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08 September 2017, Volume 44 Issue 9 Previous Issue    Next Issue

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Effects and mechanism of overexpression of Mfn2 gene on photodynamic therapy sensitivity of T47D cells in human breast cancer QIU Mei-Qing, WANG Tao, TONG Zhong-Sheng, JIA Yong-Sheng 2017, 44 (8):  641-646.  doi: 10.3760/cma.j.issn.1673422X.2017.09.001 Abstract ( 365 )   PDF (2329KB) ( 708 )   Save ObjectiveTo investigate the effects and possible mechanisms of Mfn2 gene overexpression on photodynamic therapy (PDT) sensitivity of T47D cells in human breast cancer. MethodspEGFP and pEGFPMfn2 were transfected into human breast cancer T47D cells, and then the mRNA and protein expression of Mfn2 gene in T47D cells were detected by realtime PCR (RTPCR) and Western blotting in pEGFP group and EGFPMfn2 group, respectively. After pEGFP and pEGFPMfn2 were transfected into human breast cancer T47D cells for 48 hours, methyl thiazolil tetracolium (MTT) assay was used to measure the PDT sensitivity of T47D cells in human breast cancer in pEGFP group and pEGFPMfn2 group. pEGFP+PDT group and pEGFPMfn2+PDT group were obtained by PDT irradiating pEGFP and pEGFPMfn2 which were transfected into human breast cancer T47D cells. Cell apoptosis and mitochondrial membrane potential of T47D cells were assayed by flow cytometry in pEGFP+PDT group and pEGFPMfn2+PDT group. Laser scanning confocal fluorescence microscope was applied to observe the morphological ultrastructure of mitochondria in pEGFP group, pEGFPMfn2 group, pEGFP+PDT group, and pEGFPMfn2+PDT group. ResultsRTPCR showed that after transfecting T47D cells with pEGFP, the expression of Mfn2 mRNA was 1.01±0.12. After transfecting T47D cells with pEGFPMfn2, the expression of Mfn2 mRNA was 1 067.00±41.72. There was statistical significance （t=67.541,P＜0.001）. Western blotting revealed that compared with the pEGFP group, the pEGFPMfn2 transfection group had higher expression of Mfn2 gene in T47D cells. MTT assay showed that pEGFPMfn2 transfection significantly enhanced the PDT sensitivity of T47D cells in human breast cancer compared with the pEGFP+PDT group. When the concentration of methylene blue was 5.00 μmol/ml, the survival rate of the pEGFP+PDT group and pEGFPMfn2+PDT group were (59.96%±1.21%) vs.(46.50%±1.72%), with significant difference （t=34.403, P＜0.001）. Flow cytometry assay showed that the cell apoptosis rates in pEGFPMfn2+PDT group was markedly higher compared with the pEGFP+PDT group ［(81.21±2.13)% vs. (68.82±2.64)%, P=0.024］, with statistical significance. Also, the mitochondrial membrane potential was obviously lower in pEGFPMfn2+PDT group  compared with the pEGFP+PDT group ［(1.37±0.12)% vs. (23.33±1.86)%,P＜0.001］, with statistical significance. Laser scanning confocal fluorescence microscope showed that cells in pEGFP group showed network structure, both pEGFPMfn2 group and pEGFP+PDT group could cause mitochondrial fusion, and the pEGFPMfn2+PDT group could induce mitochondrial disintegration and lose its normal morphology completely. ConclusionMfn2 may enhance the PDT sensitivity of T47D cells in human breast cancer, which is possibly related with the normal morphology alteration of mitochondria and the inducement of mitochondrial apoptosis. Related Articles | Metrics

Polyphyllin D inhibits proliferation of K562 on human leukemia cells by inducing apoptosis and differentiation CAI Hong, YANG Chun-Hui 2017, 44 (8):  647-651.  doi: 10.3760/cma.j.issn.1673422X.2017.09.002 Abstract ( 355 )   PDF (1372KB) ( 677 )   Save ObjectiveTo investigate the inhibitory effect of polyphyllin D on the proliferation of human chronic myelogenous leukemia (CML) cell line K562 cells and its mechanism. MethodsMethyl thiazolyl thiazolium (MTT) assay was used to evaluate the inhibition effect of polyphyllin D on the proliferation of K562 cells. Flow cytometry was used to determine the effect of polyphyllin D on the apoptosis of K562 cells. The related proteins were analyzed by Western blotting. ResultsThe MTT assay showed that polyphyllin D obviously inhibited the growth of K562 cells. The hemiinhibitory concentration (IC50) of 24 hours for the K562 cells was (0.8±0.1)μmol/L. Flow cytometric results demonstrated that polyphyllin D significantly induced apoptosis in a dosedependent manner, and the apoptosis rates of 0, 0.4, 0.8, 1.2 μmol/L polyphyllin D were (1.73±0.33)%, (14.47±2.57)%, (24.10±3.52)%, (31.51±4.09)% after 24 hours, with a significant difference (F=58.231, P＜0.001). Western blotting showed that polyphyllin D significantly downregulated the expression of Bcl2, and this was accompanied by upregulation of Bax, decrease of the Bcl2/Bax ratio, upregulation of cytochrome c and activation of caspase3. Otherwise, polyphyllin D obviously induced monocyte differentiation by increasing CD14 expression on the surface of K562 cells. ConclusionPolyphyllin D can significantly inhibit the proliferation of K562 cells, and the mechanism may be realized by inducing apoptosis and promoting monocyte differentiation. Related Articles | Metrics

Expression and clinical significance of long non-coding RNA SBF2-AS1 in nonsmall cell lung cancer PENG Qi, CHEN Fu-Ping, DANG Xiao-Min 2017, 44 (8):  652-655.  doi: 10.3760/cma.j.issn.1673422X.2017.09.003 Abstract ( 449 )   PDF (927KB) ( 606 )   Save ObjectiveTo investigate the expression and clinical significance of long noncoding RNA SBF2AS1 (SBF2 antisense RNA 1) in nonsmall cell lung cancer (NSCLC). MethodsRealtime quantitative polymerase chain reaction (qRTPCR) was used to detect SBF2AS1 expressions in 114 cases of NSCLC tissues and the adjacent normal tissues to analyze its relationship with clinicpathological characteristics, diagnostic value and prognosis in NSCLC. Results SBF2AS1 expression was significantly higher in the NSCLC (4.336±0.032) compared with the adjacent normal tissues (1.256±0.021), with a significant difference (t=3.594, P=0.005). The expression of SBF2AS1 was related with tumor size (χ2=13.072, P=0.001), lymphatic metastasis (χ2=6.896, P=0.009), TNM stage (χ2=8.566, P=0.003), smoking history (χ2=8.769, P=0.003) and infiltration degree (χ2=17.852, P=0.001), but was not related with age (χ2=0.141, P=0.707), sex (χ2=0.036, P=0.850) and pathological type (χ2=1.267, P=0.260). The area under the receiver operating characteristic (ROC) curve was 0.853 (95%CI: 0.7550.879, P=0.004). The sensitivity and specificity was 52.4% and 87.8%, respectively. The difference betwen low SBF2AS1 expression and high SBF2AS1 expression groups was statistically significant in overall survival time (42.3 months vs. 25.2 months, χ2=4.753, P=0.013). ConclusionThe expression of SBF2AS1 is upregulated in NSCLC and may be proved useful as a biomarker and diagnostic target for the treatment of patients with NSCLC. Related Articles | Metrics

Analysis of effectiveness of tyrosine kinase inhibitors in nonsmall cell lung cancer patients with epidermal growth factor receptor double mutations containing rare mutations WENG Yi-Ming, PENG Min, SONG Qi-Bin 2017, 44 (8):  656-661.  doi: 10.3760/cma.j.issn.1673422X.2017.09.004 Abstract ( 589 )   PDF (710KB) ( 1546 )   Save ObjectiveTo explore the effectiveness of epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors (TKIs) in nonsmall cell lung cancer (NSCLC) patients with EGFR double mutations containing rare mutations. MethodsFrom March 2007 to January 2017, NSCLC patients with EGFR double mutations containing rare mutations confirmed by histopathology and EGFR mutation detections at Renmin Hospital of Wuhan University, Zhongnan Hospital of Wuhan University and Hubei Cancer Hospital were enrolled. According to the mutation types, patients were divided into double activating mutations group and activating mutations with insensitive mutations group. The effectiveness of TKIs in NSCLC patients with EGFR double mutations containing rare mutations and different mutation types was analysis. ResultsAmong the 2 637 NSCLC patients underwent EGFR mutation detections, 19 patients were confirmed as EGFR double mutations containing rare mutations. Fifteen patients received EGFRTKIs therapy, the objective response rate (ORR), disease control rate (DCR) and median progression free survival (PFS) were 46.7% (7/15), 73.3% (11/15) and 8.1 months, respectively. In patients with double activating mutations, two patients had partial response (PR), one patient had a stable disease (SD). In the activating mutations with insensitive mutations group, five patients had PR, three patients had SD, four patients had no effect. ConclusionPatients with EGFR double mutations containing rare mutations have a general response to EGFRTKIs, and this result can provide a reference for the treatment of those patients. Related Articles | Metrics

Relationship between the decrease of serum level of carcinoembryonic antigen during perioperative period and the prognosis in patients with colon cancer HUANG Jiang, ZHANG Sheng-Jun, BAI Li-Jie, CHANG Qi 2017, 44 (8):  662-667.  doi: 10.3760/cma.j.issn.1673422X.2017.09.005 Abstract ( 1029 )   PDF (766KB) ( 948 )   Save ObjectiveTo evaluate the association between the decrease of the perioperative serum carcinoembryonic antigen (CEA) level during perioperative period and the prognosis in patients with colon cancer after a curative resection. MethodsRetrospective analysis was conducted to evaluate the relationship between preoperative serum CEA level and different clinicopathologic features in 605 cases who underwent a curative resection for colon cancer from January 2006 to April 2011. According to the preoperative serum CEA level, the patients were divided into two groups: ≤5 ng/ml and  >5 ng/ml group. The critical value of the CEA decreasing rate in preoperative serum CEA >5 ng/ml group was calculated, and the relationship between this critical value and survival rate was then analyzed. Univariate and multivariate models were used to detect the risk factors of overall survival rate (OS) and disease free survival (DFS) in preoperative serum CEA >5 ng/ml patients.  ResultsThe preoperative serum CEA levels were significantly associated with lymphatic invasion (χ2=14.122, P＜0.001), T stages (χ2=40.153, P<0.001), N stages (χ2=22.721, P<0.001) and pathological stages (χ2=38.576, P<0.001), except for sex (χ2=0.453, P=0.501), age (χ2=0.195, P=0.659) and histological stages (χ2=6.135, P=0.112). The critical values of CEA decreasing rate for OS and DFS were 48.95% and 50.81% in preoperative serum CEA >5 ng/ml group respectively. There were significant differences of 5year OS (31.37% vs. 76.63%, χ2=43.235， P＜0.001) and 5year DFS (27.69% vs. 72.10%, χ2=55.561，P＜0.001) between patients after operation whose CEA decreasing rate were lower than critical value and those whose were higher. Univariate analysis showed that the decreasing rate of CEA was an influence factor for OS (χ2=43.235， P＜0.001) and DFS (χ2=55.561， P＜0.001) of preoperative serum CEA >5 ng/ml patients. The N stages and pathological stages were both related to OS (χ2=14.683， P＜0.001； χ2=12.295， P<0.001) and DFS (χ2=16.212， P＜0.001； χ2=13.704， P<0.001) respectively. Multivariate model showed that the decreasing rate of CEA level and N stages were both associated with OS (χ2=18.885， P＜0.001； χ2=7.523， P＜0.001) and DFS (χ2=19.275， P＜0.001； χ2=6.997， P＜0.001) of preoperative serum CEA >5 ng/ml patients. ConclusionA high decreasing rate of serum CEA level after operation in colon cancer patients who have high CEA levels before the curative resection can be a protective factor for prognosis, especially when the decreasing rate is higher than the critical value. Related Articles | Metrics

Expressions and clinical significance of pAkt1 and hTERT in epithelial ovarian carcinoma LIU Ze-Ye, HU Jing, FENG Yu-Huan 2017, 44 (8):  668-671.  doi: 10.3760/cma.j.issn.1673422X.2017.09.006 Abstract ( 447 )   PDF (1150KB) ( 662 )   Save ObjectiveTo evaluate the expressions and prognostic significance of phosphorylation of protein kinase B1 (pAkt1) and human telomere reverse transcriptase (hTERT) in epithelial ovarian carcinoma. MethodsThe expressions of pAkt1 and hTERT were examined by immunohistochemical SP method in 72 cases of epithelial ovarian carcinoma and 10 normal endometrial tissues to analyze the correlation between pAkt1 and hTERT and their relationships with clinicpathological features and prognosis. ResultsThe positive expression rate of pAkt1 in epithelial ovarian carcinoma was 73.6%, and the positive expression rate of hTERT was 56.9%， compared with normal ovarian tissues, with statistical significance (χ2=20.814, P<0.001; χ2=11.389, P<0.001).The expression of pAkt1 was not associated with hTERT expression (r=0.075, P=0.532) in epithelial ovarian carcinoma. The expressions of pAkt1 and hTERT in epithelial ovarian carcinoma were correlated with tumor differentiation status (χ2=6.475, P=0.011; χ2=1.370, P=0.001). The diseasefree survival of patients with pAkt1 and hTERT positive coexpression was significantly shorter than others (8.585 months vs. 11.227 months, χ2=4.361, P=0.037), but there was no significant difference in overall survival (11.107 months∶11.695 months, χ2=0.394, P=0.530). ConclusionpAkt1 and hTERT are highly expressed in epithelial ovarian carcinoma, and high  coexpression of pAkt1 and hTERT indicates poor prognosis in epithelial ovarian carcinoma. References | Related Articles | Metrics

Application of aptamer in the study of cancer stem cells PENG Yong-Hua, PENG Li, LIANG Zhi-Man, ZHANG Xing-Mei 2017, 44 (8):  672-675.  doi: 10.3760/cma.j.issn.1673422X.2017.09.007 Abstract ( 442 )   PDF (693KB) ( 753 )   Save Cancer stem cells have selfrenewal and multilineage differentiation potentials, which play important roles in tumorigenesis, metastasis, recurrence and resistance to chemical therapy and radiotherapy, and so on. It is the hotspot of tumor research recently. Aptamer is a small molecular oligonucleotide with high targeting ability and affinity, which is a new type of nucleic acid in the diagnosis and treatment of cancer. Now more and more research is being done on the aptamer is applied in the diagnosis and treatment of cancer stem cells, which provides a new research tool for the diagnosis and treatment of cancer stem cells. Related Articles | Metrics

Research advances of LINE-1 in tumor TANG Mei-Ling, WU Jian-Xin, CHANG Hui-Bo 2017, 44 (8):  676-678.  doi: 10.3760/cma.j.issn.1673422X.2017.09.008 Abstract ( 614 )   PDF (684KB) ( 791 )   Save The abnormality of long interspersed nuclear element1 (LINE1) is closely related to the occurrence and development of tumor. Overexpression of LINE1 can promote cell proliferation and affect the prognosis and metastasis of tumor. The retrotransposition and methylation status of LINE1 have potential application value in clinical diagnosis, prognosis, disease monitoring and treatment. Related Articles | Metrics

Dysbiosis of gut microbiota drives cancer development ZHANG Bai-Hong, YUE Hong-Yun 2017, 44 (8):  679-681.  doi: 10.3760/cma.j.issn.1673422X.2017.09.009 Abstract ( 377 )   PDF (688KB) ( 821 )   Save Numerous studies support the importance of gut microbiota as environment factors in the development of cancer. The mechanisms that gut microbiota drive certain cancers include impacting immunity, modulating inflammation, inducing DNA damage, producing cancer promoting metabolites and regulating signaling pathway. Microbiomebased therapies provide potential prospects for cancer treatment. Related Articles | Metrics

Anticancer properties of fenofibrate SHEN Ya-Ting, HU Duan-Min 2017, 44 (8):  682-685.  doi: 10.3760/cma.j.issn.1673422X.2017.09.010 Abstract ( 699 )   PDF (696KB) ( 1314 )   Save Fenofibrate is a common lipidlowing drug activating peroxisome proliferatoractivated receptor alpha (PPRAα). Recent studies have found that fenofibrate possesses anticancer properties. Its specific mechanisms include inhibiting cell metabolism and formation of new tumor vessels, arresting cell circle, weakening cell motility, and inducing cell apoptosis. Those properties are partly independent of PPRAα. Due to its low sideeffects, it′s hopefully to be used as an anticancer adjuvant drug. Related Articles | Metrics

Advances of therapeutic cancer vaccines ZHANG Bai-Hong, YUE Hong-Yun 2017, 44 (8):  686-688.  doi: 10.3760/cma.j.issn.1673422X.2017.09.011 Abstract ( 471 )   PDF (690KB) ( 1720 )   Save Therapeutic cancer vaccines offer a novel avenue for the development of cancer immunotherapy. Tumor antigens can induce T cell antitumor immune responses, but lack of tumorspecific antigens has hampered clinical efficacy. Vaccine types include peptide vaccines, dendritic cell vaccines and oncolytic virus vaccines. Personalizing tumor vaccines may provide a new immunotherapeutic strategy to treat cancer. Related Articles | Metrics

Molecular targeted therapy in glioblastoma Nan Yang , ZHONG Yue 2017, 44 (8):  689-692.  doi: 10.3760/cma.j.issn.1673422X.2017.09.012 Abstract ( 436 )   PDF (697KB) ( 1033 )   Save Glioblastomas is the most common malignant primary brain tumors and the prognosis is very poor. With the development of tumor molecular biology, molecular targeted therapy for glioblastomas has become an integral part of its comprehensive treatment. Targeted therapy drugs of glioblastomas are emerging, including tyrosine kinase inhibitors, histone deacetylase inhibitors, phosphatidylinositol 3kinase inhibitors, hypoxia inducible factor1α inhibitors, sodiumpotassium pump inhibitors, et al. With the development of new molecular targeted therapy, more effective or even treatment measures of glioblastomas might be found, which can provide a new approach for the individualized treatment of glioblastomas.【Key words】 Related Articles | Metrics

Progress in the treatment of nasopharyngeal carcinoma ZHANG Lei, XU Wei 2017, 44 (8):  693-695.  doi: 10.3760/cma.j.issn.1673422X.2017.09.013 Abstract ( 510 )   PDF (688KB) ( 923 )   Save Nasopharyngeal carcinoma is a common malignant tumor. The efficiency of early stage patients with radiotherapy alone can reach 90%, the locally advanced patients still need the chemoradiotherapy treatment, molecular targeted therapy, traditional Chinese medicine therapy and so on. Intensity modulated radiotherapy has prominent advantages in nasopharyngeal carcinoma, which can significantly improve the curative effect and reduce the adverse reactions and also improve the quality of life. Related Articles | Metrics

Research process of APOBEC3B in breast cancer DONG Rong-Rong, HE Xue-Xin, JI Jia-Li 2017, 44 (8):  696-699.  doi: 10.3760/cma.j.issn.1673422X.2017.09.014 Abstract ( 481 )   PDF (696KB) ( 853 )   Save APOBEC3B is one member of APOBEC with the activity of cytosine deaminase. Researches show that APOBEC3B can take park in the development and progression of breast cancer by means of mediating the genome mutations, which can promote cancer metastasis and drug resistance, thus influencing the treatment effect of patients with cancers. APOBEC3B is closely related with clinical prognosis of breast cancer, which has a potential value in the early diagnosis and biological therapy of breast cancer and provides a new hope for the treatment of breast cancer. Related Articles | Metrics

Research progress of obesity and prognosis of breast neoplasms FU Cai-Hong, ZHANG Bao-Ying, YUAN Wen-Zhen, GUAN Quan-Lin 2017, 44 (8):  700-703.  doi: 10.3760/cma.j.issn.1673422X.2017.09.015 Abstract ( 453 )   PDF (694KB) ( 767 )   Save Studies have found that obesity is not only closely related with the occurrence and development of breast cancer, but also can significantly increase the risk of breast cancer recurrence and death, especially the occurrence of postmenopausal estrogen receptor positive breast cancer. Therefore, it is of great importance to understand the influence of obesity on the prognosis of breast cancer. The intervene of diet and lifestyle, metformin and other drugs, and other obesity targeted therapies have provided direction for future research on these influence. Related Articles | Metrics

Extended endocrine therapy of breast cancer SONG Fang-Bin, XU Jun-Ming, YAO Wu 2017, 44 (8):  704-707.  doi: 10.3760/cma.j.issn.1673422X.2017.09.016 Abstract ( 557 )   PDF (699KB) ( 845 )   Save Endocrine therapy is an important treatment of estrogen receptor (ER) positive breast cancer. However, late relapse after completion of 5year adjuvant endocrine therapy is still common. Extended endocrine therapy (EET) is a promising strategy to further reduce the risk of recurrence and increase the cure rate in earlystage patients. The decisionmaking to EET should be individually implemented by weighing the risk of late recurrence, menopausal status, side effects, and patients′ preference. Future studies are still needed to identify the patients who are most likely to benefit from EET. Related Articles | Metrics

Radiotherapy for limitedstage small cell lung cancer Cheng-Guo-Wei, SUN Li 2017, 44 (8):  708-710.  doi: 10.3760/cma.j.issn.1673422X.2017.09.017 Abstract ( 390 )   PDF (686KB) ( 734 )   Save Small cell lung cancer (SCLC) presents the characteristics of high malignant degree and distant metastasis. About 25%～30% of the patients with SCLC are confirmed to be limited stage (LS) SCLC at first visit. Early chest radiotherapy should be a better option for the timing of radiotherapy for LSSCLC, EP scheme (etoposide + cisplatin) chemotherapy combined with radiotherapy is acceptable for the sequence of radiotherapy and chemotherapy. CT, MRI, PET imaging visible tumors should be considered as the radiotherapy targets. Radiation dose and segmentation methods should be improved total dose of radiation or altered fractionated radiotherapy. Prophylactic cranial irradiation can improve the 3year survive and reduce brain metastasis rate of patients with LSSCLC. Related Articles | Metrics

Prognostic index of small cell lung cancer LIU Qing-Yu, LI Xiao-Min 2017, 44 (8):  711-713.  doi: 10.3760/cma.j.issn.1673422X.2017.09.018 Abstract ( 400 )   PDF (688KB) ( 714 )   Save The expressions of related molecular marker and immunohistochemical marker of small cell lung cancer (SCLC) are closely related to the occurrence, development, treatment and prognosis of SCLC. Although the mechanisms underlying the effects of these markers on SCLC prognosis are still unclear, further studies of these markers will better guide the clinical treatment of SCLC. Related Articles | Metrics