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08 June 2019, Volume 46 Issue 6 Previous Issue    Next Issue

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Effects of microRNA-424-5p on proliferation, migration and invasion of colorectal cancer cells by regulating OTX1 Yu Kun, Wang Weiya, Cai Xinyi, Cheng Xianshuo, Zhao Xiaofeng, Bie Yaqin, Li Qiang 2019, 46 (6):  321-326.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.001 Abstract ( 483 )   PDF (1259KB) ( 612 )   Save Objective  To investigate the correlation of the expression of microRNA-424-5p (miR-424-5p) and orthodenticle homeobox 1 (OTX1) gene in colorectal cancer (CRC) tissue, and the effects of miR-424-5p on the proliferation, migration and invasion of CRC cells HCT116. Methods  A total of 60 patients with CRC were collected from June 2017 to June 2018 in Department of Colorectal Surgery of Third Affiliated Hospital of Kunming Medical University. Real time quantitative PCR (RTqPCR) was used to detect the expression of miR-424-5p and OTX1 mRNA in 60 cases of CRC tissues, paracarcinoma tissues and CRC cell lines. The correlation between the expression of miR-424-5p and OTX1 gene was further analyzed. miR-NC (miR-NC group) and miR-424-5p-mimic (miR-424-5pmimic group) were transfected into HCT116 cells. CCK-8 assay, scratch assay and Transwell assay were used to detect the effects of miR-424-5p on the proliferation, migration and invasion of HCT116 cells. The effect of miR-424-5p on the expression of OTX1 protein was detected by Western blotting. The luciferase report assay was used to detect the influence of miR-424-5p on the luciferase activity of OTX1-3′UTR vector. ResultsThe relative expressions of OTX1 mRNA in CRC tissues and paracarcinoma tissues were 1.049±0.446 and 0.639±0.178 (t=－6.583, P<0.001); and the relative expression of miR-424-5p in CRC tissues and para-carcinoma tissues were 0.865±0.261 and 1.329±0.387 (t=7.705, P<0.001), with statistically significant differences. Negative correlation was found between the expression of miR-424-5p and OTX1 mRNA in CRC tissues (r=－0.439, P=0.015). The absorbance values of HCT116 cells transfected with miR-424-5pmimic were 0.813±0.064, 0.960±0.098, 1.287±0.192 on 72, 96 and 120 hours respectively, and those of HCT116 cells transfected with miR-NC were 1.163±0.158, 1.645±0.117 and 2.043±0.236. The proliferation ability of miR-424-5pmimic group was lower than that of miR-NC group and the differences between the two groups were statistically significant (t=3.538, P=0.024; t=7.778, P=0.001; t=4.257, P=0.013). The scratch assay showed that the migration of HCT116 cells in miR-424-5pmimic group was inhibited as compared with miR-NC group. The numbers of cells permeating septum of miR-NC and miR-424-5pmimic group were 177.104±17.834 and 35.667±13.634, and the difference was statistically significant (t=15.246, P<0.001). The relative expressions of OTX1 protein in miR-NC and miR-424-5p-mimic group were 0.862±0.121 and 0.342±0.103 respectively, and the difference was statistically significant (t＝16.286, P<0.001). Luciferase report assay showed that the luciferase activities of wt-OTX1-3′UTR and mut-OTX1-3′UTR vector were 0.305±0.095 and 0.898±0.080 after over expression of miR-424-5p, and the difference was statistically significant (P<0.001). Conclusion  The expressions of miR-424-5p and OTX1 mRNA are negatively correlated in CRC tissue. miR-424-5p can inhibit the proliferation, migration and invasion of CRC cells by down-regulating the expression of OTX1. References | Related Articles | Metrics

Observation of efficacy of paclitaxel with concurrent radiotherapy in the treatment for nasopharyngeal carcinoma patients with liver metastasis Zhou Ping, Chen Weisi, Zhang Shuang, Lin Bing, Pan Tao, Liu Sha 2019, 46 (6):  327-330.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.002 Abstract ( 605 )   PDF (694KB) ( 578 )   Save Objective  To investigate the efficacy, prognosis and safety of weekly paclitaxel with concurrent radiotherapy in nasopharyngeal carcinoma (NPC) patients with multiple liver metastases. Methods  A total of 64 NPC patients with multiple liver metastases in First Affiliated Hospital of Hainan Medical University between January 2016 and January 2018 were recruited and randomly divided into experimental group (n=32) and control group (n=32) by the method of random number table. The patients in the two groups were given palliative radiotherapy with a median dose of 30 Gy. The experimental group used weekly paclitaxel (40 mg/m2) concurrent chemotherapy, cisplatin (40 mg/m2) in the control group. Paclitaxel and cisplatin were used weekly until the end of radiotherapy. The clinical efficacy and adverse effects between the two groups were compared. Results  During the followup, 1 patient was lost to followup in the experimental group, complete remission (CR) in 6 cases (19.4%), partial remission (PR) in 9 cases (29.0%), stable disease (SD) in 7 cases (22.6%) and progressive disease (PD) in 9 cases (29.0%); 2 patients were lost to followup in the control group, CR in 4 cases (13.4%), PR in 10 cases (33.3%), SD in 9 cases (30.0%) and PD in 7 cases (23.3%). There was no significant difference between the two groups (Z=-0.060, P=0.952). The effective rates of the experimental group and the control group were 48.4% (15/31) and 46.7% (14/30) respectively, and the difference was not statistically significant (χ2=0.018, P=0.893); the tumor control rates were 71.0% (22/31) and 76.7% (23/30), with no statistically significant difference (χ2=0.256, P=0.613). The median survival time of the experimental group and the control group were 9.4 months and 8.9 months respectively, and the 1year survival rates were 14.5% and 10.0%, with no significant difference (χ2=1.136, P=0.286). Among the adverse effects, the incidence rates of allergic reaction, neurotoxicity and cardiovascular toxicity in the experimental group were higher than those in the control group ［18.8% (6/32) vs. 3.1% (1/32), 28.1% (9/32) vs. 15.6% (5/32), 31.3% (10/32) vs. 15.6% (5/32)］, with no significant differences (χ2=2.566, P=0.109; χ2=1.463, P=0.226; χ2=2.177, P=0.140). The incidence rates of granulocyte decline, platelet decline, red blood cell decline, and impaired liver and kidney function in the experimental group were lower than those in the control group ［56.3% (18/32) vs. 68.8% (22/32), 12.5% (4/32) vs. 21.9% (7/32), 15.6% (5/32) vs. 25.0% (8/32), 21.9% (7/32) vs. 28.1% (9/32)］, with no significant differences (χ2=1.067, P=0.302; χ2=0.988, P=0.320; χ2=0.868, P=0.351; χ2=0.333, P=0.564). The incidence rates of nausea and vomiting was lower than that in the control group ［(40.6% (13/32) vs. 78.1% (25/32)］, with a significant difference (χ2=9.328, P=0.002). Conclusion  Weekly paclitaxel with concurrent radiotherapy has equivalent efficacy to cisplatin and the adverse effects can be tolerated. Related Articles | Metrics

Clinical observation of earlystage breast cancer after breastconserving surgery with hypofractionated radiotherapy Zheng Linjing, Yang Dong, Hu Bing, Dong Yinping, Sun Lijun, Xia Chongsheng, Li Baosheng, Huang Wei 2019, 46 (6):  331-336.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.003 Abstract ( 793 )   PDF (622KB) ( 616 )   Save Objective  To observe the longterm effect, adverse reaction and cosmetic outcome of early-stage breast cancer with hypofractionated whole-breast irradiation (HF-WBI) after breast-conserving surgery. Methods  A total of 206 patients with stage 0-Ⅱ breast cancer after breastconserving surgery were included in Shandong Cancer Hospital Affiliated to Shandong University from May 2014 to August 2017. According to radiotherapy fraction, patients were divided into HF-WBI group and conventional wholebreast irradiation (CF-WBI) group. In HF-WBI group, 116 patients received wholebreast radiation to 42.56 Gy in 16 fractions followed by tumor bed boost of 9 Gy in 3 fractions or 10 Gy in 5 fractions. In CF-WBI group, 90 patients received whole breast radiation to 50 Gy in 25 fractions followed by tumor bed boost of 10 Gy in 5 fractions. The 2-year local recurrence rate,  2-year  mortality rate, acute adverse reaction, late adverse reaction and cosmetic outcome of the two groups were analyzed. Results  The 2-year local recurrence rates of HF-WBI group and CF-WBI group were 0.86% (1/116) and 2.22% (2/90) respectively, and there was no significant difference between the two groups (χ2=0.049, P=0.824). The 2year mortality rates of the two groups were 0.86% (1/116) and 0 (0/90) respectively, and there was no significant difference (P>0.999). There were 108 cases (93.1%) in HF-WBI group and 84 cases (93.3%) in CF-WBI group with grade 0-1 acute dermatitis, and 8 cases (6.9%) and 6 cases (6.7%) with grade 2-3 respectively, with no statistically significant difference (χ2=0.004, P=0.948). There were 97 cases (83.6%) in HFWBI group and 79 cases (87.8%) in CFWBI group with grade 01 bone marrow suppression, and 19 cases (16.4%) and 11 cases (12.2%) with grade 2-4 respectively, with no statistically significant difference (χ2=0.704, P=0.401). In the two groups, there were 1 case (0.9%) and 3 cases (3.3%) with grade 1-2 radiation pneumonitis, and 115 cases (99.1%) and 87 cases (96.7%) with no radiation pneumonitis respectively, and the difference was not statistically significant (χ2=1.626, P=0.202). There was 1 case  (0.9%, 1.1%) with grade 1 breast edema in each group, and 115 cases (99.1%) and 89 cases (98.9%) did not occur breast edema, with no statistically significant difference (χ2=0.033, P=0.857). In the late adverse reactions, there were 5 cases (4.3%) and 3 cases (3.3%) with skin pigmentation in HFWBI group and CF-WBI group respectively. There were 2 cases (1.7%, 2.2%) with grade 1 subcutaneous tissue fibrosis in each group, and there were 1 case (0.8%) and 2 cases (2.2%) with grade 1 pulmonary fibrosis respectively. The differences between the two groups were not statistically significant （χ2=0.000, P>0.999； χ2=0.000, P＞0.999； χ2=0.049, P=0.824）. The 6month, 1-year and 2-year cosmetic outcome good rates in HF-WBI and CF-WBI group were 96.5% (111/115) and 93.3% (84/90), 92.1% (105/114) and 90.0% (81/90), 91.4% (53/58) and 87.2% (41/47) respectively. The differences between the two groups were not statistically significant (χ2=0.526, P=0.468;  χ2=0.277, P=0.599;   χ2=0.476, P=0.490). The whole course of radiotherapy time in HF-WBI group was 25 days or 29 days, which was significantly shorter than the 40 days of CF-WBI group. Conclusion  HF-WBI after breastconserving surgery has the similar longterm effect, acute and late adverse reaction and cosmetic outcome compared with CF-WBI, and the treatment time is significantly shorter. It can be further promoted as the optimal adjuvant radiotherapy for earlystage breast cancer after breastconserving surgery. Related Articles | Metrics

Application value of serum LDH in advanced non-small cell lung cancer patients treated with EGFR-TKI Zheng Liping, Chen Yidan, Zhang Nan, Quan Wen, Du Junxiang, Liang Cuiwei, Gong Wuxing 2019, 46 (6):  337-341.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.004 Abstract ( 581 )   PDF (772KB) ( 481 )   Save Objective  To investigate the value of serum lactate dehydrogenase (LDH) in advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). Methods  Pretreatment LDH level, pathological characteristic, tumor staging and treatment situation of 190 advanced NSCLC patients with EGFR sensitive mutation confirmed by pathology were retrospectively collected in Zhuhai People′s Hospital of Guangdong Provice from July 2011 to July 2015. All the patients were divided into LDH normal group (LDH≤252 U/L, n=78) and elevated group (LDH>252 U/L, n=112) according to pretreatment LDH level. Imaging evaluations of the patients were performed regularly, and the progressionfree survival (PFS) and overall survival (OS) were recorded. The survival curves were plotted by Kaplan-Meier method and survival difference between patients with different LDH level was compared by logrank test. Cox regression analysis was used to analyze prognostic factors for mortality. Results  The objective response rate of the LDH normal group was 76.9% (60/78), and the elevated group was 71.4% (80/112), with no statistically significant difference (χ2=0.716, P=0.398). The disease control rate of the LDH normal group was 89.7% (70/78), and the elevated group was 85.7% (96/112), with no statistically significant difference (χ2=0.676, P=0.411). The median PFS of the LDH normal group was 11.5 months, and the elevated group was 9.7 months (χ2=5.92, P=0.015). The median OS was 31.0 months in the LDH normal group, and 26.1 months in the elevated LDH group (χ2=4.79, P=0.029). Both PFS and OS of patients with elevated LDH were shorter than those of patients with normal LDH. Cox multivariate regression analysis showed that tumor staging (HR=1.652, 95%CI: 1.386-2.259, P=0.018), PS score (HR=2.248, 95%CI: 1.507-3.846, P<0.001), carcinoembryonic antigen (CEA) level (HR=1.250, 95%CI: 1.066-1.703, P=0.037) and LDH level (HR=1.771, 95%CI: 1.324-1.947, P=0.015) were independent prognostic factors in patients with advanced NSCLC. Conclusion  Pretreatment serum LDH can not affect the objective response rate and disease control rate of EGFR-TKI in the treatment of advanced NSCLC, but can affect the PFS and OS of patients. Pretreatment serum LDH is an independent prognostic factor. Related Articles | Metrics

Efficacy and adverse reactions of apatinib in advanced gastric cancer Dong Xiangjun, Wang Chunhui, Li Min 2019, 46 (6):  342-345.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.005 Abstract ( 946 )   PDF (606KB) ( 878 )   Save Objective  To investigate the effects and adverse reactions of apatinib in advanced gastric cancer patients. Methods  Two hundred and forty cases of advanced gastric cancer patients who had failed chemotherapy were collected from January 30, 2016 to November 1, 2017 in the First Hospital of Zibo City of Shandong Province and the Central Hospital of Zibo City of Shandong Province. All patients took oral apatinib mesylate, 850 mg/time, 1 time/d, and 28 d as 1 cycle of treatment, during which clinical efficacy, adverse reaction and progression free survival (PFS) and overall survival period (OS) were evaluated. Adopting Cox regression model to analyze risk factors of PFS and OS. Results  Of all 240 patients, no patient reached complete response (CR) standard, 25 patients (10.4%) reached partial response (PR) standard, 113 patients (47.1%) reached stable disease (SD) standard, and 102 patients (42.5%) reached progressive disease (PD) standard. Objective response rate (ORR) and disease control rate (DCR) were 10.4% (25/240) and 57.5% (138/240) respectively. When apatinib was taken as a 2nd line treatment, ORR and DCR were 62.5% (5/8) and 75.0% (6/8) respectively; as 3rd line treatment, the result came to 13.9% (20/144) and 67.4% (97/144); as 4th line treatment, it was 0 and 52.4% (33/63); as 5th line treatment, it was 0 and 8.0% (2/25). Among the various adverse effects of apatinib, the most common ones observed were skin lesion (65.8%, 158/240), fatigue (57.9%, 139/240), gastrointestinal reaction (45.4%, 109/240), and hypertension (38.8%, 93/240).Cox multivariate analysis showed that the change of treatment time (HR=5.028, 95%CI: 1.13015.771, P=0.005) and body mass index (HR=21.069, 95%CI: 4.521127.116, P＜0.001) were the independent risk factors of PFS. BMI change (HR=6.550, 95%CI: 1.08038.455, P=0.039) was independent risk factor of  OS. Conclusion  For patients with advanced gastric cancer who failed with 2nd line and above chemotherapy, oral atatinib still obtain certain DCR and survival gain. Apatinib adverse reactions are various, involving a wide range of organ systems, however are generally controllable. Related Articles | Metrics

Expression and mechanisms of long non-coding RNAs SNHG15 in cancers Li Yingying, Huang Junxing 2019, 46 (6):  346-349.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.006 Abstract ( 764 )   PDF (606KB) ( 1909 )   Save As a kind of long non-coding RNAs (lncRNAs), small nucleolar RNA host gene 15 (SNHG15) is located on chromosome 7. In recent years, studies have shown that lncRNA SNHG15 is over expressed in various types of cancers such as glioma, thyroid cancer, breast cancer, lung cancer, gastric cancer, colorectal cancer, liver cancer, renal carcinoma, pancreatic cancer, osteosarcoma, and it can promote the proliferation, invasion, metastasis of malignant tumors and lead to poor prognosis of tumor patients through different signal pathways. Related Articles | Metrics

Application of selective CDK4/6 inhibitors in solid cancers therapy Zhang Baihong, Yue Hongyun 2019, 46 (6):  350-357.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.007 Abstract ( 729 )   PDF (607KB) ( 683 )   Save Cyclin-dependent kinase (CDK) inhibitors have been approved for the treatment of ER+/HER2- advanced breast cancer, and preclinical study and clinical trials are under way for multiple solid cancers. CDK4/6 inhibitors have shown good efficacy for human solid cancers, and it′s future development direction are  biomarkers, drug resistance and combined therapy in the future. Related Articles | Metrics

Profile of gene mutations and targeted treatment of brain metastases in breast cancer Yi Zongbi, Ma Fei, Xu Binghe 2019, 46 (6):  354-357.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.008 Abstract ( 1043 )   PDF (606KB) ( 869 )   Save Brain metastasis (BM) is considered one of the major causes of mortality in breast cancer patients. BM develops more frequently in triplenegative breast cancer and human epidermal growth factor receptor 2 (HER2)positive breast cancers, while the incidence of BM in hormone receptor positive is much lower. Mutations and expression of BM of breast cancer are differ from their primary tumors. Importantly, some therapeutic actionable mutations can be present in the BM while not in the primary tumors. Current targeted therapeutics in BM of breast cancers are limited, and drugs used have proven effects on the primary tumors but lack specificity for the BM. The identification of genomic and expressional alterations specific to BM are crucial to the development of BM specific targeted therapies. Related Articles | Metrics

Mechanism study of cancer-associated fibroblasts and clinical application in breast cancer Ye Jiahui, Zhang Weijie 2019, 46 (6):  358-361.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.009 Abstract ( 599 )   PDF (604KB) ( 799 )   Save The occurrence and development of breast cancer is a complex process which referring to multifactor interaction. During this process, cancerassociated fibroblasts (CAFs) secrect various growth factors and cytokines to promote the tumor progression, angiogenesis, metastasis, drug resistance. Meanwhile, it can also judge the prognosis of patients through the expression of CAFs. CAFs may offer a new therapeutic strategy against breast cancer. Related Articles | Metrics

Research progress of cancer stem cells in triplenegative breast cancer Kang Ye, Li Jianyi, Yang Xianghong 2019, 46 (6):  362-365.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.010 Abstract ( 738 )   PDF (609KB) ( 552 )   Save There are abundant cancer stem cells (CSCs) in triplenegative breast cancer (TNBC). CSCs can maintain their phenotype by unique molecular mechanism and tumor microenvironment, and can promote the chemotherapy resistance and recurrence of TNBC. Blocking these key molecules or altering tumor microenvironment can reduce CSCs, and then inhibited cancer growth and reverse chemotherapy resistance of TNBC. Related Articles | Metrics

Expression of DLL3 in small cell lung cancer and its application in targeted therapy Zuo Hao, Li Na, Chen Luojun, Liu Huali, Song Qibin 2019, 46 (6):  366-369.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.011 Abstract ( 1099 )   PDF (607KB) ( 868 )   Save Small cell lung cancer (SCLC) has a poor biological behavior, high probability of recurrence and metastasis, and limited treatment. The Notch signaling pathway is an evolutionarily conserved pathway that regulates the growth of many cell types through local cellcell interactions. It controls the differentiation, proliferation and survival of cells. As a ligand for the Notch pathway, deltalike protein 3 (DLL3) is highly expressed on the membrane of SCLC cells. DLL3 plays an important role in cancer initiation and epithelial mesenchymal transition, invasion and metastasis of SCLC. Rovalpituzumab tesirine is a conjugate of directed against DLL3, which shows great potential for SCLC therapy. Related Articles | Metrics

Application of functional imaging technology in radiotherapy for lung cancer Hao Meili, Sun Li, Ding Xiao, Lu Haijun 2019, 46 (6):  370-373.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.012 Abstract ( 604 )   PDF (604KB) ( 568 )   Save Functional imaging plays an important role in lung cancer radiotherapy. Functional imaging techniques include single photon emission computed tomography, positron emission tomography, magnetic resonance imaging, and computed tomography. Using lung function information provided by these techniques for lung cancer radiotherapy can better protect the normal function of lung tissue, optimize the radiotherapy program, and reduce the incidence of radiation pneumonitis. With the development of perfusion and imaging technology, functional imaging technology is expected to be widely used in the precise radiotherapy of lung cancer in the future. Related Articles | Metrics

Application of metronomic chemotherapy in the treatment of advanced nonsmall cell lung cancer Zhu Qingqing, Xie Chao, Song Bao, Zhang Qiujing, Liu Jie 2019, 46 (6):  374-377.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.013 Abstract ( 724 )   PDF (605KB) ( 614 )   Save Metronomic chemotherapy is a brandnew and multitarget chemotherapy strategy. Totally different from the traditional chemotherapy, metronomic chemotherapy can exert synergistic and durable antitumor effects via multiple mechanisms, including cytotoxic effect, antiangiogenesis, immune regulation and so on. Single and combined therapy modes of metronomic oral vinorelbine have good curative effects and safeties for the treatment of advanced nonsmall cell lung cancer. With the indepth understanding of metronomic chemotherapy, it will certainly become an important treatment mode for advanced nonsmall cell lung cancer. Related Articles | Metrics

Research progress on exosomederived noncoding RNAs in liquid biopsy of hepatocelluar carcinoma Zhang Fangyong, Wu Fan 2019, 46 (6):  378-381.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.014 Abstract ( 576 )   PDF (603KB) ( 736 )   Save Exosomes contain ample non-coding RNAs， which mainly function as regulating gene expression and play key roles in the occurrence and development of hepatocellular carcinoma. Exosomal non-coding RNAs are expected to become a new biopsy marker for hepatocellular carcinoma, providing a new means for early diagnosis and early treatment of hepatocellular carcinoma.Although the clinical application of exosomal noncoding RNAs is still insufficient at present, exosomal noncoding RNAs will play an increasingly important role in the diagnosis, personalized treatment and prognosis evaluation of hepatocellular carcinoma with the deepening of research. References | Related Articles | Metrics

Application of circular RNAs in colorectal cancer Yang Guodong, Yang Jiyuan 2019, 46 (6):  382-384.  doi: 10.3760/cma.j.issn.1673-422X.2019.06.015 Abstract ( 617 )   PDF (596KB) ( 549 )   Save The occurrence and development of colorectal cancer are regulated by many factors and  circular RNAs are also  involved. The studies have shown that some circular RNAs have high sensitivity and specificity in the diagnosis of colorectal cancer, and have a certain promoting effect on liver and lung metastasis of colorectal cancer involved in signal transduction, DNA repair. The expressions of some circular RNAs  are related to the survival time of patients. In addition, downregulation of partial circular RNAs enhances radiosensitivity of colorectal cancer cells and participates in a variety of tumorassociated signaling pathways in chemotherapeuticresistant colorectal cancer cells Related Articles | Metrics