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08 February 2020, Volume 47 Issue 2 Previous Issue    Next Issue

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GOLPH3 regulates proliferation and apoptosis of endometrial carcinoma cells through PI3K/AKT/GSK3β signal Luo Chuncui, Yuan Chaoyan, Chen Qingfen 2020, 47 (2):  65-69.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.001 Abstract ( 500 )   HTML ( 34 )   PDF (1100KB) ( 248 )   Save Objective To explore the mechanism of Golgi phosphoprotein 3 (GOLPH3) regulating the proliferation and apoptosis of endometrial cancer (EC) cells through PI3K/AKT/GSK3β signal. Methods Human endometrial adenocarcinoma HEC-1-B cells were divided into control group, GOLPH3 group and GOLPH3 + GDC-0941 group. GOLPH3 was over-expressed by transfection of the GOLPH3 pcDNA. The PI3K inhibitor GDC-0941 was used to block the PI3K/AKT/GSK3β pathway. Cell viability, cell proliferation and apoptosis were measured by CCK-8 method, clone formation experiment and flow cytometry, respectively. The protein phosphorylation level in PI3K/AKT/GSK3β pathway was detected by Western blotting. Results Transfection experiments were successful, and the PI3K inhibitor GDC-0941 did not affect GOLPH3 mRNA and protein expression. The relative cell viability of the control group, the GOLPH3 group and the GOLPH3 + GDC-0941 group were (100.00±4.63)%, (131.56±7.85)% and (97.85±7.36)%, and the difference among the three groups were significant (F=7.437, P<0.001). The cell viability of the GOLPH3 group was higher than that of the control group (P<0.001). The cell viability of the GOLPH3 + GDC-0941 group was lower than that of the GOLPH3 group (P<0.001). The numbers of cell clones in the three groups were 46.86±3.56, 89.32±4.78 and 46.48±4.05, and the difference was significant (F=20.437, P<0.001). GOLPH3 group had more clones than control group (P<0.001). The number of clones formed in the GOLPH3 + GDC-0941 group was less than that in the GOLPH3 group (P<0.001). The apoptosis rates of the three groups were (5.17±0.61)%, (2.34±0.56)% and (6.85±0.53)%, and the difference was significant (F=11.643, P<0.001). The apoptosis rate of the GOLPH3 group was lower than that of the control group (P<0.001), and the apoptosis rate of the GOLPH3 + GDC-0941 group was higher than that of the GOLPH3 group (P<0.001). The phosphorylated PI3K/PI3K levels of the three groups were 1.00±0.09, 3.32±0.19 and 0.93±0.06, respectively; phosphorylated AKT/AKT levels were 1.00±0.11, 4.63±0.63 and 1.15±0.16, respectively; phosphorylated GSK3β/GSK3β levels were 1.00±0.08, 4.06±0.57 and 1.04±0.14, respectively. The differences were statistically significant (F=12.532, P<0.001; F=16.792, P<0.001; F=15.311, P<0.001). The phosphorylation levels of each protein in the GOLPH3 group were higher than those in the control group (all P<0.001), and the GOLPH3 + GDC-0941 group were lower than the GOLPH3 group (all P<0.001). Conclusion In EC cells, over-expression of GOLPH3 can promote cell proliferation and inhibit apoptosis by activating the PI3K/AKT/GSK3β pathway, suggesting that GOLPH3 is involved in the occurrence and development of EC. Figures and Tables | References | Related Articles | Metrics

Relationships between serum lipids, CA153 level and breast cancer incidence and clinicopathological features of patients Zhao Yixin, Guan Yinan, Zhang Yin, Shi Xianbiao, Yao Yongzhong 2020, 47 (2):  70-76.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.002 Abstract ( 721 )   HTML ( 11 )   PDF (655KB) ( 324 )   Save Objective To explore the relationships between serum lipids, CA153 level and breast cancer incidence and clinicopathological features of patients. Methods A total of 198 patients with breast cancer diagnosed and treated at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were enrolled as the case group, and 198 healthy women were selected with 1∶1 age pairing as controls. Five milliliters of fasting venous blood was collected to measure serum lipids levels in all subjects and CA153 levels in breast cancer patients. The difference of serum lipids levels between the two groups was compared. Logistic regression model was used to analyze the risk factors of breast cancer. For 165 breast cancer patients who did not receive neoadjuvant chemotherapy, independent sample t-test was used to compare serum lipids and CA153 levels in breast cancer patients with different pathological features, and Pearson correlation analysis was used to calculate the correlation between variables and CA153. Results The triglyceride (TG) levels in the case group and the control group were (1.22±0.73) mmol/L and (1.06±0.52) mmol/L respectively, and the difference was statistically significant (t=2.559, P=0.011); the total cholesterol (TC) levels were (4.47±0.86) mmol/L and (4.99±0.80) mmol/L respectively, and the difference was statistically significant (t=-6.228, P<0.001); the high-density lipoprotein cholesterol (HDL-C) levels were (1.32±0.34) mmol/L and (1.53±0.38) mmol/L respectively, and the difference was statistically significant (t=-5.913, P<0.001). Higher TC and HDL-C levels were independent protective factors for breast cancer (OR=0.350, P<0.001; OR=0.531, P=0.013). The TC levels in lymph node positive and lymph node negative patients were (4.36±0.73) mmol/L and (4.67±0.83) mmol/L respectively, and the difference was statistically significant (t=-2.518, P=0.013); low-density lipoprotein cholesterol (LDL-C) levels were (2.53±0.58) mmol/L and (2.77±0.70) mmol/L respectively, and the difference was statistically significant (t=-2.312, P=0.022). The TC levels in patients with stage Ⅰ and stage Ⅱ/Ⅲ were (4.90±0.89) mmol/L and (4.46±0.76) mmol/L respectively, and the difference was statistically significant (t=2.855, P=0.005); LDL-C levels were (2.95±0.71) mmol/L and (2.60±0.63) mmol/L respectively, and the difference was statistically significant (t=2.705, P=0.008). The level of CA153 in triple-negative breast cancer patients [(14.94±7.45) U/ml] was significantly higher than that in non-triple-negative breast cancer patients [(11.96±5.96) U/ml], and the difference was statistically significant (t=2.359, P=0.020). The level of CA153 was positively correlated with the level of TG (r=0.167, P=0.032). Conclusion Dyslipidemia is associated with an increased risk of breast cancer. The levels of serum lipids vary among patients with different lymph node status and tumor stages. CA153 level is positively correlated with TG level to some extent. Figures and Tables | References | Related Articles | Metrics

Analysis of prognostic factors after surgical operation of lung cancer brain metastases Ma Chao, Cai Hongqing, Zhang Minjie, Ye Shilu, Meng Xiaoli, He Jie, Wan Jinghai 2020, 47 (2):  77-81.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.003 Abstract ( 712 )   HTML ( 13 )   PDF (1622KB) ( 226 )   Save Objective To analyze the prognosis-related factors of patients with surgical treatment of lung cancer brain metastases. Methods From January 2016 to November 2018, the clinical data of the patients with lung cancer brain metastases received surgical treatment in Department of Neurosurgery, Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively collected, and completed data of 83 patients were obtained. The single factor analysis was based on the log-rank method, and the multi-factor analysis was used by the Cox proportional hazard model, and the R software was used to map the influencing factors into the nomogram and verify them. Results The median overall survival (OS) of 83 patients was 27.0 months. The median OS of patients with surgery alone was 15.7 months, the median OS of patients with surgery combined with radiotherapy, chemotherapy or targeted therapy was 27.7 months, and the difference was statistically significant (χ 2=8.735, P=0.003). The results of single factor analysis showed that gender (χ 2=4.652, P=0.031), smoking history (χ 2=8.239, P=0.004), postoperative targeted treatment (χ 2=13.697, P<0.001), postoperative adjuvant therapy (χ 2=8.735, P=0.003), pathology of metastatic tumor (χ 2=11.799, P=0.001), and lung cancer molecular graded prognostic assessment (Lung-molGPA) sore (χ 2=11.333, P=0.004) affected patients' OS. The results of multivariate analysis showed that smoking history (HR=0.311, 95%CI: 0.107-0.901, P=0.031), postoperative targeted therapy (HR=3.563, 95%CI: 1.286-9.868, P=0.015), pathology of metastatic tumor (HR=0.364, 95%CI: 0.137-0.965, P=0.042), Lung-molGPA score (HR=0.595, 95%CI: 0.374-0.946, P=0.028) were independent prognostic factors for OS of patients with lung cancer brain metastases. In order to further evaluate the prognosis of patients, nomogram was drawn using these four independent prognostic factors. The model had high accuracy and could better evaluate the prognosis of patients. Conclusion Lung cancer brain metastases patients with operative indication can benefit from surgery, and active adjuvant therapy after operation can further prolong the OS of patients. The nomogram constructed by smoking, targeted therapy, pathology of metastatic tumor and Lung-molGPA score can be used to evaluate individual patient outcomes and guide clinical treatment. Figures and Tables | References | Related Articles | Metrics

Study on the mechanism of MALAT1 targeting miR-142-3p in ovarian cancer chemotherapy resistance Fan Yangyang, Wang Ying, Yuan Feng, Du Shanping, He Rongrong, Jia Yan 2020, 47 (2):  82-89.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.004 Abstract ( 505 )   HTML ( 19 )   PDF (999KB) ( 269 )   Save Objective To study the mechanism of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) targeting microRNA-142-3p (miR-142-3p) in ovarian cancer chemotherapy resistance. Methods A total of 80 ovarian cancer tissues and paired normal tissues were collected in Shaanxi Provincial People's Hospital from February 2016 to February 2019. The relative expression levels of MALAT1 and miR-142-3p in ovarian cancer tissues and paired normal tissues were detected by real-time fluorescence quantitative polymerase chain reaction (PCR), and the correlation between MALAT1 and miR-142-3p was analyzed. The effects of abnormal expressions of MALAT1 and miR-142-3p on proliferation and chemotherapy sensitivity of 5-fluorouracil (5-FU) and cisplatin of ovarian cancer Hey cells were verified by CCK-8 assay. Dual luciferase reporter gene experiment was used to detect the targeted relationship between miR-142-3p and MALAT1 (Hey cells were divided into four groups: MALAT1 wt, MALAT1 wt+miR-142-3p mimic, MALAT1 mut, MALAT1 mut+miR-142-3p mimic). RNA immunoprecipitation assay was use to confirm the binding site of MALAT1 and miR-142-3p. Results In the ovarian cancer tissues and paired normal tissues, the relative expression levels of MALAT1 were 0.000 52 (0.002 56) and 0.000 47 (0.000 89), with a statistically significant difference (Z=2.365, P=0.018); the relative expression levels of miR-142-3p were 0.001 19 (0.002 69) and 0.001 61 (0.008 48), with a statistically significant difference (Z=2.935, P=0.003). The relative expression level of MALAT1 was negatively correlated with miR-142-3p in the ovarian cancer tissues (r=-0.474, P<0.001). The relative expression level of miR-142-3p in the miR-142-3p mock group was statistically lower than that of MALAT1+miR-142-3p mimic group (0.004 18±0.001 24 vs. 0.006 51±0.000 28; t=3.174, P=0.017). The relative fluorescence concentrations of MALAT1 wt group and MALAT1 wt+miR-142-3p mimic group were 2.27±0.86 and 31.10±6.05 respectively, with a statistically significant difference (t=8.172, P<0.001). After 48, 72 and 96 hours of ovarian cancer Hey cells being transfected with MALAT1 overexpression plasmid, the absorbance (A) values of cells in the MALAT1 overexpression group were significantly greater than those in the control group (0.522±0.021 vs. 0.433±0.021; 0.644±0.012 vs. 0.544±0.051; 0.887±0.055 vs. 0.698±0.042), with statistically significant differences (all P<0.05). After MALAT1 being overexpressed in Hey cells, at 0.10 ng/μl concentration of 5-FU, the proliferation rate of cells in the overexpression group was significantly faster than that in the control group (0.615±0.036 vs. 0.506±0.042; t=4.432, P=0.002), and the cells at 1.00, 10.00, 100.00 ng/μl concentrations of 5-FU showed the same trends (all P<0.05). At 0.01 ng/μl concentration of cisplatin, the proliferation rate of cells in the overexpression group was significantly faster than that in the control group (0.777±0.015 vs. 0.733±0.039; t=2.355, P=0.023), and the cells at 0.10, 1.00, 10.00, 100.00 ng/μl concentrations of cisplatin showed the same trends (all P<0.05). After miR-142-3p being overexpressed in Hey cells, at 0.10 ng/μl concentration of 5-FU, the proliferation rate of cells in the overexpression group was significantly slower than that in the control group (0.512±0.051 vs. 0.744±0.119; t=4.028, P=0.004), and the cells at 1.00, 10.00, 100.00 ng/μl concentrations of 5-FU showed the same trends (all P<0.05). At 0.10 ng/μl concentration of cisplatin, the proliferation rate of cells in the overexpression group was significantly slower than that in the control group (0.520±0.043 vs. 0.674±0.096; t=3.441, P=0.009), and the cells at 1.00, 10.00, 100.00 ng/μl concentrations of cisplatin showed the same trends (all P<0.05). After ovarian cancer Hey cells being treated with 0.10, 1.00, 10.00, 100.00 ng/μl concentrations of 5-FU and cisplatin, the proliferation rates of cells in the MALAT1 overexpression group, MALAT1+miR-142-3p group and control group showed statistically significant differences (all P<0.05). Further pairwise comparisons revealed that the proliferation rates of cells in the MALAT1+miR-142-3p group were significantly slower than those in the MALAT1 overexpression group (all P<0.05). Conclusion MALAT1 can reduce the sensitivity of ovarian cancer cells to 5-FU and cisplatin by targeted miR-142-3p, leading to chemotherapy resistance of ovarian cancer. Figures and Tables | References | Related Articles | Metrics

Reviews

MicroRNA-125b and cancer Liu Qianqian, He Xiaolan, Tang Lin, Yuan Yixiao, Qiu Shun, Duan Lincan 2020, 47 (2):  90-92.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.005 Abstract ( 523 )   HTML ( 14 )   PDF (621KB) ( 246 )   Save MicroRNA-125b (miR-125b) has been proved to be closely related to a variety of cancers in recent years, such as lung cancer, digestive system cancers, blood cancers, etc. miR-125b plays a key role in the occurrence and development of cancers, which can evaluate the therapeutic effects of various treatment methods of cancers by detecting the expression of miR-125b, and can assist in the diagnosis of cancers. It is of great significance to explore the mechanism of miR-125b in cancers for the treatment. References | Related Articles | Metrics

Research status of immune checkpoint inhibitors in the treatment of advanced malignant tumors with hyperprogressive diseases Zhou Shengyu 2020, 47 (2):  93-97.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.006 Abstract ( 705 )   HTML ( 12 )   PDF (640KB) ( 269 )   Save Immune checkpoint inhibitors have become extremely important treatments to benefit long-term survival of patients with a variety of advanced malignant tumors. However, a small number of patients will develop hyperprogressive disease (HPD), leading to a sharp decline in survival and quality of life, and there is still a lack of effective rescue treatment. Recent studies have shown that the occurrence of HPD is related to clinical factors such as advanced age, tumor recurrence and multi-focus metastasis. The possible mechanisms include inhibitory immune regulation, regulatory T cell aggregation, abnormal inflammatory response, proto-oncogene activation, tumor suppressor gene mutation and other pathways. Reasonable screening, accurate detection, close monitoring and combined treatment may reduce the risk of immunotherapy for HPD. References | Related Articles | Metrics

New research advances of long non-coding RNA in glioma Nan Yang, Zhong Yue 2020, 47 (2):  98-102.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.007 Abstract ( 543 )   HTML ( 14 )   PDF (638KB) ( 299 )   Save Glioma is the most common primary intracranial tumor which is essentially a polygenic abnormal disease. Long non-coding RNA (lncRNA) is a class of noncoding genes with a length of more than 200 nucleotides. LncRNA plays an important role in tumorigenesis and development by regulating the expression of tumor-related genes or related signaling pathways. The abnormally expressions of lncRNA in gliomas contribute to the diversity of glioma phenotypes. In-depth study of the potential role of abnormally expressed lncRNA in the pathogenesis and pathological grading of gliomas will provide new ideas for clinical targeted treatment of gliomas. References | Related Articles | Metrics

Advances of tumor bed delineation for radiation therapy after breast-conserving surgery Yang Ya, Liu Xiaomeng, Dong Yinping, Huang Wei 2020, 47 (2):  103-106.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.008 Abstract ( 679 )   HTML ( 9 )   PDF (625KB) ( 336 )   Save Radiotherapy following breast conserving surgery is a standard treatment in early stage breast cancer, and tumor bed delineation is a very important part of radiotherapy. Traditionally, operative record, preoperative ultrasound, postoperative scar, clips and other conventional methods were used to contour tumor bed in clinical, but they still have many limitations. In recent years, there were some progress in tumor bed delineation of the new style of lumpectomy cavity filling, preoperative/postoperative MRI images with CT images and other new methods. It is expected to solve the lack of postoperative tumor bed delineation consensus and standard in the future. References | Related Articles | Metrics

Occurrence and perdictive factors of radiation pneumonitis in patients with thoracic tumor Fu Lingli, Li Ping, Zhang Rui, Han Jianglong, Fu Zhenming 2020, 47 (2):  107-111.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.009 Abstract ( 533 )   HTML ( 11 )   PDF (700KB) ( 217 )   Save Radiation pneumonitis is a common complication in the radiotherapy for thoracic malignant tumors. And the resulting respiratory failure is one of the most serious side effects. The occurrence and severity of radiation pneumonitis depend on many factors such as age, performance status scores, smoking status, lung condition, tumor sizes, tumor location, chemoradiotherapy related factors, inflammatory factors and single-nucleotide polymorphism, et al. Some imaging examinations, for example single-photon emission computed tomography and PET-CT, have been used to predict radiation pneumonitis, while its usefulness remains to be strengthened. Further researches are still needed to find the gold standard in the prediction of radiation pneumonitis. References | Related Articles | Metrics

MicroRNA-223 and digestive system tumors Zhu Zemin, Xie Zhiqin, Sun Yongkang, Tang Caixi 2020, 47 (2):  112-114.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.010 Abstract ( 392 )   HTML ( 15 )   PDF (622KB) ( 218 )   Save MicroRNA-223 (miR-223) is located on chromosome X, and is highly conserved in the process of evolution. In recent years, many studies have shown that miR-223 is abnormally expressed in a variety of digestive system tumors, such as esophageal cancer, gastric cancer, liver cancer, pancreatic cancer and colorectal cancer. MiR-223 can participate in the proliferation, apoptosis and invasion of tumor cells through a variety of signal pathways, which is expected to become a marker for the diagnosis and prognosis of digestive system tumors. References | Related Articles | Metrics

Zinc finger proteins and digestive system cancers Tian Chunfang, Sha Dan 2020, 47 (2):  115-118.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.011 Abstract ( 793 )   HTML ( 16 )   PDF (630KB) ( 296 )   Save Zinc finger proteins (ZNFs) belong to the largest transcriptional factor family in human genome. ZNFs are widely involved in the development and progression of digestive system cancers by promoting or inhibiting carcinogenesis. Studies have shown that the abnormal expressions of various ZNFs are closely related to the clinicopathologic features and prognosis of patients with digestive system cancers, including gastric cancer, liver cancer, colorectal cancer and pancreatic cancer. Exploring the underlying mechanism of ZNFs will help to provide new targets for clinical treatment of digestive system cancers. References | Related Articles | Metrics

Advances of Krüppel-like factors in hepatocellular carcinoma Zhao Chuanxi, Zhu Tingting, Liu Mingguo, Cao Lili 2020, 47 (2):  119-122.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.012 Abstract ( 485 )   HTML ( 10 )   PDF (632KB) ( 284 )   Save Krüppel-like factors (KLFs) play extremely important roles in genesis and development of tumors. Simultaneously, KLFs have been proven to affect the proliferation, differentiation and migration of hepatocellular carcinoma cells. Nine members in the KLFs family (KLF2, KLF4, KLF5, KLF6, KLF8, KLF9, KLF10, KLF14 and KLF17) are involved in the occurrence and development of hepatocellular carcinoma in various ways as an oncogene and tumor suppressor gene. Therefore, the KLFs family will hopefully become biological therapeutic targets for hepatocellular carcinoma. References | Related Articles | Metrics

Advances of Merkel cell polyomavirus in the pathogenesis of Merkel cell carcinoma Yue Zhanghui, Wang Yan, Fang Fang, Sun Jianfang 2020, 47 (2):  123-126.  doi: 10.3760/cma.j.issn.1673-422X.2020.02.013 Abstract ( 490 )   HTML ( 8 )   PDF (630KB) ( 371 )   Save Merkel cell carcinoma (MCC) is a rare, highly invasive skin tumor. In recent years, some new progress has been made in the research of MCC morphology, immunophenotype and pathogenesis. The discovery of Merkel cell polyomavirus (MCPyV) is a major breakthrough in MCC research. MCPyV-positive patients with MCC are significantly different from uninfected patients in pathogenesis, clinical characteristics and prognosis. Studies of MCPyV not only reveal some of the pathogenesis of MCC, but also contribute to exploring the tissue origin of MCC. In addition, detection of MCPyV oncoprotein antibodies in the serum can obtain prognostic information of patients with MCC. Identification of the virus status and the mutation profile of MCC tumors can better guide medication and help to develop individualized clinical treatment strategies. References | Related Articles | Metrics