Table of Content

08 June 2020, Volume 47 Issue 6 Previous Issue    Next Issue

For Selected:

Download Citations EndNote Reference Manager ProCite BibTeX RefWorks

Toggle Thumbnails

Expert Revle

Progress of new drugs on relapsed/refractory peripheral T-cell lymphoma Zhao Ke, Wang Huaqing 2020, 47 (6):  321-326.  doi: 10.3760/cma.j.cn371439-20200507-00029 Abstract ( 1015 )   HTML ( 35 )   PDF (741KB) ( 387 )   Save Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous diseases originating from post-thymic T-cells, with poor prognosis using traditional therapy, especially in patients with relapsed/refractory PTCLs (r/rPTCLs). In recent years, a variety of new anti-tumor drugs have emerged in the treatment of r/rPTCLs, including different types of enzyme inhibitors, monoclonal antibodies, immunomodulators and immune checkpoint inhibitors, which have been proved to be effective. The discovery and clinical application of new drugs are expected to improve the outcomes of the diseases. References | Related Articles | Metrics

Orginal Articles

Effects of lncRNA AFAP1-AS1 on proliferation and invasion of thyroid cancer cells and its mechanisms Cheng Hu, Liu Mingkui, Chen Tianping 2020, 47 (6):  327-332.  doi: 10.3760/cma.j.cn371439-20191129-00030 Abstract ( 516 )   HTML ( 13 )   PDF (1477KB) ( 318 )   Save Objective To explore the effects of long noncoding RNA (lncRNA) actinfilament-associated protein 1-antisense RNA1 (AFAP1-AS1) on proliferation and invasion of thyroid cancer cells and its mechanisms. Methods Quantitative real time fluorescence PCR (qRT-PCR) was performed to assess the expression of AFAP1-AS1 in normal thyroid cells and thyroid cancer cells. The thyroid cancer cell line WRO was divided into three groups, AFAP1-AS1 silencing group (AFAP1-AS1-siRNA group), negative control group (NT-siRNA group) and blank control group (Blank group). AFAP1-AS1-siRNA group and NT-siRNA group were transfected with AFAP1-AS1 siRNA and NT-siRNA respectively using LipofectamineTM 3000, and Blank group was treated with PBST. The proliferation ability was measured by CCK-8. The invasion ability was measured by Transwell assay. The expression levels of Rho A, Cyclin D1 and MMP-9 protein were measured by Western blotting. Results The relative expressions of AFAP1-AS1 in normal thyroid cell line FRTL-5, thyroid cancer cell lines SW579, CAL-62, FRO and WRO were 1.03±0.04, 2.95±0.17, 5.31±0.35, 7.26±0.49 and 9.67±0.53 respectively, and the difference among the five groups was statistically significant (F=16.932, P=0.027). The expression of AFAP1-AS1 was highest in WRO cells, therefore, the WRO cells were selected for subsequent experiments. The relative expressions of AFAP1-AS1 in AFAP1-AS1-siRNA group, NT-siRNA group and Blank group were 0.23±0.02, 1.02±0.04 and 1.03±0.05 respectively, and the difference among the three groups was statistically significant (F=13.590, P=0.006). Compared with NT-siRNA group, the expression of AFAP1-AS1 in AFAP1-AS1-siRNA group was significantly lower (P<0.001). The A450 values in the three groups were 0.68±0.06, 1.17±0.09, 1.22±0.09, and 0.96±0.08, 1.69±0.11, 1.72±0.12 respectively 3 and 4 days after transfection, and the differences were statistically significant (F=7.318, P=0.016; F=10.351, P=0.004). The differences between AFAP1-AS1-siRNA group and NT-siRNA group 3 and 4 days after transfection were statistically significant (P=0.043; P=0.013). The numbers of invasive cells in the three groups were 72.8±5.7, 145.6±8.9, 148.4±7.3, and the difference was statistically significant (F=37.273, P=0.034). The number of invasive cells in AFAP1-AS1-siRNA group was significantly less than that in NT-siRNA group (P=0.021). The expressions of Rho A protein in the three groups were 0.34±0.03, 1.02±0.04 and 1.04±0.03 respectively, and the difference was statistically significant (F=9.667, P=0.013). The expression of Rho A protein in AFAP1-AS1-siRNA group was significantly lower than that in NT-siRNA group (P=0.018). The expressions of Cyclin D1 protein in the three groups were 0.52±0.04, 1.03±0.02 and 1.05±0.04 respectively, with a statistically significant difference (F=15.464, P=0.010). The expression of Cyclin D1 in AFAP1-AS1-siRNA group was significantly lower than that in NT-siRNA group (P=0.023). The expressions of MMP-9 protein in the three groups were 0.42±0.04, 1.05±0.03 and 1.02±0.04 respectively, and the difference was statistically significant (F=10.328, P=0.032). The expression of MMP-9 in AFAP1-AS1-siRNA group was significantly lower than that in NT-siRNA group (P=0.035). Conclusion The silencing of lncRNA AFAP1-AS1 can inhibit the proliferation and invasion of thyroid cancer cells, and the mechanism may be related to the down-regulation of Rho A, Cyclin D1 and MMP-9 proteins. Figures and Tables | References | Related Articles | Metrics

Mechanisms of miR-103a-3p/CHI3L1 in proliferation and vascular mimicry of ovarian cancer cells Yang Lifen, Song Wei, Xu Dawei, Wu Jun, Gao Ran 2020, 47 (6):  333-339.  doi: 10.3760/cma.j.cn371439-20191224-00031 Abstract ( 562 )   HTML ( 26 )   PDF (1568KB) ( 298 )   Save Objective To investigate the mechanisms of microRNA (miR)-103a-3p/chitinase-3-like protein 1 (CHI3L1) in the proliferation and vascular mimicry of ovarian cancer cells and its effect on transforming growth factor-β (TGF-β) pathway. Methods The relationship between the expression level of miR-103a-3p and the overall survival rate of ovarian cancer patients was analyzed by bioinformatics. The human ovarian adenocarcinoma SKOV3 cells were divided into 4 groups: control group, miR-103a-3p mimic group, miR-103a-3p mimic+CHI3L1 group and CHI3L1 group. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the expression levels of miR-103a-3p, CHI3L1 mRNA and CHI3L1 protein respectively. The expression level of YKL-40 in cell culture fluid was detected by enzyme-linked immunosorbent assay. The cell viability, proliferation ability and angiogenesis ability of the 4 groups were detected by CCK-8 method, clone formation experiment and angiogenesis experiment. The dual luciferase report verified that miR-130a-3p targeted CHI3L1. Results The overall survival rate of ovarian cancer patients with high expression of miR-103a-3p was higher than that of patients with low expression of miR-103a-3p (χ 2=6.187, P=0.048). The differences in miR-103a-3p and CHI3L1 mRNA levels among the control group, miR-103a-3p mimic group, miR-103a-3p mimic+CHI3L1 group and CHI3L1 group were statistically significant (F=198.254, P<0.001; F=60.214, P<0.001), miR-103a-3p mimic group and miR-103a-3p mimic+CHI3L1 group had higher miR-103a-3p levels than the control group (all P<0.001), CHI3L1 group had higher CHI3L1 mRNA level than the control group (P<0.001). The expression levels of CHI3L1 protein in the 4 groups were 2.25±0.23, 1.19±0.12, 2.29±0.28 and 4.31±0.37, and the difference was statistically significant (F=18.675, P<0.001). The expression levels of YKL-40 in the cell culture fluids of the 4 groups were (1.84±0.20) ng/ml, (0.95±0.08) ng/ml, (2.64±0.25) ng/ml, (6.27±0.79) ng/ml, and the difference was statistically significant (F=35.297, P<0.001). The YKL-40 level of the CHI3L1 group was significantly higher than that of the control group (P<0.001), the miR-103a-3p mimic group was lower than the control group (P<0.001), and the miR-103a-3p mimic+CHI3L1 group was higher than the miR-103a-3p mimic group (P<0.001). The cell viabilities of the 4 groups were 100%±2.54%, 76.23%±2.13%, 104.89%±3.56% and 137.42%±2.80%, and the difference was statistically significant (F=23.584, P<0.001). The cell viability of the miR-103a-3p mimic group was significantly lower than that of the control group (P<0.001), the CHI3L1 group was higher than the control group (P<0.001), and the miR-103a-3p mimic+CHI3L1 group was higher than the miR-103a-3p mimic group (P<0.001). The number of clones formed in the 4 groups were 76.85±4.67, 21.56±2.85, 72.06±5.07 and 169.63±9.21, and the difference was statistically significant (F=31.541, P<0.001). The proliferation capacity of the miR-103a-3p mimic group was significantly lower than that of the control group (P<0.001), the CHI3L1 group was higher than the control group (P<0.001), and the miR-103a-3p mimic+CHI3L1 group was significantly higher than the miR-103a-3p mimic group (P<0.001). The differences in the relative tube lengths and the tube bramches of the 4 groups were both statistically significant (F=24.254, P<0.001; F=27.564, P<0.001). The differences in TGF-β and Smad levels of the 4 groups were both statistically significant (F=30.254, P<0.001; F=34.187, P<0.001). The results of dual luciferase experiments showed that compared with the NC group, the luciferase activity in cells co-transfected of miR-103a-3p and CHI3L1-wt was significantly reduced. The difference of luciferase activity between the cells transfected with NC and co-transfected with miR-103a-3p and CHI3L1-mut was not significant. Conclusion MiR-103a-3p can directly inhibit the expression of CHI3L1 and inhibit the proliferation and angiogenesis of ovarian cancer SKOV3 cells to inhibit ovarian lymphatic metastasis and distant metastasis, which may be related to the TGF-β pathway. Figures and Tables | References | Related Articles | Metrics

Role of docetaxel induced polyploid tumor cells in tumor recurrence Wang Lili, Zhao Song, Ouyang Mingyue, Xie Xiaodong, Xing Sining, Liu Shuo, Yu Huiying 2020, 47 (6):  340-345.  doi: 10.3760/cma.j.cn371439-20200103-00032 Abstract ( 531 )   HTML ( 15 )   PDF (2598KB) ( 331 )   Save Objective To study the migration of polyploid tumor cells induced by docetaxel, the characteristics of epithelial-mesenchymal transition, and the killing effect of immune cells on them, in order to explore the potential role of polyploid tumor cells in tumor recurrence. Methods The human non-small cell lung cancer A549 cells were treated with 1 μmol/L docetaxel for 24 h, and the cells were collected as Doc 1 d group. After drug removal, the cells were cultured in fresh and complete medium for 3 or 5 days, then the cells were collected as Doc 3 d group or Doc 5 d group respectively. The A549 cells were treated with DMSO for 24 h as control group. Immunofluorescence staining was used to detect cell morphology, flow cytometry was used to analyze cell ploidy, scratch test was used to detect cell migration, Western blotting was used to detect the expression of epithelial-mesenchymal transition related proteins, and lactate dehydrogenase release method was used to evaluate the killing activity of cytokine-induced killer (CIK) cells. Results Compared with the control group, most of the cells in the Doc 1 d group, Doc 3 d group and Doc 5 d group were apoptotic, a few of the surviving cells were significantly larger, and the nucleus was polynuclear. The proportions of polyploid cell subset (DNA content > 4N) in the control group, Doc 1 d group, Doc 3 d group and Doc 5 d group were (1.93±0.55)%, (22.97±2.37)%, (51.30±12.51)% and (67.87±8.31)% respectively, and the difference among the four groups was statistically significant (F=26.521, P<0.001). The proportion of polyploid cell subset in Doc 1 d group, Doc 3 d group and Doc 5 d group was significantly higher than that in the control group (all P<0.001). With the prolongation of withdrawal time, the proportion of polyploid cell subset in Doc 3 d group and Doc 5 d group was significantly higher than that in Doc 1 d group (P=0.009; P=0.004). After 24 h and 48 h culture, the wound healing rates of the control group were both 100%, and the wound healing rates of the Doc 3 d group were (39.10±2.12)% and (46.13±5.32)% respectively, with no significant difference (t=2.126, P=0.051). Compared with the control group at 24 h and 48 h, the cell migration abilities of Doc 3 d group were significantly lower (t=49.756, P<0.001; t=30.825, P<0.001). Compared with the control group, the expression of E-cadherin protein decreased gradually in the Doc 1 d group, Doc 3 d group and Doc 5 d group, the expression of Vimentin protein increased gradually, and the expressions of Snail protein and N-cadherin protein did not change significantly. The killing efficiencies of CIK cells against the cells of the control group, Doc 3 d group and Doc 5 d group were (27.27±1.91)%, (17.87±2.35)%, (9.47±0.51)% respectively, and the difference was statistically significant (F=11.294, P<0.001). The killing efficiency of Doc 3 d group and Doc 5 d group was significantly lower than that of the control group (P=0.004; P<0.001). The killing efficiency of Doc 5 d group was significantly lower than that of Doc 3 d group (P=0.003). Conclusion The migration ability of polyploid tumor cells induced by docetaxel is weakened, but epithelial-mesenchymal transition is likely to occur, and the killing effect of immune cells on them is reduced. Figures and Tables | References | Related Articles | Metrics

Analysis of prognostic risk factors of type Ⅰ endometrial cancer Zhou Luqiu, Liu Xianxi, Li Yan, Mao Xiguang 2020, 47 (6):  346-350.  doi: 10.3760/cma.j.cn371439-20191112-00033 Abstract ( 740 )   HTML ( 12 )   PDF (790KB) ( 235 )   Save Objective To study the risk factors affecting the prognosis of patients with type Ⅰ endometrial cancer. Methods A total of 279 patients with type Ⅰ endometrial cancer admitted to the First Affiliated Hospital of Southwest Medical University were enrolled from January 2010 to January 2015. The clinical data of all patients were retrospectively analyzed. The Kaplan-Meier method was used to estimate patients' survival rate. Cox regression risk model was used to analyze the risk factors that might affect the prognosis of patients with endometrial cancer. Results Of 279 patients with endometrial cancer, postoperative recurrence was observed in 36 patients. The 5-year disease free survival rate was 87.10%(243/279). The 2, 3 and 5-year survival rates were 95.9% (95%CI: 93.6%-98.3%), 94.3% (95%CI: 91.6%-97.2%), and 90.4% (95%CI: 86.6%-94.3%). Univariate analysis showed that obesity (HR=2.194, 95%CI: 1.031-4.671, P=0.041), myometrial invasion (HR=2.957, 95%CI: 1.382-6.329, P=0.005), tissue grading (G2: HR=3.271, 95%CI: 1.336-8.010, P=0.010; G3: HR=9.933, 95%CI: 3.565-27.672, P<0.001), tumor size (HR=8.067, 95%CI: 2.426-26.821, P=0.001), abdominal cytology (HR=3.293, 95%CI: 1.523-7.121, P=0.002), surgery-pathological staging (Ⅲ stage: HR=28.357, 95%CI: 11.516-69.828, P<0.001), nature of lymph node (HR=14.629, 95%CI: 5.023-42.606, P<0.001), cervical interstitial infiltration (HR=3.806, 95%CI: 1.653-8.764, P=0.002), accessory metastasis (HR=9.101, 95%CI: 3.831-21.622, P<0.001) and lymphovascular space invasion (HR=5.011, 95%CI: 2.233-11.249, P<0.001) were all correlated with the prognosis of the patients. Multivariate analysis showed that the independent risk factors for the prognosis of endometrial cancer patients were depth of myometrial invasion (HR=2.503, 95%CI: 1.115-5.616, P=0.026), histological grading (G2: HR=3.143, 95%CI: 1.205-8.198, P=0.019; G3: HR=3.655, 95%CI: 1.151-11.610, P=0.028), surgery-pathological staging (Ⅲ stage: HR=27.701, 95%CI: 9.608-79.869, P<0.001) and lymphovascular space invasion (HR=3.297, 95%CI: 1.370-7.936, P=0.008). Conclusion Obesity, myometrial invasion, tissue grading, tumor size, abdominal cytology, surgery-pathological staging, nature of lymph node, cervical interstitial infiltration, adnexal metastasis and lymphovascular space invasion all affect the prognosis of patients. Depth of myometrial invasion, histological grading, surgical-pathological staging and lymphovascular space invasion are independent risk factors for the prognosis of patients with Ⅰ endometrial cancer. Figures and Tables | References | Related Articles | Metrics

Review

CRYAB and tumors Dai Ang, Sun Qing 2020, 47 (6):  351-354.  doi: 10.3760/cma.j.cn371439-20200311-00034 Abstract ( 760 )   HTML ( 22 )   PDF (646KB) ( 340 )   Save AlphaB-crystallin (CRYAB) plays the role of molecular chaperone, it can maintain vascular endothelial growth factor levels and promote tumor neovascularization. Several recent studies indicate that CRYAB is abnormally expressed in various tumors such as breast cancer, lung cancer, colorectal cancer, and bladder cancer. It promotes tumor migration and invasion by promoting the resistance of tumor cells to apoptosis, regulating the secretion of matrix metalloproteinase and cadherin, and participating in the epithelial-mesenchymal transition process. The abnormal expression of CRYAB in tumor cells is significantly related to tumor stage, lymph node metastasis, overall survival and poor prognosis, and can be used as a new tumor marker. References | Related Articles | Metrics

Role of transmembrane proteins in malignant tumors Miao Qiuju, Xu Xiulian 2020, 47 (6):  355-359.  doi: 10.3760/cma.j.cn371439-20191227-00035 Abstract ( 998 )   HTML ( 26 )   PDF (653KB) ( 399 )   Save Transmembrane proteins (TMEMs) are a class of membrane proteins, also known as integral membrane proteins, that contain at least one transmembrane structure. A variety of membrane protein function has been found closely related to the proliferation, invasion and metastasis of malignant tumors: TMEM48, TMEM45A/B, TMEM14A, TMEM158 and TMEM206 have tumor promoting effects; TMEM25 and TMEM7 have antitumor effects; TMEM16A, TMEM17, TMEM97, TMEM88 and TMEM176 play heterogeneity roles in different tumors. These TMEMs can be used as potential prognostic indicators and new therapeutic targets. References | Related Articles | Metrics

Application of keratins in cancer diagnosis and prognosis Ren Meng, Gao Yan, Chen Qi, Yue Wentao 2020, 47 (6):  360-363.  doi: 10.3760/cma.j.cn371439-20200318-00036 Abstract ( 824 )   HTML ( 15 )   PDF (644KB) ( 358 )   Save Keratins are cytoskeleton proteins, which are involved in apoptotic resistance, growth and migration of cancer cells. The levels of some keratins are elevated in the serum of patients with cancers, or highly expressed in cancer tissues, and they are widely used in the diagnosis of tumor in clinic. The expressions of some keratins are negatively correlated with the prognosis of patients with cancers, and can be used as prognostic markers. Further clarifying the diagnostic and prognostic value of keratins combined with other markers detection can provide theoretical basis for the application of keratins in diagnosis and prognostic assessment of cancers. References | Related Articles | Metrics

Interferon-related signaling pathways and clinical application in tumor therapy Li Yuxiang, Wang Xinwen 2020, 47 (6):  364-367.  doi: 10.3760/cma.j.cn371439-20191230-00037 Abstract ( 1077 )   HTML ( 37 )   PDF (646KB) ( 524 )   Save Type Ⅰ, Ⅱ, Ⅲ interferons have anti-tumor potential, but the mechanism of action and clinical effect are different. Signaling pathways associated with interferon-treated tumors mainly include JAK-STAT, PI3K/AKT/mTOR, MAPK, NF-κB, c-Abl, etc. Type Ⅰ interferon has the widest clinical application and the most definite curative effect at present. Because of its serious adverse reaction and possible role in the process of cancer induction, type Ⅱ interferon has a great controversy on whether it can be used in anti-tumor therapy. The biological function of type Ⅲ interferon has good characteristics of type Ⅰ and Ⅱ interferon, but its anti-tumor medicinal value needs to be further evaluated. References | Related Articles | Metrics

Adaptive therapy of human cancers: targeting cancer evolution Zhang Dandan, Yue Hongyun, Zhang Baihong 2020, 47 (6):  368-371.  doi: 10.3760/cma.j.cn371439-20191202-00038 Abstract ( 771 )   HTML ( 22 )   PDF (638KB) ( 397 )   Save Cancer develops as result of evolution and targeting cancer evolution may be a promising cancer therapeutics. Cancer adaptive therapy is defined as targeting cancer evolution through selective adaption and co-evolution. Adaptive therapy of human cancers provides new insight into the strategies for adaption and integration through reprogramming the functions of vessel, immune, metabolism, microbiota and circadian clock, and facilitating hosts and their cancers evolution as a unit. References | Related Articles | Metrics

Mechanisms of ferroptosis and its significance in breast cancer therapy Xu Yiyue, Zhao Shaorong, Liu Jingjing, Zhang Jin 2020, 47 (6):  372-376.  doi: 10.3760/cma.j.cn371439-20191206-00039 Abstract ( 959 )   HTML ( 34 )   PDF (651KB) ( 642 )   Save Breast cancer is a malignant tumor originating from breast epithelial tissue. Ferroptosis is a novel type of programmed cell death which differs from apoptosis and necrosis. Research found that the accumulation of lipid peroxides in cells, a crucial process of ferroptosis, can be induced by multiple mechanisms. The ferroptosis regulation is closely related to the occurrence and development of breast cancer, and it induced by drugs is a potential and valuable research direction in breast cancer. References | Related Articles | Metrics

New progress on diagnosis and treatment of anorectal malignant melanoma Zhang Ruizhi, Chen Xin, Zhang Peng, Tao Kaixiong 2020, 47 (6):  377-380.  doi: 10.3760/cma.j.cn371439-20191216-00040 Abstract ( 570 )   HTML ( 16 )   PDF (642KB) ( 284 )   Save Anorectal malignant melanoma (ARMM) is a rare malignant melanoma arising from mucosa in anorectal area. Symptoms and signs of ARMM are not specific, causing high misdiagnosis rate in this disease. Cornerstone treatment of ARMM is radical excision. Although more systematic therapy including target therapy and immunotherapy have been applied to ARMM, as the understanding of ARMM deepens. The overall prognosis of ARMM is still poor due to the lack of accurate clinical classification and staging standards. References | Related Articles | Metrics

Application of circulating tumor DNA in targeted therapy and immunotherapy of metastatic melanoma Du Mingli, Li Guixiang, Wu Wenjuan, Zhao Lei 2020, 47 (6):  381-384.  doi: 10.3760/cma.j.cn371439-20191223-00041 Abstract ( 566 )   HTML ( 13 )   PDF (642KB) ( 199 )   Save Targeted therapy and immunotherapy are important methods for the treatment of metastatic melanoma, but monitoring the patient's disease progress and treatment response during the treatment is the key to accurate treatment and personalized treatment.Circulating tumor DNA (ctDNA) as a non-invasive "liquid biopsy" method, due to its high sensitivity and specificity for gene mutations, and the advantages of being qualitative, quantitative and traceable, which has shown great application value in monitoring metastatic melanoma progression, evaluating efficacy, and predicting prognosis during targeted therapy and immuno-therapy. References | Related Articles | Metrics