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Volume 26,Issue 3,2019 Table of Contents
2019, 26(3):253-259.
DOI: 10.3872/j.issn.1007-385X.2019.03.001
Abstract:
[Abstract] Gastrointestinal stromal tumors (GISTs) are the most common malignant tumor of abdominal soft tissue. It originates from Cahal (Cajal) interstitial cells or common precursor cells, and is driven by the mutated KIT gene or platelet-derived growth factor receptor alpha (PDGFRa) gene, all expressing type Ⅲ tyrosine kinase receptors. Imatinib mesylate, a tyrosine kinase receptor inhibitor, has been used for the standard treatment of advanced GIST, which has achieved remarkable results. Thus, GIST has become the most successful example of target therapy for solid tumors. In the context of the era of precision medicine, with the deepening in research of GISTs molecular biology，the molecular targeted treatment of GISTs has obtained a clear venation from the first-line, second-line and third-line of the advanced stage to the postoperative auxiliary and preoperative treatment, providing significant survival benefits for GISTs patients. This article systematically and comprehensively combed the preoperative and postoperative molecular targeting therapy from advanced GIST to early GIST, and analyzed the problems, proposed solutions and prospects for the future, aiming to provide reference for clinical application of molecular targeting drug therapy for GIST.
[Abstract] Gastrointestinal stromal tumors (GISTs) are the most common malignant tumor of abdominal soft tissue. It originates from Cahal (Cajal) interstitial cells or common precursor cells, and is driven by the mutated KIT gene or platelet-derived growth factor receptor alpha (PDGFRa) gene, all expressing type Ⅲ tyrosine kinase receptors. Imatinib mesylate, a tyrosine kinase receptor inhibitor, has been used for the standard treatment of advanced GIST, which has achieved remarkable results. Thus, GIST has become the most successful example of target therapy for solid tumors. In the context of the era of precision medicine, with the deepening in research of GISTs molecular biology，the molecular targeted treatment of GISTs has obtained a clear venation from the first-line, second-line and third-line of the advanced stage to the postoperative auxiliary and preoperative treatment, providing significant survival benefits for GISTs patients. This article systematically and comprehensively combed the preoperative and postoperative molecular targeting therapy from advanced GIST to early GIST, and analyzed the problems, proposed solutions and prospects for the future, aiming to provide reference for clinical application of molecular targeting drug therapy for GIST.
2019, 26(3):260-265.
DOI: 10.3872/j.issn.1007-385X.2019.03.002
Abstract:
[Abstract] Objective: To investigate the effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway, and to explore the mechanism. Methods: UCMSCs were isolated from human umbilical cord tissues by enzyme digestion method and cultured in vitro. The immunophenotypes of the obtained MSCs were identified by flow cytometry. The culture supernatant of UC-MSCs was collected to establish an indirect in vitro co-culture system of UC-MSCs conditioned medium and lung adenocarcinoma A549 cell line. Proliferation of A549 cells was detected by CCK-8 assay; apoptosis of A549 cells was determined by Annexin V/PI double staining, and cell cycle distribution of tumor cells was determined by PI staining. The transcription levels of apoptosis and proliferation associated downstream genes in the PI3K/AKT pathway, such as CyclinD1, BAX and Bcl-2, were detected by quantitative polymerase chain reaction (qPCR). Moreover, Wb was utilized to detect the expression levels of PI3K/AKT pathway-related proteins. Results: The culture flask was filled with fibroblast-like cells, arranged in parallel, with spiral growth after three weeks of isolation and culture of human umbilical cord tissues. The flow cytometry results revealed that the MSC markers CD73, CD90 and CD105, but not CD45 and HLA-DR, were expressed on obtained cells. After indirect in vitro co-culture of UC-MSCs conditioned medium and lung adenocarcinoma A549 cells, the proliferation rate of A549 cells was significantly decreased; the apoptosis rate was significantly increased, and the cell cycle was obviously arrested at the G1 phase as compared with the control group (all P<0.01). The transcription levels of PI3K/AKT signaling pathway-related factors, CyclinD1 and Bcl-2 were down-regulated, and the transcription level of BAX was up-regulated (all P<0.01). The total AKT was not changed, but p-AKT protein expression was decreased in a dose-dependent manner in A549 cells cultured in UC-MSCs conditioned medium (P<0.01). Conclusion: UC-MSCs can affect the proliferation and the apoptosis of A549 cells, and arrest cells in G1 phase. The main mechanism is that UC-MSCs can inhibit the PI3K/AKT signaling pathway in A549 cells, providing an experimental basis for exploring the safety and effectiveness of clinical application of UC-MSCs.
[Abstract] Objective: To investigate the effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway, and to explore the mechanism. Methods: UCMSCs were isolated from human umbilical cord tissues by enzyme digestion method and cultured in vitro. The immunophenotypes of the obtained MSCs were identified by flow cytometry. The culture supernatant of UC-MSCs was collected to establish an indirect in vitro co-culture system of UC-MSCs conditioned medium and lung adenocarcinoma A549 cell line. Proliferation of A549 cells was detected by CCK-8 assay; apoptosis of A549 cells was determined by Annexin V/PI double staining, and cell cycle distribution of tumor cells was determined by PI staining. The transcription levels of apoptosis and proliferation associated downstream genes in the PI3K/AKT pathway, such as CyclinD1, BAX and Bcl-2, were detected by quantitative polymerase chain reaction (qPCR). Moreover, Wb was utilized to detect the expression levels of PI3K/AKT pathway-related proteins. Results: The culture flask was filled with fibroblast-like cells, arranged in parallel, with spiral growth after three weeks of isolation and culture of human umbilical cord tissues. The flow cytometry results revealed that the MSC markers CD73, CD90 and CD105, but not CD45 and HLA-DR, were expressed on obtained cells. After indirect in vitro co-culture of UC-MSCs conditioned medium and lung adenocarcinoma A549 cells, the proliferation rate of A549 cells was significantly decreased; the apoptosis rate was significantly increased, and the cell cycle was obviously arrested at the G1 phase as compared with the control group (all P<0.01). The transcription levels of PI3K/AKT signaling pathway-related factors, CyclinD1 and Bcl-2 were down-regulated, and the transcription level of BAX was up-regulated (all P<0.01). The total AKT was not changed, but p-AKT protein expression was decreased in a dose-dependent manner in A549 cells cultured in UC-MSCs conditioned medium (P<0.01). Conclusion: UC-MSCs can affect the proliferation and the apoptosis of A549 cells, and arrest cells in G1 phase. The main mechanism is that UC-MSCs can inhibit the PI3K/AKT signaling pathway in A549 cells, providing an experimental basis for exploring the safety and effectiveness of clinical application of UC-MSCs.
2019, 26(3):266-272.
DOI: 10.3872/j.issn.1007-385X.2019.03.003
Abstract:
[Abstract] Objective: To explore the mechanism of miR-103 targeting PTEN (gene of phosphate and tension homology deleted on chromsome ten) and activating PI3K/AKT signaling pathway to promote dasatinib (DASA) resistance in lung cancer cells. Methods:DASA-resistant tissues and non-resistant tissues (35 samples for each) from patients treated in Department of Thoracic Surgery, the First Affiliated Hospital of Kunming Medical University from April 2014 to January 2018 were collected for this study. Expression of miR-103 was detected in DASA-resistant tissues and cell lines of lung cancer by quantitative Real-time polymerase chain reaction (qPCR). The effect of miR-103 knock-down on the proliferation, invasion and epithelial mesenchymal transition (EMT) of A549/DASA cells were measured by CCK-8 assay, Transwell and Wb, respectively. Subsequently, the dual luciferase reporter gene assay was used to verify whether PTEN was a target gene of miR-103. CCK-8, Transwell and Wb assay were further used to investigate the effect of miR-103 on malignant biological behaviors of A549/DASA cells via regulating PTEN-PI3K/AKT signaling pathway. Results: miR-103 was highly expressed in DASA-resistant tissues and A549/DASA cells (P<0.01). Knockdown of miR-103 significantly inhibited the proliferation,invasion and EMT of A549/DASA cells (P<0.05 or P<0.01). Additionally, dual luciferase reporter gene assay confirmed that miR-103 directly targeted PTEN and down-regulated its expression (P<0.01). Mechanistically, over-expression of miR-103 targeted and down-regulated PTEN to promote cell viability, invasion and EMT via activating PI3K/AKT pathway (P<0.05 or P<0.01), and further up-regulated the DASA-resistance in A549/DASA cells. Conclusion: miR-103/PTEN/PI3K/AKT signaling pathway plays a certain role in regulating DASA resistance of lung cancer, and knockdown of miR-103 expression may reverse the resistance of A549/DASA cells to DASA.
[Abstract] Objective: To explore the mechanism of miR-103 targeting PTEN (gene of phosphate and tension homology deleted on chromsome ten) and activating PI3K/AKT signaling pathway to promote dasatinib (DASA) resistance in lung cancer cells. Methods:DASA-resistant tissues and non-resistant tissues (35 samples for each) from patients treated in Department of Thoracic Surgery, the First Affiliated Hospital of Kunming Medical University from April 2014 to January 2018 were collected for this study. Expression of miR-103 was detected in DASA-resistant tissues and cell lines of lung cancer by quantitative Real-time polymerase chain reaction (qPCR). The effect of miR-103 knock-down on the proliferation, invasion and epithelial mesenchymal transition (EMT) of A549/DASA cells were measured by CCK-8 assay, Transwell and Wb, respectively. Subsequently, the dual luciferase reporter gene assay was used to verify whether PTEN was a target gene of miR-103. CCK-8, Transwell and Wb assay were further used to investigate the effect of miR-103 on malignant biological behaviors of A549/DASA cells via regulating PTEN-PI3K/AKT signaling pathway. Results: miR-103 was highly expressed in DASA-resistant tissues and A549/DASA cells (P<0.01). Knockdown of miR-103 significantly inhibited the proliferation,invasion and EMT of A549/DASA cells (P<0.05 or P<0.01). Additionally, dual luciferase reporter gene assay confirmed that miR-103 directly targeted PTEN and down-regulated its expression (P<0.01). Mechanistically, over-expression of miR-103 targeted and down-regulated PTEN to promote cell viability, invasion and EMT via activating PI3K/AKT pathway (P<0.05 or P<0.01), and further up-regulated the DASA-resistance in A549/DASA cells. Conclusion: miR-103/PTEN/PI3K/AKT signaling pathway plays a certain role in regulating DASA resistance of lung cancer, and knockdown of miR-103 expression may reverse the resistance of A549/DASA cells to DASA.
2019, 26(3):273-279.
DOI: 10.3872/j.issn.1007-385X.2019.03.004
Abstract:
[Abstract] Objective: To detect the expression of non-receptor protein tyrosine phosphatase 6 (PTPN6) in different esophageal squamous cell carcinoma (ESCC) cell lines, and to investigate its effect on proliferation, migration and invasion ability of Eca109 and Yes-2 cell lines. Methods: qPCR was applied to detect the mRNA expression of PTPN6 in different ESCC cell lines (TE1, Eca109, Kyse150,Kyse170 and Yes-2). pcDNA3.1-PTPN6 plasmid was transiently transfected into Eca109 and Yes-2 cells respectively. The expression of PTPN6 was detected by real-time PCR and Wb. The effects of PTPN6 over-expression on the biological behaviors of ESCC cells were detected by MTS, colony formation assay, wound healing assay and Transwell assay, respectively. Results: The mRNA expression of PTPN6 was remarkably reduced in ESCC cell lines (TE1, Eca109, Kyse150, Kyse170 and Yes-2) compared to normal esophageal epithelial cells (HEEpiC) (P<0.05). Compared to the mock cells, significant up-regulation of PTPN6 was detected in pcDNA3.1-PTPN6 transfected Eca109 and Yes-2 cells (all P<0.05 or P<0.01); PTPN6 over-expression led to a significant inhibition in migration and invasion ability of Eca109 and Yes-2 cells (all P<0.05). Conclusions: Over-expression of PTPN6 may inhibit the proliferation, migration and invasion of ESCC cells, which might be an important factor influencing the biological characteristics of ESCC cells.
[Abstract] Objective: To detect the expression of non-receptor protein tyrosine phosphatase 6 (PTPN6) in different esophageal squamous cell carcinoma (ESCC) cell lines, and to investigate its effect on proliferation, migration and invasion ability of Eca109 and Yes-2 cell lines. Methods: qPCR was applied to detect the mRNA expression of PTPN6 in different ESCC cell lines (TE1, Eca109, Kyse150,Kyse170 and Yes-2). pcDNA3.1-PTPN6 plasmid was transiently transfected into Eca109 and Yes-2 cells respectively. The expression of PTPN6 was detected by real-time PCR and Wb. The effects of PTPN6 over-expression on the biological behaviors of ESCC cells were detected by MTS, colony formation assay, wound healing assay and Transwell assay, respectively. Results: The mRNA expression of PTPN6 was remarkably reduced in ESCC cell lines (TE1, Eca109, Kyse150, Kyse170 and Yes-2) compared to normal esophageal epithelial cells (HEEpiC) (P<0.05). Compared to the mock cells, significant up-regulation of PTPN6 was detected in pcDNA3.1-PTPN6 transfected Eca109 and Yes-2 cells (all P<0.05 or P<0.01); PTPN6 over-expression led to a significant inhibition in migration and invasion ability of Eca109 and Yes-2 cells (all P<0.05). Conclusions: Over-expression of PTPN6 may inhibit the proliferation, migration and invasion of ESCC cells, which might be an important factor influencing the biological characteristics of ESCC cells.
2019, 26(3):280-286.
DOI: 10.3872/j.issn.1007-385X.2019.03.005
Abstract:
[Abstract] Objective: To explore the mechanism of miR-19a-3p regulating cell adhesion molecule 2 (CADM2) to inhibit the proliferation and metastasis of renal carcinoma cells via the AKT signaling pathway. Methods: A total of 42 patients with renal cancer admitted to Department of Nephrology, the First Affiliated Hospital of Suzhou University from April 2012 to November 2017 were enrolled to collect samples of surgically resected renal carcinoma tissues and paracancerous tissues. Expression of miR-19a-3p was detected in renal carcinoma tissues and 4 types of renal carcinoma cell lines such as 786-O by quantitative Real-time polymerase chain reaction (qPCR).The effects of miR-19a-3p knockdown on proliferation, invasion and epithelial mesenchymal transition (EMT) of renal carcinoma 786-O cells were evaluated by CCK-8 assay, Transwell assay and immunofluorescence, respectively. Subsequently, dual luciferase reporter assay was used to verify whether CADM2 was a target gene of miR-19a-3p. Furthermore, Wb was applied to detect the regulatory effect of miR-19a-3p on AKT signaling pathway through CADM2. Results: miR-19a-3p expression was significantly up-regulated in renal carcinoma tissues and cell lines (all P<0.01). Knockdown of miR-19a-3p could inhibit proliferation, invasion and EMT process of 786-O cells; furthermore, the results indicated that CADM2 was a direct target of miR-19a-3p and its expression was down-regulated (P<0.05 or P<0.01). Additionally, knockdown of miR-19a-3p obviously suppressed proliferation, migration and EMT process of 786-O cells via up-regulating CADM2 and blocking AKT pathway (all P<0.05 or P<0.01), thus alleviating the occurrence and development of renal carcinoma. Conclusion: The study demonstrates that miR-19a-3p has a high expression level in renal carcinoma tissues; knockdown of miR-19a-3p could significantly inhibit the proliferation, migration and EMT process of renal carcinoma tissues, and its mecha-nism may be associated with miR-19a-3p/CADM2/AKT axis.
[Abstract] Objective: To explore the mechanism of miR-19a-3p regulating cell adhesion molecule 2 (CADM2) to inhibit the proliferation and metastasis of renal carcinoma cells via the AKT signaling pathway. Methods: A total of 42 patients with renal cancer admitted to Department of Nephrology, the First Affiliated Hospital of Suzhou University from April 2012 to November 2017 were enrolled to collect samples of surgically resected renal carcinoma tissues and paracancerous tissues. Expression of miR-19a-3p was detected in renal carcinoma tissues and 4 types of renal carcinoma cell lines such as 786-O by quantitative Real-time polymerase chain reaction (qPCR).The effects of miR-19a-3p knockdown on proliferation, invasion and epithelial mesenchymal transition (EMT) of renal carcinoma 786-O cells were evaluated by CCK-8 assay, Transwell assay and immunofluorescence, respectively. Subsequently, dual luciferase reporter assay was used to verify whether CADM2 was a target gene of miR-19a-3p. Furthermore, Wb was applied to detect the regulatory effect of miR-19a-3p on AKT signaling pathway through CADM2. Results: miR-19a-3p expression was significantly up-regulated in renal carcinoma tissues and cell lines (all P<0.01). Knockdown of miR-19a-3p could inhibit proliferation, invasion and EMT process of 786-O cells; furthermore, the results indicated that CADM2 was a direct target of miR-19a-3p and its expression was down-regulated (P<0.05 or P<0.01). Additionally, knockdown of miR-19a-3p obviously suppressed proliferation, migration and EMT process of 786-O cells via up-regulating CADM2 and blocking AKT pathway (all P<0.05 or P<0.01), thus alleviating the occurrence and development of renal carcinoma. Conclusion: The study demonstrates that miR-19a-3p has a high expression level in renal carcinoma tissues; knockdown of miR-19a-3p could significantly inhibit the proliferation, migration and EMT process of renal carcinoma tissues, and its mecha-nism may be associated with miR-19a-3p/CADM2/AKT axis.
2019, 26(3):287-292.
DOI: 10.3872/j.issn.1007-385X.2019.03.006
Abstract:
[Abstract] Objective:To explore the mechanism of EYA1 (eyes absent 1) inhibiting the malignant progression of gastric cancer SGC-7901 cells through regulating PTEN/PI3K/AKT signaling pathway. Methods: Twenty-nine pairs of gastric cancer tissues and para-cancerous tissues collected at the General Surgery center, Southwest Hospital Affiliated to Military Medical University during June 2016 and June 2018 were used in this study. Wb and RT-PCR assays were used to test the mRNA and protein expressions of EYA1 in gastric cancer tissues and the paired para-cancerous tissues; Transfection with plasmid or siRNAs were used to up-regulate or down-regulate EYA1 or PTEN expression in gastric cancer SGC-7901 cells; MTT, Flow Cytometry, Wound Healing and Transwell assays were carried out to detect cell proliferation, apoptosis, metastasis and invasion abilities, respectively. Results: EYA1 expression was decreased in gastric cancer tissues as compared with the para-cancerous tissues at both mRNA and protein levels (P<0.01); EYA1 over-expression significantly enhanced the proliferation, metastasis and invasion of SGC-7901 cells (all P<0.05), and inhibited cell apoptosis (P<0.05);moreover, its over-expressionsignificantly increased the expression of PTEN, and inhibited the activation of PI3K/AKT pathway (all P<0.05 or P<0.01). However, the above effects mediated by EYA1 up-regulation were significantly impaired after the knockout of PTEN (all P<0.05 or P<0.01). Conclusion: EYA1 can inhibit the malignant progression of gastric cancer SGC-7901 cells through promoting the expression of PTEN and activating PI3K/AKT pathway.
[Abstract] Objective:To explore the mechanism of EYA1 (eyes absent 1) inhibiting the malignant progression of gastric cancer SGC-7901 cells through regulating PTEN/PI3K/AKT signaling pathway. Methods: Twenty-nine pairs of gastric cancer tissues and para-cancerous tissues collected at the General Surgery center, Southwest Hospital Affiliated to Military Medical University during June 2016 and June 2018 were used in this study. Wb and RT-PCR assays were used to test the mRNA and protein expressions of EYA1 in gastric cancer tissues and the paired para-cancerous tissues; Transfection with plasmid or siRNAs were used to up-regulate or down-regulate EYA1 or PTEN expression in gastric cancer SGC-7901 cells; MTT, Flow Cytometry, Wound Healing and Transwell assays were carried out to detect cell proliferation, apoptosis, metastasis and invasion abilities, respectively. Results: EYA1 expression was decreased in gastric cancer tissues as compared with the para-cancerous tissues at both mRNA and protein levels (P<0.01); EYA1 over-expression significantly enhanced the proliferation, metastasis and invasion of SGC-7901 cells (all P<0.05), and inhibited cell apoptosis (P<0.05);moreover, its over-expressionsignificantly increased the expression of PTEN, and inhibited the activation of PI3K/AKT pathway (all P<0.05 or P<0.01). However, the above effects mediated by EYA1 up-regulation were significantly impaired after the knockout of PTEN (all P<0.05 or P<0.01). Conclusion: EYA1 can inhibit the malignant progression of gastric cancer SGC-7901 cells through promoting the expression of PTEN and activating PI3K/AKT pathway.
2019, 26(3):293-298.
DOI: 10.3872/j.issn.1007-385X.2019.03.007
Abstract:
[Abstract] Objective: To investigate the effects of prostate cancer exosomes on the migration and invasion ability of stromal cells (WPMY-1), and to explore its mechanism. Methods: Exosomes in LNCaP-AI+F prostate cancer cell supernatant were isolated by ultracentrifugation and the typical structure of exosome was captured by electron microscope. The particle size distribution was analyzed by Zetaview, and Wb was used to identify the marker proteins and other proteins. After co-incubation of WPMY-1 cells and prostate cancer exosomes (40 μg/ml), laser confocal microscope was used to observe the uptake of PKH67-labeled exosomes by WPMY-1 cells; Transwell assay was used to detect the migration and invasion ability of WPMY-1 cells; qPCR was performed to detect the expression of three cancer-associated fibroblast (CAF)-related molecules (IL-8, PDGFB and MMP9) at mRNA level; and the phosphorylation of EGFR and ERK1/2 was analyzed by Wb. Results: Typical cup-shaped structure of exosomes was observed under electron microscope. The Zetaview results showed that the particle size distribution was concentrated at about 100 nm. The expression of exosome marker proteins CD63 and ALIX further verified that the isolated particles were exosomes. Besides, EGFR, HER2 and SRC, which were related to the progression of prostate cancer, were also enriched in exosomes. After co-incubation, confocal microscope imaging showed a number of PKH67 labeled exosomes in recipient WPMY-1 cells. Transwell experiments showed that exosomes could significantly enhance the migration and invasion ability of WPMY-1 cells (all P<0.01). Compared with the control group, increased secretion of IL-8,PDGFB and MMP9 was observed after exosome treatment (40 μg/ml) (P<0.05 or P<0.01). Wb indicated that exosomes could promote the phosphorylation of EGFR and ERK1/2 of WPMY-1 cells (P<0.01). Conclusion: Prostate cancer cell exosomes could act on the stromal cell WPMY-1 to highly express multiple CAF-related molecules, promote the phosphorylation of EGFR and ERK1/2 and enhance the migration and invasion ability of WPMY-1 cells.
[Abstract] Objective: To investigate the effects of prostate cancer exosomes on the migration and invasion ability of stromal cells (WPMY-1), and to explore its mechanism. Methods: Exosomes in LNCaP-AI+F prostate cancer cell supernatant were isolated by ultracentrifugation and the typical structure of exosome was captured by electron microscope. The particle size distribution was analyzed by Zetaview, and Wb was used to identify the marker proteins and other proteins. After co-incubation of WPMY-1 cells and prostate cancer exosomes (40 μg/ml), laser confocal microscope was used to observe the uptake of PKH67-labeled exosomes by WPMY-1 cells; Transwell assay was used to detect the migration and invasion ability of WPMY-1 cells; qPCR was performed to detect the expression of three cancer-associated fibroblast (CAF)-related molecules (IL-8, PDGFB and MMP9) at mRNA level; and the phosphorylation of EGFR and ERK1/2 was analyzed by Wb. Results: Typical cup-shaped structure of exosomes was observed under electron microscope. The Zetaview results showed that the particle size distribution was concentrated at about 100 nm. The expression of exosome marker proteins CD63 and ALIX further verified that the isolated particles were exosomes. Besides, EGFR, HER2 and SRC, which were related to the progression of prostate cancer, were also enriched in exosomes. After co-incubation, confocal microscope imaging showed a number of PKH67 labeled exosomes in recipient WPMY-1 cells. Transwell experiments showed that exosomes could significantly enhance the migration and invasion ability of WPMY-1 cells (all P<0.01). Compared with the control group, increased secretion of IL-8,PDGFB and MMP9 was observed after exosome treatment (40 μg/ml) (P<0.05 or P<0.01). Wb indicated that exosomes could promote the phosphorylation of EGFR and ERK1/2 of WPMY-1 cells (P<0.01). Conclusion: Prostate cancer cell exosomes could act on the stromal cell WPMY-1 to highly express multiple CAF-related molecules, promote the phosphorylation of EGFR and ERK1/2 and enhance the migration and invasion ability of WPMY-1 cells.
2019, 26(3):299-305.
DOI: 10.3872/j.issn.1007-385X.2019.03.008
Abstract:
[Abstract] Objective: To investigate the role of momordica protein MAP30 in multiple myeloma (MM) and the possible mechanism.Methods: Human myeloma RPMI-8226, NCI-H929 and U266 cells were treated with MAP30 at different concentration (1-10 μmol/L)and then the proliferation rates of cells were detected by CCK-8 assay. Annexin V/PI flow cytometry was used to evaluate the apoptosis rate of myeloma cells, and the expressions of apoptosis-related protein (PARP), autophagy-related proteins (LC3II, P62) and Akt/mTOR pathway-related proteins in multiple myeloma cells were also detected via Wb. The changes in cell proliferation, apoptosis and autophagy after the treatment of MAP30 combined with autophagy agonist rapamycin (Rap) or autophagy inhibitor bafilomycin (Baf) were observed by CCK-8, flow cytometry and Wb, respectively. Results: MAP30 (1-10 μmol/L) inhibited the proliferation of myeloma cells in a time- and dose-dependent manner (P<0.05 or P<0.01). With MAP30 acting on myeloma cells alone, the apoptosis and autophagy of MM cells, as well as the expression of PARP cleavage and LC3II increased while the expression of P62 decreased significantly (all P<0.05 or P<0.01). After being treated with MAP30+Baf, compared with MAP30 treatment alone, the cell proliferation was remarkably enhanced while cell apoptosis and cell autophagy were suppressed, besides, the expression of PARP cleavage and LC3II were decreased and P62 level was augmented (all P<0.05 or P<0.01). Conversely, after being treated with MAP30+Baf, compared with MAP30 treat-ment or Baf treatment alone, cell proliferation and P62 level were reduced, while apoptosis and autophagy as well as the expressions of PARP cleavage and LC3II level were increased (all P<0.05 or P<0.01). The expressions of p-AKT and p-mTOR were significantly reduced with the effect of MAP30 on myeloma cells (all P<0.05). Conclusion: MAP30 can promote the apoptosis and autophagy of myeloma cells through AKT/mTOR pathway, which may provide a new therapeutic strategy for treatment of multiple myeloma.
[Abstract] Objective: To investigate the role of momordica protein MAP30 in multiple myeloma (MM) and the possible mechanism.Methods: Human myeloma RPMI-8226, NCI-H929 and U266 cells were treated with MAP30 at different concentration (1-10 μmol/L)and then the proliferation rates of cells were detected by CCK-8 assay. Annexin V/PI flow cytometry was used to evaluate the apoptosis rate of myeloma cells, and the expressions of apoptosis-related protein (PARP), autophagy-related proteins (LC3II, P62) and Akt/mTOR pathway-related proteins in multiple myeloma cells were also detected via Wb. The changes in cell proliferation, apoptosis and autophagy after the treatment of MAP30 combined with autophagy agonist rapamycin (Rap) or autophagy inhibitor bafilomycin (Baf) were observed by CCK-8, flow cytometry and Wb, respectively. Results: MAP30 (1-10 μmol/L) inhibited the proliferation of myeloma cells in a time- and dose-dependent manner (P<0.05 or P<0.01). With MAP30 acting on myeloma cells alone, the apoptosis and autophagy of MM cells, as well as the expression of PARP cleavage and LC3II increased while the expression of P62 decreased significantly (all P<0.05 or P<0.01). After being treated with MAP30+Baf, compared with MAP30 treatment alone, the cell proliferation was remarkably enhanced while cell apoptosis and cell autophagy were suppressed, besides, the expression of PARP cleavage and LC3II were decreased and P62 level was augmented (all P<0.05 or P<0.01). Conversely, after being treated with MAP30+Baf, compared with MAP30 treat-ment or Baf treatment alone, cell proliferation and P62 level were reduced, while apoptosis and autophagy as well as the expressions of PARP cleavage and LC3II level were increased (all P<0.05 or P<0.01). The expressions of p-AKT and p-mTOR were significantly reduced with the effect of MAP30 on myeloma cells (all P<0.05). Conclusion: MAP30 can promote the apoptosis and autophagy of myeloma cells through AKT/mTOR pathway, which may provide a new therapeutic strategy for treatment of multiple myeloma.
2019, 26(3):306-311.
DOI: 10.3872/j.issn.1007-385X.2019.03.009
Abstract:
[Abstract] Objective: To investigate the potential effects of miR-455-3p on proliferation, invasion and epithelial-mesenchymal transition (EMT) process of ovarian cancer cells, and explore its molecular mechanism. Methods: The IOSE80, SKOV-3 and A2780 cells were transfected with miR-455-3p mimics and negative controls (NC) by using LipofectamineTM 2000. Quantitative polymerase chain reaction (qPCR) assay was performed to detect the mRNA expressions of miR-455-3p and fatty acid-binding protein 4 (FABP4) in IOSE80, SKOV-3 and A2780 cells. The expression levels of FABP4 and EMT-associated proteins were detected by Wb. CCK-8 assay was applied to measure cell proliferation. Cell migration was analyzed by using Transwell assay. Bioinformatics analysis was used to predict the potential target of miR-455-3p, and the targeting effect of miR-455-3p on FABP4 was verified by the dual-luciferase reporter assay system. Results: The expression of miR-455-3p was declined (all P<0.05), while the expression of FABP4 was elevated (all P<0.05) in ovarian cancer cells (SKOV-3 and A2780) in comparison with normal ovarian IOSE80 cells. Additionally, over-expression of miR-455-3p obviously inhibited cell proliferation and migration capacity of SKOV-3 cells (all P<0.05). Furthermore, over-expression of miR-455-3p impeded EMT progress by up-regulating E-cadherin expression and down-regulating N-cadherin and vimentin expression (all P<0.05). Importantly, the dual-luciferase reporter system, qPCR and Wb validated that FABP4 was a specific target gene of miR-455-3p, and miR-455-3p showed specific binding with FABP4 3’-UTR and negatively regulated the expression of FABP4 at both mRNA and protein levels. Mechanistically, over-expression of FABP4 apparently reversed the inhibitory effects of miR-455-3p on cell proliferation and migration of SKOV-3 cells (all P<0.05). Conclusion: miR-455-3p, acting as a tumor suppressor protein, can inhibit ovarian cancer cell proliferation, migration and EMT process by targeting FABP4, suggesting that miR-455-3p may be a new potential therapeutic target for ovarian cancer treatment.
[Abstract] Objective: To investigate the potential effects of miR-455-3p on proliferation, invasion and epithelial-mesenchymal transition (EMT) process of ovarian cancer cells, and explore its molecular mechanism. Methods: The IOSE80, SKOV-3 and A2780 cells were transfected with miR-455-3p mimics and negative controls (NC) by using LipofectamineTM 2000. Quantitative polymerase chain reaction (qPCR) assay was performed to detect the mRNA expressions of miR-455-3p and fatty acid-binding protein 4 (FABP4) in IOSE80, SKOV-3 and A2780 cells. The expression levels of FABP4 and EMT-associated proteins were detected by Wb. CCK-8 assay was applied to measure cell proliferation. Cell migration was analyzed by using Transwell assay. Bioinformatics analysis was used to predict the potential target of miR-455-3p, and the targeting effect of miR-455-3p on FABP4 was verified by the dual-luciferase reporter assay system. Results: The expression of miR-455-3p was declined (all P<0.05), while the expression of FABP4 was elevated (all P<0.05) in ovarian cancer cells (SKOV-3 and A2780) in comparison with normal ovarian IOSE80 cells. Additionally, over-expression of miR-455-3p obviously inhibited cell proliferation and migration capacity of SKOV-3 cells (all P<0.05). Furthermore, over-expression of miR-455-3p impeded EMT progress by up-regulating E-cadherin expression and down-regulating N-cadherin and vimentin expression (all P<0.05). Importantly, the dual-luciferase reporter system, qPCR and Wb validated that FABP4 was a specific target gene of miR-455-3p, and miR-455-3p showed specific binding with FABP4 3’-UTR and negatively regulated the expression of FABP4 at both mRNA and protein levels. Mechanistically, over-expression of FABP4 apparently reversed the inhibitory effects of miR-455-3p on cell proliferation and migration of SKOV-3 cells (all P<0.05). Conclusion: miR-455-3p, acting as a tumor suppressor protein, can inhibit ovarian cancer cell proliferation, migration and EMT process by targeting FABP4, suggesting that miR-455-3p may be a new potential therapeutic target for ovarian cancer treatment.
10 Tim-3 expression on T cell surface in patients with esophageal cancer and its clinical significance
ZHENG Yujiaa
,
YANG Huiyuna
,
b
,
WU Qiana
,
WANG Dana
,
ZHANG Zhena
,
ZHAO Songc
,
QI Yuc
,
ZHANG Yia
,
c
,
HUANG Lana
2019, 26(3):312-316.
DOI: 10.3872/j.issn.1007-385X.2019.03.010
Abstract:
[Abstract] Objective: To investigate the expression of Tim-3 on the surface of T cells in patients with esophageal cancer, and to explore its clinical significance. Methods: Fresh tumor tissues, paracancerous tissues, and peripheral blood were collected from 25 patients with esophageal cancer at the first affiliated Hospital of Zhengzhou University from September 2016 to April 2018. Peripheral blood from 10 healthy subjects was also collected during the same time period. The expressions of Tim-3, early apoptotic molecules and intrinsic factors in tumor tissues and peripheral blood PBMCs of 25 esophageal cancer patients were determined by flow cytometry.Also, the correlation between Tim-3+ T cell proportion and pathological parameters was investigated. The expression of Tim-3 in tumor tissues and paracancerous tissues was detected by fluorescence quantitative real-time polymerase chain reaction (qPCR). TCGA database was used to further verify the expression of Tim-3 in tumor tissues and paracancerous tissues, as well as its relationship with prognosis. Results: Tim-3 expression on T cells was higher in tumor tissues from esophageal cancer patients (P<0.01). Tim-3+T cell function was in an exhausted status(P<0.05 or P<0.01), and the expression of Tim-3 on the surface of T cells in esophageal cancer microenvironment was closely related to lymph node metastasis and clinical staging (all P<0.01). Conclusion: Taken together, Tim-3 expression on the surface of T cells could induce T cell dysfunction in patients with esophageal cancer, suggesting that Tim-3 may serve as a potential therapeutic target for esophageal cancer.
[Abstract] Objective: To investigate the expression of Tim-3 on the surface of T cells in patients with esophageal cancer, and to explore its clinical significance. Methods: Fresh tumor tissues, paracancerous tissues, and peripheral blood were collected from 25 patients with esophageal cancer at the first affiliated Hospital of Zhengzhou University from September 2016 to April 2018. Peripheral blood from 10 healthy subjects was also collected during the same time period. The expressions of Tim-3, early apoptotic molecules and intrinsic factors in tumor tissues and peripheral blood PBMCs of 25 esophageal cancer patients were determined by flow cytometry.Also, the correlation between Tim-3+ T cell proportion and pathological parameters was investigated. The expression of Tim-3 in tumor tissues and paracancerous tissues was detected by fluorescence quantitative real-time polymerase chain reaction (qPCR). TCGA database was used to further verify the expression of Tim-3 in tumor tissues and paracancerous tissues, as well as its relationship with prognosis. Results: Tim-3 expression on T cells was higher in tumor tissues from esophageal cancer patients (P<0.01). Tim-3+T cell function was in an exhausted status(P<0.05 or P<0.01), and the expression of Tim-3 on the surface of T cells in esophageal cancer microenvironment was closely related to lymph node metastasis and clinical staging (all P<0.01). Conclusion: Taken together, Tim-3 expression on the surface of T cells could induce T cell dysfunction in patients with esophageal cancer, suggesting that Tim-3 may serve as a potential therapeutic target for esophageal cancer.
2019, 26(3):317-322.
DOI: 10.3872/j.issn.1007-385X.2019.03.011
Abstract:
[Abstract] Objective: To investigate the association between genetic variation of kinase insert domain receptor (KDR) and the prognosis in colorectal cancer (CRC) patients received 5-FU based adjuvant chemotherapy. Methods: The clinical data of 176 CRC patients,who underwent surgical treatment at the Department of Anus and Intestine Surgery, People’s Hospital of Zhengzhou during January 2012 and December 2017, were retrospectively analyzed, and 93 cases of tumor tissues were collected for this study. The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). qPCR was used to detect the expression of KDR mRNA in colorectal cancer tissues. The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model. The expression of different genotypes of KDR was analyzed by nonparametric test. The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis, and the other variables were adjusted by Cox risk scale model. Results: Of the polymorphisms analyzed, only rs2071559 was of clinical significance.The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows: TT genotype in 95 cases (53.98%), TC genotype in 70 cases (39.77%) and CC genotype in 11 cases (6.25%); the minor allele frequency was 0.26; and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium (P=0.690). The median disease free survival (mDFS) of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years, respectively (P<0.05); The median overall survival (mOS) of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years, respectively (P<0.05). After COX model modification, the effect of TC/CC genotype on mOS was still statistically significant (OR=0.55, P<0.05). The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype (P<0.01). Conclusion: The polymorphism of KDR rs2071559 is associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNA expression of KDR.
[Abstract] Objective: To investigate the association between genetic variation of kinase insert domain receptor (KDR) and the prognosis in colorectal cancer (CRC) patients received 5-FU based adjuvant chemotherapy. Methods: The clinical data of 176 CRC patients,who underwent surgical treatment at the Department of Anus and Intestine Surgery, People’s Hospital of Zhengzhou during January 2012 and December 2017, were retrospectively analyzed, and 93 cases of tumor tissues were collected for this study. The genotype of KDR polymorphism locus was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). qPCR was used to detect the expression of KDR mRNA in colorectal cancer tissues. The correlation between the polymorphism genotypes and other variables was analyzed by logistic regression model. The expression of different genotypes of KDR was analyzed by nonparametric test. The relationship between KDR genotype and prognosis of patients was analyzed by Kaplan-Meier survival analysis, and the other variables were adjusted by Cox risk scale model. Results: Of the polymorphisms analyzed, only rs2071559 was of clinical significance.The distribution frequency of KDR rs2071559 in 176 CRC patients was as follows: TT genotype in 95 cases (53.98%), TC genotype in 70 cases (39.77%) and CC genotype in 11 cases (6.25%); the minor allele frequency was 0.26; and the distribution of three genotypes was in accordance with Hardy-Weinberg's Equilibrium (P=0.690). The median disease free survival (mDFS) of patients carrying C allele and wild type TT genotype was 4.4 and 3.2 years, respectively (P<0.05); The median overall survival (mOS) of patients with TC/CC genotype and TT genotype was 5.2 and 4.0 years, respectively (P<0.05). After COX model modification, the effect of TC/CC genotype on mOS was still statistically significant (OR=0.55, P<0.05). The mRNA expression of KDR in cancer tissues of the patients with TC/CC genotypes were significantly lower than those of the wild type TT genotype (P<0.01). Conclusion: The polymorphism of KDR rs2071559 is associated with clinical outcomes in patients with colorectal cancer. KDR rs2071559 may affect the prognosis of colorectal cancer patients by affecting the mRNA expression of KDR.
2019, 26(3):323-327.
DOI: 10.3872/j.issn.1007-385X.2019.03.012
Abstract:
[Abstract] Objective: To investigate the effect of long non-coding RNA (lncRNA) Linc01296 on cisplatin (DDP) resistance in ovarian cancer cells and the mechanism. Methods: Fifty-three cases of ovarian cancer tissues, 22 cases of borderline ovarian tumor tissues and 17 cases of benign ovarian mass tissues were collected from Department of Gynecology, Sichuan Provincial People's Hospital during October 2017 to October 2018. The differential expression of Linc01296 mRNA in above tissue samples was detected by qPCR, and its relationship with clinicopathological data was analyzed. Human ovarian cancer cell line OVCAR-3 (OVCAR-3 Control) and its DDPresistant cell line (OVCAR-3 DR) were cultured. Lentiviral vectors expressing siRNA that targeting Linc01296 or siRNA control were transfected into OVCAR-3 DR cells respectively, as siLinc01296 group and siControl group. CCK-8 assay was used to detect DDP semi-inhibitory concentration (IC50) and drug resistance index of each group; real-time fluorescence quantitative PCR (qPCR) was used to detect the mRNA expressions of Linc 01296 and tumor stem cell related genes (Oct-4 and Sox-2) in cell lines of OVCAR-3 control,DR, DR siControl and siLinc 01296; and the protein expressions of Oct-4 and Sox-2 in each group were detected by Wb. Results: DDP IC50 and drug resistance index in OVCAR-3 DR group was significantly higher than that in Control group (all P<0.01), and DDP IC50 and drug resistance index in siLinc01296 group was significantly lower than that in DR siControl group (all P<0.01), but significantly higher than that in Control group (all P<0.01). The mRNA and protein expressions of Linc01296, Oct-4 and Sox-2 in DR group were significantly higher than that in Control group (all P<0.01), while those expressions in siLinc01296 group were significantly lower than those in DR siControl group (P<0.01), and the mRNA and protein expressions of Oct-4 and Sox-2 in siLinc01296 group were higher than that in control group (P<0.01). The expression of Linc01296 in ovarian cancer tissues was significantly higher than that in borderline ovarian tumor tissues and benign ovarian mass tissues (P<0.01), which was positively correlated with lymph node metastasis and clinical stage (P<0.05). Conclusion: Linc01296 can promote the occurrence of DDP resistance via promoting the expression of cancer stem cell markers in ovarian cancer; Linc01296 is highly expressed in ovarian cancer tissues and closely related to disease progression of patients.
[Abstract] Objective: To investigate the effect of long non-coding RNA (lncRNA) Linc01296 on cisplatin (DDP) resistance in ovarian cancer cells and the mechanism. Methods: Fifty-three cases of ovarian cancer tissues, 22 cases of borderline ovarian tumor tissues and 17 cases of benign ovarian mass tissues were collected from Department of Gynecology, Sichuan Provincial People's Hospital during October 2017 to October 2018. The differential expression of Linc01296 mRNA in above tissue samples was detected by qPCR, and its relationship with clinicopathological data was analyzed. Human ovarian cancer cell line OVCAR-3 (OVCAR-3 Control) and its DDPresistant cell line (OVCAR-3 DR) were cultured. Lentiviral vectors expressing siRNA that targeting Linc01296 or siRNA control were transfected into OVCAR-3 DR cells respectively, as siLinc01296 group and siControl group. CCK-8 assay was used to detect DDP semi-inhibitory concentration (IC50) and drug resistance index of each group; real-time fluorescence quantitative PCR (qPCR) was used to detect the mRNA expressions of Linc 01296 and tumor stem cell related genes (Oct-4 and Sox-2) in cell lines of OVCAR-3 control,DR, DR siControl and siLinc 01296; and the protein expressions of Oct-4 and Sox-2 in each group were detected by Wb. Results: DDP IC50 and drug resistance index in OVCAR-3 DR group was significantly higher than that in Control group (all P<0.01), and DDP IC50 and drug resistance index in siLinc01296 group was significantly lower than that in DR siControl group (all P<0.01), but significantly higher than that in Control group (all P<0.01). The mRNA and protein expressions of Linc01296, Oct-4 and Sox-2 in DR group were significantly higher than that in Control group (all P<0.01), while those expressions in siLinc01296 group were significantly lower than those in DR siControl group (P<0.01), and the mRNA and protein expressions of Oct-4 and Sox-2 in siLinc01296 group were higher than that in control group (P<0.01). The expression of Linc01296 in ovarian cancer tissues was significantly higher than that in borderline ovarian tumor tissues and benign ovarian mass tissues (P<0.01), which was positively correlated with lymph node metastasis and clinical stage (P<0.05). Conclusion: Linc01296 can promote the occurrence of DDP resistance via promoting the expression of cancer stem cell markers in ovarian cancer; Linc01296 is highly expressed in ovarian cancer tissues and closely related to disease progression of patients.
2019, 26(3):328-332.
DOI: 10.3872/j.issn.1007-385X.2019.03.013
Abstract:
[Abstract] Objective: To explore the mechanism of long non-coding RNA POU3F3 (lncRNAPOU3F3) affecting temozolomide (TMZ)-resistance in high-grade glioma cells via regulating MGMT expression. Methods: Sixty cases of tissues from patients treated at the Department of Neurosurgery, Peking University International Hospital during January 2016 and January 2018 were collected for this study, including 12 cases from brain trauma patients (normal group), 30 cases from primary high-grade glioma patients (primary onset group) and 18 cases from recurrent high-grade glioma patients (recurrence group, accepted surgery+TMZ already). U251 cells were induced with TMZ at the concentration of 1, 2, 4 and 8 μg/ml and maintained normal growth for a week to construct TMZ-resistant U251cell line (U251 TMZ-resistance, U251-TR); and the normal control group was treated with equal volume of physiological saline.Reverse transcription polymerase chain reaction (qPCR) and Wb were used to detect the mRNA and protein expressions of POU3F3 and MGMT (methylguanine DNA methyltransferase) in normal brain tissues and glioma cells. Lentivirus transfection was used to construct U251 cell line with stable POU3F3 interference (U251-TR siPOU3F3); CCK-8 was used to detect TMZ IC50 value (the half maximal inhibitory concentration) in each group of U251 cells, and Wb was used to detect the expression of MGMT protein in each group of cells. Results: Compared with the normal group and primaryonset group, the expression of POU3F3 in recurrence group was significantly increased (P<0.01). The TMZ IC50 of U251-TR cells was significantly higher than that of U251 cells (P<0.01), and The TMZ IC50 of U251-TR siPOU3F3 cells was significantly lower than that of U251-TR cellsbut higher than that of U251 cells (all P<0.01). The protein and mRNA expressions of POU3F3 and MGMT in U251-TR cells were significantly higher than that in U251 cells (P<0.01),while those expressions in U251-TR siPOU3F3 cells were significantly lower than those in U251-TR cells (P<0.01).Conclusion: lncRNA POU3F3 is the key factor to promote TMZ resistance in human high-grade gliomas cells, which may exert certain guiding significance in the clinical treatment for TMZ resistance.
[Abstract] Objective: To explore the mechanism of long non-coding RNA POU3F3 (lncRNAPOU3F3) affecting temozolomide (TMZ)-resistance in high-grade glioma cells via regulating MGMT expression. Methods: Sixty cases of tissues from patients treated at the Department of Neurosurgery, Peking University International Hospital during January 2016 and January 2018 were collected for this study, including 12 cases from brain trauma patients (normal group), 30 cases from primary high-grade glioma patients (primary onset group) and 18 cases from recurrent high-grade glioma patients (recurrence group, accepted surgery+TMZ already). U251 cells were induced with TMZ at the concentration of 1, 2, 4 and 8 μg/ml and maintained normal growth for a week to construct TMZ-resistant U251cell line (U251 TMZ-resistance, U251-TR); and the normal control group was treated with equal volume of physiological saline.Reverse transcription polymerase chain reaction (qPCR) and Wb were used to detect the mRNA and protein expressions of POU3F3 and MGMT (methylguanine DNA methyltransferase) in normal brain tissues and glioma cells. Lentivirus transfection was used to construct U251 cell line with stable POU3F3 interference (U251-TR siPOU3F3); CCK-8 was used to detect TMZ IC50 value (the half maximal inhibitory concentration) in each group of U251 cells, and Wb was used to detect the expression of MGMT protein in each group of cells. Results: Compared with the normal group and primaryonset group, the expression of POU3F3 in recurrence group was significantly increased (P<0.01). The TMZ IC50 of U251-TR cells was significantly higher than that of U251 cells (P<0.01), and The TMZ IC50 of U251-TR siPOU3F3 cells was significantly lower than that of U251-TR cellsbut higher than that of U251 cells (all P<0.01). The protein and mRNA expressions of POU3F3 and MGMT in U251-TR cells were significantly higher than that in U251 cells (P<0.01),while those expressions in U251-TR siPOU3F3 cells were significantly lower than those in U251-TR cells (P<0.01).Conclusion: lncRNA POU3F3 is the key factor to promote TMZ resistance in human high-grade gliomas cells, which may exert certain guiding significance in the clinical treatment for TMZ resistance.
2019, 26(3):333-337.
DOI: 10.3872/j.issn.1007-385X.2019.03.014
Abstract:
[Abstract] Objective: To investigate the value of intercellular adhesion molecule 1 (ICAM-1) for the diagnosis and prognosis of pancreatic cancer. Methods: Eighty patients with pancreatic cancer (pancreatic cancer group), forty patients with benign pancreatic disease (benign disease group) who were admitted to Department of Hepatobiliary and Pancreatic Surgery in Cancer Hospital of Hubei Province from April 2015 to December 2017 were included in the study; and thirty healthy subjects during the same period were included as control. Serum ICAM-1 and carbohydrate antigen 19-9 (CA19-9) levels were determined in all the three groups. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic characteristics of ICAM-1 for pancreatic cancer. The COX regression model was used to analyze whether serum ICAM-1 was independently associated with the prognosis of patients with pancreatic cancer.Results: The levels of ICAM-1 and CA19-9 in pancreatic cancer group were significantly higher than those in benign disease group and control group (P<0.01). The level of CA19-9 in benign disease group was significantly higher than that in control group (P<0.01). ROC curve analysis showed that the area under the curve (AUC) of serum ICAM-1, CA19-9 and the combinations of both was 0.732 (95% CI: 0.658-0.807, P=0.000), 0.691 (95% CI: 0.620-0.762, P=0.000), and 0.747 (95% CI: 0.674-0.821, P=0.000), respectively. There was a significant positive correlation between ICAM-1 and CA19-9 (r=0.472, P=0.000). The survival time of patients with serum ICAM-1<2 308 U/ml was significantly longer than that of patients with ICAM-1≥2 308 U/ml (χ2=28.357,P=0.000); COX regression analysis showed that ICAM-1 ≥2 308 U/ml was an independent influence factor for prognosis, with an OR of 3.08 (2.14-7.23). Conclusion: Serum ICAM-1 contributes to the early diagnosis and prognosis evaluation of pancreatic cancer.
[Abstract] Objective: To investigate the value of intercellular adhesion molecule 1 (ICAM-1) for the diagnosis and prognosis of pancreatic cancer. Methods: Eighty patients with pancreatic cancer (pancreatic cancer group), forty patients with benign pancreatic disease (benign disease group) who were admitted to Department of Hepatobiliary and Pancreatic Surgery in Cancer Hospital of Hubei Province from April 2015 to December 2017 were included in the study; and thirty healthy subjects during the same period were included as control. Serum ICAM-1 and carbohydrate antigen 19-9 (CA19-9) levels were determined in all the three groups. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic characteristics of ICAM-1 for pancreatic cancer. The COX regression model was used to analyze whether serum ICAM-1 was independently associated with the prognosis of patients with pancreatic cancer.Results: The levels of ICAM-1 and CA19-9 in pancreatic cancer group were significantly higher than those in benign disease group and control group (P<0.01). The level of CA19-9 in benign disease group was significantly higher than that in control group (P<0.01). ROC curve analysis showed that the area under the curve (AUC) of serum ICAM-1, CA19-9 and the combinations of both was 0.732 (95% CI: 0.658-0.807, P=0.000), 0.691 (95% CI: 0.620-0.762, P=0.000), and 0.747 (95% CI: 0.674-0.821, P=0.000), respectively. There was a significant positive correlation between ICAM-1 and CA19-9 (r=0.472, P=0.000). The survival time of patients with serum ICAM-1<2 308 U/ml was significantly longer than that of patients with ICAM-1≥2 308 U/ml (χ2=28.357,P=0.000); COX regression analysis showed that ICAM-1 ≥2 308 U/ml was an independent influence factor for prognosis, with an OR of 3.08 (2.14-7.23). Conclusion: Serum ICAM-1 contributes to the early diagnosis and prognosis evaluation of pancreatic cancer.
2019, 26(3):338-345.
DOI: 10.3872/j.issn.1007-385X.2019.03.015
Abstract:
[摘要] 嵌合抗原受体T（chimeric antigen receptor T, CAR-T）细胞是通过基因工程技术将T细胞改造成针对肿瘤特异性抗原的新型杀伤细胞，具有特异性强、效率高、非MHC限制等优点，在复发/难治性血液系统肿瘤和部分实体瘤中取得良好的治疗效果。但目前CAR-T细胞治疗仍面临着缺乏“现货供应”的通用型CAR-T细胞、抑制性免疫微环境和T细胞耗竭等问题。近年来，锌指核酸酶(zinc finger nucleases, ZFNs)、转录激活子样效应因子核酸酶(transcription activator like effector nucleases,TALENs)、规律性重复短回文序列簇[clustered regularly interspaced short palindromic repeats/CRISPR-associated(Cas9)，CRISPR/Cas9]等新型基因编辑技术被广泛应用于细胞免疫治疗，为解决上述问题带来了希望。本文综述了目前CAR-T细胞治疗的研究进展及存在问题，并探讨了3 种主要的基因编辑技术改良CAR-T细胞治疗的策略，为CAR-T细胞的基础研究和临床治疗提供参考。
[摘要] 嵌合抗原受体T（chimeric antigen receptor T, CAR-T）细胞是通过基因工程技术将T细胞改造成针对肿瘤特异性抗原的新型杀伤细胞，具有特异性强、效率高、非MHC限制等优点，在复发/难治性血液系统肿瘤和部分实体瘤中取得良好的治疗效果。但目前CAR-T细胞治疗仍面临着缺乏“现货供应”的通用型CAR-T细胞、抑制性免疫微环境和T细胞耗竭等问题。近年来，锌指核酸酶(zinc finger nucleases, ZFNs)、转录激活子样效应因子核酸酶(transcription activator like effector nucleases,TALENs)、规律性重复短回文序列簇[clustered regularly interspaced short palindromic repeats/CRISPR-associated(Cas9)，CRISPR/Cas9]等新型基因编辑技术被广泛应用于细胞免疫治疗，为解决上述问题带来了希望。本文综述了目前CAR-T细胞治疗的研究进展及存在问题，并探讨了3 种主要的基因编辑技术改良CAR-T细胞治疗的策略，为CAR-T细胞的基础研究和临床治疗提供参考。
2019, 26(3):346-350.
DOI: 10.3872/j.issn.1007-385X.2019.03.016
Abstract:
[摘要]复发和转移是影响鼻咽癌患者预后和生存质量的主要原因。目前临床上主要使用基于解剖学的TNM分期标准，并不能准确反映患者的预后情况，因此需要开发新的更为精准的鼻咽癌预后判断标准。通过对鼻咽癌发病机制的研究，分子标志物在鼻咽癌预后过程的预测价值日益引起关注。本文总结了近年来在鼻咽癌增殖、生存和侵袭转移等方面的研究进展，以及在这些研究过程中发现的相关分子标志物和它们在临床预后评估中的作用，综合分析这些分子标志物差异性表达与临床患者生存之间的相关性，证明了这些分子标志物在评估患者预后中的潜在价值。随着对鼻咽癌发病机制研究的深入，将会发现更多有价值的分子标志物，这为建立更为精准的鼻咽癌预后评估方法提供了可能。
[摘要]复发和转移是影响鼻咽癌患者预后和生存质量的主要原因。目前临床上主要使用基于解剖学的TNM分期标准，并不能准确反映患者的预后情况，因此需要开发新的更为精准的鼻咽癌预后判断标准。通过对鼻咽癌发病机制的研究，分子标志物在鼻咽癌预后过程的预测价值日益引起关注。本文总结了近年来在鼻咽癌增殖、生存和侵袭转移等方面的研究进展，以及在这些研究过程中发现的相关分子标志物和它们在临床预后评估中的作用，综合分析这些分子标志物差异性表达与临床患者生存之间的相关性，证明了这些分子标志物在评估患者预后中的潜在价值。随着对鼻咽癌发病机制研究的深入，将会发现更多有价值的分子标志物，这为建立更为精准的鼻咽癌预后评估方法提供了可能。
2019, 26(3):351-354.
DOI: 10.3872/j.issn.1007-385X.2019.03.017
Abstract:
[摘要] 肿瘤微环境对肿瘤的发生、发展具有重要的调节作用。富含半胱氨酸的酸性分泌蛋白（cysteine-rich acidic secreted protein ，SPARC）和巨噬细胞作为肿瘤微环境重要基质成分，不仅对肿瘤细胞有直接的调节作用，两者的相互作用也可以影响肿瘤的各种生物学行为变化。SPARC通过维持细胞外基质紧密结构，减少巨噬细胞等免疫细胞向肿瘤区域的浸润，或通过减少巨噬细胞向M2 功能表型方向转换，抑制肿瘤进展；另一方面，M2 型巨噬细胞可以通过吞噬SPARC，从而消除SPARC对肿瘤的抑制作用。此外，巨噬细胞还可通过自身分泌的SPARC抑制肿瘤增殖和迁移等生物学行为。本文将就SPARC维持细胞外基质紧密结构，减少巨噬细胞等免疫细胞向肿瘤区域的浸润；抑制巨噬细胞向M2 功能表型方向转换，从而发挥抑瘤作用；M2 可以通过吞噬SPARC，消除SPARC对肿瘤的抑制作用;巨噬细胞来源SPARC决定细胞外基质沉积，抑制肿瘤迁移和增殖；SPARC与巨噬细胞相互作用在肿瘤免疫治疗的应用5 个方面进行综述，为巨噬细胞来源SPARC对肿瘤不同生物学行为的调节的作用深入研究提供借鉴。
[摘要] 肿瘤微环境对肿瘤的发生、发展具有重要的调节作用。富含半胱氨酸的酸性分泌蛋白（cysteine-rich acidic secreted protein ，SPARC）和巨噬细胞作为肿瘤微环境重要基质成分，不仅对肿瘤细胞有直接的调节作用，两者的相互作用也可以影响肿瘤的各种生物学行为变化。SPARC通过维持细胞外基质紧密结构，减少巨噬细胞等免疫细胞向肿瘤区域的浸润，或通过减少巨噬细胞向M2 功能表型方向转换，抑制肿瘤进展；另一方面，M2 型巨噬细胞可以通过吞噬SPARC，从而消除SPARC对肿瘤的抑制作用。此外，巨噬细胞还可通过自身分泌的SPARC抑制肿瘤增殖和迁移等生物学行为。本文将就SPARC维持细胞外基质紧密结构，减少巨噬细胞等免疫细胞向肿瘤区域的浸润；抑制巨噬细胞向M2 功能表型方向转换，从而发挥抑瘤作用；M2 可以通过吞噬SPARC，消除SPARC对肿瘤的抑制作用;巨噬细胞来源SPARC决定细胞外基质沉积，抑制肿瘤迁移和增殖；SPARC与巨噬细胞相互作用在肿瘤免疫治疗的应用5 个方面进行综述，为巨噬细胞来源SPARC对肿瘤不同生物学行为的调节的作用深入研究提供借鉴。
2019, 26(3):355-358.
DOI: 10.3872/j.issn.1007-385X.2019.03.018
Abstract:
[摘要] 目前miRNA 在癌症发生、发展中的作用得到了广泛的研究，并且在诊断、预后中已经被证明是有效生物标志物。miR-429 在肿瘤中差异表达，并通过与多个靶基因相互介导，与卵巢癌细胞的多药耐药密切相关。miR-429 通过抑制卵巢癌细胞发生上皮间质转化（epithelial-mesenchymal transition，EMT）抑制肿瘤细胞的耐药。自噬有助于提升肿瘤细胞的抗压、修复能力，并可促进肿瘤细胞的迁移、生长，miR-429 可能抑制耐药细胞的自噬从而减少卵巢癌细胞耐药的发生。本文主要对近年来关于miR-429 参与卵巢癌多药耐药机制的研究做一综述，希望能对卵巢癌多药耐药的诊断、治疗和预后判断有所帮助，为其进一步在临床应用提供指导。
[摘要] 目前miRNA 在癌症发生、发展中的作用得到了广泛的研究，并且在诊断、预后中已经被证明是有效生物标志物。miR-429 在肿瘤中差异表达，并通过与多个靶基因相互介导，与卵巢癌细胞的多药耐药密切相关。miR-429 通过抑制卵巢癌细胞发生上皮间质转化（epithelial-mesenchymal transition，EMT）抑制肿瘤细胞的耐药。自噬有助于提升肿瘤细胞的抗压、修复能力，并可促进肿瘤细胞的迁移、生长，miR-429 可能抑制耐药细胞的自噬从而减少卵巢癌细胞耐药的发生。本文主要对近年来关于miR-429 参与卵巢癌多药耐药机制的研究做一综述，希望能对卵巢癌多药耐药的诊断、治疗和预后判断有所帮助，为其进一步在临床应用提供指导。
2019, 26(3):359-361.
DOI: 10.3872/j.issn.1007-385X.2019.03.019
Abstract:
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
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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.