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Volume 32,Issue 3,2025 Table of Contents
2025, 32(3):233-238.
DOI: 10.3872/j.issn.1007-385X.2025.03.001
Abstract:
[Abstract] In the field of cancer treatment, traditional therapeutic means such as surgery, chemotherapy and radiotherapy have achieved certain results, but they are often associated with severe side effects, high recurrence rate and serious damage to normal tissues. In recent years, with the rapid development of biomaterials science, integrated biomaterials for tumor prevention, treatment, and organ protection have gradually become a research hotspot. According to dimensional structures, these biomaterials can be classified into small-molecule drugs, zero - dimensional, one - dimensional, two - dimensional, three - dimensional biomaterials, multi dimensional composites, and active biomaterials. Zero-dimensional biomaterials, such as Prussian blue nanozymes and gold nanoparticles, are enabled tumor suppression and tissue regeneration. One-dimensional materials, like nanotubes, facilitate drug loading and enhance wound healing. Two-dimensional biomaterials like laponite can be used to construct the nanocomposite system gelatin laponite-doxorubicin (GLD), which significantly enhances the killing ability against tumor cells. Three-dimensional biomaterials, such as hydrogels, are applicable for tumor therapy and tissue repair. Composites formed by zero - dimensional materials and two - or three - dimensional biomaterials can achieve long - term slow release of zero - dimensional biomaterials and simultaneously play the functions of tumor prevention and treatment and organ protection. When designing biomaterials, it is critical to holistically evaluate their strengths and limitations, leveraging nanotechnology and bioengineering strategies to achieve precise tumor targeting and organ preservation. By integrating anti-tumor drugs and tissue repair factors, these materials aim to achieve inhibition of tumor growth while promoting repair and regeneration of damaged tissues, providing new ideas and methods for tumor treatment.
[Abstract] In the field of cancer treatment, traditional therapeutic means such as surgery, chemotherapy and radiotherapy have achieved certain results, but they are often associated with severe side effects, high recurrence rate and serious damage to normal tissues. In recent years, with the rapid development of biomaterials science, integrated biomaterials for tumor prevention, treatment, and organ protection have gradually become a research hotspot. According to dimensional structures, these biomaterials can be classified into small-molecule drugs, zero - dimensional, one - dimensional, two - dimensional, three - dimensional biomaterials, multi dimensional composites, and active biomaterials. Zero-dimensional biomaterials, such as Prussian blue nanozymes and gold nanoparticles, are enabled tumor suppression and tissue regeneration. One-dimensional materials, like nanotubes, facilitate drug loading and enhance wound healing. Two-dimensional biomaterials like laponite can be used to construct the nanocomposite system gelatin laponite-doxorubicin (GLD), which significantly enhances the killing ability against tumor cells. Three-dimensional biomaterials, such as hydrogels, are applicable for tumor therapy and tissue repair. Composites formed by zero - dimensional materials and two - or three - dimensional biomaterials can achieve long - term slow release of zero - dimensional biomaterials and simultaneously play the functions of tumor prevention and treatment and organ protection. When designing biomaterials, it is critical to holistically evaluate their strengths and limitations, leveraging nanotechnology and bioengineering strategies to achieve precise tumor targeting and organ preservation. By integrating anti-tumor drugs and tissue repair factors, these materials aim to achieve inhibition of tumor growth while promoting repair and regeneration of damaged tissues, providing new ideas and methods for tumor treatment.
XU Xiujie
,
ZHANG Jingyun
,
FAN Junchen
,
JIANG Lingxin
,
ZHANG Na
,
ZHENG Mengchao
,
LONG Yufei
,
GAO Guihua
,
YAN Taoling
,
LAN Tianshu
2025, 32(3):239-246.
DOI: 10.3872/j.issn.1007-385X.2025.03.002
Abstract:
[Abstract] Objective: To construct bacterial cytoplasmic membrane nanovesicles (BMV) with overexpressing programmed death 1 (PD-1), denoted as BMV-PD-1 and evaluate the targeting efficacy of BMV-PD-1 towards transplanted lung tumor tissues in mice. Methods: The fusion plasmid ClyA-PD-1-EGFP fused by PD-1 and Cytolysin A (ClyA) was transferred into Escherichia coli BL21 Codonplus through plasmid transformation. Laser confocal microscopy, SDS-PAGE, and WB were used to detect the expression of the fusion protein ClyA-PD-1-EGFP. Bacterial membranes were extracted and processed with an extruder to generate BMV-PD-1. TEM and NTA were utilized to assess the morphology, size distribution, and zeta potential of BMV-PD-1, while WB was used to verify the presence of PD-1 protein. Laser confocal imaging was conducted to monitor the uptake of BMV-PD-1 by Lewis lung cancer cells. A C57BL/6J mouse subcutaneous transplant tumor model of LLC lung cancer cells was constructed, and the tumor targeting of BMV-PD-1 was evaluated by small animal imaging system. Results: Laser confocal microscopy images demonstrated that the plasmid ClyA-PD-1 EGFP was transferred into BL21-Codonplus and successfully expressed into protein. SDS-PAGE results suggested that ClyA-PD-1 EGFP was overexpressed in BL21-Codonplus. WB analysis indicated that PD-1 was expressed in bacteria and highly expressed in BMV-PD-1 (P < 0.001). NTA and TEM analyses revealed that BMV-PD-1 were spherical vesicles with a diameter of (145 ± 14) nm and a negative surface charge. Laser confocal imaging showed that the high expression of PD-1 significantly increased the uptake of BMV PD-1 by lung cancer cells (P < 0.01). In vivo imaging of small animals further confirmed that the high expression of PD-1 can effectively improve cancer targeting of BMV-PD-1 (P < 0.01). Conclusion: In this study, bacterial plasma membrane nanovesicles BMV-PD-1 with high PD-1 expression are successfully constructed, and it is found that PD-1 overexpression markedly improve the mouse lung cancer xenograft tissue targeting specificity of BMV-PD-1, laying the groundwork for further development of BMV-PD-1 as a carrier for targeted drug delivery systems in tumors.
[Abstract] Objective: To construct bacterial cytoplasmic membrane nanovesicles (BMV) with overexpressing programmed death 1 (PD-1), denoted as BMV-PD-1 and evaluate the targeting efficacy of BMV-PD-1 towards transplanted lung tumor tissues in mice. Methods: The fusion plasmid ClyA-PD-1-EGFP fused by PD-1 and Cytolysin A (ClyA) was transferred into Escherichia coli BL21 Codonplus through plasmid transformation. Laser confocal microscopy, SDS-PAGE, and WB were used to detect the expression of the fusion protein ClyA-PD-1-EGFP. Bacterial membranes were extracted and processed with an extruder to generate BMV-PD-1. TEM and NTA were utilized to assess the morphology, size distribution, and zeta potential of BMV-PD-1, while WB was used to verify the presence of PD-1 protein. Laser confocal imaging was conducted to monitor the uptake of BMV-PD-1 by Lewis lung cancer cells. A C57BL/6J mouse subcutaneous transplant tumor model of LLC lung cancer cells was constructed, and the tumor targeting of BMV-PD-1 was evaluated by small animal imaging system. Results: Laser confocal microscopy images demonstrated that the plasmid ClyA-PD-1 EGFP was transferred into BL21-Codonplus and successfully expressed into protein. SDS-PAGE results suggested that ClyA-PD-1 EGFP was overexpressed in BL21-Codonplus. WB analysis indicated that PD-1 was expressed in bacteria and highly expressed in BMV-PD-1 (P < 0.001). NTA and TEM analyses revealed that BMV-PD-1 were spherical vesicles with a diameter of (145 ± 14) nm and a negative surface charge. Laser confocal imaging showed that the high expression of PD-1 significantly increased the uptake of BMV PD-1 by lung cancer cells (P < 0.01). In vivo imaging of small animals further confirmed that the high expression of PD-1 can effectively improve cancer targeting of BMV-PD-1 (P < 0.01). Conclusion: In this study, bacterial plasma membrane nanovesicles BMV-PD-1 with high PD-1 expression are successfully constructed, and it is found that PD-1 overexpression markedly improve the mouse lung cancer xenograft tissue targeting specificity of BMV-PD-1, laying the groundwork for further development of BMV-PD-1 as a carrier for targeted drug delivery systems in tumors.
2025, 32(3):247-256.
DOI: 10.3872/j.issn.1007-385X.2025.03.003
Abstract:
[Abstract] Objective: The nanovesicles-hybridized selenized hyaluronic acid hydrogel (ICG-NV@SeHA) was constructed, and its mechanism of action in synergistically killing glioma GL261 cells in mice when combined with sonodynamic therapy (SDT) was systematically investigated. Methods: BMSC-derived nanovesicles (BMSC-NVs) were prepared via the extrusion method, followed by the incorporation of indocyanine green (ICG) to fabricate ICG-NV. Under the presence of EDC, hyaluronic acid (HA) was aminated using ethylenediamine (ED) to synthesize aminated HA (AHA), which was further conjugated with γ-selenobutyrolactone (SBL) via nucleophilic addition to form selenized HA (SeHA). AHA, ICG-NVs, and SBL solutions were mixed and oxidatively cross-linked to obtain ICG-NV@SeHA, followed by physical characterization. DiD-labeled ICG-NVs and ICG-NV@SeHA were co-cultured with GL261 cells for 12 h to observe cellular internalization. The biocompatibility of ICG-NVs and ICG-NV@SeHA with GL261 cells and mouse hippocampal neuronal HT22 cells was evaluated using the CCK-8 assay.GL261 cells were divided into four groups: PBS + ultrasound (US), ICG + US, ICG-NV + US, and ICG-NV@SeHA + US. Calcein-AM/PI staining and DCFH-DA fluorescent probes were employed to assess the synergistic SDT-induced cytotoxic effects on GL261 cells and intracellular reactive oxygen (ROS) generation, respectively. Cellular surface calreticulin (CRT) expression was analyzed via immunofluorescence, while enzyme-linked immunosorbent assay (ELISA) was used to measure the release of high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Results: BMSC-NVs were successfully prepared with an average particle size of approximately 154.3 nm. ICG was efficiently encapsulated into the nanovesicles with an encapsulation efficiency of 40.6%. HA was successfully aminated, achieving a grafting rate of 32.5%. Ultimately, the ICG-NV@SeHA hydrogel was successfully synthesized. Transmission electron microscopy (TEM) revealed a loose porous structure, and rheological analysis demonstrated that the storage modulus (G') exceeded the loss modulus (G''), consistent with hydrogel characteristics, along with shear-thinning behavior. Cellular experiments showed that ICG-NVs were effectively internalized by GL261 glioma cells. CCK-8 assays and Calcein-AM/PI fluorescence staining confirmed that both ICG-NVs and ICG NV@SeHA exhibited excellent biocompatibility with no significant cytotoxicity toward GL261 and HT22 cells. However, the cell viability in the ICG-NV + US and ICG-NV@SeHA + US groups was significantly reduced compared to the ICG + US group (P < 0.01 or P < 0.001) .DCFH-DA fluorescent probe assays revealed that the green fluorescence intensity in the ICG-NV + US and ICG NV@SeHA + US groups was markedly higher than in the PBS, PBS + US, and ICG + US groups (P < 0.000 1 or P < 0.001), reflecting substantial intracellular ROS production. Additionally, cell surface CRT expression was significantly upregulated (P < 0.000 1), and the release of HMGB1 and ATP in the supernatant increased (P < 0.05 or P < 0.01). Conclusion: The ICG-NV@SeHA hydrogel, which exhibits excellent mechanical properties and injectability, was successfully fabricated. Demonstrating favorable biocompatibility, this hydrogel, when combined with SDT, effectively kills glioma GL261 cells and induces immunogenic cell death (ICD). This strategy holds potential as a novel approach to prevent postoperative recurrence in glioma treatment.
[Abstract] Objective: The nanovesicles-hybridized selenized hyaluronic acid hydrogel (ICG-NV@SeHA) was constructed, and its mechanism of action in synergistically killing glioma GL261 cells in mice when combined with sonodynamic therapy (SDT) was systematically investigated. Methods: BMSC-derived nanovesicles (BMSC-NVs) were prepared via the extrusion method, followed by the incorporation of indocyanine green (ICG) to fabricate ICG-NV. Under the presence of EDC, hyaluronic acid (HA) was aminated using ethylenediamine (ED) to synthesize aminated HA (AHA), which was further conjugated with γ-selenobutyrolactone (SBL) via nucleophilic addition to form selenized HA (SeHA). AHA, ICG-NVs, and SBL solutions were mixed and oxidatively cross-linked to obtain ICG-NV@SeHA, followed by physical characterization. DiD-labeled ICG-NVs and ICG-NV@SeHA were co-cultured with GL261 cells for 12 h to observe cellular internalization. The biocompatibility of ICG-NVs and ICG-NV@SeHA with GL261 cells and mouse hippocampal neuronal HT22 cells was evaluated using the CCK-8 assay.GL261 cells were divided into four groups: PBS + ultrasound (US), ICG + US, ICG-NV + US, and ICG-NV@SeHA + US. Calcein-AM/PI staining and DCFH-DA fluorescent probes were employed to assess the synergistic SDT-induced cytotoxic effects on GL261 cells and intracellular reactive oxygen (ROS) generation, respectively. Cellular surface calreticulin (CRT) expression was analyzed via immunofluorescence, while enzyme-linked immunosorbent assay (ELISA) was used to measure the release of high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Results: BMSC-NVs were successfully prepared with an average particle size of approximately 154.3 nm. ICG was efficiently encapsulated into the nanovesicles with an encapsulation efficiency of 40.6%. HA was successfully aminated, achieving a grafting rate of 32.5%. Ultimately, the ICG-NV@SeHA hydrogel was successfully synthesized. Transmission electron microscopy (TEM) revealed a loose porous structure, and rheological analysis demonstrated that the storage modulus (G') exceeded the loss modulus (G''), consistent with hydrogel characteristics, along with shear-thinning behavior. Cellular experiments showed that ICG-NVs were effectively internalized by GL261 glioma cells. CCK-8 assays and Calcein-AM/PI fluorescence staining confirmed that both ICG-NVs and ICG NV@SeHA exhibited excellent biocompatibility with no significant cytotoxicity toward GL261 and HT22 cells. However, the cell viability in the ICG-NV + US and ICG-NV@SeHA + US groups was significantly reduced compared to the ICG + US group (P < 0.01 or P < 0.001) .DCFH-DA fluorescent probe assays revealed that the green fluorescence intensity in the ICG-NV + US and ICG NV@SeHA + US groups was markedly higher than in the PBS, PBS + US, and ICG + US groups (P < 0.000 1 or P < 0.001), reflecting substantial intracellular ROS production. Additionally, cell surface CRT expression was significantly upregulated (P < 0.000 1), and the release of HMGB1 and ATP in the supernatant increased (P < 0.05 or P < 0.01). Conclusion: The ICG-NV@SeHA hydrogel, which exhibits excellent mechanical properties and injectability, was successfully fabricated. Demonstrating favorable biocompatibility, this hydrogel, when combined with SDT, effectively kills glioma GL261 cells and induces immunogenic cell death (ICD). This strategy holds potential as a novel approach to prevent postoperative recurrence in glioma treatment.
2025, 32(3):257-263.
DOI: 10.3872/j.issn.1007-385X.2025.03.004
Abstract:
[摘 要] 外泌体作为一种天然纳米囊泡，具有卓越的生物相容性和运输能力，能够携带多种治疗性分子，被视为药物递送的优 质载体。目前，工程化外泌体的生产与构建策略，包括选择来源细胞、优化产量的方法、表面修饰与载药技术等，已有了长足的发 展，能够增强外泌体功能并克服天然外泌体的局限性，因而开发出在胰腺癌治疗中的多种应用。联合声光动力疗法，通过提高携 带光敏剂或声敏剂的稳定性从而增加治疗效果；与化疗药物结合，提高药物稳定性、靶向性和递送效率，降低毒性；协同免疫治 疗，作为癌症疫苗抗原和佐剂，增强免疫细胞对肿瘤抗原的摄取；以及用于RNA治疗，有效传递siRNA、shRNA和miRNA等核酸 分子，抑制胰腺癌细胞的增殖。工程化外泌体在胰腺癌治疗中展现出巨大潜力，有望在未来实现临床转化，推动胰腺癌治疗新策 略的开发。
[摘 要] 外泌体作为一种天然纳米囊泡，具有卓越的生物相容性和运输能力，能够携带多种治疗性分子，被视为药物递送的优 质载体。目前，工程化外泌体的生产与构建策略，包括选择来源细胞、优化产量的方法、表面修饰与载药技术等，已有了长足的发 展，能够增强外泌体功能并克服天然外泌体的局限性，因而开发出在胰腺癌治疗中的多种应用。联合声光动力疗法，通过提高携 带光敏剂或声敏剂的稳定性从而增加治疗效果；与化疗药物结合，提高药物稳定性、靶向性和递送效率，降低毒性；协同免疫治 疗，作为癌症疫苗抗原和佐剂，增强免疫细胞对肿瘤抗原的摄取；以及用于RNA治疗，有效传递siRNA、shRNA和miRNA等核酸 分子，抑制胰腺癌细胞的增殖。工程化外泌体在胰腺癌治疗中展现出巨大潜力，有望在未来实现临床转化，推动胰腺癌治疗新策 略的开发。
2025, 32(3):264-269.
DOI: 10.3872/j.issn.1007-385X.2025.03.005
Abstract:
[摘 要] 幽门螺杆菌（HP）感染与胃癌的发生有着密切的联系。国际癌症研究机构（IARC）将HP归类为1类致癌因子，治疗胃 癌和根除HP之间存在密切的关系，根除HP可以显著降低胃癌的发病风险。然而，传统的抗生素治疗策略正面临着耐药性增加 和破坏肠道微生态平衡的挑战，这促使科研人员寻求新的治疗策略。环境响应性生物材料作为一种创新的治疗手段，能够根据 体内环境的变化智能地调节药物释放，从而提高治疗效果和减少副作用。环境响应性生物材料能够通过多种机制，如pH响应、 酶响应、光响应、超声响应和磁响应等，有效杀灭HP，同时保护和修复受损的胃肠道黏膜。此外，环境响应性生物材料在中和胃 酸、抑制脲酶活性、破坏细菌膜和生物膜、以及激活自噬机制以清除胞内菌等抗HP机制中都有潜在应用前景。本文对环境响应 性生物材料在HP治疗和预防胃癌的发生中的机制和应用及未来发展方向进行述评，以期为相关研究提供新的视角和思路。
[摘 要] 幽门螺杆菌（HP）感染与胃癌的发生有着密切的联系。国际癌症研究机构（IARC）将HP归类为1类致癌因子，治疗胃 癌和根除HP之间存在密切的关系，根除HP可以显著降低胃癌的发病风险。然而，传统的抗生素治疗策略正面临着耐药性增加 和破坏肠道微生态平衡的挑战，这促使科研人员寻求新的治疗策略。环境响应性生物材料作为一种创新的治疗手段，能够根据 体内环境的变化智能地调节药物释放，从而提高治疗效果和减少副作用。环境响应性生物材料能够通过多种机制，如pH响应、 酶响应、光响应、超声响应和磁响应等，有效杀灭HP，同时保护和修复受损的胃肠道黏膜。此外，环境响应性生物材料在中和胃 酸、抑制脲酶活性、破坏细菌膜和生物膜、以及激活自噬机制以清除胞内菌等抗HP机制中都有潜在应用前景。本文对环境响应 性生物材料在HP治疗和预防胃癌的发生中的机制和应用及未来发展方向进行述评，以期为相关研究提供新的视角和思路。
2025, 32(3):270-280.
DOI: 10.3872/j.issn.1007-385X.2025.03.006
Abstract:
[Abstract] Objective: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. The diagnosis rate of early HCC is low, and most patients are diagnosed at the late stage and have a very poor prognosis. Therefore, it is urgent to explore effective early diagnosis markers and intervention targets for HCC. Cancer/testicular antigen 1A (CTAG1A) is abnormally expressed and highly immunogenic in a variety of tumors, but its expression characteristics and immunogenicity in HCC remain unclear. The aim of this study is to identify the expression and immunogenicity of CTAG1A in HCC tissues and cells, providing a new biomarker for the early diagnosis of HCC and a new potential target for clinical immunotherapy. Methods: This study screened the differentially expressed gene profiles between 10 pairs of very early HCC (BCLC stage 0 HCC) tumors and paracancerous tissues using a transcriptome microarray. The expression of CTAG1A was verified by RT-qPCR in an independent large sample (BCLC stage 0, A, B, C HCC tissues and adjacent non-tumor tissues, n=149) and various hepatocellular carcinoma cell lines. Bioinformatics tools (TepiTool of IEDB database and Swiss Model) were used to predict the MHC-Ⅰ and MHC-Ⅱ epitopes of CTAG1A. The candidate peptides were synthesized by solid-phase polypeptide synthesis method. After purification by HPLC and verification by mass spectrometry assay, the specific T cell responses of peripheral blood mononuclear cells (PBMC) of 9 HCC patients to all peptides were detected by IFN-γ enzyme-linked immunospot assay (ELISpot). The clinical samples were collected from HCC patients admitted to the Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital) from 2015 to 2022. The collection and usage of all samples were carried out with the consent of the patients, and with the approval of the Ethics Committee of Eastern Hepatobiliary Surgery Hospital (EHBHKY2015-01-017) and in strict accordance with relevant requirements and ethical regulations. Statistical analysis was performed using SPSS 30.0 software, and the diagnostic efficiency was evaluated by ROC curve. Results: Transcriptome chip screening results showed that CTAG1A expression was significantly up-regulated in the very early-stage HCC (BCLC stage 0 HCC) (|FC| = 99.16, P < 0.0001). The verification using the clinical independent samples showed its high expression in all stages of HCC and better diagnostic efficacy in early-stage HCC (BCLC stage 0 HCC AUC=0.6893, sensitivity = 85.71%; BCLC stage A HCC AUC = 0.8229, sensitivity = 83.33%). Furthermore, the expression of CTAG1A was significantly higher in multiple liver cancer cell lines than in relatively normal liver cell lines (P < 0.001). Compared with alpha-fetoprotein (AFP), CTAG1A showed better diagnostic efficacy in BCLC stage 0 and stage A HCC (ROC curve analysis of AFP showed no significant difference in early HCC, P > 0.05). Bioinformatics tools predicted that CTAG1A contained 8 MHC-type I and 4 MHC-type II epitopes. The IFN-γ ELISpot assay showed that 12 synthetic peptides could induce PBMC specific T cell response in HCC patients to varying degrees. Conclusion: CTAG1A is significantly overexpressed in early-stage HCC and has multi-epitope immunogenicity, which may activate CD8? and CD4? T cells, suggesting its potential as a target for HCC immunotherapy. It may provide a new direction for developing combined immunotherapy strategies based on mRNA vaccines or adoptive cell therapy. Compared with AFP, CTAG1A exhibits better diagnostic efficacy in early stage HCC, suggesting its potential as a marker for early diagnosis of HCC.
[Abstract] Objective: Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. The diagnosis rate of early HCC is low, and most patients are diagnosed at the late stage and have a very poor prognosis. Therefore, it is urgent to explore effective early diagnosis markers and intervention targets for HCC. Cancer/testicular antigen 1A (CTAG1A) is abnormally expressed and highly immunogenic in a variety of tumors, but its expression characteristics and immunogenicity in HCC remain unclear. The aim of this study is to identify the expression and immunogenicity of CTAG1A in HCC tissues and cells, providing a new biomarker for the early diagnosis of HCC and a new potential target for clinical immunotherapy. Methods: This study screened the differentially expressed gene profiles between 10 pairs of very early HCC (BCLC stage 0 HCC) tumors and paracancerous tissues using a transcriptome microarray. The expression of CTAG1A was verified by RT-qPCR in an independent large sample (BCLC stage 0, A, B, C HCC tissues and adjacent non-tumor tissues, n=149) and various hepatocellular carcinoma cell lines. Bioinformatics tools (TepiTool of IEDB database and Swiss Model) were used to predict the MHC-Ⅰ and MHC-Ⅱ epitopes of CTAG1A. The candidate peptides were synthesized by solid-phase polypeptide synthesis method. After purification by HPLC and verification by mass spectrometry assay, the specific T cell responses of peripheral blood mononuclear cells (PBMC) of 9 HCC patients to all peptides were detected by IFN-γ enzyme-linked immunospot assay (ELISpot). The clinical samples were collected from HCC patients admitted to the Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital) from 2015 to 2022. The collection and usage of all samples were carried out with the consent of the patients, and with the approval of the Ethics Committee of Eastern Hepatobiliary Surgery Hospital (EHBHKY2015-01-017) and in strict accordance with relevant requirements and ethical regulations. Statistical analysis was performed using SPSS 30.0 software, and the diagnostic efficiency was evaluated by ROC curve. Results: Transcriptome chip screening results showed that CTAG1A expression was significantly up-regulated in the very early-stage HCC (BCLC stage 0 HCC) (|FC| = 99.16, P < 0.0001). The verification using the clinical independent samples showed its high expression in all stages of HCC and better diagnostic efficacy in early-stage HCC (BCLC stage 0 HCC AUC=0.6893, sensitivity = 85.71%; BCLC stage A HCC AUC = 0.8229, sensitivity = 83.33%). Furthermore, the expression of CTAG1A was significantly higher in multiple liver cancer cell lines than in relatively normal liver cell lines (P < 0.001). Compared with alpha-fetoprotein (AFP), CTAG1A showed better diagnostic efficacy in BCLC stage 0 and stage A HCC (ROC curve analysis of AFP showed no significant difference in early HCC, P > 0.05). Bioinformatics tools predicted that CTAG1A contained 8 MHC-type I and 4 MHC-type II epitopes. The IFN-γ ELISpot assay showed that 12 synthetic peptides could induce PBMC specific T cell response in HCC patients to varying degrees. Conclusion: CTAG1A is significantly overexpressed in early-stage HCC and has multi-epitope immunogenicity, which may activate CD8? and CD4? T cells, suggesting its potential as a target for HCC immunotherapy. It may provide a new direction for developing combined immunotherapy strategies based on mRNA vaccines or adoptive cell therapy. Compared with AFP, CTAG1A exhibits better diagnostic efficacy in early stage HCC, suggesting its potential as a marker for early diagnosis of HCC.
2025, 32(3):281-287.
DOI: 10.3872/j.issn.1007-385X.2025.03.007
Abstract:
[Abstract] Objective: To investigate the effect of Eriocitrin on the proliferation of esophageal cancer KYSE30 cells, and to explore its possible mechanism based on ferroptosis. Methods: Esophageal cancer KYSE30 cells were divided into 8 groups: the control group (conventional culture), RSL3 group (treated with 3 μmol/L ferroptosis inducer RSL3), Eriocitrin group (treated with 75 μmol/L Eriocitrin), Eriocitrin + Fer-1 group (treated with 5 μmol/L of ferroptosis inhibitor Fer-1 and 75 μmol/L Eriocitrin), Fer-1 group (treated with 5 μmol/L Fer-1 treatment), oe-NC group (transfected with blank vector control), oe-STAT3 group (transfected with STAT3 overexpression vector) and oe-STAT3 + Eriocitrin group (transfected with STAT3 overexpression vector and then treated with 75 μmol/L Eriocitrin). Proliferation abilities of cells in each group were detected using CCK-8 assay, EdU incorporation assay and clone formation assay respectively. The levels of intracellular ferroptosis-related indicators were detected using the ELISA kits. Western blotting was used to detect the expression of STAT3/GPX4 pathway-related proteins. KYSE30 cell nude mouse subcutaneous transplanted tumor model was constructed to observe the effects of Eriocitrin and Fer-1 on the growth of transplanted tumors. Results: Eriodictyol could inhibit the proliferation and clone formation of KYSE30 cells, increase the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and Fe2+, decrease the level of glutathione (GSH) (all P < 0.05) and suppress the growth of transplanted tumors in nude mice. These effects could be reversed by Fer-1 (P < 0.05). Overexpression of STAT3 could abolish the inductive effect of eriodictyol on ferroptosis and its inhibitory effect on the STAT3/GPX4 pathway (P < 0.05). Conclusion: Eriocitrin could induce ferroptosis in esophageal cancer KYSE30 cells by inhibiting STAT3/GPX4 signaling pathway and exert significant antitumor effects in esophageal cancer.
[Abstract] Objective: To investigate the effect of Eriocitrin on the proliferation of esophageal cancer KYSE30 cells, and to explore its possible mechanism based on ferroptosis. Methods: Esophageal cancer KYSE30 cells were divided into 8 groups: the control group (conventional culture), RSL3 group (treated with 3 μmol/L ferroptosis inducer RSL3), Eriocitrin group (treated with 75 μmol/L Eriocitrin), Eriocitrin + Fer-1 group (treated with 5 μmol/L of ferroptosis inhibitor Fer-1 and 75 μmol/L Eriocitrin), Fer-1 group (treated with 5 μmol/L Fer-1 treatment), oe-NC group (transfected with blank vector control), oe-STAT3 group (transfected with STAT3 overexpression vector) and oe-STAT3 + Eriocitrin group (transfected with STAT3 overexpression vector and then treated with 75 μmol/L Eriocitrin). Proliferation abilities of cells in each group were detected using CCK-8 assay, EdU incorporation assay and clone formation assay respectively. The levels of intracellular ferroptosis-related indicators were detected using the ELISA kits. Western blotting was used to detect the expression of STAT3/GPX4 pathway-related proteins. KYSE30 cell nude mouse subcutaneous transplanted tumor model was constructed to observe the effects of Eriocitrin and Fer-1 on the growth of transplanted tumors. Results: Eriodictyol could inhibit the proliferation and clone formation of KYSE30 cells, increase the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and Fe2+, decrease the level of glutathione (GSH) (all P < 0.05) and suppress the growth of transplanted tumors in nude mice. These effects could be reversed by Fer-1 (P < 0.05). Overexpression of STAT3 could abolish the inductive effect of eriodictyol on ferroptosis and its inhibitory effect on the STAT3/GPX4 pathway (P < 0.05). Conclusion: Eriocitrin could induce ferroptosis in esophageal cancer KYSE30 cells by inhibiting STAT3/GPX4 signaling pathway and exert significant antitumor effects in esophageal cancer.
2025, 32(3):288-293.
DOI: 10.3872/j.issn.1007-385X.2025.03.008
Abstract:
[Abstract] Objective: To investigate the effects and mechanisms of glycyrrhetinic acid (GA) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma SMMC-7721 cells by regulating the β-catenin/transcription factor 4 (TCF4) signaling pathway. Methods: HCC cells SMMC-7721 were randomly separated into the control, L-GA, M-GA, H-GA groups (50, 100, 200 μmol/L GA) and the GA + LiCl group (200 μmol/L GA + 40 μmol/L β-catenin activator LiCl). The effects of GA on the proliferation, migration, invasion and apoptosis of SMMC-7721 cells were detected by plate cloning, Transwell experiment and flow cytometry. WB was applied to detect the effects of GA on the expressions of β-catenin/TCF4 signaling pathway proteins (β-catenin、TCF4) and EMT (E-cadherin, vimentin)-related proteins in SMMC-7721 cells. The model of SMMC-7721 cell transplanted tumor in nude mice was established to observe the effects of GA on the growth of transplanted tumor and the expressions of β-catenin and TCF4 proteins. Results: Compared with the control group, SMMC-7721 cell clonal number, migration and invasion numbers, β-catenin, TCF4 and vmentin protein expressions in the L-GA, M-GA and H-GA groups decreased significantly (all P < 0.05), while the apoptosis rate and the expression of E-cadherin protein increased (all P < 0.05). Compared with the H-GA group, the numbers of clones, migration and invasion, β-catenin, TCF4 and vimentin protein expressions in the GA + LiCl group increased significantly (all P < 0.05), while the apoptosis rate and E-cadherin protein expression decreased significantly (all P < 0.05). Tumor-bearing nude mouse model experiment showed that the tumor weight and volume and the positive rates of β-catenin and TCF4 proteins in the GA group were significantly lower than those in the control group (all P < 0.05). Conclusion: GA can significantly inhibit the proliferation,migration, invasion, and the EMT process of SMMC-7721 cells, thereby inhibiting the progression of HCC. Its mechanism may be achieved by inhibiting the β-catenin/TCF4 signaling pathway.
[Abstract] Objective: To investigate the effects and mechanisms of glycyrrhetinic acid (GA) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma SMMC-7721 cells by regulating the β-catenin/transcription factor 4 (TCF4) signaling pathway. Methods: HCC cells SMMC-7721 were randomly separated into the control, L-GA, M-GA, H-GA groups (50, 100, 200 μmol/L GA) and the GA + LiCl group (200 μmol/L GA + 40 μmol/L β-catenin activator LiCl). The effects of GA on the proliferation, migration, invasion and apoptosis of SMMC-7721 cells were detected by plate cloning, Transwell experiment and flow cytometry. WB was applied to detect the effects of GA on the expressions of β-catenin/TCF4 signaling pathway proteins (β-catenin、TCF4) and EMT (E-cadherin, vimentin)-related proteins in SMMC-7721 cells. The model of SMMC-7721 cell transplanted tumor in nude mice was established to observe the effects of GA on the growth of transplanted tumor and the expressions of β-catenin and TCF4 proteins. Results: Compared with the control group, SMMC-7721 cell clonal number, migration and invasion numbers, β-catenin, TCF4 and vmentin protein expressions in the L-GA, M-GA and H-GA groups decreased significantly (all P < 0.05), while the apoptosis rate and the expression of E-cadherin protein increased (all P < 0.05). Compared with the H-GA group, the numbers of clones, migration and invasion, β-catenin, TCF4 and vimentin protein expressions in the GA + LiCl group increased significantly (all P < 0.05), while the apoptosis rate and E-cadherin protein expression decreased significantly (all P < 0.05). Tumor-bearing nude mouse model experiment showed that the tumor weight and volume and the positive rates of β-catenin and TCF4 proteins in the GA group were significantly lower than those in the control group (all P < 0.05). Conclusion: GA can significantly inhibit the proliferation,migration, invasion, and the EMT process of SMMC-7721 cells, thereby inhibiting the progression of HCC. Its mechanism may be achieved by inhibiting the β-catenin/TCF4 signaling pathway.
2025, 32(3):294-300.
DOI: 10.3872/j.issn.1007-385X.2025.03.009
Abstract:
[Abstract] Objective: To investigate whether asiaticoside (ASI) regulates the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cyclic adenosine monophosphate/protein kinase A/cAMP-response element binding protein (cAMP/PKA/ CREB) signaling pathway. Methods: After determining the suitable ASI concentration and treatment duration using MTT assay, Huh7 cells were divided into the following groups: control, ASI-L (20 μmol/L), ASI-M (40 μmol/L), ASI-H (80 μmol/L), and ASI-H+ Forskolin (80 μmol/L ASI + 100 μmol/L cAMP activator Forskolin) groups. After 48 h of treatment, cell proliferation was assessed using MTT and colony formation assays; cell migration and invasion were analyzed using Transwell assays; apoptosis was detected using an Annexin V-FITC apoptosis detection kit. The secretion level of cAMP and the protein expression levels of phosphorylated PKA (p-PKA) and phosphorylated CREB (p-CREB) were evaluated using ELISA and Western blotting, respectively. A subcutaneous xenograft model was established by injecting Huh7 cells into the right abdomen of nude mice. ASI was administered by gavage at doses of 5, 15, and 45 mg/kg for 4 weeks. Tumors were then harvested and weighed. Results: Treatment with 40 μmol/L ASI for 48 hours (close to the IC??) was determined to be the appropriate concentration and duration. Compared with the control group, the ASI-L, ASI M, and ASI-H groups showed significantly reduced Huh 7 cell proliferation, colony formation, migration, invasion, cAMP levels, and expression of p-PKA/PKA and p-CREB/CREB (all P < 0.05), while apoptosis rates were significantly increased (P < 0.05). Compared with the ASI-H group, the ASI-H + Forskolin group exhibited significantly increased proliferation, colony formation, migration,invasion, cAMP level, and expression of p-PKA/PKA and p-CREB/CREB (all P < 0.05), but apoptosis was significantly reduced (all P < 0.05). In the nude mouse xenograft model, ASI at 5, 15, and 45 mg/kg markedly decreased tumor weight in nude mice (all P < 0.05). Conclusion: ASI inhibits the malignant biological behaviors and promotes apoptosis of Huh7 cells, as well as suppresses tumor growth in nude mice, by downregulating the expression of proteins in the cAMP/PKA/CREB signaling pathway.
[Abstract] Objective: To investigate whether asiaticoside (ASI) regulates the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cyclic adenosine monophosphate/protein kinase A/cAMP-response element binding protein (cAMP/PKA/ CREB) signaling pathway. Methods: After determining the suitable ASI concentration and treatment duration using MTT assay, Huh7 cells were divided into the following groups: control, ASI-L (20 μmol/L), ASI-M (40 μmol/L), ASI-H (80 μmol/L), and ASI-H+ Forskolin (80 μmol/L ASI + 100 μmol/L cAMP activator Forskolin) groups. After 48 h of treatment, cell proliferation was assessed using MTT and colony formation assays; cell migration and invasion were analyzed using Transwell assays; apoptosis was detected using an Annexin V-FITC apoptosis detection kit. The secretion level of cAMP and the protein expression levels of phosphorylated PKA (p-PKA) and phosphorylated CREB (p-CREB) were evaluated using ELISA and Western blotting, respectively. A subcutaneous xenograft model was established by injecting Huh7 cells into the right abdomen of nude mice. ASI was administered by gavage at doses of 5, 15, and 45 mg/kg for 4 weeks. Tumors were then harvested and weighed. Results: Treatment with 40 μmol/L ASI for 48 hours (close to the IC??) was determined to be the appropriate concentration and duration. Compared with the control group, the ASI-L, ASI M, and ASI-H groups showed significantly reduced Huh 7 cell proliferation, colony formation, migration, invasion, cAMP levels, and expression of p-PKA/PKA and p-CREB/CREB (all P < 0.05), while apoptosis rates were significantly increased (P < 0.05). Compared with the ASI-H group, the ASI-H + Forskolin group exhibited significantly increased proliferation, colony formation, migration,invasion, cAMP level, and expression of p-PKA/PKA and p-CREB/CREB (all P < 0.05), but apoptosis was significantly reduced (all P < 0.05). In the nude mouse xenograft model, ASI at 5, 15, and 45 mg/kg markedly decreased tumor weight in nude mice (all P < 0.05). Conclusion: ASI inhibits the malignant biological behaviors and promotes apoptosis of Huh7 cells, as well as suppresses tumor growth in nude mice, by downregulating the expression of proteins in the cAMP/PKA/CREB signaling pathway.
2025, 32(3):301-308.
DOI: 10.3872/j.issn.1007-385X.2025.03.010
Abstract:
[Abstract] Objective: To investigate the clinicohistologic and molecular pathological characteristics of invasive stratified mucin producing carcinoma (ISMC). Methods: The clinicopathological data, immunohistochemistry, alcian blue/periodic acid-Schiff (AB/ PAS) staining, molecular detection and PD-L1 expressions of 11 cases of ISMC and 4 cases of stratified mucin-producing intraepithelial lesion (SMILE) in the pathological database of Anqing Medical Center of Anhui Medical University /Anqing Municipal Hospital and the first Affiliated hospital of Wannan Medical School/Yijishan Hostital between January of 2018 and March of 2024 were retrospectively analyzed. Results: ISMC patients often presented with irregular vaginal bleeding. Morphologically, the cells containing mucus in the cytoplasm were arranged in stratified layers, surrounded by a palisade, and the tumor cells might be signet ring-shaped or have clear cytoplasm. ISMC might occur in both pure and mixed forms. ISMC had highly invasive biological characteristics. CK7, p16, p40 and (or) p63 were expressed focally or positively in the form of palisades around the cancer nests. AB-PAS staining was positive. HPV test results: HPV16/18 was positive in ISMC (1/4); HPV16/18 was positive before surgery (4/6); no HPV was detected in SMILE; all ISMC cases expressed PD-L1. Eight ISMC patients were successfully followed up for 4-39 months (average 20.50 months), and four SMILE patients for 1-25 months (average 8.25 months). All followed-up patients survived; however, one ISMC patient developed multi organ metastases post-surgery. Conclusion: ISMC has unique morphological characteristics and immunophenotypes, indicated by high invasiveness and poor prognosis. All ISMC are PD-L1 positive, suggesting that these patients may benefit from PD-L1 immunotherapy.
[Abstract] Objective: To investigate the clinicohistologic and molecular pathological characteristics of invasive stratified mucin producing carcinoma (ISMC). Methods: The clinicopathological data, immunohistochemistry, alcian blue/periodic acid-Schiff (AB/ PAS) staining, molecular detection and PD-L1 expressions of 11 cases of ISMC and 4 cases of stratified mucin-producing intraepithelial lesion (SMILE) in the pathological database of Anqing Medical Center of Anhui Medical University /Anqing Municipal Hospital and the first Affiliated hospital of Wannan Medical School/Yijishan Hostital between January of 2018 and March of 2024 were retrospectively analyzed. Results: ISMC patients often presented with irregular vaginal bleeding. Morphologically, the cells containing mucus in the cytoplasm were arranged in stratified layers, surrounded by a palisade, and the tumor cells might be signet ring-shaped or have clear cytoplasm. ISMC might occur in both pure and mixed forms. ISMC had highly invasive biological characteristics. CK7, p16, p40 and (or) p63 were expressed focally or positively in the form of palisades around the cancer nests. AB-PAS staining was positive. HPV test results: HPV16/18 was positive in ISMC (1/4); HPV16/18 was positive before surgery (4/6); no HPV was detected in SMILE; all ISMC cases expressed PD-L1. Eight ISMC patients were successfully followed up for 4-39 months (average 20.50 months), and four SMILE patients for 1-25 months (average 8.25 months). All followed-up patients survived; however, one ISMC patient developed multi organ metastases post-surgery. Conclusion: ISMC has unique morphological characteristics and immunophenotypes, indicated by high invasiveness and poor prognosis. All ISMC are PD-L1 positive, suggesting that these patients may benefit from PD-L1 immunotherapy.
2025, 32(3):309-315.
DOI: 10.3872/j.issn.1007-385X.2025.03.011
Abstract:
[Abstract] Objective: To investigate the value of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte monocyte ratio（LMR）and prognostic nutrition index (PNI) in predicting the curative effect and prognosis of patients with advanced hepatocellular carcinoma(HCC) treated with combined therapy of immune checkpoint inhibitors (ICI) and antiangiogenic drugs. Methods: The general clinical data, NLR, PLR, LMR and PNI of patients before treatment, clinical efficacy and prognosis of 85 advanced HCC patients admitted and treated with combined therapy of ICI and antiangiogenic drugs between January 2020 and December 2023 in the First Affiliated Hospital of Dali University were collected. The optimal cut-off values of NLR、PLR、LMR and PNI were obtained using receiver operating characteristic (ROC) curve, and used to divide the patients into the high and low groups. Kaplan-Meier method was used for survival analysis; Cox proportional risk model was used for the univariate and multivariate analysis of the effects of these values on the patient's OS. Results: The therapeutic effective rates in the low NLR，low PLR，high LMR and high PNI groups were respectively higher than those of the high NLR, high PLR, low LMR and low PNI groups (all P < 0.05). The patient's OS rates in the low NLR, low PLR groups were respectively significantly higher than those in the high NLR, high PLR groups (all P < 0.05). The patient’s OS rates in the high LMR, high PNI groups were respectively significantly higher than those in the low LMR, low PUI groups (all P < 0.05). NLR ≥ 1.94, male and HBV infection were independent risk factors for the prognosis of advanced HCC patients (all P < 0.05). Conclusion: NLR ≥ 1.94, male, HBV positive are risk factors influencing the efficacy and prognosis of patients. NLR ≥ 1.94 has certain clinical value in evaluating the efficacy and prognosis of combined immunotherapy and targeted therapy for advanced HCC patients.
[Abstract] Objective: To investigate the value of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte monocyte ratio（LMR）and prognostic nutrition index (PNI) in predicting the curative effect and prognosis of patients with advanced hepatocellular carcinoma(HCC) treated with combined therapy of immune checkpoint inhibitors (ICI) and antiangiogenic drugs. Methods: The general clinical data, NLR, PLR, LMR and PNI of patients before treatment, clinical efficacy and prognosis of 85 advanced HCC patients admitted and treated with combined therapy of ICI and antiangiogenic drugs between January 2020 and December 2023 in the First Affiliated Hospital of Dali University were collected. The optimal cut-off values of NLR、PLR、LMR and PNI were obtained using receiver operating characteristic (ROC) curve, and used to divide the patients into the high and low groups. Kaplan-Meier method was used for survival analysis; Cox proportional risk model was used for the univariate and multivariate analysis of the effects of these values on the patient's OS. Results: The therapeutic effective rates in the low NLR，low PLR，high LMR and high PNI groups were respectively higher than those of the high NLR, high PLR, low LMR and low PNI groups (all P < 0.05). The patient's OS rates in the low NLR, low PLR groups were respectively significantly higher than those in the high NLR, high PLR groups (all P < 0.05). The patient’s OS rates in the high LMR, high PNI groups were respectively significantly higher than those in the low LMR, low PUI groups (all P < 0.05). NLR ≥ 1.94, male and HBV infection were independent risk factors for the prognosis of advanced HCC patients (all P < 0.05). Conclusion: NLR ≥ 1.94, male, HBV positive are risk factors influencing the efficacy and prognosis of patients. NLR ≥ 1.94 has certain clinical value in evaluating the efficacy and prognosis of combined immunotherapy and targeted therapy for advanced HCC patients.
2025, 32(3):316-322.
DOI: 10.3872/j.issn.1007-385X.2025.03.012
Abstract:
[摘 要] 肿瘤相关中性粒细胞（TAN）是肿瘤微环境（TME）的重要组成部分，在调节肿瘤的生长和转移方面发挥重要作用。 TAN具有促肿瘤和抑制肿瘤两种类型，分为抗肿瘤的N1型和促肿瘤的N2型。一方面，TAN通过释放多种促炎、免疫调节和血管 生成因子等，直接或间接地作用于肿瘤细胞来促进或抑制肿瘤的发生、进展和转移。此外，TME内的多种细胞因子和趋化因子以 及其他细胞的旁分泌信号又会负调控TAN的极化。这种双向调控的产生与其本身的异质性和可塑性有关。因此，通过调控 TAN的促瘤作用，放大抑癌作用杀伤肿瘤，是一种极具希望的肿瘤治疗策略。本综述讨论了TAN在TME中的复杂双向调控作 用，并重点介绍了中性粒细胞靶向治疗在癌症治疗中的策略。
[摘 要] 肿瘤相关中性粒细胞（TAN）是肿瘤微环境（TME）的重要组成部分，在调节肿瘤的生长和转移方面发挥重要作用。 TAN具有促肿瘤和抑制肿瘤两种类型，分为抗肿瘤的N1型和促肿瘤的N2型。一方面，TAN通过释放多种促炎、免疫调节和血管 生成因子等，直接或间接地作用于肿瘤细胞来促进或抑制肿瘤的发生、进展和转移。此外，TME内的多种细胞因子和趋化因子以 及其他细胞的旁分泌信号又会负调控TAN的极化。这种双向调控的产生与其本身的异质性和可塑性有关。因此，通过调控 TAN的促瘤作用，放大抑癌作用杀伤肿瘤，是一种极具希望的肿瘤治疗策略。本综述讨论了TAN在TME中的复杂双向调控作 用，并重点介绍了中性粒细胞靶向治疗在癌症治疗中的策略。
2025, 32(3):323-330.
DOI: 10.3872/j.issn.1007-385X.2025.03.013
Abstract:
[摘 要] 肿瘤是全球第二大死因，长期以来肿瘤的防治一直是世界生物医学研究和实践中的重点。醛酮还原酶家族1成员 B10（AKR1B10）是是AKR1B亚家族的重要成员。作为一种多功能酶，其主要在消化道（如结肠、小肠和胃）的正常上皮组织中表 达，在非消化道组织中呈阴性或低表达，但在多种肿瘤组织尤其是在实体肿瘤如肝细胞癌中表达上调，并显示出与肿瘤发生、发 展和预后相关的特性，是一种可靠的血清标志物。然而，关于AKR1B10在肿瘤中作用的信息有限且零散。因此，在进一步了解 AKR1B10的功能及其机制的基础上，通过收集跨地区、大规模的临床样本数据评估AKR1B10水平，有望在临床工作上发挥 AKR1B10潜在的应用价值，助力个性化临床诊治与精确医疗的发展。
[摘 要] 肿瘤是全球第二大死因，长期以来肿瘤的防治一直是世界生物医学研究和实践中的重点。醛酮还原酶家族1成员 B10（AKR1B10）是是AKR1B亚家族的重要成员。作为一种多功能酶，其主要在消化道（如结肠、小肠和胃）的正常上皮组织中表 达，在非消化道组织中呈阴性或低表达，但在多种肿瘤组织尤其是在实体肿瘤如肝细胞癌中表达上调，并显示出与肿瘤发生、发 展和预后相关的特性，是一种可靠的血清标志物。然而，关于AKR1B10在肿瘤中作用的信息有限且零散。因此，在进一步了解 AKR1B10的功能及其机制的基础上，通过收集跨地区、大规模的临床样本数据评估AKR1B10水平，有望在临床工作上发挥 AKR1B10潜在的应用价值，助力个性化临床诊治与精确医疗的发展。
2025, 32(3):331-337.
DOI: 10.3872/j.issn.1007-385X.2025.03.014
Abstract:
[摘 要] 抗体药物偶联物（ADC）通过抗体特异性识别与毒素精准递送的协同作用，已成为肿瘤治疗领域的重要突破。本文系 统梳理ADC五大核心要素（靶点、抗体、连接子、毒素、偶联方式）的差异化研发策略，重点解析：（1）新型靶点（如肿瘤微环境相关 抗原）的挖掘策略；（2）抗体工程化改造（如亲和力优化、亚型选择、小型化设计）的创新路径；（3）连接子动态释放机制（提高亲水 性和膜渗透性）的技术突破；（4）毒素特性（低疏水性、强旁观者效应、高血浆稳定性及高单体ADC含量）的优化方向；（5）定点偶 联技术（糖基化位点改造、非天然氨基酸引入）的均质性提升方案。同时，从下一代创新ADC的布局出发，揭示ADC通过要素间 协同创新实现治疗窗口拓宽的核心逻辑，为下一代ADC设计提供理论支撑。
[摘 要] 抗体药物偶联物（ADC）通过抗体特异性识别与毒素精准递送的协同作用，已成为肿瘤治疗领域的重要突破。本文系 统梳理ADC五大核心要素（靶点、抗体、连接子、毒素、偶联方式）的差异化研发策略，重点解析：（1）新型靶点（如肿瘤微环境相关 抗原）的挖掘策略；（2）抗体工程化改造（如亲和力优化、亚型选择、小型化设计）的创新路径；（3）连接子动态释放机制（提高亲水 性和膜渗透性）的技术突破；（4）毒素特性（低疏水性、强旁观者效应、高血浆稳定性及高单体ADC含量）的优化方向；（5）定点偶 联技术（糖基化位点改造、非天然氨基酸引入）的均质性提升方案。同时，从下一代创新ADC的布局出发，揭示ADC通过要素间 协同创新实现治疗窗口拓宽的核心逻辑，为下一代ADC设计提供理论支撑。
2025, 32(3):338-343.
DOI: 10.3872/j.issn.1007-385X.2025.03.015
Abstract:
[摘 要] 消化系统肿瘤因早期诊断率低、异质性高，加之治疗仍以手术、放化疗为主，缺乏有效治疗手段，患者预后欠佳。虽然 靶向药物和免疫检查点抑制剂（ICI）的应用为消化道肿瘤的治疗提供了新的手段，但仅有部分患者对治疗产生响应。目前，过继 性细胞免疫疗法（ACT）在抗肿瘤治疗领域不断创新并取得了重要进展。因此，在了解ACT治疗作用机制的基础上，进一步分析 其在消化系统肿瘤治疗过程中存在的问题，总结采取的针对性措施及优化方案，有望为消化系统肿瘤ACT治疗提供参考，并形成 新的策略。
[摘 要] 消化系统肿瘤因早期诊断率低、异质性高，加之治疗仍以手术、放化疗为主，缺乏有效治疗手段，患者预后欠佳。虽然 靶向药物和免疫检查点抑制剂（ICI）的应用为消化道肿瘤的治疗提供了新的手段，但仅有部分患者对治疗产生响应。目前，过继 性细胞免疫疗法（ACT）在抗肿瘤治疗领域不断创新并取得了重要进展。因此，在了解ACT治疗作用机制的基础上，进一步分析 其在消化系统肿瘤治疗过程中存在的问题，总结采取的针对性措施及优化方案，有望为消化系统肿瘤ACT治疗提供参考，并形成 新的策略。
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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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.