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Volume 29,Issue 3,2022 Table of Contents
2022, 29(3):167-174.
DOI: 10.3872/j.issn.1007-385X.2022.03.001
Abstract:
As an important part of anti-tumor immunity, cytokines were once shining stars in tumor immunotherapy. Standing at the tide of the transformation of cancer immunotherapy strategy, comprehensive cytokine-based cancer immunotherapy has continuously iterated and explored through a variety of the theoretical and technological innovations as well as various optimized combinations, and gradually changed the unsatisfactory effect of tumor monotherapy, so as to create another brilliance and provide a new way for comprehensive tumor immunotherapy. The new understanding of the intercellular communication in tumor microenvironment, the research and development of novel cytokines and modified products for tumor immunity, the discovery of the unique structure of shared signaling receptors and the combination with the new generation of anti-tumor treatment have injected new vitality into the application of tumor cytokine therapy. These findings highlight the guiding role of "innovation and combination" in the design of comprehensive strategy of cytokine-based cancer immunotherapy, and also have a certain reference value for the research and development of other tumor biotherapy technologies.
As an important part of anti-tumor immunity, cytokines were once shining stars in tumor immunotherapy. Standing at the tide of the transformation of cancer immunotherapy strategy, comprehensive cytokine-based cancer immunotherapy has continuously iterated and explored through a variety of the theoretical and technological innovations as well as various optimized combinations, and gradually changed the unsatisfactory effect of tumor monotherapy, so as to create another brilliance and provide a new way for comprehensive tumor immunotherapy. The new understanding of the intercellular communication in tumor microenvironment, the research and development of novel cytokines and modified products for tumor immunity, the discovery of the unique structure of shared signaling receptors and the combination with the new generation of anti-tumor treatment have injected new vitality into the application of tumor cytokine therapy. These findings highlight the guiding role of "innovation and combination" in the design of comprehensive strategy of cytokine-based cancer immunotherapy, and also have a certain reference value for the research and development of other tumor biotherapy technologies.
2022, 29(3):175-180.
DOI: 10.3872/j.issn.1007-385X.2022.03.002
Abstract:
Objective: To explore the in vitro and in vivo cytotoxicity of fusion peptide IL-4Rα -lytic against Kaposi sarcoma- associated herpesvirus (KSHV) positive primary effusion lymphoma (PEL) cells and its safety. Methods: The cytotoxicity of IL-4Rα-lytic against KSHV + PEL cells (BCBL-1 and BCP-1) was measured by MTT assay. The IL-4Rα-lytic induced apoptosis of KSHV + PEL cells was analyzed by FCM. A BCBL-1 cell xenograft mice model was constructed. IL-4Rα-lytic was intraperitoneally injected for three consecutive weeks (3 times/week), and the inhibitory effect of IL-4Rα-lytic on the growth of BCBL-1 cell xenograft in mice was evaluated with in vivo bioluminescence imaging technology. Moreover, the toxic side effect was analyzed using H-E staining and whole blood cell analysis. Results: Fusion peptide IL-4Rα-lytic had a selective cytotoxicity against KSHV + PEL BCBL-1 and BCP-1 cells (all P<0.01) and could rapidly kill KSHV + PEL cells (all P<0.01). IL-4Rα-lytic could induce the apoptosis of KSHV + PEL BCBL-1 and BCP-1 cells (all P<0.05). IL-4Rα-lytic significantly inhibited the growth of BCBL-1 cell xenograft in mice(P<0.05) without causing obvious organ toxicity (all P<0.05) and abnormal changes in body weight (P>0.05). Conclusion: Fusion peptide IL-4Rα-lytic can significantly inhibit the growth of KSHV + PEL cells in vivo and in vitro without obvious toxic side effects, which is expected to provide a novel strategy for the treatment of PEL.
Objective: To explore the in vitro and in vivo cytotoxicity of fusion peptide IL-4Rα -lytic against Kaposi sarcoma- associated herpesvirus (KSHV) positive primary effusion lymphoma (PEL) cells and its safety. Methods: The cytotoxicity of IL-4Rα-lytic against KSHV + PEL cells (BCBL-1 and BCP-1) was measured by MTT assay. The IL-4Rα-lytic induced apoptosis of KSHV + PEL cells was analyzed by FCM. A BCBL-1 cell xenograft mice model was constructed. IL-4Rα-lytic was intraperitoneally injected for three consecutive weeks (3 times/week), and the inhibitory effect of IL-4Rα-lytic on the growth of BCBL-1 cell xenograft in mice was evaluated with in vivo bioluminescence imaging technology. Moreover, the toxic side effect was analyzed using H-E staining and whole blood cell analysis. Results: Fusion peptide IL-4Rα-lytic had a selective cytotoxicity against KSHV + PEL BCBL-1 and BCP-1 cells (all P<0.01) and could rapidly kill KSHV + PEL cells (all P<0.01). IL-4Rα-lytic could induce the apoptosis of KSHV + PEL BCBL-1 and BCP-1 cells (all P<0.05). IL-4Rα-lytic significantly inhibited the growth of BCBL-1 cell xenograft in mice(P<0.05) without causing obvious organ toxicity (all P<0.05) and abnormal changes in body weight (P>0.05). Conclusion: Fusion peptide IL-4Rα-lytic can significantly inhibit the growth of KSHV + PEL cells in vivo and in vitro without obvious toxic side effects, which is expected to provide a novel strategy for the treatment of PEL.
WANG Tian
,
ZHANG Zhengzheng
,
WANG Xiaofeng
,
ZHANG Zimeng
,
ZHANG Yuqing
,
MA Cuiqing
,
SONG Shuxia
2022, 29(3):181-188.
DOI: 10.3872/j.issn.1007-385X.2022.03.003
Abstract:
Objective: To investigate the effect of incorporating YRHQ motif into the intracellular CD3ζ region of chimeric antigen receptor (CAR) targeting HER2 (human epidermal growth factor receptor 2) on the specific killing activity and immune memory formation of CAR-T cells. Methods: DNA fragments encoding the antigen receptor H28ζ or H28ζ(YRHQ) were obtained by DNA synthesis. H28ζ-CAR-T and H28ζ(YRHQ)-CAR-T cells targeting HER2 were developed by transducing different CAR DNA fragments into T cells from healthy human peripheral blood using lentiviral vectors. The number of different CAR-T cells was counted during amplification, and CAR expression rate was detected by FCM. The CAR-T cells were incubated with HER2 positive SKOV3, MDA-MB-453 cells or HER2 negative MCF-7 cells, respectively. Then, the killing activity of CAR-T cells was measured by LDH release assay, the levels of IL-2, IFN-γ and GZMB were measured by ELISA, the phosphorylation level of STAT3 and the expression of immune checkpoint molecules TIM-3 and PD-1 were detected by WB, and the expression of CCR7 and CD45RO was detected by FCM. In addition, the phenotypes of CAR-T cells were analyzed. Results: Both H28ζ-CAR-T and H28ζ(YRHQ)-CAR-T cells had good amplification ability and expanded 4-5 folds at 7th day of culture in vitro. The expression rate of H28ζ-CAR or H28ζ(YRHQ) CAR in T cells were (33.3±2.85)% and (28.30±3.2)%, respectively. A higher cytotoxicity of H28ζ(YRHQ)-CAR-T cells than H28ζ-CAR-T cells was observed (P<0.05). After HER2 antigen stimulation, the STAT3 phosphorylation level of H28ζ(YRHQ)-CAR-T cells was significantly higher than that of H28ζ-CAR-T cells (P<0.01); however, no significant difference in the expressionof PD-1 and TIM-3 was observedbetween two CAR-T cells. The expression of CCR7 and CD45RO in the CAR-T cells without antigen stimulation was not significantly different from that in normal T cells (both P>0.05). After co-culture with SKOV3 tumor cells, compared with T cells or H28ζ(YRHQ) -CAR-T cells, the the proportion of T EM cells increased, while the proportion of the T CM cells decreased significantly in H28ζ(YRHQ)-CAR-T cells (all P<0.05). Conclusion: The incorporation of YRHQ motif in CD3 intracellular region could improve the killing potential of CAR-T cells to some extent.
Objective: To investigate the effect of incorporating YRHQ motif into the intracellular CD3ζ region of chimeric antigen receptor (CAR) targeting HER2 (human epidermal growth factor receptor 2) on the specific killing activity and immune memory formation of CAR-T cells. Methods: DNA fragments encoding the antigen receptor H28ζ or H28ζ(YRHQ) were obtained by DNA synthesis. H28ζ-CAR-T and H28ζ(YRHQ)-CAR-T cells targeting HER2 were developed by transducing different CAR DNA fragments into T cells from healthy human peripheral blood using lentiviral vectors. The number of different CAR-T cells was counted during amplification, and CAR expression rate was detected by FCM. The CAR-T cells were incubated with HER2 positive SKOV3, MDA-MB-453 cells or HER2 negative MCF-7 cells, respectively. Then, the killing activity of CAR-T cells was measured by LDH release assay, the levels of IL-2, IFN-γ and GZMB were measured by ELISA, the phosphorylation level of STAT3 and the expression of immune checkpoint molecules TIM-3 and PD-1 were detected by WB, and the expression of CCR7 and CD45RO was detected by FCM. In addition, the phenotypes of CAR-T cells were analyzed. Results: Both H28ζ-CAR-T and H28ζ(YRHQ)-CAR-T cells had good amplification ability and expanded 4-5 folds at 7th day of culture in vitro. The expression rate of H28ζ-CAR or H28ζ(YRHQ) CAR in T cells were (33.3±2.85)% and (28.30±3.2)%, respectively. A higher cytotoxicity of H28ζ(YRHQ)-CAR-T cells than H28ζ-CAR-T cells was observed (P<0.05). After HER2 antigen stimulation, the STAT3 phosphorylation level of H28ζ(YRHQ)-CAR-T cells was significantly higher than that of H28ζ-CAR-T cells (P<0.01); however, no significant difference in the expressionof PD-1 and TIM-3 was observedbetween two CAR-T cells. The expression of CCR7 and CD45RO in the CAR-T cells without antigen stimulation was not significantly different from that in normal T cells (both P>0.05). After co-culture with SKOV3 tumor cells, compared with T cells or H28ζ(YRHQ) -CAR-T cells, the the proportion of T EM cells increased, while the proportion of the T CM cells decreased significantly in H28ζ(YRHQ)-CAR-T cells (all P<0.05). Conclusion: The incorporation of YRHQ motif in CD3 intracellular region could improve the killing potential of CAR-T cells to some extent.
2022, 29(3):189-194.
DOI: 10.3872/j.issn.1007-385X.2022.03.004
Abstract:
Objective: To investigate the effects of circular RNA _000926 (circ_000926) on the proliferation and apoptosis of cervical cancer cells and its mechanism. Methods: The tumor tissues and para-cancerous tissues of 30 cervical cancer patients resected in the First Hospital of Hebei Medical University from May 2019 to September 2020 were collected. In addition, human normal cervical cell line ECt1/E6E7 and human cervical cancer cell lines (HeLa and SiHa) were also collected for this study. The expression levels of circ_000926 and miR-411-5p in tissues and cells were detected by qPCR. circ_000926 over-expression plasmids, blank plasmids, circ_000926 small interfering RNA and its negative control oligonucleotide, miR-411-5p mimic and negative control were transfected into HeLa and SiHa cells, respectively, namely pc-circ_000926 group, pc-NC group, si-circ_000926 group, si-NC group, miR-411-5p mimic group and miR-NC group. Cell viability was detected by CCK-8 assay. Cell apoptosis was detected by TUNEL assay. The targeting relationship between circ_000926 and miR-411-5p was verified by Dual-luciferase report gene assay. The protein expression levels of Ki67, BAX, Caspase-3 and Caspase-9 were detected by Western blotting assay. Results: Compared with para-cancerous tissues and normal cervical epithelial Ect1/E6E7 cells, the expression level of circ_000926 was significantly increased while the expression level of miR-411-5p was significantly decreased (all P<0.01) in cervical cancer tissues and HeLa and SiHa cells. Compared with pc-NC group, the cell proliferation viability in pc-circ_000926 group was significantly increased, the apoptosis rate and the expression of miR-411-5p were significantly decreased (all P<0.01), the protein expression of Ki67 was significantly increased(P<0.01), while the protein expression of BAX, Caspase-3 and Caspase-9 was significantly decreased (all P<0.01). Compared with si-NC group, the cell proliferation viability of si-circ_000926 group was significantly decreased (P<0.05), the cell apoptosis rate and the expression of miR-411-5p were significantly increased (all P<0.01), and the protein expression of Ki67 was significantly decreased while the protein expression of BAX, Caspase-3 and Caspase-9 was significantly increased (all P<0.01). Dual-luciferase report gene assay verified that circ_000926 negatively regulated the expression of miR-411-5p, and over-expression of miR-411-5p could reverse the effect of circ_000926 over-expression on the proliferation and apoptosis of cervical cancer cells. Conclusion: circ_000926 can promote the proliferation and inhibit the apoptosis of cervical cancer cells by adsorbing miR-411-5p.
Objective: To investigate the effects of circular RNA _000926 (circ_000926) on the proliferation and apoptosis of cervical cancer cells and its mechanism. Methods: The tumor tissues and para-cancerous tissues of 30 cervical cancer patients resected in the First Hospital of Hebei Medical University from May 2019 to September 2020 were collected. In addition, human normal cervical cell line ECt1/E6E7 and human cervical cancer cell lines (HeLa and SiHa) were also collected for this study. The expression levels of circ_000926 and miR-411-5p in tissues and cells were detected by qPCR. circ_000926 over-expression plasmids, blank plasmids, circ_000926 small interfering RNA and its negative control oligonucleotide, miR-411-5p mimic and negative control were transfected into HeLa and SiHa cells, respectively, namely pc-circ_000926 group, pc-NC group, si-circ_000926 group, si-NC group, miR-411-5p mimic group and miR-NC group. Cell viability was detected by CCK-8 assay. Cell apoptosis was detected by TUNEL assay. The targeting relationship between circ_000926 and miR-411-5p was verified by Dual-luciferase report gene assay. The protein expression levels of Ki67, BAX, Caspase-3 and Caspase-9 were detected by Western blotting assay. Results: Compared with para-cancerous tissues and normal cervical epithelial Ect1/E6E7 cells, the expression level of circ_000926 was significantly increased while the expression level of miR-411-5p was significantly decreased (all P<0.01) in cervical cancer tissues and HeLa and SiHa cells. Compared with pc-NC group, the cell proliferation viability in pc-circ_000926 group was significantly increased, the apoptosis rate and the expression of miR-411-5p were significantly decreased (all P<0.01), the protein expression of Ki67 was significantly increased(P<0.01), while the protein expression of BAX, Caspase-3 and Caspase-9 was significantly decreased (all P<0.01). Compared with si-NC group, the cell proliferation viability of si-circ_000926 group was significantly decreased (P<0.05), the cell apoptosis rate and the expression of miR-411-5p were significantly increased (all P<0.01), and the protein expression of Ki67 was significantly decreased while the protein expression of BAX, Caspase-3 and Caspase-9 was significantly increased (all P<0.01). Dual-luciferase report gene assay verified that circ_000926 negatively regulated the expression of miR-411-5p, and over-expression of miR-411-5p could reverse the effect of circ_000926 over-expression on the proliferation and apoptosis of cervical cancer cells. Conclusion: circ_000926 can promote the proliferation and inhibit the apoptosis of cervical cancer cells by adsorbing miR-411-5p.
2022, 29(3):195-201.
DOI: 10.3872/j.issn.1007-385X.2022.03.005
Abstract:
Objective: To investigate the effects of interfering with B7-H4 expression on proliferation, apoptosis, cell cycle and expression of downstream molecules in breast cancer cells. Methods: Breast cancer T47D and MCF-7 cells at logarithmic phase were transfected with siRNA specifically targeting B7-H4 (siB7-H4) or its negative control (siNC) by using Lipofectamine TM 2000, namely T47D siNC, T47D-siB7-H4, MCF-7-siNC, and MCF-7-siB7-H4 group, respectively. The efficacy of siRNA interference and its effect on the expression of cyclin D1 were verified by quantitative PCR (qPCR) and Western blotting (WB). The effects of interfering with B7-H4 on cell proliferation, cell cycle and apoptosis of breast cancer cell lines T47D and MCF-7 were detected by CCK-8 assays and flow cytometry, respectively. The effects of interfering with B7-H4 on the expression of E2F family related transcription factors were examined by qPCR. Results: The T47D and MCF-7 cell lines with B7-H4 knockdown were successfully constructed. Compared with the cells in T47D-siNC and MCF-7-siNC groups, the mRNA and protein levels of B7-H4 were significantly decreased, and the proliferation was significantly inhibited in the cells of T47D-siB7-H4 or MCF-7-siB7-H4 groups, accompanied with G1/S cell cycle arrest as well as downregulation of cyclin D1 (all P<0.01); however, there were no statistically significant differences in apoptotic rates (all P>0.05). Compared with the cells in T47D-siNC group, the mRNA levels of E2F1, E2F2, E2F7 and E2F8 in T47D cells decreased in varying degrees after interfering with B7-H4 (all P<0.01); compared with cells in MCF-7-siNC group, the mRNA levels of E2F1, E2F2, E2F3, E2f7 and E2F8 in MCF-7 cells also decreased in varying degrees after interfering with B7-H4 (P<0.05 or P<0.01). Conclusion: Interfering with B7-H4 in breast cancer cells can down-regulate the expression of cyclin D1 and E2F family related transcription factors, leading to cell cycle arrest and inhibition of cell proliferation.
Objective: To investigate the effects of interfering with B7-H4 expression on proliferation, apoptosis, cell cycle and expression of downstream molecules in breast cancer cells. Methods: Breast cancer T47D and MCF-7 cells at logarithmic phase were transfected with siRNA specifically targeting B7-H4 (siB7-H4) or its negative control (siNC) by using Lipofectamine TM 2000, namely T47D siNC, T47D-siB7-H4, MCF-7-siNC, and MCF-7-siB7-H4 group, respectively. The efficacy of siRNA interference and its effect on the expression of cyclin D1 were verified by quantitative PCR (qPCR) and Western blotting (WB). The effects of interfering with B7-H4 on cell proliferation, cell cycle and apoptosis of breast cancer cell lines T47D and MCF-7 were detected by CCK-8 assays and flow cytometry, respectively. The effects of interfering with B7-H4 on the expression of E2F family related transcription factors were examined by qPCR. Results: The T47D and MCF-7 cell lines with B7-H4 knockdown were successfully constructed. Compared with the cells in T47D-siNC and MCF-7-siNC groups, the mRNA and protein levels of B7-H4 were significantly decreased, and the proliferation was significantly inhibited in the cells of T47D-siB7-H4 or MCF-7-siB7-H4 groups, accompanied with G1/S cell cycle arrest as well as downregulation of cyclin D1 (all P<0.01); however, there were no statistically significant differences in apoptotic rates (all P>0.05). Compared with the cells in T47D-siNC group, the mRNA levels of E2F1, E2F2, E2F7 and E2F8 in T47D cells decreased in varying degrees after interfering with B7-H4 (all P<0.01); compared with cells in MCF-7-siNC group, the mRNA levels of E2F1, E2F2, E2F3, E2f7 and E2F8 in MCF-7 cells also decreased in varying degrees after interfering with B7-H4 (P<0.05 or P<0.01). Conclusion: Interfering with B7-H4 in breast cancer cells can down-regulate the expression of cyclin D1 and E2F family related transcription factors, leading to cell cycle arrest and inhibition of cell proliferation.
2022, 29(3):202-208.
DOI: 10.3872/j.issn.1007-385X.2022.03.006
Abstract:
Objective: To investigate the effect of miR-620 on the radiosensitivity of breast cancer MCF-7 cells and its mechanism. Methods: The cancer tissues and para-cancerous tissue specimens of 21 patients with breast cancer who had surgical resection in Danzhou City People's Hospital of Hainan Province from March 2017 to March 2018 were collected. In addition, breast cancer MCF-7 and BCaP-37 cells and breast epithelial HBL-100 cells were also cultured in vitro. The mRNA expression of miR-620 and inhibitor of growth 4 (ING4) in breast cancer tissues and cells was detected by qRT-PCR. MCF-7 cells were respectively transfected with miR-620 inhibitor (anti-miR-620), inhibitor negative control (anti-miR-NC), anti-miR-620 with ING4 small interfering RNA (si-ING4), and anti-miR-620 with small interfering RNA negative control (si-NC) using Lipofectamine TM 2000 lipofection technology before radiotherapy, namely IR+anti-miR-620 group, IR+anti-miR-NC group, IR+anti-miR-620+si-ING4 group, and IR+anti-miR-620+si-NC group, respectively.The cell radiosensitivity, cell proliferation activity, cell cycle distribution and apoptosis rate were detected by clone formation assay, MTT and FCM, respectively. The dual-luciferase reporter gene assay and Western blotting were used to verify the targeting relationship between miR-620 and ING4. Results: Compared with para-cancerous tissues and HBL-100 cells, the expression of miR-620 was significantly increased while the mRNA expression of ING4 was significantly reduced in breast cancer tissues and cells(all P<0.01). Compared with the IR+anti-miR-NC group, the proliferation activity and S phase cell proportion of MCF-7 cells in the IR+anti-miR-620 group were significantly decreased (all P<0.01), but the apoptosis rate, the proportion of G0-G1 phase cells, and the radiosensitivity were significantly increased (all P<0.01). Compared with the IR+anti-miR-620+si-NC group, the proliferation activity and the S-phase cell proportion of MCF-7 cells in the IR+anti-miR-620+si-ING4 group were significantly increased (all P<0.01), but the apoptosis rate, the proportion of G0-G1 phase cells, and the radiosensitivity were significantly decreased (all P<0.01). The dual-luciferase reporter gene assay showed that ING4 is a target gene of miR-620, and miR-620 targeted and negatively regulated the expression of ING4. Conclusion: Knockdown of miR-620 could inhibit the proliferation of MCF-7 cells but promote the apoptosis and radiosensitivity of MCF-7 cells by up-regulating ING4.
Objective: To investigate the effect of miR-620 on the radiosensitivity of breast cancer MCF-7 cells and its mechanism. Methods: The cancer tissues and para-cancerous tissue specimens of 21 patients with breast cancer who had surgical resection in Danzhou City People's Hospital of Hainan Province from March 2017 to March 2018 were collected. In addition, breast cancer MCF-7 and BCaP-37 cells and breast epithelial HBL-100 cells were also cultured in vitro. The mRNA expression of miR-620 and inhibitor of growth 4 (ING4) in breast cancer tissues and cells was detected by qRT-PCR. MCF-7 cells were respectively transfected with miR-620 inhibitor (anti-miR-620), inhibitor negative control (anti-miR-NC), anti-miR-620 with ING4 small interfering RNA (si-ING4), and anti-miR-620 with small interfering RNA negative control (si-NC) using Lipofectamine TM 2000 lipofection technology before radiotherapy, namely IR+anti-miR-620 group, IR+anti-miR-NC group, IR+anti-miR-620+si-ING4 group, and IR+anti-miR-620+si-NC group, respectively.The cell radiosensitivity, cell proliferation activity, cell cycle distribution and apoptosis rate were detected by clone formation assay, MTT and FCM, respectively. The dual-luciferase reporter gene assay and Western blotting were used to verify the targeting relationship between miR-620 and ING4. Results: Compared with para-cancerous tissues and HBL-100 cells, the expression of miR-620 was significantly increased while the mRNA expression of ING4 was significantly reduced in breast cancer tissues and cells(all P<0.01). Compared with the IR+anti-miR-NC group, the proliferation activity and S phase cell proportion of MCF-7 cells in the IR+anti-miR-620 group were significantly decreased (all P<0.01), but the apoptosis rate, the proportion of G0-G1 phase cells, and the radiosensitivity were significantly increased (all P<0.01). Compared with the IR+anti-miR-620+si-NC group, the proliferation activity and the S-phase cell proportion of MCF-7 cells in the IR+anti-miR-620+si-ING4 group were significantly increased (all P<0.01), but the apoptosis rate, the proportion of G0-G1 phase cells, and the radiosensitivity were significantly decreased (all P<0.01). The dual-luciferase reporter gene assay showed that ING4 is a target gene of miR-620, and miR-620 targeted and negatively regulated the expression of ING4. Conclusion: Knockdown of miR-620 could inhibit the proliferation of MCF-7 cells but promote the apoptosis and radiosensitivity of MCF-7 cells by up-regulating ING4.
2022, 29(3):209-217.
DOI: 10.3872/j.issn.1007-385X.2022.03.007
Abstract:
Objective: To investigate the expression of collagen triple helix repeat containing-1 (CTHRC1) in bladder cancer tissues and cells and its effect on the migration and invasion of bladder cancer 5637 cells as well as the related mechanisms. Methods: By referring to the bladder cancer gene expression data in TCGA and Arrayexpress databases, CTHRC1 transcriptional and translational levels were analyzed. 144 cases of bladder cancer tissues and 25 cases of para-cancerous tissues resected in the First Affiliated Hospital of Chongqing Medical University from September 2014 to December 2020 were collected for this study; in addition, human bladder cancer cells (RT4, 5637, T24, UMUC-3 and TCCSUP) and immortalized human ureteral epithelial SV-HUC-1 cells were also collected. The expression levels of CTHRC1 in human bladder cancer tissues and cell lines were detected by immunohistochemistry staining, qPCR and WB. The Kaplan-Meier curve was used to analyze the effect of CTHRC1 expression on overall survival (OS). CTHRC1 expression in 5637 cells was interfered using RNAi technology, and then the effects of CTHRC1 knockdown on migration and invasion of bladder cancer 5637 cells were detected by scratch and Transwell assays. Gene set enrichment analysis (GSEA) was used to predict potential signaling pathways associated with CTHRC1. WB was utilized to detect the effect of CTHRC1 knockdown on the expression of FAK-ERK1/2 pathway related proteins. Results: The transcriptional and translational levels of CTHRC1 were significantly up-regulated in muscle-invasive bladder cancer tissues and cells (all P<0.05), and the 5-year OS was significantly shorter in the patients with high CTHRC1 expression as compared with those with low expression (P<0.05). The migration and invasion of bladder cancer 5637 cells were reduced following CTHRC1 knockdown (all P<0.01). GSEA showed that the CTHRC1 high-expression group was mainly enriched in focal adhesion kinase (FAK), regulation of actin cytoskeleton, and FAK-ERK1/2 signaling pathways. WB assay showed that recombinant CTHRC1 protein promoted the activation of FAK-ERK1/2 signaling pathway in bladder cancer 5637 cells (P<0.05 or P<0.01). Conclusion: CTHRC1 expression is up-regulated in invasive bladder cancer and closely related to the poor prognosis of bladder cancer patients. CTHRC1 enhances the invasion and metastasis of bladder cancer cells, which may be associated with the activation of the FAK-ERK1/2 signaling pathway.
Objective: To investigate the expression of collagen triple helix repeat containing-1 (CTHRC1) in bladder cancer tissues and cells and its effect on the migration and invasion of bladder cancer 5637 cells as well as the related mechanisms. Methods: By referring to the bladder cancer gene expression data in TCGA and Arrayexpress databases, CTHRC1 transcriptional and translational levels were analyzed. 144 cases of bladder cancer tissues and 25 cases of para-cancerous tissues resected in the First Affiliated Hospital of Chongqing Medical University from September 2014 to December 2020 were collected for this study; in addition, human bladder cancer cells (RT4, 5637, T24, UMUC-3 and TCCSUP) and immortalized human ureteral epithelial SV-HUC-1 cells were also collected. The expression levels of CTHRC1 in human bladder cancer tissues and cell lines were detected by immunohistochemistry staining, qPCR and WB. The Kaplan-Meier curve was used to analyze the effect of CTHRC1 expression on overall survival (OS). CTHRC1 expression in 5637 cells was interfered using RNAi technology, and then the effects of CTHRC1 knockdown on migration and invasion of bladder cancer 5637 cells were detected by scratch and Transwell assays. Gene set enrichment analysis (GSEA) was used to predict potential signaling pathways associated with CTHRC1. WB was utilized to detect the effect of CTHRC1 knockdown on the expression of FAK-ERK1/2 pathway related proteins. Results: The transcriptional and translational levels of CTHRC1 were significantly up-regulated in muscle-invasive bladder cancer tissues and cells (all P<0.05), and the 5-year OS was significantly shorter in the patients with high CTHRC1 expression as compared with those with low expression (P<0.05). The migration and invasion of bladder cancer 5637 cells were reduced following CTHRC1 knockdown (all P<0.01). GSEA showed that the CTHRC1 high-expression group was mainly enriched in focal adhesion kinase (FAK), regulation of actin cytoskeleton, and FAK-ERK1/2 signaling pathways. WB assay showed that recombinant CTHRC1 protein promoted the activation of FAK-ERK1/2 signaling pathway in bladder cancer 5637 cells (P<0.05 or P<0.01). Conclusion: CTHRC1 expression is up-regulated in invasive bladder cancer and closely related to the poor prognosis of bladder cancer patients. CTHRC1 enhances the invasion and metastasis of bladder cancer cells, which may be associated with the activation of the FAK-ERK1/2 signaling pathway.
2022, 29(3):218-224.
DOI: 10.3872/j.issn.1007-385X.2022.03.008
Abstract:
Objective: To detect the expression of LINC00997 in gastric cardia adenocarcinoma (GCA) tissues and gastric cancer cells and analyze its relationship with the clinicopathological features and prognosis of GCA patients, as well as to explore the effect of LINC00997 knockdown on the migration, invasion and epithelial-mesenchymal transition (EMT) of SGC7901 cells. Methods: Based on the TCGA and GTEx database, the expression of LINC00997 in gastric cancer tissues and its relationship with the prognosis of gastric cancer patients were analyzed. qPCR was applied to detect the expression of LINC00997 in 68 pairs of GCA tissues and the corresponding para-cancerous tissues and gastric cancer cells. The association between its expression level and clinicopathological characteristics and prognosis of patients was also analyzed. The effects of LINC00997 knockdown on migration and invasion of gastric cancer SGC7901 cells were examined by Wound-healing assay and Transwell invasion assay, respectively. The effects of LINC00997 knockdown on the expression of EMT-related markers E-cadherin, N-cadherin and vimentin were detected by qPCR and WB methods. Results: The expression of LINC00997 in gastric cancer tissues was significantly higher than that in para-cancerous tissues (P<0.05), and the overall survival (OS) rate and disease-free survival (DFS) rate of the LINC00997 high expression group was significantly lower than that of the low expression group (P<0.05 or P<0.01). The expression of LINC00997 in 68 GCA tissues was significantly higher than that in corresponding para-cancerous tissues (P<0.01), and was correlated with lymph node metastasis, TNM stage and OS of the patients (P<0.05 or P<0.01). The migration and invasion of SGC7901 cells with LINC00997 knockdown were significantly suppressed (all P<0.01), the expression levels of N-cadherin and vimentin were decreased while the expression of E-cadherin was increased (P<0.05 or P<0.01). Conclusion: LINC00997 is highly expressed in GCA tissues and cells. The high expression of LINC00997 may promote the migration, invasion and EMT process of GCA, and is expected to become a candidate molecular marker for prognostic evaluation of patients with GCA.
Objective: To detect the expression of LINC00997 in gastric cardia adenocarcinoma (GCA) tissues and gastric cancer cells and analyze its relationship with the clinicopathological features and prognosis of GCA patients, as well as to explore the effect of LINC00997 knockdown on the migration, invasion and epithelial-mesenchymal transition (EMT) of SGC7901 cells. Methods: Based on the TCGA and GTEx database, the expression of LINC00997 in gastric cancer tissues and its relationship with the prognosis of gastric cancer patients were analyzed. qPCR was applied to detect the expression of LINC00997 in 68 pairs of GCA tissues and the corresponding para-cancerous tissues and gastric cancer cells. The association between its expression level and clinicopathological characteristics and prognosis of patients was also analyzed. The effects of LINC00997 knockdown on migration and invasion of gastric cancer SGC7901 cells were examined by Wound-healing assay and Transwell invasion assay, respectively. The effects of LINC00997 knockdown on the expression of EMT-related markers E-cadherin, N-cadherin and vimentin were detected by qPCR and WB methods. Results: The expression of LINC00997 in gastric cancer tissues was significantly higher than that in para-cancerous tissues (P<0.05), and the overall survival (OS) rate and disease-free survival (DFS) rate of the LINC00997 high expression group was significantly lower than that of the low expression group (P<0.05 or P<0.01). The expression of LINC00997 in 68 GCA tissues was significantly higher than that in corresponding para-cancerous tissues (P<0.01), and was correlated with lymph node metastasis, TNM stage and OS of the patients (P<0.05 or P<0.01). The migration and invasion of SGC7901 cells with LINC00997 knockdown were significantly suppressed (all P<0.01), the expression levels of N-cadherin and vimentin were decreased while the expression of E-cadherin was increased (P<0.05 or P<0.01). Conclusion: LINC00997 is highly expressed in GCA tissues and cells. The high expression of LINC00997 may promote the migration, invasion and EMT process of GCA, and is expected to become a candidate molecular marker for prognostic evaluation of patients with GCA.
YANG Yue
,
LIAN Bin
,
WANG Xuan
,
SI Lu
,
CHI Zhihong
,
SHENG Xinan
,
MAO Lili
,
CUI Chuanliang
,
GUO Jun
2022, 29(3):225-229.
DOI: 10.3872/j.issn.1007-385X.2022.03.009
Abstract:
Objective: To investigate the efficacy and safety of anti-PD-1 antibody combined with chemotherapy and anti-angiogenic drugs in the treatment of advanced melanoma. Methods: The clinical data of 14 patients (6 males and 8 females) with unresectable advanced melanoma who received anti-PD-1 antibody combined with chemotherapy (temozolomide±cisplatin, albumin bound paclitaxel) and anti-angiogenic drug (bevacizumab) in Peking University Cancer Hospital from April 2020 to June 2021 were collected. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety data (CTCAE 5.0). Results: All of the 14 patients with advanced melanoma were included in the survival analysis. The median follow-up time was 5.50 months (95% CI: 0-13.12 months). The median PFS was 7.43 months (95% CI: 3.07-11.79 months), and the median OS was 13.50 months (95% CI: 5.19-21.81 months). The median onset time was 1.5 months. The ORR was 28.6% (all the 4 patients were in partial remission) and the DCR was 85.7%. The adverse events were almost grade 1-2. Conclusion: Chemotherapy combined with anti-PD-1 antibody and anti-angiogenic drug showed certain efficacy and safety in patients with advanced melanoma, which might provide new ideas for the combined treatment of advanced melanoma.
Objective: To investigate the efficacy and safety of anti-PD-1 antibody combined with chemotherapy and anti-angiogenic drugs in the treatment of advanced melanoma. Methods: The clinical data of 14 patients (6 males and 8 females) with unresectable advanced melanoma who received anti-PD-1 antibody combined with chemotherapy (temozolomide±cisplatin, albumin bound paclitaxel) and anti-angiogenic drug (bevacizumab) in Peking University Cancer Hospital from April 2020 to June 2021 were collected. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety data (CTCAE 5.0). Results: All of the 14 patients with advanced melanoma were included in the survival analysis. The median follow-up time was 5.50 months (95% CI: 0-13.12 months). The median PFS was 7.43 months (95% CI: 3.07-11.79 months), and the median OS was 13.50 months (95% CI: 5.19-21.81 months). The median onset time was 1.5 months. The ORR was 28.6% (all the 4 patients were in partial remission) and the DCR was 85.7%. The adverse events were almost grade 1-2. Conclusion: Chemotherapy combined with anti-PD-1 antibody and anti-angiogenic drug showed certain efficacy and safety in patients with advanced melanoma, which might provide new ideas for the combined treatment of advanced melanoma.
2022, 29(3):230-238.
DOI: 10.3872/j.issn.1007-385X.2022.03.010
Abstract:
Objective: To investigate the expression level of glucosaminyl (N-acetyl) transferase 2 (GCNT2) in gastric cancer (GC) tissues and its role in the occurrence, development, diagnosis and prognosis of GC. Methods: By using TIMER, GEPIA2, Oncomine and UALCAN databases as well as clinical specimens of GC tissues and paired para-cancerous tissues from 25 GC patients who had surgical resection in the Affiliated Hospital of Binzhou Medical University from January 2018 to December 2019, the expression level of GCNT2 gene in GC tissues and its diagnostic and prognostic value in GC were analyzed. The main signal pathways that GCNT2 involved in and the correlation of GCNT2 with immune infiltration were analyzed by LinkedOmics, GSEA and ssGSEA. pc-GCNT2 and its negative control plasmids were transfected into gastric cancer SGC-7901 and BGC-823 cells. Colony formation assay and Traswell assay were used to detect the effect of GCNT2 on the proliferation and invasion of GC cells. WB method was used to detect the protein expression of GCNT2, STAT3 and PD-L1 in transfected cells. Results: The expression level of GCNT2 mRNA in GC tissues was significantly lower than that in para-cancerous tissues (P<0.05), and its expression level was significantly correlated with the prognosis of patients (P<0.05), which is of high value in the diagnosis of GC. The methylation status of GCNT2 in GC tissues was significantly higher than that in para-cancerous tissues. The biological processes that GCNT2 gene involved in were mainly cell morphogenesis, intercellular adhesion, multicellular biological signals and synaptic transmission, etc. Single gene GSEA analysis showed that GCNT2 mainly inhibited IL-6/JAK/STAT3 and IL-2/STAT5 signaling pathways, inflammatory response, α/γ interferon response and NF-κB expression in GC. There was a significant correlation between the expression of GCNT2 and immune infiltration in GC tissues. Over-expression of GCNT2 significantly inhibited the proliferation and invasion of GC cells (all P<0.01), and down- regulated the expression of STAT3 and PD-L1 (all P<0.01). Conclusion: GCNT2 is significantly lowly expressed in gastric cancer tissues, and is significantly related to the diagnosis and prognosis of GC patients. GCNT2 plays an important role in the occurrence and development of GC mainly through inhibiting IL-6/JAK/STAT3 signaling pathway and immune-related carcinogenic signaling pathway.
Objective: To investigate the expression level of glucosaminyl (N-acetyl) transferase 2 (GCNT2) in gastric cancer (GC) tissues and its role in the occurrence, development, diagnosis and prognosis of GC. Methods: By using TIMER, GEPIA2, Oncomine and UALCAN databases as well as clinical specimens of GC tissues and paired para-cancerous tissues from 25 GC patients who had surgical resection in the Affiliated Hospital of Binzhou Medical University from January 2018 to December 2019, the expression level of GCNT2 gene in GC tissues and its diagnostic and prognostic value in GC were analyzed. The main signal pathways that GCNT2 involved in and the correlation of GCNT2 with immune infiltration were analyzed by LinkedOmics, GSEA and ssGSEA. pc-GCNT2 and its negative control plasmids were transfected into gastric cancer SGC-7901 and BGC-823 cells. Colony formation assay and Traswell assay were used to detect the effect of GCNT2 on the proliferation and invasion of GC cells. WB method was used to detect the protein expression of GCNT2, STAT3 and PD-L1 in transfected cells. Results: The expression level of GCNT2 mRNA in GC tissues was significantly lower than that in para-cancerous tissues (P<0.05), and its expression level was significantly correlated with the prognosis of patients (P<0.05), which is of high value in the diagnosis of GC. The methylation status of GCNT2 in GC tissues was significantly higher than that in para-cancerous tissues. The biological processes that GCNT2 gene involved in were mainly cell morphogenesis, intercellular adhesion, multicellular biological signals and synaptic transmission, etc. Single gene GSEA analysis showed that GCNT2 mainly inhibited IL-6/JAK/STAT3 and IL-2/STAT5 signaling pathways, inflammatory response, α/γ interferon response and NF-κB expression in GC. There was a significant correlation between the expression of GCNT2 and immune infiltration in GC tissues. Over-expression of GCNT2 significantly inhibited the proliferation and invasion of GC cells (all P<0.01), and down- regulated the expression of STAT3 and PD-L1 (all P<0.01). Conclusion: GCNT2 is significantly lowly expressed in gastric cancer tissues, and is significantly related to the diagnosis and prognosis of GC patients. GCNT2 plays an important role in the occurrence and development of GC mainly through inhibiting IL-6/JAK/STAT3 signaling pathway and immune-related carcinogenic signaling pathway.
2022, 29(3):239-244.
DOI: 10.3872/j.issn.1007-385X.2022.03.011
Abstract:
长链非编码RNA（lncRNA）是一种长度超过200个核苷酸且不具备蛋白质编码功能的RNA分子，目前认为lncRNA可以从多个维度对DNA、RNA和蛋白质的功能进行调控。肺癌相关转录物1（LUCAT1）是最早在吸烟的肺癌患者组织中发现的一种lncRNA，越来越多的研究发现，LUCAT1在多种类型肿瘤中表达异常，可通过DNA甲基化、竞争性结合靶基因mRNA和蛋白质等多种形式参与分子调控，促进肿瘤细胞的增殖、迁移和侵袭等过程，在恶性肿瘤的发生和发展中发挥重要作用，是临床肿瘤诊断的生物标志物及治疗的潜在靶点。此外，LUCAT1在胃癌、肝细胞癌、肾癌、卵巢癌及乳腺癌等多种类型肿瘤细胞中表达上调，并与肿瘤大小、组织学分级、TNM分期和OS等临床特征显著相关。本文综述了近年来LUCAT1在促进肿瘤发生和发展的作用机制及其在不同类型肿瘤中的表达和功能，以及在预后评估中作用的研究进展。
长链非编码RNA（lncRNA）是一种长度超过200个核苷酸且不具备蛋白质编码功能的RNA分子，目前认为lncRNA可以从多个维度对DNA、RNA和蛋白质的功能进行调控。肺癌相关转录物1（LUCAT1）是最早在吸烟的肺癌患者组织中发现的一种lncRNA，越来越多的研究发现，LUCAT1在多种类型肿瘤中表达异常，可通过DNA甲基化、竞争性结合靶基因mRNA和蛋白质等多种形式参与分子调控，促进肿瘤细胞的增殖、迁移和侵袭等过程，在恶性肿瘤的发生和发展中发挥重要作用，是临床肿瘤诊断的生物标志物及治疗的潜在靶点。此外，LUCAT1在胃癌、肝细胞癌、肾癌、卵巢癌及乳腺癌等多种类型肿瘤细胞中表达上调，并与肿瘤大小、组织学分级、TNM分期和OS等临床特征显著相关。本文综述了近年来LUCAT1在促进肿瘤发生和发展的作用机制及其在不同类型肿瘤中的表达和功能，以及在预后评估中作用的研究进展。
2022, 29(3):245-250.
DOI: 10.3872/j.issn.1007-385X.2022.03.012
Abstract:
恶性肿瘤给社会和个人带来了沉重的负担，提高肿瘤的早期诊断率和治疗效果、寻找潜在的治疗靶点成为目前临床上亟待解决的问题。泛素特异性蛋白酶18 （USP18）是蛋白翻译后修饰酶的一种，具有去泛素化酶活性，能够特异性地将干扰素刺激基因15 （ISG15）从底物蛋白上移除，也可调控干扰素信号通路，阻碍ISG的表达，在感染、免疫等病理过程中发挥作用。近年的研究发现，USP18在多种类型肿瘤中高表达，在肿瘤的发生和发展中扮演了重要角色，能够影响肿瘤增殖和凋亡，调控肿瘤细胞代谢、侵袭和转移。此外，USP18还可影响肿瘤细胞的放射和化学治疗的敏感性，并调控部分免疫细胞的功能。因此，开发 USP18 的特异性抑制剂，可能成为抗肿瘤药物开发的一种新思路。
恶性肿瘤给社会和个人带来了沉重的负担，提高肿瘤的早期诊断率和治疗效果、寻找潜在的治疗靶点成为目前临床上亟待解决的问题。泛素特异性蛋白酶18 （USP18）是蛋白翻译后修饰酶的一种，具有去泛素化酶活性，能够特异性地将干扰素刺激基因15 （ISG15）从底物蛋白上移除，也可调控干扰素信号通路，阻碍ISG的表达，在感染、免疫等病理过程中发挥作用。近年的研究发现，USP18在多种类型肿瘤中高表达，在肿瘤的发生和发展中扮演了重要角色，能够影响肿瘤增殖和凋亡，调控肿瘤细胞代谢、侵袭和转移。此外，USP18还可影响肿瘤细胞的放射和化学治疗的敏感性，并调控部分免疫细胞的功能。因此，开发 USP18 的特异性抑制剂，可能成为抗肿瘤药物开发的一种新思路。
2022, 29(3):251-257.
DOI: 10.3872/j.issn.1007-385X.2022.03.013
Abstract:
细胞焦亡是近年来发现的一种新型细胞死亡的方式，是一种受焦孔素（GSDM）家族调控的炎症性程序性细胞死亡，其主要特征是膜穿孔、细胞肿胀及细胞破裂。细胞焦亡发生的机制分为由GSDMD介导的Caspase-1和Caspase-4/-5/-11依赖性经典炎症小体途径和由GSDME介导的Caspase-3和颗粒酶依赖性非经典炎症小体途径等。近年来研究显示，细胞焦亡具有抑制和促进肿瘤发生发展的双重作用，并且细胞焦亡的诱导在抗肿瘤免疫治疗中也发挥双重效应：一方面通过促进炎症因子释放，形成肿瘤微环境，抑制抗肿瘤免疫，另一方面则通过引发抗肿瘤炎症反应抑制肿瘤细胞的增殖。此外，细胞焦亡的诱导在化疗及其他联合治疗中也发挥着重要作用。进一步研究发现，中药及其提取物调控细胞焦亡的诱导对于治疗肿瘤至关重要。
细胞焦亡是近年来发现的一种新型细胞死亡的方式，是一种受焦孔素（GSDM）家族调控的炎症性程序性细胞死亡，其主要特征是膜穿孔、细胞肿胀及细胞破裂。细胞焦亡发生的机制分为由GSDMD介导的Caspase-1和Caspase-4/-5/-11依赖性经典炎症小体途径和由GSDME介导的Caspase-3和颗粒酶依赖性非经典炎症小体途径等。近年来研究显示，细胞焦亡具有抑制和促进肿瘤发生发展的双重作用，并且细胞焦亡的诱导在抗肿瘤免疫治疗中也发挥双重效应：一方面通过促进炎症因子释放，形成肿瘤微环境，抑制抗肿瘤免疫，另一方面则通过引发抗肿瘤炎症反应抑制肿瘤细胞的增殖。此外，细胞焦亡的诱导在化疗及其他联合治疗中也发挥着重要作用。进一步研究发现，中药及其提取物调控细胞焦亡的诱导对于治疗肿瘤至关重要。
2022, 29(3):258-262.
DOI: 10.3872/j.issn.1007-385X.2022.03.014
Abstract:
嵌合抗原受体T（CAR-T）细胞治疗是通过基因修饰获得携带识别肿瘤抗原特异性受体T细胞的个性化治疗方法。近年来，CAR-T细胞治疗在血液系统肿瘤的治疗中取得了巨大的成功，在实体瘤治疗方面也取得了一定进展。肺癌是世界上发病率最高的恶性肿瘤之一，而非小细胞肺癌（NSCLC）占多数且疗效差。CAR-T细胞治疗NSCLC主要在下述多个方面取得进展，包括CAR-T细胞分子结构的不断优化设计、CAR-T细胞治疗NSCLC的潜在靶标（如PD-L1、B7H3、MSLN、EGFR、PSCA、MUC1和LUNX）的发现、CAR-T细胞治疗联合放射治疗与化学治疗的机制与临床前动物实验的效果等。CAR-T细胞治疗NSCLC也存在许多困难，如CAR-T细胞在实体瘤中浸润性差、肿瘤特异性抗原缺乏、严重副作用的发生等。
嵌合抗原受体T（CAR-T）细胞治疗是通过基因修饰获得携带识别肿瘤抗原特异性受体T细胞的个性化治疗方法。近年来，CAR-T细胞治疗在血液系统肿瘤的治疗中取得了巨大的成功，在实体瘤治疗方面也取得了一定进展。肺癌是世界上发病率最高的恶性肿瘤之一，而非小细胞肺癌（NSCLC）占多数且疗效差。CAR-T细胞治疗NSCLC主要在下述多个方面取得进展，包括CAR-T细胞分子结构的不断优化设计、CAR-T细胞治疗NSCLC的潜在靶标（如PD-L1、B7H3、MSLN、EGFR、PSCA、MUC1和LUNX）的发现、CAR-T细胞治疗联合放射治疗与化学治疗的机制与临床前动物实验的效果等。CAR-T细胞治疗NSCLC也存在许多困难，如CAR-T细胞在实体瘤中浸润性差、肿瘤特异性抗原缺乏、严重副作用的发生等。
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- 《中国肿瘤生物治疗杂志》
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.