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08 May 2019, Volume 46 Issue 5 Previous Issue    Next Issue

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Curative effect observation of erlotinib plus temozolomide for recurrence/progression in patients with EGFR gene mutation in NSCLC with brain metastases after whole brain radiotherapy Yang Qiao, Liu Yao, Qiu Hui, Geng Yi, Yan Xiaohong, Hou Jie, Cui Cuihua, Dong Longke 2019, 46 (5):  257-261.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.001 Abstract ( 664 )   PDF (831KB) ( 472 )   Save Objective  To observe the clinical efficacy and safety of erlotinib plus temozolomide for recurrence/progression patients with epidermal growth factor receptor (EGFR) gene mutation in nonsmall cell lung cancer (NSCLC) with brain metastases after whole brain radiotherapy. Methods  A total of 68 EGFR gene mutation NSCLC patients with brain metastases of intracranial recurrence/progression after whole brain radiotherapy were selected from August 2013 to June 2018 in Baoji Central Hospital of Shaanxi Province and Xintai People′s Hospital of Shandong Province. All the patients were randomly divided into erlotinib group and combined treatment group (erlotinib combined with temozolomide) using random number table method. The patients in erlotinib group (34 cases) were treated with oral erlotinib 150 mg/d until progression or unacceptable adverse reaction, and the patients in combined treatment group (34 cases) were given erlotinib and oral temozolomide 150 mg/(m2·d) for 1-5 day, every 28 days was a cycle, temozolamide for 6 cycles. Comparison was made on curative effects and occurrence condition of adverse reactions between the two groups. Results  The overall response rates in the erlotinib group and combined treatment group were 11.8% (4/34) and 32.4% (11/34) respectively, and the disease control rates in the two groups were 35.3% (12/34) and 64.7% (22/34) respectively, with significant differences (χ2=4.191, P=0.041; χ2=5.882, P=0.015). The median progression-free survival in the erlotinib group and combined treatment group were 3.22 months and 5.29 months respectively, and the median overall survival in the two groups were 5.60 months and 7.90 months respectively, with significant differences (χ2=9.269, P=0.002; χ2=11.005, P=0.001). The incidence of nausea and vomiting in combined treatment group was significantly higher than that in erlotinib group ［67.6% (23/34) vs. 14.7% (5/34)］, with a significant difference (χ2=19.671, P＜0.001), but there were no significant differences in the incidences of other adverse reactions (all P＞0.05). The patients in the two groups had no more than grade Ⅲ of adverse reactions. Conclusion  The curative effect of erlotinib combined with temozolomide is better in the treatment of recurrence/progression patients with EGFR gene mutation in NSCLC with brain metastases after whole brain radiotherapy, with mild adverse reactions and good patients′ tolerance. References | Related Articles | Metrics

Curative effect analysis of 3DCRT combined with thalidomide and GEMOX regimen in advanced intrahepatic cholangiocarcinoma Zhang Yu, Xu Bin, Wang Dongmei 2019, 46 (5):  262-266.  doi: 10.3760/cma.j.issn.1673422X.2019.05.002 Abstract ( 727 )   PDF (725KB) ( 1083 )   Save Objective  To investigate the efficacy and adverse reaction of threedimensional conformal radiotherapy (3DCRT) combined with thalidomide and GEMOX regimen (gemcitabine + oxaliplatin) in patients with advanced intrahepatic cholangiocarcinoma. MethodsA total of 100 patients with advanced intrahepatic cholangiocarcinoma in 901 Hospital of Joint Logistics Support Force of Chinese People′s Liberation Army from March 2015 to June 2018 were divided into chemotherapy group (n=50) and combination group (n=50) by random number table method. The chemotherapy group was treated with thalidomide and GEMOX regimen, and the combined group was treated with 3DCRT on the basis of the chemotherapy regimen. The levels of serum tumor markers, clinical efficacy and adverse reactions of patients in the two groups were compared before and after treatment. ResultsThe levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9) in the combined group were (8.76±2.69) μg/L, (76.17±10.12)×103 U/L and (169.85±78.97)×103 U/L respectively, which were significantly lower than those of (12.46±3.47) μg/L, (104.56±14.38)×103 U/L, (312.45±71.36)×103 U/L in the chemotherapy group, with statistically  significant differences (t=5.959, P<0.001; t=11.416, P<0.001; t=9.474, P<0.001). The clinical benefit rate and the total effective rate of the combined group were respectively 64.0% (32/50) and 88.0% (44/50), which were higher than those of 42.0% (21/50) and 72.0% (36/50) in the chemotherapy group, with statistically significant differences (χ2=4.857, P=0.028; χ2=4.000, P=0.046). The incidences of leukopenia, nausea and vomiting, constipation and alopecia of patients in the combined group were 20.0% (10/50), 24.0% (12/50), 30.0% (15/50) and 12.0% (6/50) respectively, which were 14.0% (7/50), 16.0% (8/50), 24.0% (12/50) and 8.0% (4/50) respectively in the chemotherapy group, with no statistically significant differences (χ2=0.638, P=0.424; χ2=1.000, P=0.317; χ2=0.457, P=0.499; χ2=0.444, P=0.505). Conclusion 3DCRT combined with thalidomide and GEMOX regimen can significantly reduce the levels of serum tumor markers in patients with advanced intrahepatic cholangiocarcinoma, enhance the shortterm efficacy without significantly increasing and aggravating adverse reactions. References | Related Articles | Metrics

Serum levels and significances of miR-335 and miR-155 in primary gallbladder cancer Wu Tang1, Li Yingming2, Huang Congfei1, Li Xiaopei1 2019, 46 (5):  267-271.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.003 Abstract ( 620 )   PDF (753KB) ( 500 )   Save Objective To investigate the  serum levels and clinical significances of microRNA-335 (miR-335) and microRNA-155 (miR-155) in patients with primary gallbladder cancer (PCG). Methods A total of 96 PCG patients (PCG group) and 50 healthy controls (control group) admitted to the Second People′s Hospital of Hainan Province from January 2016 to October 2018 were selected. Real-time quantitative PCR (RT-PCR) was used to detect the serum levels of miR-335 and miR-155 in each group. The relationships between miR335 and miR-155 levels and clinical pathological characteristics of PCG patients were analyzed. The diagnostic value of miR-335 and miR-155 in PCG was analyzed by ROC curve. Results The serum level of miR-335 in PCG group was significantly lower than that in the control group (1.50±0.42 vs. 3.65±1.18, t=10.319, P＜0.001). The serum level of miR-155 in PCG group was significantly higher than that in the control group (3.18±0.61 vs. 0.74±0.12, t=13.627, P＜0.001). The serum levels of miR-335 and miR-155 in PCG patients were correlated with TNM stage (t=4.863, P=0.024; t=5.117, P=0.008) and lymph node metastasis (t=5.725, P＜0.001; t=6.802, P＜0.001). ROC curve analysis showed that the critical values of serum miR-335 and miR-155 for diagnosing PCG were 1.18 and 2.35, respectively. The area under the curve of the two combined diagnosis of PCG (0.920, 95%CI: 0.863-0.977) was the largest, with sensitivity and specificity of 93.8% and 85.7%. Conclusion The low serum level of miR335 and high level of miR155 are associated with the higher TNM stage and lymph node metastasis of PCG, and the combined detection of the two is helpful to improve the diagnostic rate of PCG. References | Related Articles | Metrics

Analysis of clinical efficacy and prognostic factors  of apatinib in the treatment of advanced malignant tumors Jiang Zhouna1, Zhang Jie1, Shen Qianqian1, Zhang Fang2, Lyu Wei2, Zheng Yawen2 2019, 46 (5):  272-277.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.004 Abstract ( 548 )   PDF (792KB) ( 458 )   Save Objective  To observe the clinical efficacy and safety of apatinib in the treatment of advanced malignant tumors and to analyze the prognostic indicators affecting the survival of patients. MethodsA total of 100 patients with advanced malignant tumors who were treated with apatinib at Jinan Central Hospital Affiliated to Shandong University from February 2015 to July 2018 were enrolled and their data were analyzed retrospectively. The clinical efficacy was  evaluated and the related adverse reactions were recorded. Single and multiple factor analyses were performed by Cox regression model. The predictive factors of progressionfree survival (PFS) and overall survival (OS) were analyzed. Results  One-hundred patients with advanced malignant tumors who were treated with secondline and above treatment were collected. All patients were assessable for response, no complete response was observed, 22 patients (22%) achieved   partial remission, 58 patients (58%) in  stable disease, and 20 patients (20%) appeared progressive disease. The objective response rate was 22% (22/100), the disease control rate was 80% (80/100), the median PFS was 3.6 months (95%CI: 2.74.5 months), and the median OS was 7.0 months (95%CI: 4.79.3 months). Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score (HR=0.340, 95%CI: 0.2110.546, P＜0.001), tumor  primary site  (HR=1.757, 95%CI: 1.0532.932, P=0.031), neutrophil to lymphocyte ratio (NLR) (HR=0.389, 95%CI: 0.2270.666, P=0.001), hemoglobin (HR=1.696, 95%CI: 1.0232.813, P=0.041) and proteinuria (HR=1.790, 95%CI: 1.1053.155, P=0.044)  were related to PFS; age (HR=2.082, 95%CI: 1.3203.285, P=0.002), ECOG score (HR=0.206, 95%CI: 0.1230.344, P＜0.001), tumor primary site (HR=1.784, 95%CI: 1.0772.954, P=0.025), NLR (HR=0.410, 95%CI: 0.2380.704, P=0.001), hemoglobin (HR=1.958, 95%CI: 1.1753.264, P=0.010) and albumin (HR=0.467, 95%CI: 0.2770.787, P=0.004) were related with OS. Multivariate analysis showed that PFS was related to ECOG score (HR=0.254, 95%CI: 0.1230.523, P＜0.001) and NLR (HR=0.378, 95%CI: 0.1610.888, P=0.026), and OS was related to ECOG score (HR=0.147, 95%CI: 0.0670.326, P＜0.001), NLR (HR=0.327, 95%CI: 0.1400.765, P=0.010) and hemoglobin (HR=1.975, 95%CI: 1.1013.543, P=0.022). In term of safety, the most common adverse events among 100 cases of treated patients with advanced malignant tumors  were hypertension (53, 53%), anorexia (51, 51%), fatigue (51, 51%) and anemia (50, 50%), among which the most common ones of grade 3 and 4 were hypertension (10, 10%), thrombocytopenia (8, 8%), leukopenia (7, 7%) and handfoot syndrome (6, 6%). Conclusion  Apatinib has certain clinical efficacy and manageable adverse events in the treatment of advanced malignant tumors at and above secondline treatment. ECOG score and NLR are independent predictors of PFS and OS in patients with advanced malignant tumors treated with apatinib. References | Related Articles | Metrics

Advances of homeobox gene MEOX1 in tumors Zhang Yuan, Sun Lichao 2019, 46 (5):  278-280.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.005 Abstract ( 614 )   PDF (649KB) ( 495 )   Save As a homeobox transcription factor, MEOX1 can regulate the target genes by binding the specific DNA sequence. MEOX1 not only plays essential roles in cell proliferation, migration and differentiation, but also participates in the formation of skeleton, muscle and blood vessel during embryonic development. Recent studies demonstrate that MEOX1 is over-expressed in breast cancer, lung cancer, ovarian cancer and prostate cancer tissues, which is closely associated with lymph node metastasis and poor prognosis in patients with cancer. Furthermore, MEOX1 can regulate the proliferation and migration of cancer cells, which suggests that it plays an important role in the occurrence and development of tumors. References | Related Articles | Metrics

Advances of bifunctional anti-PD-L1/TGF-β fusion protein M7824 Hu Mengxue, Xu Bin, Yu Jinming, Song Qibin 2019, 46 (5):  281-284.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.006 Abstract ( 1187 )   PDF (663KB) ( 863 )   Save With the development of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, the second generation of combined immunosuppressive agents emerge as the times require. As a bifunctional anti-PD-L1/transforming growth factor-β (TGF-β) fusion protein, M7824 can antagonize PD-L1 pathway and trap TGF-β at the same time, which can effectively enhance the immune response and reduce the occurrence of immune escape and drug resistance. The drug has achieved remarkable results in many preclinical studies, however, the indications, safety and efficacy still need to be confirmed by large-scale clinical research data. References | Related Articles | Metrics

Anti-tumor mechanism of lactoferrin Mo Xiaomei, Qin Pengfei, Zhao Na, Yan Meixing, Xu Lujie 2019, 46 (5):  285-288.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.007 Abstract ( 1173 )   PDF (658KB) ( 870 )   Save Alterations of the lactoferrin gene are associated with an increased incidence of tumor, however, the exact mechanisms involved in the antitumor activity of lactoferrin are still unclear. Several studies suggest that lactoferrin can affect the initiation and development of tumors via different mechanisms such as damaging cell membranes, inducing apoptosis, blocking cell cycle, regulating cellular immune response and inhibiting angiogenesis in different cancer cell lines. Further study about the mechanism can provide new ideas for clinical prevention and treatment of tumors. References | Related Articles | Metrics

Lysine demethylase 6 and tumors Li Longlong, Hu Kongwang 2019, 46 (5):  289-294.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.008 Abstract ( 494 )   PDF (679KB) ( 642 )   Save Lysine demethylase 6 (KDM6) is involved in the demethylation regulation of histone H3 as an important modification enzyme in epigenetic modification, and plays an important role in embryonic development, inflammation and disease development. Current researches indicate that KDM6 is involved in the occurrence and development of various tumors (pancreatic cancer, colon cancer, gastric cancer, breast cancer, bladder cancer, etc.), affects proliferation, metastasis, prognosis and chemotherapy resistance of tumors, and plays different roles due to different tumor backgrounds. References | Related Articles | Metrics

Application of the Nivolumab in the treatment of advanced non-small cell lung cancer Liu Dongqi, Chen Runze, Liu Yuhan, Zhou huan 2019, 46 (5):  295-298.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.009 Abstract ( 521 )   PDF (661KB) ( 834 )   Save Lung cancer has the highest morbidity and mortality among malignant tumors in our country. The treatment researches related to nonsmall cell lung cancer (NSCLC) such as targeted therapy and immunotherapy are the research hotspots in recent years. Nivolumab is the first programmed death-1 (PD-1) inhibitor which is allowed to enter clinical trials, and it is also the first approved drug for tumor immunotherapy in China. In June 2018, Nivolumab injection was marketed in China, and it was used in the secondline treatment for the patients with advanced NSCLC, opened up a new era of the lung cancer treatment in our country. Review the clinical research related to the Nivolumab and NSCLC, summarizing usage, dosage, adverse reactions, will provide a help for clinical application, bring more benefits for patients at the same time. References | Related Articles | Metrics

Hippo signaling pathway and colorectal cancer Gu Sijia, Sun Guozhuang, Qiao Dawei, Zhong Yi, Kong Guimei, Bu Ping 2019, 46 (5):  299-302.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.010 Abstract ( 897 )   PDF (893KB) ( 711 )   Save Hippo signaling pathway plays a significant role in the development of colorectal cancer, and acts  as an important regulatory pathway which regulates cell proliferation and cell differentiation. Multiple proteins and genes in Hippo signaling pathway, especially the downstream YAP protein, play important roles in the occurrence, metastasis, drug resistance and recurrence of colorectal cancer. YAP and other related genes can be used as targeted markers for predicting drug resistance to colorectal cancer. Hippo signaling pathway gene network can be used as targeted therapy or combination therapy, thus providing new ideas for the treatment of colorectal cancer. References | Related Articles | Metrics

Efficacy prediction and molecular mechanism of thyroid hormone levels and multi-target TKI therapy for renal cell carcinoma and hepatocellular carcinoma Sun Yueqin, Li Aimin, Luo Yue, Song Zhenghui, Zhuang Xuefen, Dai Guanqi, Liu Xinhui 2019, 46 (5):  303-306.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.011 Abstract ( 625 )   PDF (659KB) ( 453 )   Save Hypothyroidism is a common adverse reaction in clinical multi-target tyrosine kinase inhibitor  (TKI) and may be used as a predictor of efficacy of TKI drugs. Studies show that hypothyroidism is significantly associated with good prognosis in patients with renal cell carcinoma treated with multi-target TKI, which may be related to inhibition of vascular endothelial growth factor receptor pathway, potential offtarget effects and inhibition of cell proliferation. Whereas in the patients with hepatocellular carcinoma who received multi-target TKI therapy, hypothyroidism is an indicator of poor prognosis, which is related to the T3/TR pathway regulating liver cancer growth and invasion. The predictive function and mechanism of thyroid hormone levels in different tumor patients receiving multi-target TKI drugs are different, and further research is still needed. References | Related Articles | Metrics

Current status and future challenges of HPV preventive vaccine of cervical cancer Li Ang, Wei Fang 2019, 46 (5):  307-310.  doi: 10.3760/cma.j.issn.1673-422X.2019.05.012 Abstract ( 668 )   PDF (661KB) ( 971 )   Save Human papillomavirus (HPV) vaccine is approved by the the U. S. Food and Drug Administration in 2006 for female cancer prevention. There are currently three types of prophylactic HPV vaccines, and its application in developed countries can significantly reduce HPV infection rates and cervical lesion rates. In developing countries, HPV vaccination rates are low due to lack of knowledge of cervical cancer and funds. At the same time, concerns about vaccine safety have led to a reduction in vaccination rates in developed countries. Countries are facing the challenge of increasing vaccination rates. References | Related Articles | Metrics