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08 January 2024, Volume 51 Issue 1 Previous Issue    Next Issue

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Chlorogenic acid induces mitochondrial dysfunction in lung cancer A549 cells by inhibiting the PI3K-Akt pathway Zhang Keping, Zhao Yongsheng, Yang Juan, Fu Maoyong 2024, 51 (1):  21-28.  doi: 10.3760/cma.j.cn371439-20230906-00002 Abstract ( 105 )   HTML ( 18 )   PDF (2924KB) ( 65 )   Save Objective To investigate whether chlorogenic acid can inhibit the proliferation， migration， invasion and promote apoptosis of lung cancer A549 cells by causing mitochondrial dysfunction through PI3K-Akt pathway. Methods A549 cells were treated with chlorogenic acid at concentrations of 0， 25， 50， 100， 150， and 200 μg/ml for 48 h. CCK-8 assay was used to detect the cell proliferation rate and calculate the half maximal inhibitory concentration （IC50）. A549 cells were divided into three groups： control group， chlorogenic acid group （IC50） and chlorogenic acid + 740-YP group （IC50 chlorogenic acid +50 μg/ml 740YP）. After 48 h of intervention， the cell migration distance was detected by cell scratch assay. Cell invasion assay was used to detect cell invasion ability. Cell cycle， apoptosis and mitochondrial membrane potential were detected by flow cytometry. The content of malondialdehyde （MDA） in cell supernatant was detected by enzyme-linked immunosorbent assay （ELISA）. Western blotting was used to detect the protein expression of p-PI3K， p-Akt and Caspase3. Results The IC50 of chlorogenic acid to A549 cells was 57.45 μg/ml. The results of cell scratch assay showed that the 48 h migration distances of the control group， chlorogenic acid group and chlorogenic acid + 740YP group were （424.80±14.43）， （289.67±18.93） and （402.22±17.99） μm， respectively. The results of cell invasion assay showed that the numbers of invasive cells after 48 h were 96.00±6.24， 35.33±7.64 and 83.00±2.00， and the results of flow cytometry showed that the 48 h apoptosis rates were （6.15±0.17）%， （54.63±0.72）% and （17.27±0.39）%， respectively， among the three groups with statistically significant differences （F=105.98， P<0.001； F=90.62， P<0.001； F=8 321.99， P<0.001）. Compared with the control group， the cell migration distances and invasive numbers of chlorogenic acid group and chlorogenic acid + 740YP group were decreased （all P<0.05）， while the apoptosis rates were significantly increased （both P<0.001）. Compared with chlorogenic acid group， the cell migration distance of chlorogenic acid + 740YP group increased （P<0.001）， the number of cell invasion increased （P<0.001）， and the apoptosis rate decreased （P<0.001）. The results of flow cytometry showed that the proportions of cells in G0/G1 phase in the control group， chlorogenic acid group and chlorogenic acid + 740YP group were （65.75±0.58）%， （55.84±0.78）% and （55.24±1.37）%， respectively. The proportions of G2/M phase were （11.21±1.03）%， （20.23±0.62）% and （9.96±0.33）%， and the proportions of S phase were （23.04±0.49）%， （23.92±1.36）% and （34.80±1.15）%， respectively， with statistically significant differences （F=111.02， P<0.001； F=181.26， P<0.001； F=113.05， P<0.001）. Compared with the control group， the proportions of G0/G1 phase cells in chlorogenic acid group and chlorogenic acid + 740YP group decreased （both P<0.001）， and the proportion of G2/M phase in chlorogenic acid group increased （P<0.001）， and the proportion of S phase cells in chlorogenic acid + 740YP group increased （P<0.001）. Compared with chlorogenic acid group， the proportion of G2/M phase cells decreased and the proportion of S phase cells increased in chlorogenic acid + 740YP group （both P<0.001）. The results of mitochondrial membrane potential detection showed that the JC-1 fluorescence intensity of mitochondria in the control group， chlorogenic acid group and chlorogenic acid + 740YP group were 39.51±1.32， 10.05±0.19 and 21.85±1.45， respectively， with a statistically significant difference （F=508.82， P<0.001）. Compared with the control group， the fluorescence intensity of chlorogenic acid group and chlorogenic acid + 740YP group decreased （both P<0.001）. Compared with chlorogenic acid group， the fluorescence intensity of chlorogenic acid + 740YP group increased （P<0.001）. ELISA results showed that the MDA contents of the control group， chlorogenic acid group and chlorogenic acid + 740YP group were （0.47±0.01）， （0.61±0.01） and （0.56±0.01） nmol/ml， respectively， with a statistically significant difference （F=162.30， P<0.001）. Compared with the control group， MDA contents in chlorogenic acid group and chlorogenic acid + 740YP group increased （both P<0.001）. Compared with chlorogenic acid group， MDA content in chlorogenic acid + 740YP group decreased （P=0.001）. Western blotting results showed that the relative protein expression levels of p-PI3K in the control group， chlorogenic acid group and chlorogenic acid + 740YP group were 1.01±0.33， 0.28±0.14 and 0.34±0.20， respectively. The relative protein expression levels of p-Akt were 1.00±0.16， 0.43±0.05 and 0.95±0.14， and the relative protein expression levels of Caspase3 were 1.00±0.04， 1.41±0.05 and 0.70±0.13， respectively， and there were statistically significant differences （F=8.48， P=0.018； F=19.11， P=0.002； F=57.50， P<0.001）. Compared with the control group， the expressions of p-PI3K and p-Akt protein in chlorogenic acid group decreased， and the expression of Caspase3 protein increased （all P<0.05）. The expressions of p-PI3K and Caspase3 protein in chlorogenic acid + 740YP group decreased （both P<0.05）. Compared with chlorogenic acid group， the expression of p-Akt protein in chlorogenic acid + 740YP group increased， and the expression of Caspase3 protein decreased （both P<0.05）. Conclusion Chlorogenic acid may inhibit the PI3K-Akt pathway by reducing the phosphorylation of PI3K and Akt proteins， resulting in the damage of mitochondrial function and the accumulation of MDA， which eventually leads to the damage of lung cancer A549 cells function and the reduction of cells activity， and then promotes cells apoptosis. Figures and Tables | References | Related Articles | Metrics

Comparative analysis of lung cancer incidence and mortality trends and risk factors in China and the United States based on GBD data He Jiahui, Hu Qinyong 2024, 51 (1):  29-36.  doi: 10.3760/cma.j.cn371439-20230810-00003 Abstract ( 177 )   HTML ( 22 )   PDF (2193KB) ( 68 )   Save Objective To conduct comparative analysis of lung cancer incidence and mortality， as well as long-term trends in incidence and mortality rates and risk factors in China and the United States from 1990 to 2019 based on data from the Global Burden of Disease Study 2019 （GBD 2019）. Methods The GBD 2019 database was used to extract new lung cancer cases， deaths， and age-standardized rate data for the analysis of lung cancer incidence and deaths in China and the United States based on different sex and age groups from 1990 to 2019. Joinpoint software was used to calculate and analyze annual percentage change （APC） and average annual percentage change （AAPC） of age-standardized incidence rate （ASIR） and age-standardized mortality rate （ASMR） of lung cancer in China and the United States from 1990 to 2019， and to analyze the long-term trends. Risk factors associated with lung cancer mortality in China and the United States were analyzed using the disability-adjusted life years （DALYs）. Results New cases of lung cancer in China increased from 257 000 cases in 1990 to 832 900 cases in 2019， and ASIR increased from 30.20/100 000 in 1990 to 41.71/100 000 in 2019； deaths increased from 256 300 cases in 1990 to 757 200 cases in 2019， and ASMR increased from 31.18/100 000 in 1990 to 38.70/100 000 in 2019. ASIR and ASMR for lung cancer in the United States showed a decreasing trend from 1990 to 2019， with ASIR decreasing from 58.87/100 000 in 1990 to 45.13/100 000 in 2019， and ASMR decreasing from 49.35/100 000 in 1990 to 36.11/100 000 in 2019. In terms of gender， the disease burden of lung cancer in Chinese males was higher than that of females in 1990 and 2019， with new cases of lung cancer in males rising from 179 000 in 1990 to 576 200 in 2019， and ASIR rising from 44.29/100 000 in 1990 to 61.74/100 000 in 2019， mortality rising from 177 900 in 1990 to 523 200 in 2019， and ASMR rising from 46.33/100 000 in 1990 to 58.10/100 000 in 2019. The number of new cases of lung cancer in Chinese females rose from 78 100 in 1990 to 256 700 in 2019， and ASIR rose from 18.01/100 000 in 1990 to 24.76/100 000 in 2019； the number of deaths rose from 78 400 in 1990 to 234 000 in 2019， and ASMR rose from 18.63/100 000 in 1990 to 22.86/100 000 in 2019. In 2019， lung cancer incidence rates for males and females in China and the United States showed an increasing and then decreasing trend with age， with incidence rates of lung cancer in Chinese males and females peaking in the age group of 85-89 years old； and in the United States， incidence rates of lung cancer in males peaked in the age group of 85-89 years old， and incidence rates of females peaked in the age group of 80-84 years old. In 2019， it was shown that mortality rate of lung cancer among males in China increased and then decreased with age， reaching a peak in the age group of 85-89 years old， and mortality rate of lung cancer among females increased with age， reaching a peak in the age group of ≥95 years old. In the United States， lung cancer mortality rate for males and females showed an increasing and then decreasing trend with age， peaking in the 85-89 and 80-84 age groups， respectively. Incidence and mortality rates were higher for males than females in all age groups in China and the United States in 1990 and 2019. The analysis results of Joinpoint software showed that ASIR and ASMR of lung cancer in China showed an overall increasing trend from 1990 to 2019， with an AAPC of 1.16% （95%CI： 0.93%-1.38%， P<0.001） for ASIR and 0.78% （95%CI： 0.56%-1.01%， P<0.001） for ASMR， with the most obviously increasing trend in ASIR and ASMR from 1997 to 2004， the APC were 2.84% and 2.58%， respectively. Lung cancer ASIR and ASMR in the United States population showed a decreasing trend， with an AAPC of -1.08% （95%CI： -1.20%-0.96%， P<0.001） for ASIR and -1.05% （95%CI： -1.24%--0.87%， P<0.001） for ASMR. In 1990 and 2019， the major mortality-related risk factor for lung cancer in China and the United States was smoking， and the major mortality-related risk factor for lung cancer in Chinese females was environmental particulate matter pollution. Conclusion ASIR and ASMR of lung cancer in China show an increasing trend from 1990 to 2019， and ASIR and ASMR of lung cancer in the United States show a decreasing trend. In 2019， incidence rate of lung cancer in males and females in China show an increasing and then decreasing trend with age， mortality rate of lung cancer for males show an increasing and then decreasing trend with age， and mortality rate of lung cancer for females show an increasing trend with age. Lung cancer incidence and mortality rates for males and females in the United States in 2019 show an increasing and then decreasing trend with age. In both 1990 and 2019， incidence rates and mortality rates are higher for males than for females in all age groups in both China and the United States. Smoking is the major mortality-related risk factor for lung cancer in China and the United States， and environmental particulate matter pollution is the major mortality-related risk factor for lung cancer in Chinese females. 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Clinical application of MR-guided radiotherapy based on MR-linac in esophageal cancer patients Gao Xinyu, Li Zhenjiang, Sun Hongfu, Han Dan, Zhao Qian, Liu Chengxin, Huang Wei 2024, 51 (1):  37-42.  doi: 10.3760/cma.j.cn371439-20230730-00004 Abstract ( 69 )   HTML ( 18 )   PDF (1070KB) ( 45 )   Save Objective To explore the application process， efficacy and safety of MR-guided radiotherapy based on MR-linac in esophageal cancer. Methods The clinical data of patients with esophageal cancer treated with MR-linac at Shandong Cancer Hospital and Institute from September 2021 to July 2022 were retrospectively analyzed， to investigate the treatment process of esophageal cancer with MR-linac， and to analyze the efficacy and safety of patients. All patients received MR-guided radiotherapy， underwent CT and MR localization， target area delineation， and design of the Monaco treatment planning system plan. Adaptation-to-position adjustment was conducted during the pre-treatment evaluation. The median number of fractions was 25， the median single dose of planning target volume was 1.8 Gy， and the median total dose was 50.2 Gy. Median follow-up was 16 months. Results Among the 12 patients in the whole group， there were 1 case of cervical esophageal cancer， 3 cases of upper thoracic esophageal cancer， 4 cases of middle thoracic esophageal cancer and 4 cases of lower thoracic esophageal cancer， including 3 cases of neoadjuvant radiotherapy and 9 cases of radical radiotherapy. All patients had a smooth treatment process. The median treatment time was 33 min， and the patients had good compliance. For patients with radical radiotherapy， one month after radiotherapy， the number of objective remission cases was 3， and the number of disease-control cases was 9； six months after radiotherapy， the number of objective remission cases was 3， and the number of disease-control cases was 6. All patients treated with neoadjuvant radiotherapy underwent surgery within 2 months， and one patient achieved pathological complete remission. The most common acute adverse reactions were radiation esophagitis （7 cases） and leukopenia in bone marrow suppression （8 cases）， with late-stage adverse reactions being radiation pneumonia （1 case）. The adverse reactions to radiotherapy were slight， and no grade 4 or above adverse reactions were observed. Conclusion The clinical treatment process for esophageal cancer under MR-guided radiotherapy based on MR-linac is feasible， with good curative effects and mild adverse reactions. Figures and Tables | References | Related Articles | Metrics

Application and evaluation study of 3D ultrasound in image guided radiotherapy for prostate cancer Zhao Xin, Fan Xuewu, Tian Long, Hu Yimin 2024, 51 (1):  43-49.  doi: 10.3760/cma.j.cn371439-20230418-00005 Abstract ( 53 )   HTML ( 6 )   PDF (1155KB) ( 35 )   Save Objective To evaluate the accuracy of 3D ultrasound calibration in image guided radiotherapy for prostate cancer by taking cone beam CT calibration as the gold standard， and to analyze the risk factors of accuracy. Methods From December 2018 to December 2021， 51 patients with prostate cancer from the Department of Radiation Oncology， First Affiliated Hospital of Hebei North University were selected as the study subjects. They received cone beam CT calibration based on bone and 3D ultrasound calibration based on soft tissue before fraction volumetric modulated arc therapy treatment three times a week. Taking cone beam CT calibration data as the gold standard， the Bland-Altman method was used to analyze the consistency of 3D ultrasound calibration data with the former. Taking 3 mm as the allowable threshold of accuracy， the calibration accuracy of 3D ultrasound relative to cone beam CT was evaluated. Logistic regression was used to analyze the risk factors affecting the accuracy of 3D ultrasound calibration. Results A total of 765 pairs of cone beam CT and 3D ultrasound calibration data were obtained from 51 patients in left-right， superior-inferior and anterior-posterior directions. The calibration data of 3D ultrasound and cone beam CT were （1.39±0.11） and （1.13±0.07） mm in the left-right direction， （1.98±0.20） and （1.61±0.12） mm in the superior-inferior direction， （2.68±0.48） and （1.78±0.27） mm in the anterior-posterior direction， respectively， with statistically significant differences （t=-6.42， P<0.001； t=-7.07， P<0.001； t=-7.34， P<0.001）. The analysis results of Bland-Altman showed that the consistency of calibration data of the two methods were acceptable in three directions. The number of pairs of 3D ultrasound relative to cone beam CT calibration data difference <3 mm in the three directions were 676 （88.37%） on the left-right direction， 604 （78.95%） on the superior-inferior direction， and 577 （75.42%） on the anterior-posterior direction. The factors with statistically significant differences in the left-right direction included age （χ2=18.27， P<0.001）， prostate volume （χ2=14.55， P<0.001）， Charlson comorbidity index （CCI）（χ2=8.01， P=0.005） and field range （χ2=11.30， P<0.001）. Age （OR=2.02， 95%CI： 1.90-3.39， P=0.010） and the field range （OR=1.45， 95%CI： 1.18-2.55， P=0.020） were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the left-right direction. The factors with statistically significant differences in the superior-inferior direction included age （χ2=80.68， P<0.001）， body mass index （χ2=35.89， P<0.001） and field range （χ2=40.39， P<0.001）. Age （OR=1.49， 95%CI： 1.15-2.09， P=0.021） and the field range （OR=1.10， 95%CI： 1.01-1.90， P=0.034） were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the superior-inferior direction. The factors with statistically significant differences in the anterior-posterior direction included age （χ2=46.07， P<0.001）， CCI （χ2=47.97， P<0.001） and field range（χ2=11.86， P=0.001）. Age （OR=1.91， 95%CI： 1.22-3.45， P=0.015） and the field range （OR=2.89， 95%CI： 1.45-3.90， P=0.001） were the independent risk factors affecting the accuracy of 3D ultrasound calibration in the anterior-posterior direction. Conclusion The consistency and accuracy of the calibration results of 3D ultrasound relative to cone beam CT are acceptable. It is necessary to consider the patient's age and field range to reduce the impact on accuracy before conducting 3D ultrasound calibration. Figures and Tables | References | Related Articles | Metrics

Reviews

Research progress of myeloid-derived suppressor cells in tumor angiogenesis Liu Xiaodi, Su Jianfei, Zhang Jingxian, Wei Xueqin, Jia Yingjie 2024, 51 (1):  50-54.  doi: 10.3760/cma.j.cn371439-20230227-00006 Abstract ( 111 )   HTML ( 14 )   PDF (743KB) ( 77 )   Save As a kind of immunosuppressive cells， myeloid-derived suppressor cells （MDSCs） are an important component of the immune microenvironment. MDSCs play a significant role in promoting tumor immune escape. In addition， non-immunological functions such as promoting angiogenesis can also promote tumor development with the deepening of research. MDSCs can promote tumor angiogenesis directly through vascular endothelial growth factor signaling pathway， or promote tumor growth and angiogenesis by secreting cytokines such as matrix metalloprotein-9， basic fibroblast growth factor， angiogenic peptide Bv8， platelet derived growth factor， exosomes， or interacting with other cells. Exploring the expansion， activation， recruitment and angiogenesis mechanism of MDSCs will provide new ideas for regulating the individualized diagnosis and treatment based on targeted MDSCs. References | Related Articles | Metrics

Breast microbiota and breast cancer： present and future Gu Huayan, Zhu Teng, Guo Guilong 2024, 51 (1):  55-58.  doi: 10.3760/cma.j.cn371439-20230627-00007 Abstract ( 115 )   HTML ( 27 )   PDF (699KB) ( 86 )   Save In recent years, studies have found that breast microbiota differs between breast cancer tissue and normal breast tissue. Breast microbiota is closely related to the occurrence and development of breast cancer, and its mechanism includes affecting estrogen levels, lipid metabolism, immune regulation, and inflammatory response. Adjusting diet, rational use of antibiotics and oral probiotics can regulate breast microbiota, which is a new direction for the prevention and treatment of breast cancer. References | Related Articles | Metrics

Research progress of circulating tumor DNA in the diagnosis and treatment of hepatocellular carcinoma Huang Zhen, Chen Yongshun 2024, 51 (1):  59-64.  doi: 10.3760/cma.j.cn371439-20230722-00008 Abstract ( 80 )   HTML ( 14 )   PDF (735KB) ( 51 )   Save Hepatocellular carcinoma （HCC） is malignant tumor with the fourth incidence rate and the second mortality rate in China, and patients with advanced stage have lost the chance of surgical treatment, short survival period and extremely poor prognosis. Histopathological biopsy is the gold standard for clinical diagnosis of malignant tumors, but histopathological biopsy is not only invasive, but also obtains fewer tissue samples, which does not reflect the heterogeneity of tumors, and makes it difficult to dynamically monitor the progression of tumors or the efficacy of treatment. Therefore, it is clinically important to find new non-invasive strategies for early detection of HCC and to monitor the efficacy of HCC. Circulating tumor DNA is a non-invasive liquid biopsy method with simple sampling and can dynamically monitor the genomic changes of tumors, which has great application value in early diagnosis, therapeutic efficacy monitoring, and prognostic evaluation of HCC. References | Related Articles | Metrics