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Volume 31,Issue 12,2024 Table of Contents
2024, 31(12):1167-1177.
Abstract:
[Abstract] Immunotherapy has provided new approaches for tumor treatment. The immune status within the tumor microenvironment of cancer patients, characterized as‘ cold’ or‘ hot’, determines whether they will respond to immunotherapy. This article innovatively proposes the concept of‘ cell batteries (or Tesla Cell)’ to promote the‘ cold-hot switch’ of the tumor microenvironment. It reviews the current research status and progress in tumor immunotherapy, focusing on the concepts of "cold tumors" and "hot tumors, " the conversion strategies between them, as well as the types and applications of "Tesla cell"， aiming to provide a theoretical foundation for the development of new immunotherapeutic strategies for tumors.
[Abstract] Immunotherapy has provided new approaches for tumor treatment. The immune status within the tumor microenvironment of cancer patients, characterized as‘ cold’ or‘ hot’, determines whether they will respond to immunotherapy. This article innovatively proposes the concept of‘ cell batteries (or Tesla Cell)’ to promote the‘ cold-hot switch’ of the tumor microenvironment. It reviews the current research status and progress in tumor immunotherapy, focusing on the concepts of "cold tumors" and "hot tumors, " the conversion strategies between them, as well as the types and applications of "Tesla cell"， aiming to provide a theoretical foundation for the development of new immunotherapeutic strategies for tumors.
2024, 31(12):1178-1185.
Abstract:
[Abstract] Objective: To investigate the effects of β -1, 4-galactosyltransferase 2 (B4GALT2) on the proliferation, migration and invasion of human breast cancer MCF-7 and MDA-MB-231 cells, and to explore its underlying mechanism. Methods: The mRNA and protein expression of B4GALT2 in breast cancer tissues was analyzed using data from TCGA database and the CPTAC proteomics database. Immunohistochemical staining was used to validate the expression of B4GALT2 protein in breast cancer tissues of Chinese population. The correlation between B4GALT2 mRNA expression in breast cancer tissues and patient prognosis was analyzed using data from the Kaplan-Meier Plotter database. MCF-7 and MDA-MB-231 cells were routinely cultured and transfected with siNC, siRNA#1, siRNA#2, empty vector, and B4GALT2 overexpression plasmids using transfection reagents. The transfected cells were classified as NC group, siRNA#1 group, siRNA#2 group, empty vector group, and OE-B4GALT2 group accordingly. CCK-8 assay and clone formation assay were used to detect the effects of B4GALT2 knockdown on proliferation of transfected cells. Scratch healing assay and Transwell chamber assay were applied to evaluate the effects of B4GALT2 knockdown on cell migration and invasion. WB assay was used to detect the phosphorylation levels of the PI3K/AKT signaling pathway in MCF-7, MDA-MB-231 cells after B4GALT2 knockdown or overexpression. Results: B4GALT2 was highly expressed in breast cancer tissues at both mRNA and protein levels (both P < 0.01), and B4GALT2 protein was also highly expressed in Chinese breast cancer tissues (P < 0.000 1), confirming the initial findings. High B4GALT2 expression was significantly associated with shorter overall prognosis (OS), recurrence-free survival (RFS), and post-progression survival (PPS) (P < 0.01, P < 0.05, P < 0.001) in patients. After B4GALT2 knockdown, the proliferation, migration and invasion of MCF-7 and MDA-MB-231 cells were significantly suppressed (all P < 0.01), and the PI3K/AKT signaling pathway was significantly inhibited (all P < 0.01). The PI3K/AKT signaling pathway was significantly activated after B4GALT2 overexpression (all P < 0.01). Conclusion: B4GALT2 is highly expressed in breast cancer tissues. It promotes the malignant biological behaviors of MCF-7 and MDA-MB-231 cells by regulating the PI3K/AKT signaling pathway.
[Abstract] Objective: To investigate the effects of β -1, 4-galactosyltransferase 2 (B4GALT2) on the proliferation, migration and invasion of human breast cancer MCF-7 and MDA-MB-231 cells, and to explore its underlying mechanism. Methods: The mRNA and protein expression of B4GALT2 in breast cancer tissues was analyzed using data from TCGA database and the CPTAC proteomics database. Immunohistochemical staining was used to validate the expression of B4GALT2 protein in breast cancer tissues of Chinese population. The correlation between B4GALT2 mRNA expression in breast cancer tissues and patient prognosis was analyzed using data from the Kaplan-Meier Plotter database. MCF-7 and MDA-MB-231 cells were routinely cultured and transfected with siNC, siRNA#1, siRNA#2, empty vector, and B4GALT2 overexpression plasmids using transfection reagents. The transfected cells were classified as NC group, siRNA#1 group, siRNA#2 group, empty vector group, and OE-B4GALT2 group accordingly. CCK-8 assay and clone formation assay were used to detect the effects of B4GALT2 knockdown on proliferation of transfected cells. Scratch healing assay and Transwell chamber assay were applied to evaluate the effects of B4GALT2 knockdown on cell migration and invasion. WB assay was used to detect the phosphorylation levels of the PI3K/AKT signaling pathway in MCF-7, MDA-MB-231 cells after B4GALT2 knockdown or overexpression. Results: B4GALT2 was highly expressed in breast cancer tissues at both mRNA and protein levels (both P < 0.01), and B4GALT2 protein was also highly expressed in Chinese breast cancer tissues (P < 0.000 1), confirming the initial findings. High B4GALT2 expression was significantly associated with shorter overall prognosis (OS), recurrence-free survival (RFS), and post-progression survival (PPS) (P < 0.01, P < 0.05, P < 0.001) in patients. After B4GALT2 knockdown, the proliferation, migration and invasion of MCF-7 and MDA-MB-231 cells were significantly suppressed (all P < 0.01), and the PI3K/AKT signaling pathway was significantly inhibited (all P < 0.01). The PI3K/AKT signaling pathway was significantly activated after B4GALT2 overexpression (all P < 0.01). Conclusion: B4GALT2 is highly expressed in breast cancer tissues. It promotes the malignant biological behaviors of MCF-7 and MDA-MB-231 cells by regulating the PI3K/AKT signaling pathway.
2024, 31(12):1186-1193.
Abstract:
[Abstract] Objective: To construct dual-targeting (CD38 and CD138) chimeric antigen receptor (CAR) gene-modified T cells (CD38/ CD138 CAR-T cells) and explore their in vitro cytotoxicity against multiple myeloma (MM) cells. Methods: Based on the high expression of CD38 and CD138 antigens in MM cells, CD38 CAR-T cells and CD138 CAR-T cells targeting CD38 and CD138 respectively, and CD38/CD138 dual-targeted CAR-T cells targeting both CD38 and CD138 were constructed using CAR-T cell technology. The experimental groups included untreated T cells, CD38 CAR-T, CD138 CAR-T, and CD38/CD138 CAR-T cells. The phenotype of CAR-T cells was detected by flow cytometry. The cytotoxicity of various CAR-T cells against MM cells (RPMI8226 and U266) was assessed using the LDH release assay. Results: Three types of CAR-T cells, CD38 CAR-T, CD138 CAR-T, and CD38/ CD138 CAR-T cells, were successfully constructed. The CD38/CD138 CAR-T cells tended to differentiate into a memory phenotype, expressing higher levels of proliferation marker (CD25), activation marker (CD27), and lower levels of exhaustion markers (PD-1, CTLA-4, TIM-3) (all P < 0.001). Moreover, CD38/CD138 CAR-T cells were less prone to exhaustion and senescence, and expressed lower levels of r-H2AX, p-p53, p21, and p16 proteins (all P < 0.01). Under different effector-to-target cell ratios, CD38/CD138 CAR-T cells exhibited stronger cytotoxic effects against RPMI8226 and U266 cells compared to CD38 CAR-T and CD138 CAR-T cells (all P < 0.001). Conclusion: CD38/CD138 CAR-T cells targeting both CD38 and CD138 demonstrate an optimal phenotype and enhanced anti-tumor activity in vitro, offering promising potential for immunotherapy in multiple myeloma.
[Abstract] Objective: To construct dual-targeting (CD38 and CD138) chimeric antigen receptor (CAR) gene-modified T cells (CD38/ CD138 CAR-T cells) and explore their in vitro cytotoxicity against multiple myeloma (MM) cells. Methods: Based on the high expression of CD38 and CD138 antigens in MM cells, CD38 CAR-T cells and CD138 CAR-T cells targeting CD38 and CD138 respectively, and CD38/CD138 dual-targeted CAR-T cells targeting both CD38 and CD138 were constructed using CAR-T cell technology. The experimental groups included untreated T cells, CD38 CAR-T, CD138 CAR-T, and CD38/CD138 CAR-T cells. The phenotype of CAR-T cells was detected by flow cytometry. The cytotoxicity of various CAR-T cells against MM cells (RPMI8226 and U266) was assessed using the LDH release assay. Results: Three types of CAR-T cells, CD38 CAR-T, CD138 CAR-T, and CD38/ CD138 CAR-T cells, were successfully constructed. The CD38/CD138 CAR-T cells tended to differentiate into a memory phenotype, expressing higher levels of proliferation marker (CD25), activation marker (CD27), and lower levels of exhaustion markers (PD-1, CTLA-4, TIM-3) (all P < 0.001). Moreover, CD38/CD138 CAR-T cells were less prone to exhaustion and senescence, and expressed lower levels of r-H2AX, p-p53, p21, and p16 proteins (all P < 0.01). Under different effector-to-target cell ratios, CD38/CD138 CAR-T cells exhibited stronger cytotoxic effects against RPMI8226 and U266 cells compared to CD38 CAR-T and CD138 CAR-T cells (all P < 0.001). Conclusion: CD38/CD138 CAR-T cells targeting both CD38 and CD138 demonstrate an optimal phenotype and enhanced anti-tumor activity in vitro, offering promising potential for immunotherapy in multiple myeloma.
2024, 31(12):1194-1203.
Abstract:
[Abstract] Objective: To investigate the effects of Feiji Formula on the migration and invasion of lung cancer cells, as well as lung metastasis in animal models and explore its possible mechanisms. Methods: TNMplot, TCGA, and DAVID databases were used to analyze the expression of complement-related proteins (CFHR5 [complement factor H-related protein 5], MBL2 [mannose-binding lectin 2], C9 [complement component 9]) in lung metastatic tissues and their relationship with immune cell infiltration, as well as related biological processes and signaling pathways. A subcutaneous xenograft mice model was established using 2LL cells. Mice were administered 2 g/mL Feiji Formula decoction (0.2 mL per dose) via oral gavage for 21 days. The effects of Feiji Formula on the incidence of lung metastasis, the number of lung metastatic nodules, and the protein expression of CFHR5/MBL2/C9 in the lung tissues of the model mice were observed. Exosome tracing assay was performed to observe the secretion and uptake of exosomes by CTC-TJH-01 and H1299 cells. Different concentrations of Feiji Formula were applied to treat H1299 and CTC-TJH-01 cells, and its effects on cell viability, invasion, migration, and CFHR5/MBL2/C9 protein expression were detected by CCK-8, scratch healing assay,Transwell assay, and WB method. Results: Network pharmacology analysis showed that CFHR5/MBL2/C9 proteins were highly expressed in lung metastatic tissues (all P < 0.05) and were closely related to the complement system involved in immune response regulation. Compared with the control group, the Feiji Formula group demonstrated a significant reduction in the number of lung metastatic nodules (P < 0.05). Feiji Formula (0-200 μg/mL) had no significant effect on the viability of H1299 and CTC-TJH-01 cells (both P > 0.05). Both CTC-TJH-01 and H1299 cells could secrete and uptake each other's exosomes. Compared with the 0 μg/mL control group, Feiji Formula at concentrations of 50-200 μg/mL significantly inhibited the migration and invasion abilities of H1299 and CTC-TJH-01 cells (P < 0.05 or P < 0.01), and significantly reduced the protein expression levels of CFHR5 and MBL2 (P <0.05 or P <0.01). Notably, the expression level of C9 protein in CTC-TJH-01 cells increased only after treatment with 200 μg/mL Feiji Formula (P < 0.05). Conclusion: Feiji Formula can inhibit the migration and invasion of lung cancer cells as well as lung metastasis in model mice by regulating complement-associated proteins CFHR5/MBL2/C9. This effect may be related to exosome-mediated intercellular communication.
[Abstract] Objective: To investigate the effects of Feiji Formula on the migration and invasion of lung cancer cells, as well as lung metastasis in animal models and explore its possible mechanisms. Methods: TNMplot, TCGA, and DAVID databases were used to analyze the expression of complement-related proteins (CFHR5 [complement factor H-related protein 5], MBL2 [mannose-binding lectin 2], C9 [complement component 9]) in lung metastatic tissues and their relationship with immune cell infiltration, as well as related biological processes and signaling pathways. A subcutaneous xenograft mice model was established using 2LL cells. Mice were administered 2 g/mL Feiji Formula decoction (0.2 mL per dose) via oral gavage for 21 days. The effects of Feiji Formula on the incidence of lung metastasis, the number of lung metastatic nodules, and the protein expression of CFHR5/MBL2/C9 in the lung tissues of the model mice were observed. Exosome tracing assay was performed to observe the secretion and uptake of exosomes by CTC-TJH-01 and H1299 cells. Different concentrations of Feiji Formula were applied to treat H1299 and CTC-TJH-01 cells, and its effects on cell viability, invasion, migration, and CFHR5/MBL2/C9 protein expression were detected by CCK-8, scratch healing assay,Transwell assay, and WB method. Results: Network pharmacology analysis showed that CFHR5/MBL2/C9 proteins were highly expressed in lung metastatic tissues (all P < 0.05) and were closely related to the complement system involved in immune response regulation. Compared with the control group, the Feiji Formula group demonstrated a significant reduction in the number of lung metastatic nodules (P < 0.05). Feiji Formula (0-200 μg/mL) had no significant effect on the viability of H1299 and CTC-TJH-01 cells (both P > 0.05). Both CTC-TJH-01 and H1299 cells could secrete and uptake each other's exosomes. Compared with the 0 μg/mL control group, Feiji Formula at concentrations of 50-200 μg/mL significantly inhibited the migration and invasion abilities of H1299 and CTC-TJH-01 cells (P < 0.05 or P < 0.01), and significantly reduced the protein expression levels of CFHR5 and MBL2 (P <0.05 or P <0.01). Notably, the expression level of C9 protein in CTC-TJH-01 cells increased only after treatment with 200 μg/mL Feiji Formula (P < 0.05). Conclusion: Feiji Formula can inhibit the migration and invasion of lung cancer cells as well as lung metastasis in model mice by regulating complement-associated proteins CFHR5/MBL2/C9. This effect may be related to exosome-mediated intercellular communication.
FENG Siqi
,
ZHONG Yi
,
LI Shiying
,
LI Yun
,
WU Zhonghua
,
TANG Xiaowen
,
ZHOU Zhangjie
,
WU Tingting
2024, 31(12):1204-1210.
Abstract:
[Abstract] Objective: To investigate the effects of Bushen Jianpi formula (BSJP) in mediating the inhibitory effects of farnesoid X receptor (FXR) on cancer cachexia (CC) induced by hepatocellular carcinoma AH-130 cells in a rat model and its underlying mechanism. Methods: A liver cancer cachexia rat model was established by intraperitoneal injection of AH-130 cells. The rats were divided into five groups: blank control, model control, CDCA (FXR agonist), BSJP, and BSJP + CDCA groups. After modelling, the rats were treated with CDCA, BSJP, or their combination for consecutive 16 days, and their body weights were measured weekly. At the end of the experiment, the rats were sacrificed, and abdominal aortic blood, feces, and brown adipose tissues from the epididymal, inguinal, and scapular regions were collected. Liquid chromatography-mass spectrometry (LC-MS) was used to detect the composition and content of bile acids in serum and feces of rats. WB and qPCR were used to detect the expression of FXR, Wnt family member 10b (Wnt10b), β -catenin, and uncoupling protein 1 (UCP-1) in the ileum, brown adipose, and white adipose tissues of rats. Results: Compared with the blank control group, the body mass of the rats in the model group was significantly reduced (P < 0.01); compared with the model control group, the body mass of the rats in CDCA, BSJP and BSJP + CDCA groups all increased (P < 0.01). Compared with the blank control group, the epididymal, inguinal, scapular, and total brown adipose tissue mass were all elevated in the model control group (all P < 0.05); compared with the model control group, the brown fat mass in the inguinal and epididymis regions of the rats decreased significantly in all treatment groups (P < 0.05), but this decrease was not significant in the scapular region (P > 0.05); besides, the total brown fat mass decreased notably in all treatment groups compared to the model control group (all P < 0.01). LC-MS analysis showed that the composition and content of bile acids in the serum and feces of rats were altered in all groups. qPCR and WB results confirmed that, compared to the model group, BSJP and BSJP + CDCA promoted the mRNA and protein expression of FXR in the ileum, brown adipose, and white adipose tissues of rats (all P < 0.05), and decreased the mRNA and protein expression of Wnt10b, β-catenin, UCP-1 (all P < 0.05). Conclusion: The BSJP formula can inhibit hepatocellular carcinoma cell AH-130-induced cachexia in rats, alleviating the associated body weight loss and brown adipose tissue formation. The mechanism may involve the regulation of FXR and the inhibition of the expression of Wnt10b, β -catenin, and UCP-1 in brown adipose tissue through the Wnt signaling pathway.
[Abstract] Objective: To investigate the effects of Bushen Jianpi formula (BSJP) in mediating the inhibitory effects of farnesoid X receptor (FXR) on cancer cachexia (CC) induced by hepatocellular carcinoma AH-130 cells in a rat model and its underlying mechanism. Methods: A liver cancer cachexia rat model was established by intraperitoneal injection of AH-130 cells. The rats were divided into five groups: blank control, model control, CDCA (FXR agonist), BSJP, and BSJP + CDCA groups. After modelling, the rats were treated with CDCA, BSJP, or their combination for consecutive 16 days, and their body weights were measured weekly. At the end of the experiment, the rats were sacrificed, and abdominal aortic blood, feces, and brown adipose tissues from the epididymal, inguinal, and scapular regions were collected. Liquid chromatography-mass spectrometry (LC-MS) was used to detect the composition and content of bile acids in serum and feces of rats. WB and qPCR were used to detect the expression of FXR, Wnt family member 10b (Wnt10b), β -catenin, and uncoupling protein 1 (UCP-1) in the ileum, brown adipose, and white adipose tissues of rats. Results: Compared with the blank control group, the body mass of the rats in the model group was significantly reduced (P < 0.01); compared with the model control group, the body mass of the rats in CDCA, BSJP and BSJP + CDCA groups all increased (P < 0.01). Compared with the blank control group, the epididymal, inguinal, scapular, and total brown adipose tissue mass were all elevated in the model control group (all P < 0.05); compared with the model control group, the brown fat mass in the inguinal and epididymis regions of the rats decreased significantly in all treatment groups (P < 0.05), but this decrease was not significant in the scapular region (P > 0.05); besides, the total brown fat mass decreased notably in all treatment groups compared to the model control group (all P < 0.01). LC-MS analysis showed that the composition and content of bile acids in the serum and feces of rats were altered in all groups. qPCR and WB results confirmed that, compared to the model group, BSJP and BSJP + CDCA promoted the mRNA and protein expression of FXR in the ileum, brown adipose, and white adipose tissues of rats (all P < 0.05), and decreased the mRNA and protein expression of Wnt10b, β-catenin, UCP-1 (all P < 0.05). Conclusion: The BSJP formula can inhibit hepatocellular carcinoma cell AH-130-induced cachexia in rats, alleviating the associated body weight loss and brown adipose tissue formation. The mechanism may involve the regulation of FXR and the inhibition of the expression of Wnt10b, β -catenin, and UCP-1 in brown adipose tissue through the Wnt signaling pathway.
2024, 31(12):1211-1217.
Abstract:
[Abstract] Objective: To construct a primary nanobody library for human papillomavirus 16 (HPV16) L1 protein and obtain a nanobody specific to HPV16 L1 through selection and identification. Methods: HPV16 L1 protein was used as antigen to immunize alpaca, and a primary antibody library was constructed using phage display technology. After three rounds of screening, positive clones were identified by ELISA. The VHH sequence of the strongest positive clone was used for eukaryotic expression. The target nanobody was obtained after affinity purification, gel filtration chromatography, SDS PAGE and WB identification. The affinity between the nanobody and HPV16 L1 protein was evaluated using surface plasmon resonance (SPR) technology. The cytotoxicity of the nanobody was detected using CCK-8 assay. The neutralizing activity of nanobody against HPV16 pseudovirus was detected using a luciferase reporter gene assay. Results: The primary library was constructed with a capacity of 1.304 × 1010 and an abundance of 6.5 × 109 clones / mL. ELISA identified 36 positive clones. Protein monomer and dimers were expressed and purified, and the target nanobody (designated as "Nb") was successfully identified. The binding affinity of Nb to HPV16 L1 protein was 35.41 nmol/L. There was no significant difference in HaCat cell proliferation activity between Nb group and blank group (P > 0.05). Compared to the negative group, both 0.1 and 1 μmol/L Nb inhibited pseudovirus infection in 293FT cells (all P < 0.01). Conclusion: This study successfully obtained a nanobody with high purity and strong affinity that exhibited no cytotoxicity to epithelial cells and effectively inhibited HPV16 pseudovirus infection in 293FT cells. The nanobody provides a promising candidate antibody-based drug for the prevention and treatment of HPV 16 infection.
[Abstract] Objective: To construct a primary nanobody library for human papillomavirus 16 (HPV16) L1 protein and obtain a nanobody specific to HPV16 L1 through selection and identification. Methods: HPV16 L1 protein was used as antigen to immunize alpaca, and a primary antibody library was constructed using phage display technology. After three rounds of screening, positive clones were identified by ELISA. The VHH sequence of the strongest positive clone was used for eukaryotic expression. The target nanobody was obtained after affinity purification, gel filtration chromatography, SDS PAGE and WB identification. The affinity between the nanobody and HPV16 L1 protein was evaluated using surface plasmon resonance (SPR) technology. The cytotoxicity of the nanobody was detected using CCK-8 assay. The neutralizing activity of nanobody against HPV16 pseudovirus was detected using a luciferase reporter gene assay. Results: The primary library was constructed with a capacity of 1.304 × 1010 and an abundance of 6.5 × 109 clones / mL. ELISA identified 36 positive clones. Protein monomer and dimers were expressed and purified, and the target nanobody (designated as "Nb") was successfully identified. The binding affinity of Nb to HPV16 L1 protein was 35.41 nmol/L. There was no significant difference in HaCat cell proliferation activity between Nb group and blank group (P > 0.05). Compared to the negative group, both 0.1 and 1 μmol/L Nb inhibited pseudovirus infection in 293FT cells (all P < 0.01). Conclusion: This study successfully obtained a nanobody with high purity and strong affinity that exhibited no cytotoxicity to epithelial cells and effectively inhibited HPV16 pseudovirus infection in 293FT cells. The nanobody provides a promising candidate antibody-based drug for the prevention and treatment of HPV 16 infection.
ZHOU Hongshuai
,
LIN Guimiao
,
WANG Xiaomei
,
LUO Lin
,
YANG Liu
,
BIAN Dongyuan
,
LI Shasha
,
JIANG Shengzhe
,
CHEN Qiang
2024, 31(12):1218-1226.
Abstract:
[Abstract] Objective: To investigate the effects of low-dose radiation (LDR) combined with human telomerase reverse transcriptase Cterminal polypeptide 27 (hTERTC27) overexpression on the proliferation and apoptosis of lung cancer A549 cells, and to observe the in vivo antitumor effects of LDR combined with C27. Methods: The pEgr-hTERTC27 plasmid was transfected into human non-small cell lung cancer (NSCLC) A549 cells and mouse Lewis lung carcinoma (LLC) cells. Cells stably expressing C27 (A549-C27 and LLC-C27) were screened by G418 selection. The cells were divided into six groups: conventional radiation (CONV-RT) group (A549-Con), LDR group (A549-Low), C27 group (A549-C27), CONV-RT combined with C27 group (A549-C27-Con), LDR combined with C27 group (A549-C27-Low), and control group (A549-Mock). The irradiation dose in LDR group was only 36% of CONV-RT group. MTT assay was used to detect cell proliferation, and flow cytometry was used to measure cell apoptosis. LLC cell-transplanted tumor model in mice was established through subcutaneous implantation, and the animal experiment groups were similar with cell experiments. Tumor growth, volume, and mass were recorded in each group. Muscle infiltration near the transplanted tumors was observed using H-E staining. Results: Compared with A549-Mock group, the proliferative activity of A549-Con and A549-Low group was significantly decreased (all P < 0.01). Furthermore, the proliferation activity of A549-C27-Con and A549-C27-Low cells was significantly lower than that of A549-C27 cells (all P < 0.01). Compared with A549-Mock, the apoptosis rates were significantly higher in A549-Con and A549-Low groups (P < 0.01); however, no significant difference in apoptosis rates were observed among A549-C27, A549-C27-Con and A549-C27-Low groups (all P > 0.05). In tumor-bearing mice, both CONV-RT and LDR significantly reduced tumor mass compared with unirradiated mice (all P < 0.01). In addition, the tumor mass and local infiltration were significantly reduced in both LLC-C27-Low and LLC-C27-Con groups. Conclusion: LDR combined with C27 achieves similar antitumor effects to CONV-RT alone while reducing the total radiation dose in NSCLC. Moreover, LDR and C27 peptide synergize in their anti-tumor effects, with their combination reducing local tumor infiltration in transplanted tumor models.
[Abstract] Objective: To investigate the effects of low-dose radiation (LDR) combined with human telomerase reverse transcriptase Cterminal polypeptide 27 (hTERTC27) overexpression on the proliferation and apoptosis of lung cancer A549 cells, and to observe the in vivo antitumor effects of LDR combined with C27. Methods: The pEgr-hTERTC27 plasmid was transfected into human non-small cell lung cancer (NSCLC) A549 cells and mouse Lewis lung carcinoma (LLC) cells. Cells stably expressing C27 (A549-C27 and LLC-C27) were screened by G418 selection. The cells were divided into six groups: conventional radiation (CONV-RT) group (A549-Con), LDR group (A549-Low), C27 group (A549-C27), CONV-RT combined with C27 group (A549-C27-Con), LDR combined with C27 group (A549-C27-Low), and control group (A549-Mock). The irradiation dose in LDR group was only 36% of CONV-RT group. MTT assay was used to detect cell proliferation, and flow cytometry was used to measure cell apoptosis. LLC cell-transplanted tumor model in mice was established through subcutaneous implantation, and the animal experiment groups were similar with cell experiments. Tumor growth, volume, and mass were recorded in each group. Muscle infiltration near the transplanted tumors was observed using H-E staining. Results: Compared with A549-Mock group, the proliferative activity of A549-Con and A549-Low group was significantly decreased (all P < 0.01). Furthermore, the proliferation activity of A549-C27-Con and A549-C27-Low cells was significantly lower than that of A549-C27 cells (all P < 0.01). Compared with A549-Mock, the apoptosis rates were significantly higher in A549-Con and A549-Low groups (P < 0.01); however, no significant difference in apoptosis rates were observed among A549-C27, A549-C27-Con and A549-C27-Low groups (all P > 0.05). In tumor-bearing mice, both CONV-RT and LDR significantly reduced tumor mass compared with unirradiated mice (all P < 0.01). In addition, the tumor mass and local infiltration were significantly reduced in both LLC-C27-Low and LLC-C27-Con groups. Conclusion: LDR combined with C27 achieves similar antitumor effects to CONV-RT alone while reducing the total radiation dose in NSCLC. Moreover, LDR and C27 peptide synergize in their anti-tumor effects, with their combination reducing local tumor infiltration in transplanted tumor models.
2024, 31(12):1227-1234.
Abstract:
[Abstract] Objective: To investigate the correlation between peripheral blood lymphocyte immunophenotyping, cytokine levels before and after immune and anti-angiogenesis combined therapy, and treatment efficacy as well as prognosis in patients with advanced mucosal melanoma. Methods: A total of 28 patients with advanced mucosal melanoma admitted to the Drum Tower Hospital of Nanjing University School of Medicine from April 2019 to June 2022 were included in this analysis. All patients received combined treatment of camrelizumab (PD-1 inhibitor) and apatinib (anti-angiogenic drug). Peripheral blood samples were collected before treatment and after two cycles of treatment for lymphocyte immunophenotyping and cytokine level testing. The correlation between these immune markers and treatment efficacy as well as patient prognosis was evaluated. Results: After two cycles of treatment with camrelizumab and apatinib in patients with mucosal melanoma, the proportion of PD-1 positive cytotoxic T lymphocytes (CD3+ CD8+ CD279+ cells) in peripheral blood was significantly reduced (P < 0.001), while the proportion of NK cells (CD3- CD16+ CD56+ cells) was significantly increased (P = 0.0054). Pre-treatment peripheral blood IFN- γ levels were found to be associated with overall survival (OS) (P = 0.013). Patients with low IFN-γ levels had a median OS of 329 days, while the median OS for patients with high IFN-γ levels was not reached. Higher baseline IFN-γ levels were associated with a greater benefit in progressionfree survival (PFS). Conclusion: The proportion of PD-1-positive T lymphocytes, NK cells and IFN-γ levels in peripheral blood may have predictive value for the efficacy and prognosis of advanced mucosal melanoma patients undergoing immunotherapy and antiangiogenesis combined therapy. Future large-sample studies are needed to better characterize the clinical potential of these markers.
[Abstract] Objective: To investigate the correlation between peripheral blood lymphocyte immunophenotyping, cytokine levels before and after immune and anti-angiogenesis combined therapy, and treatment efficacy as well as prognosis in patients with advanced mucosal melanoma. Methods: A total of 28 patients with advanced mucosal melanoma admitted to the Drum Tower Hospital of Nanjing University School of Medicine from April 2019 to June 2022 were included in this analysis. All patients received combined treatment of camrelizumab (PD-1 inhibitor) and apatinib (anti-angiogenic drug). Peripheral blood samples were collected before treatment and after two cycles of treatment for lymphocyte immunophenotyping and cytokine level testing. The correlation between these immune markers and treatment efficacy as well as patient prognosis was evaluated. Results: After two cycles of treatment with camrelizumab and apatinib in patients with mucosal melanoma, the proportion of PD-1 positive cytotoxic T lymphocytes (CD3+ CD8+ CD279+ cells) in peripheral blood was significantly reduced (P < 0.001), while the proportion of NK cells (CD3- CD16+ CD56+ cells) was significantly increased (P = 0.0054). Pre-treatment peripheral blood IFN- γ levels were found to be associated with overall survival (OS) (P = 0.013). Patients with low IFN-γ levels had a median OS of 329 days, while the median OS for patients with high IFN-γ levels was not reached. Higher baseline IFN-γ levels were associated with a greater benefit in progressionfree survival (PFS). Conclusion: The proportion of PD-1-positive T lymphocytes, NK cells and IFN-γ levels in peripheral blood may have predictive value for the efficacy and prognosis of advanced mucosal melanoma patients undergoing immunotherapy and antiangiogenesis combined therapy. Future large-sample studies are needed to better characterize the clinical potential of these markers.
2024, 31(12):1235-1241.
Abstract:
[Abstract] Objective: To evaluate the clinical efficacy and safety of erlotinib combined with albumin-bound paclitaxel and carboplatin in the treatment of patients with EGFR-mutation positive non-small cell lung cancer (NSCLC). Methods: A total of 80 patients with EGFR-mutation positive NSCLC treated at the Department of Oncology, Xijing Hospital from May 2019 to June 2021 were retrospectively selected for this study. According to their treatment methods, the patients were divided into two groups: the study group (n = 38) and the control group (n = 42). Both groups received erlotinib targeted therapy, while the study group also received combination chemotherapy with albumin-bound paclitaxel and carboplatin. The treatment efficacy [objective response rate (ORR), disease control rate (DCR)], immune function [CD3+ , CD4+ , CD8+ , CD4+ /CD8+ , natural killer (NK) cells], survival status [3-years survival rate, overall survival (OS), progression-free survival (PFS), Karnofsky performance status (KPS) score], levels of tumor markers [carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA21-1), vascular endothelial growth factor (VEGF)], and the incidence of adverse reactions were compared between the two groups. Results: The DCR in the study group was significantly higher than that in control group (89.47% vs 42.86%) (P < 0.05). The ORR in the study group was also higher than that in control group (36.84% vs 23.81%), but the difference was not statistically significant (P > 0.05). After treatment, the study group showed significantly higher levels of CD3+ , CD4+ , NK cells and CD4+ /CD8+ ratio, and lower levels of CD8+ compared to the control group (all P < 0.05). There was no significant difference in 3-years survival rate between the two groups (P > 0.05). However, the OS and PFS of the study group were longer than those of the control group (both P < 0.05), and the KPS score was higher (P < 0.05). The levels of CEA, CYFRA21-1 and VEGF in the study group were lower than those in control group (P < 0.05). The incidence of bone marrow suppression was higher in the study group than in control group (P < 0.05). Conclusion: Erlotinib targeted therapy combined with albumin-bound paclitaxel and carboplatin demonstrates good clinical efficacy in treating EGFR-mutation positive NSCLC. It reduces immune function damage, prolongs PFS in advanced NSCLC patients, and improves their quality of life, with a good safety profile.
[Abstract] Objective: To evaluate the clinical efficacy and safety of erlotinib combined with albumin-bound paclitaxel and carboplatin in the treatment of patients with EGFR-mutation positive non-small cell lung cancer (NSCLC). Methods: A total of 80 patients with EGFR-mutation positive NSCLC treated at the Department of Oncology, Xijing Hospital from May 2019 to June 2021 were retrospectively selected for this study. According to their treatment methods, the patients were divided into two groups: the study group (n = 38) and the control group (n = 42). Both groups received erlotinib targeted therapy, while the study group also received combination chemotherapy with albumin-bound paclitaxel and carboplatin. The treatment efficacy [objective response rate (ORR), disease control rate (DCR)], immune function [CD3+ , CD4+ , CD8+ , CD4+ /CD8+ , natural killer (NK) cells], survival status [3-years survival rate, overall survival (OS), progression-free survival (PFS), Karnofsky performance status (KPS) score], levels of tumor markers [carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA21-1), vascular endothelial growth factor (VEGF)], and the incidence of adverse reactions were compared between the two groups. Results: The DCR in the study group was significantly higher than that in control group (89.47% vs 42.86%) (P < 0.05). The ORR in the study group was also higher than that in control group (36.84% vs 23.81%), but the difference was not statistically significant (P > 0.05). After treatment, the study group showed significantly higher levels of CD3+ , CD4+ , NK cells and CD4+ /CD8+ ratio, and lower levels of CD8+ compared to the control group (all P < 0.05). There was no significant difference in 3-years survival rate between the two groups (P > 0.05). However, the OS and PFS of the study group were longer than those of the control group (both P < 0.05), and the KPS score was higher (P < 0.05). The levels of CEA, CYFRA21-1 and VEGF in the study group were lower than those in control group (P < 0.05). The incidence of bone marrow suppression was higher in the study group than in control group (P < 0.05). Conclusion: Erlotinib targeted therapy combined with albumin-bound paclitaxel and carboplatin demonstrates good clinical efficacy in treating EGFR-mutation positive NSCLC. It reduces immune function damage, prolongs PFS in advanced NSCLC patients, and improves their quality of life, with a good safety profile.
2024, 31(12):1242-1247.
Abstract:
[Abstract] Objective: To investigate the expression of CD133 (also known as PROM1) in pancreatic cancer tissues and its association with clinicopathological features and prognosis of pancreatic cancer patients. Methods: The GEPIA website was used to analyze the expression of CD133 in pancreatic cancer patients from the TCGA database. The correlation between PROM1 mRNA expression and cancer stem cell family genes in human pancreatic cancer tissues was analyzed based on the TCGA database. The expression of CD133 in pancreatic cancer tissues and its clinical significance were studied by immunohistochemistry (IHC) staining. Wilcoxon rank sum test was used to analyze the difference in CD133 expression between pancreatic cancer tissues and adjacent tissues. Chi-square test was used to analyze the relationship between CD133 expression and clinicopathological characteristics in pancreatic cancer tissues. KaplanMeier method and Log-rank test were used to analyze the survival difference based on different levels of CD133 expression in pancreatic cancer tissues. The Cox model was used to evaluate the prognostic value of different indicators. Hazard ratio (HR) and 95% confidence interval (95% CI) were used to assess the strength of the association between CD133 expression and mortality risk in pancreatic cancer patients. Results: TCGA database analysis showed that the expression of CD133 was significantly up-regulated in pancreatic cancer tissues compared with adjacent tissues (P < 0.05). The mRNA expression level of PROM1 in pancreatic cancer tissues was correlated with tumor stem cell family genes, including EPCAM, POU5F1, CD24, CD44 and CXCR4. The expression level of CD133 in pancreatic cancer tissues was significantly associated with tumor differentiation, TNM stage, and lymph node metastasis (all P < 0.05). Univariate Cox model analysis showed that overall survival (OS) was significantly associated with age (HR = 0.544, 95%CI [0.299, 0.990], P < 0.05), depth of invasion (HR = 0.496, 95%CI [0.292, 0.842], P < 0.05), TNM stage (HR = 2.148, 95%CI [1.352,3.412], P < 0.05), and CD133 expression (HR = 1.935, 95%CI [1.090, 3.433], P < 0.05). Multivariate Cox model analysis showed that TNM stage (HR = 0.116, 95%CI [0.025, 0.551], P < 0.05), lymph node metastasis (HR = 0.392, 95%CI [0.160, 0.960], P < 0.05) and CD133 expression (HR = 2.080, 95%CI [1.053, 4.106], P < 0.05) were independent prognostic risk factors. Conclusion: CD133 is highly expressed in pancreatic cancer tissues, and its expression is significantly associated with the prognosis of pancreatic cancer patients. CD133 may serve as a potential new target for immunotherapy in pancreatic cancer.
[Abstract] Objective: To investigate the expression of CD133 (also known as PROM1) in pancreatic cancer tissues and its association with clinicopathological features and prognosis of pancreatic cancer patients. Methods: The GEPIA website was used to analyze the expression of CD133 in pancreatic cancer patients from the TCGA database. The correlation between PROM1 mRNA expression and cancer stem cell family genes in human pancreatic cancer tissues was analyzed based on the TCGA database. The expression of CD133 in pancreatic cancer tissues and its clinical significance were studied by immunohistochemistry (IHC) staining. Wilcoxon rank sum test was used to analyze the difference in CD133 expression between pancreatic cancer tissues and adjacent tissues. Chi-square test was used to analyze the relationship between CD133 expression and clinicopathological characteristics in pancreatic cancer tissues. KaplanMeier method and Log-rank test were used to analyze the survival difference based on different levels of CD133 expression in pancreatic cancer tissues. The Cox model was used to evaluate the prognostic value of different indicators. Hazard ratio (HR) and 95% confidence interval (95% CI) were used to assess the strength of the association between CD133 expression and mortality risk in pancreatic cancer patients. Results: TCGA database analysis showed that the expression of CD133 was significantly up-regulated in pancreatic cancer tissues compared with adjacent tissues (P < 0.05). The mRNA expression level of PROM1 in pancreatic cancer tissues was correlated with tumor stem cell family genes, including EPCAM, POU5F1, CD24, CD44 and CXCR4. The expression level of CD133 in pancreatic cancer tissues was significantly associated with tumor differentiation, TNM stage, and lymph node metastasis (all P < 0.05). Univariate Cox model analysis showed that overall survival (OS) was significantly associated with age (HR = 0.544, 95%CI [0.299, 0.990], P < 0.05), depth of invasion (HR = 0.496, 95%CI [0.292, 0.842], P < 0.05), TNM stage (HR = 2.148, 95%CI [1.352,3.412], P < 0.05), and CD133 expression (HR = 1.935, 95%CI [1.090, 3.433], P < 0.05). Multivariate Cox model analysis showed that TNM stage (HR = 0.116, 95%CI [0.025, 0.551], P < 0.05), lymph node metastasis (HR = 0.392, 95%CI [0.160, 0.960], P < 0.05) and CD133 expression (HR = 2.080, 95%CI [1.053, 4.106], P < 0.05) were independent prognostic risk factors. Conclusion: CD133 is highly expressed in pancreatic cancer tissues, and its expression is significantly associated with the prognosis of pancreatic cancer patients. CD133 may serve as a potential new target for immunotherapy in pancreatic cancer.
2024, 31(12):1248-1253.
Abstract:
[摘 要] 线粒体在肿瘤细胞中扮演多重角色，其功能变化影响肿瘤的发生、发展及治疗。它调控细胞凋亡、氧化还原平衡和信 号转导，与肿瘤干细胞维持、侵袭转移能力和化疗耐药性密切相关，成为抗肿瘤药物研发的热点。因其具有独特结构和功能，线 粒体参与了肿瘤细胞不同类型的程序性死亡，包括焦亡、凋亡、铁死亡和铜死亡等过程；在肿瘤转移过程中，线粒体通过重新调整 细胞能量代谢，使肿瘤细胞能够适应新的微环境。目前，主要的靶向线粒体的抗肿瘤药物作用机制和治疗策略有靶向线粒体膜 电位、抑制线粒体呼吸链复合物、干扰线粒体代谢途径、调节线粒体ROS水平以及影响线粒体自噬过程等。
[摘 要] 线粒体在肿瘤细胞中扮演多重角色，其功能变化影响肿瘤的发生、发展及治疗。它调控细胞凋亡、氧化还原平衡和信 号转导，与肿瘤干细胞维持、侵袭转移能力和化疗耐药性密切相关，成为抗肿瘤药物研发的热点。因其具有独特结构和功能，线 粒体参与了肿瘤细胞不同类型的程序性死亡，包括焦亡、凋亡、铁死亡和铜死亡等过程；在肿瘤转移过程中，线粒体通过重新调整 细胞能量代谢，使肿瘤细胞能够适应新的微环境。目前，主要的靶向线粒体的抗肿瘤药物作用机制和治疗策略有靶向线粒体膜 电位、抑制线粒体呼吸链复合物、干扰线粒体代谢途径、调节线粒体ROS水平以及影响线粒体自噬过程等。
2024, 31(12):1254-1259.
Abstract:
[摘 要] 髓源性抑制细胞（MDSC）是近年来发现的一群具有未成熟分化特性及强免疫抑制功能的髓系细胞，其在肿瘤组织中 数量显著增加，通过多种途径诱导机体免疫耐受和疾病进展。肿瘤诱导MDSC分化并使其在组织聚集的机制复杂，其中干扰素 调节因子8（IRF-8）作为关键的调节因子，在这一过程中起着重要作用。IRF-8属于干扰素调节因子家族，可以调控免疫反应、炎 症和肿瘤免疫。在肿瘤诱导MDSC分化的过程中，IRF-8的具体作用机制尚未完全明确，但已有研究表明其可能通过调控相关信 号通路、与其他免疫调节因子相互作用的方式影响MDSC的分化。未来研究将进一步深入探讨IRF-8在肿瘤诱导MDSC分化中 的具体作用机制，包括其如何与其他信号分子相互作用、调控哪些关键基因的表达等。这些研究将有助于理解MDSC在肿瘤免 疫中的作用，为开发针对MDSC的靶向治疗药物提供理论基础，从而恢复或重建机体的抗肿瘤功能。因此，本文探讨了IRF-8作 为肿瘤诱导MDSC分化的重要调节器，其研究进展对于揭示MDSC在肿瘤免疫中的来源、作用机制、开发新的免疫治疗策略的重 要意义。
[摘 要] 髓源性抑制细胞（MDSC）是近年来发现的一群具有未成熟分化特性及强免疫抑制功能的髓系细胞，其在肿瘤组织中 数量显著增加，通过多种途径诱导机体免疫耐受和疾病进展。肿瘤诱导MDSC分化并使其在组织聚集的机制复杂，其中干扰素 调节因子8（IRF-8）作为关键的调节因子，在这一过程中起着重要作用。IRF-8属于干扰素调节因子家族，可以调控免疫反应、炎 症和肿瘤免疫。在肿瘤诱导MDSC分化的过程中，IRF-8的具体作用机制尚未完全明确，但已有研究表明其可能通过调控相关信 号通路、与其他免疫调节因子相互作用的方式影响MDSC的分化。未来研究将进一步深入探讨IRF-8在肿瘤诱导MDSC分化中 的具体作用机制，包括其如何与其他信号分子相互作用、调控哪些关键基因的表达等。这些研究将有助于理解MDSC在肿瘤免 疫中的作用，为开发针对MDSC的靶向治疗药物提供理论基础，从而恢复或重建机体的抗肿瘤功能。因此，本文探讨了IRF-8作 为肿瘤诱导MDSC分化的重要调节器，其研究进展对于揭示MDSC在肿瘤免疫中的来源、作用机制、开发新的免疫治疗策略的重 要意义。
2024, 31(12):1260-1266.
Abstract:
[摘 要] 乳腺癌是全球女性最常见的恶性肿瘤，其复发和耐药问题亟须新的治疗方法。脂质代谢在乳腺癌进展过程中发挥了 关键作用，有望成为乳腺癌的潜在治疗靶点。目前，靶向乳腺癌脂质代谢的主要策略包括：抑制脂肪酸从头合成、阻断外源性脂 质摄取、靶向特定脂质合成途径的酶和信号分子等。多种靶向脂质代谢药物（如TVB-2640、他汀类等）在临床前和临床试验中显 示出抗乳腺癌潜力。靶向脂质代谢可以增强化疗、放疗和免疫治疗效果，有助于克服激素治疗的抗性。但仍然需要解决好药物 的递送、特异性和耐药性等问题。未来研究需深入理解乳腺癌脂质代谢调控机制，开发高特异性的抑制剂，探索联合治疗策略， 实现个体化治疗，以提高整体疗效和患者生存质量。
[摘 要] 乳腺癌是全球女性最常见的恶性肿瘤，其复发和耐药问题亟须新的治疗方法。脂质代谢在乳腺癌进展过程中发挥了 关键作用，有望成为乳腺癌的潜在治疗靶点。目前，靶向乳腺癌脂质代谢的主要策略包括：抑制脂肪酸从头合成、阻断外源性脂 质摄取、靶向特定脂质合成途径的酶和信号分子等。多种靶向脂质代谢药物（如TVB-2640、他汀类等）在临床前和临床试验中显 示出抗乳腺癌潜力。靶向脂质代谢可以增强化疗、放疗和免疫治疗效果，有助于克服激素治疗的抗性。但仍然需要解决好药物 的递送、特异性和耐药性等问题。未来研究需深入理解乳腺癌脂质代谢调控机制，开发高特异性的抑制剂，探索联合治疗策略， 实现个体化治疗，以提高整体疗效和患者生存质量。
2024, 31(12):1267-1270.
Abstract:
[摘 要] 回顾1例胰腺癌臀部软组织转移患者的临床资料。该患者在胰腺癌根治术后1年余出现左臀部疼痛，血清CA199水 平显著升高，穿刺活检病理证实为胰腺癌臀部软组织转移，十分罕见。结合患者体力状况及既往多线治疗病史，采用了原位疫苗 整合模式治疗，治疗后臀部软组织转移灶消失，达到完全缓解。胰腺癌软组织转移十分罕见，原位疫苗整合治疗模式为这种难治 性多线治疗后的软组织转移灶的治疗提供了新思路和新方法。
[摘 要] 回顾1例胰腺癌臀部软组织转移患者的临床资料。该患者在胰腺癌根治术后1年余出现左臀部疼痛，血清CA199水 平显著升高，穿刺活检病理证实为胰腺癌臀部软组织转移，十分罕见。结合患者体力状况及既往多线治疗病史，采用了原位疫苗 整合模式治疗，治疗后臀部软组织转移灶消失，达到完全缓解。胰腺癌软组织转移十分罕见，原位疫苗整合治疗模式为这种难治 性多线治疗后的软组织转移灶的治疗提供了新思路和新方法。
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 刊号：ISSN 1007-385X
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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.