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Volume 25,Issue 9,2018 Table of Contents
2018, 25(9):847-853.
DOI: 10.3872/j.issn.1007-385X.2018.09.001
Abstract:
[Abstract] Due to the long-lasting, scalable, multi-targeting characteristics of T-cell immunity, T-cell-based tumor immunotherapy is considered to be the most likely means of bringing about tumor healing in addition to surgery. Especially in recent years, accumulating clinical data have confirmed the safety and effectiveness of cell therapy represented by chimeric antigen receptor modified T (CAR-T) cell. Among these, CAR-T therapy targeting CD19 has become a model therapy for genetic modified T cell therapy research in most institutions because of its remarkable effects. However, both practice and theory have suggested that CAR-T therapy faces more complicated problems in the treatment of solid tumors. How to use CAR-T cells to treat solid tumors reasonably and effectively still requires constant exploration and understanding. Here, we briefly summarize the current status of clinical practice of CAR-T cell therapy and its treatment of solid tumors, propose problems that need to be solved, and discuss the future research directions, in order to provide reference and research ideas for the treatment of solid tumors by CAR-T cells.
[Abstract] Due to the long-lasting, scalable, multi-targeting characteristics of T-cell immunity, T-cell-based tumor immunotherapy is considered to be the most likely means of bringing about tumor healing in addition to surgery. Especially in recent years, accumulating clinical data have confirmed the safety and effectiveness of cell therapy represented by chimeric antigen receptor modified T (CAR-T) cell. Among these, CAR-T therapy targeting CD19 has become a model therapy for genetic modified T cell therapy research in most institutions because of its remarkable effects. However, both practice and theory have suggested that CAR-T therapy faces more complicated problems in the treatment of solid tumors. How to use CAR-T cells to treat solid tumors reasonably and effectively still requires constant exploration and understanding. Here, we briefly summarize the current status of clinical practice of CAR-T cell therapy and its treatment of solid tumors, propose problems that need to be solved, and discuss the future research directions, in order to provide reference and research ideas for the treatment of solid tumors by CAR-T cells.
2018, 25(9):854-858.
DOI: 10.3872/j.issn.1007-385X.2018.09.002
Abstract:
[Abstract] Chimeric antigen receptor modified T (CAR-T) cell, a novel adoptive immunotherapy strategy, has been used successfully against hematological tumors. However, in solid tumors, due to multiple immunosuppressive cells, immunosuppressive molecules, and extracellular matrix play a suppressive role in the cytotoxic effects of migrating CAR-T cells and severely inhibit the antitumor efficacy of CAR-T cells in the tumor microenvironment of solid tumors. Simultaneously, tumor heterogeneity, lacking proper tumor antigens,poor homing ability at solid tumor sites, along with off-target effect, resulting in poor therapeutic effect of CAR-T cells in solid tumors.Compared with hematological tumors, solid tumors have complex biological characteristics, and thus targeted strategies are demanded to ensure long-term efficacy of CAR-T cells against tumors. This review makes a summary of the development of CAR-T cells, the confusion in solid tumors and the progress of treatment strategies.
[Abstract] Chimeric antigen receptor modified T (CAR-T) cell, a novel adoptive immunotherapy strategy, has been used successfully against hematological tumors. However, in solid tumors, due to multiple immunosuppressive cells, immunosuppressive molecules, and extracellular matrix play a suppressive role in the cytotoxic effects of migrating CAR-T cells and severely inhibit the antitumor efficacy of CAR-T cells in the tumor microenvironment of solid tumors. Simultaneously, tumor heterogeneity, lacking proper tumor antigens,poor homing ability at solid tumor sites, along with off-target effect, resulting in poor therapeutic effect of CAR-T cells in solid tumors.Compared with hematological tumors, solid tumors have complex biological characteristics, and thus targeted strategies are demanded to ensure long-term efficacy of CAR-T cells against tumors. This review makes a summary of the development of CAR-T cells, the confusion in solid tumors and the progress of treatment strategies.
2018, 25(9):859-864.
DOI: 10.3872/j.issn.1007-385X.2018.09.003
Abstract:
[Abstract] Chimeric antigen receptor modified T (CAR-T) cell therapy has achieved excellent clinical efficacy in patients with hematological malignancies (especially for patients with CD19 positive), and is regarded as a major advance in cancer therapy in recent years.It aroused scientists’strong interest in developing CAR-T cell products for the treatment of cancers. However, there are still some problems in the treatment of CAR-T cells. For examples, some patients lose the opportunity of CAR-T cell therapy while waiting for CAR-T cell culture, some unique adverse events during treatment of CAR-T cell therapy may endanger the patients’life, and the efficacy of CAR-T cell therapy is unsatisfactory on solid tumors. Even for hematological malignancies, some patients will eventually relapse and lead to treatment failure. Therefore, exploring methods to improve the efficacy, diagnosis the unique adverse events of CAR-T cell therapy early and give appropriately management, expand potentially benefiting populations of CAR-T cell therapy are issues that need to be addressed in current CAR-T cell therapy research.
[Abstract] Chimeric antigen receptor modified T (CAR-T) cell therapy has achieved excellent clinical efficacy in patients with hematological malignancies (especially for patients with CD19 positive), and is regarded as a major advance in cancer therapy in recent years.It aroused scientists’strong interest in developing CAR-T cell products for the treatment of cancers. However, there are still some problems in the treatment of CAR-T cells. For examples, some patients lose the opportunity of CAR-T cell therapy while waiting for CAR-T cell culture, some unique adverse events during treatment of CAR-T cell therapy may endanger the patients’life, and the efficacy of CAR-T cell therapy is unsatisfactory on solid tumors. Even for hematological malignancies, some patients will eventually relapse and lead to treatment failure. Therefore, exploring methods to improve the efficacy, diagnosis the unique adverse events of CAR-T cell therapy early and give appropriately management, expand potentially benefiting populations of CAR-T cell therapy are issues that need to be addressed in current CAR-T cell therapy research.
4 IL-6 promotes MDSCs infiltration and immunosuppression in breast cancer by inducing SOCS3 deficiency
2018, 25(9):865-871.
DOI: 10.3872/j.issn.1007-385X.2018.09.004
Abstract:
Objective: To investigate the immunosuppressive effect and underlying molecular mechanisms of Myeloid-derived suppressor cells (MDSCs) on T cells activity through IL-6activatingSTAT3/IDO signaling pathway. Methods: Twenty pairs of cancer tissues and the corresponding adjacent normal tissues from breast cancer patients treated at Tianjin Medical University Cancer Institute and Hospital from November 2015 to February 2016 were collected for this study; in the meanwhile, peripheral blood samples from 40 healthy donorswere also collected.CD33+ cells in tumor tissues and CD33 + CD14 + cells in peripheral blood of helthy donors were sorted out with MicroBeads technology. CD33+cells were in vitro co-cultured with breast cancer cell line MDA-MB-231 to induce MDSCs. Flow cytometry was used to detect the proportion of CD45+CD13+CD33+CD14-CD15- MDSCs.Western Blotting was used to detect the expression ofSOCS1，SOCS3, JAK1, JAK2, TYK2, STAT1, STAT3 and their phosphorylation levels. qRT-PCR was used to detect the expression of IL-6 and SOCS1-3. CCK8 was used to detect the T cell proliferation.Annexin V staining was used to detect T cell apoptosis. ELISA was used to detect IL-10 and IFN-γ secreted by T cells. Results: There were MDSCs infiltration in all 20 cases of breast cancer tissues for different levels (15.3%~58.1%), with a mean level of (29.82 ±11.46%); the infiltration of IL-6high group was significantly higher than that of the IL-6 low group [ （13.75±3.44）% vs（4.31±1.50）%，P<0.05], indicating that IL-6 expression was positively correlated with MDSCs infiltration (R2=0.4399, P<0.01). In vitro experiments showed that tumor-derived IL-6 significantly promoted the generation and immunosuppressive activity of MDSCs (P<0.05), which could be reversed by the blocking of IL-6. In the meanwhile, the expression of SOCS3 in MDSCs that induced in vitro was absent,which can be inhibited by blocking IL-6 (P<0.05). Conclusion: The study has demonstrated that tumor-derived IL-6 stimulates the continuous activation of the JAK/STAT signaling pathway and the absence of SOCS3 expression in MDSCs, thereby promoting the infiltration,generation and immunological activity of MDSCs. Therefore, IL-6 signaling pathway can be used as therapeutic target to weaken MDSCs generation and reverse MDSCs activity.
Objective: To investigate the immunosuppressive effect and underlying molecular mechanisms of Myeloid-derived suppressor cells (MDSCs) on T cells activity through IL-6activatingSTAT3/IDO signaling pathway. Methods: Twenty pairs of cancer tissues and the corresponding adjacent normal tissues from breast cancer patients treated at Tianjin Medical University Cancer Institute and Hospital from November 2015 to February 2016 were collected for this study; in the meanwhile, peripheral blood samples from 40 healthy donorswere also collected.CD33+ cells in tumor tissues and CD33 + CD14 + cells in peripheral blood of helthy donors were sorted out with MicroBeads technology. CD33+cells were in vitro co-cultured with breast cancer cell line MDA-MB-231 to induce MDSCs. Flow cytometry was used to detect the proportion of CD45+CD13+CD33+CD14-CD15- MDSCs.Western Blotting was used to detect the expression ofSOCS1，SOCS3, JAK1, JAK2, TYK2, STAT1, STAT3 and their phosphorylation levels. qRT-PCR was used to detect the expression of IL-6 and SOCS1-3. CCK8 was used to detect the T cell proliferation.Annexin V staining was used to detect T cell apoptosis. ELISA was used to detect IL-10 and IFN-γ secreted by T cells. Results: There were MDSCs infiltration in all 20 cases of breast cancer tissues for different levels (15.3%~58.1%), with a mean level of (29.82 ±11.46%); the infiltration of IL-6high group was significantly higher than that of the IL-6 low group [ （13.75±3.44）% vs（4.31±1.50）%，P<0.05], indicating that IL-6 expression was positively correlated with MDSCs infiltration (R2=0.4399, P<0.01). In vitro experiments showed that tumor-derived IL-6 significantly promoted the generation and immunosuppressive activity of MDSCs (P<0.05), which could be reversed by the blocking of IL-6. In the meanwhile, the expression of SOCS3 in MDSCs that induced in vitro was absent,which can be inhibited by blocking IL-6 (P<0.05). Conclusion: The study has demonstrated that tumor-derived IL-6 stimulates the continuous activation of the JAK/STAT signaling pathway and the absence of SOCS3 expression in MDSCs, thereby promoting the infiltration,generation and immunological activity of MDSCs. Therefore, IL-6 signaling pathway can be used as therapeutic target to weaken MDSCs generation and reverse MDSCs activity.
5 IL-12 reverses inhibitory effect of cisplatin on immune function of human NK cells and its mechanism
2018, 25(9):872-877.
DOI: 10.3872/j.issn.1007-385X.2018.09.005
Abstract:
Objective: To investigate the reverse effect and mechanism of IL-12 on chemotherapeutic medicine suppressing the immune function of NK cells. Methods: Purified NK cells were stimulated with PMA plus Ionomycin in the presence or absent of Cisplatin (DDP) and IL-12. The levels of IFN- γ and TNF- α in culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA); The content of IFN-γ and TNF-α, TRAIL (TNF-related apoptosis inducing ligand) and transcription factors including T-bet and p-STAT-4 in NK cells were analyzed by Flow cytometry. The cytotoxicity of purified NK cells (pretreated with/without chemotherapeutics and IL-12 for 48 h) to Jurkat cells was measured by Flow cytometry. Results: Chemotherapeutics significantly inhibited the production of IFN-γ, TNF-α and the expression of TRAIL in NK cells, which were significantly reversed by IL-12 (P<0.05 or P<0.01). Further study revealed that chemotherapeutics down-regulated while IL-12 reversed the expression of p-STAT4 to restore cytokine production.In addition, DDP also inhibited but IL-12 recovered the cytotoxicity of NK cells against tumor cells by inducing the expression of TRAIL (P<0.05 or P<0.01). Conclusion: Chemotherapeutics inhibited the cytotoxicity of NK cells and its secretion of cytokines (IFN-γ and TNF-α), which were reversed by IL-12 via up-regulating TRAIL and p-STAT-4; this might provide experimental evidence for the clinical application of IL-12 for rebuild the immune function of tumor patients receiving chemotherapy.
Objective: To investigate the reverse effect and mechanism of IL-12 on chemotherapeutic medicine suppressing the immune function of NK cells. Methods: Purified NK cells were stimulated with PMA plus Ionomycin in the presence or absent of Cisplatin (DDP) and IL-12. The levels of IFN- γ and TNF- α in culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA); The content of IFN-γ and TNF-α, TRAIL (TNF-related apoptosis inducing ligand) and transcription factors including T-bet and p-STAT-4 in NK cells were analyzed by Flow cytometry. The cytotoxicity of purified NK cells (pretreated with/without chemotherapeutics and IL-12 for 48 h) to Jurkat cells was measured by Flow cytometry. Results: Chemotherapeutics significantly inhibited the production of IFN-γ, TNF-α and the expression of TRAIL in NK cells, which were significantly reversed by IL-12 (P<0.05 or P<0.01). Further study revealed that chemotherapeutics down-regulated while IL-12 reversed the expression of p-STAT4 to restore cytokine production.In addition, DDP also inhibited but IL-12 recovered the cytotoxicity of NK cells against tumor cells by inducing the expression of TRAIL (P<0.05 or P<0.01). Conclusion: Chemotherapeutics inhibited the cytotoxicity of NK cells and its secretion of cytokines (IFN-γ and TNF-α), which were reversed by IL-12 via up-regulating TRAIL and p-STAT-4; this might provide experimental evidence for the clinical application of IL-12 for rebuild the immune function of tumor patients receiving chemotherapy.
2018, 25(9):878-883.
DOI: 10.3872/j.issn.1007-385X.2018.09.006
Abstract:
Objective: To explore the effect and possible mechanisms of has-miR-150-5p targeting HIF1α to regulate malignant biological behaviors of glioblastoma (GBM) U-251MG cells. Methods: Real-time quantitative PCR (RT-PCR) was used to detect the expression of miR-150-5p and hypoxia inducible factor 1 (HIF1α) in U-251MG cells. Luciferase report assay was carried out to verify the biological relationship between miR-150-5p and HIF1α and their biological functions in U-251MG cells. The protein expressions of miR-150-5pand HIF1α in U-251MG cells were detected by western blotting. The ability of cell migration was detected by wound healing test and cell invasion ability was detected by transwell test. Results: After miR-150-5p mimic transfection, the mRNA expression of HIF1α was significantly reduced in U-251MG cells (P<0.01). Bioinformatics prediction and luciferase reporter assay demonstrated that miR-150-5p down-regulated HIF1α through directly binding to HIF1α 3’- untranslated region (3’-UTR) (all P<0.05). In U-251MG cells, miR-150-5p over-expression significantly inhibited HIF1α expression, cell invasion and migration (all P<0.05). Conclusion: miR-150-5p inhibits cell invasion and metastasis through negative regulation of HIF1α, indicating that miR-150-5p and HIF1α were both potential therapeutic targets for glioblastoma.
Objective: To explore the effect and possible mechanisms of has-miR-150-5p targeting HIF1α to regulate malignant biological behaviors of glioblastoma (GBM) U-251MG cells. Methods: Real-time quantitative PCR (RT-PCR) was used to detect the expression of miR-150-5p and hypoxia inducible factor 1 (HIF1α) in U-251MG cells. Luciferase report assay was carried out to verify the biological relationship between miR-150-5p and HIF1α and their biological functions in U-251MG cells. The protein expressions of miR-150-5pand HIF1α in U-251MG cells were detected by western blotting. The ability of cell migration was detected by wound healing test and cell invasion ability was detected by transwell test. Results: After miR-150-5p mimic transfection, the mRNA expression of HIF1α was significantly reduced in U-251MG cells (P<0.01). Bioinformatics prediction and luciferase reporter assay demonstrated that miR-150-5p down-regulated HIF1α through directly binding to HIF1α 3’- untranslated region (3’-UTR) (all P<0.05). In U-251MG cells, miR-150-5p over-expression significantly inhibited HIF1α expression, cell invasion and migration (all P<0.05). Conclusion: miR-150-5p inhibits cell invasion and metastasis through negative regulation of HIF1α, indicating that miR-150-5p and HIF1α were both potential therapeutic targets for glioblastoma.
2018, 25(9):884-890.
DOI: 10.3872/j.issn.1007-385X.2018.09.007
Abstract:
Objective: To explore the molecular mechanism of miR-195-5p targeting FGF2 to inhibit the proliferation, apoptosis, invasion and migration of endometrial cancer HEC-1B cells. Methods: After culture and transfection, HEC-1B cells were divided into 4 groups: HEC-1B group, miR-195-5p mimic group, pLV-FGF2 group and miR-195-5p+FGF2 group. The expressions of miR-195-5p and mRNA levels of FGF2 were detected by qRT-PCR. The targeted relationship of miR-195-5p and FGF2 was verified by luciferase assay. The protein expression of FGF2 was examined by Western blotting; Proliferation of HEC-1B cells was measured by CCK-8;Apoptosis was tested by flow cytometry; HEC-1B cell invasion was detected by transwell, and migration was measured by scratch assay.Results: Compared with HEC-1B group, the expression of miR-195-5p in miR-195-5p mimic group was elevated while FGF2 mRNA level was declined (all P<0.01). Luciferase assay indicated that FGF2 was a target of miR-195-5p. Compared with HEC-1B group, the protein level of FGF2 in miR-195-5p mimic group was decreased, and the protein levels of FGF2 in pLV-FGF2 group were enhanced (P<0.01). The protein levels of FGF2 in miR-195-5p+FGF2 group were lower than that in pLV-FGF2 group (all P<0.01). The proliferation in miR-195-5p mimic group was lower than HEC-1B group (P<0.01), while the proliferation in pLV-FGF2 group was higher than that in HEC-1B group (all P<0.01). Compared with HEC-1B group, apoptosis in miR-195-5p mimic group was increased,and apoptosis in pLV-FGF2 group was decreased (P<0.01); moreover, apoptosis in miR-195-5p+FGF2 group was higher than that in pLV-FGF2 group (P<0.01). Compared with HEC-1B group, the number of invasive cells per field and the rate of wound healing in miR-195-5p mimic group were decreased, while those in pLV-FGF2 group was enhanced (P<0.01); moreover, the number of invasive cells per field and the rate of wound healing in miR-195-5p+FGF2 group was lower than those in pLV-FGF2 group (all P<0.01). Conclusion:miR-195-5p inhibits proliferation, invasion and migration and promotes apoptosis of endometrial cancer HEC-1B cells by target-ing FGF2, and could be used as a treatment target of endometrial cancer.
Objective: To explore the molecular mechanism of miR-195-5p targeting FGF2 to inhibit the proliferation, apoptosis, invasion and migration of endometrial cancer HEC-1B cells. Methods: After culture and transfection, HEC-1B cells were divided into 4 groups: HEC-1B group, miR-195-5p mimic group, pLV-FGF2 group and miR-195-5p+FGF2 group. The expressions of miR-195-5p and mRNA levels of FGF2 were detected by qRT-PCR. The targeted relationship of miR-195-5p and FGF2 was verified by luciferase assay. The protein expression of FGF2 was examined by Western blotting; Proliferation of HEC-1B cells was measured by CCK-8;Apoptosis was tested by flow cytometry; HEC-1B cell invasion was detected by transwell, and migration was measured by scratch assay.Results: Compared with HEC-1B group, the expression of miR-195-5p in miR-195-5p mimic group was elevated while FGF2 mRNA level was declined (all P<0.01). Luciferase assay indicated that FGF2 was a target of miR-195-5p. Compared with HEC-1B group, the protein level of FGF2 in miR-195-5p mimic group was decreased, and the protein levels of FGF2 in pLV-FGF2 group were enhanced (P<0.01). The protein levels of FGF2 in miR-195-5p+FGF2 group were lower than that in pLV-FGF2 group (all P<0.01). The proliferation in miR-195-5p mimic group was lower than HEC-1B group (P<0.01), while the proliferation in pLV-FGF2 group was higher than that in HEC-1B group (all P<0.01). Compared with HEC-1B group, apoptosis in miR-195-5p mimic group was increased,and apoptosis in pLV-FGF2 group was decreased (P<0.01); moreover, apoptosis in miR-195-5p+FGF2 group was higher than that in pLV-FGF2 group (P<0.01). Compared with HEC-1B group, the number of invasive cells per field and the rate of wound healing in miR-195-5p mimic group were decreased, while those in pLV-FGF2 group was enhanced (P<0.01); moreover, the number of invasive cells per field and the rate of wound healing in miR-195-5p+FGF2 group was lower than those in pLV-FGF2 group (all P<0.01). Conclusion:miR-195-5p inhibits proliferation, invasion and migration and promotes apoptosis of endometrial cancer HEC-1B cells by target-ing FGF2, and could be used as a treatment target of endometrial cancer.
LI Xiuzhen
,
XUE Qingjie
,
LU Hai
,
NIE Shangdan
,
WANG Hui
,
LI Yunqing
,
ZHAO Longyu
,
TAN Wenbing
2018, 25(9):891-897.
DOI: 10.3872/j.issn.1007-385X.2018.09.008
Abstract:
Objective: To investigate the role of CpG ODN (CpG oligodeoxynucleotide) adjuvant in enhancing the anti-bladder cancer response induced by MAGE-3 (melanoma antigen gene -3) antigen and its molecular mechanism. Methods: Mononuclear cells were isolated from HLA-A2 type peripheral blood of healthy donors by Ficoll method to prepare mature DC by conventional means. DC surface markers were detected by flow cytometry. MTT assay was used to detect the promotion effect of DCs sensitized by different means (MAGE-3, CpGODN, MAGE-3+CpG ODN, irrelevant control antigen) on the proliferation of T lymphocytes and the killing effect of CTL on BIU-87 tumor cells. The tumor mass of nude mice bearing BIU-87 bladder cell xenograft were examined on Day 7 and 11 after CpG ODN+MAGE-3 sensitized DC treatment. The expression of Bcl-2/Bax protein was detected by Western blotting while the proliferation level of xenograft cells was detected by MTT assay. Results: DCs sensitized by CpG ODN combined with MAGE-3 antigenic peptides could promote the proliferation of T lymphocytes and significantly enhance the killing effect of CTL on target BIU-87 cells (P<0.05). Compared with other sensitized DCs, in vivo experiments showed that 7 and 11 days after treatment, both the tumor volume and weight were significantly reduced (all P<0.05), and the proliferation ability of xenograft tumor was decreased (P<0.05). Compared with other sensitization means, CpG ODN+MAGE-3 especially exhibited obvious inhibitive effect on tumor growth on Day 11, and significantly promoted the proliferation of splenic monocytes of tumor bearing mice (P<0.01); moreover, Bcl-2 expression in xenograft tissues significantly decreased（P<0.01）while Bax expression significantly increased（P<0.05 or P<0.01）on Day 3 after treatment. Conclusion:CpG ODN can promote the inhibitory effect of MAGE-3 sensitized DC on bladder cancer BIU-87 cells, which will provide experimental basis for clinical application of DC vaccine in bladder cancer treatment.
Objective: To investigate the role of CpG ODN (CpG oligodeoxynucleotide) adjuvant in enhancing the anti-bladder cancer response induced by MAGE-3 (melanoma antigen gene -3) antigen and its molecular mechanism. Methods: Mononuclear cells were isolated from HLA-A2 type peripheral blood of healthy donors by Ficoll method to prepare mature DC by conventional means. DC surface markers were detected by flow cytometry. MTT assay was used to detect the promotion effect of DCs sensitized by different means (MAGE-3, CpGODN, MAGE-3+CpG ODN, irrelevant control antigen) on the proliferation of T lymphocytes and the killing effect of CTL on BIU-87 tumor cells. The tumor mass of nude mice bearing BIU-87 bladder cell xenograft were examined on Day 7 and 11 after CpG ODN+MAGE-3 sensitized DC treatment. The expression of Bcl-2/Bax protein was detected by Western blotting while the proliferation level of xenograft cells was detected by MTT assay. Results: DCs sensitized by CpG ODN combined with MAGE-3 antigenic peptides could promote the proliferation of T lymphocytes and significantly enhance the killing effect of CTL on target BIU-87 cells (P<0.05). Compared with other sensitized DCs, in vivo experiments showed that 7 and 11 days after treatment, both the tumor volume and weight were significantly reduced (all P<0.05), and the proliferation ability of xenograft tumor was decreased (P<0.05). Compared with other sensitization means, CpG ODN+MAGE-3 especially exhibited obvious inhibitive effect on tumor growth on Day 11, and significantly promoted the proliferation of splenic monocytes of tumor bearing mice (P<0.01); moreover, Bcl-2 expression in xenograft tissues significantly decreased（P<0.01）while Bax expression significantly increased（P<0.05 or P<0.01）on Day 3 after treatment. Conclusion:CpG ODN can promote the inhibitory effect of MAGE-3 sensitized DC on bladder cancer BIU-87 cells, which will provide experimental basis for clinical application of DC vaccine in bladder cancer treatment.
9 Phenotypes of CIK cells prepared by ATG-F culture system and its killing effect against K562 cells
2018, 25(9):898-903.
DOI: 10.3872/j.issn.1007-385X.2018.09.009
Abstract:
Objective: To investigate the function of CIK (cytokine induced killer) cells cultured using ATG-F (anti-human T lymphocyte rabbit immunoglobulin-Fresenius) and IFN - γ , IL-2 system and its feasibility in clinical practice. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors and were used to culture CIK cells by different activating antibodies;the total cell count was calculated on Day 7 and 14. The CIK cell composition, cell surface activation and proportion of inhibitory receptor molecular in ATG-F group, CD3 group and TG (Thymoglobulin) group were analyzed by Flow cytometry, and the cytotoxicity of CIK cells against K562 cells were also determined by flow cytometry at day 14 in ATG-F high-dose group, CD3 group and TG group. Results: CIK cells were successfully cultured by ATG-F, IFN- γ , IL-2 system. The proliferation rate of ATGF high-dose group was significantly higher than that in TG group (27.25±1.25 vs 16.60±1.72, P<0.01), but the proportion of CD3+CD56+ cells showed no statistical difference compare with the CD3 group (P>0.05). The percentage of CD3-CD56+ NK cells in ATG-F high-dose group was significantly higher than that in TG group and CD3 group [(11.19±2.60）% vs（5.66±1.00）%,（1.42±0.51）% ，P<0.01], while the proportion of CD4+T cells was significantly lower than that in CD3, TG group [(4.35±1.47）% vs （26.88±5.01）%,（14.52±6.22）%, P<0.01]; the proportion of CD56+CD94+, CD56+CD158a+, CD56+CD158b cells was significantly higher than those in CD3 group (all P<0.01). The ATG-F high does group showed significantly higher cytotoxicity against K562 cells than that of CD3 group at the target/effect ratio of 1∶10. Conclusion: CIK cells cultured by ATG-F culture system has higher NK cell proportion than other ordinary culture system, and its activated receptor has more stronger cytotoxicity against K562 cells.
Objective: To investigate the function of CIK (cytokine induced killer) cells cultured using ATG-F (anti-human T lymphocyte rabbit immunoglobulin-Fresenius) and IFN - γ , IL-2 system and its feasibility in clinical practice. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors and were used to culture CIK cells by different activating antibodies;the total cell count was calculated on Day 7 and 14. The CIK cell composition, cell surface activation and proportion of inhibitory receptor molecular in ATG-F group, CD3 group and TG (Thymoglobulin) group were analyzed by Flow cytometry, and the cytotoxicity of CIK cells against K562 cells were also determined by flow cytometry at day 14 in ATG-F high-dose group, CD3 group and TG group. Results: CIK cells were successfully cultured by ATG-F, IFN- γ , IL-2 system. The proliferation rate of ATGF high-dose group was significantly higher than that in TG group (27.25±1.25 vs 16.60±1.72, P<0.01), but the proportion of CD3+CD56+ cells showed no statistical difference compare with the CD3 group (P>0.05). The percentage of CD3-CD56+ NK cells in ATG-F high-dose group was significantly higher than that in TG group and CD3 group [(11.19±2.60）% vs（5.66±1.00）%,（1.42±0.51）% ，P<0.01], while the proportion of CD4+T cells was significantly lower than that in CD3, TG group [(4.35±1.47）% vs （26.88±5.01）%,（14.52±6.22）%, P<0.01]; the proportion of CD56+CD94+, CD56+CD158a+, CD56+CD158b cells was significantly higher than those in CD3 group (all P<0.01). The ATG-F high does group showed significantly higher cytotoxicity against K562 cells than that of CD3 group at the target/effect ratio of 1∶10. Conclusion: CIK cells cultured by ATG-F culture system has higher NK cell proportion than other ordinary culture system, and its activated receptor has more stronger cytotoxicity against K562 cells.
2018, 25(9):904-912.
DOI: 10.3872/j.issn.1007-385X.2018.09.010
Abstract:
Objective: To screen related genes of melanoma-associated antigen-A11 (MAGE-A11) in breast cancer cells based on highthroughput DNA microarray technology, and to validate from the aspects of quantity and function. Methods: DNA microarray was used to screen the differently-expresseddown-stream mRNAs of MAGE-A11 in breast cancercelllines (MCF-7, MDA-MB-231 and BT-549).Cluster analysis was applied on representative genes and quantitative RT-PCR was used to validate. CCK-8, scratch wound healing assay and Transwell assaywere used to detect the effect of MAGE-A11 on the proliferation,migration and invasion of breast cancer cells.Results: Over-expression of MAGE-A11 caused the differential expression of 1608 down-stream genes in 3 breast cancer cell lines,which was associated with various cell functions such as protein ubiquitination,cell proliferation and apoptosis, tumor invasion and metastasis.qRT-PCR validated that the expression of ZNF-451, CENPTJ, CDK13, API5 and LMO7, which were highly expressed in microarray,were also significantly higher than those in control group (P<0.01);in addition, SHPRH, PML, MARK2, LIMA1 and ANGPTL4,which were low-expressed in microarray, were also significantly lower than those in control group (P<0.01). MAGE-A11transfection directly increased the proliferation of breast cancer MCF-7, MDA-MB-231 and BT-549 cells at 72 h (all P<0.01); compared with control group after transfectionexhibited obvious wound healing at 48 h (P<0.05 or P<0.01) and significantly increased trans-membrane cell numbers (all P<0.01). Conclusion: Many differentially expressed genes related to ubiquitination, cell proliferation and apoptosis, tumor invasion and migration were screened in MCF-7, MDA-MB-231 and BT-549 breast cancer cells. Among them, 10 typical differentially expressed genes were identified in terms of quantity and function.
Objective: To screen related genes of melanoma-associated antigen-A11 (MAGE-A11) in breast cancer cells based on highthroughput DNA microarray technology, and to validate from the aspects of quantity and function. Methods: DNA microarray was used to screen the differently-expresseddown-stream mRNAs of MAGE-A11 in breast cancercelllines (MCF-7, MDA-MB-231 and BT-549).Cluster analysis was applied on representative genes and quantitative RT-PCR was used to validate. CCK-8, scratch wound healing assay and Transwell assaywere used to detect the effect of MAGE-A11 on the proliferation,migration and invasion of breast cancer cells.Results: Over-expression of MAGE-A11 caused the differential expression of 1608 down-stream genes in 3 breast cancer cell lines,which was associated with various cell functions such as protein ubiquitination,cell proliferation and apoptosis, tumor invasion and metastasis.qRT-PCR validated that the expression of ZNF-451, CENPTJ, CDK13, API5 and LMO7, which were highly expressed in microarray,were also significantly higher than those in control group (P<0.01);in addition, SHPRH, PML, MARK2, LIMA1 and ANGPTL4,which were low-expressed in microarray, were also significantly lower than those in control group (P<0.01). MAGE-A11transfection directly increased the proliferation of breast cancer MCF-7, MDA-MB-231 and BT-549 cells at 72 h (all P<0.01); compared with control group after transfectionexhibited obvious wound healing at 48 h (P<0.05 or P<0.01) and significantly increased trans-membrane cell numbers (all P<0.01). Conclusion: Many differentially expressed genes related to ubiquitination, cell proliferation and apoptosis, tumor invasion and migration were screened in MCF-7, MDA-MB-231 and BT-549 breast cancer cells. Among them, 10 typical differentially expressed genes were identified in terms of quantity and function.
2018, 25(9):913-919.
DOI: 10.3872/j.issn.1007-385X.2018.09.011
Abstract:
Objective: To investigate the specific killing effect of magnetic nanoparticles Fe3O4@PEI induced targeted suicide gene therapy combined with magnetic fluid hyperthermia on hepatoma xenograft. Methods: The suicide gene targeting hepatoma p[HRE]AFP-HSVTK and tumor cell imaging reporter gene vector p[HRE]AFP-Luc were constructed by sub-cloning gene recombination method, and tested by restriction endonuclease gel electrophoresis. Fe3O4 nano-particles were prepared by co-precipitation method and modified by Polyethyleneimine (PEI) to obtain the magnetic nano-particles Fe3O4@PEI,which could be used as carrier for tumor gene therapy and a medium for magnetic fluid hyperthermia treatment; and the characterization of Fe3O4@PEI was identified by transmission electron microscopy,particle size analyzer and Fourier transform infrared spectroscopy. The reporter genes p[HRE]AFP-Luc were delivered into the nude mice bearing xenografts via tail vein by Fe3O4@PEI, then the bioluminescence signals of mice were observed in an IVIS system. After the treatment of p[HRE]AFP-HSVTK/Fe3O4@PEI, the tumor cell inhibition rate was examined by MTT assay, the cell apoptosis was tested by Flow cytometry, the in vivo tumor development rate and tumor inhibition rate was tested by animal experiment, and the sub-cellular construction of tumor cells was observed by Transmission electron microscopy. Results: Nano-particles Fe3O4@PEI and recombinant vectors p[HRE]AFP-HSVTK and p[HRE]AFP-Luc were successfully constructed; after tale vein injection, image signals were detected only in tumor tissues via IVIS system, but no obvious pathologic damage in other major organs. In the in vitro cell killing test, the cell proliferation inhibition rate and the cell apoptosis rate in combination group was higher than that in hyperthermia treatment group and gene treatment group [inhibition rate: (76.02±7.33)% vs (42.31±4.28)%，(47.76±4.81)%, all P<0.05; apoptosis rate: (34.05±3.41)% vs (14.41±1.55)%，(11.64±1.20)%，all P<0.01]. The in vivo treatment showed that tumor volume development significantly slowed-down and even decreased in combination treatment group, and the tumor mass were significantly smaller than those of the single treatment groups (all P<0.05); and the tumor cell sub - cellular structure showed obvious apoptotic morphology. Conclusion: the suicide gene p [HRE]AFP-HSVTK has specific killing effect on hepatoma cells, Fe3O4@PEI can be used as effective gene treatment carrier and media of magnetic heperthermia treatment; Fe3O4@PEI mediated target treatment combined with magnetic fluid hyperthermia treatment could specifically inhibit the hepatoma xenograft.
Objective: To investigate the specific killing effect of magnetic nanoparticles Fe3O4@PEI induced targeted suicide gene therapy combined with magnetic fluid hyperthermia on hepatoma xenograft. Methods: The suicide gene targeting hepatoma p[HRE]AFP-HSVTK and tumor cell imaging reporter gene vector p[HRE]AFP-Luc were constructed by sub-cloning gene recombination method, and tested by restriction endonuclease gel electrophoresis. Fe3O4 nano-particles were prepared by co-precipitation method and modified by Polyethyleneimine (PEI) to obtain the magnetic nano-particles Fe3O4@PEI,which could be used as carrier for tumor gene therapy and a medium for magnetic fluid hyperthermia treatment; and the characterization of Fe3O4@PEI was identified by transmission electron microscopy,particle size analyzer and Fourier transform infrared spectroscopy. The reporter genes p[HRE]AFP-Luc were delivered into the nude mice bearing xenografts via tail vein by Fe3O4@PEI, then the bioluminescence signals of mice were observed in an IVIS system. After the treatment of p[HRE]AFP-HSVTK/Fe3O4@PEI, the tumor cell inhibition rate was examined by MTT assay, the cell apoptosis was tested by Flow cytometry, the in vivo tumor development rate and tumor inhibition rate was tested by animal experiment, and the sub-cellular construction of tumor cells was observed by Transmission electron microscopy. Results: Nano-particles Fe3O4@PEI and recombinant vectors p[HRE]AFP-HSVTK and p[HRE]AFP-Luc were successfully constructed; after tale vein injection, image signals were detected only in tumor tissues via IVIS system, but no obvious pathologic damage in other major organs. In the in vitro cell killing test, the cell proliferation inhibition rate and the cell apoptosis rate in combination group was higher than that in hyperthermia treatment group and gene treatment group [inhibition rate: (76.02±7.33)% vs (42.31±4.28)%，(47.76±4.81)%, all P<0.05; apoptosis rate: (34.05±3.41)% vs (14.41±1.55)%，(11.64±1.20)%，all P<0.01]. The in vivo treatment showed that tumor volume development significantly slowed-down and even decreased in combination treatment group, and the tumor mass were significantly smaller than those of the single treatment groups (all P<0.05); and the tumor cell sub - cellular structure showed obvious apoptotic morphology. Conclusion: the suicide gene p [HRE]AFP-HSVTK has specific killing effect on hepatoma cells, Fe3O4@PEI can be used as effective gene treatment carrier and media of magnetic heperthermia treatment; Fe3O4@PEI mediated target treatment combined with magnetic fluid hyperthermia treatment could specifically inhibit the hepatoma xenograft.
12 Sulforaphone enhances differentiation of memory precursor CD8+ cells by mTOR/p-S6 signaling pathway
2018, 25(9):920-927.
DOI: 10.3872/j.issn.1007-385X.2018.09.012
Abstract:
Objective: To investigate the effect of sulforaphane (SFN) on CD8+ T cells differentiation, phenotype and the secretion of intracellular cytokines, as well as to study the underlying molecular mechanism. Methods: In the in vitro culture experiment, the cells were categorized into control group, SNF 10 mmol/L group and SNF 20 mmol/L group according to the SNF concentration. The effect of SFN treatment on CD8+ T cells differentiation, phenotype and cytokine secretion were detected by flow cytometry, and the effect of mTOR siRNA on the expression of CD127 and LKRG1 in CD8+T cells was also detected by flow cytometry. Expression of Bcl-2 and Bcl-6 were analyzed by qRT-PCR. The effect of SFN on apoptosis of CD8+T cells was examined by Annexin-V/PI staining. The protein expressions of p-mTOR, p-S6 and b-actin were detected by western blotting. Results: SFN significantly promoted the formation of memory precursor CD8+ T cells and decreased the expression level of PD-1 and Tim-3 in CD8+T cells(P<0.01); meanwhile, after the treatment of SFN, the expressions of anti-apoptosis genes Bcl-2 and Bcl-6 were significantly increased while the apoptosis of CD8+ T cells was significantly inhibited and the protein expressions of p-mTOR and p-S6 were also significantly inhibited(P<0.05 or P<0.01).Moreover, mTOR siRNA could significantly increasethe expression of CD127 and decrease the expression of LKRG1 (all P<0.01).Conclusion: Sulforaphone promotes the formation of memory precursor CD8+T cells possibly by inhibiting the p-mTOR signaling pathway,and this could obtain more T cells to provide new thoughts for clinical immunotherapy.
Objective: To investigate the effect of sulforaphane (SFN) on CD8+ T cells differentiation, phenotype and the secretion of intracellular cytokines, as well as to study the underlying molecular mechanism. Methods: In the in vitro culture experiment, the cells were categorized into control group, SNF 10 mmol/L group and SNF 20 mmol/L group according to the SNF concentration. The effect of SFN treatment on CD8+ T cells differentiation, phenotype and cytokine secretion were detected by flow cytometry, and the effect of mTOR siRNA on the expression of CD127 and LKRG1 in CD8+T cells was also detected by flow cytometry. Expression of Bcl-2 and Bcl-6 were analyzed by qRT-PCR. The effect of SFN on apoptosis of CD8+T cells was examined by Annexin-V/PI staining. The protein expressions of p-mTOR, p-S6 and b-actin were detected by western blotting. Results: SFN significantly promoted the formation of memory precursor CD8+ T cells and decreased the expression level of PD-1 and Tim-3 in CD8+T cells(P<0.01); meanwhile, after the treatment of SFN, the expressions of anti-apoptosis genes Bcl-2 and Bcl-6 were significantly increased while the apoptosis of CD8+ T cells was significantly inhibited and the protein expressions of p-mTOR and p-S6 were also significantly inhibited(P<0.05 or P<0.01).Moreover, mTOR siRNA could significantly increasethe expression of CD127 and decrease the expression of LKRG1 (all P<0.01).Conclusion: Sulforaphone promotes the formation of memory precursor CD8+T cells possibly by inhibiting the p-mTOR signaling pathway,and this could obtain more T cells to provide new thoughts for clinical immunotherapy.
2018, 25(9):928-933.
DOI: 10.3872/j.issn.1007-385X.2018.09.013
Abstract:
Objective: To investigate the expression of Formin-2（FMN2）protein in gastric cancer tissues and its correlation to clinicopathological features of gastric cancer patients, as well to explore its effect on the proliferation of gastric adenocarcinoma AGS cells.Methods: 84 cases of gastric adenocarcinoma tissues and corresponding para-cancerous tissues were surgically collected from patients treated in the First Affiliated Hospital of Air Force Military Medical University from September 2015 to September 2017. The expression of FMN2 in gastric adenocarcinoma tissues was detected by immunohistochemical staining and analyzed with RNA-Seq data-sets GEPIA. The relationship between FMN2 protein expression in gastric adenocarcinoma tissues and its clinicopathological features was also explored. MTT assay was used to detect the effect of FMN2 on AGS cell proliferation activity, and Western blotting was used to detect the effect of FMN2 on the expression of apoptosis-related protein caspase-3 in AGS cells. Results: The expression level of FMN2 in gastric adenocarcinoma tissues was significantly lower than that in matched adjacent tissues and the expression level of FMN2 was closely related to the TNM stage and differentiation of gastric adenocarcinoma (all P<0.05). Compared to AGS control group, the proliferation activity of AGS/FMN2 was significantly decreased and the expression of apoptosis-related gene Caspase-3 was markedly increased (all P<0.05). Conclusion: The expression of FMN2 was significantly decreased in gastric adenocarcinoma tissues and its low expression is closely related to the degree of tumor differentiation and clinical TNM stage. Moreover, FMN2 over-expression significantly decreased the proliferation of AGS cells. FMN2 may function as independent risk factor for the prognosis of gastric adenocarcinoma,which may provide new ideas for the treatment of gastric adenocarcinoma.
Objective: To investigate the expression of Formin-2（FMN2）protein in gastric cancer tissues and its correlation to clinicopathological features of gastric cancer patients, as well to explore its effect on the proliferation of gastric adenocarcinoma AGS cells.Methods: 84 cases of gastric adenocarcinoma tissues and corresponding para-cancerous tissues were surgically collected from patients treated in the First Affiliated Hospital of Air Force Military Medical University from September 2015 to September 2017. The expression of FMN2 in gastric adenocarcinoma tissues was detected by immunohistochemical staining and analyzed with RNA-Seq data-sets GEPIA. The relationship between FMN2 protein expression in gastric adenocarcinoma tissues and its clinicopathological features was also explored. MTT assay was used to detect the effect of FMN2 on AGS cell proliferation activity, and Western blotting was used to detect the effect of FMN2 on the expression of apoptosis-related protein caspase-3 in AGS cells. Results: The expression level of FMN2 in gastric adenocarcinoma tissues was significantly lower than that in matched adjacent tissues and the expression level of FMN2 was closely related to the TNM stage and differentiation of gastric adenocarcinoma (all P<0.05). Compared to AGS control group, the proliferation activity of AGS/FMN2 was significantly decreased and the expression of apoptosis-related gene Caspase-3 was markedly increased (all P<0.05). Conclusion: The expression of FMN2 was significantly decreased in gastric adenocarcinoma tissues and its low expression is closely related to the degree of tumor differentiation and clinical TNM stage. Moreover, FMN2 over-expression significantly decreased the proliferation of AGS cells. FMN2 may function as independent risk factor for the prognosis of gastric adenocarcinoma,which may provide new ideas for the treatment of gastric adenocarcinoma.
2018, 25(9):934-939.
DOI: 10.3872/j.issn.1007-385X.2018.09.014
Abstract:
Objective: To modify traditional prognostic model for patients with ER/PR+ , HER2- breast cancer to meet the actual requirements in current clinical practice. Methods: 335 patients with ER/PR+, HER2- breast cancer, who were admitted in Department of Breast Surgery, Shanghai Huangpu Center Hospital from January 2009 to December 2009, were enrolled in this study. 97 variables were incorporated into the model, using SCAD variable selection method, after fully considering whether covariates existing a log-linear relationship, reasonable determination of the cut-off value of the covariates in non-logarithmic linear relationship (piecewise linear relationship) and collinear and interaction, then we set up a new Cox regression prognostic model for traditional ER/PR+ , HER2-type breast cancer patients with traditional immunohistochemical indicators, and further establish its nomogram model. On this basis, a nomogram of the survival probability of 1-, 3-, and 5- years after surgery was established; The discrimination and calibration of model were compared to evaluate the predictive ability of the model. Results: The Cox regression model shows that the prognosis of patients are associated with the histologic grade, lymph node metastasis, Ki67, PR and age etc. Among them, the histologic grade and lymph node metastasis have log-linear relationship with prognosis; Ki67, PR and age have non-log-linear relationship with prognosis and the reasonable cut-off values are Ki67(60%)，PR（20%）and age（55 years old）. Area under the receiver operating characteristic (ROC)curve（AUC）of this Cox model for 1- , 3- and 5- year survival after surgery are all above 0.85, indicating high discrimination. The Gr?nnesby-Borgan goodness-of-fit test statistics of this model is 1.37 with P>0.05, indicating good calibration. Conclusion: The modified nomogram.could accurately, directly and effectively predict the survival probability of patients, which may exert good guidance for the clinical practice for patients with breast cancer.
Objective: To modify traditional prognostic model for patients with ER/PR+ , HER2- breast cancer to meet the actual requirements in current clinical practice. Methods: 335 patients with ER/PR+, HER2- breast cancer, who were admitted in Department of Breast Surgery, Shanghai Huangpu Center Hospital from January 2009 to December 2009, were enrolled in this study. 97 variables were incorporated into the model, using SCAD variable selection method, after fully considering whether covariates existing a log-linear relationship, reasonable determination of the cut-off value of the covariates in non-logarithmic linear relationship (piecewise linear relationship) and collinear and interaction, then we set up a new Cox regression prognostic model for traditional ER/PR+ , HER2-type breast cancer patients with traditional immunohistochemical indicators, and further establish its nomogram model. On this basis, a nomogram of the survival probability of 1-, 3-, and 5- years after surgery was established; The discrimination and calibration of model were compared to evaluate the predictive ability of the model. Results: The Cox regression model shows that the prognosis of patients are associated with the histologic grade, lymph node metastasis, Ki67, PR and age etc. Among them, the histologic grade and lymph node metastasis have log-linear relationship with prognosis; Ki67, PR and age have non-log-linear relationship with prognosis and the reasonable cut-off values are Ki67(60%)，PR（20%）and age（55 years old）. Area under the receiver operating characteristic (ROC)curve（AUC）of this Cox model for 1- , 3- and 5- year survival after surgery are all above 0.85, indicating high discrimination. The Gr?nnesby-Borgan goodness-of-fit test statistics of this model is 1.37 with P>0.05, indicating good calibration. Conclusion: The modified nomogram.could accurately, directly and effectively predict the survival probability of patients, which may exert good guidance for the clinical practice for patients with breast cancer.
2018, 25(9):940-944.
DOI: 10.3872/j.issn.1007-385X.2018.09.015
Abstract:
[摘要]环状RNA（circular RNA，circRNA）是一类新近发现的内源性非编码RNA，具有闭合环状结构，由RNA剪切而成。随着高通量测序技术和生物信息学技术的发展，circRNA 不再被认为是RNA剪切过程中的随机产物，其生物学意义和功能受到越来越多的重视。circRNA不具有5’端帽子和3’端poly(A)尾结构,所以其结构较其他非编码RNA稳定。circRNA与多种肿瘤的发生发展密切相关，因此被认为可能是一种新型生物标志物及治疗靶点。本文就circRNA 的特征、形成机制、生物学功能与恶性肿瘤的相关性进行综述，并对具有代表性的肿瘤环状RNA调控机制进行概括总结。
[摘要]环状RNA（circular RNA，circRNA）是一类新近发现的内源性非编码RNA，具有闭合环状结构，由RNA剪切而成。随着高通量测序技术和生物信息学技术的发展，circRNA 不再被认为是RNA剪切过程中的随机产物，其生物学意义和功能受到越来越多的重视。circRNA不具有5’端帽子和3’端poly(A)尾结构,所以其结构较其他非编码RNA稳定。circRNA与多种肿瘤的发生发展密切相关，因此被认为可能是一种新型生物标志物及治疗靶点。本文就circRNA 的特征、形成机制、生物学功能与恶性肿瘤的相关性进行综述，并对具有代表性的肿瘤环状RNA调控机制进行概括总结。
2018, 25(9):945-949.
DOI: 10.3872/j.issn.1007-385X.2018.09.016
Abstract:
[摘要]长链非编码RNA（long non-coding RNA，lncRNA）最初被认为是不具有功能的“转录噪声”，但越来越多的研究发现，lncRNA的失调在很多肿瘤中起着癌基因或抑癌基因的作用，是癌症发展的关键分子。PANDAR作为一种重要的lncRNA受到了诸多关注。有研究证明，PANDAR在许多肿瘤中特异性表达，在大多数肿瘤中上调，但在非小细胞肺癌中显著下调，PANDAR的特异性表达与肿瘤大小、TNM分期和总生存率显著相关。本文通过对lncRNA PANDAR在恶性肿瘤细胞中的主要作用模式、表达情况、作用机制及对各类肿瘤发生发展的影响进行综述，旨在为临床恶性肿瘤生物学诊治疗提供新的靶标。
[摘要]长链非编码RNA（long non-coding RNA，lncRNA）最初被认为是不具有功能的“转录噪声”，但越来越多的研究发现，lncRNA的失调在很多肿瘤中起着癌基因或抑癌基因的作用，是癌症发展的关键分子。PANDAR作为一种重要的lncRNA受到了诸多关注。有研究证明，PANDAR在许多肿瘤中特异性表达，在大多数肿瘤中上调，但在非小细胞肺癌中显著下调，PANDAR的特异性表达与肿瘤大小、TNM分期和总生存率显著相关。本文通过对lncRNA PANDAR在恶性肿瘤细胞中的主要作用模式、表达情况、作用机制及对各类肿瘤发生发展的影响进行综述，旨在为临床恶性肿瘤生物学诊治疗提供新的靶标。
2018, 25(9):950-954.
DOI: 10.3872/j.issn.1007-385X.2018.09.017
Abstract:
[摘要]间变性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）是一种受体型酪氨酸激酶，被认为是肿瘤的驱动基因，它的变异会改变自身激酶活性，进而激活下游信号分子，使细胞增殖调控出现紊乱，从而导致肿瘤的发生。ALK的体细胞变异主要有融合和突变两类，ALK融合在肺癌中已有较多研究，并已研发出相关小分子靶向药物，而ALK突变则在神经胶质瘤中研究相对较多。本文将阐述ALK融合及突变的研究现状及其与肿瘤发生发展的关系，为个性化医疗及靶向药物的研发提供一定的理论线索。
[摘要]间变性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）是一种受体型酪氨酸激酶，被认为是肿瘤的驱动基因，它的变异会改变自身激酶活性，进而激活下游信号分子，使细胞增殖调控出现紊乱，从而导致肿瘤的发生。ALK的体细胞变异主要有融合和突变两类，ALK融合在肺癌中已有较多研究，并已研发出相关小分子靶向药物，而ALK突变则在神经胶质瘤中研究相对较多。本文将阐述ALK融合及突变的研究现状及其与肿瘤发生发展的关系，为个性化医疗及靶向药物的研发提供一定的理论线索。
18 Correlation between abnormal glucose and lipid metabolism and occurrence and development of cancers
2018, 25(9):955-959.
DOI: 10.3872/j.issn.1007-385X.2018.09.018
Abstract:
[摘要] 流行病学研究表明，糖尿病患者中肿瘤的发病风险显著提高，但两者的相关性及发生机制尚未完全阐明。有文献报道，个体的能量稳态、糖脂类代谢、炎症反应等在糖尿病相关肿瘤的发生和进展中发挥了重要作用。本文从糖脂代谢异常、相关信号通路基因表达异常对肿瘤发生发展的影响及其作用机制等方面进行综述，期望为与糖尿病相关肿瘤发生的预防和治疗提供相关依据。
[摘要] 流行病学研究表明，糖尿病患者中肿瘤的发病风险显著提高，但两者的相关性及发生机制尚未完全阐明。有文献报道，个体的能量稳态、糖脂类代谢、炎症反应等在糖尿病相关肿瘤的发生和进展中发挥了重要作用。本文从糖脂代谢异常、相关信号通路基因表达异常对肿瘤发生发展的影响及其作用机制等方面进行综述，期望为与糖尿病相关肿瘤发生的预防和治疗提供相关依据。
2018, 25(9):960-962.
DOI: 10.3872/j.issn.1007-385X.2018.09.019
Abstract:
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.