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Volume 33,Issue 1,2026 Table of Contents
2026, 33(1):1-11.
DOI: 10.3872/j.issn.1007-385X.2026.01.001
Abstract:
[Abstract] While murine models remain the cornerstone of biomedical research and play important roles in the exploration of human disease mechanism and therapeutic strategies, inherent genetic and immunological discrepancies between species constitute a major barrier to the translational success of basic research. Humanized immune system mouse models have therefore emerged with great significance and broad translational potential. This review systematically outlines the evolution of humanized immune system mouse models and delineates the key technical development and optimizing strategies from first-generation models relying on cell or tissue transplantation to second-generation and more refined genetically engineered models, driven by the incorporation of human cytokine expression and CRISPR/Cas9 technology. Special attention is given to technical advancements of the new-generation model in optimizing myeloid and NK cell development and accurately recapitulating the human tumor immune microenvironment. Additionally, this article provides an in-depth analysis of the application and challenges of these humanized immune system mouse models in the evaluation of immune checkpoint inhibitors, bispecific antibodies, antibody-drug conjugates, immune cell therapies and other therapeutic modalities, as well as toxicity prediction such as cytokine release syndrome. Concluding with a perspective on the development of immune system humanized and personalized models in precision medicine and pre-clinical assessment, this review aims to offer insights into optimizing new drug development strategies and promoting translational success rates.
[Abstract] While murine models remain the cornerstone of biomedical research and play important roles in the exploration of human disease mechanism and therapeutic strategies, inherent genetic and immunological discrepancies between species constitute a major barrier to the translational success of basic research. Humanized immune system mouse models have therefore emerged with great significance and broad translational potential. This review systematically outlines the evolution of humanized immune system mouse models and delineates the key technical development and optimizing strategies from first-generation models relying on cell or tissue transplantation to second-generation and more refined genetically engineered models, driven by the incorporation of human cytokine expression and CRISPR/Cas9 technology. Special attention is given to technical advancements of the new-generation model in optimizing myeloid and NK cell development and accurately recapitulating the human tumor immune microenvironment. Additionally, this article provides an in-depth analysis of the application and challenges of these humanized immune system mouse models in the evaluation of immune checkpoint inhibitors, bispecific antibodies, antibody-drug conjugates, immune cell therapies and other therapeutic modalities, as well as toxicity prediction such as cytokine release syndrome. Concluding with a perspective on the development of immune system humanized and personalized models in precision medicine and pre-clinical assessment, this review aims to offer insights into optimizing new drug development strategies and promoting translational success rates.
2026, 33(1):12-19.
DOI: 10.3872/j.issn.1007-385X.2026.01.002
Abstract:
[Abstract] Objective: To study the effects of circular RNA CEMIP (circCEMIP) on the proliferation, migration and invasion of bladder cancer UMUC-3 cells and its molecular mechanism. Methods: Expression of circCEMIP in bladder cancer tissues was analyzed using The Cancer Genome Atlas (TCGA) database, and its correlations with the clinical stage and overall survival of bladder cancer patients were evaluated. The expression levels of circCEMIP in bladder cancer cell lines (5637, UMUC-3, MGH-U3, J82, and T24) were detected by qPCR. Using RNA interference technology, UMUC-3 cells were transfected with si-circCEMIP, negative control (si-NC), anti-miR-335, and negative control (anti-miR-NC), respectively, and assigned into four groups: the si-circCEMIP group, the si-NC group, the si-circCEMIP + anti-miR-335 group, and the si-circCEMIP + anti-miR-NC group. Colony formation assay, wound healing assay, and Transwell assay were used to detect the effects of the expressions of circCEMIP and miR-335 on the proliferation, migration, and invasion of UMUC-3 cells, respectively. Dual-luciferase reporter gene assay was performed to verify the targeting relationship between circCEMIP and miR-335. WB analysis was used to detect the expression of proteins related to the VEGF-C signaling pathway. A UMUC-3 cell nude mouse subcutaneous xenograft model was established to observe the effect of circCEMIP knockdown on the growth of bladder cancer xenografts. Results: circCEMIP was highly expressed in bladder cancer tissues (P < 0.01) and its expression level was positively correlated with the clinical stage of bladder cancer patients (P < 0.01). The survival rate of bladder cancer patients with high expression of circCEMIP was comparatively lower (P < 0.01). circCEMIP in bladder cancer cell lines 5637, UMUC-3, MGH-U3, J82, and T24 was highly expressed (all P < 0.01). circCEMIP knockdown significantly reduced the proliferation, migration, and invasion abilities of UMUC-3 cells (all P < 0.01). circCEMIP can be target bound to miR-335 (P < 0.01), and circCEMIP knockdown could significantly upregulate the expression of miR-335 (P < 0.01). Suppression of miR-335 expression could reverse the inhibitory effect of circCEMIP knockdown on the proliferation, migration, and invasion of UMUC-3 cells (all P < 0.01). Knockdown of circCEMIP could significantly downregulate the expressions of VEGF-C, MMP-2, MMP-9, and β-catenin proteins in the VEGF-C signaling pathway (all P < 0.01). Suppression of miR-335 expression could partially reverse the inhibitory effect of circCEMIP knockdown on the expressions of VEGF-C signaling pathway proteins (all P < 0.01). In vivo experiments confirmed that silencing circCEMIP inhibited the growth of bladder cancer xenografts in nude mice (P < 0.01). Conclusion: Knockdown of circCEMIP suppresses the proliferation, migration and invasion of bladder cancer UMUC-3 cells by upregulating miR-335.
[Abstract] Objective: To study the effects of circular RNA CEMIP (circCEMIP) on the proliferation, migration and invasion of bladder cancer UMUC-3 cells and its molecular mechanism. Methods: Expression of circCEMIP in bladder cancer tissues was analyzed using The Cancer Genome Atlas (TCGA) database, and its correlations with the clinical stage and overall survival of bladder cancer patients were evaluated. The expression levels of circCEMIP in bladder cancer cell lines (5637, UMUC-3, MGH-U3, J82, and T24) were detected by qPCR. Using RNA interference technology, UMUC-3 cells were transfected with si-circCEMIP, negative control (si-NC), anti-miR-335, and negative control (anti-miR-NC), respectively, and assigned into four groups: the si-circCEMIP group, the si-NC group, the si-circCEMIP + anti-miR-335 group, and the si-circCEMIP + anti-miR-NC group. Colony formation assay, wound healing assay, and Transwell assay were used to detect the effects of the expressions of circCEMIP and miR-335 on the proliferation, migration, and invasion of UMUC-3 cells, respectively. Dual-luciferase reporter gene assay was performed to verify the targeting relationship between circCEMIP and miR-335. WB analysis was used to detect the expression of proteins related to the VEGF-C signaling pathway. A UMUC-3 cell nude mouse subcutaneous xenograft model was established to observe the effect of circCEMIP knockdown on the growth of bladder cancer xenografts. Results: circCEMIP was highly expressed in bladder cancer tissues (P < 0.01) and its expression level was positively correlated with the clinical stage of bladder cancer patients (P < 0.01). The survival rate of bladder cancer patients with high expression of circCEMIP was comparatively lower (P < 0.01). circCEMIP in bladder cancer cell lines 5637, UMUC-3, MGH-U3, J82, and T24 was highly expressed (all P < 0.01). circCEMIP knockdown significantly reduced the proliferation, migration, and invasion abilities of UMUC-3 cells (all P < 0.01). circCEMIP can be target bound to miR-335 (P < 0.01), and circCEMIP knockdown could significantly upregulate the expression of miR-335 (P < 0.01). Suppression of miR-335 expression could reverse the inhibitory effect of circCEMIP knockdown on the proliferation, migration, and invasion of UMUC-3 cells (all P < 0.01). Knockdown of circCEMIP could significantly downregulate the expressions of VEGF-C, MMP-2, MMP-9, and β-catenin proteins in the VEGF-C signaling pathway (all P < 0.01). Suppression of miR-335 expression could partially reverse the inhibitory effect of circCEMIP knockdown on the expressions of VEGF-C signaling pathway proteins (all P < 0.01). In vivo experiments confirmed that silencing circCEMIP inhibited the growth of bladder cancer xenografts in nude mice (P < 0.01). Conclusion: Knockdown of circCEMIP suppresses the proliferation, migration and invasion of bladder cancer UMUC-3 cells by upregulating miR-335.
2026, 33(1):20-27.
DOI: 10.3872/j.issn.1007-385X.2026.01.003
Abstract:
[Abstract] Objective: To investigate the effects and mechanisms of glycocholic acid (GCA) on the radiosensitivity of mice with lung adenocarcinoma A549 cell transplantation tumors. Methods: A lung adenocarcinoma A549 cell xenograft nude mouse model was established and randomized into four groups: the transplanted tumor control group (the control group), the GCA group, the radiotherapy (RT) group, and the GCA + RT group. The RT group and the GCA + RT group received a single 10 Gy irradiation; the GCA group and the GCA + RT group were gavaged with GCA at 280 mg/kg once daily for 7 consecutive days. Tumor volumes were monitored with two days between two measurements. After the last treatment mice were sacrificed and transplanted tumor tissues were collected. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in transplantation tumor tissues were detected. qPCR and Western blot (WB) were used to detect the mRNA and protein expression levels of key radiation-related genes (MCM6, ITGA6, CASP3, etc.) respectively. Histomorphology was examined by H-E staining. External validation of candidate genes was performed using GEO datasets (GSE276500, GSE294906, and GSE218171) and TCGA. Results: GCA alone showed modest inhibition effect on tumor growth, whereas the GCA + RT group with combined radioactive therapy exhibited reduced radiosensitivity compared to the RT group with RT alone (P < 0.05). GCA treatment significantly increased SOD activity (P < 0.01) and decreased GSH-Px activity (P < 0.01) in transplanted tumor tissues, indicating that GCA might change antioxidant enzyme balance and reduce radiation-induced oxidative stress in transplanted tumors. GCA interference upregulated the mRNA expressions of MCM6 and ITGA6 and downregulated the mRNA expression of CASP3 in transplanted tumors (all P < 0.05). The expression of MCM6 protein was significantly higher in the transplanted tumor tissues of the GCA + RT group than that of the control group (P < 0.05). H-E staining showed partial tumor necrosis in the GCA group, while the necrotic area in the GCA + RT group grew smaller than that in the RT group. GEO and TCGA database analyses supported the association of high MCM6/ITGA6 expressions with radioresistance and poorer prognosis. Conclusion: GCA reduces the radiosensitivity of A549 xenografts by changing oxidative stress and key signaling network, such as enhancing SOD, lowering GSH-Px, and upregulating ITGA6 or MCM6.
[Abstract] Objective: To investigate the effects and mechanisms of glycocholic acid (GCA) on the radiosensitivity of mice with lung adenocarcinoma A549 cell transplantation tumors. Methods: A lung adenocarcinoma A549 cell xenograft nude mouse model was established and randomized into four groups: the transplanted tumor control group (the control group), the GCA group, the radiotherapy (RT) group, and the GCA + RT group. The RT group and the GCA + RT group received a single 10 Gy irradiation; the GCA group and the GCA + RT group were gavaged with GCA at 280 mg/kg once daily for 7 consecutive days. Tumor volumes were monitored with two days between two measurements. After the last treatment mice were sacrificed and transplanted tumor tissues were collected. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in transplantation tumor tissues were detected. qPCR and Western blot (WB) were used to detect the mRNA and protein expression levels of key radiation-related genes (MCM6, ITGA6, CASP3, etc.) respectively. Histomorphology was examined by H-E staining. External validation of candidate genes was performed using GEO datasets (GSE276500, GSE294906, and GSE218171) and TCGA. Results: GCA alone showed modest inhibition effect on tumor growth, whereas the GCA + RT group with combined radioactive therapy exhibited reduced radiosensitivity compared to the RT group with RT alone (P < 0.05). GCA treatment significantly increased SOD activity (P < 0.01) and decreased GSH-Px activity (P < 0.01) in transplanted tumor tissues, indicating that GCA might change antioxidant enzyme balance and reduce radiation-induced oxidative stress in transplanted tumors. GCA interference upregulated the mRNA expressions of MCM6 and ITGA6 and downregulated the mRNA expression of CASP3 in transplanted tumors (all P < 0.05). The expression of MCM6 protein was significantly higher in the transplanted tumor tissues of the GCA + RT group than that of the control group (P < 0.05). H-E staining showed partial tumor necrosis in the GCA group, while the necrotic area in the GCA + RT group grew smaller than that in the RT group. GEO and TCGA database analyses supported the association of high MCM6/ITGA6 expressions with radioresistance and poorer prognosis. Conclusion: GCA reduces the radiosensitivity of A549 xenografts by changing oxidative stress and key signaling network, such as enhancing SOD, lowering GSH-Px, and upregulating ITGA6 or MCM6.
PENG Xiaomei
,
LUO Shunyuan
,
SHI Xinpeng
,
ZUO Haojian
,
CAO Luyang
,
CHEN Han
,
ZHOU Haitao
,
LUO Xiaoyong
2026, 33(1):28-36.
DOI: 10.3872/j.issn.1007-385X.2026.01.004
Abstract:
[Abstract] Objective: To explore the mechanisms by which DNA methyltransferase 1 (DNMT1) promotes the proliferation and migration of colorectal cancer (CRC) HCT8 cells through the stabilization of enhancer of zeste homolog 2 (EZH2). Methods: Bioinformatic analysis was performed to evaluate the expression level of DNMT1 in CRC tissues. Western blotting (WB) analysis was used to determine DNMT1 expression levels in CRC cell lines HCT8 and SW620, as well as in normal colon epithelial cells NCM460. HCT8 cells, after transfection with siRNA or lentivirus, were assigned to the following groups: the siNC group, the siDNMT1 group, the Vector group, the DNMT1-OE group, the siTRAF6 group, the siEZH2 group, the siEZH2 + DNMT1-OE group. The effects of DNMT1 knockdown or overexpression on the proliferation and migration of HCT8 cells were assessed by colony formation assay, CCK-8 assay, Transwell assay, and scratch assay. The protein and mRNA levels of EZH2 were measured by WB and quantitative realtime PCR (qPCR), respectively. EZH2 ubiquitination levels were examined using immunoprecipitation (IP). Intracellular colocalization of TRAF6 and EZH2 was evaluated by immunofluorescence double staining. The reversing effects of EZH2 on DNMT1 was confirmed by colony formation and wound healing (scratch) assays. Cancerous tissue and adjacent tissue specimens of 12 CRC patients surgically removed at Luoyang Central Hospital affiliated to Zhengzhou University between 2022 and 2025 were collected and immunohistochemical staining was performed to detect the expression levels of DNMT1, TRAF6, and EZH2 in CRC tissue samples. Results: DNMT1 expression was significantly higher in CRC tissues than in adjacent non-tumor tissues (P < 0.01), and its expression was also upregulated in CRC cells (P < 0.05). Knockdown of DNMT1 markedly inhibited the proliferation (P < 0.01) and migration (P < 0.01) of HCT8 cells, whereas overexpression of DNMT1 produced the opposite effects (both P < 0.01). DNMT1 positively regulated EZH2 at the protein level (P < 0.01) but did not affect its mRNA expression (P > 0.05). MG132 restored the protein expression of EZH2 (P < 0.01) and increased EZH2 ubiquitination levels in the siDNMT1 group, DNMT1 negatively regulated TRAF6 expression (P < 0.01). TRAF6 and EZH2 co-localized in cytoplasm, and IP confirmed that they bound directly. Knockdown of TRAF6 reduced EZH2 ubiquitination levels. EZH2 knockdown reversed the promotive effects of DNMT1 on HCT8 cell proliferation (P < 0.01) and migration (P < 0.01). DNMT1 and EZH2 were highly expressed in CRC tissues (P < 0.01), whereas TRAF6 expression was significantly lower in CRC tissues than in adjacent non-tumor tissues (P < 0.05). Conclusion: DNMT1 promotes the proliferation and migration of CRC cells through suppressing the stabilization of EZH2 by TRAF6. DNMT1, TRAF6, and EZH2 are expected to become diagnostic markers and therapeutic targets for CRC.
[Abstract] Objective: To explore the mechanisms by which DNA methyltransferase 1 (DNMT1) promotes the proliferation and migration of colorectal cancer (CRC) HCT8 cells through the stabilization of enhancer of zeste homolog 2 (EZH2). Methods: Bioinformatic analysis was performed to evaluate the expression level of DNMT1 in CRC tissues. Western blotting (WB) analysis was used to determine DNMT1 expression levels in CRC cell lines HCT8 and SW620, as well as in normal colon epithelial cells NCM460. HCT8 cells, after transfection with siRNA or lentivirus, were assigned to the following groups: the siNC group, the siDNMT1 group, the Vector group, the DNMT1-OE group, the siTRAF6 group, the siEZH2 group, the siEZH2 + DNMT1-OE group. The effects of DNMT1 knockdown or overexpression on the proliferation and migration of HCT8 cells were assessed by colony formation assay, CCK-8 assay, Transwell assay, and scratch assay. The protein and mRNA levels of EZH2 were measured by WB and quantitative realtime PCR (qPCR), respectively. EZH2 ubiquitination levels were examined using immunoprecipitation (IP). Intracellular colocalization of TRAF6 and EZH2 was evaluated by immunofluorescence double staining. The reversing effects of EZH2 on DNMT1 was confirmed by colony formation and wound healing (scratch) assays. Cancerous tissue and adjacent tissue specimens of 12 CRC patients surgically removed at Luoyang Central Hospital affiliated to Zhengzhou University between 2022 and 2025 were collected and immunohistochemical staining was performed to detect the expression levels of DNMT1, TRAF6, and EZH2 in CRC tissue samples. Results: DNMT1 expression was significantly higher in CRC tissues than in adjacent non-tumor tissues (P < 0.01), and its expression was also upregulated in CRC cells (P < 0.05). Knockdown of DNMT1 markedly inhibited the proliferation (P < 0.01) and migration (P < 0.01) of HCT8 cells, whereas overexpression of DNMT1 produced the opposite effects (both P < 0.01). DNMT1 positively regulated EZH2 at the protein level (P < 0.01) but did not affect its mRNA expression (P > 0.05). MG132 restored the protein expression of EZH2 (P < 0.01) and increased EZH2 ubiquitination levels in the siDNMT1 group, DNMT1 negatively regulated TRAF6 expression (P < 0.01). TRAF6 and EZH2 co-localized in cytoplasm, and IP confirmed that they bound directly. Knockdown of TRAF6 reduced EZH2 ubiquitination levels. EZH2 knockdown reversed the promotive effects of DNMT1 on HCT8 cell proliferation (P < 0.01) and migration (P < 0.01). DNMT1 and EZH2 were highly expressed in CRC tissues (P < 0.01), whereas TRAF6 expression was significantly lower in CRC tissues than in adjacent non-tumor tissues (P < 0.05). Conclusion: DNMT1 promotes the proliferation and migration of CRC cells through suppressing the stabilization of EZH2 by TRAF6. DNMT1, TRAF6, and EZH2 are expected to become diagnostic markers and therapeutic targets for CRC.
2026, 33(1):37-44.
DOI: 10.3872/j.issn.1007-385X.2026.01.005
Abstract:
[Abstract] Objective: To explore the molecular mechanism of spindlin1 (SPIN1) in promoting the migration and invasion of gastric adenocarcinoma cells. Methods: The correlations between SPIN1 mRNA expression and epithelial-mesenchymal transition (EMT) score and angiogenesis fraction in gastric adenocarcinoma tissues were analyzed by TCGA database. Tissue microarrays were constructed from a total of 52 surgically resected gastric adenocarcinoma specimens collected in Affiliated Provincial Hospital of Shandong First Medical University between August 2018 and November 2021. Each case included matched samples of gastric adenocarcinoma tissue, adjacent non?tumor tissue, and lymph node metastasis. The expression levels and correlation of SPIN1 and STAT3 in the gastric adenocarcinoma tissue samples were subsequently detected using immunohistochemistry. The effect of interfering with SPIN1 on the invasion and migration of gastric adenocarcinoma cells was investigated by Transwell chamber experiment. The GEPIA2 website was used to analyze the expression correlation between the SPIN1 gene and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway-related factor in gastric adenocarcinoma. Subsequently, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were employed to detect changes in the expression levels of JAK/STAT pathway-related mRNAs and proteins following SPIN1 interference. Results: Analysis of TCGA data showed that SPIN1 expression was positively correlated with both EMT and angiogenesis scores (both P < 0.05). Elevated expressions of SPIN1 and STAT3 were observed in gastric adenocarcinoma tissues and lymph node metastases (both P < 0.05) while they were negatively expressed in adjacent gastric mucosal tissues. A statistically significant positive correlation was found between SPIN1 and STAT3 expression (P < 0.05). Knockdown of SPIN1 significantly reduced the migratory and invasive capacities of gastric adenocarcinoma cells (P < 0.05 or P < 0.01). Furthermore, GEPIA2 analysis demonstrated significant positive correlations between the SPIN1 gene and the expression levels of JAK1, JAK2, STAT1, STAT2, and STAT3 (all P < 0.05). SPIN1 interference specifically reduced mRNA expressions of JAK2 and STAT3, while no significant changes were detected in JAK1, STAT1, or STAT2 mRNA levels. Western blotting confirmed that SPIN1 knockdown significantly decreased protein expression levels of JAK2, STAT3, phosphorylated JAK2 (p-JAK2), and phosphorylated STAT3 (p-STAT3) (all P < 0.01), whereas SPIN1 overexpression significantly upregulated the expressions of these proteins (all P < 0.01). Conclusion: SPIN1 can promote the migration and invasion of gastric adenocarcinoma cells by participating in the JAK2/STAT3 signaling pathway.
[Abstract] Objective: To explore the molecular mechanism of spindlin1 (SPIN1) in promoting the migration and invasion of gastric adenocarcinoma cells. Methods: The correlations between SPIN1 mRNA expression and epithelial-mesenchymal transition (EMT) score and angiogenesis fraction in gastric adenocarcinoma tissues were analyzed by TCGA database. Tissue microarrays were constructed from a total of 52 surgically resected gastric adenocarcinoma specimens collected in Affiliated Provincial Hospital of Shandong First Medical University between August 2018 and November 2021. Each case included matched samples of gastric adenocarcinoma tissue, adjacent non?tumor tissue, and lymph node metastasis. The expression levels and correlation of SPIN1 and STAT3 in the gastric adenocarcinoma tissue samples were subsequently detected using immunohistochemistry. The effect of interfering with SPIN1 on the invasion and migration of gastric adenocarcinoma cells was investigated by Transwell chamber experiment. The GEPIA2 website was used to analyze the expression correlation between the SPIN1 gene and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway-related factor in gastric adenocarcinoma. Subsequently, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were employed to detect changes in the expression levels of JAK/STAT pathway-related mRNAs and proteins following SPIN1 interference. Results: Analysis of TCGA data showed that SPIN1 expression was positively correlated with both EMT and angiogenesis scores (both P < 0.05). Elevated expressions of SPIN1 and STAT3 were observed in gastric adenocarcinoma tissues and lymph node metastases (both P < 0.05) while they were negatively expressed in adjacent gastric mucosal tissues. A statistically significant positive correlation was found between SPIN1 and STAT3 expression (P < 0.05). Knockdown of SPIN1 significantly reduced the migratory and invasive capacities of gastric adenocarcinoma cells (P < 0.05 or P < 0.01). Furthermore, GEPIA2 analysis demonstrated significant positive correlations between the SPIN1 gene and the expression levels of JAK1, JAK2, STAT1, STAT2, and STAT3 (all P < 0.05). SPIN1 interference specifically reduced mRNA expressions of JAK2 and STAT3, while no significant changes were detected in JAK1, STAT1, or STAT2 mRNA levels. Western blotting confirmed that SPIN1 knockdown significantly decreased protein expression levels of JAK2, STAT3, phosphorylated JAK2 (p-JAK2), and phosphorylated STAT3 (p-STAT3) (all P < 0.01), whereas SPIN1 overexpression significantly upregulated the expressions of these proteins (all P < 0.01). Conclusion: SPIN1 can promote the migration and invasion of gastric adenocarcinoma cells by participating in the JAK2/STAT3 signaling pathway.
HAN Panpan
,
CHEN Xujing
,
CHEN Hanyi
,
WANG Shuyan
,
ZHAN Sijian
,
MO Shengshui
,
CHEN Lili
,
FENG Yaru
,
LIN Wei
,
WANG Jianxun
2026, 33(1):45-50.
DOI: 10.3872/j.issn.1007-385X.2026.01.006
Abstract:
[Abstract] Objective: To generate low-affinity CD117-targeting CAR-T cells and investigate their in vitro cytotoxic effects on acute myeloid leukemia (AML) Kasumi-1 cells. Methods: Low-affinity CD117-targeting monoclonal antibody (barzolvolimab) and Fab-79D VH and VL sequences were retrieved for the design of single-chain variable fragments (scFvs) with a VH-(G4S)?-VL configuration. These scFvs were then integrated individually into canonical second-generation chimeric antigen receptor (CAR) constructs harboring the 4-1BB costimulatory domain. Subsequent to gene synthesis, the resultant CAR sequences were subcloned into the pMFG retroviral vectors, yielding the CD117-79D CAR and CD117-0159 CAR plasmids, respectively. The two CAR plasmids were subjected to separate retroviral packaging and production procedures. After validation of viral titers, the recombinant retroviruses were transduced into activated T cells to generate CD117-79D CAR-T and CD117-0159 CAR-T cell products. The CAR-positive fractions of the two CAR-T cell populations were quantified utilizing flow cytometry. Untransduced T cells and the two engineered CAR-T cells were co-cultured independently with CD117 ? Kasumi-1 cells. Thereafter, the apoptotic rates of Kasumi-1 cells were detected via flow cytometry for the comparative evaluation of the anti-tumor activity of the two CAR-T cell products. Results: CD117-79D CAR-T and CD117-0159 CAR-T cells were successfully constructed, with positive rates of (59.4 ± 2.6)% and (62.5 ± 1.2)% , respectively. Untransduced T cells, CD117-79D CAR-T cells, and CD117-0159 CAR-T cells all exhibited stable proliferation in in vitro cultivation, and no statistically significant difference was observed in their proliferative abilities (all P > 0.05). Results of the in vitro cytotoxicity assay against Kasumi-1 cells demonstrated that, in varying effector-to-target ratios, both CD117-79D CAR-T and CD117-0159 CAR-T cells exerted significantly enhanced cytotoxicity compared with untransduced T cells (P < 0.05 or P < 0.01). However, no statistically significant difference was detected in the killing efficiency between the two CAR-T cell products (P > 0.05). Conclusion: CD117-79D CAR-T and CD117-0159 CAR-T cells with low-affinity were successfully generated. In vitro experiments verified that these CAR-T cells could effectively eliminate CD117? Kasumi-1 cells, thereby providing experimental evidence for the targeted therapy of AML.
[Abstract] Objective: To generate low-affinity CD117-targeting CAR-T cells and investigate their in vitro cytotoxic effects on acute myeloid leukemia (AML) Kasumi-1 cells. Methods: Low-affinity CD117-targeting monoclonal antibody (barzolvolimab) and Fab-79D VH and VL sequences were retrieved for the design of single-chain variable fragments (scFvs) with a VH-(G4S)?-VL configuration. These scFvs were then integrated individually into canonical second-generation chimeric antigen receptor (CAR) constructs harboring the 4-1BB costimulatory domain. Subsequent to gene synthesis, the resultant CAR sequences were subcloned into the pMFG retroviral vectors, yielding the CD117-79D CAR and CD117-0159 CAR plasmids, respectively. The two CAR plasmids were subjected to separate retroviral packaging and production procedures. After validation of viral titers, the recombinant retroviruses were transduced into activated T cells to generate CD117-79D CAR-T and CD117-0159 CAR-T cell products. The CAR-positive fractions of the two CAR-T cell populations were quantified utilizing flow cytometry. Untransduced T cells and the two engineered CAR-T cells were co-cultured independently with CD117 ? Kasumi-1 cells. Thereafter, the apoptotic rates of Kasumi-1 cells were detected via flow cytometry for the comparative evaluation of the anti-tumor activity of the two CAR-T cell products. Results: CD117-79D CAR-T and CD117-0159 CAR-T cells were successfully constructed, with positive rates of (59.4 ± 2.6)% and (62.5 ± 1.2)% , respectively. Untransduced T cells, CD117-79D CAR-T cells, and CD117-0159 CAR-T cells all exhibited stable proliferation in in vitro cultivation, and no statistically significant difference was observed in their proliferative abilities (all P > 0.05). Results of the in vitro cytotoxicity assay against Kasumi-1 cells demonstrated that, in varying effector-to-target ratios, both CD117-79D CAR-T and CD117-0159 CAR-T cells exerted significantly enhanced cytotoxicity compared with untransduced T cells (P < 0.05 or P < 0.01). However, no statistically significant difference was detected in the killing efficiency between the two CAR-T cell products (P > 0.05). Conclusion: CD117-79D CAR-T and CD117-0159 CAR-T cells with low-affinity were successfully generated. In vitro experiments verified that these CAR-T cells could effectively eliminate CD117? Kasumi-1 cells, thereby providing experimental evidence for the targeted therapy of AML.
LIU Yanhua
,
WANG Hongjuan
,
BAO Bojun
,
ZHU Junya
,
YI Nan
,
JI Yifei
,
HUANG Wei
,
ZHANG Li
,
LIU Guoliang
2026, 33(1):51-58.
DOI: 10.3872/j.issn.1007-385X.2026.01.007
Abstract:
[Abstract] Objective: To investigate the effects of ginkgolide B (GKB) on the proliferation, migration, apoptosis, and epithelialmesenchymal transition (EMT) of liver cancer cells by regulating the protein kinase R-like endoplasmic reticulum kinase (PERK)/ activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway. Methods: Human liver cancer cells MHCC-97H were randomly assigned into the control group, the GKB group, the GSK2656157 (PERK inhibitors) group, and the GKB + GSK2656157 group. After intervention with GKB and PERK inhibitors GSK2656157 on different groups, MTT assay and EdU staining were used to detect the proliferation activity and proliferation rate of cells in each group. Scratch assay and flow cytometry were used to detect the migration and apoptosis of cells in each group, respectively. Western blotting (WB) was used to detect the expression levels of EMT and PERK/ATF4/CHOP signaling pathway related proteins in each group. The MHCC-97H nude mouse transplant tumor model was constructed, and the tumor volumes of each group were measured after grouping and drug intervention. Immunohistochemistry and TUNEL staining were used to detect the proliferation and apoptosis of tumor cells in each group. In addition, WB was used to detect the expression levels of EMT and PERK/ATF4/CHOP signaling pathway related proteins in transplant tumor tissues of each group. Results: Compared with those in the control group, the cell activity, proliferation rate, migration rate, tumor volume, Ki-67 positive cell ratio, and relative expressions of MMP2, N-cadherin, and MMP9 proteins decreased significantly in the GKB group (all P < 0.05), while the apoptosis rate, TUNEL positive cell ratio, and the expressions of p-PERK/PERK, E-cadherin, ATF4, and CHOP proteins increased significantly (all P < 0.05). The changes in various indicators in the GSK2656157 group were the opposite of those in the GKB group (all P < 0.05). Compared with those in the GKB group, the cell activity, proliferation rate, migration rate, tumor volume, Ki-67 positive cell ratio, and expressions of MMP2, N-cadherin, and MMP9 proteins increased significantly in the GKB + GSK2656157 group (all P < 0.05), while the apoptosis rate, TUNEL positive cell ratio, and the expressions of p-PERK/PERK, E-cadherin, ATF4, and CHOP proteins reduced significantly (all P < 0.05). Conclusion: GKB can inhibit the proliferation, migration, and EMT of liver cancer MHCC-97H cells and promote their apoptosis by activating the PERK/ATF4/CHOP signaling pathway.
[Abstract] Objective: To investigate the effects of ginkgolide B (GKB) on the proliferation, migration, apoptosis, and epithelialmesenchymal transition (EMT) of liver cancer cells by regulating the protein kinase R-like endoplasmic reticulum kinase (PERK)/ activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway. Methods: Human liver cancer cells MHCC-97H were randomly assigned into the control group, the GKB group, the GSK2656157 (PERK inhibitors) group, and the GKB + GSK2656157 group. After intervention with GKB and PERK inhibitors GSK2656157 on different groups, MTT assay and EdU staining were used to detect the proliferation activity and proliferation rate of cells in each group. Scratch assay and flow cytometry were used to detect the migration and apoptosis of cells in each group, respectively. Western blotting (WB) was used to detect the expression levels of EMT and PERK/ATF4/CHOP signaling pathway related proteins in each group. The MHCC-97H nude mouse transplant tumor model was constructed, and the tumor volumes of each group were measured after grouping and drug intervention. Immunohistochemistry and TUNEL staining were used to detect the proliferation and apoptosis of tumor cells in each group. In addition, WB was used to detect the expression levels of EMT and PERK/ATF4/CHOP signaling pathway related proteins in transplant tumor tissues of each group. Results: Compared with those in the control group, the cell activity, proliferation rate, migration rate, tumor volume, Ki-67 positive cell ratio, and relative expressions of MMP2, N-cadherin, and MMP9 proteins decreased significantly in the GKB group (all P < 0.05), while the apoptosis rate, TUNEL positive cell ratio, and the expressions of p-PERK/PERK, E-cadherin, ATF4, and CHOP proteins increased significantly (all P < 0.05). The changes in various indicators in the GSK2656157 group were the opposite of those in the GKB group (all P < 0.05). Compared with those in the GKB group, the cell activity, proliferation rate, migration rate, tumor volume, Ki-67 positive cell ratio, and expressions of MMP2, N-cadherin, and MMP9 proteins increased significantly in the GKB + GSK2656157 group (all P < 0.05), while the apoptosis rate, TUNEL positive cell ratio, and the expressions of p-PERK/PERK, E-cadherin, ATF4, and CHOP proteins reduced significantly (all P < 0.05). Conclusion: GKB can inhibit the proliferation, migration, and EMT of liver cancer MHCC-97H cells and promote their apoptosis by activating the PERK/ATF4/CHOP signaling pathway.
2026, 33(1):59-65.
DOI: 10.3872/j.issn.1007-385X.2026.01.008
Abstract:
[Abstract] Objective: To investigate the effects and mechanisms of galangin (Gal) on the apoptosis and autophagy of gastric cancer NCI-N87 cells through regulating the AMPK/mTOR/ULK1 signaling pathway. Methods: Gastric cancer NCI-N87 cells were assigned into the control group, the dorsomorphin (DM, AMPK inhibitor) group, the Gal low-dose (Gal-L) group, the Gal high-dose (Gal-H) group, and the Gal-H + DM group. Cell proliferation, apoptosis, migration, and invasion abilities were detected using MTT assay, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blotting was used to detect the expression levels of PCNA, cleaved caspase-3 (C-caspase-3), immune evasion-related protein (B7H1), EMT, and AMPK/mTOR/ULK1 signaling pathway proteins. A NCI-N87 cell xenograft tumor model was established in nude mice to observe the inhibitory effects of Gal and 5-FU on the growth of transplant tumors. Results: Compared with the control group, the DM group exhibited significantly increased proliferation activity, scratch healing rate, number of invasive cells, and protein expression levels of N-cadherin, vimentin, PCNA, B7H1, p62, and p-mTOR/ mTOR in NCI-N87 cells (all P < 0.05), along with significantly decreased apoptosis rate and protein expression levels of C-caspase-3, E-cadherin, LC3Ⅱ/LC3Ⅰ, p-AMPK/AMPK, and p-ULK1/ULK1 (all P < 0.05). In contrast, both the Gal-L and Gal-H groups showed significantly decreased proliferation activity, scratch healing rate, number of invasive cells, and protein expression levels of N-cadherin, vimentin, PCNA, B7H1, p62, and p-mTOR/mTOR in NCI-N87 cells (all P < 0.05), while displaying significantly increased apoptosis rate and protein expression levels of C-caspase-3, E-cadherin, LC3Ⅱ/LC3Ⅰ, p-AMPK/AMPK, and p-ULK1/ULK1 (all P < 0.05). DM could partially reverse the inhibitory effect of Gal on the malignant biological behaviors of NCI-N87 cells (P < 0.05). Compared with the control group, both the Gal group and the 5-FU group exhibited significant reductions in tumor volume and mass, as well as a significant increase in the apoptosis rate of tumor tissue cells in nude mice (P < 0.05). Conclusion: Gal can promote the autophagy and apoptosis in gastric cancer NCI-N87 cells, inhibit their proliferation, migration, and invasion, which may be related to the activation of the AMPK/mTOR/ULK1 signaling pathway.
[Abstract] Objective: To investigate the effects and mechanisms of galangin (Gal) on the apoptosis and autophagy of gastric cancer NCI-N87 cells through regulating the AMPK/mTOR/ULK1 signaling pathway. Methods: Gastric cancer NCI-N87 cells were assigned into the control group, the dorsomorphin (DM, AMPK inhibitor) group, the Gal low-dose (Gal-L) group, the Gal high-dose (Gal-H) group, and the Gal-H + DM group. Cell proliferation, apoptosis, migration, and invasion abilities were detected using MTT assay, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blotting was used to detect the expression levels of PCNA, cleaved caspase-3 (C-caspase-3), immune evasion-related protein (B7H1), EMT, and AMPK/mTOR/ULK1 signaling pathway proteins. A NCI-N87 cell xenograft tumor model was established in nude mice to observe the inhibitory effects of Gal and 5-FU on the growth of transplant tumors. Results: Compared with the control group, the DM group exhibited significantly increased proliferation activity, scratch healing rate, number of invasive cells, and protein expression levels of N-cadherin, vimentin, PCNA, B7H1, p62, and p-mTOR/ mTOR in NCI-N87 cells (all P < 0.05), along with significantly decreased apoptosis rate and protein expression levels of C-caspase-3, E-cadherin, LC3Ⅱ/LC3Ⅰ, p-AMPK/AMPK, and p-ULK1/ULK1 (all P < 0.05). In contrast, both the Gal-L and Gal-H groups showed significantly decreased proliferation activity, scratch healing rate, number of invasive cells, and protein expression levels of N-cadherin, vimentin, PCNA, B7H1, p62, and p-mTOR/mTOR in NCI-N87 cells (all P < 0.05), while displaying significantly increased apoptosis rate and protein expression levels of C-caspase-3, E-cadherin, LC3Ⅱ/LC3Ⅰ, p-AMPK/AMPK, and p-ULK1/ULK1 (all P < 0.05). DM could partially reverse the inhibitory effect of Gal on the malignant biological behaviors of NCI-N87 cells (P < 0.05). Compared with the control group, both the Gal group and the 5-FU group exhibited significant reductions in tumor volume and mass, as well as a significant increase in the apoptosis rate of tumor tissue cells in nude mice (P < 0.05). Conclusion: Gal can promote the autophagy and apoptosis in gastric cancer NCI-N87 cells, inhibit their proliferation, migration, and invasion, which may be related to the activation of the AMPK/mTOR/ULK1 signaling pathway.
2026, 33(1):66-76.
DOI: 10.3872/j.issn.1007-385X.2026.01.009
Abstract:
[Abstract] Objective: To investigate the expression characteristics and prognostic significance of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and the uridine diphosphate-glucuronate decarboxylase 1 (UXS1) as well as the molecular mechanisms of the synergistic interaction between them in hepatocellular carcinoma (HCC). Methods: Transcriptomic data from multiple public databases, including UALCAN, cBioPortal, ENCORI, TISCH2, and GDSC were integrated to analyze the expressions, prognosis, functional enrichment, and drug sensitivity of IGF2BP3 and UXS1. Single-cell RNA sequencing (scRNA-seq) data from the GEO repository were further collected to examine cell-cell communication and single-cell metabolic activity, thereby systematically analyzing the specific function of the IGF2BP3- UXS1 axis in HCC. Results: The expressions of IGF2BP3 and UXS1 were significantly upregulated in HCC tissues, and high expressions of either gene were associated with markedly shorter overall survival (both P < 0.05). CRISPR-mediated knockout of IGF2BP3 or UXS1 substantially suppressed the proliferative capacity of multiple HCC cell lines. scRNA-seq analysis revealed broad expressions of both genes across hepatic cell population: IGF2BP3 expression was upregulated during late-stage hepatocyte differentiation, whereas UXS1 was highly expressed during early and mid differentiation stages. High expressions of IGF2BP3 or UXS1 significantly activated the MIF signaling pathway. Elevated expression of IGF2BP3 weakened the interactions between fibroblast-tumor cells, while high expression of UXS1 enhanced T-cell signal transduction. A significant positive correlation was observed between the expressions of IGF2BP3 and UXS1 (r = 0.432, P < 0.05). Silencing of the IGF2BP3 binding site resulted in changes in UXS1 expression levels (F = 0.333). Functional enrichment analyses indicated that IGF2BP3 and UXS1 synergistically regulated key biological processes, including energy metabolism and protein translation. Moreover, both genes showed strong associations with multiple glycometabolic pathways in high-expression tumor subpopulations. Patients with high IGF2BP3 or UXS1 expressions exhibited heightened sensitivity to uprosertib and pronounced resistance to navitoclax. Conclusion: IGF2BP3 and UXS1 are highly expressed in HCC. Both genes promote malignant biological behaviors of HCC by regulating coordinated reprogramming of glucose metabolism.
[Abstract] Objective: To investigate the expression characteristics and prognostic significance of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and the uridine diphosphate-glucuronate decarboxylase 1 (UXS1) as well as the molecular mechanisms of the synergistic interaction between them in hepatocellular carcinoma (HCC). Methods: Transcriptomic data from multiple public databases, including UALCAN, cBioPortal, ENCORI, TISCH2, and GDSC were integrated to analyze the expressions, prognosis, functional enrichment, and drug sensitivity of IGF2BP3 and UXS1. Single-cell RNA sequencing (scRNA-seq) data from the GEO repository were further collected to examine cell-cell communication and single-cell metabolic activity, thereby systematically analyzing the specific function of the IGF2BP3- UXS1 axis in HCC. Results: The expressions of IGF2BP3 and UXS1 were significantly upregulated in HCC tissues, and high expressions of either gene were associated with markedly shorter overall survival (both P < 0.05). CRISPR-mediated knockout of IGF2BP3 or UXS1 substantially suppressed the proliferative capacity of multiple HCC cell lines. scRNA-seq analysis revealed broad expressions of both genes across hepatic cell population: IGF2BP3 expression was upregulated during late-stage hepatocyte differentiation, whereas UXS1 was highly expressed during early and mid differentiation stages. High expressions of IGF2BP3 or UXS1 significantly activated the MIF signaling pathway. Elevated expression of IGF2BP3 weakened the interactions between fibroblast-tumor cells, while high expression of UXS1 enhanced T-cell signal transduction. A significant positive correlation was observed between the expressions of IGF2BP3 and UXS1 (r = 0.432, P < 0.05). Silencing of the IGF2BP3 binding site resulted in changes in UXS1 expression levels (F = 0.333). Functional enrichment analyses indicated that IGF2BP3 and UXS1 synergistically regulated key biological processes, including energy metabolism and protein translation. Moreover, both genes showed strong associations with multiple glycometabolic pathways in high-expression tumor subpopulations. Patients with high IGF2BP3 or UXS1 expressions exhibited heightened sensitivity to uprosertib and pronounced resistance to navitoclax. Conclusion: IGF2BP3 and UXS1 are highly expressed in HCC. Both genes promote malignant biological behaviors of HCC by regulating coordinated reprogramming of glucose metabolism.
2026, 33(1):77-83.
DOI: 10.3872/j.issn.1007-385X.2026.01.010
Abstract:
[Abstract] Objective: To investigate the clinicopathological characteristics and heterogeneity of the tumor immune microenvironment in hepatoid adenocarcinoma of the stomach (HAS), identify prognostic biomarkers, and elucidate the mechanisms underlying its aggressive phenotype and poor therapeutic response in order to provide a rationale for developing improved diagnostic and therapeutic strategies. Methods: A retrospective analysis was conducted on clinical information and pathological specimens from 65 HAS patients treated at the First Affiliated Hospital of Naval Medical University and the Second Affiliated Hospital of Naval Medical University between January 2013 and May 2025. Immunohistochemistry was employed to detect the expression patterns of molecules, such as hepatoid differentiation markers and neuroendocrine markers. Prognosis-related targets were identified using Kaplan-Meier survival analysis. Multispectral immunohistochemistry was utilized to characterize the spatial distribution of immune cell subsets within tumor regions, thereby elucidating the distinctive features of HAS immune microenvironment. Results: Among the 65 patients (male: 54 [83.1%]; female: 11 [16.9%]; median age: 68 years), tumors predominantly occurred in the gastric cardia (40%), followed by the antrum (32.3%) and the gastric body (27.7%). The median follow-up time was 23.18 months. Fifteen patients died; 46 survived and 4 were lost to follow-up. On pathological examination, the tumor specimens collected in gastric endoscopy and surgery presented mainly as firm, grayish-white masses which, under microscope, appeared to have intertwining distribution of moderately-to-poorly differentiated gastric adenocarcinoma and hepatocellular carcinoma (HCC)-like differentiation regions. Patients with neuroendocrine differentiation demonstrated higher lymph node involvement and shorter overall survival. Immune microenvironment analysis demonstrated that HAS, with sparse immune infiltration, presented a "cold tumor" phenotype. Immune cells were primarily localized at the periphery of gastric adenocarcinoma glands and lymphocyte infiltration was rarely seen within HCC-like differentiation regions. Conclusion: HAS exhibits highly aggressive biological behavior. Radical resection is the main therapy. Neuroendocrine differentiation suggests poor prognosis and is a key biomarker for personalized therapy. Deficient immune cell infiltration may correlate with its poor response to immunotherapy.
[Abstract] Objective: To investigate the clinicopathological characteristics and heterogeneity of the tumor immune microenvironment in hepatoid adenocarcinoma of the stomach (HAS), identify prognostic biomarkers, and elucidate the mechanisms underlying its aggressive phenotype and poor therapeutic response in order to provide a rationale for developing improved diagnostic and therapeutic strategies. Methods: A retrospective analysis was conducted on clinical information and pathological specimens from 65 HAS patients treated at the First Affiliated Hospital of Naval Medical University and the Second Affiliated Hospital of Naval Medical University between January 2013 and May 2025. Immunohistochemistry was employed to detect the expression patterns of molecules, such as hepatoid differentiation markers and neuroendocrine markers. Prognosis-related targets were identified using Kaplan-Meier survival analysis. Multispectral immunohistochemistry was utilized to characterize the spatial distribution of immune cell subsets within tumor regions, thereby elucidating the distinctive features of HAS immune microenvironment. Results: Among the 65 patients (male: 54 [83.1%]; female: 11 [16.9%]; median age: 68 years), tumors predominantly occurred in the gastric cardia (40%), followed by the antrum (32.3%) and the gastric body (27.7%). The median follow-up time was 23.18 months. Fifteen patients died; 46 survived and 4 were lost to follow-up. On pathological examination, the tumor specimens collected in gastric endoscopy and surgery presented mainly as firm, grayish-white masses which, under microscope, appeared to have intertwining distribution of moderately-to-poorly differentiated gastric adenocarcinoma and hepatocellular carcinoma (HCC)-like differentiation regions. Patients with neuroendocrine differentiation demonstrated higher lymph node involvement and shorter overall survival. Immune microenvironment analysis demonstrated that HAS, with sparse immune infiltration, presented a "cold tumor" phenotype. Immune cells were primarily localized at the periphery of gastric adenocarcinoma glands and lymphocyte infiltration was rarely seen within HCC-like differentiation regions. Conclusion: HAS exhibits highly aggressive biological behavior. Radical resection is the main therapy. Neuroendocrine differentiation suggests poor prognosis and is a key biomarker for personalized therapy. Deficient immune cell infiltration may correlate with its poor response to immunotherapy.
WANG Haoqiang
,
LIU Baiyang
,
YANG Ning
,
LIU Peng
,
CHENG Donghai
,
PENG Lijun
,
WANG Xianci
,
HUANG Xueqin
,
DONG Enlai
,
JIANG Yiming
,
ZHOU Juan
,
XIE Bo
2026, 33(1):84-90.
DOI: 10.3872/j.issn.1007-385X.2026.01.011
Abstract:
[Abstract] Objective: To investigate the clinical characteristics and prognostic factors of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) who received PD-1 inhibitor-based immunotherapy. Methods: A retrospective analysis was conducted on 95 patients with NPC diagnosed at General Hospital of the Southern Theater Command between March 2019 and July 2024. Clinical data, peripheral blood biochemical parameters, and immunological indicators were collected. Kaplan-Meier survival curves were used for prognostic comparisons. Log-rank test was used for comparison among groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results: Among the 95 patients, 81 were male and 14 were female, with a median age of 49.72 years (16-74 years). A total of 91 patients (95.79%) had stage Ⅳ disease. All patients received immunotherapy with or without chemotherapy. The median progression-free survival (mPFS) was 10.5 months, with an objective response rate (ORR) of 70.53% and a disease control rate (DCR) of 89.47%. Patients receiving platinum-based regimens had significantly longer PFS than those receiving non-platinum regimens. The paclitaxel + cisplatin + fluorouracil (TPF) regimen showed a longer PFS compared with the gemcitabine + cisplatin (GP) and paclitaxel + cisplatin (TP) regimen, although the differences were not statistically significant. No significant PFS differences were observed among different PD-1 inhibitor subgroups. Univariate and multivariate Cox analyses identified tumor recurrence status, baseline plasma EBV DNA status, number of treatment cycles, and baseline peripheral blood immune-inflammation index SII as independent efficacy predictors of PD-1 inhibitor-based therapy for patients with recurrent or metastatic NPC (all P < 0.05). Non-recurrent disease, baseline plasma EBV DNA positivity, 4 or more treatment cycles, and baseline peripheral blood SII < 772.81 were associated with better outcomes. Conclusion: In recurrent or metastatic NPC patients treated with PD-1 inhibitors, non-recurrent disease, baseline EBV DNA positivity, 4 or more treatment cycles, and peripheral blood SII < 772.81 were associated with prolonged PFS. These factors may help early identification of patients with suboptimal immunotherapy responses and enable timely individualized intervention.
[Abstract] Objective: To investigate the clinical characteristics and prognostic factors of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) who received PD-1 inhibitor-based immunotherapy. Methods: A retrospective analysis was conducted on 95 patients with NPC diagnosed at General Hospital of the Southern Theater Command between March 2019 and July 2024. Clinical data, peripheral blood biochemical parameters, and immunological indicators were collected. Kaplan-Meier survival curves were used for prognostic comparisons. Log-rank test was used for comparison among groups. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results: Among the 95 patients, 81 were male and 14 were female, with a median age of 49.72 years (16-74 years). A total of 91 patients (95.79%) had stage Ⅳ disease. All patients received immunotherapy with or without chemotherapy. The median progression-free survival (mPFS) was 10.5 months, with an objective response rate (ORR) of 70.53% and a disease control rate (DCR) of 89.47%. Patients receiving platinum-based regimens had significantly longer PFS than those receiving non-platinum regimens. The paclitaxel + cisplatin + fluorouracil (TPF) regimen showed a longer PFS compared with the gemcitabine + cisplatin (GP) and paclitaxel + cisplatin (TP) regimen, although the differences were not statistically significant. No significant PFS differences were observed among different PD-1 inhibitor subgroups. Univariate and multivariate Cox analyses identified tumor recurrence status, baseline plasma EBV DNA status, number of treatment cycles, and baseline peripheral blood immune-inflammation index SII as independent efficacy predictors of PD-1 inhibitor-based therapy for patients with recurrent or metastatic NPC (all P < 0.05). Non-recurrent disease, baseline plasma EBV DNA positivity, 4 or more treatment cycles, and baseline peripheral blood SII < 772.81 were associated with better outcomes. Conclusion: In recurrent or metastatic NPC patients treated with PD-1 inhibitors, non-recurrent disease, baseline EBV DNA positivity, 4 or more treatment cycles, and peripheral blood SII < 772.81 were associated with prolonged PFS. These factors may help early identification of patients with suboptimal immunotherapy responses and enable timely individualized intervention.
2026, 33(1):91-98.
DOI: 10.3872/j.issn.1007-385X.2026.01.012
Abstract:
[摘 要] 受基因调控及缺氧微环境等因素影响，胃癌细胞有着与正常细胞不同的代谢模式。胃癌细胞代谢重编程主要表现为 无氧糖酵解水平上调、谷氨酰胺成瘾及脂质代谢失调等特征。代谢重编程不仅能为胃癌细胞生长供给必需的物质与能量，其代 谢物还可作为信号分子调控基因表达及代谢途径，进而深度参与胃癌细胞增殖、分化与转移过程，对胃癌的发生发展及临床诊疗 具有关键影响。目前，基于胃癌细胞代谢重编程的基础探索与临床干预策略是胃癌治疗的重要突破口。本文通过回顾胃癌细胞 代谢重编程的特点、调控机制、病理作用等方面的基础研究及相应诊疗策略，为胃癌的预防、诊断及治疗提供新的思路。
[摘 要] 受基因调控及缺氧微环境等因素影响，胃癌细胞有着与正常细胞不同的代谢模式。胃癌细胞代谢重编程主要表现为 无氧糖酵解水平上调、谷氨酰胺成瘾及脂质代谢失调等特征。代谢重编程不仅能为胃癌细胞生长供给必需的物质与能量，其代 谢物还可作为信号分子调控基因表达及代谢途径，进而深度参与胃癌细胞增殖、分化与转移过程，对胃癌的发生发展及临床诊疗 具有关键影响。目前，基于胃癌细胞代谢重编程的基础探索与临床干预策略是胃癌治疗的重要突破口。本文通过回顾胃癌细胞 代谢重编程的特点、调控机制、病理作用等方面的基础研究及相应诊疗策略，为胃癌的预防、诊断及治疗提供新的思路。
13 The advantages and disadvantages of CRISPR-Cas9 technology in screening tumor therapeutic targets
2026, 33(1):99-104.
DOI: 10.3872/j.issn.1007-385X.2026.01.013
Abstract:
[摘 要] 成簇规律间隔短回文重复系统及相关蛋白9（CRISPR-Cas9）作为高效、特异的基因编辑工具，已在人类疾病，尤其是 肿瘤治疗领域被广泛研究。本文系统梳理CRISPR-Cas9的特点、机制与优势，重点分析该技术在肿瘤治疗靶点筛选中的新突破 与前沿应用，阐明CRISPR-Cas9在肿瘤生物治疗靶点筛选技术中的核心地位。同时，直面CRISPR-Cas9技术筛选靶点在当前临 床研究中面临的诸多挑战，深入探讨其局限性和关键瓶颈问题，展望其优化策略和未来发展趋势。
[摘 要] 成簇规律间隔短回文重复系统及相关蛋白9（CRISPR-Cas9）作为高效、特异的基因编辑工具，已在人类疾病，尤其是 肿瘤治疗领域被广泛研究。本文系统梳理CRISPR-Cas9的特点、机制与优势，重点分析该技术在肿瘤治疗靶点筛选中的新突破 与前沿应用，阐明CRISPR-Cas9在肿瘤生物治疗靶点筛选技术中的核心地位。同时，直面CRISPR-Cas9技术筛选靶点在当前临 床研究中面临的诸多挑战，深入探讨其局限性和关键瓶颈问题，展望其优化策略和未来发展趋势。
2026, 33(1):105-110.
DOI: 10.3872/j.issn.1007-385X.2026.01.014
Abstract:
[摘 要] 脂滴（LD）作为细胞内脂质储存和调控的关键细胞器，与肿瘤细胞的增殖、侵袭、转移及耐药密切相关。脂滴包被蛋白 （PLIN）家族在 LD 代谢调控中发挥着关键作用，其中 PLIN3 在多种肿瘤中高表达，与不良预后、肿瘤侵袭及耐药密切相关。 PLIN3广泛表达于多种细胞，主要定位于LD表面和细胞质，通过促进LD形成、稳定脂质储存及调控脂肪酸氧化维持能量平衡。 研究表明，PLIN3参与调控肿瘤细胞脂质代谢重编程、自噬以及免疫微环境等途径，其表达上调为肿瘤细胞提供更多的脂肪酸用 于β-氧化供能，维持其在应激环境下的生存。此外，PLIN3促进M2型肿瘤相关巨噬细胞极化，同时影响肿瘤细胞与T细胞的相 互作用，从而重塑肿瘤免疫微环境。PLIN3还通过激活Wnt/β-catenin、PI3K/Akt/mTOR等促癌信号通路，促进上皮-间质转化和耐 药性。本文综述了PLIN3在肿瘤中关键调控机制、研究进展以及作为治疗靶点的潜力，为开发特异性抑制剂和联合疗法提供理 论基础，为肿瘤的精准治疗提供新策略。
[摘 要] 脂滴（LD）作为细胞内脂质储存和调控的关键细胞器，与肿瘤细胞的增殖、侵袭、转移及耐药密切相关。脂滴包被蛋白 （PLIN）家族在 LD 代谢调控中发挥着关键作用，其中 PLIN3 在多种肿瘤中高表达，与不良预后、肿瘤侵袭及耐药密切相关。 PLIN3广泛表达于多种细胞，主要定位于LD表面和细胞质，通过促进LD形成、稳定脂质储存及调控脂肪酸氧化维持能量平衡。 研究表明，PLIN3参与调控肿瘤细胞脂质代谢重编程、自噬以及免疫微环境等途径，其表达上调为肿瘤细胞提供更多的脂肪酸用 于β-氧化供能，维持其在应激环境下的生存。此外，PLIN3促进M2型肿瘤相关巨噬细胞极化，同时影响肿瘤细胞与T细胞的相 互作用，从而重塑肿瘤免疫微环境。PLIN3还通过激活Wnt/β-catenin、PI3K/Akt/mTOR等促癌信号通路，促进上皮-间质转化和耐 药性。本文综述了PLIN3在肿瘤中关键调控机制、研究进展以及作为治疗靶点的潜力，为开发特异性抑制剂和联合疗法提供理 论基础，为肿瘤的精准治疗提供新策略。
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 ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.