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Volume 33,Issue 7,2026 Table of Contents
2026, 33(7):709-718.
DOI: 10.3872/j.issn.1007-385X.2026.07.001
Abstract:
Neoadjuvant immunotherapy combined with chemotherapy (NICT) has become a standard treatment modality for patients with resectable non-small cell lung cancer (NSCLC). However, approximately 80% of patients still have residual disease (non- pathological complete response, non-pCR) after surgery. These patients exhibit significantly poorer long-term survival compared with those achieving pCR, with a 5-year overall survival rate of approximately 55%, representing a major challenge in current perioperative therapy. Drawing on the successful experience of implementing adjuvant intensification strategies (e.g., ado-trastuzumab emtansine and capecitabine) for non-pCR patients in breast cancer, this article explores the optimization of adjuvant treatment strategies for the non- pCR population following NICT in NSCLC. We focus on analyzing various promising adjuvant intensification approaches, including anti-angiogenic agents, antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), personalized neoantigen vaccines, radiotherapy, and oral chemotherapy agents, aiming to eradicate drug-resistant residual tumor clones. Furthermore, we propose that fine- grained risk stratification based on the residual viable tumor (RVT) proportion and dynamic monitoring of molecular residual disease (MRD) should be implemented. Establishing a risk-adaptive model integrating RVT and MRD status holds promise for achieving an individualized adjuvant intensification strategy, with the goal of improving survival outcomes for non-pCR NSCLC patients. This review provides a theoretical basis and future research directions for adjuvant intensification in patients with non-pCR NSCLC.
Neoadjuvant immunotherapy combined with chemotherapy (NICT) has become a standard treatment modality for patients with resectable non-small cell lung cancer (NSCLC). However, approximately 80% of patients still have residual disease (non- pathological complete response, non-pCR) after surgery. These patients exhibit significantly poorer long-term survival compared with those achieving pCR, with a 5-year overall survival rate of approximately 55%, representing a major challenge in current perioperative therapy. Drawing on the successful experience of implementing adjuvant intensification strategies (e.g., ado-trastuzumab emtansine and capecitabine) for non-pCR patients in breast cancer, this article explores the optimization of adjuvant treatment strategies for the non- pCR population following NICT in NSCLC. We focus on analyzing various promising adjuvant intensification approaches, including anti-angiogenic agents, antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), personalized neoantigen vaccines, radiotherapy, and oral chemotherapy agents, aiming to eradicate drug-resistant residual tumor clones. Furthermore, we propose that fine- grained risk stratification based on the residual viable tumor (RVT) proportion and dynamic monitoring of molecular residual disease (MRD) should be implemented. Establishing a risk-adaptive model integrating RVT and MRD status holds promise for achieving an individualized adjuvant intensification strategy, with the goal of improving survival outcomes for non-pCR NSCLC patients. This review provides a theoretical basis and future research directions for adjuvant intensification in patients with non-pCR NSCLC.
2026, 33(7):719-730.
DOI: 10.3872/j.issn.1007-385X.2026.07.002
Abstract:
Objective: To construct and optimize chimeric antigen receptor T (CAR-T) cells targeting sialic acid-binding immunoglobulin- like lectin 6 (Siglec-6), and to evaluate their targeted cytotoxicity against acute myeloid leukemia (AML) cells, preliminary in vivo efficacy and short-term safety, thereby providing experimental evidence for Siglec-6 as an immunotherapeutic target for AML. Methods: A recombinant CAR gene targeting Siglec-6 was designed. Three humanized single-chain variable fragments (scFvs) were screened, and the effects of different co-stimulatory domains, including 4-1BB, CD28, ICOS, HVEM, TMIGD2 and OX40, on CAR-T cell function were compared within a second-generation CAR framework. Siglec-6 CAR-T cells were generated by lentiviral transduction of primary human T cells, and CAR positivity and cellular phenotypes were detected by flow cytometry. Surface expression of Siglec-6 on U937, MV4-11 and K562 cells was examined, and 293T-Siglec-6 overexpression (OE) cells, U937-Siglec-6 knockout (KO) cells, and U937-Luc/U937-Siglec-6 KO-Luc cell models were established. Flow cytometry-based cytotoxicity assays, ELISA, real-time cell analysis (RTCA) and luciferase bioluminescence assays were used to evaluate the in vitro cytotoxic activity and target specificity of CAR-T cells. A U937-Luc xenograft leukemia model was established to assess in vivo antitumor efficacy, and short-term safety was evaluated based on body weight, bioluminescence imaging, peripheral blood T-cell levels, hematoxylin-eosin staining of major organs, organ indices and serum biochemical parameters. Results: Among the three candidate CAR-T cells, CAR-T-1 showed superior performance in terms of CAR expression level, short-term cytotoxic activity and feasibility for subsequent construct development. Comparison of different co-stimulatory domains showed that 4-1BB-CAR-T cells exhibited relatively stable CAR positivity and stronger in vitro cytotoxic activity under multiple effector-to-target ratios. Siglec-6 CAR-T cells effectively killed Siglec-6-positive U937 and MV4-11 cells and significantly promoted the release of IFN-γ and TNF-α (P < 0.000 1), whereas no obvious cytotoxicity was observed against Siglec-6-negative K562 cells. The 293T-Siglec-6 overexpression model and U937-Siglec-6 KO model further confirmed that this cytotoxic effect was clearly dependent on Siglec-6 targeting. After antigen stimulation, Siglec-6 CAR-T cells differentiated into effector phenotypes and were significantly activated (P < 0.000 1), accompanied by increased expression of some exhaustion-related markers (P < 0.01). In vivo experiments showed that Siglec-6 CAR-T treatment reduced tumor burden and prolonged survival in U937-Luc tumor-bearing mice. During short-term observation, no obvious difference in body weight change was observed between the two groups, and hematoxylin-eosin staining of major organs revealed no apparent morphological injury, although some organ indices and serum biochemical parameters differed between groups (P < 0.01). Conclusion: Siglec-6 CAR-T cells specifically killed Siglec-6-positive AML cells and exerted preliminary anti-leukemic activity in an AML xenograft model, and the underlying mechanism may be associated with the target- dependent recognition of Siglec-6, the activation of CAR-T cells and the increased secretion level of IFN-γ/TNF-α.
Objective: To construct and optimize chimeric antigen receptor T (CAR-T) cells targeting sialic acid-binding immunoglobulin- like lectin 6 (Siglec-6), and to evaluate their targeted cytotoxicity against acute myeloid leukemia (AML) cells, preliminary in vivo efficacy and short-term safety, thereby providing experimental evidence for Siglec-6 as an immunotherapeutic target for AML. Methods: A recombinant CAR gene targeting Siglec-6 was designed. Three humanized single-chain variable fragments (scFvs) were screened, and the effects of different co-stimulatory domains, including 4-1BB, CD28, ICOS, HVEM, TMIGD2 and OX40, on CAR-T cell function were compared within a second-generation CAR framework. Siglec-6 CAR-T cells were generated by lentiviral transduction of primary human T cells, and CAR positivity and cellular phenotypes were detected by flow cytometry. Surface expression of Siglec-6 on U937, MV4-11 and K562 cells was examined, and 293T-Siglec-6 overexpression (OE) cells, U937-Siglec-6 knockout (KO) cells, and U937-Luc/U937-Siglec-6 KO-Luc cell models were established. Flow cytometry-based cytotoxicity assays, ELISA, real-time cell analysis (RTCA) and luciferase bioluminescence assays were used to evaluate the in vitro cytotoxic activity and target specificity of CAR-T cells. A U937-Luc xenograft leukemia model was established to assess in vivo antitumor efficacy, and short-term safety was evaluated based on body weight, bioluminescence imaging, peripheral blood T-cell levels, hematoxylin-eosin staining of major organs, organ indices and serum biochemical parameters. Results: Among the three candidate CAR-T cells, CAR-T-1 showed superior performance in terms of CAR expression level, short-term cytotoxic activity and feasibility for subsequent construct development. Comparison of different co-stimulatory domains showed that 4-1BB-CAR-T cells exhibited relatively stable CAR positivity and stronger in vitro cytotoxic activity under multiple effector-to-target ratios. Siglec-6 CAR-T cells effectively killed Siglec-6-positive U937 and MV4-11 cells and significantly promoted the release of IFN-γ and TNF-α (P < 0.000 1), whereas no obvious cytotoxicity was observed against Siglec-6-negative K562 cells. The 293T-Siglec-6 overexpression model and U937-Siglec-6 KO model further confirmed that this cytotoxic effect was clearly dependent on Siglec-6 targeting. After antigen stimulation, Siglec-6 CAR-T cells differentiated into effector phenotypes and were significantly activated (P < 0.000 1), accompanied by increased expression of some exhaustion-related markers (P < 0.01). In vivo experiments showed that Siglec-6 CAR-T treatment reduced tumor burden and prolonged survival in U937-Luc tumor-bearing mice. During short-term observation, no obvious difference in body weight change was observed between the two groups, and hematoxylin-eosin staining of major organs revealed no apparent morphological injury, although some organ indices and serum biochemical parameters differed between groups (P < 0.01). Conclusion: Siglec-6 CAR-T cells specifically killed Siglec-6-positive AML cells and exerted preliminary anti-leukemic activity in an AML xenograft model, and the underlying mechanism may be associated with the target- dependent recognition of Siglec-6, the activation of CAR-T cells and the increased secretion level of IFN-γ/TNF-α.
2026, 33(7):731-736.
DOI: 10.3872/j.issn.1007-385X.2026.07.003
Abstract:
Objective: To investigate the effect of sinensetin on malignant biological behaviors of endometrial cancer cells through regulation of the Fas/FasL signaling pathway. Methods: Human endometrial cancer cell lines Ishikawa (ISK), RL95-2, AN3-CA, and KLE were selected as research subjects. The CCK-8 assay was initially used to screen the inhibitory effect of sinensetin on the proliferation of these four cell lines (treatment with 120 μmol/L for 48 h). Based on this, ISK cells, which were more sensitive to sinensetin, were selected for subsequent experiments and divided into the following groups: control group, L-sinensetin group (40 μmol/L), M-sinensetin group (80 μmol/L), H-sinensetin group (120 μmol/L), H-sinensetin + si-NC group, and H-sinensetin + si-Fas group. The CCK-8 assay, colony formation assay, Transwell assay, and flow cytometry were used to detect cell proliferation, invasion, and apoptosis, respectively. Vasculogenic mimicry assay was performed to assess the vasculogenic mimicry-forming ability of cells in each group, while WB was employed to detect the protein expression levels of Fas, FasL, and cleaved caspase-8 in each group. Results: Sinensetin inhibited the proliferation of endometrial cancer cell lines ISK, RL95-2, AN3-CA, and KLE (all P < 0.01), with the most pronounced effect observed in ISK cells. In ISK cells, compared with the control group, the levels of cell proliferation, number of colonies, number of invading cells, and number of vasculogenic mimicry branches in the L-sinensetin group, M-sinensetin group, and H-sinensetin group gradually decreased, while the apoptosis rate and the protein expression levels of Fas, FasL, and cleaved caspase-8 gradually increased. Moreover, higher concentrations of sinensetin were associated with more pronounced changes in the above indicators (P < 0.01). Compared with the H-sinensetin + si-NC group, the H-sinensetin + si-Fas group showed increased cell proliferation, number of colonies, number of invading cells, and number of vasculogenic mimicry branches, as well as decreased apoptosis rate and reduced protein expression levels of Fas, FasL, and cleaved caspase-8 in ISK cells (P < 0.01). Conclusion: Sinensetin inhibits proliferation, invasion, and vasculogenic mimicry of endometrial cancer cells and induces apoptosis, which may be associated with the activation of the Fas/FasL signaling pathway.
Objective: To investigate the effect of sinensetin on malignant biological behaviors of endometrial cancer cells through regulation of the Fas/FasL signaling pathway. Methods: Human endometrial cancer cell lines Ishikawa (ISK), RL95-2, AN3-CA, and KLE were selected as research subjects. The CCK-8 assay was initially used to screen the inhibitory effect of sinensetin on the proliferation of these four cell lines (treatment with 120 μmol/L for 48 h). Based on this, ISK cells, which were more sensitive to sinensetin, were selected for subsequent experiments and divided into the following groups: control group, L-sinensetin group (40 μmol/L), M-sinensetin group (80 μmol/L), H-sinensetin group (120 μmol/L), H-sinensetin + si-NC group, and H-sinensetin + si-Fas group. The CCK-8 assay, colony formation assay, Transwell assay, and flow cytometry were used to detect cell proliferation, invasion, and apoptosis, respectively. Vasculogenic mimicry assay was performed to assess the vasculogenic mimicry-forming ability of cells in each group, while WB was employed to detect the protein expression levels of Fas, FasL, and cleaved caspase-8 in each group. Results: Sinensetin inhibited the proliferation of endometrial cancer cell lines ISK, RL95-2, AN3-CA, and KLE (all P < 0.01), with the most pronounced effect observed in ISK cells. In ISK cells, compared with the control group, the levels of cell proliferation, number of colonies, number of invading cells, and number of vasculogenic mimicry branches in the L-sinensetin group, M-sinensetin group, and H-sinensetin group gradually decreased, while the apoptosis rate and the protein expression levels of Fas, FasL, and cleaved caspase-8 gradually increased. Moreover, higher concentrations of sinensetin were associated with more pronounced changes in the above indicators (P < 0.01). Compared with the H-sinensetin + si-NC group, the H-sinensetin + si-Fas group showed increased cell proliferation, number of colonies, number of invading cells, and number of vasculogenic mimicry branches, as well as decreased apoptosis rate and reduced protein expression levels of Fas, FasL, and cleaved caspase-8 in ISK cells (P < 0.01). Conclusion: Sinensetin inhibits proliferation, invasion, and vasculogenic mimicry of endometrial cancer cells and induces apoptosis, which may be associated with the activation of the Fas/FasL signaling pathway.
2026, 33(7):737-745.
DOI: 10.3872/j.issn.1007-385X.2026.07.004
Abstract:
Objective: To investigate the expression characteristics and clinical significance of cytochrome c oxidase assembly factor 6 (COA6) in gastric cancer, as well as its regulatory effects and molecular mechanisms on the malignant biological behaviors of gastric cancer cells. Methods: The TIMER 2.0, The Human Protein Atlas (HPA), and UALCAN public databases were utilized to analyze the mRNA expression levels and partial protein expression information of COA6 in pan-cancer tissues, and to assess its association with clinicopathological features. Lentiviral vectors carrying COA6 knockdown and overexpression sequences were constructed and transfected into human gastric cancer SGC-7901 and MGC-803 cell lines to establish stably modified COA6 cell models. For the knockdown experiment, three experimental groups (shCOA6?1, shCOA6?2, shCOA6?3) and a negative control group (shCOA6-NC) were established; for the overexpression experiment, an OE group (COA6 overexpression) and a Vector group (empty lentivirus control) were set up. WB was performed to verify the efficiencies of COA6 knockdown and overexpression in each group. Subsequently, cell proliferative activity was determined via cell counting assay, cell invasive capacity was evaluated using Transwell assay, and cell migratory ability was examined by wound healing assay. Annexin V-FITC/PI double staining combined with flow cytometry was adopted to quantify cellular apoptosis, and WB was also used to detect the phosphorylation levels of core proteins in the AMPK/mTOR signaling pathway. Results: COA6 was aberrantly expressed in multiple cancers, and its expression level was associated with clinical stage, pathological grade, lymph node metastasis, and TP53 mutation status in gastric cancer. Functionally, COA6 knockdown inhibited malignant phenotypes and promoted apoptosis (all P < 0.000 1), while overexpression had opposite effects. Mechanistically, COA6 knockdown increased p-AMPK levels and decreased p-mTOR levels. This effect was reversed by treatment with the AMPK inhibitor Compound C, which abrogated the COA6 knockdown-induced increase in p-AMPK and decrease in p-mTOR. Conclusion: COA6 is highly expressed in gastric cancer and is associated with several clinicopathological features. It may promote proliferation, invasion, and migration, while inhibiting apoptosis of gastric cancer cells by regulating the AMPK/mTOR signaling pathway.
Objective: To investigate the expression characteristics and clinical significance of cytochrome c oxidase assembly factor 6 (COA6) in gastric cancer, as well as its regulatory effects and molecular mechanisms on the malignant biological behaviors of gastric cancer cells. Methods: The TIMER 2.0, The Human Protein Atlas (HPA), and UALCAN public databases were utilized to analyze the mRNA expression levels and partial protein expression information of COA6 in pan-cancer tissues, and to assess its association with clinicopathological features. Lentiviral vectors carrying COA6 knockdown and overexpression sequences were constructed and transfected into human gastric cancer SGC-7901 and MGC-803 cell lines to establish stably modified COA6 cell models. For the knockdown experiment, three experimental groups (shCOA6?1, shCOA6?2, shCOA6?3) and a negative control group (shCOA6-NC) were established; for the overexpression experiment, an OE group (COA6 overexpression) and a Vector group (empty lentivirus control) were set up. WB was performed to verify the efficiencies of COA6 knockdown and overexpression in each group. Subsequently, cell proliferative activity was determined via cell counting assay, cell invasive capacity was evaluated using Transwell assay, and cell migratory ability was examined by wound healing assay. Annexin V-FITC/PI double staining combined with flow cytometry was adopted to quantify cellular apoptosis, and WB was also used to detect the phosphorylation levels of core proteins in the AMPK/mTOR signaling pathway. Results: COA6 was aberrantly expressed in multiple cancers, and its expression level was associated with clinical stage, pathological grade, lymph node metastasis, and TP53 mutation status in gastric cancer. Functionally, COA6 knockdown inhibited malignant phenotypes and promoted apoptosis (all P < 0.000 1), while overexpression had opposite effects. Mechanistically, COA6 knockdown increased p-AMPK levels and decreased p-mTOR levels. This effect was reversed by treatment with the AMPK inhibitor Compound C, which abrogated the COA6 knockdown-induced increase in p-AMPK and decrease in p-mTOR. Conclusion: COA6 is highly expressed in gastric cancer and is associated with several clinicopathological features. It may promote proliferation, invasion, and migration, while inhibiting apoptosis of gastric cancer cells by regulating the AMPK/mTOR signaling pathway.
2026, 33(7):746-753.
DOI: 10.3872/j.issn.1007-385X.2026.07.005
Abstract:
Objective: To investigate the effects of curcumin and its metabolite tetrahydrocurcumin on reversing doxorubicin resistance in MCF-7/ADR breast cancer cells and to explore the possible mechanisms. Methods: The inhibitory effects of curcumin and tetrahydrocurcumin on MCF-7/ADR cell proliferation and their effects on the reversal of doxorubicin resistance were assessed using the CCK-8 assay. Cell migration and invasion were evaluated using wound-healing and Transwell assays, respectively. Apoptosis was analyzed by flow cytometry. The mRNA levels of glutathione S-transferase pi 1 (GSTP1), Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3), as well as the protein levels of GSTP1, JAK1, phosphorylated JAK1 (p-JAK1), STAT3, and phosphorylated STAT3 (p-STAT3), were measured by quantitative real-time PCR and WB assay, respectively. Results: Both curcumin and tetrahydrocurcumin inhibited MCF-7/ADR cell proliferation in a concentration-dependent manner. The IC?? of tetrahydrocurcumin (18.62 ± 2.15) μmol/L was significantly lower than that of curcumin (37.45 ± 3.28) μmol/L (P < 0.05). Both compounds enhanced the inhibitory effect of doxorubicin on MCF-7/ADR cell proliferation, and the resistance reversal index of tetrahydrocurcumin (4.82) was significantly higher than that of curcumin (2.96) (P < 0.05). Compared with the 0 μmol/L groups, both compounds inhibited MCF-7/ADR cell migration and invasion in a concentration-dependent manner, promoted apoptosis, and downregulated GSTP1, JAK1, and STAT3 mRNA expression as well as GSTP1, p-JAK1, and p-STAT3 protein expression (all P < 0.05). Treatment with 80 μmol/L curcumin or tetrahydrocurcumin significantly reduced the wound-healing rate and the number of invading cells and significantly increased the apoptosis rate (all P < 0.05). Conclusion: Curcumin and its metabolite tetrahydrocurcumin can reverse doxorubicin resistance in MCF-7/ADR breast cancer cells, possibly by inhibiting cell migration and invasion, promoting apoptosis, downregulating GSTP1 expression, and suppressing the phosphorylation of JAK1 and STAT3.
Objective: To investigate the effects of curcumin and its metabolite tetrahydrocurcumin on reversing doxorubicin resistance in MCF-7/ADR breast cancer cells and to explore the possible mechanisms. Methods: The inhibitory effects of curcumin and tetrahydrocurcumin on MCF-7/ADR cell proliferation and their effects on the reversal of doxorubicin resistance were assessed using the CCK-8 assay. Cell migration and invasion were evaluated using wound-healing and Transwell assays, respectively. Apoptosis was analyzed by flow cytometry. The mRNA levels of glutathione S-transferase pi 1 (GSTP1), Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3), as well as the protein levels of GSTP1, JAK1, phosphorylated JAK1 (p-JAK1), STAT3, and phosphorylated STAT3 (p-STAT3), were measured by quantitative real-time PCR and WB assay, respectively. Results: Both curcumin and tetrahydrocurcumin inhibited MCF-7/ADR cell proliferation in a concentration-dependent manner. The IC?? of tetrahydrocurcumin (18.62 ± 2.15) μmol/L was significantly lower than that of curcumin (37.45 ± 3.28) μmol/L (P < 0.05). Both compounds enhanced the inhibitory effect of doxorubicin on MCF-7/ADR cell proliferation, and the resistance reversal index of tetrahydrocurcumin (4.82) was significantly higher than that of curcumin (2.96) (P < 0.05). Compared with the 0 μmol/L groups, both compounds inhibited MCF-7/ADR cell migration and invasion in a concentration-dependent manner, promoted apoptosis, and downregulated GSTP1, JAK1, and STAT3 mRNA expression as well as GSTP1, p-JAK1, and p-STAT3 protein expression (all P < 0.05). Treatment with 80 μmol/L curcumin or tetrahydrocurcumin significantly reduced the wound-healing rate and the number of invading cells and significantly increased the apoptosis rate (all P < 0.05). Conclusion: Curcumin and its metabolite tetrahydrocurcumin can reverse doxorubicin resistance in MCF-7/ADR breast cancer cells, possibly by inhibiting cell migration and invasion, promoting apoptosis, downregulating GSTP1 expression, and suppressing the phosphorylation of JAK1 and STAT3.
2026, 33(7):754-762.
DOI: 10.3872/j.issn.1007-385X.2026.07.006
Abstract:
Objective: To investigate the effects of FOXK1 on the proliferation, migration and invasion of laryngeal squamous cell carcinoma (LSCC) and the prognosis of patients, as well as its molecular mechanism. Methods: RT-qPCR and immunohistochemistry were applied to determine FOXK1 expression in LSCC tissues and TU177 cells, with subsequent analysis of its association with clinicopathological parameters and patient prognosis. FOXK1 overexpression and knockdown vectors were constructed and transfected into LSCC cell line TU177. MTS assay, colony formation assay, scratch wound healing assay, and Transwell assay were employed to detect changes in the malignant biological behaviors of cells. RT-qPCR was employed to detect the mRNA expression of epithelial- mesenchymal transition (EMT)-related factors, and Western blotting was used to detect the protein expression of PI3K/AKT signaling pathway-related proteins. Combined with bioinformatics prediction and functional rescue experiments, the regulatory effect of FOXK1 on AKT2 was verified. Results: FOXK1 was highly expressed in LSCC tissues and cells (P < 0.01), and was mainly localized in the cell nucleus; high FOXK1 expression was associated with a higher TNM stage (P < 0.05), and a lower 5-year survival rate (P < 0.05); FOXK1 overexpression significantly promoted the proliferation, migration and invasion of TU177 cells and induced EMT (P < 0.01 or P < 0.05), whereas FOXK1 knockdown produced the opposite effects; FOXK1 upregulated AKT2 expression and activated the PI3K/ AKT signaling pathway; knockdown of AKT2 partially reversed the promoting effects of FOXK1 overexpression on proliferation, migration, invasion and EMT progression (P < 0.01 or P < 0.05). Conclusion: FOXK1 is highly expressed in LSCC and is closely associated with tumor progression and poor prognosis. FOXK1 may activate the PI3K/AKT pathway by upregulating AKT2 expression, thereby inducing EMT and promoting the malignant biological behaviors of LSCC cells.
Objective: To investigate the effects of FOXK1 on the proliferation, migration and invasion of laryngeal squamous cell carcinoma (LSCC) and the prognosis of patients, as well as its molecular mechanism. Methods: RT-qPCR and immunohistochemistry were applied to determine FOXK1 expression in LSCC tissues and TU177 cells, with subsequent analysis of its association with clinicopathological parameters and patient prognosis. FOXK1 overexpression and knockdown vectors were constructed and transfected into LSCC cell line TU177. MTS assay, colony formation assay, scratch wound healing assay, and Transwell assay were employed to detect changes in the malignant biological behaviors of cells. RT-qPCR was employed to detect the mRNA expression of epithelial- mesenchymal transition (EMT)-related factors, and Western blotting was used to detect the protein expression of PI3K/AKT signaling pathway-related proteins. Combined with bioinformatics prediction and functional rescue experiments, the regulatory effect of FOXK1 on AKT2 was verified. Results: FOXK1 was highly expressed in LSCC tissues and cells (P < 0.01), and was mainly localized in the cell nucleus; high FOXK1 expression was associated with a higher TNM stage (P < 0.05), and a lower 5-year survival rate (P < 0.05); FOXK1 overexpression significantly promoted the proliferation, migration and invasion of TU177 cells and induced EMT (P < 0.01 or P < 0.05), whereas FOXK1 knockdown produced the opposite effects; FOXK1 upregulated AKT2 expression and activated the PI3K/ AKT signaling pathway; knockdown of AKT2 partially reversed the promoting effects of FOXK1 overexpression on proliferation, migration, invasion and EMT progression (P < 0.01 or P < 0.05). Conclusion: FOXK1 is highly expressed in LSCC and is closely associated with tumor progression and poor prognosis. FOXK1 may activate the PI3K/AKT pathway by upregulating AKT2 expression, thereby inducing EMT and promoting the malignant biological behaviors of LSCC cells.
2026, 33(7):763-775.
DOI: 10.3872/j.issn.1007-385X.2026.07.007
Abstract:
Objective: To investigate the expression of β -galactoside α2, 6-sialyltransferase 1 (ST6GAL1) and dual-specificity phosphatase 26 (DUSP26) in colorectal cancer (CRC), and their effects on macrophage polarization and tumor progression. Methods: A total of 126 patients with CRC were enrolled. Immunohistochemical staining was used to detect the expression of ST6GAL1 and DUSP26 proteins in cancer tissues and adjacent tissues. Western blotting, co-immunoprecipitation, exosome characterization, flow cytometry, ELISA, and immunofluorescence were performed to analyze the effects of ST6GAL1, DUSP26, and related signaling pathways on CRC cell-derived exosomes, M2 macrophage polarization, mitochondrial function, and endoplasmic reticulum stress. ST6GAL1 knockout (ST6GAL1-KO) and DUSP26 overexpression (DUSP26-OE) cell models were established using CRISPR/Cas9 and lentiviral systems, respectively. A mouse tumor model was used to evaluate the effects of combined ST6GAL1 knockout and DUSP26 overexpression (ST6GAL1-KO + DUSP26-OE) intervention on tumor growth, cell proliferation, and apoptosis. Results: The positive rate of ST6GAL1 protein was significantly higher in CRC tissues than in adjacent normal tissues, whereas the positive rate of DUSP26 protein was significantly lower in CRC tissues than in adjacent normal tissues (both P < 0.001). ST6GAL1 protein expression was significantly higher in CRC cells than in normal colonic epithelial cells, whereas DUSP26 protein expression and the p-JNK/ JNK and p-c-JUN/c-JUN ratios were significantly lower than those in normal colonic epithelial cells (all P < 0.05). CRC cell- derived exosomes significantly promoted M2 macrophage polarization and upregulated the expression of the downstream proteins p-Syk, p-PI3K, and p-AKT, as well as the mitochondrial dysfunction-associated protein DRP1, and the endoplasmic reticulum stress- related proteins CHOP and GRP78 (all P < 0.01). Exosomes derived from DUSP26-OE or ST6GAL1-KO CRC cells inhibited these effects (P < 0.05 or P < 0.01). Animal experiments showed that tumor volume was significantly lower in the ST6GAL1-KO and DUSP26-OE groups than in the Vector group, and the combined ST6GAL1-KO and DUSP26-OE intervention group showed the most pronounced tumor-suppressive effect (all P < 0.001). In the combined intervention group, the positive rate of the cell proliferation marker PCNA was significantly decreased, whereas the number of TUNEL-positive cells was significantly increased (P < 0.05 or P < 0.001). ST6GAL1-KO and DUSP26-OE significantly reduced the positive rates of GRP78 and DRP1 and the proportion of M2 macrophages in mice. Conclusion: In CRC, high ST6GAL1 expression may participate in the regulation of M2 macrophage polarization and stress-related protein expression by affecting exosomal sialylation levels, while low DUSP26 expression may weaken the negative regulation of ST6GAL1 expression mediated by JNK-related pathways. Combined intervention targeting both factors exerted a more pronounced inhibitory effect on xenograft tumor growth.
Objective: To investigate the expression of β -galactoside α2, 6-sialyltransferase 1 (ST6GAL1) and dual-specificity phosphatase 26 (DUSP26) in colorectal cancer (CRC), and their effects on macrophage polarization and tumor progression. Methods: A total of 126 patients with CRC were enrolled. Immunohistochemical staining was used to detect the expression of ST6GAL1 and DUSP26 proteins in cancer tissues and adjacent tissues. Western blotting, co-immunoprecipitation, exosome characterization, flow cytometry, ELISA, and immunofluorescence were performed to analyze the effects of ST6GAL1, DUSP26, and related signaling pathways on CRC cell-derived exosomes, M2 macrophage polarization, mitochondrial function, and endoplasmic reticulum stress. ST6GAL1 knockout (ST6GAL1-KO) and DUSP26 overexpression (DUSP26-OE) cell models were established using CRISPR/Cas9 and lentiviral systems, respectively. A mouse tumor model was used to evaluate the effects of combined ST6GAL1 knockout and DUSP26 overexpression (ST6GAL1-KO + DUSP26-OE) intervention on tumor growth, cell proliferation, and apoptosis. Results: The positive rate of ST6GAL1 protein was significantly higher in CRC tissues than in adjacent normal tissues, whereas the positive rate of DUSP26 protein was significantly lower in CRC tissues than in adjacent normal tissues (both P < 0.001). ST6GAL1 protein expression was significantly higher in CRC cells than in normal colonic epithelial cells, whereas DUSP26 protein expression and the p-JNK/ JNK and p-c-JUN/c-JUN ratios were significantly lower than those in normal colonic epithelial cells (all P < 0.05). CRC cell- derived exosomes significantly promoted M2 macrophage polarization and upregulated the expression of the downstream proteins p-Syk, p-PI3K, and p-AKT, as well as the mitochondrial dysfunction-associated protein DRP1, and the endoplasmic reticulum stress- related proteins CHOP and GRP78 (all P < 0.01). Exosomes derived from DUSP26-OE or ST6GAL1-KO CRC cells inhibited these effects (P < 0.05 or P < 0.01). Animal experiments showed that tumor volume was significantly lower in the ST6GAL1-KO and DUSP26-OE groups than in the Vector group, and the combined ST6GAL1-KO and DUSP26-OE intervention group showed the most pronounced tumor-suppressive effect (all P < 0.001). In the combined intervention group, the positive rate of the cell proliferation marker PCNA was significantly decreased, whereas the number of TUNEL-positive cells was significantly increased (P < 0.05 or P < 0.001). ST6GAL1-KO and DUSP26-OE significantly reduced the positive rates of GRP78 and DRP1 and the proportion of M2 macrophages in mice. Conclusion: In CRC, high ST6GAL1 expression may participate in the regulation of M2 macrophage polarization and stress-related protein expression by affecting exosomal sialylation levels, while low DUSP26 expression may weaken the negative regulation of ST6GAL1 expression mediated by JNK-related pathways. Combined intervention targeting both factors exerted a more pronounced inhibitory effect on xenograft tumor growth.
2026, 33(7):776-784.
DOI: 10.3872/j.issn.1007-385X.2026.07.008
Abstract:
恶性肿瘤是全球性重大公共卫生问题。溶瘤病毒（OV）作为新型肿瘤免疫疗法，可靶向裂解肿瘤细胞并激活机体系统性抗肿瘤免疫，具有独特治疗价值。然而，天然OV存在安全性、靶向能力、体内递送效率及宿主抗病毒免疫清除等问题，使其临床转化进程受限。因此，基于工程化改造策略的新一代OV成为当前的研究热点。该策略通过基因编辑改良病毒靶向复制特性、导入功能基因逆转肿瘤微环境（TME）免疫抑制效应并结合新型递送技术突破给药屏障，显著提升OV疗效。目前，OV的临床研究已从单药治疗走向多手段联合治疗，与免疫检查点抑制剂（ICI）、放化疗和细胞疗法联用在多项研究中展现出良好前景。依托合成生物学与基因编辑技术，OV逐步迈向可编辑、可响应、个体化研发。本文综述OV的工程化改造方案，以期为突破现有治疗瓶颈提供助力，为联合疗法与个体化抗肿瘤方案的设计提供参考。
恶性肿瘤是全球性重大公共卫生问题。溶瘤病毒（OV）作为新型肿瘤免疫疗法，可靶向裂解肿瘤细胞并激活机体系统性抗肿瘤免疫，具有独特治疗价值。然而，天然OV存在安全性、靶向能力、体内递送效率及宿主抗病毒免疫清除等问题，使其临床转化进程受限。因此，基于工程化改造策略的新一代OV成为当前的研究热点。该策略通过基因编辑改良病毒靶向复制特性、导入功能基因逆转肿瘤微环境（TME）免疫抑制效应并结合新型递送技术突破给药屏障，显著提升OV疗效。目前，OV的临床研究已从单药治疗走向多手段联合治疗，与免疫检查点抑制剂（ICI）、放化疗和细胞疗法联用在多项研究中展现出良好前景。依托合成生物学与基因编辑技术，OV逐步迈向可编辑、可响应、个体化研发。本文综述OV的工程化改造方案，以期为突破现有治疗瓶颈提供助力，为联合疗法与个体化抗肿瘤方案的设计提供参考。
9 Advances in the establishment and clinical application of circulating tumor cell-derived organoids
2026, 33(7):785-792.
DOI: 10.3872/j.issn.1007-385X.2026.07.009
Abstract:
循环肿瘤细胞衍生类器官（CTCDO）整合了液体活检与类器官技术的优势，能够在体外重建患者肿瘤的三维结构与生理功能，为肿瘤研究提供独特的活细胞模型。本文综述了CTCDO在构建技术、验证方法及临床转化中的研究进展。首先，重点介绍CTCDO构建的核心技术流程，包括基于生物特性和物理特性的综合策略捕获与富集高活性循环肿瘤细胞（CTC），建立成分明确且可标准化扩增的三维培养体系，以及工程化扩增与高维动态表征的创新融合。其次，阐述基于“基因-病理-功能”整合框架的CTCDO模型验证体系及其在重现肿瘤异质性和药物应答方面的可靠性。最后，进一步探讨当前面临的CTC稀有性、培养成功率低及标准化不足等挑战，并展望CTCDO向高通量集成化、免疫共培养及自动化方向的发展前景。
循环肿瘤细胞衍生类器官（CTCDO）整合了液体活检与类器官技术的优势，能够在体外重建患者肿瘤的三维结构与生理功能，为肿瘤研究提供独特的活细胞模型。本文综述了CTCDO在构建技术、验证方法及临床转化中的研究进展。首先，重点介绍CTCDO构建的核心技术流程，包括基于生物特性和物理特性的综合策略捕获与富集高活性循环肿瘤细胞（CTC），建立成分明确且可标准化扩增的三维培养体系，以及工程化扩增与高维动态表征的创新融合。其次，阐述基于“基因-病理-功能”整合框架的CTCDO模型验证体系及其在重现肿瘤异质性和药物应答方面的可靠性。最后，进一步探讨当前面临的CTC稀有性、培养成功率低及标准化不足等挑战，并展望CTCDO向高通量集成化、免疫共培养及自动化方向的发展前景。
2026, 33(7):793-800.
DOI: 10.3872/j.issn.1007-385X.2026.07.010
Abstract:
周细胞向肌成纤维细胞样及肿瘤相关成纤维细胞（CAF）样表型转化是器官纤维化及肿瘤基质重塑中的重要细胞学过程。本文围绕该过程的转化证据、核心分子网络、疾病情境特异性及潜在干预策略进行综述。现有研究表明，在器官纤维化中，部分周细胞可获得肌成纤维细胞样表型，参与细胞外基质（ECM）沉积、组织结构破坏和功能损害；在肿瘤微环境（TME）中，周细胞可发生CAF样表型转化，进而通过基质重塑、免疫排斥和旁分泌信号等方式促进肿瘤进展及治疗抵抗。该过程主要受转化生长因子β（TGF-β）/Smad 与血小板源性生长因子（PDGF）/血小板源性生长因子受体β（PDGFR-β）信号轴调控，并受Notch、Hippo/YAP、Toll样受体4（TLR4）/NF-κB等通路影响。基于上述认识，靶向周细胞病理性表型转化的策略主要包括抑制促纤维化信号通路、改善周细胞-内皮细胞相互作用及识别并干预特定促纤维化细胞亚群。系统解析该过程及其微环境相互作用，有助于拓展抗纤维化治疗靶点，并为改善肿瘤免疫治疗及其他生物治疗疗效提供理论依据。
周细胞向肌成纤维细胞样及肿瘤相关成纤维细胞（CAF）样表型转化是器官纤维化及肿瘤基质重塑中的重要细胞学过程。本文围绕该过程的转化证据、核心分子网络、疾病情境特异性及潜在干预策略进行综述。现有研究表明，在器官纤维化中，部分周细胞可获得肌成纤维细胞样表型，参与细胞外基质（ECM）沉积、组织结构破坏和功能损害；在肿瘤微环境（TME）中，周细胞可发生CAF样表型转化，进而通过基质重塑、免疫排斥和旁分泌信号等方式促进肿瘤进展及治疗抵抗。该过程主要受转化生长因子β（TGF-β）/Smad 与血小板源性生长因子（PDGF）/血小板源性生长因子受体β（PDGFR-β）信号轴调控，并受Notch、Hippo/YAP、Toll样受体4（TLR4）/NF-κB等通路影响。基于上述认识，靶向周细胞病理性表型转化的策略主要包括抑制促纤维化信号通路、改善周细胞-内皮细胞相互作用及识别并干预特定促纤维化细胞亚群。系统解析该过程及其微环境相互作用，有助于拓展抗纤维化治疗靶点，并为改善肿瘤免疫治疗及其他生物治疗疗效提供理论依据。
11 Research advances in mesenchymal stem cell-derived exosomes for the treatment of hepatic fibrosis
2026, 33(7):801-807.
DOI: 10.3872/j.issn.1007-385X.2026.07.011
Abstract:
肝纤维化（HF）是肝损伤后异常修复的核心病理过程，是肝硬化和肝细胞癌发生发展的重要基础，其发生涉及肝细胞损伤、慢性炎症、肝星状细胞（HSC）活化及细胞外基质（ECM）过度沉积等复杂病理过程。现有临床干预仍以病因控制为主，终末期患者主要依赖肝移植，疗效及可及性均存在局限，因此开发能够阻断或逆转纤维化进程的新型治疗策略具有重要意义。间充质干细胞来源外泌体（MSC-Exo）作为一种新兴的无细胞治疗策略，可通过递送miRNA、蛋白质等生物活性物质，调节炎症反应、阻断促纤维化信号、保护肝细胞并促进再生修复、调控细胞自噬与铁死亡并拮抗氧化应激，从多环节发挥抗纤维化作用。本文围绕MSC-Exo治疗HF的主要机制、作为药物递送载体的研究进展及临床转化挑战进行综述。综合现有研究，MSC-Exo在临床前模型中显示出一定抗纤维化潜力，但相关证据主要来源于细胞和动物实验，仍存在来源异质性、制备与质控标准不统一、体内靶向递送效率不足及临床验证缺乏等问题。未来需通过标准化生产、工程化改造和多中心前瞻性研究进一步验证其安全性与有效性，以推动MSC-Exo向HF精准治疗转化。
肝纤维化（HF）是肝损伤后异常修复的核心病理过程，是肝硬化和肝细胞癌发生发展的重要基础，其发生涉及肝细胞损伤、慢性炎症、肝星状细胞（HSC）活化及细胞外基质（ECM）过度沉积等复杂病理过程。现有临床干预仍以病因控制为主，终末期患者主要依赖肝移植，疗效及可及性均存在局限，因此开发能够阻断或逆转纤维化进程的新型治疗策略具有重要意义。间充质干细胞来源外泌体（MSC-Exo）作为一种新兴的无细胞治疗策略，可通过递送miRNA、蛋白质等生物活性物质，调节炎症反应、阻断促纤维化信号、保护肝细胞并促进再生修复、调控细胞自噬与铁死亡并拮抗氧化应激，从多环节发挥抗纤维化作用。本文围绕MSC-Exo治疗HF的主要机制、作为药物递送载体的研究进展及临床转化挑战进行综述。综合现有研究，MSC-Exo在临床前模型中显示出一定抗纤维化潜力，但相关证据主要来源于细胞和动物实验，仍存在来源异质性、制备与质控标准不统一、体内靶向递送效率不足及临床验证缺乏等问题。未来需通过标准化生产、工程化改造和多中心前瞻性研究进一步验证其安全性与有效性，以推动MSC-Exo向HF精准治疗转化。
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