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Volume 30,Issue 6,2023 Table of Contents
ZHOU Jingsheng
,
WANG Zhen
,
XIN Zhongyuan
,
XU Kehao
,
REN Yufei
,
CHEN Cuimin
,
LIANG Hao
,
ZHANG Tinglin
,
GAO Jie
2023, 30(6).
Abstract:
Objective: To construct hollow copper sulfide nanocarrier with lipid to improve the endocytosis efficiency of copper sulfide, and to further investigate the effect and mechanism of killing melanoma cells by chemodynamic therapy (CDT) combined with photothermal therapy (PTT) in near-infrared second region (NIR-II). Methods: Firstly, cationic liposome (LIP) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome coated copper sulfide nanocarriers (CuS@LIP). Secondly, the photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1064 nm laser irradiation. The catalytic activity of CuS@LIP to catalyze H2O2 was verified by detecting system of hydrogen peroxide (H2O2) and 3,3",5,5" -tetramethylbenzidine (TMB). Finally, the cell viability of B16-F10 melanoma cells were determined with a series of CuS and CuS@LIP with various concentration gradient under 1064 nm laser via CCK-8 method, and the appropriate CuS@LIP concentration was screened for subsequent experiments, and cell viability was detected by Calcein-AM/PI method and Annexin V-FITC/PI staining and flow cytometry were used to determine the apoptosis rate. Results: The average particle size of CuS@LIP was 178.23 ± 6.46 nm and the average Zeta potential was 20.47±0.93 mV. The highest temperature of 80 μg/mL CuS@LIP at 1064 nm laser irradiation was 65.4 ℃, which was higher than that of CuS at 63.4 ℃. The end point temperature of CuS@LIP is basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP has the same catalytic activity as CuS. The results of CCK-8 showed that CuS@LIP had no significant effect on the cell activity in vitro when it was less than 20 μg/ml, but the killing effect was significantly increased by 58.18% after laser irradiation(P<0.001). The rate of dead cells increased from 2.68% to 19.81% (P<0.001). The apoptosis rate was 19.34% in the NIR group compared with 13.36% in the non-light group (P<0.01). Conclusion: CuS@LIP can be endocytosed by melanoma cells with high efficiency, and maintain the catalytic property of H2O2 used in chemodynamic therapy. At the same time, the near infrared laser irradiation showed better anti-melanoma and killing effect of photothermal therapy. Therefore, CuS@LIP represents an excellent antitumor approach towards melanoma.
Objective: To construct hollow copper sulfide nanocarrier with lipid to improve the endocytosis efficiency of copper sulfide, and to further investigate the effect and mechanism of killing melanoma cells by chemodynamic therapy (CDT) combined with photothermal therapy (PTT) in near-infrared second region (NIR-II). Methods: Firstly, cationic liposome (LIP) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome coated copper sulfide nanocarriers (CuS@LIP). Secondly, the photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1064 nm laser irradiation. The catalytic activity of CuS@LIP to catalyze H2O2 was verified by detecting system of hydrogen peroxide (H2O2) and 3,3",5,5" -tetramethylbenzidine (TMB). Finally, the cell viability of B16-F10 melanoma cells were determined with a series of CuS and CuS@LIP with various concentration gradient under 1064 nm laser via CCK-8 method, and the appropriate CuS@LIP concentration was screened for subsequent experiments, and cell viability was detected by Calcein-AM/PI method and Annexin V-FITC/PI staining and flow cytometry were used to determine the apoptosis rate. Results: The average particle size of CuS@LIP was 178.23 ± 6.46 nm and the average Zeta potential was 20.47±0.93 mV. The highest temperature of 80 μg/mL CuS@LIP at 1064 nm laser irradiation was 65.4 ℃, which was higher than that of CuS at 63.4 ℃. The end point temperature of CuS@LIP is basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP has the same catalytic activity as CuS. The results of CCK-8 showed that CuS@LIP had no significant effect on the cell activity in vitro when it was less than 20 μg/ml, but the killing effect was significantly increased by 58.18% after laser irradiation(P<0.001). The rate of dead cells increased from 2.68% to 19.81% (P<0.001). The apoptosis rate was 19.34% in the NIR group compared with 13.36% in the non-light group (P<0.01). Conclusion: CuS@LIP can be endocytosed by melanoma cells with high efficiency, and maintain the catalytic property of H2O2 used in chemodynamic therapy. At the same time, the near infrared laser irradiation showed better anti-melanoma and killing effect of photothermal therapy. Therefore, CuS@LIP represents an excellent antitumor approach towards melanoma.
2023, 30(6):455-463.
DOI: 10.3872/j.issn.1007-385X.2023.06.001
Abstract:
Immunotherapy based on immune checkpoint inhibitor (ICI) has become the main treatment strategy for advanced non-small cell lung cancer (NSCLC)．By releasing immune checkpoint mediated immunosuppression, ICI restores the body's immune balance, improves the anti-tumor response rate, and significantly improves the prognosis of patients with advanced NSCLC. However, many problems remain unsolved in ICI treatment for advanced NSCLC. The present article will focus on the full-course management of ICI immunotherapy in advanced NSCLC patients, including prediction of immunotherapy efficacy, special patients screening before the initiation of ICI therapy, choice of the ICI drugs, development of new generation ICI drugs, restart of ICI immunotherapy after immune-related adverse event, ICI resistance, and the management of immune-related adverse events, in order to provide guidance for immunotherapy for advanced NSCLC patients.
Immunotherapy based on immune checkpoint inhibitor (ICI) has become the main treatment strategy for advanced non-small cell lung cancer (NSCLC)．By releasing immune checkpoint mediated immunosuppression, ICI restores the body's immune balance, improves the anti-tumor response rate, and significantly improves the prognosis of patients with advanced NSCLC. However, many problems remain unsolved in ICI treatment for advanced NSCLC. The present article will focus on the full-course management of ICI immunotherapy in advanced NSCLC patients, including prediction of immunotherapy efficacy, special patients screening before the initiation of ICI therapy, choice of the ICI drugs, development of new generation ICI drugs, restart of ICI immunotherapy after immune-related adverse event, ICI resistance, and the management of immune-related adverse events, in order to provide guidance for immunotherapy for advanced NSCLC patients.
ZHANG Mengya
,
ZHOU Jingsheng
,
WANG Zhen
,
XIN Zhongyuan
,
XU Kehao
,
REN Yufei
,
CHEN Cuimin
,
LIANG Hao
,
ZHANG Tinglin
,
GAO Jie
2023, 30(6):464-472.
DOI: 10.3872/j.issn.1007-385X.2023.06.002
Abstract:
Objective: To construct a hollow copper sulfide nano-enzyme lipid composite nanocarrier CuS@LIP, and to further investigate the effect and mechanism of CuS@LIP combined laser irradiation on killing melanoma B6-F10 cells. Methods: (2, 3-dioleoyloxy-propyl) -3-trimethylammonium-propane (chloride salt) (DOTAP) cationic liposomes (LIPs) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome-coated copper sulfide nanocarriers (CuS@LIP). The photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1 064 nm laser irradiation. The peroxidase-like activity of CuS@LIP was verified by a catalytic activity detecting system of hydrogen peroxide (H2O2) and 3, 3', 5, 5' -tetramethylbenzidine(TMB). B16-F10 cells were treated respectively with a series of mass concentration gradients of CuS or CuS@LIP with or without laser. The cell viability of B16-F10 cells was determined via CCK-8 assay. Calcein-AM/PI staining and Annexin Ⅴ-FITC/PI staining combined with flow cytometry detected the effects of 20 μg/mL CuS or CuS@LIP on the cell viability and apoptosis of B16-F10 cells under laser or non-laser irradiation, respectively. Results: The average particle size of successfully prepared CuS@LIP was (178.23±6.46) nm and the average Zeta potential was (20.47±0.93) mV. The highest temperature of 80 μg/mL CuS@LIP under laser irradiation was 65.4 ℃, which was higher than that of CuS at 63.4 ℃. The endpoint temperature of CuS@LIP was basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP had the same peroxidase-like catalytic activity as CuS. CuS@LIP had no significant effect on the proliferation activity of B16-F10 cells in vitro when it was less than 20 μg/mL (P>0.05), but the survival rate was significantly reduced by 58.18% after laser irradiation ([29.76±3.60]% vs [87.95±8.18]%, P<0.000 1). The apoptosis rate was significantly increased ([19.34±4.41]% vs [13.36±0.86]% , P<0.01). Conclusion: The prepared CuS@LIP has physical and chemical properties, good photothermal properties and excellent peroxidase-like catalytic activity that meet the design requirements,and it shows a better effect of killing B16-F10 cells when combined with laser irradiation.
Objective: To construct a hollow copper sulfide nano-enzyme lipid composite nanocarrier CuS@LIP, and to further investigate the effect and mechanism of CuS@LIP combined laser irradiation on killing melanoma B6-F10 cells. Methods: (2, 3-dioleoyloxy-propyl) -3-trimethylammonium-propane (chloride salt) (DOTAP) cationic liposomes (LIPs) were applied to encapsulate copper sulfide (CuS) to construct cationic liposome-coated copper sulfide nanocarriers (CuS@LIP). The photothermal properties and stability of CuS and CuS@LIP at different concentrations were studied under 1 064 nm laser irradiation. The peroxidase-like activity of CuS@LIP was verified by a catalytic activity detecting system of hydrogen peroxide (H2O2) and 3, 3', 5, 5' -tetramethylbenzidine(TMB). B16-F10 cells were treated respectively with a series of mass concentration gradients of CuS or CuS@LIP with or without laser. The cell viability of B16-F10 cells was determined via CCK-8 assay. Calcein-AM/PI staining and Annexin Ⅴ-FITC/PI staining combined with flow cytometry detected the effects of 20 μg/mL CuS or CuS@LIP on the cell viability and apoptosis of B16-F10 cells under laser or non-laser irradiation, respectively. Results: The average particle size of successfully prepared CuS@LIP was (178.23±6.46) nm and the average Zeta potential was (20.47±0.93) mV. The highest temperature of 80 μg/mL CuS@LIP under laser irradiation was 65.4 ℃, which was higher than that of CuS at 63.4 ℃. The endpoint temperature of CuS@LIP was basically unchanged through the cyclic test of three laser on/off switches. In addition, CuS@LIP had the same peroxidase-like catalytic activity as CuS. CuS@LIP had no significant effect on the proliferation activity of B16-F10 cells in vitro when it was less than 20 μg/mL (P>0.05), but the survival rate was significantly reduced by 58.18% after laser irradiation ([29.76±3.60]% vs [87.95±8.18]%, P<0.000 1). The apoptosis rate was significantly increased ([19.34±4.41]% vs [13.36±0.86]% , P<0.01). Conclusion: The prepared CuS@LIP has physical and chemical properties, good photothermal properties and excellent peroxidase-like catalytic activity that meet the design requirements,and it shows a better effect of killing B16-F10 cells when combined with laser irradiation.
2023, 30(6):473-481.
DOI: 10.3872/j.issn.1007-385X.2023.06.003
Abstract:
Objective: To investigate the role of sclerostin domain-containing protein 1 (SOSTDC1) in regulating malignant biological behaviors of cervical cancer (CC) cells and its molecular mechanism through in vitro experiments. Methods: Fifty-three cervical cancer tissues and corresponding paracancerous tissues were collected from biopsy or surgical resection at Fujian Cancer Hospital between August 2020 and May 2022，immunohistochemistry was used to investigate SOSTDC1 expression in CC and adjacent cervical tissue specimens. qPCR was performed to detect SOSTDC1 mRNA expression levels in normal cervical tissues and CC cells. CC cells SiHa and CaSki transfected with SOSTDC1 over-expression lentiviruses (OE-sostdc1) and negative control (NC) viruses were divided into SiHa-OE-sostdc1 group, SiHa-NC group, CaSki-OE-sostdc1 group and CaSki-NC group. WST-1, colony formation, and Transwell assays were used to detect the proliferative, colony-formative, migratory and invasive abilities of SiHa and CaSki cells in all the groups.The expressions of proteins related to BMP, Wnt/β -catenin signaling pathways, and epithelial mesenchymal transition (EMT) were detected by Western blotting. qPCR and WB arrays were performed on CC cells treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5'-Aza-CdR) to detect the changes in the expressions of SOSTDC1 mRNA and proteins. Methylation-specific PCR (MSP) assay was performed to analyze the level of gene promoter methylation of SOSTDC1 in 5 pairs of CC and para-cancerous tissue samples, while qPCR was used to detect SOSTDC1 mRNA levels in the tissues. Results: The expression of SOSTDC1 protein was significantly reduced in CC tissues compared with para-cancerous tissues (P<0.01), and low SOSTDC1 expression was found to be correlated with lymph node metastasis and FIGO staging (all P<0.05). The expression levels of SOSTDC1 mRNA were significantly reduced in C33A, HeLa, SiHa and CaSki cells compared with normal cervical HUCEC cells. Over-expression of SOSTDC1 significantly inhibited the proliferative, migratory, and invasive abilities of SiHa and CaSki cells (all P<0.05). WB analysis showed that over-expression of SOSTDC1 significantly inhibited the expressions of p-Smad, Dvl2/3, β -catenin, vimentin, N-cadherin and Snail proteins in SiHa and CaSki cells (all P<0.05). The levels of SOSTDC1 mRNA and protein in SiHa and CaSki cells treated with 5'-Aza-CdR treatment were significantly increased (all P<0.05). MSP analysis showed that compared with in para-cancerous tissues, the SOSTDC1 gene promoter was highly methylated in CC tissues, while the expression of SOSTDC1 mRNA was down-regulated (P<0.01). Conclusion: SOSTDC1 is downregulated in cervical cancer tissues, and low SOSTDC1 expression is correlated with malignant progression of tumors. SOSTDC1 may suppress the proliferative, migratory, and invasive abilities of SiHa and CaSki cells through blocking BMP and Wnt/β-catenin signaling pathways.
Objective: To investigate the role of sclerostin domain-containing protein 1 (SOSTDC1) in regulating malignant biological behaviors of cervical cancer (CC) cells and its molecular mechanism through in vitro experiments. Methods: Fifty-three cervical cancer tissues and corresponding paracancerous tissues were collected from biopsy or surgical resection at Fujian Cancer Hospital between August 2020 and May 2022，immunohistochemistry was used to investigate SOSTDC1 expression in CC and adjacent cervical tissue specimens. qPCR was performed to detect SOSTDC1 mRNA expression levels in normal cervical tissues and CC cells. CC cells SiHa and CaSki transfected with SOSTDC1 over-expression lentiviruses (OE-sostdc1) and negative control (NC) viruses were divided into SiHa-OE-sostdc1 group, SiHa-NC group, CaSki-OE-sostdc1 group and CaSki-NC group. WST-1, colony formation, and Transwell assays were used to detect the proliferative, colony-formative, migratory and invasive abilities of SiHa and CaSki cells in all the groups.The expressions of proteins related to BMP, Wnt/β -catenin signaling pathways, and epithelial mesenchymal transition (EMT) were detected by Western blotting. qPCR and WB arrays were performed on CC cells treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5'-Aza-CdR) to detect the changes in the expressions of SOSTDC1 mRNA and proteins. Methylation-specific PCR (MSP) assay was performed to analyze the level of gene promoter methylation of SOSTDC1 in 5 pairs of CC and para-cancerous tissue samples, while qPCR was used to detect SOSTDC1 mRNA levels in the tissues. Results: The expression of SOSTDC1 protein was significantly reduced in CC tissues compared with para-cancerous tissues (P<0.01), and low SOSTDC1 expression was found to be correlated with lymph node metastasis and FIGO staging (all P<0.05). The expression levels of SOSTDC1 mRNA were significantly reduced in C33A, HeLa, SiHa and CaSki cells compared with normal cervical HUCEC cells. Over-expression of SOSTDC1 significantly inhibited the proliferative, migratory, and invasive abilities of SiHa and CaSki cells (all P<0.05). WB analysis showed that over-expression of SOSTDC1 significantly inhibited the expressions of p-Smad, Dvl2/3, β -catenin, vimentin, N-cadherin and Snail proteins in SiHa and CaSki cells (all P<0.05). The levels of SOSTDC1 mRNA and protein in SiHa and CaSki cells treated with 5'-Aza-CdR treatment were significantly increased (all P<0.05). MSP analysis showed that compared with in para-cancerous tissues, the SOSTDC1 gene promoter was highly methylated in CC tissues, while the expression of SOSTDC1 mRNA was down-regulated (P<0.01). Conclusion: SOSTDC1 is downregulated in cervical cancer tissues, and low SOSTDC1 expression is correlated with malignant progression of tumors. SOSTDC1 may suppress the proliferative, migratory, and invasive abilities of SiHa and CaSki cells through blocking BMP and Wnt/β-catenin signaling pathways.
2023, 30(6):482-488.
DOI: 10.3872/j.issn.1007-385X.2023.06.004
Abstract:
Objective: To explore the characteristics and functions of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) after 10 passages (P10-hUC-MSC). Methods: Human umbilical cord was obtained from Xiamen Hongai Hospital (ethical lot number: HAXM-MEC-20201012-037-01), hUC-MSCs were isolated, collected, cultured and passaged, and P1-, P10- hUC-MSCs were collected. FCM was used to detect cell phenotypes. Senescence-associated β-galactosidase staining method and Annexin-Ⅴflow cytometry were adopted to detect end-stage cell senescence and apoptosis, respectively. Colchicine treatment was used to detect chromosomal stability. In vitro lipogenesis and osteogenesis induction assay was used to examine the ability of multidirectional differentiation of the cells. After co-culture with peripheral blood mononuclear cells (PBMC) at different ratios, the T-lymphocyte subsets and phenotypes were detected by FCM. Results: The phenotypes of P10-hUC-MSCs were similar to that of P1-hUC-MSCs, showing negative expression of CD45, CD34 and HLA-DR, but high positive expression rate (over 95%) of CD105 and CD90. Both groups of P1-hUC-MSCs and P10-hUC-MSCs showed positive β-galactosidase expression and early apoptotic characteristics, with no significant difference (P>0.05), and the cell chromosomes remained stable without transformation. Both P1- and P10-hUC-MSCs could be successfully induced and differentiated into adipocytes and osteoblasts in vitro withoutsignificant differences (P>0.05). When P10-hUC-MSCs and PBMCs were co-cultured in the ratio of 1∶1, the proportion of CD4+/CD8+ T cells and CD4+ Treg cells, and PD-1 expression were all significantly upregulated ( all P<0.01). Conclusion: The long-term passaged P10-hUC-MSCs still maintain their biological characteristics and safety, and possess multi-differentiation and immunomodulatory ability,which provide preliminary experimental basis and guidance for maximizing its damage repair and prevention effects in radiotherapy.
Objective: To explore the characteristics and functions of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) after 10 passages (P10-hUC-MSC). Methods: Human umbilical cord was obtained from Xiamen Hongai Hospital (ethical lot number: HAXM-MEC-20201012-037-01), hUC-MSCs were isolated, collected, cultured and passaged, and P1-, P10- hUC-MSCs were collected. FCM was used to detect cell phenotypes. Senescence-associated β-galactosidase staining method and Annexin-Ⅴflow cytometry were adopted to detect end-stage cell senescence and apoptosis, respectively. Colchicine treatment was used to detect chromosomal stability. In vitro lipogenesis and osteogenesis induction assay was used to examine the ability of multidirectional differentiation of the cells. After co-culture with peripheral blood mononuclear cells (PBMC) at different ratios, the T-lymphocyte subsets and phenotypes were detected by FCM. Results: The phenotypes of P10-hUC-MSCs were similar to that of P1-hUC-MSCs, showing negative expression of CD45, CD34 and HLA-DR, but high positive expression rate (over 95%) of CD105 and CD90. Both groups of P1-hUC-MSCs and P10-hUC-MSCs showed positive β-galactosidase expression and early apoptotic characteristics, with no significant difference (P>0.05), and the cell chromosomes remained stable without transformation. Both P1- and P10-hUC-MSCs could be successfully induced and differentiated into adipocytes and osteoblasts in vitro withoutsignificant differences (P>0.05). When P10-hUC-MSCs and PBMCs were co-cultured in the ratio of 1∶1, the proportion of CD4+/CD8+ T cells and CD4+ Treg cells, and PD-1 expression were all significantly upregulated ( all P<0.01). Conclusion: The long-term passaged P10-hUC-MSCs still maintain their biological characteristics and safety, and possess multi-differentiation and immunomodulatory ability,which provide preliminary experimental basis and guidance for maximizing its damage repair and prevention effects in radiotherapy.
2023, 30(6):489-496.
DOI: 10.3872/j.issn.1007-385X.2023.06.005
Abstract:
Objective: To explore the impact of pyroptosis related gene GSDME on the prognosis of patients with nasopharyngeal carcinoma and its interaction with the immune microenvironment. Methods: Gene expression profile and clinical data of 548 patients with nasopharyngeal carcinoma were obtained from TCGA database. Differential expression analysis and GO-KEGG enrichment analysis of GSDME were conducted using R language. Immunohistochemical maps of GSDME protein in nasopharyngeal carcinoma tissues and corresponding para-carcinoma tissues were obtained from The Human Protein Atlas database. The interacting proteins of GSDME were explored by using STRING database. The correlation between GSDME expression and infiltration of 24 kinds of immune cells in nasopharyngeal carcinoma tissues was analyzed by ssGSEA algorithm, the correlation between GSDME expression and immune checkpoint molecules was analyzed by Spearman method, and the correlation between GSDME expression and cytokine expression was analyzed by using TISIDB database. Univariate and multivariate COX regression analyses were used to screen the risk factors for prognosis, based on which, the nomogram and calibration curve were drawn. Survival analysis and risk analysis were performed in nasopharyngeal carcinoma patients based on GSDME expression levels. The mRNA expression of GSDME and four chemokines in Chinese nasopharyngeal carcinoma tissues was verified by qPCR. Results: Analysis of database data showed that GSDME was highly expressed in nasopharyngeal carcinoma tissues compared with paraneoplastic tissues (P<0.01), GO-KEGG enrichment analysis showed that GSDME was involved in immune response, cell pyroptosis-related signaling pathways, and GSDME expression was correlated with immune cell infiltration, cytokine and immune checkpoint molecule expression. qPCR examination of Chinese nasopharyngeal carcinoma tissues verified the bioinformatics predictions; GSDME expression, N stage and M stage were risk factors for the prognosis of nasopharyngeal carcinoma patients, and the nomogram and calibration curve based on risk factors could better predict the OS of nasopharyngeal carcinoma patients, and patients with high GSDME expression in nasopharyngeal carcinoma tissues had poor prognosis. Conclusion: GSDME is highly expressed in nasopharyngeal carcinoma tissues and is associated with patient's poor prognosis. High GSDME expression is associated with the pro-cancer effect of the immune microenvironment in nasopharyngeal carcinoma, which may be a potential target for immunotherapy.
Objective: To explore the impact of pyroptosis related gene GSDME on the prognosis of patients with nasopharyngeal carcinoma and its interaction with the immune microenvironment. Methods: Gene expression profile and clinical data of 548 patients with nasopharyngeal carcinoma were obtained from TCGA database. Differential expression analysis and GO-KEGG enrichment analysis of GSDME were conducted using R language. Immunohistochemical maps of GSDME protein in nasopharyngeal carcinoma tissues and corresponding para-carcinoma tissues were obtained from The Human Protein Atlas database. The interacting proteins of GSDME were explored by using STRING database. The correlation between GSDME expression and infiltration of 24 kinds of immune cells in nasopharyngeal carcinoma tissues was analyzed by ssGSEA algorithm, the correlation between GSDME expression and immune checkpoint molecules was analyzed by Spearman method, and the correlation between GSDME expression and cytokine expression was analyzed by using TISIDB database. Univariate and multivariate COX regression analyses were used to screen the risk factors for prognosis, based on which, the nomogram and calibration curve were drawn. Survival analysis and risk analysis were performed in nasopharyngeal carcinoma patients based on GSDME expression levels. The mRNA expression of GSDME and four chemokines in Chinese nasopharyngeal carcinoma tissues was verified by qPCR. Results: Analysis of database data showed that GSDME was highly expressed in nasopharyngeal carcinoma tissues compared with paraneoplastic tissues (P<0.01), GO-KEGG enrichment analysis showed that GSDME was involved in immune response, cell pyroptosis-related signaling pathways, and GSDME expression was correlated with immune cell infiltration, cytokine and immune checkpoint molecule expression. qPCR examination of Chinese nasopharyngeal carcinoma tissues verified the bioinformatics predictions; GSDME expression, N stage and M stage were risk factors for the prognosis of nasopharyngeal carcinoma patients, and the nomogram and calibration curve based on risk factors could better predict the OS of nasopharyngeal carcinoma patients, and patients with high GSDME expression in nasopharyngeal carcinoma tissues had poor prognosis. Conclusion: GSDME is highly expressed in nasopharyngeal carcinoma tissues and is associated with patient's poor prognosis. High GSDME expression is associated with the pro-cancer effect of the immune microenvironment in nasopharyngeal carcinoma, which may be a potential target for immunotherapy.
2023, 30(6):497-504.
DOI: 10.3872/j.issn.1007-385X.2023.06.006
Abstract:
Objective: To investigate the effects of inhibin subunit beta A antisense RNA 1 (INHBA-AS1) on epithelial-interstitial transformation (EMT) and ornithine metabolic pathway of cervical cancer cells and its mechanism. Methods: Cervical cancer HeLa cells were routinely cultured in vitro and the experiment was divided into 10 groups: control group, negative control (NC) group, sh-INHBA-AS1 group, PluriSIn 1 [stearyl CoA desaturase (SCD) inhibitor] group, NC+PluriSIn 1 group, sh-INHBA-AS1+PluriSIn 1 Group, 10058-F4(c-Myc inhibitor) group, NC+10058-F4 group, sh-INHBA-AS1+10058-F4 group, sh-INHBA-AS1+OE-c-Myc group. The proliferation ability of cells in each group was detected by plate cloning assay; the apoptosis of cells in each group was detected by flow cytometry; the invasion and migration abilities of cells in each group were detected by Transwell assay; the expressions of INHBA-AS1, c-Myc, SCD and EMT-related genes (N-cadherin, TGF-β and ZEB1) in cells of each group were detected by qPCR; the expressions of c-Myc, SCD, EMT-associated (N-cadherin, TGF-β and ZEB1), S-adenosine-methionine decarboxylase (SAMDC) and spermidine/spermine N1 acetyltransferase (SSAT) proteins in each group were detected by WB method, and the content of ornithine decarboxylase (ODC) in cell supernatant was detected by ELISA.Results: The proliferation, invasion and migration abilities of HeLa cells were significantly decreased after INHBA-AS1 expression was knocked down (all P<0.05). The apoptosis rate was significantly increased (P<0.05). The results of qPCR and WB assay showed that knockdown of INHBA-AS1 could significantly inhibit the expressions of c-Myc, SCD, N-cadherin, TGF-β, ZEB1, and SAMDC in HeLa cells by (all P<0.05), promote the expression of SSAT (P<0.05) and decrease the content of ODC in HeLa cell supernatant (P<0.05). These effects were more significant after further knockdown of INHBA-AS1 compared with c-Myc inhibitor and SCD inhibitor treatments (all P<0.05). Compared with sh-INHBA-AS1 group, further over-expression of c-Myc significantly increased HeLa cell proliferation (P<0.05), SCD and N-cadherin protein expression levels (P<0.05), and the content of ODCin cell supernatant (P<0.05). Conclusion: INHBA-AS1 can regulate the expression of SCD through c-Myc, participate in the ornithine metabolism and EMT process of HeLa cells, and promote the proliferation,invasion, and migration of HeLa cells.
Objective: To investigate the effects of inhibin subunit beta A antisense RNA 1 (INHBA-AS1) on epithelial-interstitial transformation (EMT) and ornithine metabolic pathway of cervical cancer cells and its mechanism. Methods: Cervical cancer HeLa cells were routinely cultured in vitro and the experiment was divided into 10 groups: control group, negative control (NC) group, sh-INHBA-AS1 group, PluriSIn 1 [stearyl CoA desaturase (SCD) inhibitor] group, NC+PluriSIn 1 group, sh-INHBA-AS1+PluriSIn 1 Group, 10058-F4(c-Myc inhibitor) group, NC+10058-F4 group, sh-INHBA-AS1+10058-F4 group, sh-INHBA-AS1+OE-c-Myc group. The proliferation ability of cells in each group was detected by plate cloning assay; the apoptosis of cells in each group was detected by flow cytometry; the invasion and migration abilities of cells in each group were detected by Transwell assay; the expressions of INHBA-AS1, c-Myc, SCD and EMT-related genes (N-cadherin, TGF-β and ZEB1) in cells of each group were detected by qPCR; the expressions of c-Myc, SCD, EMT-associated (N-cadherin, TGF-β and ZEB1), S-adenosine-methionine decarboxylase (SAMDC) and spermidine/spermine N1 acetyltransferase (SSAT) proteins in each group were detected by WB method, and the content of ornithine decarboxylase (ODC) in cell supernatant was detected by ELISA.Results: The proliferation, invasion and migration abilities of HeLa cells were significantly decreased after INHBA-AS1 expression was knocked down (all P<0.05). The apoptosis rate was significantly increased (P<0.05). The results of qPCR and WB assay showed that knockdown of INHBA-AS1 could significantly inhibit the expressions of c-Myc, SCD, N-cadherin, TGF-β, ZEB1, and SAMDC in HeLa cells by (all P<0.05), promote the expression of SSAT (P<0.05) and decrease the content of ODC in HeLa cell supernatant (P<0.05). These effects were more significant after further knockdown of INHBA-AS1 compared with c-Myc inhibitor and SCD inhibitor treatments (all P<0.05). Compared with sh-INHBA-AS1 group, further over-expression of c-Myc significantly increased HeLa cell proliferation (P<0.05), SCD and N-cadherin protein expression levels (P<0.05), and the content of ODCin cell supernatant (P<0.05). Conclusion: INHBA-AS1 can regulate the expression of SCD through c-Myc, participate in the ornithine metabolism and EMT process of HeLa cells, and promote the proliferation,invasion, and migration of HeLa cells.
MA Lihua
,
WANG Jing
,
LYU Shujie
,
SHU Yan
,
LI Wenming
,
HE Yuan
,
ZHANG Yan
,
ZHAO Hua
,
SHI Ruifang
,
WANG Zhongda
,
WANG Zixuan
,
ZHU Yue
,
YAO Lu
,
JIA Shaochang
,
IANG Longwei
2023, 30(6):505-510.
DOI: 10.3872/j.issn.1007-385X.2023.06.007
Abstract:
Objective: To evaluate the clinical efficacy and safety of tumor-specific individualized multi-target dendritic cell-cytokine-induced killer cell (DC-CIK) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods: The clinical data of patients with advanced NSCLC who underwent tumor-specific individualized multi-target DC-CIK therapy in the Biotherapy Department of the Eastern Theater General Hospital from October 1, 2019 to October 31, 2022 were retrospectively analyzed. The clinical data and adverse reactions of NSCLC patients were collected. The short-term clinical efficacy was evaluated by the changes of tumor markers in serum before and after the DC-CIK treatment, and the expression of lymphocyte subsets and various cytokines in patients before and after the treatment was detected by flow cytometry. Mass spectrometry was used to detect the changes in the number of targets before and after the treatment. Results: A total of 52 patients with advanced NSCLC were enrolled, including 21 females and 31 males; the age ranged from 32 to 71, with an average age of (50.97±10.72) years old and a median age of 47.5 years old. After DC-CIK treatment, there were 0 cases of CR, 0 cases of PR, 27 cases of SD and 25 cases of PD. Compared with pre-treatment, (1) there was no significant difference in the levels of CEA and CYFRA21-1 after treatment, but the level of CA125 was significantly decreased (P<0.01); (2) there was no significant change in the lymphocyte subsets of patients after treatment; (3) the levels of IL-2, IL-4, IFN-γ, and TNF-α in the peripheral blood of patients were significantly increased (all P<0.01), while the levels of IL-6, IL-10, and IL-17 did not change significantly; (4) the number of targets decreased significantly after treatment. There was no serious adverse reactions occurred during the DC-CIK treatment. Conclusion: Tumor-specific individualized multi-target autologous DC-CIK therapy is safe for patients with advanced NSCLC and can induce anti-tumor immune response in patients, thus bringing clinical benefits.
Objective: To evaluate the clinical efficacy and safety of tumor-specific individualized multi-target dendritic cell-cytokine-induced killer cell (DC-CIK) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods: The clinical data of patients with advanced NSCLC who underwent tumor-specific individualized multi-target DC-CIK therapy in the Biotherapy Department of the Eastern Theater General Hospital from October 1, 2019 to October 31, 2022 were retrospectively analyzed. The clinical data and adverse reactions of NSCLC patients were collected. The short-term clinical efficacy was evaluated by the changes of tumor markers in serum before and after the DC-CIK treatment, and the expression of lymphocyte subsets and various cytokines in patients before and after the treatment was detected by flow cytometry. Mass spectrometry was used to detect the changes in the number of targets before and after the treatment. Results: A total of 52 patients with advanced NSCLC were enrolled, including 21 females and 31 males; the age ranged from 32 to 71, with an average age of (50.97±10.72) years old and a median age of 47.5 years old. After DC-CIK treatment, there were 0 cases of CR, 0 cases of PR, 27 cases of SD and 25 cases of PD. Compared with pre-treatment, (1) there was no significant difference in the levels of CEA and CYFRA21-1 after treatment, but the level of CA125 was significantly decreased (P<0.01); (2) there was no significant change in the lymphocyte subsets of patients after treatment; (3) the levels of IL-2, IL-4, IFN-γ, and TNF-α in the peripheral blood of patients were significantly increased (all P<0.01), while the levels of IL-6, IL-10, and IL-17 did not change significantly; (4) the number of targets decreased significantly after treatment. There was no serious adverse reactions occurred during the DC-CIK treatment. Conclusion: Tumor-specific individualized multi-target autologous DC-CIK therapy is safe for patients with advanced NSCLC and can induce anti-tumor immune response in patients, thus bringing clinical benefits.
2023, 30(6):511-516.
DOI: 10.3872/j.issn.1007-385X.2023.06.008
Abstract:
近年来研究发现gasdermin D（GSDMD）作为细胞焦亡的关键效应分子与肿瘤发生发展密切相关，GSDMD介导的细胞焦亡是一把双刃剑，一方面，焦亡引起的长期炎症反应会促进正常细胞向肿瘤细胞的转化，帮助肿瘤细胞实现免疫逃逸，促进肿瘤生长和转移；另一方面，GSDMD会介导肿瘤细胞的焦亡，引起的炎性因子释放招募免疫细胞至病变部位，同时调控肿瘤细胞增殖，抑制肿瘤的发生发展。GSDMD介导的细胞焦亡具有抗肿瘤治疗的潜在价值，目前，多种抗癌药物通过GSDMD触发细胞焦亡发挥抗肿瘤作用，同时GSDMD介导的细胞焦亡也为免疫检查点治疗提供新思路，具有广阔的研究前景。
近年来研究发现gasdermin D（GSDMD）作为细胞焦亡的关键效应分子与肿瘤发生发展密切相关，GSDMD介导的细胞焦亡是一把双刃剑，一方面，焦亡引起的长期炎症反应会促进正常细胞向肿瘤细胞的转化，帮助肿瘤细胞实现免疫逃逸，促进肿瘤生长和转移；另一方面，GSDMD会介导肿瘤细胞的焦亡，引起的炎性因子释放招募免疫细胞至病变部位，同时调控肿瘤细胞增殖，抑制肿瘤的发生发展。GSDMD介导的细胞焦亡具有抗肿瘤治疗的潜在价值，目前，多种抗癌药物通过GSDMD触发细胞焦亡发挥抗肿瘤作用，同时GSDMD介导的细胞焦亡也为免疫检查点治疗提供新思路，具有广阔的研究前景。
2023, 30(6):517-522.
DOI: 10.3872/j.issn.1007-385X.2023.06.009
Abstract:
肿瘤生物治疗的重要性日渐获得各方关注，而溶瘤病毒疗法作为肿瘤免疫治疗的一个分支也已成为研究热点。呼肠孤病毒（ReoV）地缘分布广泛，因其天然对肿瘤细胞具有靶向性及人体感染后几乎无症状而被认为是理想的溶瘤病毒载体，目前被广泛应用于临床试验。肿瘤细胞常伴有RAS基因的过度表达，会抑制对病毒有拮抗作用的激酶表达，造成ReoV大量复制致使肿瘤细胞发生凋亡、坏死、自噬等直接溶瘤效应；此外，ReoV 感染肿瘤细胞后释放的促炎性细胞因子和趋化因子逆转了TME的免疫抑制状态，可激活并招募固有免疫效应细胞杀死肿瘤细胞，并促进适应性抗肿瘤免疫反应的产生。另外，ReoV与放化疗、其他免疫制剂的联用可增强了肿瘤治疗的效果。本文从溶瘤ReoV的生物学特性方面，重点介绍了ReoV的基本特征与感染机制及ReoV 的肿瘤嗜性；同时，总结了溶瘤ReoV 的溶瘤机制，主要包括ReoV 诱导程序性细胞死亡及ReoV 诱导非程序性死亡；概括了溶瘤ReoV 所诱导的抗肿瘤免疫反应，如溶瘤ReoV 诱导的抗肿瘤固有免疫、溶瘤ReoV 诱导的获得性抗肿瘤免疫等，并介绍了溶瘤ReoV联合用药的效果。随着溶瘤作用机制的探明及临床试验的开展，溶瘤ReoV在肿瘤的生物治疗中的应用将更为广阔。
肿瘤生物治疗的重要性日渐获得各方关注，而溶瘤病毒疗法作为肿瘤免疫治疗的一个分支也已成为研究热点。呼肠孤病毒（ReoV）地缘分布广泛，因其天然对肿瘤细胞具有靶向性及人体感染后几乎无症状而被认为是理想的溶瘤病毒载体，目前被广泛应用于临床试验。肿瘤细胞常伴有RAS基因的过度表达，会抑制对病毒有拮抗作用的激酶表达，造成ReoV大量复制致使肿瘤细胞发生凋亡、坏死、自噬等直接溶瘤效应；此外，ReoV 感染肿瘤细胞后释放的促炎性细胞因子和趋化因子逆转了TME的免疫抑制状态，可激活并招募固有免疫效应细胞杀死肿瘤细胞，并促进适应性抗肿瘤免疫反应的产生。另外，ReoV与放化疗、其他免疫制剂的联用可增强了肿瘤治疗的效果。本文从溶瘤ReoV的生物学特性方面，重点介绍了ReoV的基本特征与感染机制及ReoV 的肿瘤嗜性；同时，总结了溶瘤ReoV 的溶瘤机制，主要包括ReoV 诱导程序性细胞死亡及ReoV 诱导非程序性死亡；概括了溶瘤ReoV 所诱导的抗肿瘤免疫反应，如溶瘤ReoV 诱导的抗肿瘤固有免疫、溶瘤ReoV 诱导的获得性抗肿瘤免疫等，并介绍了溶瘤ReoV联合用药的效果。随着溶瘤作用机制的探明及临床试验的开展，溶瘤ReoV在肿瘤的生物治疗中的应用将更为广阔。
11 Progress in the application of injectable hydrogel delivery system in local immunotherapy of tumors
2023, 30(6):523-527.
DOI: 10.3872/j.issn.1007-385X.2023.06.010
Abstract:
近年来免疫治疗迅速发展，然而有一些患者对免疫治疗的反应低，这可能和药物疗效、药物滞留以及全身不良反应等因素有关。作为投递载体之一的可注射水凝胶系统具有易于应用、增高局部药物浓度、延长药物滞留时间、良好的生物相容性等优势，受到越来越多研究者的关注。作为投递系统之一，它常被应用于局部免疫治疗的肿瘤内注射给药，在增强抗肿瘤治疗效果方面发挥着越来越重要的作用。本文概述了目前常用的水凝胶递送系统的构成及其特点，重点介绍可注射水凝胶系统作为局部免疫治疗或免疫联合化疗的药物投递系统的研究，同时分析了对可注射水凝胶系统应用中的存在问题解决策略。随着可注射水凝胶系统的深入研究，相信该投递系统在优化局部免疫治疗领域将发挥重要的作用。
近年来免疫治疗迅速发展，然而有一些患者对免疫治疗的反应低，这可能和药物疗效、药物滞留以及全身不良反应等因素有关。作为投递载体之一的可注射水凝胶系统具有易于应用、增高局部药物浓度、延长药物滞留时间、良好的生物相容性等优势，受到越来越多研究者的关注。作为投递系统之一，它常被应用于局部免疫治疗的肿瘤内注射给药，在增强抗肿瘤治疗效果方面发挥着越来越重要的作用。本文概述了目前常用的水凝胶递送系统的构成及其特点，重点介绍可注射水凝胶系统作为局部免疫治疗或免疫联合化疗的药物投递系统的研究，同时分析了对可注射水凝胶系统应用中的存在问题解决策略。随着可注射水凝胶系统的深入研究，相信该投递系统在优化局部免疫治疗领域将发挥重要的作用。
2023, 30(6):528-532.
DOI: 10.3872/j.issn.1007-385X.2023.06.011
Abstract:
肠道微生物群与宿主形成共生关系，在许多方面对人身体健康是有益。肠道和肝脏的解剖、功能联系密切，肠-肝轴在维持肠道微生物群和肝脏功能的稳态、免疫调节以及营养支持等方面具有重要作用。肠道微生物群稳态的改变会影响胆汁酸代谢，肠屏障的破坏会影响LPS-TLR4的平衡，这些变化在肝细胞癌（HCC）发生发展中发挥重要作用。根据目前的研究进展，利用益生菌、粪便微生物群移植和抗生素治疗等可能是未来有效的HCC预防和治疗策略。
肠道微生物群与宿主形成共生关系，在许多方面对人身体健康是有益。肠道和肝脏的解剖、功能联系密切，肠-肝轴在维持肠道微生物群和肝脏功能的稳态、免疫调节以及营养支持等方面具有重要作用。肠道微生物群稳态的改变会影响胆汁酸代谢，肠屏障的破坏会影响LPS-TLR4的平衡，这些变化在肝细胞癌（HCC）发生发展中发挥重要作用。根据目前的研究进展，利用益生菌、粪便微生物群移植和抗生素治疗等可能是未来有效的HCC预防和治疗策略。
2023, 30(6):533-537.
DOI: 10.3872/j.issn.1007-385X.2023.06.012
Abstract:
免疫检查点抑制剂（ICI）延长了晚期癌症患者的生存期，然而随着ICI 在抗癌治疗中的广泛应用，却涌现出新的、罕见的免疫相关不良反应（irAE）。本文报道1例由程序性死亡受体-1（PD-1）抑制剂信迪利单抗所致的罕见irAE—免疫性输尿管炎/膀胱炎。患者为55岁肺腺癌（T4N3M1，Ⅳ期），女性，在给予“贝伐珠单抗”联合“信迪利单抗”治疗4个疗程后，出现尿频、尿急、尿痛及肉眼血尿等症状治疗。尿常规显示红细胞和白细胞明显增多，尿液培养和细胞学检查均为阴性，泌尿系统彩超及全程CT显示双侧输尿管全程扩张、管壁增厚、周围多发渗出、膀胱壁增厚、周围多发渗出。经多学科会诊（MDT）及文献检索后，患者被诊断为免疫性输尿管炎/膀胱炎。本文还回顾了文献报道的病例，以阐明其临床特征，为免疫性输尿管炎/膀胱炎的临床早诊断、适当处理及治疗提供有益的帮助。
免疫检查点抑制剂（ICI）延长了晚期癌症患者的生存期，然而随着ICI 在抗癌治疗中的广泛应用，却涌现出新的、罕见的免疫相关不良反应（irAE）。本文报道1例由程序性死亡受体-1（PD-1）抑制剂信迪利单抗所致的罕见irAE—免疫性输尿管炎/膀胱炎。患者为55岁肺腺癌（T4N3M1，Ⅳ期），女性，在给予“贝伐珠单抗”联合“信迪利单抗”治疗4个疗程后，出现尿频、尿急、尿痛及肉眼血尿等症状治疗。尿常规显示红细胞和白细胞明显增多，尿液培养和细胞学检查均为阴性，泌尿系统彩超及全程CT显示双侧输尿管全程扩张、管壁增厚、周围多发渗出、膀胱壁增厚、周围多发渗出。经多学科会诊（MDT）及文献检索后，患者被诊断为免疫性输尿管炎/膀胱炎。本文还回顾了文献报道的病例，以阐明其临床特征，为免疫性输尿管炎/膀胱炎的临床早诊断、适当处理及治疗提供有益的帮助。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.