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Volume 27,Issue 12,2020 Table of Contents
2020, 27(12):1313-1318.
DOI: 10.3872/j.issn.1007-385X.2020.12.001
Abstract:
In recent years, investigation on immune checkpoint inhibitors has made exciting progress in anti-tumor therapy. Through continuous exploration, there is a deeper understanding of intermolecular interaction patterns among PD-L1, PD-1, CD80, CTLA-4, etc.In addition to classically acting as a T cell inhibitory receptor, PD-L1 was found to be co-expressed with PD-1 or CD80 on the same cell and play a positive immunoregulatory function through cis-interaction, significantly affecting the interaction network between tumor cells and immune cells and the efficacy of immunotherapy, and bringing new changes to the understanding of the mechanisms of cancer immunotherapy. This review provides an in-depth analysis of the cis-PD-L1/PD-1 and cis-PD-L1/CD80 pathways and their interactions with a complex network of CTLA-4 and CD28 molecules, finally outlines the effects of blocking this cis-interaction pathway on T cell signaling, cytotoxic function, and the efficacy of anti-tumor immunotherapy.
In recent years, investigation on immune checkpoint inhibitors has made exciting progress in anti-tumor therapy. Through continuous exploration, there is a deeper understanding of intermolecular interaction patterns among PD-L1, PD-1, CD80, CTLA-4, etc.In addition to classically acting as a T cell inhibitory receptor, PD-L1 was found to be co-expressed with PD-1 or CD80 on the same cell and play a positive immunoregulatory function through cis-interaction, significantly affecting the interaction network between tumor cells and immune cells and the efficacy of immunotherapy, and bringing new changes to the understanding of the mechanisms of cancer immunotherapy. This review provides an in-depth analysis of the cis-PD-L1/PD-1 and cis-PD-L1/CD80 pathways and their interactions with a complex network of CTLA-4 and CD28 molecules, finally outlines the effects of blocking this cis-interaction pathway on T cell signaling, cytotoxic function, and the efficacy of anti-tumor immunotherapy.
2020, 27(12):1319-1327.
DOI: 10.3872/j.issn.1007-385X.2020.12.002
Abstract:
Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components in tumor microenvironment,which not only provide physical support for tumor cells, but also play a key role in promoting or delaying tumor occurrence and development. CAFs are a highly abundant and heterogeneous mesenchymal cell line, which contain a large number of cell subsets with different phenotypes and functions. Targeted therapies for CAFs also emerge as demanded. In order to improve the understanding of CAFs in malignant tumors, we elucidate the heterogeneity of CAFs origins, phenotypes and related functions, as well as the research progress of their application in targeted therapy.
Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components in tumor microenvironment,which not only provide physical support for tumor cells, but also play a key role in promoting or delaying tumor occurrence and development. CAFs are a highly abundant and heterogeneous mesenchymal cell line, which contain a large number of cell subsets with different phenotypes and functions. Targeted therapies for CAFs also emerge as demanded. In order to improve the understanding of CAFs in malignant tumors, we elucidate the heterogeneity of CAFs origins, phenotypes and related functions, as well as the research progress of their application in targeted therapy.
2020, 27(12):1328-1335.
DOI: 10.3872/j.issn.1007-385X.2020.12.003
Abstract:
Objective: To explore the role of miR-9-5p in the biological behaviors of breast cancer cells and its possible regulatory mechanism. Methods: online OncomiR database was used to analyze the differential expression of miR-9-5p in breast cancer tissues andnormal breast tissues. qPCR was used to detect the miR-9-5p expression in breast cancer cell lines and normal breast cells. Based on target gene prediction software TargetScan, ONECUT2 (one cut homeobox 2) was predicted to be the target gene of miR-9-5p. Dual luciferase reporter system was used to validate the relationship between miR-9-5p and its promising target gene ONECUT2. MDA-231 cells were transfected with miR-9-5p mimic, ONECUT2 siRNAs as well as the corresponding control sequences. The protein and mRNA levels of stemness-associated gene NOTCH1, NANOG and SOX9 (SRY (sex-determing region of Y chromosome)-Box transcription Factor 9) were detected by WB and qPCR. The effect of transfection on proliferation, apoptosis and chemo-resistance of cells was detected by BrdU method,Annexin Ⅴ method and MTS Assay, respectively. The ALDEFLUOR experiment was used to detect the effects of miR-9-5p and its target gene ONECUT2 on tumor stemness. NSG mouse breast cancer chemotherapy model was established, and the in vivo experiments further verified the effect of ONECUT2 on tumor malignant biological behaviors, such as cell stemness and chemo-resistance. Results: miR-9-5p was highly expressed in breast cancer tissues (P=0.007) and breast cancer MDA-231 cell line (P=0.0005), and was positively correlated with the poor prognosis of breast cancer patients (P=0.0016). Compared to control group, miR-9-5p could target and negatively regulate ONECUT2 expression, further increase ALDH+ cell population (P=0.0006), as well as increase the expressions of stemness-associated genes NOTCH1,NANOG and SOX9. Besides, miR-9-5p increased the anti-apoptosis ability (P=0.0003) and chemo-resistance of MDA-231 cells; however,miR-9-5p/ONECUT2 exerted no significant effect on the proliferation ability of MDA-231 cells (P>0.05). Compared with the control group,the volume of xenografts in mice of MDA-231/ONECUT2 group after DTX chemotherapy was significantly lower than that in the control group (P<0.05), and the protein expressions of NOTCH1, SOX9 and the mRNA expression of ABC transporter in the transplanted tumor tissues were significantly reduced (P<0.05 or P<0.01). Conclusions: The highly expressed miR-9-5p in breast cancer induces tumor stemness and anti-apoptotic ability by targeting ONECUT2 and enhances its resistance to chemotherapy.
Objective: To explore the role of miR-9-5p in the biological behaviors of breast cancer cells and its possible regulatory mechanism. Methods: online OncomiR database was used to analyze the differential expression of miR-9-5p in breast cancer tissues andnormal breast tissues. qPCR was used to detect the miR-9-5p expression in breast cancer cell lines and normal breast cells. Based on target gene prediction software TargetScan, ONECUT2 (one cut homeobox 2) was predicted to be the target gene of miR-9-5p. Dual luciferase reporter system was used to validate the relationship between miR-9-5p and its promising target gene ONECUT2. MDA-231 cells were transfected with miR-9-5p mimic, ONECUT2 siRNAs as well as the corresponding control sequences. The protein and mRNA levels of stemness-associated gene NOTCH1, NANOG and SOX9 (SRY (sex-determing region of Y chromosome)-Box transcription Factor 9) were detected by WB and qPCR. The effect of transfection on proliferation, apoptosis and chemo-resistance of cells was detected by BrdU method,Annexin Ⅴ method and MTS Assay, respectively. The ALDEFLUOR experiment was used to detect the effects of miR-9-5p and its target gene ONECUT2 on tumor stemness. NSG mouse breast cancer chemotherapy model was established, and the in vivo experiments further verified the effect of ONECUT2 on tumor malignant biological behaviors, such as cell stemness and chemo-resistance. Results: miR-9-5p was highly expressed in breast cancer tissues (P=0.007) and breast cancer MDA-231 cell line (P=0.0005), and was positively correlated with the poor prognosis of breast cancer patients (P=0.0016). Compared to control group, miR-9-5p could target and negatively regulate ONECUT2 expression, further increase ALDH+ cell population (P=0.0006), as well as increase the expressions of stemness-associated genes NOTCH1,NANOG and SOX9. Besides, miR-9-5p increased the anti-apoptosis ability (P=0.0003) and chemo-resistance of MDA-231 cells; however,miR-9-5p/ONECUT2 exerted no significant effect on the proliferation ability of MDA-231 cells (P>0.05). Compared with the control group,the volume of xenografts in mice of MDA-231/ONECUT2 group after DTX chemotherapy was significantly lower than that in the control group (P<0.05), and the protein expressions of NOTCH1, SOX9 and the mRNA expression of ABC transporter in the transplanted tumor tissues were significantly reduced (P<0.05 or P<0.01). Conclusions: The highly expressed miR-9-5p in breast cancer induces tumor stemness and anti-apoptotic ability by targeting ONECUT2 and enhances its resistance to chemotherapy.
2020, 27(12):1336-1344.
DOI: 10.3872/j.issn.1007-385X.2020.12.004
Abstract:
Objective:To explore the anti-tumor effect of CAR-T cells secreting PD-1 scFv on gastric cancer. Method: We selected EGFR as the target of CAR-T cells and constructed second-generation EGFR-CAR-T cells (EGFR BB-z) and fourth-generation EGFRCAR-T cells secreting PD-1 scFv (EGFR BB-z/E30). The anti-tumor activity was examined after in vitro activation and long-term stimulation, and its tumor suppression ability was validated through a mouse gastric cell xenograft model. Results: EGFR was highly expressed in gastric cancer tissues and cells (all P<0.01). EGFR BB-z and EGFR BB-z/E30 cells were successfully obtained by lentivirus infection. In vitro experiments showed that compared with EGFR BB-Z, EGFR BB-Z/E30 had longer long-term proliferation ability and stronger tumor killing activity (all P<0.01). In vivo experiments also validated that EGFR BB-z/E30 had obvious tumor inhibitory function in subcutaneous gastric tumor cell transplanted xenograft model and patient-derived tumor xenograft model (PDX)(all P<0.01). It also significantly increased T cell infiltration in tumor site and decreased the expression level of PD-1 (P<0.01 or P<0.05) on EGFR BB-z/E30 cell surface as well as the high secretion of IFN-γ (P<0.05). Conclusion: EGFR-CAR-T cell EGFR BB-z/E30 secreting PD-1 scFv can significantly inhibit the progression of gastric cancer and provide a potential new strategy for the treatment of gastric cancer.
Objective:To explore the anti-tumor effect of CAR-T cells secreting PD-1 scFv on gastric cancer. Method: We selected EGFR as the target of CAR-T cells and constructed second-generation EGFR-CAR-T cells (EGFR BB-z) and fourth-generation EGFRCAR-T cells secreting PD-1 scFv (EGFR BB-z/E30). The anti-tumor activity was examined after in vitro activation and long-term stimulation, and its tumor suppression ability was validated through a mouse gastric cell xenograft model. Results: EGFR was highly expressed in gastric cancer tissues and cells (all P<0.01). EGFR BB-z and EGFR BB-z/E30 cells were successfully obtained by lentivirus infection. In vitro experiments showed that compared with EGFR BB-Z, EGFR BB-Z/E30 had longer long-term proliferation ability and stronger tumor killing activity (all P<0.01). In vivo experiments also validated that EGFR BB-z/E30 had obvious tumor inhibitory function in subcutaneous gastric tumor cell transplanted xenograft model and patient-derived tumor xenograft model (PDX)(all P<0.01). It also significantly increased T cell infiltration in tumor site and decreased the expression level of PD-1 (P<0.01 or P<0.05) on EGFR BB-z/E30 cell surface as well as the high secretion of IFN-γ (P<0.05). Conclusion: EGFR-CAR-T cell EGFR BB-z/E30 secreting PD-1 scFv can significantly inhibit the progression of gastric cancer and provide a potential new strategy for the treatment of gastric cancer.
5 Antitumor activity of chimeric antigen receptor NK-92 cells targeting PSCA anainst cervical cancer
2020, 27(12):1345-1350.
DOI: 10.3872/j.issn.1007-385X.2020.12.005
Abstract:
Objective: To construct and verify the anti-tumor activity of chimeric antigen receptor (CAR) modified NK-92 cells (CAR-NK-92 cells) targeting prostate stem cell antigen (PSCA) in cervical cancer. Methods: Lentiviral vector expressing CAR targeting PSCA was constructed, and PSCA CAR-NK-92 cells were obtained by lentivirus transfection. The expression of PSCA in human cervical cancer cells was determined by Flow cytometry and Western blotting. The killing effect of PSCA CAR-NK-92 cells against cervical cancer cells was verified by co-incubation of effector and target cells in vitro, and the tumor inhibitory ability of PSCA CAR-NK-92 cells was verified with the nude mice xenograft model in vivo. Results: PSCA CAR-NK-92 cells were successfully constructed. PSCA was highly expressed in human cervical cancer Hela and MS751 cells (all P<0.01). In vitro co-incubation results showed that PSCA CAR-NK-92 cells could lyse PSCA+ cervical cancer transplanted tumor in a dose-dependent manner. In vivo antitumor data showed that PSCA CAR-NK-92 cells significantly inhibited the growth of cervical cancer cells compared with NK-92 cells transfected with vehicle vectors (P<0.01). In addition, PSCA CAR-NK-92 cells could effectively infiltrate tumor tissues and promote the secretion of anti-tumor cytokines TNF-α and IFN-γ (all P<0.01). Conclusion: The CAR-NK-92 targeting PSCA shows good antitumor effect on PSCA+ tumor cells both in vitro and in vivo, and has potential to be a therapeutic strategy for cervical cancer.
Objective: To construct and verify the anti-tumor activity of chimeric antigen receptor (CAR) modified NK-92 cells (CAR-NK-92 cells) targeting prostate stem cell antigen (PSCA) in cervical cancer. Methods: Lentiviral vector expressing CAR targeting PSCA was constructed, and PSCA CAR-NK-92 cells were obtained by lentivirus transfection. The expression of PSCA in human cervical cancer cells was determined by Flow cytometry and Western blotting. The killing effect of PSCA CAR-NK-92 cells against cervical cancer cells was verified by co-incubation of effector and target cells in vitro, and the tumor inhibitory ability of PSCA CAR-NK-92 cells was verified with the nude mice xenograft model in vivo. Results: PSCA CAR-NK-92 cells were successfully constructed. PSCA was highly expressed in human cervical cancer Hela and MS751 cells (all P<0.01). In vitro co-incubation results showed that PSCA CAR-NK-92 cells could lyse PSCA+ cervical cancer transplanted tumor in a dose-dependent manner. In vivo antitumor data showed that PSCA CAR-NK-92 cells significantly inhibited the growth of cervical cancer cells compared with NK-92 cells transfected with vehicle vectors (P<0.01). In addition, PSCA CAR-NK-92 cells could effectively infiltrate tumor tissues and promote the secretion of anti-tumor cytokines TNF-α and IFN-γ (all P<0.01). Conclusion: The CAR-NK-92 targeting PSCA shows good antitumor effect on PSCA+ tumor cells both in vitro and in vivo, and has potential to be a therapeutic strategy for cervical cancer.
2020, 27(12):1351-1357.
DOI: 10.3872/j.issn.1007-385X.2020.12.006
Abstract:
Objective：To explore the regulatory effect of miR-9 on biological behaviors of small cell lung cancer (SCLC) cells by targeting zinc finger E-box binding homeobox 2 (ZEB2), and to analyze the role of miR-9 in SCLC and its possible mechanism.Methods: qPCR, WB and immunohistochemistry methods were used to detect the mRNA and protein expressions of ZEB2 in cancer tissues and corresponding adjacent tissues of 67 SCLC patients who received surgical treatment at the Department of Oncology, Fourth Hospital of Hebei Medical University from February 2018 to November 2019. TargetScan was used to predict the potential target gene of miR-9, which was later verified by Dual luciferase reporter gene assay, qPCR and WB methods. CCK-8 method, Flow cytometry and Transwell experiment were used to detect the effect of miR-9 and ZEB2 over-expression on the biological behaviors of NCI-H446 cells,and WB was used to detect the protein expressions of E-cadherin, N-cadherin and Vimentin in cells. NCI-H446 cells overexpressing miR-9 were used to construct SCLC nude mouse xenograft model, and the effect of miR-9 on the growth of xenografts was observed.Results: The mRNA and protein expression levels of ZEB2 in SCLC tissues were significantly higher than those in adjacent tissues (P<0.01). There is a potential binding site on the 3' UTR of ZEB2 to bind with miR-9. Compared with the control group, the mRNA and protein expression levels of ZEB2 in NCI-H446 cells of the miR-9 over-expression group were significantly reduced (P<0.01); the proliferation, migration and invasion abilities of NCI-H446 cells were significantly suppressed (P<0.05 or P<0.01), and the expression of EMT protein was reduced; However, simultaneous over-expression of ZEB2 could reverse above effects. In in vivo experiments, the size and weight of transplanted tumors in the miR-9 over-expression group were significantly lower than those in the control group (P<0.05 or P<0.01). The expression of ZEB2 protein in the tumor tissues of nude mice in the miR-9 overexpression group was significantly lower than that in the control group (P<0.01). Conclusion: miR-9 can inhibit the biological behaviors of SCLC cells and the growth of NCI-H446 transplanted tumors in nude mice by targeting and regulating ZEB2.
Objective：To explore the regulatory effect of miR-9 on biological behaviors of small cell lung cancer (SCLC) cells by targeting zinc finger E-box binding homeobox 2 (ZEB2), and to analyze the role of miR-9 in SCLC and its possible mechanism.Methods: qPCR, WB and immunohistochemistry methods were used to detect the mRNA and protein expressions of ZEB2 in cancer tissues and corresponding adjacent tissues of 67 SCLC patients who received surgical treatment at the Department of Oncology, Fourth Hospital of Hebei Medical University from February 2018 to November 2019. TargetScan was used to predict the potential target gene of miR-9, which was later verified by Dual luciferase reporter gene assay, qPCR and WB methods. CCK-8 method, Flow cytometry and Transwell experiment were used to detect the effect of miR-9 and ZEB2 over-expression on the biological behaviors of NCI-H446 cells,and WB was used to detect the protein expressions of E-cadherin, N-cadherin and Vimentin in cells. NCI-H446 cells overexpressing miR-9 were used to construct SCLC nude mouse xenograft model, and the effect of miR-9 on the growth of xenografts was observed.Results: The mRNA and protein expression levels of ZEB2 in SCLC tissues were significantly higher than those in adjacent tissues (P<0.01). There is a potential binding site on the 3' UTR of ZEB2 to bind with miR-9. Compared with the control group, the mRNA and protein expression levels of ZEB2 in NCI-H446 cells of the miR-9 over-expression group were significantly reduced (P<0.01); the proliferation, migration and invasion abilities of NCI-H446 cells were significantly suppressed (P<0.05 or P<0.01), and the expression of EMT protein was reduced; However, simultaneous over-expression of ZEB2 could reverse above effects. In in vivo experiments, the size and weight of transplanted tumors in the miR-9 over-expression group were significantly lower than those in the control group (P<0.05 or P<0.01). The expression of ZEB2 protein in the tumor tissues of nude mice in the miR-9 overexpression group was significantly lower than that in the control group (P<0.01). Conclusion: miR-9 can inhibit the biological behaviors of SCLC cells and the growth of NCI-H446 transplanted tumors in nude mice by targeting and regulating ZEB2.
2020, 27(12):1358-1364.
DOI: 10.3872/j.issn.1007-385X.2020.12.007
Abstract:
Objective: To investigate the effect of RG108 on the proliferation and apoptosis of human non-small cell lung cancer (NSCLC) cell lines (A549, H1299) and explore its molecular mechanism. Methods: A549 and H1299 cells were cultured in vitro and treated with different concentrations of RG108. The cell proliferation, cell cycle and apoptosis were detected by MTT assay and Flow cytometry, respectively. qPCR and Western blotting (WB) were used to detect the TFPI-2 mRNA and protein expressions as well as the expression of TMPRSS4 in cells. Meanwhile, the methylation status and degree of TFPI-2 promoter in cells were detected with Methylation-specific PCR (MSP) and colorimetry. Finally, siRNA-TFPI-2 and pcDNA3.0-TMPRSS4 plasmids were used to silence TFPI-2 or overexpress TMPRSS4, and then the changes in cell proliferation and apoptosis were detected. Results: After treatment with RG108, the proliferation rate of A549 and H1299 cells were significantly decreased (all P<0.05), while the apoptosis rate were significantly increased(P<0.05), the cell cycle were arrested in G1/S phase (P<0.05), and the intracellular mRNA and protein expressions of TFPI-2 were significantly increased (P<0.01 or P<0.05). Meanwhile, the methylase degree in TFPI-2 promoter region and the expression of TMPRSS4 in cells were all significanly decreased ( all P<0.05). After TFPI-2 silence, the proliferation levels of A549 and H1299 cells were significantly increased(all P<0.05); however, the apoptosis rate of A549 and H1299 cells were significantly reduced after transfection with pcDNA3.0-TMPRSS4(all P<0.05). Conclusion: RG108 can inhibit proliferation of A549 and H1299 cells and promote apoptosis by inhibiting the methylation of TFPI-2 and negatively regulates the expression of TMPRSS4.
Objective: To investigate the effect of RG108 on the proliferation and apoptosis of human non-small cell lung cancer (NSCLC) cell lines (A549, H1299) and explore its molecular mechanism. Methods: A549 and H1299 cells were cultured in vitro and treated with different concentrations of RG108. The cell proliferation, cell cycle and apoptosis were detected by MTT assay and Flow cytometry, respectively. qPCR and Western blotting (WB) were used to detect the TFPI-2 mRNA and protein expressions as well as the expression of TMPRSS4 in cells. Meanwhile, the methylation status and degree of TFPI-2 promoter in cells were detected with Methylation-specific PCR (MSP) and colorimetry. Finally, siRNA-TFPI-2 and pcDNA3.0-TMPRSS4 plasmids were used to silence TFPI-2 or overexpress TMPRSS4, and then the changes in cell proliferation and apoptosis were detected. Results: After treatment with RG108, the proliferation rate of A549 and H1299 cells were significantly decreased (all P<0.05), while the apoptosis rate were significantly increased(P<0.05), the cell cycle were arrested in G1/S phase (P<0.05), and the intracellular mRNA and protein expressions of TFPI-2 were significantly increased (P<0.01 or P<0.05). Meanwhile, the methylase degree in TFPI-2 promoter region and the expression of TMPRSS4 in cells were all significanly decreased ( all P<0.05). After TFPI-2 silence, the proliferation levels of A549 and H1299 cells were significantly increased(all P<0.05); however, the apoptosis rate of A549 and H1299 cells were significantly reduced after transfection with pcDNA3.0-TMPRSS4(all P<0.05). Conclusion: RG108 can inhibit proliferation of A549 and H1299 cells and promote apoptosis by inhibiting the methylation of TFPI-2 and negatively regulates the expression of TMPRSS4.
2020, 27(12):1365-1371.
DOI: 10.3872/j.issn.1007-385X.2020.12.008
Abstract:
Objective: To investigate the effect of double oxidase 2 (DUOX2) on the sensitivity of colorectal cancer (CRC) cells to 5-fluorouracil (5-FU). Methods: CRC cell lines DLD-1, SW480, HCT116, SW620 and normal intestinal epithelial cell line NCM460 were selected, and the expression of DUOX2 in these cell lines were detected by qPCR. DUOX2 expression in HT-29 and HCT116 cells was stably knocked down by lentivirus infection technique. The knockdown efficiency was detected by qPCR and WB. Cells in sh-Control and sh-DUOX2 groups were treated with 5-FU at different concentrations (0, 5, 10, 20, 40, 80, 120 μg/ml). The effects of 5-FU on cell proliferation, apoptosis and cell cycle were detected by CCK-8 method and flow cytometry. HT29 cell transplanted xenograft model in nude mice was constructed to observe the effect of DUOX2 gene on the treatment efficacy of 5-FU. Results: the expression level of DUOX2 mRNA in CRC cells was significantly higher than that in NCM460 cells (P<0.05 or P<0.01). Compared with sh-Control group, the mRNA and protein expressions of DUOX2 in sh-DUOX2 group were significantly decreased (all P<0.01);the sensitivity of cells to 5-FU was enhanced, the apoptosis rate and the ratio of cells at G0/G1 phase were significantly increased (all P<0.01), and the ratio of cells at G2 and S phase was significantly decreased (all P<0.01). There was no significant difference in tumor volume and mass between sh-Control group and sh-DUOX2 group without 5-FU treatment (all P>0.05), but the volume and mass of transplanted tumor in sh-DUOX2+5-FU group after 5-FU treatment was significantly lower than that in sh-Control+5-FU group (all P<0.01). Conclusion: The sensitivity of CRC cells to 5-FU can be significantly enhanced by knocking down DUOX2 gene.
Objective: To investigate the effect of double oxidase 2 (DUOX2) on the sensitivity of colorectal cancer (CRC) cells to 5-fluorouracil (5-FU). Methods: CRC cell lines DLD-1, SW480, HCT116, SW620 and normal intestinal epithelial cell line NCM460 were selected, and the expression of DUOX2 in these cell lines were detected by qPCR. DUOX2 expression in HT-29 and HCT116 cells was stably knocked down by lentivirus infection technique. The knockdown efficiency was detected by qPCR and WB. Cells in sh-Control and sh-DUOX2 groups were treated with 5-FU at different concentrations (0, 5, 10, 20, 40, 80, 120 μg/ml). The effects of 5-FU on cell proliferation, apoptosis and cell cycle were detected by CCK-8 method and flow cytometry. HT29 cell transplanted xenograft model in nude mice was constructed to observe the effect of DUOX2 gene on the treatment efficacy of 5-FU. Results: the expression level of DUOX2 mRNA in CRC cells was significantly higher than that in NCM460 cells (P<0.05 or P<0.01). Compared with sh-Control group, the mRNA and protein expressions of DUOX2 in sh-DUOX2 group were significantly decreased (all P<0.01);the sensitivity of cells to 5-FU was enhanced, the apoptosis rate and the ratio of cells at G0/G1 phase were significantly increased (all P<0.01), and the ratio of cells at G2 and S phase was significantly decreased (all P<0.01). There was no significant difference in tumor volume and mass between sh-Control group and sh-DUOX2 group without 5-FU treatment (all P>0.05), but the volume and mass of transplanted tumor in sh-DUOX2+5-FU group after 5-FU treatment was significantly lower than that in sh-Control+5-FU group (all P<0.01). Conclusion: The sensitivity of CRC cells to 5-FU can be significantly enhanced by knocking down DUOX2 gene.
2020, 27(12):1372-1377.
DOI: 10.3872/j.issn.1007-385X.2020.12.009
Abstract:
Objective: To investigate the effect of miR-3195 on the proliferation of laryngeal carcinoma Hep-2 cells and its molecular mechanism. Methods: From January 2008 to August 2012, the laryngeal cancer tissues and their corresponding paracancerous tissues from 29 patients with laryngeal cancer who were admitted to the Department of Otorhinolaryngology, Chenzhou First People's Hospital Affiliated to teaching hospital of University of South China were selected for this study. qPCR was used to detect the expression of miR-3195 in laryngeal carcinoma and the paracancerous tissues; Hep-2 cell line with stable and high expression of miR-3195 was constructed. The proliferation of miR-3195 over-expressed Hep-2 cells and the control cells was observed by MTT method. A nude mouse xenograft model was established to observe the proliferation of miR-3195 overexpressed Hep-2 cells in nude mice. Bioinformatics tools were used to predict the target gene of miR-3195; the luciferase vector of TBX1 3'UTR was constructed, and its luciferase activity was examined with dual luciferase detection system; Western blotting was used to detect the TBX1 protein expression in miR-3195 over-expressed cells and control cells. Results: The expression of miR-3195 in laryngeal carcinoma tissues was significantly lower than that in paracancerous tissues (P<0.01); miR-3195 up-regulation could inhibit the proliferation of Hep-2 cells (P<0.01) and significantly inhibit the growth of transplanted tumors in nude mice (P<0.05); The results of the Dual luciferase reporter gene assay indicated that miR-3195 might targetedly bind to TBX1 (P<0.05), and Western blotting proved that miR-3195 could inhibit the expression of TBX1 protein (P<0.05). Conclusion: miR-3195 has a significant inhibitory effect on the proliferation of Hep-2 cells, and its molecular mechanism may be related to the negative regulation of TBX1 expression.
Objective: To investigate the effect of miR-3195 on the proliferation of laryngeal carcinoma Hep-2 cells and its molecular mechanism. Methods: From January 2008 to August 2012, the laryngeal cancer tissues and their corresponding paracancerous tissues from 29 patients with laryngeal cancer who were admitted to the Department of Otorhinolaryngology, Chenzhou First People's Hospital Affiliated to teaching hospital of University of South China were selected for this study. qPCR was used to detect the expression of miR-3195 in laryngeal carcinoma and the paracancerous tissues; Hep-2 cell line with stable and high expression of miR-3195 was constructed. The proliferation of miR-3195 over-expressed Hep-2 cells and the control cells was observed by MTT method. A nude mouse xenograft model was established to observe the proliferation of miR-3195 overexpressed Hep-2 cells in nude mice. Bioinformatics tools were used to predict the target gene of miR-3195; the luciferase vector of TBX1 3'UTR was constructed, and its luciferase activity was examined with dual luciferase detection system; Western blotting was used to detect the TBX1 protein expression in miR-3195 over-expressed cells and control cells. Results: The expression of miR-3195 in laryngeal carcinoma tissues was significantly lower than that in paracancerous tissues (P<0.01); miR-3195 up-regulation could inhibit the proliferation of Hep-2 cells (P<0.01) and significantly inhibit the growth of transplanted tumors in nude mice (P<0.05); The results of the Dual luciferase reporter gene assay indicated that miR-3195 might targetedly bind to TBX1 (P<0.05), and Western blotting proved that miR-3195 could inhibit the expression of TBX1 protein (P<0.05). Conclusion: miR-3195 has a significant inhibitory effect on the proliferation of Hep-2 cells, and its molecular mechanism may be related to the negative regulation of TBX1 expression.
2020, 27(12):1378-1382.
DOI: 10.3872/j.issn.1007-385X.2020.12.010
Abstract:
Objective: To investigate the expression and clinical significance of long non-coding RNA (lncRNA) HOTTIP in tissues of patients with endometrial carcinoma. Methods: A total of 109 cases of patients with endometrial carcinoma who underwent surgery in Xingxiang Central Hospital from April 2012 to April 2014 were selected. The endometrial carcinoma tissue and its corresponding adjacent tissue (more than 5 cm from the cancer margin) were obtained. The expressions of HOTTIP in endometrial carcinoma and adjacent tissues were detected by qRT-PCR. All patients were followed up from the first postoperative day. The follow-up deadline was April 30, 2019. The end-point event was death and the patient's survival time was recorded. Results: The relative expression level of HOTTIP in endometrial carcinoma tissues was (2.55±0.21), which was higher than that in the adjacent tissue (1.03±0.16) (t=60.631,P<0.01). The differences of the relative expression levels of HOTTIP in endometrial carcinoma tissues between different FIGO stage,histological grade, depth of myometrial invasion, lymphatic vascular infiltration status and lymph node metastasis were statistically significant (all P<0.05). Kaplan-Meier survival analysis showed that the 5-year survival rate and the survival time in the low expression group were higher than those in the high expression group [78.57% vs 37.04%, (70.67±4.94) months vs (42.14±3.65) months], the difference was statistically significant (χ2 =12.839, P<0.01). Cox proportional hazards regression model analysis showed that the FIGO stage [HR=2.248 (95%CI: 1.034-4.887)], myometrial invasion depth [HR=3.055 (95%CI: 1.668-5.592)], lymph node metastasis [HR=3.811 (95%CI: 1.786-8.131)] and the expression of HOTTIP [HR=2.649 (95%CI: 1.026-6.842)] were all independent influence factors for the prognosis of patients with endometrial carcinoma. Conclusion: lncRNA HOTTIP is highly expressed in endometrial carcinoma tissues and associated with malignant progression of patients. It is an independent influencing factor for patients’prognosis.
Objective: To investigate the expression and clinical significance of long non-coding RNA (lncRNA) HOTTIP in tissues of patients with endometrial carcinoma. Methods: A total of 109 cases of patients with endometrial carcinoma who underwent surgery in Xingxiang Central Hospital from April 2012 to April 2014 were selected. The endometrial carcinoma tissue and its corresponding adjacent tissue (more than 5 cm from the cancer margin) were obtained. The expressions of HOTTIP in endometrial carcinoma and adjacent tissues were detected by qRT-PCR. All patients were followed up from the first postoperative day. The follow-up deadline was April 30, 2019. The end-point event was death and the patient's survival time was recorded. Results: The relative expression level of HOTTIP in endometrial carcinoma tissues was (2.55±0.21), which was higher than that in the adjacent tissue (1.03±0.16) (t=60.631,P<0.01). The differences of the relative expression levels of HOTTIP in endometrial carcinoma tissues between different FIGO stage,histological grade, depth of myometrial invasion, lymphatic vascular infiltration status and lymph node metastasis were statistically significant (all P<0.05). Kaplan-Meier survival analysis showed that the 5-year survival rate and the survival time in the low expression group were higher than those in the high expression group [78.57% vs 37.04%, (70.67±4.94) months vs (42.14±3.65) months], the difference was statistically significant (χ2 =12.839, P<0.01). Cox proportional hazards regression model analysis showed that the FIGO stage [HR=2.248 (95%CI: 1.034-4.887)], myometrial invasion depth [HR=3.055 (95%CI: 1.668-5.592)], lymph node metastasis [HR=3.811 (95%CI: 1.786-8.131)] and the expression of HOTTIP [HR=2.649 (95%CI: 1.026-6.842)] were all independent influence factors for the prognosis of patients with endometrial carcinoma. Conclusion: lncRNA HOTTIP is highly expressed in endometrial carcinoma tissues and associated with malignant progression of patients. It is an independent influencing factor for patients’prognosis.
11 Expression of Wip1 in serum of patients with small cell lung cancer and its clinical significance
2020, 27(12):1383-1387.
DOI: 10.3872/j.issn.1007-385X.2020.12.011
Abstract:
Objective: To investigate the expression of wild type p53 induced phosphatase 1 (Wip1) in small cell lung cancer (SCLC) cells and the serum of SCLC patient and its relationship with clinical prognosis. Methods: Real time quantitative PCR (qPCR) was used to detect the expression of Wip1 in SCLC cells and serum samples. Results: The expression of Wip1 in drug-resistant SCLC cells was significantly higher than that in sensitive cell lines (P<0.01). The expression of Wip1 in serum of SCLC group was significantly higher than that of normal control group (P<0.05); the expression of Wip1 in serum of patients with chemotherapy resistance was significantly higher than that in patients with chemotherapy sensitivity (all P<0.05); the serum Wip1 level was correlated with disease stage, chemotherapy sensitivity and survival status of SCLC patients (all P<0.05). The area under ROC curve of Wip1 predicting the prognosis of SCLC was 0.836 (95%CI: 0.8230-0.9600, P<0.01); the expression lever of Wip1 was significantly correlated with progression free survival and overall survival time of SCLC patients (all P<0.05). Disease stage, chemosensitivity and Wip1 expression were independent prognostic factors for SCLC patients (all P<0.05). Conclusion: The expression of Wip1 in serum of SCLC patients may be related to chemotherapy sensitivity and prognosis. Wip1 may be a potential biomarker for therapeutic efficacy and prognosis evaluation of SCLC patients.
Objective: To investigate the expression of wild type p53 induced phosphatase 1 (Wip1) in small cell lung cancer (SCLC) cells and the serum of SCLC patient and its relationship with clinical prognosis. Methods: Real time quantitative PCR (qPCR) was used to detect the expression of Wip1 in SCLC cells and serum samples. Results: The expression of Wip1 in drug-resistant SCLC cells was significantly higher than that in sensitive cell lines (P<0.01). The expression of Wip1 in serum of SCLC group was significantly higher than that of normal control group (P<0.05); the expression of Wip1 in serum of patients with chemotherapy resistance was significantly higher than that in patients with chemotherapy sensitivity (all P<0.05); the serum Wip1 level was correlated with disease stage, chemotherapy sensitivity and survival status of SCLC patients (all P<0.05). The area under ROC curve of Wip1 predicting the prognosis of SCLC was 0.836 (95%CI: 0.8230-0.9600, P<0.01); the expression lever of Wip1 was significantly correlated with progression free survival and overall survival time of SCLC patients (all P<0.05). Disease stage, chemosensitivity and Wip1 expression were independent prognostic factors for SCLC patients (all P<0.05). Conclusion: The expression of Wip1 in serum of SCLC patients may be related to chemotherapy sensitivity and prognosis. Wip1 may be a potential biomarker for therapeutic efficacy and prognosis evaluation of SCLC patients.
TANG Jingling
,
YANG Yuan
,
WU Xueli
,
XIU Jin
,
LI Xiaoyang
,
LIU Honglin
,
HU Pingsheng
,
WU Chaoyang
,
GE Huixin
2020, 27(12):1388-1392.
DOI: 10.3872/j.issn.1007-385X.2020.12.012
Abstract:
Objective: To observe the clinical effect of adoptive immunocyte infusion combined with immunodeprivation in the treatment of castration-resistant prostate cancer. Methods: The information of 35 patients with castration resistant prostate cancer, who were treated in the Affiliated Guizhou Provincial Cancer Hospital of Guizhou Medical University from 2011 to 2018 was collected.According to different treatments, these patients were divided into biotherapy group (18 cases) and non-biotherapy group (17 cases).Patients in the non-biotherapy group were treated with abiraterone or docetaxel, while the patients in biotherapy group were treated with cytotoxic T lymphocytes (CTL) in combination with cyclophosphamide (CTX). The treatment efficacy in the biotherapy group and the non-biotherapy group was evaluated by comparing the changes of prostate cancer-specific antigen (PSA), improvement of subjective indicators (bone pain, sleep, physical strength) and clinical efficacy before and after treatment. Results: (1) PSA level: after treatment,PSA was decreased in both groups; the biotherapy group had an obvious decrease (P<0.01), which was more significant than the decrease in non-biotherapy group (P<0.05). (2) Clinical efficacy: The clinical efficacy of patients after CTL treatment was significantly different from that of non-biotherapy group (P<0.01). (3) Subjective indicators: The bone pain, sleep and physical strength of the patients in the biotherapy group were significantly improved after treatment, and there was a significant difference as compared with patients of the non-biological treatment group (P<0.01). (4) Overall survival: The median survival of the patients receiving biotherapy was 4 months longer than patients from non-biological treatment group, but the difference was insignificant (P=0.3935). Conclusion:CTL combined with CTX in the treatment of castration resistant prostate cancer can significantly reduce PSA and improve the quality of life of patients.
Objective: To observe the clinical effect of adoptive immunocyte infusion combined with immunodeprivation in the treatment of castration-resistant prostate cancer. Methods: The information of 35 patients with castration resistant prostate cancer, who were treated in the Affiliated Guizhou Provincial Cancer Hospital of Guizhou Medical University from 2011 to 2018 was collected.According to different treatments, these patients were divided into biotherapy group (18 cases) and non-biotherapy group (17 cases).Patients in the non-biotherapy group were treated with abiraterone or docetaxel, while the patients in biotherapy group were treated with cytotoxic T lymphocytes (CTL) in combination with cyclophosphamide (CTX). The treatment efficacy in the biotherapy group and the non-biotherapy group was evaluated by comparing the changes of prostate cancer-specific antigen (PSA), improvement of subjective indicators (bone pain, sleep, physical strength) and clinical efficacy before and after treatment. Results: (1) PSA level: after treatment,PSA was decreased in both groups; the biotherapy group had an obvious decrease (P<0.01), which was more significant than the decrease in non-biotherapy group (P<0.05). (2) Clinical efficacy: The clinical efficacy of patients after CTL treatment was significantly different from that of non-biotherapy group (P<0.01). (3) Subjective indicators: The bone pain, sleep and physical strength of the patients in the biotherapy group were significantly improved after treatment, and there was a significant difference as compared with patients of the non-biological treatment group (P<0.01). (4) Overall survival: The median survival of the patients receiving biotherapy was 4 months longer than patients from non-biological treatment group, but the difference was insignificant (P=0.3935). Conclusion:CTL combined with CTX in the treatment of castration resistant prostate cancer can significantly reduce PSA and improve the quality of life of patients.
2020, 27(12):1393-1398.
DOI: 10.3872/j.issn.1007-385X.2020.12.013
Abstract:
Objective: To screen the key genes associated with esophageal adenocarcinoma by using TCGA and GEO databases, and to analyze their biological functions, relevant signaling pathways and clinical significance. Methods: The esophageal adenocarcinoma data downloaded from TCGA database and GSE92396 microarray data from GEO database were integrated. The analysis of differentially expressed genes (DEGs) were performed by using DEseq2 and Limma packages of R software to obtain the co-differentially expressed genes, which were then chosen for the GO function enrichment analysis and KEGG pathway analysis with clusterProfiler package of R software. The key node genes that regulate the protein expressions in esophageal adenocarcinoma were screened out by protein-protein interaction (PPI) network analysis using the string website and Cytoscape 3.7.2 software. The correlation between key node genes and the survival of patients was further analyzed by combining with TCGA database. Results: By analyzing the chip data of 90 cases of adenocarcinoma tissues and 18 cases of normal esophageal tissues from databases, a total of 521 co-differentially expressed genes were obtained, including 356 upregulated genes and 165 downregulated genes. These genes were closely related to the metabolicassociated functions mainly involving epidermis development, epidermal cell differentiation and signaling pathways involving cytokinecytokine receptor interaction, etc. The PPI network analysis revealed 15 key node genes. The survival time for patients with low CXCL8 and CCL20 expression was significantly longer compared with the patients with high expression level (median survival: 32.4 vs 19.7 months, P<0.05; 32.4 vs 13.9 months, P<0.05). Conclusion: These results show that CXCL8 and CCL20 may play an important role in the occurrence, development and prognosis of esophageal adenocarcinoma, and may be used as potential indicators to judge the prognosis of patients.
Objective: To screen the key genes associated with esophageal adenocarcinoma by using TCGA and GEO databases, and to analyze their biological functions, relevant signaling pathways and clinical significance. Methods: The esophageal adenocarcinoma data downloaded from TCGA database and GSE92396 microarray data from GEO database were integrated. The analysis of differentially expressed genes (DEGs) were performed by using DEseq2 and Limma packages of R software to obtain the co-differentially expressed genes, which were then chosen for the GO function enrichment analysis and KEGG pathway analysis with clusterProfiler package of R software. The key node genes that regulate the protein expressions in esophageal adenocarcinoma were screened out by protein-protein interaction (PPI) network analysis using the string website and Cytoscape 3.7.2 software. The correlation between key node genes and the survival of patients was further analyzed by combining with TCGA database. Results: By analyzing the chip data of 90 cases of adenocarcinoma tissues and 18 cases of normal esophageal tissues from databases, a total of 521 co-differentially expressed genes were obtained, including 356 upregulated genes and 165 downregulated genes. These genes were closely related to the metabolicassociated functions mainly involving epidermis development, epidermal cell differentiation and signaling pathways involving cytokinecytokine receptor interaction, etc. The PPI network analysis revealed 15 key node genes. The survival time for patients with low CXCL8 and CCL20 expression was significantly longer compared with the patients with high expression level (median survival: 32.4 vs 19.7 months, P<0.05; 32.4 vs 13.9 months, P<0.05). Conclusion: These results show that CXCL8 and CCL20 may play an important role in the occurrence, development and prognosis of esophageal adenocarcinoma, and may be used as potential indicators to judge the prognosis of patients.
2020, 27(12):1399-1405.
DOI: 10.3872/j.issn.1007-385X.2020.12.014
Abstract:
Objective: To explore the expression and biological significance of GABRE gene in colon cancer by mining data in the Oncomine and TCGA databases. Methods: The expression of the GABRE gene in colon cancer tissues and its correlation with the prognosis of patients were analyzed using the Oncomine and TCGA databases. The upstream miRNA targeting GABRE gene was identified using TargetScan, starBase, mirDIP, and miRWalk, and its expression and relationship with prognosis of colon cancer were analyzed. Furthermore, the GABRE co-expression genes were screened using the LinkedOmics database, and the GO enrichment analysis and KEGG pathway analysis were carried out. Results: The results showed that GABRE was highly expressed in colon cancer and indicated a poor prognosis (all P<0.05). The Venn diagram indicated that hsa-miR-370-3p targeted GABRE, and its expression was markedly increased in normal tissues (P<0.01). The expression of GABRE was positively correlated with the expressions of OGT and FAM156A genes, whereas negatively correlated with the expressions of ATP5A1 and MPDU1 genes (all P<0.05). GO biological process function and KEGG pathway enrichment analysis suggested that the GABRE gene may be involved in biological processes including protein dealkylation and regulation of cyclin-dependent protein kinase activity and enriched in taurine metabolism and NF-κB signaling pathway. Conclusions: GABRE gene is highly expressed in patients with colon cancer and indicates a poor prognosis,suggesting that the gene may serve as a potential novel target for the diagnosis and treatment of colon cancer.
Objective: To explore the expression and biological significance of GABRE gene in colon cancer by mining data in the Oncomine and TCGA databases. Methods: The expression of the GABRE gene in colon cancer tissues and its correlation with the prognosis of patients were analyzed using the Oncomine and TCGA databases. The upstream miRNA targeting GABRE gene was identified using TargetScan, starBase, mirDIP, and miRWalk, and its expression and relationship with prognosis of colon cancer were analyzed. Furthermore, the GABRE co-expression genes were screened using the LinkedOmics database, and the GO enrichment analysis and KEGG pathway analysis were carried out. Results: The results showed that GABRE was highly expressed in colon cancer and indicated a poor prognosis (all P<0.05). The Venn diagram indicated that hsa-miR-370-3p targeted GABRE, and its expression was markedly increased in normal tissues (P<0.01). The expression of GABRE was positively correlated with the expressions of OGT and FAM156A genes, whereas negatively correlated with the expressions of ATP5A1 and MPDU1 genes (all P<0.05). GO biological process function and KEGG pathway enrichment analysis suggested that the GABRE gene may be involved in biological processes including protein dealkylation and regulation of cyclin-dependent protein kinase activity and enriched in taurine metabolism and NF-κB signaling pathway. Conclusions: GABRE gene is highly expressed in patients with colon cancer and indicates a poor prognosis,suggesting that the gene may serve as a potential novel target for the diagnosis and treatment of colon cancer.
2020, 27(12):1406-1410.
DOI: 10.3872/j.issn.1007-385X.2020.12.015
Abstract:
羧基末端结合蛋白（C-terminal Binding Protein，CtBP）是在多种肿瘤组织中过表达的致癌共转录因子，参与早期发育、细胞周期调控和转化。以往研究证明CtBP与肿瘤的发生发展有密切关系，能够介导阻遏肿瘤抑制基因的转录，促进上皮细胞间充质，并且可以作为凋亡拮抗剂。CtBP蛋白的功能缺失会导致转录失衡，是肿瘤研究的重要方面。因此，开发靶向CtBP的辅助抑制因子治疗可能成为治疗多种肿瘤的有效方法。本篇综述主要介绍了CtBP的结构、在肿瘤进展中的作用以及靶向CtBP的抑制剂的研究进展。
羧基末端结合蛋白（C-terminal Binding Protein，CtBP）是在多种肿瘤组织中过表达的致癌共转录因子，参与早期发育、细胞周期调控和转化。以往研究证明CtBP与肿瘤的发生发展有密切关系，能够介导阻遏肿瘤抑制基因的转录，促进上皮细胞间充质，并且可以作为凋亡拮抗剂。CtBP蛋白的功能缺失会导致转录失衡，是肿瘤研究的重要方面。因此，开发靶向CtBP的辅助抑制因子治疗可能成为治疗多种肿瘤的有效方法。本篇综述主要介绍了CtBP的结构、在肿瘤进展中的作用以及靶向CtBP的抑制剂的研究进展。
2020, 27(12):1411-1415.
DOI: 10.3872/j.issn.1007-385X.2020.12.016
Abstract:
嵌合抗原受体基因修饰T淋巴细胞（chimeric antigen receptor gene modified-T lymphocytes，CAR-T）疗法是主要应用于血液肿瘤和多种实体瘤的一种治疗方法。尽管其临床疗效良好，有巨大的应用潜力和发展前景，但接受CAR-T细胞治疗后获得缓解的大部分患者病情会再次复发。近年来，随着CAR-T细胞疗法的不断探索，探明了越来越多的复发机制，主要为CAR-T细胞体内持久性有限，靶抗原丢失和调变等。本文结合近年来发表文献对CAR-T细胞治疗后复发的机制进行详解，并从CAR设计、T细胞亚型选择、CAR-T细胞制备、CAR-T细胞质控以及CAR-T细胞应用全链条的关注和管理对其应对策略进行总结。
嵌合抗原受体基因修饰T淋巴细胞（chimeric antigen receptor gene modified-T lymphocytes，CAR-T）疗法是主要应用于血液肿瘤和多种实体瘤的一种治疗方法。尽管其临床疗效良好，有巨大的应用潜力和发展前景，但接受CAR-T细胞治疗后获得缓解的大部分患者病情会再次复发。近年来，随着CAR-T细胞疗法的不断探索，探明了越来越多的复发机制，主要为CAR-T细胞体内持久性有限，靶抗原丢失和调变等。本文结合近年来发表文献对CAR-T细胞治疗后复发的机制进行详解，并从CAR设计、T细胞亚型选择、CAR-T细胞制备、CAR-T细胞质控以及CAR-T细胞应用全链条的关注和管理对其应对策略进行总结。
2020, 27(12):1416-1422.
DOI: 10.3872/j.issn.1007-385X.2020.12.017
Abstract:
软组织肉瘤（soft tissue sarcoma, STS）是20岁以下人群恶性肿瘤死亡的5大原因之一，传统的治疗方法疗效不佳且患者耐受性差，而免疫治疗为攻克STS提供了新途径。STS细胞表面多种高免疫原性抗原可作为工程化T细胞的攻击靶点，过继细胞疗法（adoptive T-cell therapy，ACT）在STS中具有较大的应用潜力。靶向HER2的CAR-T细胞疗法和靶向NY-ESO-1的TCR-T细胞疗法分别在临床试验中产生了临床获益，但其疗效也受到肿瘤免疫微环境的影响。STS部分肿瘤抗原在正常组织也有表达，可被CAR-T或TCR-T细胞错误攻击而引起严重的毒副作用。为进一步增强ACT治疗STS的有效性和安全性，联合免疫检查点抑制剂的综合治疗、CAR-T设计中导入自杀基因等新治疗策略已进入STS的临床治疗。随着二代测序技术的进步，对STS各亚型免疫学性质有了更深入的研究，对免疫治疗在STS中的应用会更加“特异性”和“个体化”。
软组织肉瘤（soft tissue sarcoma, STS）是20岁以下人群恶性肿瘤死亡的5大原因之一，传统的治疗方法疗效不佳且患者耐受性差，而免疫治疗为攻克STS提供了新途径。STS细胞表面多种高免疫原性抗原可作为工程化T细胞的攻击靶点，过继细胞疗法（adoptive T-cell therapy，ACT）在STS中具有较大的应用潜力。靶向HER2的CAR-T细胞疗法和靶向NY-ESO-1的TCR-T细胞疗法分别在临床试验中产生了临床获益，但其疗效也受到肿瘤免疫微环境的影响。STS部分肿瘤抗原在正常组织也有表达，可被CAR-T或TCR-T细胞错误攻击而引起严重的毒副作用。为进一步增强ACT治疗STS的有效性和安全性，联合免疫检查点抑制剂的综合治疗、CAR-T设计中导入自杀基因等新治疗策略已进入STS的临床治疗。随着二代测序技术的进步，对STS各亚型免疫学性质有了更深入的研究，对免疫治疗在STS中的应用会更加“特异性”和“个体化”。
2020, 27(12):1423-1430.
DOI: 10.3872/j.issn.1007-385X.2020.12.018
Abstract:
约2/3的晚期上皮性卵巢癌患者经标准治疗后最终会复发。标准治疗后使用靶向药物维持治疗可延长无铂间隔，降低出现继发性铂耐药的风险，增加后续治疗时铂类药物的选择，提高患者下次含铂化疗的应答率，可延长患者的无进展生存期和总生存率。继VEGF抑制剂贝伐珠单抗（bevacizumab）被推荐用于上皮性卵巢癌维持治疗后，多项维持治疗研究成果已公布，维持治疗的方案根据乳腺癌易感基因（breast cancer susceptibility gene，BRCA）状态和初治是否使用贝伐珠单抗进行了更新：BRCA 1/2 突变的患者 ，初始治疗中如果使用贝伐珠单抗 ，维持治疗可以用聚二磷酸腺苷核糖聚合酶[poly(ADP-ribose)polymerase，PARP]抑制剂奥拉帕尼联合贝伐珠单抗或者奥拉帕尼单药或者尼拉帕尼单药，而对于初始治疗时未使用贝伐珠单抗的患者，推荐使用奥拉帕尼或者尼拉帕尼维持；无BRCA突变的患者，在初始治疗中如果使用贝伐珠单抗，推荐用奥拉帕尼联合贝伐珠单抗或单药贝伐珠单抗，初始治疗中未使用过贝伐珠单抗的患者推荐使用尼拉帕尼维持。PD-1/PD-L1抑制剂的多项临床研究也正在开展。本文主要对微血管生成抑制剂、PARP抑制剂、PD-1/PD-L1抑制剂治疗上皮性卵巢癌的最新研究进展进行综述。
约2/3的晚期上皮性卵巢癌患者经标准治疗后最终会复发。标准治疗后使用靶向药物维持治疗可延长无铂间隔，降低出现继发性铂耐药的风险，增加后续治疗时铂类药物的选择，提高患者下次含铂化疗的应答率，可延长患者的无进展生存期和总生存率。继VEGF抑制剂贝伐珠单抗（bevacizumab）被推荐用于上皮性卵巢癌维持治疗后，多项维持治疗研究成果已公布，维持治疗的方案根据乳腺癌易感基因（breast cancer susceptibility gene，BRCA）状态和初治是否使用贝伐珠单抗进行了更新：BRCA 1/2 突变的患者 ，初始治疗中如果使用贝伐珠单抗 ，维持治疗可以用聚二磷酸腺苷核糖聚合酶[poly(ADP-ribose)polymerase，PARP]抑制剂奥拉帕尼联合贝伐珠单抗或者奥拉帕尼单药或者尼拉帕尼单药，而对于初始治疗时未使用贝伐珠单抗的患者，推荐使用奥拉帕尼或者尼拉帕尼维持；无BRCA突变的患者，在初始治疗中如果使用贝伐珠单抗，推荐用奥拉帕尼联合贝伐珠单抗或单药贝伐珠单抗，初始治疗中未使用过贝伐珠单抗的患者推荐使用尼拉帕尼维持。PD-1/PD-L1抑制剂的多项临床研究也正在开展。本文主要对微血管生成抑制剂、PARP抑制剂、PD-1/PD-L1抑制剂治疗上皮性卵巢癌的最新研究进展进行综述。
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
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.