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Volume 32,Issue 4,2025 Table of Contents
2025, 32(4):347-355.
DOI: 10.3872/j.issn.1007-385X.2025.04.001
Abstract:
[Abstract] Alternative splicing, a post-transcriptional regulatory mechanism of gene expression, contributes to the diversity of the transcriptome and proteome in eukaryotes. However, aberrant alternative splicing serves as a significant driver of tumor progression, where abnormal splicing in tumor cells, immune cells, and other cell types within the tumor microenvironment collectively results in malignant behaviors of cancer cells, immune evasion, and the immunosuppressive milieu that supports tumor advancement. Targeting tumor-associated spliceosomes, splicing regulatory factors, splicing isoforms and variants, as well as tumor neoantigens generated by aberrant alternative splicing, has emerged as a novel strategy in cancer biotherapy. Some alternative splicing-based antitumor biotherapy programs have progressed to phase Ⅰ clinical trials. Alternative splicing-based tumor therapy still faces scientific and technological challenges such as safety, optimization of long-read sequencing and bioinformatics algorithm, and nucleic acid drug delivery. Addressing these challenges will provide new tumor therapy strategies and open up new frontiers for precisely screening tumor-related targets and highly immunogenic neoantigens, overcoming drug resistance in traditional therapies, and enhancing the efficacy of immune checkpoint blockade, CAR-T cell therapy, and other treatments.
[Abstract] Alternative splicing, a post-transcriptional regulatory mechanism of gene expression, contributes to the diversity of the transcriptome and proteome in eukaryotes. However, aberrant alternative splicing serves as a significant driver of tumor progression, where abnormal splicing in tumor cells, immune cells, and other cell types within the tumor microenvironment collectively results in malignant behaviors of cancer cells, immune evasion, and the immunosuppressive milieu that supports tumor advancement. Targeting tumor-associated spliceosomes, splicing regulatory factors, splicing isoforms and variants, as well as tumor neoantigens generated by aberrant alternative splicing, has emerged as a novel strategy in cancer biotherapy. Some alternative splicing-based antitumor biotherapy programs have progressed to phase Ⅰ clinical trials. Alternative splicing-based tumor therapy still faces scientific and technological challenges such as safety, optimization of long-read sequencing and bioinformatics algorithm, and nucleic acid drug delivery. Addressing these challenges will provide new tumor therapy strategies and open up new frontiers for precisely screening tumor-related targets and highly immunogenic neoantigens, overcoming drug resistance in traditional therapies, and enhancing the efficacy of immune checkpoint blockade, CAR-T cell therapy, and other treatments.
2025, 32(4):356-363.
DOI: 10.3872/j.issn.1007-385X.2025.04.002
Abstract:
[Abstract] Objective: To investigate the impact of locally IL-2-secreting CAR-T cells (Syn.CD19.IL-2 CAR-T cells) constructed using a novel single-vector SynNotch system on the function of conventional CD19 CAR-T cells. Methods: Building upon our previously established single-vector SynNotch system, the CD19-specific FMC63 antibody was integrated with an IL-2 expression module to prepare Syn.CD19.IL-2 CAR-T cells through T cell transduction using a self-inactivating retroviral vector. For validation experiments, cells were divided into the Syn.CD19.IL-2 CAR-T cell group and the untransduced T cells group. ELISA was used to detect IL-2 secretion levels after antigen stimulation. The CFSE staining assay was implemented to evaluate the effects of IL-2 secretion on the proliferation of CD19 CAR-T cells when CD19 CAR-T cells were co-cultured with Raji-Luc or SW620-CD19-Luc cells in the presence of Syn. CD19. IL-2 CAR-T cells. Flow cytometry was employed to detect CD69 expression and monitor the activation status of CD19 CAR-T cells when co-cultured with Raji-Luc cells in the condition of Syn.CD19.IL-2 CAR-T cells secreting IL-2. Results: The self-inactivating retroviral vector Syn.CD19.IL-2 CAR were successfully constructed and Syn.CD19.IL-2 CAR-T cells with a viral titer >1 × 10? copies/mL and transduction efficiency of 37.1% were generated. After antigen stimulation, SynNotch CAR-T cells demonstrated significantly elevated IL-2 secretion compared with the untransduced T cell group (P < 0.001). When Syn. CD19.IL-2 CAR-T cells secreted IL-2, the CD19 CAR-T cells exhibited enhanced proliferative capacity and elevated activation level (all P < 0.001). Conclusion: Successfully constructed Syn.CD19.IL-2 CAR-T cells can significantly enhance the proliferative capacity and activation ability of conventional CD19 CAR-T cells.
[Abstract] Objective: To investigate the impact of locally IL-2-secreting CAR-T cells (Syn.CD19.IL-2 CAR-T cells) constructed using a novel single-vector SynNotch system on the function of conventional CD19 CAR-T cells. Methods: Building upon our previously established single-vector SynNotch system, the CD19-specific FMC63 antibody was integrated with an IL-2 expression module to prepare Syn.CD19.IL-2 CAR-T cells through T cell transduction using a self-inactivating retroviral vector. For validation experiments, cells were divided into the Syn.CD19.IL-2 CAR-T cell group and the untransduced T cells group. ELISA was used to detect IL-2 secretion levels after antigen stimulation. The CFSE staining assay was implemented to evaluate the effects of IL-2 secretion on the proliferation of CD19 CAR-T cells when CD19 CAR-T cells were co-cultured with Raji-Luc or SW620-CD19-Luc cells in the presence of Syn. CD19. IL-2 CAR-T cells. Flow cytometry was employed to detect CD69 expression and monitor the activation status of CD19 CAR-T cells when co-cultured with Raji-Luc cells in the condition of Syn.CD19.IL-2 CAR-T cells secreting IL-2. Results: The self-inactivating retroviral vector Syn.CD19.IL-2 CAR were successfully constructed and Syn.CD19.IL-2 CAR-T cells with a viral titer >1 × 10? copies/mL and transduction efficiency of 37.1% were generated. After antigen stimulation, SynNotch CAR-T cells demonstrated significantly elevated IL-2 secretion compared with the untransduced T cell group (P < 0.001). When Syn. CD19.IL-2 CAR-T cells secreted IL-2, the CD19 CAR-T cells exhibited enhanced proliferative capacity and elevated activation level (all P < 0.001). Conclusion: Successfully constructed Syn.CD19.IL-2 CAR-T cells can significantly enhance the proliferative capacity and activation ability of conventional CD19 CAR-T cells.
2025, 32(4):364-370.
DOI: 10.3872/j.issn.1007-385X.2025.04.003
Abstract:
[Abstract] Objective: To investigate the expression of homeobox protein C4 (HOXC4) in gastric cancer tissues and cells, as well as its effects on the proliferation, migration and invasion of gastric cancer cells and the underlying mechanisms. Methods: The cancer and adjacent tissue specimens surgically removed from 16 patients with advanced gastric cancer at the Department of Oncology, Nanyang First People’s Hospital, between May 2020 and April 2021 were collected. Additionally, human normal gastric epithelial cells (GES-1) and gastric cancer cell lines (AGS, SGC-790, and MGC-803) were included. Western blot (WB) was performed to detect HOXC4 expression in gastric cancer tissues and cells. RNA interference technology was used to knockdown or overexpress HOXC4 in SGC-790 and AGS cells, with experimental groups divided as follows: the sh-HOXC4#1 group, sh-HOXC4#2 group, sh-Con group, sh-HOXC4 + pc-integrin β1 group, pc-HOXC4 group, pc-Con group, and pc-HOXC4 + pc-integrin β1 group. EdU assay, CCK-8 assay, and Transwell assay were employed to evaluate the effects of HOXC4 knockdown or overexpression on cell viability, proliferation, migration,invasion, and integrin β1 expression in each group. A tumor-bearing mouse model was established using HOXC4-knockdown AGS cells to observe the impact of HOXC4 knockdown on tumor volume and the expressions of Ki67 and integrin β1 proteins in xenograft tissues. Results: The expression of HOXC4 in gastric cancer tissues and cells was significantly up-regulated (all P < 0.01). Compared with those in the sh-Con group, the expression levels of HOXC4 and integrin β1 in SGC-790 and AGS cells, and the cell viability, proliferation, migration and invasion ability decreased significantly in sh-HOXC4#1 and sh-HOXC4#2 groups (all P < 0.01).Compared with those in the sh-HOXC4 group, the cell viability, invasion and migration abilities of cells in the sh-HOXC4 + pc-integrin β1 group increased significantly (all P < 0.01). Compared with those in the pc-Con group, the cell viability, invasion and migration abilities of cells in the pc-HOXC4 group increased significantly (all P < 0.01). Compared with those in the pc-HOXC4 group, the cell viability, invasion and migration abilities of cells in the pc-HOXC4+integrin β1-shRNA group decreased significantly (all P < 0.01). Compared with those in the sh-Con group, the tumor grew slowly, and the volume decreased, and the expressions of Ki67 and integrin β1 decreased significantly in the sh-HOXC4#1 and sh-HOXC4#2 groups (all P < 0.01). Conclusion: The expression of HOXC4 is up-regulated in gastric cancer tissues and cells, and it promotes the proliferation, migration and invasion of gastric cancer cells by activating the integrin β1 signaling pathway.
[Abstract] Objective: To investigate the expression of homeobox protein C4 (HOXC4) in gastric cancer tissues and cells, as well as its effects on the proliferation, migration and invasion of gastric cancer cells and the underlying mechanisms. Methods: The cancer and adjacent tissue specimens surgically removed from 16 patients with advanced gastric cancer at the Department of Oncology, Nanyang First People’s Hospital, between May 2020 and April 2021 were collected. Additionally, human normal gastric epithelial cells (GES-1) and gastric cancer cell lines (AGS, SGC-790, and MGC-803) were included. Western blot (WB) was performed to detect HOXC4 expression in gastric cancer tissues and cells. RNA interference technology was used to knockdown or overexpress HOXC4 in SGC-790 and AGS cells, with experimental groups divided as follows: the sh-HOXC4#1 group, sh-HOXC4#2 group, sh-Con group, sh-HOXC4 + pc-integrin β1 group, pc-HOXC4 group, pc-Con group, and pc-HOXC4 + pc-integrin β1 group. EdU assay, CCK-8 assay, and Transwell assay were employed to evaluate the effects of HOXC4 knockdown or overexpression on cell viability, proliferation, migration,invasion, and integrin β1 expression in each group. A tumor-bearing mouse model was established using HOXC4-knockdown AGS cells to observe the impact of HOXC4 knockdown on tumor volume and the expressions of Ki67 and integrin β1 proteins in xenograft tissues. Results: The expression of HOXC4 in gastric cancer tissues and cells was significantly up-regulated (all P < 0.01). Compared with those in the sh-Con group, the expression levels of HOXC4 and integrin β1 in SGC-790 and AGS cells, and the cell viability, proliferation, migration and invasion ability decreased significantly in sh-HOXC4#1 and sh-HOXC4#2 groups (all P < 0.01).Compared with those in the sh-HOXC4 group, the cell viability, invasion and migration abilities of cells in the sh-HOXC4 + pc-integrin β1 group increased significantly (all P < 0.01). Compared with those in the pc-Con group, the cell viability, invasion and migration abilities of cells in the pc-HOXC4 group increased significantly (all P < 0.01). Compared with those in the pc-HOXC4 group, the cell viability, invasion and migration abilities of cells in the pc-HOXC4+integrin β1-shRNA group decreased significantly (all P < 0.01). Compared with those in the sh-Con group, the tumor grew slowly, and the volume decreased, and the expressions of Ki67 and integrin β1 decreased significantly in the sh-HOXC4#1 and sh-HOXC4#2 groups (all P < 0.01). Conclusion: The expression of HOXC4 is up-regulated in gastric cancer tissues and cells, and it promotes the proliferation, migration and invasion of gastric cancer cells by activating the integrin β1 signaling pathway.
2025, 32(4):371-377.
DOI: 10.3872/j.issn.1007-385X.2025.04.004
Abstract:
[Abstract] Objective: To investigate the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) in pancreatic cancer tissues and its impact on tumor progression, and to explore its role in clinical diagnosis and prognosis evaluation of pancreatic cancer. Methods: Using the GEPIA2 data analysis platform, the expression of KCNN4 in pancreatic cancer tissues and its correlation with patient prognosis were analyzed by integrating data from the TCGA and GTEx databases. Cancerous and adjacent non cancerous tissues from 24 patients with pancreatic cancer who underwent surgical resection at ChangHai Hospital of the Naval Medical University were collected. The expression of KCNN4 in pancreatic cancer tissues was validated using qPCR, Western blotting, and immunohistochemical staining. The expression of KCNN4 in human pancreatic cancer cell lines BXPC3 and PANC-1 was knocked down using shRNA. CCK-8 and colony formation assays were performed to detect tumor cell proliferation and growth. A murine KPC cell pancreatic cancer model was established to investigate the effects of KCNN4 knockdown on the growth of orthotopic pancreatic tumor and overall survival (OS) in mice. Results: Analysis of TCGA and GTEx data revealed that KCNN4 was highly expressed in pancreatic cancer tissues (P < 0.05) and was associated with shortened OS and disease-free survival (DFS) in patients (both P < 0.05). The expression levels of KCNN4 mRNA and protein were significantly elevated in pancreatic cancer tissues compared with those in adjacent non-cancerous tissues (all P < 0.01). Knockdown of KCNN4 led to significantly reduced growth rates and fewer colony formations in pancreatic cancer cells (both P < 0.01). The murine orthotopic pancreatic tumor experiment revealed that KCNN4 knockdown inhibited tumor progression and prolonged the OS of mice. Conclusion: KCNN4, highly expressed in pancreatic cancer tissues, promotes pancreatic cancer cell proliferation and tumor progression, and its expression is closely associated with patient prognosis, suggesting that KCNN4 may serve as a promising target for clinical diagnosis and prognosis evaluation of pancreatic cancer.
[Abstract] Objective: To investigate the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) in pancreatic cancer tissues and its impact on tumor progression, and to explore its role in clinical diagnosis and prognosis evaluation of pancreatic cancer. Methods: Using the GEPIA2 data analysis platform, the expression of KCNN4 in pancreatic cancer tissues and its correlation with patient prognosis were analyzed by integrating data from the TCGA and GTEx databases. Cancerous and adjacent non cancerous tissues from 24 patients with pancreatic cancer who underwent surgical resection at ChangHai Hospital of the Naval Medical University were collected. The expression of KCNN4 in pancreatic cancer tissues was validated using qPCR, Western blotting, and immunohistochemical staining. The expression of KCNN4 in human pancreatic cancer cell lines BXPC3 and PANC-1 was knocked down using shRNA. CCK-8 and colony formation assays were performed to detect tumor cell proliferation and growth. A murine KPC cell pancreatic cancer model was established to investigate the effects of KCNN4 knockdown on the growth of orthotopic pancreatic tumor and overall survival (OS) in mice. Results: Analysis of TCGA and GTEx data revealed that KCNN4 was highly expressed in pancreatic cancer tissues (P < 0.05) and was associated with shortened OS and disease-free survival (DFS) in patients (both P < 0.05). The expression levels of KCNN4 mRNA and protein were significantly elevated in pancreatic cancer tissues compared with those in adjacent non-cancerous tissues (all P < 0.01). Knockdown of KCNN4 led to significantly reduced growth rates and fewer colony formations in pancreatic cancer cells (both P < 0.01). The murine orthotopic pancreatic tumor experiment revealed that KCNN4 knockdown inhibited tumor progression and prolonged the OS of mice. Conclusion: KCNN4, highly expressed in pancreatic cancer tissues, promotes pancreatic cancer cell proliferation and tumor progression, and its expression is closely associated with patient prognosis, suggesting that KCNN4 may serve as a promising target for clinical diagnosis and prognosis evaluation of pancreatic cancer.
2025, 32(4):378-385.
DOI: 10.3872/j.issn.1007-385X.2025.04.005
Abstract:
[Abstract] Objective: To investigate the effect of circular RNA (cireRNA) pumilio RNA binding family member 1 (PUM1) on the proliferation, migration, invasion and apoptosis of endometrial cancer (EC) Ishikawa cells by regulating the miR-337-3p/ nucleophosmin 1 (NPM1) axis. Methods: Ishikawa cells were selected and plasmid sh-circPUM1 and its negative control (sh-NC), anti-miR-337-3p and its negative control (anti-NC) were transfected into Ishikawa cells by RNA interference. The experiment cells were divided into the control group (non-transfected cells), sh-NC group, sh-circPUM1 group, sh-circPUM1 + anti-NC group and sh-circPUM1 + anti-miR-337-3p group. The qPCR method was applied to detect the expressions of circPUM1, miR-337-3p, and NPM1 mRNA in Ishikawa cells in each group. CCK-8 method, EdU staining method, Transwell assay, and flow cytometry were applied respectively to detect the effects of knocking down circPUM1 on the proliferation, migration, invasion and apoptosis of Ishikawa cells. Western blot was applied to detect the changes in the expressions of PCNA, NPM1, MMP-9, SNAIL, E-cadherin, BAX and C-caspase-3 proteins in Ishikawa cells. Dual luciferase reporter gene experiment was applied to verify the targeting relationship between circPUM1 and miR-337-3p, and between miR-337-3p and NPM1. Results: Cell proliferation ability, EdU positive cell rate, migration and invasion numbers, circPUM1, NPM1 mRNA and protein, the expressions of PCNA, NPM1, MMP-9 and SNAIL protein in Ishikawa cells in the sh-circPUM1 group were significantly lower than those in the sh-NC group and Control group (all P < 0.05); the apoptosis rate, the expressions of miR-337-3p, E-cadherin, BAX, and C-caspase-3 proteins were significantly higher than those in the sh-NC group and the Control group (all P < 0.05). Compared with those in the sh-circPUM1 group and the sh-circPUM1 + anti-NC group, the apoptosis rate, miR-337-3p, the expressions of E-cadherin, BAX, and C-caspase-3 proteins in the sh-circPUM1 + anti-miR 337-3p group were significantly lower (all P < 0.05); Cell proliferation ability, EdU positive cell rate, migration and invasion numbers, NPM1 mRNA and protein, the expressions of PCNA, NPM1, MMP-9, and SNAIL proteins were significantly higher (all P < 0.05). CircPUM1 might target and negatively regulate miR-337-3p, and miR-337-3p might target and negatively regulate NPM1. Conclusion: Knocking down circPUM1 can inhibit the malignant biological behavior of Ishikawa cells, which might be achieved by targeting the miR-337-3p/NPM1 axis.
[Abstract] Objective: To investigate the effect of circular RNA (cireRNA) pumilio RNA binding family member 1 (PUM1) on the proliferation, migration, invasion and apoptosis of endometrial cancer (EC) Ishikawa cells by regulating the miR-337-3p/ nucleophosmin 1 (NPM1) axis. Methods: Ishikawa cells were selected and plasmid sh-circPUM1 and its negative control (sh-NC), anti-miR-337-3p and its negative control (anti-NC) were transfected into Ishikawa cells by RNA interference. The experiment cells were divided into the control group (non-transfected cells), sh-NC group, sh-circPUM1 group, sh-circPUM1 + anti-NC group and sh-circPUM1 + anti-miR-337-3p group. The qPCR method was applied to detect the expressions of circPUM1, miR-337-3p, and NPM1 mRNA in Ishikawa cells in each group. CCK-8 method, EdU staining method, Transwell assay, and flow cytometry were applied respectively to detect the effects of knocking down circPUM1 on the proliferation, migration, invasion and apoptosis of Ishikawa cells. Western blot was applied to detect the changes in the expressions of PCNA, NPM1, MMP-9, SNAIL, E-cadherin, BAX and C-caspase-3 proteins in Ishikawa cells. Dual luciferase reporter gene experiment was applied to verify the targeting relationship between circPUM1 and miR-337-3p, and between miR-337-3p and NPM1. Results: Cell proliferation ability, EdU positive cell rate, migration and invasion numbers, circPUM1, NPM1 mRNA and protein, the expressions of PCNA, NPM1, MMP-9 and SNAIL protein in Ishikawa cells in the sh-circPUM1 group were significantly lower than those in the sh-NC group and Control group (all P < 0.05); the apoptosis rate, the expressions of miR-337-3p, E-cadherin, BAX, and C-caspase-3 proteins were significantly higher than those in the sh-NC group and the Control group (all P < 0.05). Compared with those in the sh-circPUM1 group and the sh-circPUM1 + anti-NC group, the apoptosis rate, miR-337-3p, the expressions of E-cadherin, BAX, and C-caspase-3 proteins in the sh-circPUM1 + anti-miR 337-3p group were significantly lower (all P < 0.05); Cell proliferation ability, EdU positive cell rate, migration and invasion numbers, NPM1 mRNA and protein, the expressions of PCNA, NPM1, MMP-9, and SNAIL proteins were significantly higher (all P < 0.05). CircPUM1 might target and negatively regulate miR-337-3p, and miR-337-3p might target and negatively regulate NPM1. Conclusion: Knocking down circPUM1 can inhibit the malignant biological behavior of Ishikawa cells, which might be achieved by targeting the miR-337-3p/NPM1 axis.
2025, 32(4):386-391.
DOI: 10.3872/j.issn.1007-385X.2025.04.006
Abstract:
[Abstract] Objective: To investigate the expression of circular RNA hsa_circ_0046701 in glioma tissues and its effect on the proliferation, migration and invasion of glioma U251 cells. Methods: Tumor tissue specimens and clinical data of fifty-two glioma patients treated surgically in Putuo People's Hospital Affiliated to Tongji University between June 2022 and March 2023 were collected, and another 30 normal brain tissue specimens were collected as controls. The expression level of hsa_circ_0046701 in glioma tissues was detected by qPCR to analyze the relationship between the level and clinical characteristics of the patient. Kaplan-Meier method was used to analyze the relationship between hsa_circ_0046701 level and survival prognosis. Using RNA interference technology, circ_0046701 overexpression and empty vector, siRNA-circ_0046701 and negative control (si-NC) plasmid were transfected into glioma U251 cells, respectively. The experiment cells were divided into the circ 0046701 OE group, Vector group, si-circ_0046701 group and si-NC group. CCK-8 method and Transwell assay were applied to detect the proliferation, migration and invasion abilities of cells in each group. Western blotting was applied to detect the expressions of vimentin, Snail, E-cadherin and cyclin D1 proteins in cells of each group. Results: The expression level of hsa_circ_0046701 in glioma tissues was significantly higher than that in normal brain tissues (P < 0.01). The percentage of patients with WHO glioma grading (grades Ⅲ~Ⅳ) in the hsa_circ_0046701 high-expression group was significantly higher than that of the hsa_circ_0046701 low expression group (P < 0.01). The OS of patients in the high expression group was significantly shorter than that of the low-expression group. Compared with those in the si-NC group, the proliferation ability of U251 cells in the si-circ_0046701 group was significantly reduced (P < 0.05 or P < 0.01), and the numbers of migrated and invaded cells decreased significantly (both P < 0.01). The expressions of vimentin, Snail, and cyclin D1 proteins in the cells was significantly reduced (all P < 0.01), while the expression of E-cadherin protein increased significantly (P < 0.01). Compared with those in the Vector group, the proliferation ability of U251cells in the circ_0046701 OE group increased significantly (P < 0.01); the numbers of migrated and invaded cells increased significantly (both P < 0.01); the expressions of vimentin, Snail, and cyclin D1 proteins in the cells increaseds significantly (all P < 0.01), and the expression of E-cadherin protein decreased significantly (P < 0.01). Conclusion: Circular RNA hsa_circ_0046701 is highly expressed in glioma tissues, and is correlated with poor patient prognosis. Knockdown of hsa_circ_0046701 expression could inhibit the proliferation, migration and invasion of glioma U251cells.
[Abstract] Objective: To investigate the expression of circular RNA hsa_circ_0046701 in glioma tissues and its effect on the proliferation, migration and invasion of glioma U251 cells. Methods: Tumor tissue specimens and clinical data of fifty-two glioma patients treated surgically in Putuo People's Hospital Affiliated to Tongji University between June 2022 and March 2023 were collected, and another 30 normal brain tissue specimens were collected as controls. The expression level of hsa_circ_0046701 in glioma tissues was detected by qPCR to analyze the relationship between the level and clinical characteristics of the patient. Kaplan-Meier method was used to analyze the relationship between hsa_circ_0046701 level and survival prognosis. Using RNA interference technology, circ_0046701 overexpression and empty vector, siRNA-circ_0046701 and negative control (si-NC) plasmid were transfected into glioma U251 cells, respectively. The experiment cells were divided into the circ 0046701 OE group, Vector group, si-circ_0046701 group and si-NC group. CCK-8 method and Transwell assay were applied to detect the proliferation, migration and invasion abilities of cells in each group. Western blotting was applied to detect the expressions of vimentin, Snail, E-cadherin and cyclin D1 proteins in cells of each group. Results: The expression level of hsa_circ_0046701 in glioma tissues was significantly higher than that in normal brain tissues (P < 0.01). The percentage of patients with WHO glioma grading (grades Ⅲ~Ⅳ) in the hsa_circ_0046701 high-expression group was significantly higher than that of the hsa_circ_0046701 low expression group (P < 0.01). The OS of patients in the high expression group was significantly shorter than that of the low-expression group. Compared with those in the si-NC group, the proliferation ability of U251 cells in the si-circ_0046701 group was significantly reduced (P < 0.05 or P < 0.01), and the numbers of migrated and invaded cells decreased significantly (both P < 0.01). The expressions of vimentin, Snail, and cyclin D1 proteins in the cells was significantly reduced (all P < 0.01), while the expression of E-cadherin protein increased significantly (P < 0.01). Compared with those in the Vector group, the proliferation ability of U251cells in the circ_0046701 OE group increased significantly (P < 0.01); the numbers of migrated and invaded cells increased significantly (both P < 0.01); the expressions of vimentin, Snail, and cyclin D1 proteins in the cells increaseds significantly (all P < 0.01), and the expression of E-cadherin protein decreased significantly (P < 0.01). Conclusion: Circular RNA hsa_circ_0046701 is highly expressed in glioma tissues, and is correlated with poor patient prognosis. Knockdown of hsa_circ_0046701 expression could inhibit the proliferation, migration and invasion of glioma U251cells.
2025, 32(4):392-397.
DOI: 10.3872/j.issn.1007-385X.2025.04.007
Abstract:
[Abstract] Objective: To explore the intervention effect of Jianpifuwei granule (JPFWG) on gastric mucosal injury in rats with precancerous lesions of gastric cancer (PLGC) by regulating the IL-6/JAK/STAT3 signaling pathway and its mechanism. Methods: The PLGC model rats were established by MNNG combined with composite factors, and randomly divided into 6 groups (20 rats/group): the blank group (untreated), model group (treated with normal saline), Weimeisu group (0.05 g/mL Weimeisu), JPFWG low-dose group (JPFWG-L，0.088 g/mL), JPFWG medium-dose group (JPFWG-M，0.176 g/mL) and JPFWG high-dose group (JPFWG-H， 0.351 g/mL). After being treated with Weimeisu and different doses of JPFWG for 12 weeks, the animals were anesthetized and sacrificed, and the gastric tissues were collected. The pathological changes of gastric mucosa were observed by H-E staining, and the expression levels of IL-6-mediated JAK/STAT3 signaling pathway factors (including IL-6, JAK and STAT3) and the mRNA and proteins of their downstream target genes c-Myc and cyclin D1 in gastric mucosal tissues were detected by immunohistochemistry, qPCR and WB. Results: Compared with that in the model group, the gastric mucosal inflammatory cell infiltration was reduced in the Weimeisu group and the low, medium, and high dose groups of JPFWG; pathological condition was improved, most obviously in the high dose group of JPFWG; The protein expressions of IL-6, JAK1 and STAT3 decreased significantly (P < 0.05 or P < 0.01). The expressions of mRNA and proteins of c-Myc and cyclin D1 in the gastric mucosal tissues of the rats in the Weimeisu group and JPFWG-H group decreased significantly (P < 0.05 or P < 0.01). Conclusion: JPFWG can improve the histopathological changes of gastric mucosa in rats with PLGC, and its mechanism may be down-regulating the expressions of c-Myc and cyclin D1 through regulating IL-6/JAK/STAT3 signal pathway, thus blocking inflammation-cancer transformation process.
[Abstract] Objective: To explore the intervention effect of Jianpifuwei granule (JPFWG) on gastric mucosal injury in rats with precancerous lesions of gastric cancer (PLGC) by regulating the IL-6/JAK/STAT3 signaling pathway and its mechanism. Methods: The PLGC model rats were established by MNNG combined with composite factors, and randomly divided into 6 groups (20 rats/group): the blank group (untreated), model group (treated with normal saline), Weimeisu group (0.05 g/mL Weimeisu), JPFWG low-dose group (JPFWG-L，0.088 g/mL), JPFWG medium-dose group (JPFWG-M，0.176 g/mL) and JPFWG high-dose group (JPFWG-H， 0.351 g/mL). After being treated with Weimeisu and different doses of JPFWG for 12 weeks, the animals were anesthetized and sacrificed, and the gastric tissues were collected. The pathological changes of gastric mucosa were observed by H-E staining, and the expression levels of IL-6-mediated JAK/STAT3 signaling pathway factors (including IL-6, JAK and STAT3) and the mRNA and proteins of their downstream target genes c-Myc and cyclin D1 in gastric mucosal tissues were detected by immunohistochemistry, qPCR and WB. Results: Compared with that in the model group, the gastric mucosal inflammatory cell infiltration was reduced in the Weimeisu group and the low, medium, and high dose groups of JPFWG; pathological condition was improved, most obviously in the high dose group of JPFWG; The protein expressions of IL-6, JAK1 and STAT3 decreased significantly (P < 0.05 or P < 0.01). The expressions of mRNA and proteins of c-Myc and cyclin D1 in the gastric mucosal tissues of the rats in the Weimeisu group and JPFWG-H group decreased significantly (P < 0.05 or P < 0.01). Conclusion: JPFWG can improve the histopathological changes of gastric mucosa in rats with PLGC, and its mechanism may be down-regulating the expressions of c-Myc and cyclin D1 through regulating IL-6/JAK/STAT3 signal pathway, thus blocking inflammation-cancer transformation process.
2025, 32(4):398-404.
DOI: 10.3872/j.issn.1007-385X.2025.04.008
Abstract:
[Abstract] Objective: To investigate the effects of long non-coding RNA (lncRNA) endogenous Bornavirus-like nucleoprotein 3 pseudogene (EBLN3P) on the proliferation, migration and epithelial-mesenchymal transition (EMT) of thyroid cancer B-CPAP cells by regulating the miR-369-3p/CCND1 axis. Methods: 20 samples of thyroid cancer and corresponding adjacent tissue specimens surgically removed at Hainan Cancer Hospital between May 2020 and May 2021, as well as thyroid cancer B-CPAP cells were collected. The levels of EBLN3P, miR-369-3p and CCND1 mRNA in cancer tissues and cells were detected using qPCR and Western blot (WB) methods. The dual-luciferase reporter gene assay was used to validate the targeting relationship among lncRNA EBLN3P, CCND1 and miR-369-3p. B-CPAP cells were randomly divided into the control group, sh-NC group, sh-EBLN3P group, sh-EBLN3P + anti-NC group and sh-EBLN3P + anti-miR-369-3p group. The colony formation assay was used to detect the number of colony formation in each group. The scratch wound healing assay and Transwell assay were performed to evaluate cell migration ability. WB was used to detect the expression of EMT-related proteins. The nude mouse xenograft model of B-CPAP cells was constructed to observe the effect of silencing EBLN3P on the growth of xenograft tumors. Results: The expressions of lncRNA EBLN3P and CCND1 mRNA were up-regulated, and the expression of miR-369-3p was down-regulated in thyroid cancer tissues and B-CPAP cells (all P < 0.05). lncRNA EBLN3P had binding sites with miR-369-3p, and CCND1 had binding sites with miR-369-3p, and there was a targeting relationship. Compared with those in the sh-NC group, the number of clone formation, the scratch healing rate and the number of cell migration in the sh-EBLN3P group decreased (all P < 0.05); the expressions of EBLN3P, CCND1, Ki67, MMP-2, N-cadherin and vimentin was down-regulated; the expressions of miR-369-3p and E-cadherin was up-regulated (all P < 0.05). Compared with those in the sh-EBLN3P + anti-NC group, the expression of miR-369-3p in the sh-EBLN3P + anti-miR-369-3p group was down-regulated; the number of clone formation, scratch healing rate and the number of cell migration increased (all P < 0.05); the expressions of CCND1, Ki67, MMP-2, N-cadherin and vimentin was up-regulated; the expression of E-cadherin was down-regulated (all P < 0.05). Compared with those in the sh-NC group, the volume and weight of B-CPAP cell nude mouse xenograft tumors in the sh-EBLN3P group were significantly reduced (both P < 0.05). Conclusion: The expression of lncRNA EBLN3P is up-regulated in thyroid cancer cells and tissues. Silencing EBLN3P can inhibit the proliferation, migration and EMT of thyroid cancer B-CPAP cells by targeting and regulating the miR-369-3p/CCND1 axis.
[Abstract] Objective: To investigate the effects of long non-coding RNA (lncRNA) endogenous Bornavirus-like nucleoprotein 3 pseudogene (EBLN3P) on the proliferation, migration and epithelial-mesenchymal transition (EMT) of thyroid cancer B-CPAP cells by regulating the miR-369-3p/CCND1 axis. Methods: 20 samples of thyroid cancer and corresponding adjacent tissue specimens surgically removed at Hainan Cancer Hospital between May 2020 and May 2021, as well as thyroid cancer B-CPAP cells were collected. The levels of EBLN3P, miR-369-3p and CCND1 mRNA in cancer tissues and cells were detected using qPCR and Western blot (WB) methods. The dual-luciferase reporter gene assay was used to validate the targeting relationship among lncRNA EBLN3P, CCND1 and miR-369-3p. B-CPAP cells were randomly divided into the control group, sh-NC group, sh-EBLN3P group, sh-EBLN3P + anti-NC group and sh-EBLN3P + anti-miR-369-3p group. The colony formation assay was used to detect the number of colony formation in each group. The scratch wound healing assay and Transwell assay were performed to evaluate cell migration ability. WB was used to detect the expression of EMT-related proteins. The nude mouse xenograft model of B-CPAP cells was constructed to observe the effect of silencing EBLN3P on the growth of xenograft tumors. Results: The expressions of lncRNA EBLN3P and CCND1 mRNA were up-regulated, and the expression of miR-369-3p was down-regulated in thyroid cancer tissues and B-CPAP cells (all P < 0.05). lncRNA EBLN3P had binding sites with miR-369-3p, and CCND1 had binding sites with miR-369-3p, and there was a targeting relationship. Compared with those in the sh-NC group, the number of clone formation, the scratch healing rate and the number of cell migration in the sh-EBLN3P group decreased (all P < 0.05); the expressions of EBLN3P, CCND1, Ki67, MMP-2, N-cadherin and vimentin was down-regulated; the expressions of miR-369-3p and E-cadherin was up-regulated (all P < 0.05). Compared with those in the sh-EBLN3P + anti-NC group, the expression of miR-369-3p in the sh-EBLN3P + anti-miR-369-3p group was down-regulated; the number of clone formation, scratch healing rate and the number of cell migration increased (all P < 0.05); the expressions of CCND1, Ki67, MMP-2, N-cadherin and vimentin was up-regulated; the expression of E-cadherin was down-regulated (all P < 0.05). Compared with those in the sh-NC group, the volume and weight of B-CPAP cell nude mouse xenograft tumors in the sh-EBLN3P group were significantly reduced (both P < 0.05). Conclusion: The expression of lncRNA EBLN3P is up-regulated in thyroid cancer cells and tissues. Silencing EBLN3P can inhibit the proliferation, migration and EMT of thyroid cancer B-CPAP cells by targeting and regulating the miR-369-3p/CCND1 axis.
WANG Yu
,
WEI Zhuojun
,
WANG Lin
,
WANG Ruiqi
,
CHEN Huan
,
CHENG Qi
,
LIN Xiao
,
MA Honglian
,
XU Yujin
2025, 32(4):405-412.
DOI: 10.3872/j.issn.1007-385X.2025.04.009
Abstract:
[Abstract] Objective: To explore the predictive and prognostic value of prognostic nutritional index (PNI) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing induction chemotherapy combined with immune sequential radiotherapy. Methods: A retrospective analysis was conducted on clinical data from 126 locally advanced ESCC patients who had undergone induction chemotherapy combined with immune sequential radiotherapy at Zhejiang Cancer Hospital between May 2019 and August 2023. Receiver operating characteristic (ROC) curves were used to determine optimal PNI cutoff values within 1 week before induction chemoimmunotherapy, within 1 week before radiotherapy, and at 4 ± 1 weeks after radiotherapy initiation, with subsequent patient stratification. The Kaplan-Meier method was used to generate survival curves and the log-rank test was used to compare overall survival (OS) and progression-free survival (PFS) between groups. Cox regression analysis was employed to identify factors affecting the prognosis of locally advanced ESCC patients undergoing induction chemoimmunotherapy combined with sequential radiotherapy. Results: A total of 126 locally advanced ESCC patients, 118 males and 8 females, with a median age of 65 years (44-78 years) were included. The optimal critical values of PNI before induction chemoimmunotherapy, before radiotherapy and during radiotherapy identified using ROC curves were 46.2, 48.3 and 37.9. The median OS and PFS were 47.3 and 28.2 months in the group with PNI ≥ 48.3 before radiotherapy, and 18.7 and 15.2 months in the group with PNI < 48.3 before radiotherapy, respectively (P < 0.01, P < 0.05). The median OS was not reached and the median PFS was 25.7 months in the group with PNI ≥ 37.9 in radiotherapy, and the median OS and PFS were 17.0 and 12.5 months in the group with PNI < 37.9 in radiotherapy, respectively (P < 0.01, P < 0.05). The median OS was not reached and the median PFS was 28.4 months in the group with elevated PNI after induction chemoimmunization; the median OS and PFS were 20.4 and 16.0 months in the group with reduced PNI (P < 0.01, P < 0.05). Multifactorial analysis showed that PNI in radiotherapy [HR = 2.292, 95% CI (1.264, 4.159), P < 0.05], and change in PNI after induction of chemoimmunization [HR = 2.120, 95% CI (1.007, 4.463), P < 0.05] were factors affecting OS. Conclusion: PNI during radiotherapy and changes in PNI after induction chemoimmunity correlate with patients' treatment efficacy and prognosis, and can be used as important indicators to predict the benefits of induction chemoimmunization combined with sequential radiotherapy for ESCC.
[Abstract] Objective: To explore the predictive and prognostic value of prognostic nutritional index (PNI) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing induction chemotherapy combined with immune sequential radiotherapy. Methods: A retrospective analysis was conducted on clinical data from 126 locally advanced ESCC patients who had undergone induction chemotherapy combined with immune sequential radiotherapy at Zhejiang Cancer Hospital between May 2019 and August 2023. Receiver operating characteristic (ROC) curves were used to determine optimal PNI cutoff values within 1 week before induction chemoimmunotherapy, within 1 week before radiotherapy, and at 4 ± 1 weeks after radiotherapy initiation, with subsequent patient stratification. The Kaplan-Meier method was used to generate survival curves and the log-rank test was used to compare overall survival (OS) and progression-free survival (PFS) between groups. Cox regression analysis was employed to identify factors affecting the prognosis of locally advanced ESCC patients undergoing induction chemoimmunotherapy combined with sequential radiotherapy. Results: A total of 126 locally advanced ESCC patients, 118 males and 8 females, with a median age of 65 years (44-78 years) were included. The optimal critical values of PNI before induction chemoimmunotherapy, before radiotherapy and during radiotherapy identified using ROC curves were 46.2, 48.3 and 37.9. The median OS and PFS were 47.3 and 28.2 months in the group with PNI ≥ 48.3 before radiotherapy, and 18.7 and 15.2 months in the group with PNI < 48.3 before radiotherapy, respectively (P < 0.01, P < 0.05). The median OS was not reached and the median PFS was 25.7 months in the group with PNI ≥ 37.9 in radiotherapy, and the median OS and PFS were 17.0 and 12.5 months in the group with PNI < 37.9 in radiotherapy, respectively (P < 0.01, P < 0.05). The median OS was not reached and the median PFS was 28.4 months in the group with elevated PNI after induction chemoimmunization; the median OS and PFS were 20.4 and 16.0 months in the group with reduced PNI (P < 0.01, P < 0.05). Multifactorial analysis showed that PNI in radiotherapy [HR = 2.292, 95% CI (1.264, 4.159), P < 0.05], and change in PNI after induction of chemoimmunization [HR = 2.120, 95% CI (1.007, 4.463), P < 0.05] were factors affecting OS. Conclusion: PNI during radiotherapy and changes in PNI after induction chemoimmunity correlate with patients' treatment efficacy and prognosis, and can be used as important indicators to predict the benefits of induction chemoimmunization combined with sequential radiotherapy for ESCC.
2025, 32(4):413-417.
DOI: 10.3872/j.issn.1007-385X.2025.04.010
Abstract:
[Abstract] Objective: To evaluate the clinical efficacy and safety of DC-CIK cell immunotherapy as an adjuvant to cetuximab combined with CAPEOX (oxaliplatin + capecitabine) chemotherapy regimen in the treatment of advanced colorectal cancer (CRC) with all RAS gene wild-type and BRAF gene wild-type. Methods: A retrospective analysis was conducted on the clinical data of 52 cases of advanced CRC treated in the Oncology Department of in the General Hospital of the Eastern Theatre Command between December 2020 and October 2023, with 26 cases in the control group and the observation group respectively. The observation group received DC-CIK cell therapy in addition to chemotherapy given to the control group. The clinical efficacy and adverse reactions of patients were recorded, and the recent efficacy, quality of life score, incidence of chemotherapy adverse reactions, the changes in tumour markers, and immune indicators before and after treatment were analysed. Results: Compared with those in the control group, the disease control rate (DCR) and quality of life of advanced CRC patients in the observation group were significantly improved (both P < 0.05). The incidence of diarrheal/constipation and tumour marker CA72-4 were significantly reduced (all P < 0.05), and the NK cell count increased significantly (P < 0.05). Conclusion: DC-CIK cell immunotherapy, when used as an adjuvant to cetuximab in combination with the CAPEOX chemotherapy regimen in patients with advanced CRC, is safe and feasible. It can significantly improve the DCR and bring significant clinical benefits to patients.
[Abstract] Objective: To evaluate the clinical efficacy and safety of DC-CIK cell immunotherapy as an adjuvant to cetuximab combined with CAPEOX (oxaliplatin + capecitabine) chemotherapy regimen in the treatment of advanced colorectal cancer (CRC) with all RAS gene wild-type and BRAF gene wild-type. Methods: A retrospective analysis was conducted on the clinical data of 52 cases of advanced CRC treated in the Oncology Department of in the General Hospital of the Eastern Theatre Command between December 2020 and October 2023, with 26 cases in the control group and the observation group respectively. The observation group received DC-CIK cell therapy in addition to chemotherapy given to the control group. The clinical efficacy and adverse reactions of patients were recorded, and the recent efficacy, quality of life score, incidence of chemotherapy adverse reactions, the changes in tumour markers, and immune indicators before and after treatment were analysed. Results: Compared with those in the control group, the disease control rate (DCR) and quality of life of advanced CRC patients in the observation group were significantly improved (both P < 0.05). The incidence of diarrheal/constipation and tumour marker CA72-4 were significantly reduced (all P < 0.05), and the NK cell count increased significantly (P < 0.05). Conclusion: DC-CIK cell immunotherapy, when used as an adjuvant to cetuximab in combination with the CAPEOX chemotherapy regimen in patients with advanced CRC, is safe and feasible. It can significantly improve the DCR and bring significant clinical benefits to patients.
TAN Siyi
,
WANG Xiaolu
,
WANG Qin
,
DU Shiyao
,
YIN Fangtao
,
YANG Yiqi
,
SUN Wu
,
LIU Juan
,
ZHOU Xia
,
LIU Baorui
,
LI Rutian
2025, 32(4):418-424.
DOI: 10.3872/j.issn.1007-385X.2025.04.011
Abstract:
[Abstract] Objective: To evaluate the efficacy and safety of radiotherapy as a combined mode with in-situ vaccine for patients with advanced soft tissue sarcoma (STS). Methods: The clinical data of 12 patients with advanced STS who received combination therapy mode at the Cancer Center of Gulou Hospital Affiliated to the School of Medicine of Nanjing University between December 2020 and September 2024 were retrospectively analyzed. All 12 patients received combined therapy. The main radiotherapeutic approach was hypofractionated radiotherapy. The targeted therapy mainly involved Anlotinib (in 10 cases) or Apatinib (in 2 cases). Immunotherapy mainly involved PD-1 antibodies. The primary endpoint was disease control rate (DCR), and the secondary endpoints were objective response rate (ORR) and safety. Results: Among the 12 STS patients who received combined treatment, 0 cases achieved CR, 4 cases achieved PR; 7 cases had SD, and 1 case had PD. The ORR was 33%, and the DCR was 91.7%, among which the DCR of the target lesions was 100%. Among the 12 patients, 9 patients experienced grade Ⅰ to grade Ⅱ adverse reactions. The most frequently occurring hematological adverse reactions were anemia (6 cases) and abnormal results of liver function tests (3 cases). The most frequently occurring non-hematological adverse reactions were proteinuria (5 cases), hypertension (4 cases), abnormal thyroid function (3 cases), anorexia (3 cases), and nausea and vomiting (2 cases). Only 2 cases had grade Ⅲ hematological toxicity, and 1 case had grade Ⅲ pneumothorax. Conclusion: Radiotherapy as a combined therapy mode with in situ vaccine can achieve a higher DCR in advanced soft tissue sarcomas without serious adverse reactions. This combined treatment modality demonstrates good efficacy and safety.
[Abstract] Objective: To evaluate the efficacy and safety of radiotherapy as a combined mode with in-situ vaccine for patients with advanced soft tissue sarcoma (STS). Methods: The clinical data of 12 patients with advanced STS who received combination therapy mode at the Cancer Center of Gulou Hospital Affiliated to the School of Medicine of Nanjing University between December 2020 and September 2024 were retrospectively analyzed. All 12 patients received combined therapy. The main radiotherapeutic approach was hypofractionated radiotherapy. The targeted therapy mainly involved Anlotinib (in 10 cases) or Apatinib (in 2 cases). Immunotherapy mainly involved PD-1 antibodies. The primary endpoint was disease control rate (DCR), and the secondary endpoints were objective response rate (ORR) and safety. Results: Among the 12 STS patients who received combined treatment, 0 cases achieved CR, 4 cases achieved PR; 7 cases had SD, and 1 case had PD. The ORR was 33%, and the DCR was 91.7%, among which the DCR of the target lesions was 100%. Among the 12 patients, 9 patients experienced grade Ⅰ to grade Ⅱ adverse reactions. The most frequently occurring hematological adverse reactions were anemia (6 cases) and abnormal results of liver function tests (3 cases). The most frequently occurring non-hematological adverse reactions were proteinuria (5 cases), hypertension (4 cases), abnormal thyroid function (3 cases), anorexia (3 cases), and nausea and vomiting (2 cases). Only 2 cases had grade Ⅲ hematological toxicity, and 1 case had grade Ⅲ pneumothorax. Conclusion: Radiotherapy as a combined therapy mode with in situ vaccine can achieve a higher DCR in advanced soft tissue sarcomas without serious adverse reactions. This combined treatment modality demonstrates good efficacy and safety.
2025, 32(4):425-431.
DOI: 10.3872/j.issn.1007-385X.2025.04.012
Abstract:
[摘 要] 蛋白质棕榈酰化作为一种可逆的翻译后修饰，通过动态调控底物蛋白的膜定位、稳定性和相互作用参与肿瘤发生发 展。本文系统总结了由DHHC家族酶催化、酰基蛋白硫酯酶（APT）介导去修饰的棕榈酰化循环对肿瘤关键信号通路的调控机 制，包括增强AKT膜锚定以促进存活信号的转导、调控RAS亚细胞分布以驱动增殖，以及稳定β-catenin以激活Wnt信号通路。 此外，该修饰还通过重编程糖脂代谢、调控铁死亡或凋亡的敏感性，以及影响免疫检查点蛋白的功能，塑造肿瘤微环境。靶向棕 榈酰化酶或开发去棕榈酰化抑制剂为肿瘤治疗提供了新的策略；然而，如何实现时空特异性的精准调控仍然是一个挑战。深入 解析棕榈酰化网络与肿瘤异质性的关联将推动精准治疗发展。
[摘 要] 蛋白质棕榈酰化作为一种可逆的翻译后修饰，通过动态调控底物蛋白的膜定位、稳定性和相互作用参与肿瘤发生发 展。本文系统总结了由DHHC家族酶催化、酰基蛋白硫酯酶（APT）介导去修饰的棕榈酰化循环对肿瘤关键信号通路的调控机 制，包括增强AKT膜锚定以促进存活信号的转导、调控RAS亚细胞分布以驱动增殖，以及稳定β-catenin以激活Wnt信号通路。 此外，该修饰还通过重编程糖脂代谢、调控铁死亡或凋亡的敏感性，以及影响免疫检查点蛋白的功能，塑造肿瘤微环境。靶向棕 榈酰化酶或开发去棕榈酰化抑制剂为肿瘤治疗提供了新的策略；然而，如何实现时空特异性的精准调控仍然是一个挑战。深入 解析棕榈酰化网络与肿瘤异质性的关联将推动精准治疗发展。
2025, 32(4):432-436.
DOI: 10.3872/j.issn.1007-385X.2025.04.013
Abstract:
[摘 要] 致癌基因的激活和抗肿瘤治疗均可诱导肿瘤细胞发生衰老。衰老细胞以高度稳定的细胞周期停滞和衰老相关分泌 表型（SASP）为特征。通过诱导肿瘤细胞衰老并清除衰老细胞，为肿瘤治疗提供了新的策略和广阔前景。本综述系统探讨细胞 衰老与肿瘤之间的内在关系，深入阐述抗肿瘤治疗诱导的肿瘤细胞衰老的分子机制，总结衰老细胞清除剂在抗肿瘤治疗中的最 新研究进展，为临床利用细胞衰老策略治疗肿瘤提供了理论依据和潜在方向。
[摘 要] 致癌基因的激活和抗肿瘤治疗均可诱导肿瘤细胞发生衰老。衰老细胞以高度稳定的细胞周期停滞和衰老相关分泌 表型（SASP）为特征。通过诱导肿瘤细胞衰老并清除衰老细胞，为肿瘤治疗提供了新的策略和广阔前景。本综述系统探讨细胞 衰老与肿瘤之间的内在关系，深入阐述抗肿瘤治疗诱导的肿瘤细胞衰老的分子机制，总结衰老细胞清除剂在抗肿瘤治疗中的最 新研究进展，为临床利用细胞衰老策略治疗肿瘤提供了理论依据和潜在方向。
2025, 32(4):437-441.
DOI: 10.3872/j.issn.1007-385X.2025.04.014
Abstract:
[摘 要] 免疫检查点抑制剂（ICI）在晚期非小细胞肺癌（NSCLC）治疗中取得了显著进展，极大地改善了患者的生存期，但是获 得性耐药（ADR）的出现严重限制了其长期疗效。目前，针对NSCLC免疫治疗ADR的机制尚未完全阐明，临床应对策略亦亟需 优化。本文系统综述了NSCLC免疫治疗ADR的临床特征、分子机制及潜在干预策略，重点探讨肿瘤微环境（TME）的免疫抑制 特性以及相关宿主因素对耐药的影响，提出基于中西医结合的多模式联合治疗策略，为克服ADR提供了理论依据。
[摘 要] 免疫检查点抑制剂（ICI）在晚期非小细胞肺癌（NSCLC）治疗中取得了显著进展，极大地改善了患者的生存期，但是获 得性耐药（ADR）的出现严重限制了其长期疗效。目前，针对NSCLC免疫治疗ADR的机制尚未完全阐明，临床应对策略亦亟需 优化。本文系统综述了NSCLC免疫治疗ADR的临床特征、分子机制及潜在干预策略，重点探讨肿瘤微环境（TME）的免疫抑制 特性以及相关宿主因素对耐药的影响，提出基于中西医结合的多模式联合治疗策略，为克服ADR提供了理论依据。
2025, 32(4):442-448.
DOI: 10.3872/j.issn.1007-385X.2025.04.015
Abstract:
[摘 要] 嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）疗法作为一种新兴的肿瘤免疫治疗方法，突破了传统疗法的局限 性，能够精准靶向肿瘤细胞，显著改善了复发难治性多发性骨髓瘤（RRMM）患者的生存预后，为多发性骨髓瘤（MM）的免疫治疗 开辟了新的方向。然而，CAR-T细胞疗法在MM的应用中仍存在诸多限制因素。研究发现，CAR-T细胞桥接治疗在控制肿瘤进 展、降低肿瘤负荷和提高适合接受CAR-T细胞治疗的患者比例等方面发挥重要作用，但桥接治疗相关规范尚不成熟。本文系统 回顾了RRMM中CAR-T细胞疗法作为桥接治疗的研究进展，深入探讨了桥接治疗的临床价值、适用患者人群以及方案选择，为 CAR-T细胞疗法的优化和临床应用提供了参考与指导。
[摘 要] 嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）疗法作为一种新兴的肿瘤免疫治疗方法，突破了传统疗法的局限 性，能够精准靶向肿瘤细胞，显著改善了复发难治性多发性骨髓瘤（RRMM）患者的生存预后，为多发性骨髓瘤（MM）的免疫治疗 开辟了新的方向。然而，CAR-T细胞疗法在MM的应用中仍存在诸多限制因素。研究发现，CAR-T细胞桥接治疗在控制肿瘤进 展、降低肿瘤负荷和提高适合接受CAR-T细胞治疗的患者比例等方面发挥重要作用，但桥接治疗相关规范尚不成熟。本文系统 回顾了RRMM中CAR-T细胞疗法作为桥接治疗的研究进展，深入探讨了桥接治疗的临床价值、适用患者人群以及方案选择，为 CAR-T细胞疗法的优化和临床应用提供了参考与指导。
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.