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08 November 2020, Volume 47 Issue 11 Previous Issue    Next Issue

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Study on the effect of docosahexaenoic acid combined with cisplatin on the growth of human gastric cancer xenografts in nude mice and its mechanism Xu Liben, Wu Chaoyang, Wang Yuandong 2020, 47 (11):  656-662.  doi: 10.3760/cma.j.cn371439-20200123-00096 Abstract ( 360 )   HTML ( 20 )   PDF (11069KB) ( 89 )   Save Objective To study the effects of docosahexaenoic acid (DHA) combined with cisplatin on the growth of human gastric cancer xenografts in nude mice, and to explore the mechanism of combined anti-tumor. Methods The models of human gastric cancer transplanted in 28 nude mice were established. The models were randomly divided into control group, DHA group, cisplatin group and combined group, with 7 mice in each group. After 2 weeks of treatment with normal saline, DHA, cisplatin and cisplatin + DHA, the growth of nude mice was observed, the changes of tumor volume and tumor weight were recorded; the morphological changes of cells in each group were observed by HE staining; the apoptosis rate was detected by flow cytometry, the protein expressions of nuclear factor-κB (NF-κB)/p65 and survivin were detected by immunohistochemistry, and the mRNA expressions of NF-κB/p65 and survivin was detected by reverse transcription-PCR. Results Three days after treatment, the tumor volumes in the control group, DHA group, cisplatin group and combined group were (3.13±0.25) cm3, (2.32±0.19)cm3, (1.00±0.08) cm3, (0.50±0.15) cm3, and there was a statistical difference among the four groups (F=314.050, P<0.001). The tumor volumes of the control group, DHA group and cisplatin group were all bigger than that of the combined group (P<0.001; P<0.001; P=0.002). The tumor weights of the control group, DHA group, cisplatin group and combined group were (2.86±0.34) g, (2.14±0.22) g, (1.43±0.18) g, (0.73±0.03) g, and there was a significant difference among the four groups (F=45.570, P<0.001). The tumor weights of the control group, DHA group and cisplatin group were all higher than that of the combined group (P=0.001; P<0.001; P<0.001). HE staining showed that apoptosis of tumor cells was observed in each treatment group, and the combined group was more obvious. The apoptotic rates of the control group, DHA group, cisplatin group and combined group were (3.89±1.03)%, (7.46±0.81)%, (14.85±1.10)%, (24.68±1.17)%, with a significant difference (F=545.620, P<0.001), and the control group, DHA group and cisplatin group were all lower than the combined group (all P<0.001). The relative expression levels of NF-κB/p65 protein in the control group, DHA group, cisplatin group and combined group were 0.389±0.027, 0.312±0.032, 0.258±0.031, 0.163±0.036, with a significant difference (F=78.050, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.018). The relative expression levels of survivin protein in the control group, DHA group, cisplatin group and combined group were 0.480±0.040, 0.366±0.052, 0.305±0.027, 0.197±0.032, with a significant difference (F=115.135, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.012). The relative expressions of NF-κB/p65 mRNA in the control group, DHA group, cisplatin group and combined group were 0.902±0.020, 0.780±0.040, 0.560±0.040, 0.350±0.030, with a significant difference (F=1 468.705, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.026). The relative expressions of survivin mRNA in the control group, DHA group, cisplatin group and combined group were 0.890±0.050, 0.760±0.020, 0.510±0.030, 0.280±0.040, with a significant difference (F=2 099.107, P<0.001), and the control group, DHA group and cisplatin group were all higher than the combined group (P<0.001; P<0.001; P=0.030). Conclusion DHA combined with cisplatin can inhibit the growth of transplanted tumor in nude mice. The mechanism may be related to down regulating the expression of survivin and NF-κB/p65, inducing apoptosis and increasing the sensitivity of chemotherapy drugs. Figures and Tables | References | Related Articles | Metrics

Predictive value of NRS-2002 on the efficacy and prognosis of chemoradiotherapy in patients with lymph node metastasis after esophagectomy of thoracic esophageal squamous cell carcinoma Guo Xinwei, Zhang Han, Cao Yun, Zhou Juying, Liu Yangchen, Ye Hongxun, Ji Shengjun 2020, 47 (11):  663-668.  doi: 10.3760/cma.j.cn371439-20200318-00097 Abstract ( 448 )   HTML ( 17 )   PDF (8635KB) ( 70 )   Save Objective To explore the predictive value of nutritional risk screening-2002 (NRS-2002) on the efficacy and prognosis of chemoradiotherapy (CRT) in patients with lymph node metastasis (LNM) after esophagectomy of thoracic esophageal squamous cell carcinoma (ESCC). Methods From January 2013 to December 2016, 140 patients with LNM after esophagectomy of thoracic ESCC receiving curative radiotherapy (RT) only or concurrent CRT in the Department of Radiation Oncology, Affiliated Taixing People's Hospital of Bengbu Medical College were retrospectively analyzed. According to the median hemoglobin before treatment, the patients were divided into two groups: hemoglobin<127 g/L group (n=65) and hemoglobin≥127 g/L group (n=75). According to NRS-2002 tool standard, the nutritional risk was scored and grouped by the best cutoff value, patients were divided into NRS-2002<3 group (n=65) and NRS-2002≥3 group (n=75). The logistic regression was used to analyze the factors influencing the short-term efficacy. Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univariate and multivariate analyses were carried out by Cox proportional hazards model. Finally, receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to confirm the prediction accuracy of NRS-2002 in efficacy and survival prognosis. Results The treatment effective rate of the whole group was 65.0% (91/140). The effective rates of the patients in hemoglobin<127 g/L group and hemoglobin≥127 g/L group were 52.3% (34/65) and 76.0% (57/75) respectively, and there was a statistically significant difference (χ2=8.592, P=0.003). The effective rates of the patients in NRS-2002<3 group and NRS-2002≥3 group were 81.5% (53/65) and 50.7% (38/75) respectively, and there was a statistically significant difference (χ 2=14.588, P<0.001). The univariate logistic regression analysis showed that the short-term efficacy of CRT was highly associated with treatment method (HR=1.322, 95%CI: 1.121-3.632, P=0.012), hemoglobin (HR=0.346, 95%CI: 0.169-0.711, P=0.004) and NRS-2002 score (HR=3.374, 95%CI: 1.185-9.611, P<0.001). Multivariate logistic regression analysis found that treatment method (HR=1.125, 95%CI: 1.098-2.927, P=0.042) and NRS-2002 score (HR=3.868, 95%CI: 1.723-8.685, P<0.001) were independent factors for short-term effect of CRT. The median overall survival (OS) of all patients was 16.0 months (95%CI: 14.3-17.7), the 1-, 2- and 3-year survival rates were 69.3%, 28.6% and 21.4%, respectively. In the hemoglobin<127 g/L group, the 1-, 2-, and 3-year survival rates were 62.1%, 21.5% and 10.8%, and in the hemoglobin≥127 g/L group, the 1-, 2-, and 3-year survival rates were 74.7%, 34.7% and 30.7%, with a statistically significant difference (χ 2=7.370, P=0.007). In the NRS-2002<3 group, the 1-, 2-, and 3-year survival rates were 89.2%, 50.8% and 43.1%, and in the NRS-2002≥3 group, the 1-, 2-, and 3-year survival rates were 52.0%, 9.3% and 2.7%, with a statistically significant difference (χ 2=48.778, P<0.001). Cox univariate factor analysis found that treatment method (HR=1.375, 95%CI: 1.108-1.968, P=0.019), hemoglobin (HR=0.607, 95%CI: 0.417-0.885, P=0.009) and NRS-2002 score (HR=0.471, 95%CI: 0.349-0.636, P<0.001) were closely related to OS of patients with LNM after esophagectomy of thoracic ESCC. However, Cox multivariate analysis showed that only NRS-2002 score (HR=0.494, 95%CI: 0.365-0.669, P<0.001) was an independent prognostic factor for OS. ROC curve showed that NRS-2002 score predicted AUC of short-term efficacy and OS were 0.669 (95%CI: 0.576-0.762, P=0.001) and 0.798 (95%CI: 0.719-0.878, P<0.001), respectively. Conclusion Thoracic ESCC patients with LNM receiving CRT after esophagectomy with NRS-2002 score<3 before treatment have a better short-term efficacy and long-term survival. Figures and Tables | References | Related Articles | Metrics

Efficacy and safety evaluation of apatinib combined with albumin-bound paclitaxel in the treatment of elderly patients with relapsed and metastatic gastric cancer Gao Shuang, Hu Changlu 2020, 47 (11):  669-674.  doi: 10.3760/cma.j.cn371439-20200406-00098 Abstract ( 1989 )   HTML ( 27 )   PDF (4036KB) ( 276 )   Save Objective To observe the clinical efficacy and adverse reactions of apatinib combined with albumin-bound paclitaxel in elderly patients with relapsed and metastatic gastric cancer. Methods A total of 72 elderly patients with relapsed and metastatic gastric cancer diagnosed in the Department of Oncology, West District of the First Affiliated Hospital of University of Science & Technology of China from June 1, 2017 to June 1, 2019 were chosen. The patients were divided into control group (n=36) and study group (n=36) using random number table method. The control group received only albumin-bound paclitaxel chemotherapy, and the study group continued oral apatinib based on the control group's chemotherapy, every 3 weeks for one chemotherapy cycle, a total of 4 cycles. The short-term efficacy, median overall survival (OS), median progression-free survival (PFS), serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 72-4 (CA72-4) and adverse reactions were compared between the two groups. Results The objective response rate and disease control rate of the study group were 55.56% (20/36) and 77.78% (28/36) respectively, which were higher than those of the control group [30.56% (11/36) and 55.56% (20/36)], and there were statistically significant differences (χ2=4.589, P=0.032; χ2=4.000, P=0.046). After 4 cycles treatment, the serum CEA, CA199 and CA72-4 levels in the study group were (12.5±3.3) μg/L, (35.6±6.7) U/ml, (13.5±2.2) U/ml respectively, which were lower than those in the control group [(22.8±4.1) μg/L, (55.6±7.4) U/ml, (21.7±3.4) U/ml], and there were statistically significant differences (t=7.008, P=0.017; t=9.365, P=0.008; t=8.862, P=0.011). The incidences of gastrointestinal reactions and myelosuppression were 38.89% (14/36) and 44.44% (16/36) in the study group, and 36.11% (13/36) and 41.67% (15/36) in the control group respectively, with no significant differences (χ2=0.059, P=0.808; χ2=0.057, P=0.811). The incidences of hypertension, hand-foot syndrome, oral mucositis and proteinuria in the study group were 27.78% (10/36), 41.67% (15/36), 27.78% (10/36) and 16.67% (6/36) respectively, which were higher than those in the control group [8.33% (3/36), 16.67% (6/36), 5.56% (2/36) and 2.78% (1/36)], and there were statistically significant differences (χ2=4.600, P=0.032; χ2=5.445, P=0.020; χ2=6.400, P=0.011; χ2=3.956, P=0.047), which could be tolerated after symptomatic treatment. The median OS and PFS of the study group were 18.2 months and 16.1 months, which were longer than those of the control group (11.8 months and 8.0 months), and there were statistically significant differences (χ2=6.821, P=0.015; χ2=5.868, P=0.018). Conclusion Apatinib combined with albumin-bound paclitaxel is superior to albumin-bound paclitaxel single-agent chemotherapy in elderly patients with relapsed and metastatic gastric cancer, which can prolong the PFS and OS, and the adverse reactions are tolerable. Figures and Tables | References | Related Articles | Metrics

Value of P16/Ki-67 double staining detection in screening cervical cancer and precancerous lesions Song Mingze, Cheng Yiming, Li Gang, Wang Zhenming, Li Shirong 2020, 47 (11):  675-681.  doi: 10.3760/cma.j.cn371439-20191224-00099 Abstract ( 1042 )   HTML ( 26 )   PDF (6469KB) ( 251 )   Save Objective To explore the value and clinical significance of double staining detection of P16/Ki-67 in the screening of cervical cancer and precancerous lesions. Methods Patients admitted to Department of Gynecology of Weifang People's Hospital of Shandong Province from September 2018 to May 2019 were selected, including 110 patients with cervical intraepithelial neoplasia (CIN) below grade 2, 31 patients with CIN2, 27 patients with CIN3, and 12 patients with cervical cancer. The sensitivity, specificity, positive predictive value and negative predictive value of human papillomavirus (HPV) DNA, thinprep cytologic test (TCT) and P16/Ki-67 double staining detection as primary screening method for cervical cancer and precancerous lesions were evaluated, and the feasibility of P16/Ki-67 double staining detection as shunt for high-risk HPV positive patients was discussed. Results The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of <CIN2 grade were 80.91%, 75.45%, 81.82%, the specificities were 91.43%, 87.14%, 97.14%, the positive predictive values were 93.68%, 90.22%, 97.83%, and the negative predictive values were 75.29%, 69.32%, 77.27% respectively, with statistically significant differences (χ 2=1.593, P=0.042; χ 2=4.736, P=0.034; χ 2=4.667, P=0.037; χ 2=1.564, P=0.048). The specificity of P16/Ki-67 double staining detection was higher than that of HPV DNA and TCT, and the sensitivity and positive predictive value were higher than those of TCT (all P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of CIN2 grade were 90.32%, 83.87%, 96.77%, with a statistically significant difference (χ 2=2.952, P=0.029); the specificities were 80.91%, 75.45%, 81.82%, with no significant difference (χ 2=2.505, P=0.066); the positive predictive values were 57.10%, 49.10%, 60.00%, with no significant difference (χ 2=1.939, P=0.079); and the negative predictive values were 96.70%, 94.30%, 98.90%, with a statistically significant difference (χ 2=3.175, P=0.013). The sensitivity and negative predictive value of P16/Ki-67 double staining detection were higher than those of TCT (both P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of CIN3 grade were 92.59%, 96.30%, 96.30%, with no significant difference (χ 2=0.497, P=0.780); the specificities were 80.91%, 75.45%, 81.82%, with a statistically significant difference (χ 2=4.677, P=0.036); the positive predictive values were 54.30%, 49.10%, 56.50%, with a statistically significant difference (χ 2=1.760, P=0.045); and the negative predictive values were 97.80%, 98.80%, 98.90%, with no significant difference (χ 2=0.441, P=0.802). The specificity and positive predictive value of P16/Ki-67 double staining detection were higher than those of TCT (both P<0.012 5). The sensitivities of HPV DNA, TCT and P16/Ki-67 double staining detection in the diagnosis of cervical cancer were 91.67%, 75.00%, 100.00%, with a statistically significant difference (χ 2=3.293, P=0.034); the specificities were 80.91%, 75.45%, 81.82%, the positive predictive values were 34.40%, 25.00%, 37.50%, and the negative predictive values were 98.90%, 96.50%, 100.00% respectively, with no significant differences (χ2=2.736, P=0.255; χ 2=1.834, P=0.400; χ 2=3.075, P=0.081). The sensitivity of P16/Ki-67 double staining detection was higher than that of TCT (P<0.012 5). For the shunt of high-risk HPV positive patients, the sensitivities of P16/Ki-67 double stain detection and TCT were 98.44% and 89.06%, the specificities were 85.71% and 61.90%, and the negative predictive values were 94.70% and 65.00% respectively, with statistically significant differences (χ 2=4.800, P=0.028; χ 2=3.079, P=0.039; χ 2=5.284, P=0.022); the positive predictive values were 95.50% and 87.70%, with no significant difference (χ 2=2.565, P=0.109). Conclusion Cytology P16/Ki-67 double staining detection is more specific than HPV DNA and TCT in the diagnosis of <CIN2 grade, and its sensitivity and positive predictive value are higher than those of TCT; the sensitivity and negative predictive value of diagnosis of CIN2 grade are higher than TCT; the specificity and positive predictive value of diagnosis of CIN3 grade are higher than those of TCT; the sensitivity of diagnosis of cervical cancer is higher than that of TCT. In the shunt of high-risk HPV positive patients, P16/Ki-67 double staining detection provides a more sensitive and accurate shunt path. Figures and Tables | References | Related Articles | Metrics

Reviews

Uncoupling proteins and tumor Dai Yueyu, Song Qibin, Hu Weiguo 2020, 47 (11):  682-685.  doi: 10.3760/cma.j.cn371439-20200401-00100 Abstract ( 729 )   HTML ( 18 )   PDF (2845KB) ( 257 )   Save Uncoupling proteins (UCPs) belongs to the mitochondrial carrier protein family on the mitochondrial inner membrane, mainly including UCP1, UCP2 and UCP3. Studies have shown that UCPs participate in the occurrence and development of malignant tumors through lipid browning. Tumor cells secrete zinc-α2-glycoprotein to stimulate the peroxidosomal proliferator-activated receptor, induce lipid browning and express UCP1, and promote the growth of tumor. Phospholipase C-like 1 upregulates UCP1 expression, consumes abnormal lipids, reduces the ability of tumor cell colony formation, and inhibits tumor migration and invasion. In addition, PGC-1 α and PGC-1 β, the co-factors of tumor suppressor p53, can enhance the expression of UCP1 in p53-deficient adipose cells, and the up-regulation of UCP2 can help tumor cells escape apoptosis mediated by p53, activate the reactive oxygen species system, and enhance the vitality and proliferation of tumors. References | Related Articles | Metrics

Clinical application of multimodal magnetic resonance imaging in glioma Zhang Wen, Song Qibin, Hu Weiguo 2020, 47 (11):  686-690.  doi: 10.3760/cma.j.cn371439-20200529-00101 Abstract ( 745 )   HTML ( 14 )   PDF (3888KB) ( 277 )   Save Multimodal magnetic resonance imaging is an emerging brain imaging technology that integrates multiple functions of magnetic resonance imaging technology. It has the advantages of high accuracy, high distinguishability and low invasiveness, and also can provide more comprehensive and systematic brain tissue information in the anatomical, functional and molecular levels. In recent years, with the continuous development of magnetic resonance imaging technology, multimodal magnetic resonance technology has been widely used in the clinical diagnosis and treatment of glioma. Therefore, understanding the principles of multimodal magnetic resonance imaging technology and its application in grading, differential diagnosis and prognostic assessment of glioma can help clinicians make better diagnosis and treatment decisions. References | Related Articles | Metrics

Research progress in surgical treatment of thymic epithelial tumors Tang Huanyu, Huang Heng, Jiang Kaiyuan, He Xi, Wei Zhenting, Yang Jiechen, Tian Dong 2020, 47 (11):  691-694.  doi: 10.3760/cma.j.cn371439-20200224-00102 Abstract ( 398 )   HTML ( 14 )   PDF (2926KB) ( 224 )   Save Thymic epithelial tumor (TET) is the most common primary tumor of anterior mediastinum. Currently surgical treatment is still the main treatment. Median sternotomy is the first widely used method for tumor resection, but it will cause great trauma for patients. In recent years, the research on minimally invasive surgery has made rapid progress, from video-assisted thoracoscopic surgery to rapidly promoted subxiphoid approach video-assisted thoracoscopic surgery and robotic-assisted thoracic surgery. Although the advantages and disadvantages of various surgical methods and the scope of adaptation are still controversial, a large number of studies have confirmed that minimally invasive surgery has better efficacy and safety for TET. References | Related Articles | Metrics

Heart protection in the treatment of breast cancer Liu Guibin, Gao Jie, Ma Ying 2020, 47 (11):  695-699.  doi: 10.3760/cma.j.cn371439-20200406-00103 Abstract ( 507 )   HTML ( 11 )   PDF (3973KB) ( 167 )   Save Breast cancer patients have a higher risk of cardiovascular disease, older age, lower ejection fraction, history of coronary artery disease, cardiac risk factors, anthracycline combined with trastuzumab or radiotherapy will increase the risk of cardiac events after treatment. Echocardiographic monitoring the heart condition, especially for those patients with traditional heart risk factors such as hypertension, diabetes, hyperlipidemia and obesity or with low left ventricular ejection fraction at normal baseline, can reduce cardiac risk events. Elevated troponin and early myocardial deformation during anthracycline therapy may indicate a decrease in ejection fraction, but further studies are needed to prove the clinical benefits of routine screening and early treatment. For patients with breast cancer, smoking cessation,regular exercise, healthy diet and maintaining a healthy weight, etc., can reduce the risk of cardiovascular disease. References | Related Articles | Metrics

Drug treatment advances towards metastatic biliary tract cancer Liu Xiaojun, Li Shuping, Wang Wei 2020, 47 (11):  700-704.  doi: 10.3760/cma.j.cn371439-20200304-00104 Abstract ( 435 )   HTML ( 12 )   PDF (3697KB) ( 2848 )   Save The median overall survival is shorter than 1 year and chemotherapy is still the main treatment for patients with metastatic biliary tract cancer (BTC). Over the recent years, novel molecular targeted therapy and immunotherapy have been extensively tested in this disease. Among them, fibroblast growth factor receptors inhibitors, anti-vasculature therapy and c-Met inhibitors and other new drugs have achieved encouraging curative effect in the treatment of metastatic BTC. Meanwhile, immune checkpoint inhibitors and bifunctional immune agents hold great promise for this type of cancers. Some ongoing phase Ⅲ trials may change the clinical status and improve the outcome for patients with metastatic BTC. References | Related Articles | Metrics