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Volume 30,Issue 11,2023 Table of Contents
2023, 30(11):943-943.
DOI: 10.3872/j.issn.1007-385X.2023.11.001
Abstract:
2023, 30(11):944-949.
DOI: 10.3872/j.issn.1007-385X.2023.11.002
Abstract:
The incidence of tumors has been increasing due to the continuous extension of human life span and the rapid development of early diagnosis. Simultaneously，the improvement of the comprehensive curative effects of tumors has kept the tumor survival population expanding. Under the principle of adhering to traditional Chinese medicine (TCM) discipline development rules，we should inherit the essence of Chinese civilization，TCM classics and the practical experience of TCM doctors of past dynasties，and actively integrate modern scientific concepts and technologies such as oncology， immunology，system biology and artificial intelligence，etc． These views help to enrich the prevention and control theory and technical system of “strengthening vital qi to treat cancer”，and are further conducive to promoting the innovative development of oncology and the improvement of comprehensive curative effects．
The incidence of tumors has been increasing due to the continuous extension of human life span and the rapid development of early diagnosis. Simultaneously，the improvement of the comprehensive curative effects of tumors has kept the tumor survival population expanding. Under the principle of adhering to traditional Chinese medicine (TCM) discipline development rules，we should inherit the essence of Chinese civilization，TCM classics and the practical experience of TCM doctors of past dynasties，and actively integrate modern scientific concepts and technologies such as oncology， immunology，system biology and artificial intelligence，etc． These views help to enrich the prevention and control theory and technical system of “strengthening vital qi to treat cancer”，and are further conducive to promoting the innovative development of oncology and the improvement of comprehensive curative effects．
2023, 30(11):950-956.
DOI: 10.3872/j.issn.1007-385X.2023.11.003
Abstract:
Objective: To investigate the characteristics of “Declined of Vital Qi” in the characterization of immune function decline caused by aging based on a mouse model of progressive aging. Methods: C57BL/6 mice of different months (2, 6 and 15 months) were used to detect and compare the specific abundance of T cells, myeloid-derived suppressor cells (MDSC) and their subpopulations in peripheral blood and spleen of mice by flow cytometry. Results: In the peripheral blood, T cell subsets CD3+CD4+CD44-CD62L+ naive CD4+ T cells (2 vs 6 months old, P=0.137; 2 vs 15 months old, P=0.004; 6 vs 15 months old, P=0.105) and CD3+CD8+CD44-CD62L+ naive CD8+ T cells (2 vs 6 months old, P=0.179; 2 vs 15 months old, P=0.001; 6 vs 15 months old, P=0.015) showed a decrease in proportion to aging. However, the proportion of CD3+CD4+CD44+CD62L+ central memory CD8+ T cells increased with aging (2 vs 6 months old, P=0.01; 2 vs 15 months old, P=0.007; 6 vs 15 months old, P=0.164). The results in spleen experiment showed the same trend. At the same time, the proportion of CD8+ T cells increased gradually with aging (2 vs 6 months old, P=0.027; 2 vs 15 months old, P<0.001; 6 vs 15 months old. P<0.001). The subsets of activated CD8+ T cells with phenotype CD8+CD28+ also increased with age (2 vs 6 months old, P=0.863; 2 vs 15 months old, P=0.016; 6 vs 15 months old, P=0.024). Conclusion: In the process of “Declined of Vital Qi” caused by aging, the changes of different immune cell subsets do not all reflect the characteristics of immunosuppression, although the overall immune function decreases. A single phenotype is difficult to reflect the change of overall immune function.
Objective: To investigate the characteristics of “Declined of Vital Qi” in the characterization of immune function decline caused by aging based on a mouse model of progressive aging. Methods: C57BL/6 mice of different months (2, 6 and 15 months) were used to detect and compare the specific abundance of T cells, myeloid-derived suppressor cells (MDSC) and their subpopulations in peripheral blood and spleen of mice by flow cytometry. Results: In the peripheral blood, T cell subsets CD3+CD4+CD44-CD62L+ naive CD4+ T cells (2 vs 6 months old, P=0.137; 2 vs 15 months old, P=0.004; 6 vs 15 months old, P=0.105) and CD3+CD8+CD44-CD62L+ naive CD8+ T cells (2 vs 6 months old, P=0.179; 2 vs 15 months old, P=0.001; 6 vs 15 months old, P=0.015) showed a decrease in proportion to aging. However, the proportion of CD3+CD4+CD44+CD62L+ central memory CD8+ T cells increased with aging (2 vs 6 months old, P=0.01; 2 vs 15 months old, P=0.007; 6 vs 15 months old, P=0.164). The results in spleen experiment showed the same trend. At the same time, the proportion of CD8+ T cells increased gradually with aging (2 vs 6 months old, P=0.027; 2 vs 15 months old, P<0.001; 6 vs 15 months old. P<0.001). The subsets of activated CD8+ T cells with phenotype CD8+CD28+ also increased with age (2 vs 6 months old, P=0.863; 2 vs 15 months old, P=0.016; 6 vs 15 months old, P=0.024). Conclusion: In the process of “Declined of Vital Qi” caused by aging, the changes of different immune cell subsets do not all reflect the characteristics of immunosuppression, although the overall immune function decreases. A single phenotype is difficult to reflect the change of overall immune function.
2023, 30(11):957-964.
DOI: 10.3872/j.issn.1007-385X.2023.11.004
Abstract:
Objective: To explore the immunological mechanism of the effective components in Jinfukang, astragaloside Ⅳ and paris saponins Ⅶ, in inhibiting lung cancer Lewis cells metastasis based on the theory of "Deficiency of Vital Qi and Hidden Toxin". Methods: The animal model of lung cancer metastasis was established by injecting Lewis cells into the tail vein of C57BL/6J mice.The model mice were randomly divided into a treatment group and a control group according to the random table method, 8 mice per group. The treatment group was intervened with Jinfukang effective components, astragaloside Ⅳ (25 mg/kg) and with paris saponins Ⅶ (2.5 mg/kg). Four weeks later, the lung and liver metastases were observed. The histopathological changes of lung and liver metastatic foci were observed by H-E staining. The proportions of NK cells in peripheral blood and spleen tissues were detected by flow cytometry. The levels of TNF-α and IFN-γ in serum were detected by ELISA. The protein expression of Ki-67 in the metastatic foci was detected by immunohistochemical method, and the infiltration of NK cells and the secretion of IFN-γ in the metastatic foci were detected by immunofluorescence. The NK cells in the spleen of healthy mice were separated by immunomagnetic beads and co-cultured with astragaloside Ⅳ (5 μmol/L), paris saponins Ⅶ (0.5 μmol/L), and Lewis cells that intervened by both drugs. The degranulation level of NK cells was detected by flow cytometry, and the killing activity of NK cells against Lewis cells was detected by LDH method. Results: Compared with the control group, the number and load of lung and liver metastases were significantly decreased (both P<0.05), The transfer load is also significantly reduced (both P<0.05), and the expression of Ki-67 protein in the metastatic foci was significantly reduced (P<0.05) in the mice treated with astragaloside Ⅳ and paris saponins Ⅶ; the infiltration level of NK cells in metastatic tumor tissue was significantly increased, and IFN-γ was released from intracellular to extracellular of NK cells. In addition, the proportion of NK cells in spleen decreased significantly (P<0.05), while the level of NK cells in peripheral blood increased significantly (P<0.05). The level of IFN- γ in serum of mice decreased significantly (P<0.05), while the level of TNF- α increased significantly (all P<0.05). In vitro study found that the degranulation level of NK cells increased significantly (P<0.05) after single or combined intervention of astragaloside Ⅳ and paris saponins Ⅶ, which, however, had no significant effect on the killing activity of NK cells against Lewis cells (P>0.05). Conclusion: The combined use of astragaloside Ⅳ and paris saponins Ⅶ, the effective components of Jinfukang, can promote the infiltration of NK cells into tumor tissues and increase the secretion of IFN-γ to inhibit the the lung and liver metastasis of Lewis cells, provides a convincing experimental case for the "Deficiency of Vital Qi and Hidden Toxin" theory.
Objective: To explore the immunological mechanism of the effective components in Jinfukang, astragaloside Ⅳ and paris saponins Ⅶ, in inhibiting lung cancer Lewis cells metastasis based on the theory of "Deficiency of Vital Qi and Hidden Toxin". Methods: The animal model of lung cancer metastasis was established by injecting Lewis cells into the tail vein of C57BL/6J mice.The model mice were randomly divided into a treatment group and a control group according to the random table method, 8 mice per group. The treatment group was intervened with Jinfukang effective components, astragaloside Ⅳ (25 mg/kg) and with paris saponins Ⅶ (2.5 mg/kg). Four weeks later, the lung and liver metastases were observed. The histopathological changes of lung and liver metastatic foci were observed by H-E staining. The proportions of NK cells in peripheral blood and spleen tissues were detected by flow cytometry. The levels of TNF-α and IFN-γ in serum were detected by ELISA. The protein expression of Ki-67 in the metastatic foci was detected by immunohistochemical method, and the infiltration of NK cells and the secretion of IFN-γ in the metastatic foci were detected by immunofluorescence. The NK cells in the spleen of healthy mice were separated by immunomagnetic beads and co-cultured with astragaloside Ⅳ (5 μmol/L), paris saponins Ⅶ (0.5 μmol/L), and Lewis cells that intervened by both drugs. The degranulation level of NK cells was detected by flow cytometry, and the killing activity of NK cells against Lewis cells was detected by LDH method. Results: Compared with the control group, the number and load of lung and liver metastases were significantly decreased (both P<0.05), The transfer load is also significantly reduced (both P<0.05), and the expression of Ki-67 protein in the metastatic foci was significantly reduced (P<0.05) in the mice treated with astragaloside Ⅳ and paris saponins Ⅶ; the infiltration level of NK cells in metastatic tumor tissue was significantly increased, and IFN-γ was released from intracellular to extracellular of NK cells. In addition, the proportion of NK cells in spleen decreased significantly (P<0.05), while the level of NK cells in peripheral blood increased significantly (P<0.05). The level of IFN- γ in serum of mice decreased significantly (P<0.05), while the level of TNF- α increased significantly (all P<0.05). In vitro study found that the degranulation level of NK cells increased significantly (P<0.05) after single or combined intervention of astragaloside Ⅳ and paris saponins Ⅶ, which, however, had no significant effect on the killing activity of NK cells against Lewis cells (P>0.05). Conclusion: The combined use of astragaloside Ⅳ and paris saponins Ⅶ, the effective components of Jinfukang, can promote the infiltration of NK cells into tumor tissues and increase the secretion of IFN-γ to inhibit the the lung and liver metastasis of Lewis cells, provides a convincing experimental case for the "Deficiency of Vital Qi and Hidden Toxin" theory.
ZHU Zhiming
,
ZHOU Qichun
,
WANG Juanjuan
,
DENG Zhiyin
,
TANG Qing
,
WU Wanyin
,
WANG Xi
,
WAN Xinliang
,
MO Handan
,
WANG Sumei
2023, 30(11):965-972.
DOI: 10.3872/j.issn.1007-385X.2023.11.005
Abstract:
Objective: To explore the specific effect and mechanism of kaempferol on inducing autophagy in non-small cell lung cancer (NSCLC) NCI-H1650 cells. Methods: Human NSCLC cell line NCI-H1650 was cultured and treated with kaempferol at different concentrations. The effects of kaempferol on NSCLC cell viability and proliferation were observed by CCK-8, MTT and EdU methods. LC3 adenovirus infection experiment was performed to investigate the effect of kaempferol on NSCLC cell autophagy. Western blot was used to detect the expression of key proteins of cell autophagy and relevant molecules of Met/PI3K/Akt/mTOR signaling pathway. Meanwhile, qPCR was used to detect the mRNA expression of Met in NCI-H1650 cells after kaempferol treatment. The transplanted tumor model of nude mice was established by using luciferase labeled A549-luc cells. The tumor growth was observed by in vivo animal imaging, and the expression of autophagy related key proteins and molecules of Met/PI3K/Akt/mTOR signaling pathway in the xenograft tissues were detected by Western blot. Results: Kaempferol significantly inhibited the proliferation of NCI-H1650 cells (P<0.05). After kaempferol treatment, the number of autophagosomes in NCI-H1650 cells was significantly increased (P<0.05), the expressions of autophagy related key proteins, LC3B and beclin1, were significantly increased (all P<0.05), and the expression of P62 was significantly decreased (P<0.05). Kaempferol significantly inhibited the mRNA and protein expression of Met, and inhibited the protein expression of p-PI3K p85, PI3K p85, p-Akt and p-mTOR (all P<0.05). Kaempferol inhibited the growth of transplanted tumor (P<0.05) and affected autophagy and the expression of Met/PI3K/Akt/mTOR pathway-related proteins in nude mouse tumor models (all P<0.05). Conclusion: Kaempferol induces autophagy in NSCLC NCI-H1650 cells by affecting the Met/PI3K/Akt/mTOR pathway, which in turn inhibites their proliferative capacity.
Objective: To explore the specific effect and mechanism of kaempferol on inducing autophagy in non-small cell lung cancer (NSCLC) NCI-H1650 cells. Methods: Human NSCLC cell line NCI-H1650 was cultured and treated with kaempferol at different concentrations. The effects of kaempferol on NSCLC cell viability and proliferation were observed by CCK-8, MTT and EdU methods. LC3 adenovirus infection experiment was performed to investigate the effect of kaempferol on NSCLC cell autophagy. Western blot was used to detect the expression of key proteins of cell autophagy and relevant molecules of Met/PI3K/Akt/mTOR signaling pathway. Meanwhile, qPCR was used to detect the mRNA expression of Met in NCI-H1650 cells after kaempferol treatment. The transplanted tumor model of nude mice was established by using luciferase labeled A549-luc cells. The tumor growth was observed by in vivo animal imaging, and the expression of autophagy related key proteins and molecules of Met/PI3K/Akt/mTOR signaling pathway in the xenograft tissues were detected by Western blot. Results: Kaempferol significantly inhibited the proliferation of NCI-H1650 cells (P<0.05). After kaempferol treatment, the number of autophagosomes in NCI-H1650 cells was significantly increased (P<0.05), the expressions of autophagy related key proteins, LC3B and beclin1, were significantly increased (all P<0.05), and the expression of P62 was significantly decreased (P<0.05). Kaempferol significantly inhibited the mRNA and protein expression of Met, and inhibited the protein expression of p-PI3K p85, PI3K p85, p-Akt and p-mTOR (all P<0.05). Kaempferol inhibited the growth of transplanted tumor (P<0.05) and affected autophagy and the expression of Met/PI3K/Akt/mTOR pathway-related proteins in nude mouse tumor models (all P<0.05). Conclusion: Kaempferol induces autophagy in NSCLC NCI-H1650 cells by affecting the Met/PI3K/Akt/mTOR pathway, which in turn inhibites their proliferative capacity.
2023, 30(11):973-980.
DOI: 10.3872/j.issn.1007-385X.2023.11.006
Abstract:
Objective： To investigate the inhibitory effect of Kanglaite injection (KLTi) on the biological behaviors of lung adenocarcinoma A549 cells by regulating cholesterol metabolism. Methods: An in vitro monoculture model of A549 cells was established. A blank control group (CON group), a KLTi group, a cisplatin group (DDP group) and a KLTi + DDP group were set and given corresponding drug intervention, respectively. CCK-8 method was used to detect the effects of different interventions on the proliferation of A549 cells, and IC50 values were determined for subsequent experiments. The effects of different drugs on the malignant biological behaviors of A549 cells were compared by cell scratch assay, plate clonogenesis assay and Transwell invasion assay, and the late apoptosis of A549 cells were detected by flow cytometry. The expression of epithelial-mesenchymal transition (EMT) related proteins was detected by WB method, and the release level of pro-inflammatory factors was detected by ELISA. Colorimetric method was used to detect the difference of cholesterol content in 106 cells among groups. The difference in the expression levels of membrane channel protein ATP binding cassette transport protein A1 (ABCA1) and functional proteins ATP citrate lyase (ACLY) and peptidylprolyl isomerase B (PPIB) related to cholesterol metabolism was determined by using WB assay. Results: KLTi and DDP inhibited A549 cells in a time- and dose-dependent manner (both P<0.05). Finally, 2 mg/mL KLTi, 3 μg/mL DDP and 48 h of intervention were chosen as intervention dose for follow-up experiments. KLTi alone or combined with DDP could inhibit the clone formation, migration and invasion and promote the late apoptosis of A549 cells, with more prominent effect in the KLTi+DDP group (P<0.05 or P<0.01). KLTi alone or in combination with DDP could improve the EMT process of A549 cells by regulating the proteinexpression of E-cadherin, vimentin and snail (P<0.05 or P<0.01) and down-regulate the release of pro-inflammatory cytokines IL-6 and IL-8 (P<0.05 or P<0.01). KLTi alone or in combination with DDP could significantly reduce the cholesterol content of A549 cells (P<0.05 or P<0.01) and had a regulatory effect on ABCA1, ACLY and PPIB, with more prominent effects in the KLTi+DDP group (P<0.05 or P<0.01). Conclusion: KLTi inhibits the proliferation, migration, invasion and EMT process of lung adenocarcinoma A549 cells possibly by regulating cholesterol metabolism levels and related channel proteins.
Objective： To investigate the inhibitory effect of Kanglaite injection (KLTi) on the biological behaviors of lung adenocarcinoma A549 cells by regulating cholesterol metabolism. Methods: An in vitro monoculture model of A549 cells was established. A blank control group (CON group), a KLTi group, a cisplatin group (DDP group) and a KLTi + DDP group were set and given corresponding drug intervention, respectively. CCK-8 method was used to detect the effects of different interventions on the proliferation of A549 cells, and IC50 values were determined for subsequent experiments. The effects of different drugs on the malignant biological behaviors of A549 cells were compared by cell scratch assay, plate clonogenesis assay and Transwell invasion assay, and the late apoptosis of A549 cells were detected by flow cytometry. The expression of epithelial-mesenchymal transition (EMT) related proteins was detected by WB method, and the release level of pro-inflammatory factors was detected by ELISA. Colorimetric method was used to detect the difference of cholesterol content in 106 cells among groups. The difference in the expression levels of membrane channel protein ATP binding cassette transport protein A1 (ABCA1) and functional proteins ATP citrate lyase (ACLY) and peptidylprolyl isomerase B (PPIB) related to cholesterol metabolism was determined by using WB assay. Results: KLTi and DDP inhibited A549 cells in a time- and dose-dependent manner (both P<0.05). Finally, 2 mg/mL KLTi, 3 μg/mL DDP and 48 h of intervention were chosen as intervention dose for follow-up experiments. KLTi alone or combined with DDP could inhibit the clone formation, migration and invasion and promote the late apoptosis of A549 cells, with more prominent effect in the KLTi+DDP group (P<0.05 or P<0.01). KLTi alone or in combination with DDP could improve the EMT process of A549 cells by regulating the proteinexpression of E-cadherin, vimentin and snail (P<0.05 or P<0.01) and down-regulate the release of pro-inflammatory cytokines IL-6 and IL-8 (P<0.05 or P<0.01). KLTi alone or in combination with DDP could significantly reduce the cholesterol content of A549 cells (P<0.05 or P<0.01) and had a regulatory effect on ABCA1, ACLY and PPIB, with more prominent effects in the KLTi+DDP group (P<0.05 or P<0.01). Conclusion: KLTi inhibits the proliferation, migration, invasion and EMT process of lung adenocarcinoma A549 cells possibly by regulating cholesterol metabolism levels and related channel proteins.
2023, 30(11):981-986.
DOI: 10.3872/j.issn.1007-385X.2023.11.007
Abstract:
Objective: To observe the effect of Fuzheng formulas on the peripheral blood levels of 12 soluble immune checkpoint molecules in patients with advanced non-small cell lung cancer (NSCLC) treated with third-line therapy, and to analyze the relationship between the baseline level of soluble immune checkpoints and the progression-free survival (PFS) of NSCLC patients. Methods: A total of 72 patients with advanced NSCLC who received third-line treatment (Fuzheng formulas combined with standard Western medicine treatment regimen) in the Department of Oncology, Longhua Hospital from October 2020 to April 2023 were enrolled. The LEGENDplexTM multi-factor kit was used to detect the expression level of soluble immune checkpoint molecules before and after 4 cycles of treatment, and the correlation between their baseline levels and PFS prognosis was analyzed. Results: After 4 cycles of treatment, sCD137, sTGF- β1, sPD-L1, sPD-L2 and other indicators were significantly decreased (P<0.05 or P<0.01). Kaplan-Meier survival analysis showed that the PFS of patients with high sPD-L2 level was shorter than that of patients with low sPD-L2 level (P<0.05). COX multivariate analysis showed that sPD-L2 expression level was an independent impact factor for PFS in advanced NSCLC patients treated with third-line therapy (P<0.05). Conclusion: Fuzheng formulas have a certain regulatory effect on the levels of soluble immune checkpoint molecules. A high level of sPD-L2 indicates shorter PFS in patients with advanced NSCLC, and sPD-L2 may be an independent impact factor for PFS in advanced NSCLC patients undergoing third-line treatment.
Objective: To observe the effect of Fuzheng formulas on the peripheral blood levels of 12 soluble immune checkpoint molecules in patients with advanced non-small cell lung cancer (NSCLC) treated with third-line therapy, and to analyze the relationship between the baseline level of soluble immune checkpoints and the progression-free survival (PFS) of NSCLC patients. Methods: A total of 72 patients with advanced NSCLC who received third-line treatment (Fuzheng formulas combined with standard Western medicine treatment regimen) in the Department of Oncology, Longhua Hospital from October 2020 to April 2023 were enrolled. The LEGENDplexTM multi-factor kit was used to detect the expression level of soluble immune checkpoint molecules before and after 4 cycles of treatment, and the correlation between their baseline levels and PFS prognosis was analyzed. Results: After 4 cycles of treatment, sCD137, sTGF- β1, sPD-L1, sPD-L2 and other indicators were significantly decreased (P<0.05 or P<0.01). Kaplan-Meier survival analysis showed that the PFS of patients with high sPD-L2 level was shorter than that of patients with low sPD-L2 level (P<0.05). COX multivariate analysis showed that sPD-L2 expression level was an independent impact factor for PFS in advanced NSCLC patients treated with third-line therapy (P<0.05). Conclusion: Fuzheng formulas have a certain regulatory effect on the levels of soluble immune checkpoint molecules. A high level of sPD-L2 indicates shorter PFS in patients with advanced NSCLC, and sPD-L2 may be an independent impact factor for PFS in advanced NSCLC patients undergoing third-line treatment.
2023, 30(11):987-991.
DOI: 10.3872/j.issn.1007-385X.2023.11.008
Abstract:
肿瘤转移是导致实体瘤患者死亡的主要原因。髓源性抑制细胞（MDSC）可介导转移靶器官免疫抑制，诱导转移前微环境形成，促进肿瘤细胞休眠重激活并增殖，最终形成影像学可检测的转移灶。肿瘤来源外泌体能够通过细胞间通信，诱导骨髓细胞分化为MDSC，促进靶器官对MDSC的募集，介导MDSC的免疫抑制功能，为肿瘤细胞生存营造局部免疫抑制微环境（局部正虚），进而促进癌症转移或发生。本文聚焦肿瘤来源外泌体介导MDSC促进靶器官免疫抑制的作用及机制进行综述，以期从干预转移前微环境形成的角度，为防治恶性肿瘤转移提供参考。
肿瘤转移是导致实体瘤患者死亡的主要原因。髓源性抑制细胞（MDSC）可介导转移靶器官免疫抑制，诱导转移前微环境形成，促进肿瘤细胞休眠重激活并增殖，最终形成影像学可检测的转移灶。肿瘤来源外泌体能够通过细胞间通信，诱导骨髓细胞分化为MDSC，促进靶器官对MDSC的募集，介导MDSC的免疫抑制功能，为肿瘤细胞生存营造局部免疫抑制微环境（局部正虚），进而促进癌症转移或发生。本文聚焦肿瘤来源外泌体介导MDSC促进靶器官免疫抑制的作用及机制进行综述，以期从干预转移前微环境形成的角度，为防治恶性肿瘤转移提供参考。
2023, 30(11):992-996.
DOI: 10.3872/j.issn.1007-385X.2023.11.009
Abstract:
转移是癌症患者死亡的主要原因。肿瘤细胞从原发灶脱落后内渗进入血管，成为循环肿瘤细胞（CTC），在外周循环中存活下来的CTC 外渗侵入靶器官发生定植并增殖形成转移灶。中性粒细胞作为固有免疫细胞，其可与CTC 结合成簇，促进CTC 逃避免疫监视并在外周循环中存活，同时促进CTC 黏附毛细血管壁并破坏内皮细胞连接以增加CTC 外渗机率，然后促进CTC进入靶器官后的定植与增殖，最终促进肿瘤的转移。“正虚伏毒”理论是癌症转移亚临床阶段的核心病机，伏毒（CTC）与正气之间的博弈规律是破解转移发生机制的关键步骤，从抑制CTC与中性粒细胞之间相互作用着手，破坏两者间的黏附作用，或利用中性粒细胞对CTC的趋向性设计治疗方案，可能为干预肿瘤转移提供新方向。
转移是癌症患者死亡的主要原因。肿瘤细胞从原发灶脱落后内渗进入血管，成为循环肿瘤细胞（CTC），在外周循环中存活下来的CTC 外渗侵入靶器官发生定植并增殖形成转移灶。中性粒细胞作为固有免疫细胞，其可与CTC 结合成簇，促进CTC 逃避免疫监视并在外周循环中存活，同时促进CTC 黏附毛细血管壁并破坏内皮细胞连接以增加CTC 外渗机率，然后促进CTC进入靶器官后的定植与增殖，最终促进肿瘤的转移。“正虚伏毒”理论是癌症转移亚临床阶段的核心病机，伏毒（CTC）与正气之间的博弈规律是破解转移发生机制的关键步骤，从抑制CTC与中性粒细胞之间相互作用着手，破坏两者间的黏附作用，或利用中性粒细胞对CTC的趋向性设计治疗方案，可能为干预肿瘤转移提供新方向。
2023, 30(11):997-1008.
DOI: 10.3872/j.issn.1007-385X.2023.11.010
Abstract:
Objective： To explore the biological function and prognostic value of the glutathione peroxidase (GPX) family in gliomas. Methods: The correlation of gene expression of GPX isoforms in gliomas, protein interactions, gene mutations, the relationship between GPX expression and the prognosis of glioma patients, and the gene set enrichment analysis of GPX7 and 8 were analyzed using various databases such as TCGA, GTEx, and CGGA; the correlation analysis of the expression of GPX8 with the immune cell infiltration and the expression of immune checkpoint molecules in glioma; and the correlation analysis of GPX8 expression with IC50 of chemotherapeutic agents in glioma. The correlation between GPX8 expression and IC50 of chemotherapeutic drugs was analyzed; the expression of GPX mRNA, protein and related immune checkpoint molecules in glioma tissues and control tissues of Chinese people (Specimens were collected from five cases of glioma and three cases of severe traumatic brain injury surgically removed by neurosurgery at Fengxian District Central Hospital, Shanghai, China, between October 20, 2022 and December 20, 2022.) were detected by qPCR, WB and immunofluorescence techniques for validation. Results: Database analysis showed that there were interactions and correlation of gene expression levels among GPX isoforms in gliomas (P<0.05 or P<0.01), and there were single-nucleotide and copy-number variations of several GPX isoforms in glioma tissues; there were significant differences of GPX isoforms in different types of immune cells and tumor cells of glioma tissues; and high expression levels of GPX1, 4, 7, and 8 (all P<0.05) were correlated with poor prognosis of glioma patients (P<0.01). 7 and 8 were highly expressed in glioma tissues (all P<0.05), and correlated with poor prognosis of glioma patients (P<0.01); qPCR and WB assays for GPX7 and 8 expression in human glioma tissues verified the correctness of the database information; the expression of GPX7 and 8 in gliomas has an independent prognostic value; GSEA analysis showed that GPX7 and 8 are associated with the glioma cell cycle and the immune pathway; GBM and LGG are associated with GBM and LGG; and GPX7 and 8 are associated with GBM and LGG are associated with GBM and LGG. related; GPX8 expression was significantly correlated with immune scores in GBM and LGG (P<0.01); GPX8 may induce infiltration of suppressive immune cells in gliomas leading to immunosuppression; there was a positive correlation between GPX8 expression and the expression of several immune checkpoint molecules in gliomas (P<0.01); there was a significant positive correlation between GPX8 expression and the IC50 of the chemotherapeutic agents (P<0.01), and its high expression could lead to the resistance of glioma to chemotherapeutic drugs. Conclusion: GPX8 expression is significantly high in gliomas, and GPX8 expression may induce infiltration of suppressor immune cells in gliomas, which is strongly associated with multiple immunosuppression points, with the IC50 of multiple chemotherapeutic agents, and with patient prognosis, which may serve as a potential target for immunotherapy of gliomas.
Objective： To explore the biological function and prognostic value of the glutathione peroxidase (GPX) family in gliomas. Methods: The correlation of gene expression of GPX isoforms in gliomas, protein interactions, gene mutations, the relationship between GPX expression and the prognosis of glioma patients, and the gene set enrichment analysis of GPX7 and 8 were analyzed using various databases such as TCGA, GTEx, and CGGA; the correlation analysis of the expression of GPX8 with the immune cell infiltration and the expression of immune checkpoint molecules in glioma; and the correlation analysis of GPX8 expression with IC50 of chemotherapeutic agents in glioma. The correlation between GPX8 expression and IC50 of chemotherapeutic drugs was analyzed; the expression of GPX mRNA, protein and related immune checkpoint molecules in glioma tissues and control tissues of Chinese people (Specimens were collected from five cases of glioma and three cases of severe traumatic brain injury surgically removed by neurosurgery at Fengxian District Central Hospital, Shanghai, China, between October 20, 2022 and December 20, 2022.) were detected by qPCR, WB and immunofluorescence techniques for validation. Results: Database analysis showed that there were interactions and correlation of gene expression levels among GPX isoforms in gliomas (P<0.05 or P<0.01), and there were single-nucleotide and copy-number variations of several GPX isoforms in glioma tissues; there were significant differences of GPX isoforms in different types of immune cells and tumor cells of glioma tissues; and high expression levels of GPX1, 4, 7, and 8 (all P<0.05) were correlated with poor prognosis of glioma patients (P<0.01). 7 and 8 were highly expressed in glioma tissues (all P<0.05), and correlated with poor prognosis of glioma patients (P<0.01); qPCR and WB assays for GPX7 and 8 expression in human glioma tissues verified the correctness of the database information; the expression of GPX7 and 8 in gliomas has an independent prognostic value; GSEA analysis showed that GPX7 and 8 are associated with the glioma cell cycle and the immune pathway; GBM and LGG are associated with GBM and LGG; and GPX7 and 8 are associated with GBM and LGG are associated with GBM and LGG. related; GPX8 expression was significantly correlated with immune scores in GBM and LGG (P<0.01); GPX8 may induce infiltration of suppressive immune cells in gliomas leading to immunosuppression; there was a positive correlation between GPX8 expression and the expression of several immune checkpoint molecules in gliomas (P<0.01); there was a significant positive correlation between GPX8 expression and the IC50 of the chemotherapeutic agents (P<0.01), and its high expression could lead to the resistance of glioma to chemotherapeutic drugs. Conclusion: GPX8 expression is significantly high in gliomas, and GPX8 expression may induce infiltration of suppressor immune cells in gliomas, which is strongly associated with multiple immunosuppression points, with the IC50 of multiple chemotherapeutic agents, and with patient prognosis, which may serve as a potential target for immunotherapy of gliomas.
2023, 30(11):1009-1015.
DOI: 10.3872/j.issn.1007-385X.2023.11.011
Abstract:
Objective: To investigate the correlation between DEAD box RNA helicases 10 (DDX10) and Bystin-like（BYSL）in colorectal cancer (CRC) tissues and colon cancer DLD-1 cells and its clinical significance. Methods: A total of 78 pairs of CRC tissues and corresponding paracancerous tissues surgically resected in the Second Affiliated Hospital of Fujian Medical University from March 2017 to March 2018 were collected for this study. The expression levels of DDX10 and BYSL in the cancer and paracancerous tissues were detected by immunohistochemistry EnVision method.SiDDX10 and siNC were transfected into DLD-1 cells by transient transfection technology, respectively. The effect of DDX10 expression on BYSL in colorectal cancer cells was detected by PCR. CCK-8 and transwell assays were used to verify the effect of DDX10 and BYSL on proliferation, migration and invasion of colorectal cancer cells. Results: The immunohistochemistry EnVision results showed that the expression levels of DDX10 (73.08%) and BYSL (74.36%) were significantly higher in colorectal cancer tissues compared with paracancerous tissues. The results of chi-square test showed that the differences in DDX10 and BYSL expression were statistically significant in CRC patients with different tumor stages and different lymph node metastasis and recurrence status (all P<0.05). Pearson correlation analysis showed that DDX10 expression waspositively correlated with BYSL expression (r=0.636, P<0.001). Kaplan-Meier survival analysis showed that the high expression of DDX10 and BYSL was correlated with a worse prognosis of patients. Logistic regression analysis proved that DDX10 and BYSL were independent risk factors for CRC recurrence. The results of CCK-8 assay and Transwell assay showed that suppressing the expression of DDX10 could decrease the expression of BYSL and inhibit the proliferation, migration and invasion of colorectal cancer cells (all P<0.05). Conclusion: DDX10 and BYSL are highly expressed in CRC tissues, and they are positively associated with each other. Higher expression levels of DDX10 and BYSL are associated with poorer patient prognosis and were independent risk factors for CRC recurrence. Suppressing the expression of DDX10 can decrease the expression of BYSL, and inhibit the proliferation, migration and invasion of colorectal cancer cells.
Objective: To investigate the correlation between DEAD box RNA helicases 10 (DDX10) and Bystin-like（BYSL）in colorectal cancer (CRC) tissues and colon cancer DLD-1 cells and its clinical significance. Methods: A total of 78 pairs of CRC tissues and corresponding paracancerous tissues surgically resected in the Second Affiliated Hospital of Fujian Medical University from March 2017 to March 2018 were collected for this study. The expression levels of DDX10 and BYSL in the cancer and paracancerous tissues were detected by immunohistochemistry EnVision method.SiDDX10 and siNC were transfected into DLD-1 cells by transient transfection technology, respectively. The effect of DDX10 expression on BYSL in colorectal cancer cells was detected by PCR. CCK-8 and transwell assays were used to verify the effect of DDX10 and BYSL on proliferation, migration and invasion of colorectal cancer cells. Results: The immunohistochemistry EnVision results showed that the expression levels of DDX10 (73.08%) and BYSL (74.36%) were significantly higher in colorectal cancer tissues compared with paracancerous tissues. The results of chi-square test showed that the differences in DDX10 and BYSL expression were statistically significant in CRC patients with different tumor stages and different lymph node metastasis and recurrence status (all P<0.05). Pearson correlation analysis showed that DDX10 expression waspositively correlated with BYSL expression (r=0.636, P<0.001). Kaplan-Meier survival analysis showed that the high expression of DDX10 and BYSL was correlated with a worse prognosis of patients. Logistic regression analysis proved that DDX10 and BYSL were independent risk factors for CRC recurrence. The results of CCK-8 assay and Transwell assay showed that suppressing the expression of DDX10 could decrease the expression of BYSL and inhibit the proliferation, migration and invasion of colorectal cancer cells (all P<0.05). Conclusion: DDX10 and BYSL are highly expressed in CRC tissues, and they are positively associated with each other. Higher expression levels of DDX10 and BYSL are associated with poorer patient prognosis and were independent risk factors for CRC recurrence. Suppressing the expression of DDX10 can decrease the expression of BYSL, and inhibit the proliferation, migration and invasion of colorectal cancer cells.
12 The role of iron metabolism in tumor immune microenvironment and its application in tumor therapy
2023, 30(11):1016-1020.
DOI: 10.3872/j.issn.1007-385X.2023.11.012
Abstract:
铁代谢的动态平衡是维持细胞代谢正常的基本条件，而肿瘤免疫微环境（TIME）的铁代谢在肿瘤发生发展中扮演着重要角色，具有针对肿瘤细胞和免疫细胞的双面性的特点，并且在原发性和转移性肿瘤以及各类免疫细胞的不同亚型中体现异质性。TIME 中的巨噬细胞和中性粒细胞等免疫细胞铁代谢失调，以及T细胞和中性粒细胞等免疫细胞诱导的铁死亡均可调控肿瘤的发生发展。近年来免疫相关治疗迅速发展，以TIME铁代谢作为治疗靶标的铁螯合剂、铁相关纳米粒子、铁代谢联合放疗或免疫检查点阻断疗法等为肿瘤患者的治疗和预后提供了新思路，随着TIME 铁代谢的研究不断深入，针对其代谢特点进行调控，将可以为肿瘤免疫治疗领域提供更多的治疗手段。
铁代谢的动态平衡是维持细胞代谢正常的基本条件，而肿瘤免疫微环境（TIME）的铁代谢在肿瘤发生发展中扮演着重要角色，具有针对肿瘤细胞和免疫细胞的双面性的特点，并且在原发性和转移性肿瘤以及各类免疫细胞的不同亚型中体现异质性。TIME 中的巨噬细胞和中性粒细胞等免疫细胞铁代谢失调，以及T细胞和中性粒细胞等免疫细胞诱导的铁死亡均可调控肿瘤的发生发展。近年来免疫相关治疗迅速发展，以TIME铁代谢作为治疗靶标的铁螯合剂、铁相关纳米粒子、铁代谢联合放疗或免疫检查点阻断疗法等为肿瘤患者的治疗和预后提供了新思路，随着TIME 铁代谢的研究不断深入，针对其代谢特点进行调控，将可以为肿瘤免疫治疗领域提供更多的治疗手段。
2023, 30(11):1021-1026.
DOI: 10.3872/j.issn.1007-385X.2023.11.013
Abstract:
近年来，化疗基础上加用抗表皮生长因子受体2 药物、抗血管生成药物及免疫检查点抑制剂，不仅可提高晚期胃癌（GC）患者治疗的有效率，而且可明显改善患者预后。然而，目前晚期GC患者治疗后的生存获益远落后于肺癌、结直肠癌及乳腺癌等实体肿瘤，靶向治疗仍需进一步探索。随着分子生物学技术的发展，新的治疗靶点如Claudin 18.2、基质金属蛋白酶（MMP）、Dickkopf相关蛋白1（DKK-1）、RAD3相关蛋白激酶（ATR）被发现在GC细胞中表达，针对这些靶点的药物逐渐在临床治疗中崭露头角，并显示出较好的临床应用前景。阐述晚期GC治疗中靶点的作用机制及靶向药物的研究进展，对提高GC的临床治疗疗效具有重要意义。
近年来，化疗基础上加用抗表皮生长因子受体2 药物、抗血管生成药物及免疫检查点抑制剂，不仅可提高晚期胃癌（GC）患者治疗的有效率，而且可明显改善患者预后。然而，目前晚期GC患者治疗后的生存获益远落后于肺癌、结直肠癌及乳腺癌等实体肿瘤，靶向治疗仍需进一步探索。随着分子生物学技术的发展，新的治疗靶点如Claudin 18.2、基质金属蛋白酶（MMP）、Dickkopf相关蛋白1（DKK-1）、RAD3相关蛋白激酶（ATR）被发现在GC细胞中表达，针对这些靶点的药物逐渐在临床治疗中崭露头角，并显示出较好的临床应用前景。阐述晚期GC治疗中靶点的作用机制及靶向药物的研究进展，对提高GC的临床治疗疗效具有重要意义。
2023, 30(11):1027-1031.
DOI: 10.3872/j.issn.1007-385X.2023.11.014
Abstract:
食管癌（EC）是临床常见的恶性肿瘤之一，近年来免疫治疗的应用使EC患者的预后得到了改善，但患者对免疫治疗的应答有着明显的异质性，且欠缺有效的疗效预测生物标志物，无法精准筛选获益人群，存在原发性耐药，因此需要寻找新型免疫治疗靶点使更多患者获益。黑色素瘤相关抗原A3（MAGE-A3）是一种癌-睾丸抗原，在正常组织中几乎不表达，而在多种恶性肿瘤组织中呈现高表达，参与肿瘤细胞的增殖、侵袭和转移等多种生物学过程。MAGE-A3基因具有限制性表达和良好的免疫原性，是良好的EC免疫治疗靶点，对EC的诊断、治疗和预后判断等具有良好的应用价值。由于MAGE-A3基因在EC组织中高表达，并与不良预后相关。目前针对MAGE-A3基因靶点的肿瘤疫苗和过继性细胞免疫治疗等疗法均展现出良好的应用前景。
食管癌（EC）是临床常见的恶性肿瘤之一，近年来免疫治疗的应用使EC患者的预后得到了改善，但患者对免疫治疗的应答有着明显的异质性，且欠缺有效的疗效预测生物标志物，无法精准筛选获益人群，存在原发性耐药，因此需要寻找新型免疫治疗靶点使更多患者获益。黑色素瘤相关抗原A3（MAGE-A3）是一种癌-睾丸抗原，在正常组织中几乎不表达，而在多种恶性肿瘤组织中呈现高表达，参与肿瘤细胞的增殖、侵袭和转移等多种生物学过程。MAGE-A3基因具有限制性表达和良好的免疫原性，是良好的EC免疫治疗靶点，对EC的诊断、治疗和预后判断等具有良好的应用价值。由于MAGE-A3基因在EC组织中高表达，并与不良预后相关。目前针对MAGE-A3基因靶点的肿瘤疫苗和过继性细胞免疫治疗等疗法均展现出良好的应用前景。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.