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08 May 2022, Volume 49 Issue 5 Previous Issue    Next Issue

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Study on the mechanism of procyanidin mediated anti gastric cancer SNU-1 cell line by inducing the production of reactive oxygen species Yang Ya, Ning Xiaofei, Li Bingliang, Yao Hui, Shan Changping, Lyu Min 2022, 49 (5):  257-262.  doi: 10.3760/cma.j.cn371439-20220210-00048 Abstract ( 191 )   HTML ( 24 )   PDF (2258KB) ( 124 )   Save Objective To investigate the effect and molecular mechanism of procyanidin on the proliferation, apoptosis and reactive oxygen species （ROS） level of gastric cancer cell line SNU-1 in vitro. Methods SNU-1 cells were divided into control group and 12.5, 50.0, 200.0 μg/ml procyanidin groups. The effect of procyanidin on the proliferation of SNU-1 cells was detected by CCK-8 assay. The apoptosis level and ROS positive rate of cells were detected by flow cytometry, and 2 mmol/L glutathione was added to SNU-1 cells added with 200.0 μg/ml procyanidin to detect the apoptosis level and ROS positive rate of cells. The expression of apoptosis-related protein in cells was detected by Western blotting. Results The results of CCK-8 experiment showed that the proliferation activities of SNU-1 cells in the control group and the 12.5, 50.0, 200.0 μg/ml procyanidin groups were 3.69±0.30, 3.29±0.41, 0.91±0.39, 0.45±0.22 respectively, with a statistically significant difference （F=279.84, P<0.001）. Compared with the control group, the proliferation activities of SNU-1 cells in the three procyanidin groups were significantly inhibited （P=0.006, P<0.001, P<0.001）. The results of flow cytometry showed that the early apoptosis rates of SNU-1 cells in the control group and the 12.5, 50.0, 200.0 μg/ml procyanidin groups were （0.00±0.00）%, （0.00±0.00）%, （0.09±0.07）% and （0.45±0.22）% respectively, with a statistically significant difference （F=7.14, P=0.003）. The 50.0 and 200.0 μg/ml procyanidin groups increased significantly compared with the control group （P=0.003, P=0.007）. The late apoptosis rates of SNU-1 cells in the four groups were （0.00±0.00）%, （0.01±0.00）%, （6.98±0.77）% and （33.32±2.78）% respectively, with a statistically significant difference （F=654.28, P=0.003）. The 50.0 and 200.0 μg/ml procyanidin groups increased significantly compared with the control group （P<0.001, P<0.001）. The positive rates of ROS in SNU-1 cells in the four groups were （0.02±0.01）%, （0.10±0.05）%, （1.15±0.26）% and （1.58±0.22）% respectively, with a statistically significant difference （F=162.24, P<0.001）. The 50.0 and 200.0 μg/ml procyanidin groups increased significantly compared with the control group （P<0.001, P<0.001）. The positive rates of ROS in SNU-1 cells in the 200.0 μg/ml procyanidin group and the glutathione intervention group were （1.25±0.63）% and （0.13±0.02）% respectively, with a statistically significant difference （t=5.39, P=0.001）. The early apoptosis rates of the two groups were （10.56±3.24）% and （2.09±0.24）% respectively, and the late apoptosis rates were （29.65±6.01）% and （23.63±1.52）% respectively, with statistically significant differences （t=2.61, P=0.048; t=3.97, P=0.012）. The expressions of Bcl-2 protein in SNU-1 cells in the control group and the 12.5, 50.0, 200.0 μg/ml procyanidin groups were 1.00±0.00, 0.83±0.05, 0.60±0.14 and 0.41±0.23 respectively, with a statistically significant difference （F=10.63, P=0.004）. The 50.0 and 200.0 μg/ml procyanidin groups decreased significantly compared with the control group （P<0.001, P<0.001）. Conclusion Procyanidin can inhibit proliferation and promote apoptosis of gastric cancer SNU-1 cells in vitro, which may be achieved by increasing intracellular ROS levels and reducing Bcl-2 protein expression. Figures and Tables | References | Related Articles | Metrics

Study on the biological characteristics of polyploid cervical cancer HeLa cells induced by radiation Xiong Chan, Yan Ying, Xie Xiaodong, Meng Fanjie, Yu Huiying 2022, 49 (5):  263-269.  doi: 10.3760/cma.j.cn371439-20220214-00049 Abstract ( 214 )   HTML ( 15 )   PDF (1723KB) ( 124 )   Save Objective To investigate the biological characteristics of proliferation, apoptosis, migration and invasion of radiation-induced polyploid cervical cancer HeLa cells, and to analyze the potential facilitation of polyploid HeLa cells in cervical cancer recurrence after radiotherapy. Methods HeLa cells were irradiated by 6 MV-X ray with 7 Gy and 14 Gy, the cells were cultured until the third day, and then they were recorded as 7 Gy group and 14 Gy group respectively. The unirradiated HeLa cells were recognized as the control group. The cell morphology was checked under optical microscope. Flow cytometry was used to determine cell ploidy. MTT assay was applied to detect cell proliferation. Flow cytometry by AnnexinⅤ-FITC/PI double labeling was used to detect apoptosis. The ability of migration and invasion was detected by Transwell assay. The expression levels of STAT3 signal pathway-related proteins were analyzed by Western blotting. Results Compared with the control group, the volume of HeLa cells in 7 Gy group and 14 Gy group increased significantly. The percentages of polyploid HeLa cell subsets in the control group, 7 Gy group and 14 Gy group were （6.33±1.26）%, （21.13±0.50）% and （46.07±1.68）% respectively, with a statistically significant difference （F=780.47, P<0.001）. The absorbance values in the control group, 7 Gy group and 14 Gy group of polyploidy HeLa cells were 0.21±0.01, 0.23±0.02, 0.16±0.01 at 24 h, 0.37±0.03, 0.38±0.06, 0.21±0.00 at 48 h, 0.66±0.02, 0.55±0.01, 0.28±0.01 at 72 h, and there were statistically significant differences （F=31.62, P=0.001; F=20.10, P=0.002; F=708.52, P<0.001）. Further pairwise comparison showed that the proliferation abilities of polyploidy HeLa cells of the 14 Gy group at 24, 48 and 72 h were significantly lower than those of the control group and the 7 Gy group （all P<0.05）. The proportions of apoptotic cell subset in the control group, 7 Gy group and 14 Gy group were （3.67±1.16）%, （3.07±0.81）%, （3.83±0.91）%, the proportions of early apoptotic subset were （2.33±0.35）%, （2.13±0.61）%, （2.23±0.32）%, and the proportions of late apoptotic subset were （1.33±0.81）%, （0.93±0.31）%, （1.60±0.60）% respectively. There were no statistically significant differences （F=0.52, P=0.620; F=0.15, P=0.864; F=0.92, P=0.450）. The migrated numbers of cells in the control group, 7 Gy group and 14 Gy group were 297.40±26.53, 121.33±15.16, 18.40±4.79, and the invaded numbers were 195.67±20.26, 63.60±6.91, 9.47±3.23 respectively, with statistically significant differences （F=647.28, P<0.001; F=213.94, P<0.001）. Compared with the control group, the migration and invasion abilities of polyploid HeLa cells in the 7 Gy and the 14 Gy groups were significantly decreased, and the migration and invasion abilities of polyploid HeLa cells in the 14 Gy group were significantly lower than those in the 7 Gy group （all P<0.001）. The expression levels of P-STAT3 （Tyr 705） and Bcl-2 in radiation-induced polyploidy HeLa cells were higher than those in the control group, and the expression levels were further increased with the increase of radiation dose. Compared with the control group, the expression levels of Survivin and Mcl-1 in polyploid HeLa cells in the 14 Gy group were up-regulated （both P<0.05）. There was no significant difference in Bcl-xL expression among the three groups （F=0.52, P=0.618）. Conclusion The proliferation, migration and invasion abilities of polyploid HeLa cells are reduced by radiation, and the proportion of apoptotic subset is not significantly changed, but the activation of STAT3 signaling pathway is accompanied by up-regulation of downstream anti-apoptotic related proteins, which is favorable for the polyploid tumor cells to be the potential risk factor of recurrent cervical cancer after radiotherapy. Figures and Tables | References | Related Articles | Metrics

Predictive value of tissue TSR for the efficacy of immunotherapy in non-small lung cancer Xiao Mengxia, Yao Yi, Gao Likun, Song Qibin 2022, 49 (5):  270-275.  doi: 10.3760/cma.j.cn371439-20211123-00050 Abstract ( 241 )   HTML ( 21 )   PDF (1371KB) ( 130 )   Save Objective To explore the value of tumor stroma ratio （TSR） in non-small lung cancer （NSCLC） tissue in predicting the efficacy of tumor immunotherapy. Methods The clinical and histopathological data of patients with stage ⅢB-Ⅳ NSCLC treated with immune checkpoint inhibitors in the Renmin Hospital of Wuhan University from January 2017 to December 2020 were collected. Taking 50% as the TSR boundary value, the patients were divided into low TSR group （≤50%） and high TSR group （>50%）. The histopathological features, 4-cycle objective response rate （ORR） and disease control rate （DCR）, 6-cycle ORR and DCR, and progression-free survival （PFS） were compared between the two groups. Univariate and multivariate Cox regression models were used to analyze the prognostic factors related to PFS. Results A total of 50 patients were included, including 27 with low TSR and 23 with high TSR. There were no significant differences between the two groups in age （χ2=0.59, P=0.441）, gender （P=0.578）, smoking history （χ2=0.12, P=0.730）, histopathological type （χ2=2.33, P=0.313）, TNM stage （χ2=0.22, P=0.636）, 4-cycle ORR （χ2=0.48, P=0.487） and DCR （P=0.593）, 6-cycle ORR （χ2=0.05, P=0.818） and DCR （P=0.641）. The incidence of brain metastasis was higher in the high TSR group than that in the low TSR group [34.8% （8/23） vs. 7.4%（2/27）, χ2=4.23, P=0.040]. Kaplan-Meier survival analysis showed that the PFS in the low TSR group was significantly longer than that in the high TSR group （15.6 months vs. 10.2 months, χ2=13.84, P<0.001）. Univariate analysis showed that TSR value （HR=0.29, 95%CI： 0.14-0.58, P<0.001） and brain metastasis （HR=2.38, 95%CI： 1.12-5.05, P=0.024） were correlated with the worse prognosis of NSCLC patients. Multivariate Cox regression analysis showed that TSR value was an independent prognostic factor for NSCLC immunotherapy （HR=0.32, 95%CI： 0.14-0.70, P=0.004）. Conclusion TSR is an independent predictor of immunotherapy for NSCLC, but whether it can predict the short-term efficacy of immunotherapy for advanced NSCLC still needs further research. Figures and Tables | References | Related Articles | Metrics

Clinical efficacy and safety of camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in the treatment of HER-2 negative advanced gastric cancer Tang Lin, Xiang Mingyue, Zhang Jianbo, Wang Lili, Gong Heyi, Han Dali 2022, 49 (5):  276-281.  doi: 10.3760/cma.j.cn371439-20220111-00051 Abstract ( 329 )   HTML ( 22 )   PDF (967KB) ( 159 )   Save Objective To explore the clinical efficacy and safety of the camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in human epidermal growth factor receptor-2 （HER-2） negative advanced gastric cancer. Methods A total of 66 patients with HER-2 negative advanced gastric cancer and first-line treatment failure in Shandong Cancer Hospital Affiliated to Shandong First Medical University from March 2018 to September 2021 were selected. They were divided into study group （n=22） and control group （n=44） according to the different treatment regimens. The patients in the study group were treated with camrelizumab combined with apatinib and chemotherapy, and the patients in the control group were treated with chemotherapy alone. The short-term efficacy, progression-free survival （PFS）, overall survival （OS） and the occurrence of adverse reactions were compared, and Cox regression analysis was used to analyze the influencing factors of prognosis. Results After at least 2-4 cycles of treatment, the ORR in the study group and the control group were 9.1% （2/22） and 0 （0/44） respectively, with no statistically significant difference （P=0.108）. DCR in the two groups were 77.3% （17/22） and 45.5% （20/44） respectively, with a statistically significant difference （χ2=6.03, P=0.014）. The study group didn’t reach median OS and the median OS in the control group was 11.7 months, with no statistically significant difference （χ2=1.59, P=0.207）. The study group didn’t reach median PFS and the median PFS in the control group was 3.2 months, with a statistically significant difference （χ2=10.13, P=0.001）. Multivariate Cox regression analysis showed that treatment method was an independent influencing factor for PFS in patients with HER-2 negative advanced gastric cancer （HR=0.33, 95%CI： 0.15-0.75, P=0.008）. In terms of adverse reactions, there was a statistically significant difference in the incidence of elevated alanine aminotransferase between the study group and the control group [31.8% （7/22） vs. 6.8% （3/44）, χ2=5.32, P=0.021]. There were no adverse-related deaths in both groups. Conclusion Compared with chemotherapy alone, camrelizumab combined with apatinib and chemotherapy as a second-line or later therapy in HER-2 negative advanced gastric cancer can prolong PFS and improve DCR, but the incidence of elevated alanine aminotransferase increases significantly. Figures and Tables | References | Related Articles | Metrics

Expressions of HSP90α and HSP90β in colorectal cancer tissues and their clinical significances Chen Cunbao, Lu Shoutang, Wang Ruogu, Yang Jianshu, Li Jianqi, Zhen Yanan, Xu Zhongfa 2022, 49 (5):  282-284.  doi: 10.3760/cma.j.cn371439-20211210-00052 Abstract ( 277 )   HTML ( 26 )   PDF (1266KB) ( 137 )   Save Objective To study the expressions of heat shock protein （HSP）90α and HSP90β in colorectal cancer and paracancer tissues, and to investigate the relationships between HSP90α, HSP90β and clinicopathological features of colorectal cancer patients, and to analyze their correlation. Methods The tumor tissues and paracancer tissues of 117 patients with colorectal cancer were selected from the Department of Gastrointestinal Surgery, Third Affiliated Hospital of Shandong First Medical University from January 2016 to December 2020. The expression levels of HSP90α and HSP90β were detected by immunohistochemistry, and the relationships between the two proteins and clinicopathological features and the correlation of their expressions were analyzed. Results The positive expression rates of HSP90α in colorectal cancer tissues and paracancer tissues were 74.4% （87/117） and 12.0% （14/117）, and there was a statistically significant difference （χ2=92.83, P<0.001）. The positive expression rate of HSP90β in colorectal cancer tissues and paracancer tissues was 61.5% （72/117） and 10.3% （12/117）, and there was a statistically significant difference （χ2=66.86, P<0.001）. The expression of HSP90α was correlated with tumor location （χ2=8.67, P=0.003）, vascular invasion （χ2=8.68, P=0.003）, lymph node metastasis （χ2=8.52, P=0.004）, T stage （χ2=21.07, P<0.001）, N stage （χ2=11.94, P=0.003）, M stage （χ2=5.37, P=0.020）, pathological stage （χ2=25.64, P<0.001）. The expression of HSP90β was correlated with lymph node metastasis （χ2=4.03, P=0.045）, T stage （χ2=11.09, P=0.007）, N stage （χ2=6.56, P=0.038）, M stage （χ2=12.43, P<0.001）, pathological stage （χ2=17.34, P=0.001）. There was a positive correlation between the expressions of the two proteins in colorectal cancer tissues （r=0.42, P<0.001）. Conclusion The expressions of HSP90α and HSP90β in colorectal cancer tissues are significantly higher than those in paracancer tissues, and they are related to lymph node metastasis and pathological stage. There is a positive correlation between the two proteins, which may be involved in the occurrence and development of colorectal cancer and are expected to become new tumor markers. Figures and Tables | References | Related Articles | Metrics

Clinical efficacy and safety of ixazomib-based therapy in the treatment of relapsed or refractory multiple myeloma Gao Shan, Lu Minqiu, Shi Lei, Chu Bin, Fang Lijuan, Xiang Qiuqing, Wang Yutong, Ding Yuehua, Bao Li 2022, 49 (5):  286-291.  doi: 10.3760/cma.j.cn371439-20211202-00053 Abstract ( 262 )   HTML ( 14 )   PDF (793KB) ( 169 )   Save Objective To investigate the clinical efficacy and safety of ixazomib-based therapy in patients with relapsed or refractory multiple myeloma （RRMM）. Methods A retrospective analysis was performed on the efficacy and adverse reactions of 53 RRMM patients treated with a combined regimen containing ixazomib in the Hematology Department of Beijing Jishuitan Hospital from July 8, 2018 to November 30, 2020. Among them, 6 patients received ID regimen （ixazomib + dexamethasone）, 30 patients received ID regimen + immunomodulator, and 17 patients received ID regimen + other chemotherapy drugs. Results Fifty-three patients with RRMM received ixazomib-based therapy. The median previous treatment line was 3, the median treatment course was 6 （2-30）, and the median follow-up time was 21 months （2-32 months）. The overall response rate （ORR） was 54.7% （29/53） after 2 courses of treatment. Among them, 26.4% （14/53） had very good partial response （VGPR） and 28.3% （15/53） had partial response （PR）. The ORR of the ID regimen group, ID regimen + immunomodulator group and ID regimen + other chemotherapy group were 83.3% （5/6）, 56.7% （17/30） and 41.2% （7/17） respectively, with no statistically significant difference among the three groups （P=0.208）. The median time to progression （TTP） of 53 patients was 8 months （1-24 months）. The most frequent adverse events of ixazomib treatment were gastrointestinal reactions such as nausea, vomit and diarrhea, with an incidence of 37.7% （20/53）, and the incidence of grade 3-4 was 5.7% （3/53）. The most common hematological adverse events were thrombocytopenia （15.1%, 8/53）, neutropenia （11.3%, 6/53） and anemia （9.4%, 5/53）. Grade 1-2 peripheral neurotoxicity occurred in only 7.5% （4/53） of patients. Conclusion Ixazomib has good efficacy and safety for the patients with RRMM in the real world. Figures and Tables | References | Related Articles | Metrics

Reviews

Research progress of metformin in tumor immunotherapy Ning Tingting, Hu Qinyong 2022, 49 (5):  292-295.  doi: 10.3760/cma.j.cn371439-20220228-00054 Abstract ( 280 )   HTML ( 30 )   PDF (730KB) ( 215 )   Save In recent decades, immune checkpoint inhibitors （ICIs） have ushered in a new era in oncology treatment. Despite the remarkable efficacy of ICIs, there are still many patients who do not benefit from immunotherapy alone. Combination therapy is currently the main research direction in China and abroad. Metformin can enhance the number and function of T cells, affect macrophage polarization, promote natural killer cell activation and regulate immune checkpoint expression. A large number of preclinical and clinical studies are exploring the efficacy and safety of ICIs in combination with metformin in different tumors. References | Related Articles | Metrics

Application of antibody-drug conjugates in the treatment of non-small cell lung cancer Zhang Jingxian, Yi Dan, Li Xiaojiang 2022, 49 (5):  296-301.  doi: 10.3760/cma.j.cn371439-20220309-00055 Abstract ( 260 )   HTML ( 16 )   PDF (748KB) ( 194 )   Save Antibody-drug conjugates （ADCs） have overcome the limitations of traditional chemotherapy and targeted therapy with unique advantage of antibody targeting, and made breakthrough achievements in the treatment of lung cancer. At present, the researches of ADCs in non-small cell lung cancer mainly involve HER2, HER3, TROP2, MET, CEACAM5. Many ADCs have passed rigorous clinical trials, and have shown good safety and efficacy, which provides theoretical basis for individualized treatment of lung cancer. References | Related Articles | Metrics

Correlations between genomic and transcriptome characteristics and immune in hepatocellular carcinoma Sun Xiaoke, Yang Yu 2022, 49 (5):  302-306.  doi: 10.3760/cma.j.cn371439-20220221-00056 Abstract ( 253 )   HTML ( 21 )   PDF (733KB) ( 128 )   Save Hepatocellular carcinoma is a common malignant tumor in China, and its global incidence continues to rise and the mortality rate is high. Aberrations in the liver genome lead to malignant transformation of cells and the development of hepatocellular carcinoma, which are also potential therapeutic targets. Different immune cell components in the hepatocellular carcinoma microenvironment, such as tumor-associated macrophages, neutrophils, can promote tumor progression, and cytotoxic T lymphocytes can destroy tumor cells. Different characteristic gene phenotypes in cells can promote or inhibit immune tolerance, which can explain the potential reasons for the sensitivity or resistance of hepatocellular carcinoma patients to immunotherapy, and provide a reference for the exploration of new immunotherapy targets. Further deepening the understanding of the genomic and transcriptomic features in hepatocellular carcinoma and its correlation with immunotherapy can provide new ideas for clinical diagnosis and treatment. Figures and Tables | References | Related Articles | Metrics

Research progress on prognostic factors of cervical cancer Yuan Chenyang, Zhou Juying 2022, 49 (5):  307-313.  doi: 10.3760/cma.j.cn371439-20220303-00057 Abstract ( 286 )   HTML ( 21 )   PDF (761KB) ( 169 )   Save At present, the clinical judgment of cervical cancer prognosis is mainly based on common pathological factors, such as tumor size, lymph node metastasis, and the depth of interstitial invasion. In recent years, with the advancement of technology, many biomarkers have been proved to be closely related to the diagnosis and prognosis of cervical cancer. Hematological parameters and other medical diseases also affect the survival of cervical cancer patients to some extent. References | Related Articles | Metrics