 7 Previous Issue    Next Issue

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Experimental study on bi-chimeric antigen receptors modified T- lymphocytes targeting on acute myeloid leukemia Zhang Yun, Ji Xiluan, Luo Zhaoxia, Yang Shun, Shang Yanhong, Xie Liang, Jia Youchao, Li Jieming, Zang Aimin, Jiang Shu 2018, 45 (7):  385-390.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.001 Abstract ( 482 )   PDF (1504KB) ( 682 )   Save Objective  To study the cytotoxicity of bi-chimeric antigen receptors modified T- lymphocytes (BiCAR-T) on the human acute myeloid leukemia (AML) cell line HL60 in vitro and the antitumor effects of BiCAR-T on the NOD SCID mouse model of AML in vivo. Methods  The BiCAR-T were prepared and the expression of chimeric antigen receptor (CAR) of prepared BiCAR-T was analyzed by flow cytometry. In vitro study was divided into two groups: the experiment group (BiCAR-T) and the control group (T lymphocyte). The killing rate of BiCAR-T in vitro on HL60 cells was determined by CCK8 assay and the level of interferon-γ (IFN-γ) secreted from BiCAR-T co-culturing with HL60 cells for 48 hours was detected by enzyme linked immunosorbent assay (ELISA) at different effect/target ratios (5∶1, 10∶1, 20∶1). The NOD SCID mice AML model was established by the injection of HL60 cells through tail vein and  used to assess the antitumor effects in vivo. The mice were randomly divided into three groups according to the random number table: the blank control group receiving 0.9% NaCl 0.2 ml through tail vein， the model group and the treatment group receiving 1×107 HL60 cells in 0.2 ml phosphate buffer saline (PBS). After 20 days, the treatment group was injected with 2×107 BiCAR-T in 0.2 ml PBS 3 times a week for 2 weeks, while the other two groups received 0.9% NaCl 0.2 ml. The pathological changes in the mice livers and spleens were observed after 2 weeks of treatment. Results  The CAR expression rates of BiCAR-T were more than 50.00%. In vitro experiments proved that the killing rates of BiCAR-T in the experimental group and T lymphocytes in the control group on HL60 cells were (25.43±1.32)% vs. (16.18±0.75)%, (50.33±3.11)%  vs. (25.47±1.27)%, and (85.89±3.96)% vs. (49.45±2.77)% at different effect/target ratios (5∶1, 10∶1, 20∶1). The killing efficiency of BiCAR-T and T lymphocytes on HL60 cells was significantly different (F=404.17, P＜0.001); the killing efficiency of BiCAR-T and T lymphocytes on HL60 cells was significantly different at different effect/target ratios (F=548.09, P＜0.001); and the killing efficiency on HL60 cells in the experimental group (BiCAR-T) was significantly higher than that in the control group  (T lymphocytes) at different effect/target ratios (F=45.36, P＜0.001). The IFN-γ levels secreted from BiCAR-T in the experiment group and T lymphocytes in the control group coculturing with HL60 cells after 48 h were (435.65±20.44)pg/ml vs. (356.75±19.87)pg/ml, (1 639.98±95.75)pg/ml vs. (1 109.37±80.98)pg/ml, and (3 467.43±187.54)pg/ml vs. (2 245.52±112.66)pg/ml.  The IFN-γ level in the experiment group (BiCAR-T)  and the control group  (T lymphocytes) was significantly different (F=156.24, P＜0.001); the IFN-γ level was significantly different at different effect/target ratios (F=857.67, P＜0.001); the IFN-γ level in the experimental group  (BiCAR-T) was significantly higher than that in the control group  (T lymphocytes) at different effect/target ratios of 5∶1, 10∶1, 20∶1, respectively (F=46.31, P＜0.001). The result of hematoxylineosin staining (HE) staining showed that leukocyte infiltration in the treatment group was significantly decreased compared with the model group. Conclusion  The experimental results showed that BiCAR-T is a kind of efficient targeted immunocyte modified by gene engineering, and it can significantly inhibit leukocyte infiltration of AML in vivo and in vitro. Related Articles | Metrics

Correlation analysis and clinical significance of lymph node metastasis in right recurrent laryngeal nerve of papillary thyroid carcinoma Chen Hongcun, Li Liang, Jiang Ming, Zhang Jun, Yao Baozhong, Jiang You, Liao Lifang 2018, 45 (7):  391-394.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.002 Abstract ( 1031 )   PDF (723KB) ( 650 )   Save Objective  To explore the correlation factors and clinical significance of lymph node metastasis in right recurrent laryngeal nerve of thyroid papillary carcinoma (PTC). Methods  Ninty-eight consecutive patients with PTC who were underwent total thyroidectomy with routine central lymph node dissection in the Second People′s Hospital of Hefei from January 2015 to August 2017 were analyzed. The right paratracheal lymph nodes in the central compartment lymph nodes were divided into the  level Ⅵ-A (anterior) and level Ⅵ-B (posterior, that was lymph node posterior to recurrent laryngeal nerve) compartments by recurrent laryngeal nerve. The lymph node metastasis of Ⅵ-B area during central compartment lymph node dissection was analyzed. We drew the receiver-operating characteristic curve (ROC) for right neck Ⅵ-A number of lymph node metastasis, and calculated the area under the curve (AUC) and Youden index. Results  Among 98 cases, 16 cases occurred Ⅵ-B district lymph node metastasis (16.33%). Single factor analysis results showed that lymph node metastasis in Ⅵ-B area of PTC patients were related to the tumor size (χ2=12.864, P＜0.001), tumor capsular invasion (χ2=16.354, P＜0.001), the right neck Ⅵ-A area lymph node metastasis (χ2=16.065, P＜0.001), tumor number (χ2=15.593, P＜0.001) and neck lymph node metastasis  (χ2=21.098, P＜0.001), but they were not related to the patients′ gender, age and lesion location (all P＞0.05). Lymph node metastasis in Ⅵ-B area of PTC patients were related to the number of right neck Ⅵ-A area lymph node metastasis. When the number of right neck Ⅵ-A metastatic lymph nodes was 2.5, the sensitivity and specificity were 70.60% and 70.00% respectively, AUC was 0.754, and Youden index was 0.406. Conclusion  For patients with PTC, primary tumor diameter ＞1 cm, tumor extracapsular invasion, Ⅵ-A area lymph node metastasis, multiple tumor and lateral cervical lymph node metastasis were the predictive factors for the lymph node metastasis in Ⅵ-B area. When the number of right neck Ⅵ-A area metastatic lymph nodes was greater than 3, we should dissect Ⅵ-B area. Related Articles | Metrics

Clinical comparative study of two kinds of modified radical mastectomy in the treatment of breast cancer patients for Ⅰ-Ⅱa stage Qiu Han, Kong Jun 2018, 45 (7):  395-399.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.003 Abstract ( 732 )   PDF (663KB) ( 595 )   Save Objective  To compare the clinical effects and safety of conventional modified radical mastectomy and modified radical mastectomy for reserved nipple areola in the treatment of breast cancer patients for Ⅰ-Ⅱa stage. Methods  One hundred breast cancer patients for Ⅰ-Ⅱa stage were chosen in the period from October 2011 to October 2013 in the central hospital of Jinzhou City and were randomly divided into two groups according to the random number table: the control group (50 patients) with conventional modified radical mastectomy and the observation group (50 patients) with modified radical mastectomy for reserved nipple areola. The operation time, the intraoperative blood loss, the number of lymph node dissection, the surgical aesthetic score, Functional Assessment of Cancer Therapy-Breast (FACT-B) score, the postoperative complication incidence, the 3 years follow-up of local recurrence rate, distant metastasis and survival rate in both groups were compared. Results  The operation time ［(163.36±39.13)min vs. (144.74±34.62)min］ and the intrao-perative blood loss ［(128.10±22.52)ml vs. (114.32±18.89)ml］ of the observation group were significantly higher than the control group, with significant differences (t=3.10, P＜0.001; t=2.87, P＜0.001). There was no significant difference in the number of lymph node dissection between the two groups ［(15.19±3.38) vs. (14.68±3.14), t=0.61, P=0.480］. The surgical aesthetic score in 6 months ［(9.61±0.38) vs. (7.28±0.84)］ and 12 months ［(9.32±0.46) vs. (7.05±0.76)］  after operation of the observation group were significantly higher than those of the control group (t=3.22, P＜0.001; t=3.51, P＜0.001). The social/family status score ［(22.86±5.21) vs. (19.23±4.38)］, functional status score ［(15.85±3.18) vs. (9.32±2.39)］, emotional status score  ［(18.85±3.98) vs. (15.32±2.39)］ and total score ［(95.73±14.16) vs. (82.26±10.35)］ of the observation group were significantly better than those of the control group (t=3.56, P＜0.001; t=3.19, P＜0.001; t=3.51, P＜0.001; t=3.24, P＜0.001). There was no significant difference in the postoperative complication incidence (24.00% vs. 16.00%) between the two groups (χ2=1.00, P=0.320). There were no significant differences in the local recurrence rate (0 vs. 2.00%) and the distant metastasis (4.00% vs. 6.00%) in 3 years followup between the two groups (P=1.000; χ2=0.00, P=1.000). The survival rates of the two groups were both 100.00%. Conclusion  Compared with conventional modified radical mastectomy, modified radical mastectomy for reserved nipple areola in the treatment of breast cancer patients for I-IIa stage can efficiently improve the surgical aesthetics, the overall quality of life and cannot increase the risk of longterm recurrence and metastasis. Related Articles | Metrics

Predictive role of preoperative hematological inflammatory markers for patients with thoracic esophageal squamous cell carcinoma receiving surgery Guo Xinwei, Zhou Shaobing, Liu Yangchen, Ji Shengjun, Gao Fei. 2018, 45 (7):  400-407.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.004 Abstract ( 448 )   PDF (1428KB) ( 654 )   Save ObjectiveTo investigate the prognostic values of systemic inflammatory markers, including preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and the lymphocyte-to-monocyte ratio (LMR), in patients with esophageal squamous cell carcinoma (ESCC) by curative esophagectomy. Methods  A total of 117 patients with ESCC from January 2010 to December 2012 in Affiliated Taixing People′s Hospital of Yangzhou University were retrospectively analyzed. They were treated with standard curative esophagectomy. These patients were divided into NLR≥2.8 group and NLR＜2.8 group, PLR≥127.3 group and PLR＜127.3 group, LMR≥3.8 group and LMR＜3.8 group for comparing the patients′ general survival conditions and analyzing the influence on the progression-free survival (PFS) and overall survival (OS) rates  according to the median values 2.8, 127.3, 3.8 of NLR, PLR and LMR, respectively. The COX proportional hazards models of NLR, PLR and LMR were used to carry out univariate and multivariate analyses for PFS and OS. The evaluation of prognostic values of NLR, PLR and LMR were carried by receiver operating characteristic (ROC) curve. Results  For 117 patients, the median PFS time was 17 months, and the PFS rates at the 1-, 3- and 5-year period were 66.7%, 21.4% and 17.9%, respectively; the median OS time was 36 months, and the OS rates at the 1-, 3- and 5-year time were 94.9%, 46.2% and 28.2%, separately. In addition, a close relationship was identified between high NLR, high PLR, low LMR and tumor relapse (all P<0.05). Furthermore, in the NLR<2.8 group, the median PFS time was 24 months (95%CI: 19.788-28.212),  and the 1-, 3-, 5-year PFS rates were 78.9%, 35.1% and 31.6% separately, while in the NLR≥2.8 group, the median PFS time was 13 months (95%CI: 10.153-15.847), and the 1-, 3-, 5-year PFS rates were 55.0%, 8.3% and 5.0%, respectively (χ2=15.601, P<0.001). In the PLR<127.3 group, the median PFS time was 24 months (95%CI: 19.891-28.109), and the 1-, 3-, 5-year PFS rates were 78.0%, 30.5% and 27.1%. In the PLR≥127.3 group, the median PFS time was 15 months (95%CI: 11.832-18.168), and the 1-, 3-, 5-year PFS rates were 55.2%, 12.1% and 8.6% (χ2=7.621, P=0.006). In the LMR<3.8 group, the median PFS time was 14 months (95%CI: 11.534-16.466), and the 1-, 3-, 5-year PFS rates were 57.9%, 8.8% and 5.3%, while in the LMR≥3.8 group, the median PFS time was 21 months (95%CI: 16.783-25.217), and the 1-, 3-, 5-year PFS rates were 75.0%, 33.3% and 30.0% (χ2=10.201, P=0.001). Correspondingly, the median OS time was 42 months (95%CI: 29.188-48.282) and the 1-, 3-, 5-year OS rates were 98.2%, 56.1% and 47.4% in the NLR<2.8 group. While the median OS time was 27 months (95%CI: 20.358-33.642) and the 1-, 3-, 5-year OS rates were 91.7%, 36.7% and 10.0% in the NLR≥2.8 group (χ2=19.161, P<0.001). The median OS time was 38 months (95%CI: 31.31044.690) and the 1-, 3-, 5-year OS rates were 94.9%, 54.2% and 37.3% in the PLR<127.3 group and the median OS time was 27 months (95%CI: 19.537-34.463) and the 1-, 3-, 5-year OS rates were 93.1%, 37.9% and 19.6% in the PLR≥127.3 group (χ2=7.019, P=0.008). The median OS time was 30 months (95%CI: 23.659-36.341) and the 1-, 3-, 5-year OS rates were 91.2%, 36.8% and 12.3% in the LMR<3.8 group. While the median OS time was 38 months (95%CI: 27.878-48.121) and the 1-, 3-, 5-year OS rates were 95.0%, 55.3% and 43.3% in the LMR≥3.8 group (χ2=10.201, P=0.001). In univariate analysis, the following factors were significantly associated with poor PFS: T stage (HR=1.292, 95%CI: 1.077-2.211, P=0.048), N stage(HR=1.773, 95%CI: 1.186-2.651, P=0.005), TNM stage (HR=1.768, 95%CI: 1.181-2.645, P=0.006), NLR (HR=2.193, 95%CI: 1.450-3.316, P＜0.001), PLR(HR=1.722, 95%CI: 1.149-2.581, P=0.009) and LMR (HR=0.531, 95%CI: 0.353-0.799, P=0.002). The univariate analysis further revealed that T stage (HR=1.982, 95%CI: 1.162-3.383, P=0.012), N stage (HR=1.910, 95%CI: 1.243-2.934, P=0.003）, TNM stage (HR=2.115, 95%CI: 1.375-3.252, P=0.001), NLR (HR=2.599, 95%CI: 1.657-4.078, P＜0.001), PLR (HR=1.764, 95%CI: 1.145-2.717, P=0.010) and LMR (HR=0.470, 95%CI: 0.3030.728, P=0.001) were also significantly associated with poor OS. Furthermore, multivariate COX regression analysis showed that TNM stage (HR=1.608, 95%CI: 1.057-2.445, P=0.026) and NLR (HR=1.886, 95%CI: 1.133-3.138, P=0.015) were independent prognostic factors for PFS in patients with ESCC after surgery. Correspondingly, TNM stage (HR=1.867, 95%CI: 1.190-2.928, P=0.007) and NLR （HR=2.226, 95%CI: 1.292-3.835, P=0.004) were also independent prognostic factors for OS in ESCC patients following surgery. Finally, ROC curves of NLR, PLR and LMR for PFS predictive values were as follows: the area under the curve (AUC) for NLR, PLR and LMR were 0.725 (95%CI: 0.615-0.835, P=0.001), 0.657 (95%CI: 0.533-0.781, P=0.025) and 0.290 (95%CI: 0.178-0.402, P=0.003), respectively. ROC curve analysis of NLR, PLR and LMR in diagnostic value of OS indicated that the AUC was 0.731 (95%CI: 0.632-0.829, P＜0.001) for NLR, 0.613 (95%CI: 0.501-0.726, P=0.057) for PLR and 0.308 (95%CI: 0.205-0.412, P=0.053) for LMR. Conclusion  NLR is superior to PLR and LMR in predicting the survival outcome of patients with ESCC, and NLR is of great value in predicting the survival and prognosis of patients with thoracic ESCC after operation. Related Articles | Metrics

Observation of curative effect of sorafenib for patients with advanced hepatocellular carcinoma Gao Bincheng, Guo Hui, Sun Le, Zhong Min, Cui Lichun 2018, 45 (7):  408-411.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.005 Abstract ( 522 )   PDF (714KB) ( 545 )   Save Objective  To observe the clinical curative effet and survival condition of sorafenib for patients with advanced hepatocellular carcinoma. Methods  Sixty-six patients with hepatocellular carcinoma during January 2013 to January 2015 in Chang′an Hospital were included. All patients were randomly divided into transcatheter arterial chemoembolization (TACE) group (n=33) and sorafenib+TACE group (n=33) according to the random digital table method. Followed up for 2 years, we observed the clinical curative effect, including 6-months survival rate, 1-year survival rate, the changes of serum alpha fetoprotein level before and after the treatment, survival time and related adverse reactions. Results  The disease control rate of sorafenib+TACE group was 84.85% (28/33), which was significantly higher than that of TACE group (60.61%, 20/33), and the difference was statistically significant (χ2=4.889, P=0.027). The median survival time of patients with sorafenib+TACE group was 20.30 months, which was longer than that of TACE group (12.50 months), and the difference was statistically significant (χ2=29.570, P=0.000). The 6-months and 1-year survival rates in patients with sorafenib+TACE group were 93.93% and 75.76%, respectively, which were significantly higher than those of TACE group (84.85%, 51.52%). The rate of 1-year recurrence and metastasis of sorafenib+TACE group was 21.21%, which was lower than that of TACE group (39.39%), and the difference was statistically significant (χ2=2.908, P=0.041). After 6 months treatment, the serum level of alpha fetoprotein in patients with sorafenib+TACE group was (1 911.53±457.86)ng/ml, which was significantly lower than that of TACE group ［(2 979.83±842.71)ng/ml］, and the difference was statistically significant (t=11.996, P=0.001). The median survival time of patients with Child-Pugh A was significantly longer than that of patients with ChildPugh B (20.50 months vs. 13.95 months), with a significant difference (χ2=3.973, P=0.046). Patients in sorafenib+TACE group and TACE group had adverse reactions including nausea, vomiting and abnormal liver function, and there was significant difference in the incidence of untoward effects (87.88% vs. 60.61%; χ2=6.418, P=0.011). Conclusion  The application of sorafenib therapy in the treatment of advanced hepatocellular carcinoma based on TACE can effectively improve the disease control rate, prolong the survival time of patients and improve the survival rate of patients. References | Related Articles | Metrics

Expressions of TNF-α, TNFR1 and TNFR2 in different cervical lesions and their relationships with clinicopathological characteristics Tian Yun, Zeng Jian, Zhai Guangyu 2018, 45 (7):  412-418.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.006 Abstract ( 561 )   PDF (1611KB) ( 654 )   Save Objective  To investigate the expressions of tumor necrosis factor-alpha (TNF-α),  tumor necrosis factor receptor (TNFR)1 and TNFR2 in different cervical lesions and their relationships with clinicopathological characteristics. Methods  Forty-one cases of cervical squamous cell carcinoma (CSCC) patients (CSCC group) treated in 254th Hospital of People′s Liberation Army from January 2015 to December 2017 were selected as the subjects. Forty-nine cases of high grde squmous intrepithelial lesion (HSIL) (HSIL group) and fifty cases of uterine myoma (normal group) were selected as control groups. The expression of TNF-α in cervical tissues of different lesions was detected by immunohistochemistry. The expressions of TNF-α mRNA, TNFR1 mRNA and TNFR2 mRNA were detected by quantificational real-time polymerase chain reaction (qRT-PCR). The expression level of TNFR1 and TNFR2 proteins are measured by Western blotting. The relationships between the expression level of TNF-α mRNA, TNFR1 mRNA and the clinicopathological characteristics of patients were analyzed. Results  The positive rates of TNF-α in the normal group, the HSIL group and the CSCC group were 8.0% (4/50), 59.2% (29/49) and 73.2% (30/41). The difference between three groups was statistically significant (χ2=44.786, P<0.001). The positive rates of the HSIL group and the CSCC group were significantly higher than that in the normal group, the difference was statistically significant (χ2=29.175, P<0.001; χ2=40.883, P<0.001), but there was no statistical difference in the positive rates of TNFα in CSCC group and HSIL group (χ2=1.934, P=0.164).The results of qRT-PCR showed that the expressions of TNF-α mRNA in normal group, HSIL group and CSCC group were 1.32±0.21, 3.64±0.41 and 7.51±1.42. The difference of TNF-α mRNA expression among three groups was statistically significant (F=655.800, P<0.001). The expressions level of TNF-α mRNA in HSIL group and CSCC group were significantly higher than that in normal group (t=31.747, P<0.001; t=51.012, P<0.001), and the expression level of CSCC group was significantly higher than that in HSIL group (t=20.039, P<0.001). The expression levels of TNFR1 mRNA in the normal group, the HSIL group and the CSCC group were 0.42±0.13, 0.89±0.21 and 2.23±0.46. The relative expression of TNFR1 mRNA between the three groups was statistically significant (F=465.900, P<0.001). The expression levels of TNFR1 mRNA in group HSIL and CSCC were significantly higher than that in normal group (t=13.357, P<0.001; t=26.587, P<0.001), and the expression level of CSCC group was significantly higher than that in HSIL group (t=18.407, P<0.001). The expression of TNFR2 mRNA in the normal group, the HSIL group and the CSCC group were 0.38±0.14, 0.41±0.11 and 0.44±0.12. There was no significant difference between three groups (F=2.633, P=0.075). Western blottting showed that the expression intensity of TNFR1 in the normal group, the HSIL group and the CSCC group were 0.84±0.18, 1.95±0.21 and 3.38±0.73, the difference was statistically significant (F=398.000, P<0.001). The expression intensity of TNFR1 in group HSIL and CSCC were significantly higher than that in normal group (t=18.273, P<0.001; t=39.894, P<0.001), and the expression in CSCC group was also significantly higher than that in group HSIL (t=22.357, P<0.001). The expression intensity of TNRF2 in normal group, HSIL group and CSCC group were 0.98±0.15, 1.02±0.17, 1.07±0.21, and the difference was not statistically significant (F=2.938, P=0.056). The results of protein detection were in accordance with the results of mRNA detection. The expression of TNF-α mRNA in the CSCC tissues was related to the size of the tumor (t=-8.868, P<0.001), the degree of differentiation (t=-5.644, P<0.001), the clinical stage (t=-19.329, P<0.001), the depth of infiltration (t=-11.170, P<0.001), and lymph node metastasis (t=-8.339, P<0.001). The expression of TNFR1 mRNA was closely related to the tumor size (t=-13.309, P<0.001), degree of differentiation (t=-13.449, P<0.001), clinical stage (t=-12.949, P<0.001), depth of infiltration (t=-18.124, P<0.001), and lymph node metastasis (t=-20.506, P<0.001). Conclusion  In cervical cancer tissues, the expression intensity of TNF-α and TNFR1 increased abnormally, while TNFR2 did not change significantly. The expressions of TNF-α and TNFR1 are positively correlated with the malignancy of cervical cancer. They are potential signals of cervical cancer and are expected to become new therapeutic targets. However, the activation of TNFR2 to downstream signaling pathway is significantly weaker than that of TNFR1. Related Articles | Metrics

Clinic observation of bone metastasis treated with apatinib combined with radiotherapy Han Tingting， Shi Mingwei， Wu Liming， Wang Yingjie， Wang Fan 2018, 45 (7):  419-422.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.007 Abstract ( 619 )   PDF (833KB) ( 578 )   Save Objective  To evaluate the clinical efficacy and safety of apatinib combined with radiotherapy in patients with bone metastasis. Methods  Thirty-one patients admitted to Radiation Oncology of the First Affiliated Hospital of Anhui Medical University with bone metastasis were recruited from April 2016 to February 2017. All patients were received apatinib 500 mg/d orally combined with radiotherapy (30~40 Gy/10~20 F) until disease progression or intolerable toxicity occurred. Clinical efficacy and safety were observed. Results  The total response rate was 93.55% (29/31), 25.81% (8/31) had complete response, 58.06% (18/31) had moderate response, 9.68% (3/31) had mild response,  and 6.45% (2/31) had no response; The time to exert its effect after the treatment was 6 days, and its median maintenance time was 7 months. The lesions complete response was 3.23% (1/31), partial response was 51.61% (16/31), became stable in 13 patients (41.94%), and deteriorated in 1 patient (3.23%), and the total control rate was 96.78%. The patients Karnofsky score increased obviously after the treatment (83.71±5.77 vs. 78.87±7.49), and the difference was statistically significant (t=4.23, P=0.006). The median local progressionfree survival and median overall survival  were 6 months and 7 months, respectively. The main adverse reactions were hypertension, hand-foot syndrome， proteinuria and bone marrow depression. The rates of hypertension, hand-foot syndrome, proteinuria and bone marrow depression were 35.48% (11/31), 25.81% (8/31), 16.13% (5/31), and 16.13% (5/31), respectively. Conclusion  Radiotherapy combined with apatinib is effective and tolerable for bone metastasis patients. Related Articles | Metrics

Beta 2-microglobulin and tumors Wang Juan, Zhong Chunsheng, Zhang Chaoyang 2018, 45 (7):  423-426.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.008 Abstract ( 816 )   PDF (653KB) ( 887 )   Save Beta 2-microglobulin (β2-MG) has low expression levels in tissues and cells of normal organisms, but its expression levels is increasing in tumor. The main function of β2-MG is to regulate signal transduction in tumor cells and promote tumor cell growth and angiogenesis. High level expression of β2-MG is associated with the occurrence, progression, metastasis and prognosis of human tumors and can serve as an independent indicator of tumor prognosis. It has been confirmed in a variety of tumor cells that agent targeting β2-MG is expected to become a new generation of targeted drugs. Related Articles | Metrics

Role of tumor-derived exosomes in tumor metastasis Dong Haiyan, Pang Xiaoyan, Dou Lei, Li Fengxin, Tian Dongli, Zhang Yi 2018, 45 (7):  427-431.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.009 Abstract ( 574 )   PDF (654KB) ( 684 )   Save Tumor-derived exosomes (TEXs) are small membrane vesicles secreted by tumor cells. They contain various proteins and RNA which make they serve as functional mediators in cell interaction. TEXs can alter the components of extracellular matrix and induces epithelial-mesenchymal transition of tumor cells, which enhance the invasiveness of tumor cells. TEXs regulate immunity through multiple pathways, allowing circulating tumor cells to escape immune surveillance. TEXs promote premetastatic microenvironment in target organ before metastasis and induce angiogenesis after circulating tumor cells colonization. Understanding the role and mechanism of TEXs in this process can effectively block relevant signaling pathways which may provide new targeted therapies for clinic. Related Articles | Metrics

Research progress of interferon induced glioma cell apoptosis Lu Di, Zhang Jundong, Guo Geng, Wang Xiaogang 2018, 45 (7):  432-435.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.010 Abstract ( 410 )   PDF (654KB) ( 412 )   Save Glioma is a central nervous system tumor, which originates neuroderm and expresses the high malignant degree. Due to the particularity of the usual location, it makes the treatment of glioma difficult to achieve the desired effect. Interferon is a kind of important cytokines, and it has some biological characteristics, such as inducing apoptosis, inhibiting of tumor growth, and pathological angiogenesis, regulating immune function and so on. Studies have shown that there are many key molecules in the interferon signaling pathways, and these molecules play an important role in the occurrence and development of glioma cell apoptosis. Explore the key molecules and its mechanism of action in the process of Interferon inducing glioma, which may provide new clinical strategies for diagnosis and treatment of glioma. Related Articles | Metrics

Roles of physical therapies in chemosensitization of non-small cell lung cancer Liang Heng, Li Liya 2018, 45 (7):  436-439.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.011 Abstract ( 376 )   PDF (652KB) ( 623 )   Save Chemotherapy is an important treatment of non-small cell lung cancer (NSCLC), the efficiency of chemotherapy directly affects the survival rate and living quality of patients. Studies show that physical therapies such as hyperthermia, tumor treating fields, alternating microcurrent, hyperbaric oxygen treatment and photodynamic therapy play chemosensitization effects in NSCLC by means of improving the concentrations of chemotherapeutic agents in tumor cells, promoting tumor cell apoptosis, inhibiting the expressions of multidrug resistance gene and protein and other ways. Related Articles | Metrics

Application of methylation detection of SEPT9 gene in early diagnosis of colorectal cancer Dai Chunyang, Li Ming 2018, 45 (7):  440-443.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.012 Abstract ( 653 )   PDF (712KB) ( 745 )   Save SEPT9 gene belongs to a member of SEPT gene family. In recent years, it has been found that SEPT9 gene is highly methylated in colorectal cancer cells. Detecting SEPT9 gene methylation in the development of colorectal cancer, the application of different specimen types for the detection of SEPT9 gene methylation and the development of SEPT9 gene methylation detection methods can provide evidence for early diagnosis of colorectal cancer. Related Articles | Metrics

Drug resistance mechanism and treatment strategy for targeted therapy of melanoma Jin Lan, Kang Xiaojing 2018, 45 (7):  444-448.  doi: 10.3760/cma.j.issn.1673-422X.2018.07.013 Abstract ( 744 )   PDF (662KB) ( 1308 )   Save Drug resistance of targeted therapy gradually emerges in the treatment of melanoma. Currently known mechanisms of drug resistance include reactivation of mitogenactivated protein kinase (MAPK) pathway, activation of MAPK alternative pathway, effects of tumor microenvironment, and abnormal expression of microRNA. Through the combination of targeted drugs, immunological combination therapy and other strategies can delay the occurrence of drug resistance, thereby prolonging the survival of patients. Related Articles | Metrics