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Journal of International Oncology 2024, 51 (1): 1-20. DOI:10.3760/cma.j.cn371439-20231221-00001 Abstract（ 174） HTML（ 60） PDF（pc）（2788KB）（ 131） Knowledge map Save Table and Figures|Reference|Related Articles|Metrics|Comments（0）

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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 Journal of International Oncology 2024, 51 (1): 29-36. DOI:10.3760/cma.j.cn371439-20230810-00003 Abstract（ 139） HTML（ 13） PDF（pc）（2193KB）（ 32） Knowledge map Save ObjectiveTo 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）. MethodsThe 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）. ResultsNew 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. ConclusionASIR 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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Advances in immunotherapy for breast cancer Sa Qiang, Xu Hangcheng, Wang Jiayu Journal of International Oncology 2024, 51 (4): 227-234. DOI:10.3760/cma.j.cn371439-20231017-00038 Abstract（ 133） HTML（ 5） PDF（pc）（764KB）（ 45） Knowledge map Save According to the latest global cancer burden data for 2020 released by the WHO's International Agency for Research on Cancer， breast cancer has become the malignant tumor with the highest incidence worldwide. Based on existing internal medicine treatment means like chemotherapy， targeted therapy and endocrine therapy， the development of immunotherapy provides novel solutions for the treatment of breast cancer. To date， the clinical research of immunotherapy in various molecular types and stages of breast cancer has reached certain achievements. In addition， the exploration of joint application with other therapies， predictive markers for efficacy， and immune-related adverse effects is also ongoing. The research and development in the field of breast cancer immunotherapy holds a promising prospect， and approaching research advances will promote the further application of immunotherapy in breast cancer. Table and Figures|Reference|Related Articles|Metrics|Comments（0）

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Mechanism of hydrogen sulfide in tumorigenesis and development and its donor-mediated anti-tumor effects Zhu Yi, Chen Jian Journal of International Oncology 2023, 50 (12): 729-733. DOI:10.3760/cma.j.cn371439-20230605-00137 Abstract（ 125） HTML（ 4） PDF（pc）（740KB）（ 26） Knowledge map Save Hydrogen sulfide is a gas signaling molecule in the human body that can influence angiogenesis， regulate tumor cell apoptosis and autophagy， and interact with other signaling molecules in the tumor microenvironment. It plays a role in inhibiting tumorigenesis and development through various pathways. Hydrogen sulfide donors primarily exhibit anti-tumor effects， and many studies are focused on using various donors to release hydrogen sulfide in a controlled manner and maintain therapeutic concentrations. Traditional Chinese medicine shows great potential. The mechanisms of hydrogen sulfide action are complex and diverse， and further research is needed to explore and confirm them， providing a theoretical basis for the development of therapeutic drugs regulating hydrogen sulfide. Reference|Related Articles|Metrics|Comments（0）

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Research progress of NADPH oxidase 2 in malignant tumors Liu Xiaojie, Huang Junxing Journal of International Oncology 2023, 50 (10): 618-621. DOI:10.3760/cma.j.cn371439-20230428-00117 Abstract（ 123） HTML（ 21） PDF（pc）（721KB）（ 72） Knowledge map Save Reduced nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 2 （Nox2） acts as a source of reactive oxygen species， which participates in and influences normal physiological function of human body. Nowadays， many studies have found that Nox2 is related to prognosis of patients， drug resistance and molecular targeted therapy in various malignant tumors， such as acute myeloid leukemia， gastric cancer， colorectal cancer， ovarian cancer， lung cancer and esophageal cancer. What's more， it may be a novel biomarker and a potential therapeutic target for malignant tumors. Reference|Related Articles|Metrics|Comments（0）

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Research progress of habitat analysis in radiomics of malignant tumors Fu Yi, Ma Chenying, Zhang Lu, Zhou Juying Journal of International Oncology 2024, 51 (5): 292-297. DOI:10.3760/cma.j.cn371439-20240108-00049 Abstract（ 117） HTML（ 3） PDF（pc）（722KB）（ 37） Knowledge map Save Nowadays， the research on traditional radiomics has gradually matured. However， it usually regards the tumor as a whole， and high-throughput data are often generated in the entire tumor region， which cannot express clear spatial heterogeneity. In order to explore the potential biological information within tumors and realize individualized precise diagnosis and treatment， habitat analysis technology emerges at the historic moment， which provides a new way of thinking to identify tumor microenvironment. On the basis of traditional radiomics， the tumor cell population with similar characteristics is clustered， and the tumor is segmented into multiple sub-regions. Therefore， the study of tumor is no longer limited by the subjective differences of observers in the description of imaging features， and the information of tumor spatial heterogeneity is ideally obtained. Reference|Related Articles|Metrics|Comments（0）

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Research progress on intestinal flora and non-surgical treatment of the colorectal cancer Gao Fan, Wang Ping, Du Chao, Chu Yanliu Journal of International Oncology 2024, 51 (6): 376-381. DOI:10.3760/cma.j.cn371439-20240429-00065 Abstract（ 108） HTML（ 3） PDF（pc）（744KB）（ 11） Knowledge map Save In recent years， intestinal flora has gradually become the focus of research on the treatment of malignant neoplasms. Intestinal opportunistic pathogens （such asFusobacterium nucleatum，Bacteroides fragilis）， intestinal probiotics （such asClostridium butyricum，Lactic acid bacteria） and intestinal pathogenic bacteria （such asSalmonella，Shigella） can affect the efficacy and related adverse reactions of radiotherapy， chemotherapy and immunotherapy for the colorectal cancer （CRC） by influencing signaling pathways， modulating autophagy， regulating immune response， producing metabolites and toxins， and transplanting fecal bacteria. At the same time， it provides a large number of potential targets for targeted therapy of the CRC. Further research on the relationship between intestinal flora and non-surgical treatment of the CRC can provide references for basic and clinical research of non-surgical treatment of the CRC. Reference|Related Articles|Metrics|Comments（0）

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Pemetrexed clinical trial for intrathecal injection chemotherapy based on cerebrospinal fluid pharmacokinetics in patients with leptomeningeal metastasis from lung adenocarcinoma Xie Yu, Zheng Shengnan, Huang Mingmin, Guo Aibin, Yin Zhenyu, Lin Yongjuan Journal of International Oncology 2023, 50 (10): 585-591. DOI:10.3760/cma.j.cn371439-20230612-00112 Abstract（ 108） HTML（ 26） PDF（pc）（770KB）（ 45） Knowledge map Save ObjectiveTo investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis （LM） from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy.MethodsA total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapyviaOmmaya capsule at Nanjing Drum Tower Hospital， Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected， and divided into 30， 40 and 50 mg groups （n=10，n=4，n=7）according to pemetrexed dose. Cerebrospinal fluid was collected at 0， 0.5， 1， 2， 4， 6， 12， 24 and 48 h after the first intrathecal injection chemotherapy， and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid， to clarify the drug-related pharmacokinetic parameters， and to compare the differences in pemetrexed concentration among groups. Finally， cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles.ResultsThere were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0， 0.5， 1， 2， 4， 6， 12， 24 and 48 h after the first intrathecal injection chemotherapy （30 mg group：F=20.56，P<0.001； 40 mg group：F=27.06，P<0.001； 50 mg group：F=28.63，P<0.001）， and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5， 1， 2， 4， 6 and 12 h compared to 0 h after intrathecal injection chemotherapy （allP<0.05）. Compared to the 30 mg group， cerebrospinal fluid drug concentrations in the 50 mg group increased at 1， 2， 4， 6， 12 and 24 h after intrathecal injection chemotherapy， with statistically significant differences （allP<0.05）. Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve （AUC）0-∞of the 30， 40 and 50 mg groups were （5 696.12±283.32）， （7 886.29±396.57）， and （14 202.70±440.19） h·mg/L， respectively， with a statistically significant difference （F=1 159.00，P<0.001）； AUC0-∞increased in the 50 mg group compared to the 30 and 40 mg groups （bothP<0.05）； AUC0-∞increased in the 40 mg group compared to the 30 mg group （P<0.05）. The half-lives of three groups were （8.75±0.23）， （11.29±0.59） and （16.42±1.23） h， respectively， with a statistically significant difference （F=206.80，P<0.001）； half-life was longer in the 50 mg group compared to the 30 and 40 mg groups （bothP<0.05）； half-life was longer in the 40 mg group compared to the 30 mg group （P<0.05）. The peak time of three groups were （1.55±0.10）， （1.00±0.01）， （1.43±0.11） h， respectively， with a statistically significant difference （F=48.11，P<0.001）； the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group （bothP<0.05）. Clearance of three groups were （7.02±2.46）， （5.80±1.25） and （3.66±1.32） L/h， respectively， with a statistically significant difference （F=6.02，P=0.009）； clearance was decreased in the 50 mg group compared to the 30 mg group （P<0.05）. The peak concentration of three groups were （540.45±32.25）， （820.75±46.47） and （1 014.78±64.96） mg/L， respectively， with a statistically significant difference （F=207.70，P<0.001）； peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups （bothP<0.05）； peak concentration increased in the 40 mg group compared to the 30 mg group （P<0.05）. Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy， in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were （13.76±4.79）， （11.41±7.08）， （9.41±2.59） and （7.86±4.02） mg/L， respectively； 40 mg group were （14.45±6.59）， （12.87±15.73）， （11.24±2.48） and （9.09±3.38） mg/L， respectively； 50 mg group were （12.94±10.34）， （9.72±7.62）， （8.15±8.17） and （4.34±4.21） mg/L， respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group （F=4.04，P=0.016）， and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 （bothP<0.05）. There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups （F=0.28，P=0.837；F=3.57，P=0.066）.ConclusionReversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid； dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma. Table and Figures|Reference|Related Articles|Metrics|Comments（0）

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Research progress of EBV in tumor immune microenvironment and immunotherapy of nasopharyngeal carcinoma Xu Fenglin, Wu Gang Journal of International Oncology 2024, 51 (6): 359-363. DOI:10.3760/cma.j.cn371439-20240119-00062 Abstract（ 99） HTML（ 3） PDF（pc）（698KB）（ 19） Knowledge map Save Nasopharyngeal carcinoma is a type of cancer closely related to Epstein-Barr virus （EBV） infection and is accompanied by high-level immune cell infiltration around the cancer nest. There are two immune cells with opposite functions in the tumor immune microenvironment （TIME） of EBV-positive nasopharyngeal carcinoma. However， due to the effects of EBV surface membrane proteins and interferon-γ and the high expression of programmed death receptor-1， TIME behaves as immunosuppressive effects. Immunotherapy utilizes the immunosuppressive properties of TIME to alter the level of immune response， thereby inhibiting the progression of nasopharyngeal cancer. Immunotherapy methods for EBV-related nasopharyngeal carcinoma include immune checkpoint inhibitors， cellular immunotherapy， tumor vaccines and oncolytic virus immunotherapy. Further exploration of the relationship between EBV and TIME and the role of EBV in the immunotherapy strategy for nasopharyngeal carcinoma can provide a basis for precise immunotherapy of EBV-positive nasopharyngeal carcinoma. Reference|Related Articles|Metrics|Comments（0）

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Breast microbiota and breast cancer： present and future Gu Huayan, Zhu Teng, Guo Guilong Journal of International Oncology 2024, 51 (1): 55-58. DOI:10.3760/cma.j.cn371439-20230627-00007 Abstract（ 96） HTML（ 21） PDF（pc）（699KB）（ 65） Knowledge map 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. Reference|Related Articles|Metrics|Comments（0）

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Research progress of myeloid-derived suppressor cells in tumor angiogenesis Liu Xiaodi, Su Jianfei, Zhang Jingxian, Wei Xueqin, Jia Yingjie Journal of International Oncology 2024, 51 (1): 50-54. DOI:10.3760/cma.j.cn371439-20230227-00006 Abstract（ 93） HTML（ 9） PDF（pc）（743KB）（ 53） Knowledge map 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. Reference|Related Articles|Metrics|Comments（0）

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Identification of critical radioresistance genes in esophageal squamous cell carcinoma by whole exome sequencing Chen Zhiming, Chen Junjie, Li Li, Ding Qian, Han Yunan, Zhao Hongyu Journal of International Oncology 2023, 50 (10): 592-599. DOI:10.3760/cma.j.cn371439-20220916-00113 Abstract（ 91） HTML（ 16） PDF（pc）（1870KB）（ 22） Knowledge map Save ObjectiveTo compare the genetic spectrums of esophageal squamous cell carcinoma （ESCC） patients with different prognosis after postoperative radiotherapy and to screen the genetic variants associated with radiotherapy resistance.MethodsA total of 32 ESCC patients who received radical surgery and postoperative adjuvant radiotherapy in Affiliated Hospital of Nantong University from January 2015 to December 2019 were selected as the study objects. According to whether there was any recurrence in the radiation field within 1 year， they were divided into a recurrence group （radiotherapy resistance group，n=16） and a stable group （radiotherapy sensitive group，n=16）. Genomic DNA was extracted from patients and high-throughput sequencing was performed using whole exome sequencing （WES） technology. Biological information analysis software Trimmomatic， BWA and Picard were used to process the data and the alignment files were obtained by GATK comparison， then Vardict software was used to screen out various genetic variants from the sequencing data. The disease free survival （DFS） and overall survival （OS） were estimated by Kaplan-Meier method. Cox proportional hazard regression model was used to analyze the independent risk factors of DFS and OS of ESCC patients.ResultsAfter quality control of the sample data， 26 patients were finally included in this study for follow-up analysis， 13 in each of the recurrence and stable groups. The median tumor mutation burden of non-silent tumors in the whole group was 0.95 mutations/Mb. The substitution types of mutant bases were mainly C>T conversion， followed by C>G transmutation. The genetic variants with the highest frequency were single nucleotide polymorphism （SNP） （75.1%）， deletion mutation （13.7%） and insertion mutation （10.5%）. The number of tumor-specific mutations in the recurrence group was slightly higher than that in the stable group （median mutation number was 36 and 34， respectively）， and the top ten gene profiles of mutation frequency were significantly different between the two groups. In the recurrence group， 392 unique mutated genes were detected， and the top five were MUC19， NPIPA5， EPPK1， FLG and FOXG1. In the stable group， 192 unique mutation genes were detected， and the top five were TCHH， WNK1， AIM1L， COL6A5 and DPCR1. The median DFS and OS were 15.0 months （95%CI： 10.1 months-not reached） and 26.2 months （95%CI： 19.8 months-not reached） in the recurrence group respectively， and no recurrence or metastasis occurred in the stable group. Univariate analysis showed that GRIK2 （χ2=6.81，P=0.009）， MUC4 （χ2=4.25，P=0.039）， MUC5B （χ2=4.03，P=0.045）， PRRG1 （χ2=5.15，P=0.023） gene mutations， 3p deletion （χ2=4.16，P=0.041） and 14q deletion （χ2=7.09，P=0.008） were correlated with DFS. FLG （χ2=6.41，P=0.011）， NPIPA5 （χ2=4.57，P=0.033）， PKD1L2 （χ2=6.41，P=0.011）， FOXG1 （χ2=4.57，P=0.033） gene mutations， 3p deletion （χ2=3.88，P=0.049）， 14q deletion （χ2=5.66，P=0.017） and 18p deletion （χ2=3.85，P=0.050） were associated with OS. Multivariate analysis showed that 14q deletion （HR=3.65， 95%CI： 1.18-11.32，P=0.025） was an independent risk factor for DFS of ESCC patients with postoperative adjuvant radiotherapy， and FLG （HR=8.94， 95%CI： 1.52-52.74，P=0.016）， NPIPA5 （HR=6.36， 95%CI： 1.23-33.03，P=0.028） gene mutation and 14q deletion （HR=3.82， 95%CI： 1.18-12.31，P=0.025） were independent risk factors for OS of ESCC patients with postoperative adjuvant radiotherapy.ConclusionThe WES results suggest that the types and rates of gene mutations of the ESCC patients with postoperative adjuvant radiotherapy in the recurrence and stable groups are basically the same， but the mutation spectrum of the two groups is significantly different. FLG， NPIPA5 gene mutations and 14q deletion can be used as molecular markers to predict the prognosis of ESCC patients treated with postoperative adjuvant radiotherapy. Table and Figures|Reference|Related Articles|Metrics|Comments（0）

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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 Journal of International Oncology 2024, 51 (1): 21-28. DOI:10.3760/cma.j.cn371439-20230906-00002 Abstract（ 89） HTML（ 13） PDF（pc）（2924KB）（ 39） Knowledge map Save ObjectiveTo 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. MethodsA549 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 （IC 50）. A549 cells were divided into three groups： control group， chlorogenic acid group （IC 50） and chlorogenic acid + 740-YP group （IC 50chlorogenic 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. ResultsThe IC 50of 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 G 0/G 1phase 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 G 2/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 G 0/G 1phase cells in chlorogenic acid group and chlorogenic acid + 740YP group decreased （both P<0.001）， and the proportion of G 2/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 G 2/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）. ConclusionChlorogenic 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. Table and Figures|Reference|Related Articles|Metrics|Comments（0）

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Research progress of locoregional interventional therapies combined with immune checkpoint inhibitors for intermediate-advanced hepatocellular carcinoma Tian Jinming, Yang Jijin Journal of International Oncology 2023, 50 (10): 636-640. DOI:10.3760/cma.j.cn371439-20230428-00121 Abstract（ 88） HTML（ 16） PDF（pc）（761KB）（ 40） Knowledge map Save According to the International Agency for Research on Cancer （IARC） of the World Health Organization， the number of people with primary liver cancer is predicted to exceed 1 million per year by 2025， making it a major threat to human life and health. According to "Standardization for Diagnosis and Treatment of Hepatocellular Carcinoma （2022 edition）" issued by the National Health Commission of China， locoregional interventional therapy represented by ablation and transcatheter arterial chemoembolization （TACE） has become the main treatment for unresectable intermediate-advanced hepatocellular carcinoma （HCC）， in which the indications for TACE include patients with stage Ⅰb to Ⅲb HCC. Locoregional interventional therapy has been proved to have a clear immune activation effect， and with the gradual promotion of immune checkpoint inhibitors in clinical trials and applications at home and abroad， the combination therapy of locoregional intervention and immune checkpoint inhibitors has shown a more effective objective response rate， slower progression time and longer survival， bringing new hope to patients with inoperable intermediate-advanced HCC. Reference|Related Articles|Metrics|Comments（0）

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Research progress of memantine hydrochloride in the treatment of radiation-induced cognitive dysfunction and its combined application with vitamins Wang Jin, Li Ruoyang, Zhao Xuewei, Li Hui, Zhou Zhiguo, Zhao Jingxia Journal of International Oncology 2023, 50 (10): 622-626. DOI:10.3760/cma.j.cn371439-20230418-00118 Abstract（ 87） HTML（ 11） PDF（pc）（763KB）（ 22） Knowledge map Save Radiation-induced cognitive dysfunction （RICD） has an insidious onset and there is a lack of effective prevention and treatment measures. The efficacy of memantine hydrochloride as a classical treatment drug is limited， and it is inevitable to seek multi-target combination drugs. In recent years， the protective effect of vitamin E and vitamin D on cognitive function has been widely recognized. Several basic studies have shown that vitamin E can play a role in the combination of medication by protecting neurons and reducing the adverse effects caused by memantine hydrochloride； Vitamin D and memantine hydrochloride have also become a hot topic of research due to their significant synergistic effects. The combination of memantine hydrochloride and vitamin therapy is expected to bring additional benefits to RICD patients. Reference|Related Articles|Metrics|Comments（0）

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Recent progresses of targeted therapy and immunotherapy of hepatocellular carcinoma Jiang Shan, Xu Ximing Journal of International Oncology 2023, 50 (11): 688-695. DOI:10.3760/cma.j.cn371439-20230605-00130 Abstract（ 87） HTML（ 6） PDF（pc）（762KB）（ 30） Knowledge map Save Hepatocellular carcinoma （HCC） is one of the most common malignancies in the world，with a high incidence and fatality rate in China. Since sorafenib opened up a new era of targeted therapy for HCC，drug developers around the world have made a lot of efforts and contributions to the exploration of systematic therapy for HCC. In recent years，novel molecular targeted agents，immune checkpoint inhibitors and their combined treatment regimens in advanced HCC have been implemented for many large samples，international multi-center clinical trials. The results show that the therapeutic effect of immunotherapy combined with targeted therapy and dual immunotherapy have significant advantages compared with that of targeted or immune monotherapy，and have satisfactory safety while prolonging survival and improving the quality of life of patients. Reference|Related Articles|Metrics|Comments（0）

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Clinical efficacy of anlotinib monotherapy in second-line treatment of extensive stage small cell lung cancer with poor PS score Huang Rui, Zhang Yunqing Journal of International Oncology 2023, 50 (12): 705-710. DOI:10.3760/cma.j.cn371439-20230715-00133 Abstract（ 87） HTML（ 30） PDF（pc）（770KB）（ 49） Knowledge map Save ObjectiveTo investigate the clinical efficacy and safety of anlotinib monotherapy in second-line treatment of extensive stage small cell lung cancer （ES-SCLC） with poor performance status （PS） score after treatment failure with first-line standard regimen.MethodsThirty-three patients with ES-SCLC who failed to receive first-line standard treatment and had poor PS score were selected from Fuyang People's Hospital of Anhui Province from January 2021 to December 2022. All patients were given anrotinib 10 mg orally for second-line treatment， which was taken for 2 weeks and stopped for 1 week， with every 21 days being a cycle period， until the disease progressed or the patient became intolerable. Objective response rate （ORR）， disease control rate （DCR） and adverse reactions were observed. Progression-free survival （PFS） was estimated by Kaplan-Meier method， and the influencing factors of PFS were analyzed by Cox regression model.ResultsAfter at least 2 cycles of anlotinib monotherapy， there were no complete remission， 5 cases of partial remission， 17 cases of stable disease， 11 cases of progressive disease. ORR was 15.2% （5/33）， DCR was 66.7% （22/33）. The median PFS was 3.7 months （95%CI： 2.9-4.5 months）. Univariate analysis showed that first-line recurrence time （χ2=4.90，P=0.027）， brain metastases （χ2=12.42，P<0.001）， liver metastases （χ2=11.05，P=0.001） and controlling nutritional status （CONUT） score （χ2=12.43，P<0.001） were the influential factors of PFS in ES-SCLC patients with poor PS score and first-line treatment failure of anlotinib monotherapy. Multivariate analysis showed that brain metastases （HR=3.21， 95%CI： 1.24-8.29，P=0.016）， liver metastases （HR=2.80， 95%CI： 1.03-7.61，P=0.044） and CONUT score （HR=2.72， 95%CI： 1.16-6.38，P=0.021） were independent influencing factors of PFS in ES-SCLC patients with first-line treatment failure of anlotinib monotherapy and poor PS score. Common adverse reactions were fatigue， hypertension， anorexia，etc. Most of the adverse reactions were grade 1-2， with the incidence of grade 3 adverse reactions being 9.1% （3/33）， and no grade 4-5 adverse reactions occurred.ConclusionThe clinical efficacy of anlotinib monotherapy in second-line treatment of ES-SCLC with poor PS score and failure of first-line standard regimen is good， and the adverse reactions are controllable. Table and Figures|Reference|Related Articles|Metrics|Comments（0）

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Predictive value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma treated with immunotherapy combined with targeted therapy Jiang Shan, Xu Yangtao, Liu Xin, Chen Wenliang, Xu Ximing Journal of International Oncology 2023, 50 (10): 600-607. DOI:10.3760/cma.j.cn371439-20230704-00114 Abstract（ 84） HTML（ 24） PDF（pc）（1599KB）（ 38） Knowledge map Save ObjectiveTo investigate the prognostic value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma （HCC） receiving immunotherapy combined with targeted therapy.MethodsThe clinical data of a total of 120 patients with advanced HCC who received immunotherapy combined with targeted therapy at Cancer Center of Renmin Hospital of Wuhan University from December 2019 to March 2022 were analyzed retrospectively. Receiver operating characteristic （ROC） curve was used to calculate the optimal cut-off values of neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， lymphocyte-to-monocyte ratio （LMR）， systemic immune inflammation index （SII） and prognostic nutritional index （PNI）. According to the optimal cut-off values， the study objects were divided into high value group and low value group. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the factors associated with prognosis.ResultsBy the end of follow-up， 74 patients died and 46 survived. The median follow-up time was 23.0 months， the median overall survival （mOS） was 15.6 months， and the median progression-free survival （mPFS） was 13.1 months. ROC curve analysis showed that the optimal cut-off values of NLR， PLR， SII， LMR and PNI were 3.45， 131.87， 626.21， 2.12 and 43.30， respectively. The mPFS （18.3 monthsvs.8.7 months） and mOS （26.6 monthsvs.10.9 months） of patients in the low-NLR group （n=75） were longer than those of the high-NLR group （n=45）， and there were statistically significant differences （χ2=55.64，P<0.001；χ2=64.14，P<0.001）. The mPFS （17.9 monthsvs.10.9 months） and mOS （24.5 monthsvs.13.5 months） of patients in the low-PLR group （n=55） were longer than those of the high-PLR group （n=65）， and there were statistically significant differences （χ2=5.27，P=0.023；χ2=11.84，P<0.001）. The mPFS （18.0 monthsvs.10.7 months） and mOS （25.7 monthsvs.12.8 months） of patients in the low-SII group （n=75） were longer than those of the high-SII group （n=45）， and there were statistically significant differences （χ2=24.46，P<0.001；χ2=25.42，P<0.001）. The mPFS （18.2 monthsvs.10.9 months） and mOS （26.6 monthsvs.13.2 months） of patients in the high-LMR group （n=56） were longer than those of the low-LMR group （n=64）， and there were statistically significant differences （χ2=19.25，P<0.001；χ2=19.92，P<0.001）. The mPFS （17.9 monthsvs.10.9 months） and mOS （25.4 monthsvs.13.4 months） of patients in the high-PNI group （n=62） were longer than those of the low-PNI group （n=58）， and there were statistically significant differences （χ2=13.69，P<0.001；χ2=19.07，P<0.001）. Univariate analysis showed that Barcelona clinic liver cancer （BCLC） stage （HR=1.83， 95%CI： 1.17-2.87，P=0.008）， Child-Pugh grade （HR=2.21， 95%CI： 1.47-3.34，P<0.001）， modified albumin-bilirubin （mALBI） grade （HR=1.35， 95%CI： 1.01-1.81，P=0.045）， extrahepatic metastases （HR=2.18， 95%CI： 1.47-3.25，P<0.001）， NLR （HR=1.40， 95%CI： 1.28-1.54，P<0.001）， PLR （HR=1.00， 95%CI： 1.00-1.01，P=0.001）， SII （HR=1.00， 95%CI： 1.00-1.00，P<0.001）， LMR （HR=0.64， 95%CI： 0.51-0.79，P<0.001） and PNI （HR=0.95， 95%CI： 0.93-0.98，P=0.001） were correlated with PFS； BCLC stage （HR=2.18， 95%CI： 1.21-3.91，P=0.009）， Child-Pugh grade （HR=2.57， 95%CI： 1.61-4.09，P<0.001）， Eastern Cooperative Oncology Group performance status score （HR=1.59， 95%CI： 1.01-2.51，P=0.044）， mALBI grade （HR=1.60， 95%CI： 1.17-2.17，P=0.003）， extrahepatic metastasis （HR=2.51， 95%CI： 1.59-3.96，P<0.001）， NLR （HR=1.45， 95%CI： 1.32-1.60，P<0.001）， PLR （HR=1.01， 95%CI： 1.01-1.01，P<0.001）， SII （HR=1.01， 95%CI： 1.01-1.01，P<0.001）， LMR （HR=0.57， 95%CI： 0.40-0.72，P<0.001） and PNI （HR=0.92， 95%CI： 0.89-0.96，P<0.001） were correlated with OS. Multivariate analysis showed that extrahepatic metastasis （HR=1.78， 95%CI： 1.10-2.87，P=0.018） and NLR （HR=1.46， 95%CI： 1.24-1.73，P<0.001） were independent influencing factors for PFS； extrahepatic metastasis （HR=2.09， 95%CI： 1.21-3.61，P=0.009）， NLR （HR=1.56， 95%CI： 1.29-1.88，P<0.001）， SII （HR=1.00， 95%CI： 1.00-1.00，P=0.025）， LMR （HR=0.59， 95%CI： 0.45-0.78，P=0.008） and PNI （HR=0.93， 95%CI： 0.88-0.99，P=0.013） were independent influencing factors for OS.ConclusionNLR and extrahepatic metastasis can be regarded as important indicators to predict PFS in patients with advanced HCC receiving immunotherapy combined with targeted therapy， and NLR， SII， LMR， PNI and extrahepatic metastasis can be regarded as important indicators to predict OS in patients with advanced HCC receiving immunotherapy combined with targeted therapy. High NLR， high SII， low LMR， low PNI and extrahepatic metastasis indicate poor prognosis of HCC patients. 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Progress of MCL-1 and its inhibitors in hematologic malignancies Teng Yuan, Li Lijuan, Zhang Liansheng Journal of International Oncology 2024, 51 (2): 119-122. DOI:10.3760/cma.j.cn371439-20230612-00018 Abstract（ 84） HTML（ 4） PDF（pc）（735KB）（ 27） Knowledge map Save Myeloid cell leukemia-1 （MCL-1）is an anti-apoptotic protein that plays a key role in promoting cell survival in multiple myeloma，acute myeloid leukemia and non-Hodgkin lymphoma. MCL-1 is highly expressed in a variety of hematological malignancies，which is one of the important factors leading to poor prognosis and chemoresistance in patients with hematological malignancies. Therefore，MCL-1 is an important therapeutic target for hematological malignancies. Several MCL-1 inhibitors have entered clinical trials，including S63845，AZD5991，S64315，AMG-176，and AMG-397. The treatment plans used for hematological malignancies include monotherapy with MCL-1 inhibitors，as well as combination therapy with B cell lymphoma 2 inhibitors or immunomodulatory drugs，all indicating that MCL-1 inhibitors may be a breakthrough point for targeted treatment of hematological malignancies. Reference|Related Articles|Metrics|Comments（0）

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Chinese expert consensus on issues related to radiotherapy management of cancer patients under the back ground of COVID-19 （2023 Edition） Radiation Oncology Treatment Physician Branch, Chinese Medical Doctor Association； Radiation Oncology Therapy Branch, Chinese Medical Association； Chinese Association of Radiation Therapy, China Anti-Cancer Association Journal of International Oncology 2023, 50 (10): 577-584. DOI:10.3760/cma.j.cn371439-20230706-00111 Abstract（ 82） HTML（ 26） PDF（pc）（837KB）（ 111） Knowledge map Save The ongoing COVID-19 pandemic has posed unprecedented challenges to global healthcare systems and has had a specific impact on the standard treatment of cancer patients worldwide， including radiotherapy. Resource constraints can lead to a decline in treatment capacity， and to reduce the risk of cancer patients being exposed to the novel coronavirus， the number of radiotherapy visits must be limited. Based on existing clinical evidence， radiation oncologists need to make radiotherapy decisions that reduce the risk of infection without compromising efficacy. The COVID-19 pandemic is nearing its end， but more infectious variants or other viruses may emerge and spread. Therefore， the Radiation Oncology Treatment Physician Branch of the Chinese Medical Doctor Association， the Radiation Oncology Therapy Branch of the Chinese Medical Association， and the Chinese Association of Radiation Therapy of the China Anti-Cancer Association refer to a number of relevant guidelines and the latest updates on patients with malignant tumors during the COVID-19 epidemic at home and abroad. According to China's national conditions， medical system and COVID-19 epidemic characteristics， the "Chinese expert consensus on issues related to radiotherapy management of cancer patients under the background of COVID-19 （2023 Edition）" is formulated. Table and Figures|Reference|Related Articles|Metrics|Comments（0）