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Volume 22,Issue 3,2015 Table of Contents
2015, 22(3):281-289.
DOI: 10.3872/j.issn.1007-385X.2015.3.001
Abstract:
Ovarian cancer is a malignant tumour that poses a serious threat to women's health. In most cases of ovarian cancer, drug resistance develops in the course of post-surgery chemotherapy. It has been well documented that DNA methylation is one of the important regulatory mechanisms underlying the development of multidrug resistance in ovarian cancer patients. However, the relationship between DNA methylation and drug resistance and clinical prognosis has yet to further understood. Through an electronic search of the PubMed database, we have identified 26 methylated genes that have been reported to be associated with the regulation of ovarian cancer drug resistance. Among these genes, at least half respond to ovarian cancer drug resistance by directly or indirectly regulating signaling pathways involved in cell apoptosis. Moreover, we have performed an integrated analysis of the relationship between these 26 methylated genes and the behaviour and prognosis of malignant ovarian cancer and have found that DNA methylation is primarily associated with poor prognosis. Herein in this review paper, we attempt to present the general information on the 26 identified methylated genes related to drug resistance, outline the putative molecular mechanisms through which DNA methylation affect drug resistance and discuss the possible strategies for reverse how the DNA methylation-induced drug resistance to improve prognosis in malignant ovarian cancer.
Ovarian cancer is a malignant tumour that poses a serious threat to women's health. In most cases of ovarian cancer, drug resistance develops in the course of post-surgery chemotherapy. It has been well documented that DNA methylation is one of the important regulatory mechanisms underlying the development of multidrug resistance in ovarian cancer patients. However, the relationship between DNA methylation and drug resistance and clinical prognosis has yet to further understood. Through an electronic search of the PubMed database, we have identified 26 methylated genes that have been reported to be associated with the regulation of ovarian cancer drug resistance. Among these genes, at least half respond to ovarian cancer drug resistance by directly or indirectly regulating signaling pathways involved in cell apoptosis. Moreover, we have performed an integrated analysis of the relationship between these 26 methylated genes and the behaviour and prognosis of malignant ovarian cancer and have found that DNA methylation is primarily associated with poor prognosis. Herein in this review paper, we attempt to present the general information on the 26 identified methylated genes related to drug resistance, outline the putative molecular mechanisms through which DNA methylation affect drug resistance and discuss the possible strategies for reverse how the DNA methylation-induced drug resistance to improve prognosis in malignant ovarian cancer.
Zhang Yanjun
,
Yuan Xiangfei
,
Zhang Xiaolong
,
Zhang Qing
,
Lu Yang
,
Yang Yuanyuan
,
Wu jie
,
Xiong Dong-sheng
,
Fan Dongmei
2015, 22(3):290-298.
DOI: 10.3872/j.issn.1007-385X.2015.3.002
Abstract:
Objective: To evaluate the effect of a CD20 promoter-driven recombinant adenovirus-soluble trimeric tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) vector on the growth of lymphoma cells in vitro . Methods: An adenoviral vector encoding stTRAIL driven by the CD20 promoter whose activity was confirmed in lymphoma cell lines by luciferase assay was constructed. The constructed vector was infected into CD20 positive and CD20 negative lymphoma cell lines respectively. Protein content of stTRAIL was assessed by Western blotting and cell viability was determined by MTT assay in infected cells. Results: Soluble trimeric TRAIL protein was detected in CD20 positive lymphoma cells but not in CD20 negative lymphoma cells after infection with AdP20-stTRAIL ( P <0.05). Overexpression of stTRAIL in BJAB cells resulted in a significant increase in apoptotic cell death ( P <0.05). Conclusion: The CD20 promotor is capable of enhancing stTRAIL transcription in CD20 positive lymphoma cells, thereby having significant clinical implications in targeted cancer therapy.
Objective: To evaluate the effect of a CD20 promoter-driven recombinant adenovirus-soluble trimeric tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) vector on the growth of lymphoma cells in vitro . Methods: An adenoviral vector encoding stTRAIL driven by the CD20 promoter whose activity was confirmed in lymphoma cell lines by luciferase assay was constructed. The constructed vector was infected into CD20 positive and CD20 negative lymphoma cell lines respectively. Protein content of stTRAIL was assessed by Western blotting and cell viability was determined by MTT assay in infected cells. Results: Soluble trimeric TRAIL protein was detected in CD20 positive lymphoma cells but not in CD20 negative lymphoma cells after infection with AdP20-stTRAIL ( P <0.05). Overexpression of stTRAIL in BJAB cells resulted in a significant increase in apoptotic cell death ( P <0.05). Conclusion: The CD20 promotor is capable of enhancing stTRAIL transcription in CD20 positive lymphoma cells, thereby having significant clinical implications in targeted cancer therapy.
2015, 22(3):299-303.
DOI: 10.3872/j.issn.1007-385X.2015.3.003
Abstract:
Objective: To optimize the preparation of liposome particles co-modified with transferrin and arginine-glycine-aspartic acid (RGD) peptide and evaluate the efficiency of the prepared particles in targeting lung cancer cells in vitro and in vivo ． Methods： Liposome particles modified, respectively, with vehicle (LP), transferrin (TF-LP), RGD peptide (RGD-LP) and TF and RGD (TF/RGD-LP) were prepared by a film-ultrasonic method. The appearance, size and Zeta potential of the particles were determined. The efficiency of these various particles in targeting lung cancer cells were assessed by cellular uptake assays in A549 cells and in a multicellular tumor spheroid model in vitro and by a imaging assay in solid tumors in nude mice in vivo . Results： TF/RGD-LP particles were 122.8±11.5 nm in diameter with an average Zeta potential of 6.4±3.85 mV. TF/RGF-LP particles were uptake by A549 cells 2.8, 2.2 and 3.9 times more efficiently than TF-LP, RGD-LP and LP particles respectively. In consistent with in vitro findings, TF/RGD-LP particles were most efficient among the types of particles tested in penetrating solid tumor spheroids in vivo. Conclusion： Co-modification with transferrin and RGD peptide can enhance the ability of liposomes to penetrate lung cancer cells and thus may offer a better antitumor agent delivery system.
Objective: To optimize the preparation of liposome particles co-modified with transferrin and arginine-glycine-aspartic acid (RGD) peptide and evaluate the efficiency of the prepared particles in targeting lung cancer cells in vitro and in vivo ． Methods： Liposome particles modified, respectively, with vehicle (LP), transferrin (TF-LP), RGD peptide (RGD-LP) and TF and RGD (TF/RGD-LP) were prepared by a film-ultrasonic method. The appearance, size and Zeta potential of the particles were determined. The efficiency of these various particles in targeting lung cancer cells were assessed by cellular uptake assays in A549 cells and in a multicellular tumor spheroid model in vitro and by a imaging assay in solid tumors in nude mice in vivo . Results： TF/RGD-LP particles were 122.8±11.5 nm in diameter with an average Zeta potential of 6.4±3.85 mV. TF/RGF-LP particles were uptake by A549 cells 2.8, 2.2 and 3.9 times more efficiently than TF-LP, RGD-LP and LP particles respectively. In consistent with in vitro findings, TF/RGD-LP particles were most efficient among the types of particles tested in penetrating solid tumor spheroids in vivo. Conclusion： Co-modification with transferrin and RGD peptide can enhance the ability of liposomes to penetrate lung cancer cells and thus may offer a better antitumor agent delivery system.
Su Wenmei
,
Lin Yanming
,
Luo Liang
,
Liang Yahai
,
Liu Meilian
,
Lai Zhennan
,
Yang Zhixiong
,
Liang Rong
2015, 22(3):304-309.
DOI: 10.3872/j.issn.1007-385X.2015.3.004
Abstract:
Objective: To investigate the role of miR-135a in regulating multi-drug resistance of small cell lung cancer. Methods: The expression of miR-135a was assessed by qRT-PCR in peripheral blood samples collected from 48 patients with SCLC admitted to our department between Janurary 2008 and December 2013, which include both chemotherapy responders (28 patients) and non-responders (20 patients). The relationships between miR-135a expression and treatment response, clinical pathological features, and prognosis of patients were analyzed. We also determined the expression of miR-135a in the drug-sensitive SCLC H69 cells and drug-resistant H69AR cell line by qRT-PCR and examined the effects of miR-135a mimics and inhibitor on the sensitivities of H69 and H69AR to chemotherapy drugs ADM, DDP, VP-16 by CCK-8 assay. Results: The level of miR-135a was significantly increased in SCLC non-responders compared with that in the responders \[(2.174±3.981） vs （-1.963±3.750）， P <0.001\]. While it is not correlated with gender and age of the patients ( P >0.05), miR-135a level is statistically correlated with clinical stage, chemosensitivity and overall survival (all P <0.05). The expression of miR-135a was also markedly increased in H69AR cells compared with that in the H69 cells \[(7.841±0.392) vs (1.047±0.081)， P <0.01\]. The drug-sensitivities H69 cells became more resistant to chemotherapeutics DDP, ADM and VP-16 after transfected with miR-135a mimics, and exhibited significantly increased IC 50 \[(18.58±1.37) vs (159.27±3.29)，（24.37±2.63） vs （129.19±2.64），and（48.55±2.59） vs （359.87±2.92）μg/ml，all P <0.01\]. Furthermore, the drug-resistant H69AR cells became more sensitive to these drugs when miR135a was downregulated, and had markedly decreased IC 50 \[(247.09±11.55) vs (76.64±10.00)，（150.83±8.03） vs （40.72±5.06），（436.63±61.19） vs （163.35±20.00）μg/ml；all P <0.01\]. Conclusion: In small cell lung cancer, miR-135a participates in the regulation of the sensitivities to multi-chemotheraputic drugs, and downregulation of miR-135a may reverses the multidrug resistance.
Objective: To investigate the role of miR-135a in regulating multi-drug resistance of small cell lung cancer. Methods: The expression of miR-135a was assessed by qRT-PCR in peripheral blood samples collected from 48 patients with SCLC admitted to our department between Janurary 2008 and December 2013, which include both chemotherapy responders (28 patients) and non-responders (20 patients). The relationships between miR-135a expression and treatment response, clinical pathological features, and prognosis of patients were analyzed. We also determined the expression of miR-135a in the drug-sensitive SCLC H69 cells and drug-resistant H69AR cell line by qRT-PCR and examined the effects of miR-135a mimics and inhibitor on the sensitivities of H69 and H69AR to chemotherapy drugs ADM, DDP, VP-16 by CCK-8 assay. Results: The level of miR-135a was significantly increased in SCLC non-responders compared with that in the responders \[(2.174±3.981） vs （-1.963±3.750）， P <0.001\]. While it is not correlated with gender and age of the patients ( P >0.05), miR-135a level is statistically correlated with clinical stage, chemosensitivity and overall survival (all P <0.05). The expression of miR-135a was also markedly increased in H69AR cells compared with that in the H69 cells \[(7.841±0.392) vs (1.047±0.081)， P <0.01\]. The drug-sensitivities H69 cells became more resistant to chemotherapeutics DDP, ADM and VP-16 after transfected with miR-135a mimics, and exhibited significantly increased IC 50 \[(18.58±1.37) vs (159.27±3.29)，（24.37±2.63） vs （129.19±2.64），and（48.55±2.59） vs （359.87±2.92）μg/ml，all P <0.01\]. Furthermore, the drug-resistant H69AR cells became more sensitive to these drugs when miR135a was downregulated, and had markedly decreased IC 50 \[(247.09±11.55) vs (76.64±10.00)，（150.83±8.03） vs （40.72±5.06），（436.63±61.19） vs （163.35±20.00）μg/ml；all P <0.01\]. Conclusion: In small cell lung cancer, miR-135a participates in the regulation of the sensitivities to multi-chemotheraputic drugs, and downregulation of miR-135a may reverses the multidrug resistance.
2015, 22(3):310-314.
DOI: 10.3872/j.issn.1007-385X.2015.3.005
Abstract:
Objective: To characterize the biological features of Angelica sinensis polysaccharide (ASP) and evaluate its effect on the proliferation, immunotype and cytotoxicity of cytokine induced killer cells (CIK) derived from human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were obtained from healthy adult donors and induced to differentiate into CIK cells with interferon-γ (1 000 IU/ml) and anti-human CD3 (50 ng/ml). CIK cells were then treated with ASP every 3 days at 0, 12.5, 25, 50 and 100 μg/ml, respectively. At 10 days after treatment, the number of CIK cells was counted by computer-based cell counter, the proportion of CD3+CD4+, CD3+CD8+ and CD3+CD56+ cells were analyzed by flow cytometry , and the cytotoxicity of CIK cells were tested by CCK-8 method. Results: At the end of 16 day treatment, above 90% of CIK cells remained viable in all treatment groups, and the proliferative activity was significantly higher ( P <0.05) in CIK cells treated with 100 μg/ml ASP (56.98±3.00)×106 than in cells treated with 0 μg/ml ASP (43.81±2.14)×106. While the CD3+CD56+ cell ratio was significantly increased ( P <0.05) in CIK cells treated with 50 μg/ml ASP (26.65±3.71)% or 100 μg/ml ASP(28.36±4.28%) as compared with the control（20.75±3.56)% , there were no statistical differences in the proportion of CD3+CD4+ or CD3+CD8+ cells among the different groups ( P >0.05). The cytotoxic activity of CIK cells against K562 cells was significantly increased ( P <0.05) after treatment with 100 μg/ml ASP as compared with 0 μg/ml ASP at an effector-target ratio of 40∶1 (84.19±5.88)% vs （8.05±5.95)%, 20∶1（76.69±6.54)% vs (64.55±9.44)% or 10:1（72.32±9.22)% vs (61.45±8.22)%. Conclusion: Angelica sinensis polysaccharide can enhance the proliferative and cytotoxic activities of CIK cells in dose- and time-dependent manners.
Objective: To characterize the biological features of Angelica sinensis polysaccharide (ASP) and evaluate its effect on the proliferation, immunotype and cytotoxicity of cytokine induced killer cells (CIK) derived from human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were obtained from healthy adult donors and induced to differentiate into CIK cells with interferon-γ (1 000 IU/ml) and anti-human CD3 (50 ng/ml). CIK cells were then treated with ASP every 3 days at 0, 12.5, 25, 50 and 100 μg/ml, respectively. At 10 days after treatment, the number of CIK cells was counted by computer-based cell counter, the proportion of CD3+CD4+, CD3+CD8+ and CD3+CD56+ cells were analyzed by flow cytometry , and the cytotoxicity of CIK cells were tested by CCK-8 method. Results: At the end of 16 day treatment, above 90% of CIK cells remained viable in all treatment groups, and the proliferative activity was significantly higher ( P <0.05) in CIK cells treated with 100 μg/ml ASP (56.98±3.00)×106 than in cells treated with 0 μg/ml ASP (43.81±2.14)×106. While the CD3+CD56+ cell ratio was significantly increased ( P <0.05) in CIK cells treated with 50 μg/ml ASP (26.65±3.71)% or 100 μg/ml ASP(28.36±4.28%) as compared with the control（20.75±3.56)% , there were no statistical differences in the proportion of CD3+CD4+ or CD3+CD8+ cells among the different groups ( P >0.05). The cytotoxic activity of CIK cells against K562 cells was significantly increased ( P <0.05) after treatment with 100 μg/ml ASP as compared with 0 μg/ml ASP at an effector-target ratio of 40∶1 (84.19±5.88)% vs （8.05±5.95)%, 20∶1（76.69±6.54)% vs (64.55±9.44)% or 10:1（72.32±9.22)% vs (61.45±8.22)%. Conclusion: Angelica sinensis polysaccharide can enhance the proliferative and cytotoxic activities of CIK cells in dose- and time-dependent manners.
2015, 22(3):315-321.
DOI: 10.3872/j.issn.1007-385X.2015.3.006
Abstract:
Objective: To investigate the effects of chemokine receptors CXCR4 and CXCR7 downregulation by siRNA on the biological characteristics of endometrial carcinoma cell HEC-1-A. Methods： siRNAs targeting CXCR4 and CXCR7 were transfected into HEC-1-A by using LipofectamineTM2000. The downregulation of CXCR4 and CXCR7 was assessed by RT-PCR and immunoblotting. The effects of altered CXCR4 and CXCR7 expression on cell proliferation, invasion and apoptosis were measured by CCK-8, Transwell and FCM respectively. Results： Both CXCR4 and CXCR7 were highly expressed in HEC-1-A cell lines. After transfected with specific siRNA, the expression of CXCR4 and CXCR7 gene and protein were downregulated markedly. The proliferation and invasion ability of HEC-1-A cells were significantly decreased compared to those transfected with control siRNA, and the cells were arrested in S phase. Conclusion： Knocking down CXCR4 and CXCR7 inhibits the proliferation and invasion ability of human endometrial cancer cell line HEC-1-A, suggesting that they are potential targets for endometrial cancer therapy.
Objective: To investigate the effects of chemokine receptors CXCR4 and CXCR7 downregulation by siRNA on the biological characteristics of endometrial carcinoma cell HEC-1-A. Methods： siRNAs targeting CXCR4 and CXCR7 were transfected into HEC-1-A by using LipofectamineTM2000. The downregulation of CXCR4 and CXCR7 was assessed by RT-PCR and immunoblotting. The effects of altered CXCR4 and CXCR7 expression on cell proliferation, invasion and apoptosis were measured by CCK-8, Transwell and FCM respectively. Results： Both CXCR4 and CXCR7 were highly expressed in HEC-1-A cell lines. After transfected with specific siRNA, the expression of CXCR4 and CXCR7 gene and protein were downregulated markedly. The proliferation and invasion ability of HEC-1-A cells were significantly decreased compared to those transfected with control siRNA, and the cells were arrested in S phase. Conclusion： Knocking down CXCR4 and CXCR7 inhibits the proliferation and invasion ability of human endometrial cancer cell line HEC-1-A, suggesting that they are potential targets for endometrial cancer therapy.
7 Effect of annexinA7 knockdown on the proliferation and apoptosis of stomach carcinoma MGC-803 cells
2015, 22(3):322-325.
DOI: 10.3872/j.issn.1007-385X.2015.3.007
Abstract:
Objective: To investigate the effect of ANXA7 on the proliferation and apoptosis of human stomach carcinoma MGC-803 cells by downregulating ANXA7 expression using RNA interference technique. Methods: The MGC-803 cells were transfected with lipofectineTM2000 alone (blank control), scrambled siRNA (negative control), and siRNA targeted ANXA7 (experiment group). After 48 hours, ANXA7 expression was examined by immunoblotting. The proliferation and growth of transected cells were assessed by MTT and colony formation assays. Apoptosis of the cells was analyzed by flow cytometry. Results: The expression of ANXA7 was significantly decreased in cells transfected with ANXA7 siRNA compared with these in the two controls \[(21.79±1.72)% vs (99.87±5.13)% and (93.45±4.89)%, P <0.05\]. When ANXA7 expression was decreased, the proliferation and colony formation abilities of MGC-803 cells were markedly inhibited \[(0.97±0.06) vs (1.21±0.07) and (1.25±0.08), P <0.05; and (183±21) vs (363±35) and (348±27), P <0.05\], whereas the apoptosis of the cells was not affected statistically \[ P >0.05\]. Conclusion: ANXA7 regulates the proliferation and colony formation of MGC-803 cells, and appears not involved in their apoptosis.
Objective: To investigate the effect of ANXA7 on the proliferation and apoptosis of human stomach carcinoma MGC-803 cells by downregulating ANXA7 expression using RNA interference technique. Methods: The MGC-803 cells were transfected with lipofectineTM2000 alone (blank control), scrambled siRNA (negative control), and siRNA targeted ANXA7 (experiment group). After 48 hours, ANXA7 expression was examined by immunoblotting. The proliferation and growth of transected cells were assessed by MTT and colony formation assays. Apoptosis of the cells was analyzed by flow cytometry. Results: The expression of ANXA7 was significantly decreased in cells transfected with ANXA7 siRNA compared with these in the two controls \[(21.79±1.72)% vs (99.87±5.13)% and (93.45±4.89)%, P <0.05\]. When ANXA7 expression was decreased, the proliferation and colony formation abilities of MGC-803 cells were markedly inhibited \[(0.97±0.06) vs (1.21±0.07) and (1.25±0.08), P <0.05; and (183±21) vs (363±35) and (348±27), P <0.05\], whereas the apoptosis of the cells was not affected statistically \[ P >0.05\]. Conclusion: ANXA7 regulates the proliferation and colony formation of MGC-803 cells, and appears not involved in their apoptosis.
2015, 22(3):326-330.
DOI: 10.3872/j.issn.1007-385X.2015.3.008
Abstract:
Objective: To investigatethe expression of Neuritin in non-small lung cancer-vascular endothelial cells (NSCLC-VECs) and its potential role in the development ofvessels in non-small lung cancer. Methods: We have cultivated and identified NSCLC-VECs and human pulmonary microvascular endothelial cells (HPMEC) by using anti-FactorⅧ and CD34 antibodies. The expression ofneuritin in these cells were examined through RT-PCR and immunoblotting. Results: After pressurized filtration, we obtainedstably passaged NSCLC-VECs and HPMECs, which express endothelial cells specific markers FactorⅧ and CD34. The level of neuritin mRNA in NSCLC-VECs is significantly higher than that of HPMEC\[(0.95±0.09） vs （0.64±0.05）， P <0.05\]. At protein level, neuritin expression in NSCLC-VECs is more than 4-fold higher than that in HPMEC\[(1.15±0.11） vs （0.27±0.14）， P <0.05\]. Conclusion： Neuritin isoverexpressed in human NSCLC-VECs andmay contribute to tumor angiogenesis. The differentialexpression also suggests that neuritinis a potential therapeutictarget fornon-small cell lung cancer.
Objective: To investigatethe expression of Neuritin in non-small lung cancer-vascular endothelial cells (NSCLC-VECs) and its potential role in the development ofvessels in non-small lung cancer. Methods: We have cultivated and identified NSCLC-VECs and human pulmonary microvascular endothelial cells (HPMEC) by using anti-FactorⅧ and CD34 antibodies. The expression ofneuritin in these cells were examined through RT-PCR and immunoblotting. Results: After pressurized filtration, we obtainedstably passaged NSCLC-VECs and HPMECs, which express endothelial cells specific markers FactorⅧ and CD34. The level of neuritin mRNA in NSCLC-VECs is significantly higher than that of HPMEC\[(0.95±0.09） vs （0.64±0.05）， P <0.05\]. At protein level, neuritin expression in NSCLC-VECs is more than 4-fold higher than that in HPMEC\[(1.15±0.11） vs （0.27±0.14）， P <0.05\]. Conclusion： Neuritin isoverexpressed in human NSCLC-VECs andmay contribute to tumor angiogenesis. The differentialexpression also suggests that neuritinis a potential therapeutictarget fornon-small cell lung cancer.
2015, 22(3):331-336.
DOI: 10.3872/j.issn.1007-385X.2015.3.009
Abstract:
Objective: To study the possible role for the JAK-STAT signaling pathway in the pathogenesis of rectal cancer. Methods: Cancerous and non-cancerous (control) tissue specimens were collected at surgical resection from 50 rectal cancer patients and 50 non-rectal cancer patients, respectively, who were admitted to our hospital between May, 2013 and May, 2014. Levels of STAT3, p-STAT3 and the two major protein molecules, cyclin D1 and Bcl2, downstream of the JAK-STAT signal pathway in these clinical specimens were assessed by Western blotting analysis and were analyzed statistically for their correlations with the clinical pathological features of the patients. To further evaluate the influence of STAT3 on rectal cancer cell growth, the proliferative activity and invasion ability of colonic carcinoma Colo320 cells after siRNA-mediated silencing of the STAT3 gene was assessed by MTT Transwell migration assays, respectively. Results： Levels of STAT3 were significantly higher in rectal cancer specimens than in non-cancerous control specimens ( P <0.01), so were levels of p-STAT3, cyclin D1 and Bcl2 ( P <0.05). STAT3 protein levels in cancerous specimens were significantly correlated with the differentiation degree and lymphatic metastasis of rectal cancer ( P <0.05), but not with the tumor size ( P >0.05). STAT3 silencing resulted in significant decreases in Colo320 cell proliferation, invasion and metastasis ( P <0.05). Conclusion: STAT3 is involved in the proliferation, invasion and metastasis of colorectal cancer through a JAK-STAT signaling-dependent mechanism and thus may serve as a potential therapeutic target for colorectal cancer.
Objective: To study the possible role for the JAK-STAT signaling pathway in the pathogenesis of rectal cancer. Methods: Cancerous and non-cancerous (control) tissue specimens were collected at surgical resection from 50 rectal cancer patients and 50 non-rectal cancer patients, respectively, who were admitted to our hospital between May, 2013 and May, 2014. Levels of STAT3, p-STAT3 and the two major protein molecules, cyclin D1 and Bcl2, downstream of the JAK-STAT signal pathway in these clinical specimens were assessed by Western blotting analysis and were analyzed statistically for their correlations with the clinical pathological features of the patients. To further evaluate the influence of STAT3 on rectal cancer cell growth, the proliferative activity and invasion ability of colonic carcinoma Colo320 cells after siRNA-mediated silencing of the STAT3 gene was assessed by MTT Transwell migration assays, respectively. Results： Levels of STAT3 were significantly higher in rectal cancer specimens than in non-cancerous control specimens ( P <0.01), so were levels of p-STAT3, cyclin D1 and Bcl2 ( P <0.05). STAT3 protein levels in cancerous specimens were significantly correlated with the differentiation degree and lymphatic metastasis of rectal cancer ( P <0.05), but not with the tumor size ( P >0.05). STAT3 silencing resulted in significant decreases in Colo320 cell proliferation, invasion and metastasis ( P <0.05). Conclusion: STAT3 is involved in the proliferation, invasion and metastasis of colorectal cancer through a JAK-STAT signaling-dependent mechanism and thus may serve as a potential therapeutic target for colorectal cancer.
2015, 22(3):337-342.
DOI: 10.3872/j.issn.1007-385X.2015.3.010
Abstract:
Objective: The present study was undertaken to examine the expression of ADAMTS1 and ADAMTS18 at mRNA and protein levels in esophagus squamous cell carcinoma (ESCC) for exploring their potential roles in the development and progress of the cancer. Methods: Tumor and adjacent noncancerous tissues were collected through surgical resection from 72 ESCC patients admitted to the Fourth Affiliated Hospital of Hebei Medical University between June 2008 and August 2011. The expression of ADAMTS1 and ADAMTS18 in ESCC tumor and adjacent tissues was examined with RT-PCR and immunohistochemistry to detect corresponding mRNA and protein. Results：①The level of ADAMTS1 mRNA in ESCC tumor tissues was significantly lower than that in adjacent non-tumor tissues (0.394±0.123 vs 0.895±0.276) ( P <0.01). Moreover, the level of ADAMTS1 mRNA in ESCC tumor tissues from patients with lymph node metastasis was significantly higher than that in ESCC tumor tissues from patients without lymph node metastasis (0.482±0.157 vs 0.298±0.102) ( P <0.05). ②The expression of ADAMTS18 mRNA in ESCC tumor tissues was significantly lower than that in adjacent non-tumor tissues (0.361±0.115 vs 0.879±0.265) ( P <0.01). Further, The mRNA level of ADAMTS18 mRNA in high/moderate differentiated ESCC was significantly higher than that in low differentiated ESCC (0.496±0.153 vs 0.232±0.088) ( P <0.05). ③The immunohistochemical positive rates of ADAMTS1 and ADAMTS18 in ESCC were significantly lower than that in adjacent non-tumor tissues \[38.9%(28/72) and 34.7%(25/72) vs 94.4%(68/72) and 93.1%(67/72) ( P <0.01)\]. Similar to its mRNA level, ADAMTS18 expression in high/moderate differentiated ESCC was significantly higher than that in low differentiated group \[45.4%(20/44) vs 17.8%(5/28) ( P <0.05)\]. ④There was no significant correlation between the expression of ADAMTS1 and ADAMTS18 in ESCC ( χ 2=1.338, P >0.05). Conclusion： Aberrant low expression of ADAMTS1 is associated with the development of ESCC and it lymph node metastasis, whereas reduced ADAMTS18 expression is closely related to ESCC development and its differentiation status. There are no correlation between the expression of ADAMTS1 and ADAMTS18 in ESCC.
Objective: The present study was undertaken to examine the expression of ADAMTS1 and ADAMTS18 at mRNA and protein levels in esophagus squamous cell carcinoma (ESCC) for exploring their potential roles in the development and progress of the cancer. Methods: Tumor and adjacent noncancerous tissues were collected through surgical resection from 72 ESCC patients admitted to the Fourth Affiliated Hospital of Hebei Medical University between June 2008 and August 2011. The expression of ADAMTS1 and ADAMTS18 in ESCC tumor and adjacent tissues was examined with RT-PCR and immunohistochemistry to detect corresponding mRNA and protein. Results：①The level of ADAMTS1 mRNA in ESCC tumor tissues was significantly lower than that in adjacent non-tumor tissues (0.394±0.123 vs 0.895±0.276) ( P <0.01). Moreover, the level of ADAMTS1 mRNA in ESCC tumor tissues from patients with lymph node metastasis was significantly higher than that in ESCC tumor tissues from patients without lymph node metastasis (0.482±0.157 vs 0.298±0.102) ( P <0.05). ②The expression of ADAMTS18 mRNA in ESCC tumor tissues was significantly lower than that in adjacent non-tumor tissues (0.361±0.115 vs 0.879±0.265) ( P <0.01). Further, The mRNA level of ADAMTS18 mRNA in high/moderate differentiated ESCC was significantly higher than that in low differentiated ESCC (0.496±0.153 vs 0.232±0.088) ( P <0.05). ③The immunohistochemical positive rates of ADAMTS1 and ADAMTS18 in ESCC were significantly lower than that in adjacent non-tumor tissues \[38.9%(28/72) and 34.7%(25/72) vs 94.4%(68/72) and 93.1%(67/72) ( P <0.01)\]. Similar to its mRNA level, ADAMTS18 expression in high/moderate differentiated ESCC was significantly higher than that in low differentiated group \[45.4%(20/44) vs 17.8%(5/28) ( P <0.05)\]. ④There was no significant correlation between the expression of ADAMTS1 and ADAMTS18 in ESCC ( χ 2=1.338, P >0.05). Conclusion： Aberrant low expression of ADAMTS1 is associated with the development of ESCC and it lymph node metastasis, whereas reduced ADAMTS18 expression is closely related to ESCC development and its differentiation status. There are no correlation between the expression of ADAMTS1 and ADAMTS18 in ESCC.
2015, 22(3):343-347.
DOI: 10.3872/j.issn.1007-385X.2015.3.011
Abstract:
Objective: To assess the diagnostic value of KISS1 mRNA in peripheral blood from patients with epithelial ovarian cancer (EOC) through comparison with CA125 measurement. Methods: Peripheral bloods were collected from 20 healthy individuals and 40 EOC patients, admitted into the Second Affiliated Hospital of Nantong University between January 2010 and January 2014, the day before the planned operations. The level of KISS1 mRNA in these blood samples was quantitated by RT-PCR, and in comparison, CA125 level in the same group of samples was measured by a chemiluminescence-based immunoassay. Results: KISS1 mRNA level in the peripheral blood from EOC patients of all stages was significantly higher than that of the healthy group ( P <0.01). However, the mRNA level in blood from patients with early EOC (FIGO Ⅰ & Ⅱ) was not significantly different from that of the advanced EOC (FIGO Ⅲ & Ⅳ) patients ( P >0.05). In contrast, CA125 level of the advanced EOC group was significantly higher than that of the early EOC group and the healthy group ( P <0.01). However, no significant differences of CA125 levels were found between the early EOC patients and the healthy volunteers ( P >0.05). When the cutoff values of receptive operator character curve (ROC) for the KISS1 mRNA were set to be 0.51 and 0.72, the corresponding positive predictive values (PPV) were 0.58 and 1.0, and the negative predictive values (NPV) were 0.92 and 0.7 respectively. When the cutoff values were 20 U/ml and 100U/ml for CA125 levels, the PPV were 0.72 and 1.0, and the NPV were 0.87 and 0.81, indicating that both KISS1 mRNA and CA125 levels have a moderate diagnostic efficiency ( P =0.34) for EOC. While the KISS1 mRNA level has a higher diagnostic value than that of CA125 for early stages of EOC ( P =0.018), CA125 measurement is more valuable than the KISS1 mRNA level in diagnosing advanced EOC ( P <0.018). Conclusion: KISS1 mRNA in peripheral blood is a potential novel biomarker. When deployed together with CA125 assay, it would likely improve the diagnosis of EOC, especially for the early stage cancer.
Objective: To assess the diagnostic value of KISS1 mRNA in peripheral blood from patients with epithelial ovarian cancer (EOC) through comparison with CA125 measurement. Methods: Peripheral bloods were collected from 20 healthy individuals and 40 EOC patients, admitted into the Second Affiliated Hospital of Nantong University between January 2010 and January 2014, the day before the planned operations. The level of KISS1 mRNA in these blood samples was quantitated by RT-PCR, and in comparison, CA125 level in the same group of samples was measured by a chemiluminescence-based immunoassay. Results: KISS1 mRNA level in the peripheral blood from EOC patients of all stages was significantly higher than that of the healthy group ( P <0.01). However, the mRNA level in blood from patients with early EOC (FIGO Ⅰ & Ⅱ) was not significantly different from that of the advanced EOC (FIGO Ⅲ & Ⅳ) patients ( P >0.05). In contrast, CA125 level of the advanced EOC group was significantly higher than that of the early EOC group and the healthy group ( P <0.01). However, no significant differences of CA125 levels were found between the early EOC patients and the healthy volunteers ( P >0.05). When the cutoff values of receptive operator character curve (ROC) for the KISS1 mRNA were set to be 0.51 and 0.72, the corresponding positive predictive values (PPV) were 0.58 and 1.0, and the negative predictive values (NPV) were 0.92 and 0.7 respectively. When the cutoff values were 20 U/ml and 100U/ml for CA125 levels, the PPV were 0.72 and 1.0, and the NPV were 0.87 and 0.81, indicating that both KISS1 mRNA and CA125 levels have a moderate diagnostic efficiency ( P =0.34) for EOC. While the KISS1 mRNA level has a higher diagnostic value than that of CA125 for early stages of EOC ( P =0.018), CA125 measurement is more valuable than the KISS1 mRNA level in diagnosing advanced EOC ( P <0.018). Conclusion: KISS1 mRNA in peripheral blood is a potential novel biomarker. When deployed together with CA125 assay, it would likely improve the diagnosis of EOC, especially for the early stage cancer.
2015, 22(3):348-353.
DOI: 10.3872/j.issn.1007-385X.2015.3.012
Abstract:
Objective: To investigate the relationship between the Arg280His and Arg399Gln single nucleotide polymorphisms (SNPs) in the DNA repair gene XRCC1 and susceptibility to hepatocellular carcinoma（HCC）in members of liver cancer family of Zhuang population in Fusui county of Guangxi． Methods: Seventy-nine members of the 20 liver cancer families and 40 volunteers from 10 normal family groups were enrolled in this study. Genotypes of XRCC1 Arg399Gln（rs25487）and Arg280His（rs25489) SNPs were determined by Time of Flight Mass Spectrometer (MS-TOF) analysis. The potential association between the XRCC1 rg399Gln（rs25487）and Arg280His（rs25489）polymorphisms and HCC risk was evaluated by non-conditional logistic regression analysis. Results: In the normal control families, the risk of HCC for members with AG and AA genotypes in rs25487 was 9 (95% CI=0.828- 97.780， P =0.071 ) and 5.143 (95% CI=0.445-59.45， P =0.190) times higher than that of members with GG genotype. In the liver cancer families, the risk of HCC for members with AG and AA genotypes in this SNP was 4 (95% CI=0.689-23.230， P =0.122) and 2.857 (95% CI= 0.464～17.583， P =0.257）times higher than that of members with GG genotype. For SNP rs25489, the risk of HCC for members of the normal control families with GA genotype was 2.4 (95% CI= 0.530-10.877， P =0.256 ) times higher than that of members with GG genotype. In the liver cancer families, the risk of HCC for members with GA genotype was 1.02 （95% CI=0.286-3.650， P =0.973） times higher than that of members with GG. Conclusion: There is no statistic significant correlation between Arg399Gln（rs25487）and Arg280his（rs25489）polymorphisms in XRCC1 gene and susceptibility to HCC in family with liver cancer in Fusui county of Guangxi province.
Objective: To investigate the relationship between the Arg280His and Arg399Gln single nucleotide polymorphisms (SNPs) in the DNA repair gene XRCC1 and susceptibility to hepatocellular carcinoma（HCC）in members of liver cancer family of Zhuang population in Fusui county of Guangxi． Methods: Seventy-nine members of the 20 liver cancer families and 40 volunteers from 10 normal family groups were enrolled in this study. Genotypes of XRCC1 Arg399Gln（rs25487）and Arg280His（rs25489) SNPs were determined by Time of Flight Mass Spectrometer (MS-TOF) analysis. The potential association between the XRCC1 rg399Gln（rs25487）and Arg280His（rs25489）polymorphisms and HCC risk was evaluated by non-conditional logistic regression analysis. Results: In the normal control families, the risk of HCC for members with AG and AA genotypes in rs25487 was 9 (95% CI=0.828- 97.780， P =0.071 ) and 5.143 (95% CI=0.445-59.45， P =0.190) times higher than that of members with GG genotype. In the liver cancer families, the risk of HCC for members with AG and AA genotypes in this SNP was 4 (95% CI=0.689-23.230， P =0.122) and 2.857 (95% CI= 0.464～17.583， P =0.257）times higher than that of members with GG genotype. For SNP rs25489, the risk of HCC for members of the normal control families with GA genotype was 2.4 (95% CI= 0.530-10.877， P =0.256 ) times higher than that of members with GG genotype. In the liver cancer families, the risk of HCC for members with GA genotype was 1.02 （95% CI=0.286-3.650， P =0.973） times higher than that of members with GG. Conclusion: There is no statistic significant correlation between Arg399Gln（rs25487）and Arg280his（rs25489）polymorphisms in XRCC1 gene and susceptibility to HCC in family with liver cancer in Fusui county of Guangxi province.
2015, 22(3):354-361.
DOI: 10.3872/j.issn.1007-385X.2015.3.013
Abstract:
Objective: To evaluate the effect and safety of intrapleural injection of in vitro expanded immature dendritic cells (DC) for the treatment of malignant pleural effusion. Methods: Peripheral blood mononuclear cells were collected from 6 patients with chemo-resistant malignant pleural effusion and cultured with cytokines to expand immature DC in vitro . The cells were then intrapleurally injected into the patients (5~10)×107 every 4 weeks for 3 times as a course of treatment. The changes of pleural effusion and side effects in each patient were examined. T cell and NK cell subsets in the pleural effusion were analyzed by flow cytometry. Results: Overall, 2 renal cell carcinoma patients had complete responses, 1 lung cancer patients had partial response, 1 lung cancer patients had SD, and 2 other patients had PD. Therefore, the response rate was 50% (3/6) and the benefit rate was 66.7%. Duration of the response of the 2 renal cell carcinoma patients was 26 weeks and 147 weeks respectively. After DC treatment, the percentages of T and NK cells increased in the pleural effusion, but only the increase of NK cells is statistically significant. Conclusion: This pilot study indicated that intrapleural injection of none-antigen loaded immature DCs is well-tolerated, has positive effect on the management of malignant pleural effusions, which is likely mediated by NK cells. These results suggest that DC immunotherapy is a promising method to treat malignant pleural effusions in the future.
Objective: To evaluate the effect and safety of intrapleural injection of in vitro expanded immature dendritic cells (DC) for the treatment of malignant pleural effusion. Methods: Peripheral blood mononuclear cells were collected from 6 patients with chemo-resistant malignant pleural effusion and cultured with cytokines to expand immature DC in vitro . The cells were then intrapleurally injected into the patients (5~10)×107 every 4 weeks for 3 times as a course of treatment. The changes of pleural effusion and side effects in each patient were examined. T cell and NK cell subsets in the pleural effusion were analyzed by flow cytometry. Results: Overall, 2 renal cell carcinoma patients had complete responses, 1 lung cancer patients had partial response, 1 lung cancer patients had SD, and 2 other patients had PD. Therefore, the response rate was 50% (3/6) and the benefit rate was 66.7%. Duration of the response of the 2 renal cell carcinoma patients was 26 weeks and 147 weeks respectively. After DC treatment, the percentages of T and NK cells increased in the pleural effusion, but only the increase of NK cells is statistically significant. Conclusion: This pilot study indicated that intrapleural injection of none-antigen loaded immature DCs is well-tolerated, has positive effect on the management of malignant pleural effusions, which is likely mediated by NK cells. These results suggest that DC immunotherapy is a promising method to treat malignant pleural effusions in the future.
2015, 22(3):358-362.
DOI: 10.3872/j.issn.1007-385X.2015.3.014
Abstract:
Objective: To assess the influence of the receptor expression changes in locally recurred tumors on the prognosis of breast cancer patients. Methods: The primary and recurrent tumor sections from 56 patients admitted to our department from January 2008 to December 2013 for both primary and recurrent breast cancers were investigated. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2(Her-2) was examined by immunohistochemistry. The association between changes of the receptors expression and overall survival (OS) of patients was then analyzed. Results:（1）The positive rates of the ER, PR, and Her-2 in the primary tumor and recurrent tumor sections were 64.29% and 55.36%, 53.57% and 39.29%, and 37.50% and 35.71 respectively. (2) The rates of altered expression between the primary and recurrent tumors for ER, PR, and Her-2 are 33.93% (16/56) 37.50% (21/56), and 8.93% (5/56). (3) Among 56 breast cancer patients, there were 22 death (39.29%) during the investigation period, the median survival time was 21.5 months, and the survival rates for 1 -5 years were 87.23%, 75.65%, 70.11%, 60.22%, 42.86%. Kaplian-Meier analysis revealed that alterations of ER and PR expression in primary and recurrent tumors affect OS of the patients. Patients whose ER and PR expression in primary and recurrent tumors changed from negative to positive have better prognosis than those who had ER and PR expression changed from positive to negative (P<0.05). There were not enough positive sections in this cohort to evaluate the effects Her-2 alterations. (4) Multivariable analysis indicated that age, tumor pathological type, stage, and metastasis, ER and PR expression are all independent prognostic factors for the OS of breast cancer.patients. Conclusion: The alteration of ER and PR expression in primary and recurrent tumors of breast cancer patients affects their OS. Assessing these changes will benefit the treatment and prognosis evaluation.
Objective: To assess the influence of the receptor expression changes in locally recurred tumors on the prognosis of breast cancer patients. Methods: The primary and recurrent tumor sections from 56 patients admitted to our department from January 2008 to December 2013 for both primary and recurrent breast cancers were investigated. The expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2(Her-2) was examined by immunohistochemistry. The association between changes of the receptors expression and overall survival (OS) of patients was then analyzed. Results:（1）The positive rates of the ER, PR, and Her-2 in the primary tumor and recurrent tumor sections were 64.29% and 55.36%, 53.57% and 39.29%, and 37.50% and 35.71 respectively. (2) The rates of altered expression between the primary and recurrent tumors for ER, PR, and Her-2 are 33.93% (16/56) 37.50% (21/56), and 8.93% (5/56). (3) Among 56 breast cancer patients, there were 22 death (39.29%) during the investigation period, the median survival time was 21.5 months, and the survival rates for 1 -5 years were 87.23%, 75.65%, 70.11%, 60.22%, 42.86%. Kaplian-Meier analysis revealed that alterations of ER and PR expression in primary and recurrent tumors affect OS of the patients. Patients whose ER and PR expression in primary and recurrent tumors changed from negative to positive have better prognosis than those who had ER and PR expression changed from positive to negative (P<0.05). There were not enough positive sections in this cohort to evaluate the effects Her-2 alterations. (4) Multivariable analysis indicated that age, tumor pathological type, stage, and metastasis, ER and PR expression are all independent prognostic factors for the OS of breast cancer.patients. Conclusion: The alteration of ER and PR expression in primary and recurrent tumors of breast cancer patients affects their OS. Assessing these changes will benefit the treatment and prognosis evaluation.
2015, 22(3):363-368.
DOI: 10.3872/j.issn.1007-385X.2015.3.015
Abstract:
Objective: To evaluate the effectiveness of chemotherapy combined with adoptive transfer of cytokine-Induced killer cells (CIK) in the treatment of gastric cancer. Methods: We searched for randomized controlled clinical trials of gastric cancer treatment in PubMed, EMBASE, Web of Science, Chorane, CNKI, and VIP database from January 1990 to March 2014. Meta analysis was performed with the Revman 5.2 software. Results: We found 5 studies that enrolled 306 patients met the criteria. Analysis of the data indicated that, compared with chemotherapy alone, chemotherapy combined with adoptive transfer of CIK in the treatment of gastric cancer improved the short and long term responses. The detail short term remission rate and long term (1, 2, and 3 years) survival rates are as follow: short term （RR=2.14，95% CI: 1.20~ 3.79， P =0.01， I 2=0%）, 1-year (RR=1.13，95% CI: 1.03~1.24， P =0.09， I 2=50%), 2-year（RR=1.22，95% CI: 1.11~1.44， P =0.46， I 2=0%), 3-year（RR=1.34，95% CI: 1.10~1.63， P =0.5， I 2=0%）. The combined therapy also significant prolonged the progress-free survival of patients (RR= 2.65，95% CI：229~3.01\]， P <0.001， I 2=98%). Conclusion: Chemotherapy combined with adoptive transfer of CIK can improve the overall response and progress-free survival of gastric cancer patients.
Objective: To evaluate the effectiveness of chemotherapy combined with adoptive transfer of cytokine-Induced killer cells (CIK) in the treatment of gastric cancer. Methods: We searched for randomized controlled clinical trials of gastric cancer treatment in PubMed, EMBASE, Web of Science, Chorane, CNKI, and VIP database from January 1990 to March 2014. Meta analysis was performed with the Revman 5.2 software. Results: We found 5 studies that enrolled 306 patients met the criteria. Analysis of the data indicated that, compared with chemotherapy alone, chemotherapy combined with adoptive transfer of CIK in the treatment of gastric cancer improved the short and long term responses. The detail short term remission rate and long term (1, 2, and 3 years) survival rates are as follow: short term （RR=2.14，95% CI: 1.20~ 3.79， P =0.01， I 2=0%）, 1-year (RR=1.13，95% CI: 1.03~1.24， P =0.09， I 2=50%), 2-year（RR=1.22，95% CI: 1.11~1.44， P =0.46， I 2=0%), 3-year（RR=1.34，95% CI: 1.10~1.63， P =0.5， I 2=0%）. The combined therapy also significant prolonged the progress-free survival of patients (RR= 2.65，95% CI：229~3.01\]， P <0.001， I 2=98%). Conclusion: Chemotherapy combined with adoptive transfer of CIK can improve the overall response and progress-free survival of gastric cancer patients.
2015, 22(3):369-374.
DOI: 10.3872/j.issn.1007-385X.2015.3.016
Abstract:
胰腺癌的细胞治疗为生物治疗的一个分支，它是通过在体外培养效应细胞后回输至患者体内，激发和增强机体的免疫功能，以达到杀伤肿瘤细胞并控制肿瘤的目的。胰腺癌的细胞免疫治疗已有较长的历史，从淋巴因子激活的杀伤细胞(lymphocyte activated killer cells, LAKs)、肿瘤浸润性淋巴细胞（tumor infiltrating lymphocytes, TILs）到近年来研究较多的细胞因子诱导的杀伤性细胞（cytokine induced killer cells, CIKs）、树突状细胞（dendritic cells, DCs）以及传统的细胞毒性T淋巴细胞（cytotoxic lymphocytes, CTLs)。同时，生物科学技术的发展使研究得以大规模分析，并且借由这些统计分析，基础医学和药物研发及临床治疗已不再相互孤立存在。近几年，以上几种类型的细胞在胰腺癌的传统治疗基础上又有了一些新的改进与突破。本文就近几年来胰腺癌细胞治疗中常用的五种细胞在临床转化中的研究新进展做一介绍。
胰腺癌的细胞治疗为生物治疗的一个分支，它是通过在体外培养效应细胞后回输至患者体内，激发和增强机体的免疫功能，以达到杀伤肿瘤细胞并控制肿瘤的目的。胰腺癌的细胞免疫治疗已有较长的历史，从淋巴因子激活的杀伤细胞(lymphocyte activated killer cells, LAKs)、肿瘤浸润性淋巴细胞（tumor infiltrating lymphocytes, TILs）到近年来研究较多的细胞因子诱导的杀伤性细胞（cytokine induced killer cells, CIKs）、树突状细胞（dendritic cells, DCs）以及传统的细胞毒性T淋巴细胞（cytotoxic lymphocytes, CTLs)。同时，生物科学技术的发展使研究得以大规模分析，并且借由这些统计分析，基础医学和药物研发及临床治疗已不再相互孤立存在。近几年，以上几种类型的细胞在胰腺癌的传统治疗基础上又有了一些新的改进与突破。本文就近几年来胰腺癌细胞治疗中常用的五种细胞在临床转化中的研究新进展做一介绍。
2015, 22(3):375-380.
DOI: 10.3872/j.issn.1007-385X.2015.3.017
Abstract:
肺癌是最常见且致死率最高的癌症之一，其恶性程度高、病情发展迅速，且术后复发率高，治疗效果不理想。生物治疗是继手术、化疗和放疗之后的第四种肿瘤综合治疗模式，生物治疗技术之一的免疫细胞治疗能够激活机体的抗肿瘤能力并重建患者免疫功能，主要包括树突状细胞(dendritic cell，DC)、细胞因子诱导的杀伤细胞(cytokine induced killer cells，CIK)、DC-CIK、自然杀伤T(natural killer T，NKT)细胞及γδ T细胞等疗法。肺癌的细胞治疗已在基础研究和临床试验领域确定了其抗肿瘤效应，进一步通过基因工程修饰、双特异性抗体和免疫卡控点分子干预等手段增强免疫细胞的特异性、识别功能和抗肿瘤能力是未来免疫治疗的重要手段。本文介绍DC疫苗、CIK细胞及DC-CIK等对肺癌治疗临床转化的研究进展。
肺癌是最常见且致死率最高的癌症之一，其恶性程度高、病情发展迅速，且术后复发率高，治疗效果不理想。生物治疗是继手术、化疗和放疗之后的第四种肿瘤综合治疗模式，生物治疗技术之一的免疫细胞治疗能够激活机体的抗肿瘤能力并重建患者免疫功能，主要包括树突状细胞(dendritic cell，DC)、细胞因子诱导的杀伤细胞(cytokine induced killer cells，CIK)、DC-CIK、自然杀伤T(natural killer T，NKT)细胞及γδ T细胞等疗法。肺癌的细胞治疗已在基础研究和临床试验领域确定了其抗肿瘤效应，进一步通过基因工程修饰、双特异性抗体和免疫卡控点分子干预等手段增强免疫细胞的特异性、识别功能和抗肿瘤能力是未来免疫治疗的重要手段。本文介绍DC疫苗、CIK细胞及DC-CIK等对肺癌治疗临床转化的研究进展。
2015, 22(3):381-384.
DOI: 10.3872/j.issn.1007-385X.2015.3.018
Abstract:
目的：探讨CIK细胞联合多西他赛、奥沙利铂、替吉奥治疗晚期胃癌患者的疗效及安全性。方法：收集2011年1月至2012年1月在我院收治的66例晚期胃癌患者，分为实验组30例：CIK联合多西他赛、奥沙利铂、替吉奥治疗患者；对照组36例：为同期单纯用多西他赛、奥沙利铂、替吉奥治疗患者。治疗后随访36个月，研究主要终点为无进展生存期（PFS），次要终点为总生存期（OS）；采用流式细胞术检测2组患者在化疗前与经6周期化疗结束后1个月的外周血淋巴细胞亚群的变化。结果：①实验组的近期有效率（53.30% vs 36.10%， P =0.16）及疾病控制率（86.70% vs 83.30%， P =0.97）与对照组的差异均无统计学意义；②治疗前后比较，对照组外周血淋巴细胞亚群表达水平无显著差异（ P >0.05）；实验组CD3+、CD3+CD4+、CD3+CD8+表达水平均有所提高（均 P <0.05）；③与对照组相比，实验组治疗后患者的生活质量（QOL）评分率显著升高（86.70% vs 50.00%， P =0.002）；生存期PFS\[（16.67±12.26） vs （9.65±9.01）个月， P =0.031\]及OS\[（18.89±11.70） vs （1.78±8.64）个月， P =0.039 ]均有明显延长。结论：CIK联合多西他赛、奥沙利铂、替吉奥治疗晚期胃癌可能起到协同作用，能延长PFS和OS。
目的：探讨CIK细胞联合多西他赛、奥沙利铂、替吉奥治疗晚期胃癌患者的疗效及安全性。方法：收集2011年1月至2012年1月在我院收治的66例晚期胃癌患者，分为实验组30例：CIK联合多西他赛、奥沙利铂、替吉奥治疗患者；对照组36例：为同期单纯用多西他赛、奥沙利铂、替吉奥治疗患者。治疗后随访36个月，研究主要终点为无进展生存期（PFS），次要终点为总生存期（OS）；采用流式细胞术检测2组患者在化疗前与经6周期化疗结束后1个月的外周血淋巴细胞亚群的变化。结果：①实验组的近期有效率（53.30% vs 36.10%， P =0.16）及疾病控制率（86.70% vs 83.30%， P =0.97）与对照组的差异均无统计学意义；②治疗前后比较，对照组外周血淋巴细胞亚群表达水平无显著差异（ P >0.05）；实验组CD3+、CD3+CD4+、CD3+CD8+表达水平均有所提高（均 P <0.05）；③与对照组相比，实验组治疗后患者的生活质量（QOL）评分率显著升高（86.70% vs 50.00%， P =0.002）；生存期PFS\[（16.67±12.26） vs （9.65±9.01）个月， P =0.031\]及OS\[（18.89±11.70） vs （1.78±8.64）个月， P =0.039 ]均有明显延长。结论：CIK联合多西他赛、奥沙利铂、替吉奥治疗晚期胃癌可能起到协同作用，能延长PFS和OS。
2015, 22(3):385-387.
DOI: 10.3872/j.issn.1007-385X.2015.3.019
Abstract:
目的：探讨组织因子途径抑制物2（tissue factor pathway inhibitor 2，TFPI-2）蛋白在结直肠癌、癌旁组织及正常结肠黏膜组织中的表达情况。方法：选取2011年5月至2011年10月在上海交通大学附属新华医院肛肠外科住院手术切除并经病理证实的结直肠癌组织及相应癌旁组织标本各50份，同时收集在上海建工医院体检行肠镜活检的正常结直肠黏膜组织23例，应用免疫组化法检测TFPI-2蛋白在结直肠癌组织、癌旁组织及正常结直肠黏膜组织中的表达。结果：与癌旁组织及正常黏膜组织相比，TFPI-2蛋白在结直肠癌中呈阴性表达（0/50），明显低于癌旁黏膜组织\[24%（12/50）\]及正常肠黏膜组织\[78.3%（18/23）\]，3组TFPI-2蛋白的表达差异有统计学意义（P<0.01）。结论：TFPI-2蛋白在结直肠癌组织及正常结直肠黏膜组织中的表达存在差异，可能与结直肠癌的发生、发展相关。
目的：探讨组织因子途径抑制物2（tissue factor pathway inhibitor 2，TFPI-2）蛋白在结直肠癌、癌旁组织及正常结肠黏膜组织中的表达情况。方法：选取2011年5月至2011年10月在上海交通大学附属新华医院肛肠外科住院手术切除并经病理证实的结直肠癌组织及相应癌旁组织标本各50份，同时收集在上海建工医院体检行肠镜活检的正常结直肠黏膜组织23例，应用免疫组化法检测TFPI-2蛋白在结直肠癌组织、癌旁组织及正常结直肠黏膜组织中的表达。结果：与癌旁组织及正常黏膜组织相比，TFPI-2蛋白在结直肠癌中呈阴性表达（0/50），明显低于癌旁黏膜组织\[24%（12/50）\]及正常肠黏膜组织\[78.3%（18/23）\]，3组TFPI-2蛋白的表达差异有统计学意义（P<0.01）。结论：TFPI-2蛋白在结直肠癌组织及正常结直肠黏膜组织中的表达存在差异，可能与结直肠癌的发生、发展相关。
2015, 22(3):388-392.
DOI: 10.3872/j.issn.1007-385X.2015.3.020
Abstract:
唾液酸结合性免疫球蛋白样凝集素（sialic acid-binding Ig-like lectins，Siglecs）是一类免疫球蛋白超家族（immunoglobulin superfamily, IgSF）成员，可通过识别含有唾液酸的糖链结构，介导细胞与细胞或病原体间的相互作用，在固有免疫和适应性免疫中发挥重要的调控作用。近年来研究表明，Siglec家族成员参与免疫细胞活化、增殖以及凋亡的调控；同时，Siglec家族成员也参与免疫耐受的调控，并在自身免疫病、炎症反应以及肿瘤发生中发挥重要的免疫调控作用；因此，越来越多的靶向Siglecs抗体或糖基化配体的治疗药物被相继研发并用于淋巴瘤、白血病和自身免疫疾病等多种Siglecs相关疾病的治疗。现就Siglecs参与免疫调控及其在抗自身免疫病和抗肿瘤发生中的研究进展作一综述。
唾液酸结合性免疫球蛋白样凝集素（sialic acid-binding Ig-like lectins，Siglecs）是一类免疫球蛋白超家族（immunoglobulin superfamily, IgSF）成员，可通过识别含有唾液酸的糖链结构，介导细胞与细胞或病原体间的相互作用，在固有免疫和适应性免疫中发挥重要的调控作用。近年来研究表明，Siglec家族成员参与免疫细胞活化、增殖以及凋亡的调控；同时，Siglec家族成员也参与免疫耐受的调控，并在自身免疫病、炎症反应以及肿瘤发生中发挥重要的免疫调控作用；因此，越来越多的靶向Siglecs抗体或糖基化配体的治疗药物被相继研发并用于淋巴瘤、白血病和自身免疫疾病等多种Siglecs相关疾病的治疗。现就Siglecs参与免疫调控及其在抗自身免疫病和抗肿瘤发生中的研究进展作一综述。
2015, 22(3):393-398.
DOI: 10.3872/j.issn.1007-385X.2015.3.021
Abstract:
结直肠癌是最常见的恶性肿瘤之一，尽管联合应用手术、化疗、放疗可提高患者的生存率，但仍有大量患者因术后转移和复发死亡。循环肿瘤细胞及循环肿瘤DNA对结直肠癌的早期诊断、疗效监测、预后评估以及个体化治疗方案制定均有重要意义，已成为近年来研究的热点。本文对近年来结直肠癌循环肿瘤细胞及循环肿瘤DNA的检测技术及其在早期诊断、疗效监测和预后判断中的应用进展作一综述。
结直肠癌是最常见的恶性肿瘤之一，尽管联合应用手术、化疗、放疗可提高患者的生存率，但仍有大量患者因术后转移和复发死亡。循环肿瘤细胞及循环肿瘤DNA对结直肠癌的早期诊断、疗效监测、预后评估以及个体化治疗方案制定均有重要意义，已成为近年来研究的热点。本文对近年来结直肠癌循环肿瘤细胞及循环肿瘤DNA的检测技术及其在早期诊断、疗效监测和预后判断中的应用进展作一综述。
2015, 22(3):399-403.
DOI: 10.3872/j.issn.1007-385X.2015.3.022
Abstract:
近年来，长链非编码RNA(long non-coding RNA, lncRNA)逐渐成为研究热点。其中肺腺癌转移相关转录本1(metastasis-associated lung adenocarcinoma transcript 1, MALAT1)在多种肿瘤发生、发展中的作用受到越来越多的关注。MALAT1首先作为重要的预后标志物发现于早期非小细胞肺癌（non-smallcell lung cancer，NSCL）中，其与肺癌细胞转移能力密切相关。由于肿瘤细胞转移为恶性肿瘤的基本生物学特征，是肿瘤复发及致死的主要原因，因此了解MALAT1调节恶性肿瘤转移的机制有助于为恶性肿瘤的治疗提供新的理论指导。本文就MALAT1和肿瘤转移关系的研究进展作一综述。
近年来，长链非编码RNA(long non-coding RNA, lncRNA)逐渐成为研究热点。其中肺腺癌转移相关转录本1(metastasis-associated lung adenocarcinoma transcript 1, MALAT1)在多种肿瘤发生、发展中的作用受到越来越多的关注。MALAT1首先作为重要的预后标志物发现于早期非小细胞肺癌（non-smallcell lung cancer，NSCL）中，其与肺癌细胞转移能力密切相关。由于肿瘤细胞转移为恶性肿瘤的基本生物学特征，是肿瘤复发及致死的主要原因，因此了解MALAT1调节恶性肿瘤转移的机制有助于为恶性肿瘤的治疗提供新的理论指导。本文就MALAT1和肿瘤转移关系的研究进展作一综述。
2015, 22(3):404-108.
DOI: 10.3872/j.issn.1007-385X.2015.3.023
Abstract:
MicroRNAs（miRNA）是一类内源性小分子非编码RNA，在转录后水平调控基因的表达。半数以上的miRNA定位于与肿瘤发生相关的染色体区域或脆性位点，超过一半的miRNA与癌症发生相关。目前研究表明，一些miRNA与5-氟尿嘧啶（5-Fu）的抗肿瘤化疗敏感性有密切关系，miRNA可通过调控药物代谢相关酶，如胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）和胸苷酸磷酸化酶（TP）等，调控细胞凋亡（主要是Bcl-2、Bcl-xL、Bax等）以及细胞周期从而影响5-Fu化疗敏感性。此外，miRNA还可通过其他一些机制如调控上皮间质转化（EMT）、多药耐药（MDR）和肿瘤干细胞（CSCs）等影响5-Fu化疗敏感性。
MicroRNAs（miRNA）是一类内源性小分子非编码RNA，在转录后水平调控基因的表达。半数以上的miRNA定位于与肿瘤发生相关的染色体区域或脆性位点，超过一半的miRNA与癌症发生相关。目前研究表明，一些miRNA与5-氟尿嘧啶（5-Fu）的抗肿瘤化疗敏感性有密切关系，miRNA可通过调控药物代谢相关酶，如胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）和胸苷酸磷酸化酶（TP）等，调控细胞凋亡（主要是Bcl-2、Bcl-xL、Bax等）以及细胞周期从而影响5-Fu化疗敏感性。此外，miRNA还可通过其他一些机制如调控上皮间质转化（EMT）、多药耐药（MDR）和肿瘤干细胞（CSCs）等影响5-Fu化疗敏感性。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.