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2026,33(8):811-821, DOI: 10.3872/j.issn.1007-385X.2026.08.001
Abstract:
Circulating tumor cells (CTCs), regarded as the “seed cells” of tumor metastasis, are closely associated with tumor progression, therapeutic response, and patient prognosis through changes in their abundance, molecular phenotypes, and functional states. With the development of precision oncology, CTC detection has gradually evolved from simple enumeration toward molecular subtyping and therapeutic decision support. In recent years, nanopeptide-based CTC enrichment and subtyping platforms have emerged as promising liquid biopsy technologies. By integrating peptide-functionalized magnetic nanobead-mediated enrichment with multidimensional molecular profiling, these platforms can improve the capture of rare CTCs and provide a cellular basis for therapeutic target detection, treatment monitoring, and early warning of drug resistance. The nanopeptide-based CTC detection technology developed by the National Center for Nanoscience and Technology, China (NCNST) has established a clinically accessible detection system with high sensitivity and specificity, promoting the transition of CTC detection from “quantitative assessment” to a 2.0 era centered on molecular subtyping and treatment decision support. This review focuses on the core principles, key technological breakthroughs, and clinical translational value of nanopeptide-based CTC detection platforms in precision cancer biotherapy, and discusses the challenges related to standardization, cost control, level of clinical evidence, and translation into companion diagnostics, to provide a reference for optimizing precision biotherapeutic strategies in oncology.
Circulating tumor cells (CTCs), regarded as the “seed cells” of tumor metastasis, are closely associated with tumor progression, therapeutic response, and patient prognosis through changes in their abundance, molecular phenotypes, and functional states. With the development of precision oncology, CTC detection has gradually evolved from simple enumeration toward molecular subtyping and therapeutic decision support. In recent years, nanopeptide-based CTC enrichment and subtyping platforms have emerged as promising liquid biopsy technologies. By integrating peptide-functionalized magnetic nanobead-mediated enrichment with multidimensional molecular profiling, these platforms can improve the capture of rare CTCs and provide a cellular basis for therapeutic target detection, treatment monitoring, and early warning of drug resistance. The nanopeptide-based CTC detection technology developed by the National Center for Nanoscience and Technology, China (NCNST) has established a clinically accessible detection system with high sensitivity and specificity, promoting the transition of CTC detection from “quantitative assessment” to a 2.0 era centered on molecular subtyping and treatment decision support. This review focuses on the core principles, key technological breakthroughs, and clinical translational value of nanopeptide-based CTC detection platforms in precision cancer biotherapy, and discusses the challenges related to standardization, cost control, level of clinical evidence, and translation into companion diagnostics, to provide a reference for optimizing precision biotherapeutic strategies in oncology.
2026,33(8):822-829, DOI: 10.3872/j.issn.1007-385X.2026.08.002
Abstract:
Objective: To investigate the effects of the HSP90β-targeting monoclonal antibody 2G1 on the biological characteristics of MG-63 sphere cells, an osteosarcoma stem cell (OSC)-enriched model, and to explore its association with changes in Wnt signaling-related proteins. Methods: MG-63 sphere cells were generated from the human osteosarcoma cell line MG-63 by serum-free suspension culture. The target antigen recognized by monoclonal antibody 2G1 was identified by immunofluorescence co-localization and co-immunoprecipitation assays. Flow cytometry was used to determine the expression of cell surface HSP90β in parental MG-63 cells and MG-63 sphere cells. Methylcellulose sphere formation, Transwell migration, and invasion assays were performed to evaluate the effects of 2G1 on the sphere-forming, migratory, and invasive capacities of MG-63 sphere cells. A nude mouse subcutaneous xenograft model was established to assess the effect of 2G1 on the tumorigenic potential of MG-63 sphere cells in vivo. Transcriptome sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Western blotting were further performed to investigate alterations in signaling pathways and the expression of proteins associated with stem-like characteristics, epithelial-mesenchymal transition (EMT)-related markers, and the Wnt/β-catenin signaling pathway following 2G1 treatment. Results: Immunofluorescence co-localization and co-immunoprecipitation demonstrated that HSP90β was the target antigen recognized by monoclonal antibody 2G1. Flow cytometric analysis showed that the proportion of HSP90β-positive cells on the cell surface was significantly higher in MG-63 sphere cells than in parental MG-63 cells [(20.77 ± 1.29)% vs (2.87 ± 0.33)%, P < 0.001]. Compared with the control group, 2G1 treatment significantly reduced the number of spheres formed (82.67 ± 4.70 vs 42.67 ± 4.00), migrated cells (117.00 ± 5.57 vs 78.33 ± 5.03), and invaded cells (130.70 ± 5.03 vs 89.33 ± 5.03) (all P < 0.001). In the nude mouse xenograft model, 2G1 treatment suppressed tumor growth, with tumor weight and tumor volume inhibition rates of (31.83 ± 16.36)% and (22.00 ± 15.48)% , respectively. Transcriptome sequencing identified 698 differentially expressed genes, including 329 upregulated and 369 downregulated genes. KEGG enrichment analysis indicated enrichment of differentially expressed genes in the Wnt signaling pathway. Western blotting analysis further demonstrated that the expression levels of SOX2, OCT4, N-cadherin, phosphorylated β-catenin (p-β-catenin), and c-Myc were significantly decreased, whereas E-cadherin expression was significantly increased following 2G1 treatment (all P < 0.001). Conclusion: Cell surface HSP90β is highly expressed in MG-63 sphere cells. Targeting HSP90β with monoclonal antibody 2G1 suppresses the sphere-forming, migratory, invasive, and tumorigenic capacities of MG-63 sphere cells and alters the expression levels of stem cell markers, EMT-related markers, and Wnt/β?catenin signaling pathway proteins. These findings suggest that HSP90β may contribute to the regulation of osteosarcoma stem-like characteristics in MG-63 sphere cells and may represent a potential therapeutic target for osteosarcoma.
Objective: To investigate the effects of the HSP90β-targeting monoclonal antibody 2G1 on the biological characteristics of MG-63 sphere cells, an osteosarcoma stem cell (OSC)-enriched model, and to explore its association with changes in Wnt signaling-related proteins. Methods: MG-63 sphere cells were generated from the human osteosarcoma cell line MG-63 by serum-free suspension culture. The target antigen recognized by monoclonal antibody 2G1 was identified by immunofluorescence co-localization and co-immunoprecipitation assays. Flow cytometry was used to determine the expression of cell surface HSP90β in parental MG-63 cells and MG-63 sphere cells. Methylcellulose sphere formation, Transwell migration, and invasion assays were performed to evaluate the effects of 2G1 on the sphere-forming, migratory, and invasive capacities of MG-63 sphere cells. A nude mouse subcutaneous xenograft model was established to assess the effect of 2G1 on the tumorigenic potential of MG-63 sphere cells in vivo. Transcriptome sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Western blotting were further performed to investigate alterations in signaling pathways and the expression of proteins associated with stem-like characteristics, epithelial-mesenchymal transition (EMT)-related markers, and the Wnt/β-catenin signaling pathway following 2G1 treatment. Results: Immunofluorescence co-localization and co-immunoprecipitation demonstrated that HSP90β was the target antigen recognized by monoclonal antibody 2G1. Flow cytometric analysis showed that the proportion of HSP90β-positive cells on the cell surface was significantly higher in MG-63 sphere cells than in parental MG-63 cells [(20.77 ± 1.29)% vs (2.87 ± 0.33)%, P < 0.001]. Compared with the control group, 2G1 treatment significantly reduced the number of spheres formed (82.67 ± 4.70 vs 42.67 ± 4.00), migrated cells (117.00 ± 5.57 vs 78.33 ± 5.03), and invaded cells (130.70 ± 5.03 vs 89.33 ± 5.03) (all P < 0.001). In the nude mouse xenograft model, 2G1 treatment suppressed tumor growth, with tumor weight and tumor volume inhibition rates of (31.83 ± 16.36)% and (22.00 ± 15.48)% , respectively. Transcriptome sequencing identified 698 differentially expressed genes, including 329 upregulated and 369 downregulated genes. KEGG enrichment analysis indicated enrichment of differentially expressed genes in the Wnt signaling pathway. Western blotting analysis further demonstrated that the expression levels of SOX2, OCT4, N-cadherin, phosphorylated β-catenin (p-β-catenin), and c-Myc were significantly decreased, whereas E-cadherin expression was significantly increased following 2G1 treatment (all P < 0.001). Conclusion: Cell surface HSP90β is highly expressed in MG-63 sphere cells. Targeting HSP90β with monoclonal antibody 2G1 suppresses the sphere-forming, migratory, invasive, and tumorigenic capacities of MG-63 sphere cells and alters the expression levels of stem cell markers, EMT-related markers, and Wnt/β?catenin signaling pathway proteins. These findings suggest that HSP90β may contribute to the regulation of osteosarcoma stem-like characteristics in MG-63 sphere cells and may represent a potential therapeutic target for osteosarcoma.
2026,33(8):830-839, DOI: 10.3872/j.issn.1007-385X.2026.08.003
Abstract:
Objective: To investigate the role of RING finger protein 8 (RNF8) in cisplatin (CDDP) sensitivity in endometrial cancer (EC) and its possible mechanism. Methods: The expression level of RNF8 in endometrial cancer tissues and its copy number variation profile were analyzed using an online database. Lentivirus-mediated shRNA was used to stably knock down RNF8 expression in Ishikawa cells, followed by CDDP treatment. The cells were grouped: sh-NC + solvent control, sh-RNF8 + solvent control, sh-NC + CDDP, and sh-RNF8 + CDDP. An inhibition experiment was conducted using the sh-RNF8 + CDDP + KU60019 combination. CCK-8 assays, colony formation assays, Annexin V-FITC/PI flow cytometry, Hoechst 33258/PI staining, WB, and γ-H2AX immunofluorescence were used to assess cell viability, colony formation, apoptosis, DNA damage, and the expression of proteins related to the ATM/CHK2 pathway. Results: RNF8 was significantly overexpressed in endometrial cancer tissues and cells. RNF8 knockdown reduced cell viability and IC50, inhibited colony formation, and further enhanced CDDP-induced apoptosis. Meanwhile, the expression of BAX, Cleaved-Caspase-3, and γ-H2AX increased, while the expression of BCL-2, p-ATM, p-CHK2, and RAD21 decreased. Treatment with KU60019 further promoted DNA damage and apoptosis, and reduced cell viability. Conclusion: RNF8 may promote DNA damage response and reduce the sensitivity of endometrial cancer cells to CDDP via the ATM/CHK2 axis. Knocking down RNF8 increases DNA damage and enhances sensitivity to CDDP.
Objective: To investigate the role of RING finger protein 8 (RNF8) in cisplatin (CDDP) sensitivity in endometrial cancer (EC) and its possible mechanism. Methods: The expression level of RNF8 in endometrial cancer tissues and its copy number variation profile were analyzed using an online database. Lentivirus-mediated shRNA was used to stably knock down RNF8 expression in Ishikawa cells, followed by CDDP treatment. The cells were grouped: sh-NC + solvent control, sh-RNF8 + solvent control, sh-NC + CDDP, and sh-RNF8 + CDDP. An inhibition experiment was conducted using the sh-RNF8 + CDDP + KU60019 combination. CCK-8 assays, colony formation assays, Annexin V-FITC/PI flow cytometry, Hoechst 33258/PI staining, WB, and γ-H2AX immunofluorescence were used to assess cell viability, colony formation, apoptosis, DNA damage, and the expression of proteins related to the ATM/CHK2 pathway. Results: RNF8 was significantly overexpressed in endometrial cancer tissues and cells. RNF8 knockdown reduced cell viability and IC50, inhibited colony formation, and further enhanced CDDP-induced apoptosis. Meanwhile, the expression of BAX, Cleaved-Caspase-3, and γ-H2AX increased, while the expression of BCL-2, p-ATM, p-CHK2, and RAD21 decreased. Treatment with KU60019 further promoted DNA damage and apoptosis, and reduced cell viability. Conclusion: RNF8 may promote DNA damage response and reduce the sensitivity of endometrial cancer cells to CDDP via the ATM/CHK2 axis. Knocking down RNF8 increases DNA damage and enhances sensitivity to CDDP.
2026,33(8):840-847, DOI: 10.3872/j.issn.1007-385X.2026.08.004
Abstract:
Objective: To investigate the conditions and mechanisms by which hypoxia induced the nuclear translocation of aconitase 2 (ACO2) and to explore the effects of ACO2 nuclear translocation on the proliferation, migration, and invasion of hepatocellular carcinoma PLC/PRF/5 cells. Methods: The expression and subcellular localization of ACO2 in human liver cancer tissues were analyzed using the Human Protein Atlas (HPA) database. The potential nuclear localization signal (NLS) of ACO2 was predicted by the NLStradamus website, and an NLS-deficient mutant gene (ACO2ΔNLS) was constructed using genetic engineering techniques. Wild-type (ACO2WT) and mutant (ACO2ΔNLS) plasmids were transfected into human hepatocellular carcinoma PLC/PRF/5 cells, and cells in each transfection group were then cultured under either normoxic or hypoxic (1% O?) conditions. The mechanisms underlying hypoxia-induced nuclear translocation of ACO2 were examined by immunofluorescence staining. The proliferation, migration, and invasion abilities of PLC/PRF/5 cells were assessed using EdU staining, wound healing assay, and Transwell invasion assay. The expression levels of ACO2 in nuclear and cytoplasmic fractions, as well as the levels of migration-and invasion-related proteins MMP2 and MMP9, were detected by WB. Results: HPA database analysis revealed high expression of ACO2 in both the nucleus and cytoplasm of liver cancer cells. Immunofluorescence staining and WB assay results demonstrated that hypoxia significantly induced the nuclear translocation of ACO2 in an NLS-dependent manner (all P < 0.01). Functional experiments showed that hypoxia-induced nuclear translocation of ACO2 further significantly enhanced the proliferation, migration (all P < 0.05), and invasion (all P < 0.05) abilities of PLC/PRF/5 cells. WB analysis indicated that ACO2 nuclear translocation up-regulated the expression levels of migration-and invasion-related proteins MMP2 and MMP9 (all P < 0.05). Conclusion: Hypoxia could induce the nuclear translocation of ACO2 in an NLS-dependent manner, thereby promoting the proliferation, migration, and invasion abilities of PLC/PRF/5 cells.
Objective: To investigate the conditions and mechanisms by which hypoxia induced the nuclear translocation of aconitase 2 (ACO2) and to explore the effects of ACO2 nuclear translocation on the proliferation, migration, and invasion of hepatocellular carcinoma PLC/PRF/5 cells. Methods: The expression and subcellular localization of ACO2 in human liver cancer tissues were analyzed using the Human Protein Atlas (HPA) database. The potential nuclear localization signal (NLS) of ACO2 was predicted by the NLStradamus website, and an NLS-deficient mutant gene (ACO2ΔNLS) was constructed using genetic engineering techniques. Wild-type (ACO2WT) and mutant (ACO2ΔNLS) plasmids were transfected into human hepatocellular carcinoma PLC/PRF/5 cells, and cells in each transfection group were then cultured under either normoxic or hypoxic (1% O?) conditions. The mechanisms underlying hypoxia-induced nuclear translocation of ACO2 were examined by immunofluorescence staining. The proliferation, migration, and invasion abilities of PLC/PRF/5 cells were assessed using EdU staining, wound healing assay, and Transwell invasion assay. The expression levels of ACO2 in nuclear and cytoplasmic fractions, as well as the levels of migration-and invasion-related proteins MMP2 and MMP9, were detected by WB. Results: HPA database analysis revealed high expression of ACO2 in both the nucleus and cytoplasm of liver cancer cells. Immunofluorescence staining and WB assay results demonstrated that hypoxia significantly induced the nuclear translocation of ACO2 in an NLS-dependent manner (all P < 0.01). Functional experiments showed that hypoxia-induced nuclear translocation of ACO2 further significantly enhanced the proliferation, migration (all P < 0.05), and invasion (all P < 0.05) abilities of PLC/PRF/5 cells. WB analysis indicated that ACO2 nuclear translocation up-regulated the expression levels of migration-and invasion-related proteins MMP2 and MMP9 (all P < 0.05). Conclusion: Hypoxia could induce the nuclear translocation of ACO2 in an NLS-dependent manner, thereby promoting the proliferation, migration, and invasion abilities of PLC/PRF/5 cells.
2026,33(8):848-856, DOI: 10.3872/j.issn.1007-385X.2026.08.005
Abstract:
Objective: To investigate the antitumor effects and potential mechanisms of the β-catenin/CREB-binding protein (CBP) pathway inhibitor PRI-724 combined with imatinib in BCR-ABL1-positive chronic myeloid leukemia (CML) cells and xenograft models. Methods: Human K562 cells and murine 32D myeloid cells stably expressing wild-type BCR-ABL1 (32D-WT) or T315I-mutant BCR-ABL1 (32D-T315I) were used for in vitro experiments. The effects of imatinib, PRI-724, and their combination on cell viability were detected using the CCK-8 assay, and the half-maximal inhibitory concentration (IC50) and combination index (CI) were calculated. Senescence-associated phenotypes were examined by SA-β-gal staining. Co-immunoprecipitation (Co-IP) was used to detect the effect of PRI-724 on the interaction between β-catenin and CBP/p300. For in vivo experiments, subcutaneous xenograft models were established in nude mice using K562, 32D-WT, and 32D-T315I cells. Untreated, imatinib, PRI?724, and imatinib + PRI?724 groups were established, and each group received the corresponding treatment, and tumor growth was monitored. The in vivo CI was calculated based on tumor growth inhibition (TGI). WB was used to detect the expression of PI3K/AKT signaling pathway-related proteins, nuclear β-catenin/CBP, and downstream effectors c-Myc and Cyclin D1 in tumor tissues. Results: Imatinib and PRI-724 inhibited K562, 32D-WT, and 32D-T315I cells in a concentration-dependent manner. The IC50 values of imatinib in K562, 32D-WT, and 32D- T315I cells were 0.860, 0.594, and 1.646 μmol/L, respectively; the IC50 values of PRI-724 in the above three cell types were 1.120, 0.761, and 0.756 μmol/L, respectively. Compared with 32D-WT cells, 32D-T315I cells showed reduced sensitivity to imatinib, whereas no obvious decrease in sensitivity to PRI-724 was observed. The CI values of imatinib + PRI-724 in K562, 32D-WT, and 32D-T315I cells were 0.635, 0.780, and 0.689, respectively, suggesting a synergistic inhibitory effect in vitro. SA- β-gal staining showed that, compared with imatinib monotherapy, PRI-724 monotherapy increased the proportion of SA- β-gal-positive cells in all three cell models, and the combination further increased this proportion. Co-IP results showed that, after PRI-724 treatment, the level of CBP co-precipitated with β-catenin was decreased, whereas the level of p300 co-precipitated with β-catenin was increased. In vivo experiments showed that, compared with the imatinib monotherapy group, the imatinib + PRI-724 combination group showed further reductions in tumor volume and tumor weight. However, the in vivo CI values calculated using the TGI-based response-additivity approach in the K562, 32D-WT, and 32D-T315I xenograft models were all > 1, suggesting that, under the current dose and administration regimen, the in vivo combination effect of the two drugs did not reach the expected additive effect and may have shown an antagonistic trend. WB showed that, compared with the imatinib monotherapy group, the combination treatment group had lower p-PI3K/PI3K and p-AKT/ AKT ratios and lower expression levels of nuclear β-catenin, CBP, c-Myc, and Cyclin D1 in tumor tissues. Conclusion: PRI-724 combined with imatinib exhibits a synergistic inhibitory effect in vitro and further suppresses tumor growth in vivo compared with imatinib monotherapy. The underlying mechanism may be related to modulation of the β-catenin/CBP/p300 complex, inhibition of the PI3K/AKT signaling pathway, and downregulation of c-Myc and Cyclin D1 expression.
Objective: To investigate the antitumor effects and potential mechanisms of the β-catenin/CREB-binding protein (CBP) pathway inhibitor PRI-724 combined with imatinib in BCR-ABL1-positive chronic myeloid leukemia (CML) cells and xenograft models. Methods: Human K562 cells and murine 32D myeloid cells stably expressing wild-type BCR-ABL1 (32D-WT) or T315I-mutant BCR-ABL1 (32D-T315I) were used for in vitro experiments. The effects of imatinib, PRI-724, and their combination on cell viability were detected using the CCK-8 assay, and the half-maximal inhibitory concentration (IC50) and combination index (CI) were calculated. Senescence-associated phenotypes were examined by SA-β-gal staining. Co-immunoprecipitation (Co-IP) was used to detect the effect of PRI-724 on the interaction between β-catenin and CBP/p300. For in vivo experiments, subcutaneous xenograft models were established in nude mice using K562, 32D-WT, and 32D-T315I cells. Untreated, imatinib, PRI?724, and imatinib + PRI?724 groups were established, and each group received the corresponding treatment, and tumor growth was monitored. The in vivo CI was calculated based on tumor growth inhibition (TGI). WB was used to detect the expression of PI3K/AKT signaling pathway-related proteins, nuclear β-catenin/CBP, and downstream effectors c-Myc and Cyclin D1 in tumor tissues. Results: Imatinib and PRI-724 inhibited K562, 32D-WT, and 32D-T315I cells in a concentration-dependent manner. The IC50 values of imatinib in K562, 32D-WT, and 32D- T315I cells were 0.860, 0.594, and 1.646 μmol/L, respectively; the IC50 values of PRI-724 in the above three cell types were 1.120, 0.761, and 0.756 μmol/L, respectively. Compared with 32D-WT cells, 32D-T315I cells showed reduced sensitivity to imatinib, whereas no obvious decrease in sensitivity to PRI-724 was observed. The CI values of imatinib + PRI-724 in K562, 32D-WT, and 32D-T315I cells were 0.635, 0.780, and 0.689, respectively, suggesting a synergistic inhibitory effect in vitro. SA- β-gal staining showed that, compared with imatinib monotherapy, PRI-724 monotherapy increased the proportion of SA- β-gal-positive cells in all three cell models, and the combination further increased this proportion. Co-IP results showed that, after PRI-724 treatment, the level of CBP co-precipitated with β-catenin was decreased, whereas the level of p300 co-precipitated with β-catenin was increased. In vivo experiments showed that, compared with the imatinib monotherapy group, the imatinib + PRI-724 combination group showed further reductions in tumor volume and tumor weight. However, the in vivo CI values calculated using the TGI-based response-additivity approach in the K562, 32D-WT, and 32D-T315I xenograft models were all > 1, suggesting that, under the current dose and administration regimen, the in vivo combination effect of the two drugs did not reach the expected additive effect and may have shown an antagonistic trend. WB showed that, compared with the imatinib monotherapy group, the combination treatment group had lower p-PI3K/PI3K and p-AKT/ AKT ratios and lower expression levels of nuclear β-catenin, CBP, c-Myc, and Cyclin D1 in tumor tissues. Conclusion: PRI-724 combined with imatinib exhibits a synergistic inhibitory effect in vitro and further suppresses tumor growth in vivo compared with imatinib monotherapy. The underlying mechanism may be related to modulation of the β-catenin/CBP/p300 complex, inhibition of the PI3K/AKT signaling pathway, and downregulation of c-Myc and Cyclin D1 expression.
2026,33(8):857-866, DOI: 10.3872/j.issn.1007-385X.2026.08.006
Abstract:
Objective: This study aimed to investigate the effects of miR-532-3p on thyroid cancer TPC-1 cell proliferation and glycolysis and to preliminarily explore the underlying mechanism by targeting dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST). Methods: The basal expression of miR-532-3p was assessed in normal thyroid Nthy-ori 3-1 cells and thyroid cancer cell lines TPC-1, FTC-133, and IHH-4. TPC-1 cells were selected for subsequent experiments and divided into mimic-NC group, miR-532-3p mimic group, inhibitor-NC group, miR-532-3p inhibitor group, mimic-NC + pcDNA-NC group, mimic-NC+pcDNA-DDOST group, miR-532-3p mimic + pcDNA-NC group, and miR-532-3p mimic + pcDNA-DDOST group. The targeting relationship between miR-532-3p and DDOST was detected by dual-luciferase reporter gene assay. Cell proliferation was detected by the CCK-8 method. Gene and protein expression levels were detected by reverse transcription quantitative PCR (RT-qPCR) and Western blotting. The TPC-1 cells were subcutaneously injected into the right posterior axillary region of nude mice to establish a xenograft tumor model of thyroid carcinoma, and the growth status of the tumors was recorded. Ki-67 and DDOST expression in xenograft tumor tissues was detected by immunohistochemistry. Lactate concentration and glucose consumption were measured using the corresponding assay kits. Results: Compared with normal thyroid cells Nthy-ori 3-1, the expression levels of miR-532-3p in thyroid cancer cell lines (TPC-1, FTC-133, IHH-4) were significantly decreased (P < 0.05), with the lowest level observed in TPC-1 cells. The expression of DDOST was significantly increased (P < 0.05). Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis and downregulated DDOST expression (P < 0.05). Moreover, these effects were reversed by DDOST overexpression (P < 0.05). Overexpression of miR-532-3p inhibited thyroid cancer xenograft growth and reduced DDOST expression in xenograft tumor tissues (P < 0.05). Conclusion: Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis by targeting DDOST and suppressed thyroid cancer xenograft growth in nude mice.
Objective: This study aimed to investigate the effects of miR-532-3p on thyroid cancer TPC-1 cell proliferation and glycolysis and to preliminarily explore the underlying mechanism by targeting dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST). Methods: The basal expression of miR-532-3p was assessed in normal thyroid Nthy-ori 3-1 cells and thyroid cancer cell lines TPC-1, FTC-133, and IHH-4. TPC-1 cells were selected for subsequent experiments and divided into mimic-NC group, miR-532-3p mimic group, inhibitor-NC group, miR-532-3p inhibitor group, mimic-NC + pcDNA-NC group, mimic-NC+pcDNA-DDOST group, miR-532-3p mimic + pcDNA-NC group, and miR-532-3p mimic + pcDNA-DDOST group. The targeting relationship between miR-532-3p and DDOST was detected by dual-luciferase reporter gene assay. Cell proliferation was detected by the CCK-8 method. Gene and protein expression levels were detected by reverse transcription quantitative PCR (RT-qPCR) and Western blotting. The TPC-1 cells were subcutaneously injected into the right posterior axillary region of nude mice to establish a xenograft tumor model of thyroid carcinoma, and the growth status of the tumors was recorded. Ki-67 and DDOST expression in xenograft tumor tissues was detected by immunohistochemistry. Lactate concentration and glucose consumption were measured using the corresponding assay kits. Results: Compared with normal thyroid cells Nthy-ori 3-1, the expression levels of miR-532-3p in thyroid cancer cell lines (TPC-1, FTC-133, IHH-4) were significantly decreased (P < 0.05), with the lowest level observed in TPC-1 cells. The expression of DDOST was significantly increased (P < 0.05). Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis and downregulated DDOST expression (P < 0.05). Moreover, these effects were reversed by DDOST overexpression (P < 0.05). Overexpression of miR-532-3p inhibited thyroid cancer xenograft growth and reduced DDOST expression in xenograft tumor tissues (P < 0.05). Conclusion: Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis by targeting DDOST and suppressed thyroid cancer xenograft growth in nude mice.
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Objective: To develop a chimeric costimulatory receptor targeting CD7 and prepare γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: γδ T cells expressing the CD7-targeting chimeric costimulatory receptor (CD7-DAP10-CCR-γδ T) were constructed. Using lentiviral transduction, the receptor was introduced into human peripheral blood-derived γδ T cells from healthy donors, followed by ex vivo expansion with artificial antigen-presenting cell (aAPC) expressing CD64, CD86, and CD137L. The cytotoxic activity of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and normal primary αβ T cells was assessed using the Annexin V/7-AAD assay. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. Tumor burden was monitored regularly via in vivo imaging, and body weight changes and survival rates were recorded. Results: CD7-DAP10-CCR-γδ T cells were successfully expanded using aAPC, achieving an average expansion fold exceeding 10000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In the T-ALL xenograft model, treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared to the PBS control group. Conclusion: This study establishes a robust aAPC-driven protocol for generating CD7-DAP10-CCR-γδ T cells with scalable expansion ( > 10 000-fold) and CD7-specific anti-tumor efficacy. The engineered cells exhibited selective cytotoxicity against T-ALL while sparing normal T cells, highlighting their therapeutic promise for relapsed/refractory T-ALL with mitigated on-target/off-tumor risks.
Objective: To develop a chimeric costimulatory receptor targeting CD7 and prepare γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: γδ T cells expressing the CD7-targeting chimeric costimulatory receptor (CD7-DAP10-CCR-γδ T) were constructed. Using lentiviral transduction, the receptor was introduced into human peripheral blood-derived γδ T cells from healthy donors, followed by ex vivo expansion with artificial antigen-presenting cell (aAPC) expressing CD64, CD86, and CD137L. The cytotoxic activity of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and normal primary αβ T cells was assessed using the Annexin V/7-AAD assay. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. Tumor burden was monitored regularly via in vivo imaging, and body weight changes and survival rates were recorded. Results: CD7-DAP10-CCR-γδ T cells were successfully expanded using aAPC, achieving an average expansion fold exceeding 10000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In the T-ALL xenograft model, treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared to the PBS control group. Conclusion: This study establishes a robust aAPC-driven protocol for generating CD7-DAP10-CCR-γδ T cells with scalable expansion ( > 10 000-fold) and CD7-specific anti-tumor efficacy. The engineered cells exhibited selective cytotoxicity against T-ALL while sparing normal T cells, highlighting their therapeutic promise for relapsed/refractory T-ALL with mitigated on-target/off-tumor risks.
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2012,19(5):550-555, DOI: 10.3872/j.issn.1007-385X.2012.5.018
Abstract:
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
2016,23(2):149-160, DOI: 10.3872/j.issn.1007-385X.2016.02.001
Abstract:
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
2018,25(1):23-27, DOI: 10.3872/j.issn.1007-385X.2018.01.004
Abstract:
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
2010,17(1):57-61, DOI: 10.3872/j.issn.1007-385X.2010.1.011
Abstract:
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
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