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Volume 16,Issue 6,2009 Table of Contents
2009, 16(6):547-556.
DOI: 10.3872/j.issn.1007-385X.2009.6.001
Abstract:
Cancer stem cells (CSC) are capable of selfrenewal and can proliferate into a heterogeneous bulk with cancer progeny population, which is the main reason for recurrence and metastasis of cancer. Metastatic cancer stem cells (MCSC) have the properties of CSC and the ability of metastasis. Metastasis happens at both the late and early stages of tumorigenesis. MCSC are different from CSC in origin, epithelialmesenchymal transition (EMT), mesenchymalepithelial transition (MET), and microenvironment of target organs (niche), etc. Therefore, MCSC is the foundation of cancer metastasis. Antimetastasis strategies include killing CSC, blocking EMT and MET of CSC, inhibiting MCSC adhesion to microvessels, and destroying MCSC dependentniche. This review introduces the possible sources, biological features of MCSC, the possible breakthrough in MCSC research, and MCSCtargeted antimetastasis strategy, hoping to provide reference for researches about tumor metastasis mechanisms and antimetastasis strategies.
Cancer stem cells (CSC) are capable of selfrenewal and can proliferate into a heterogeneous bulk with cancer progeny population, which is the main reason for recurrence and metastasis of cancer. Metastatic cancer stem cells (MCSC) have the properties of CSC and the ability of metastasis. Metastasis happens at both the late and early stages of tumorigenesis. MCSC are different from CSC in origin, epithelialmesenchymal transition (EMT), mesenchymalepithelial transition (MET), and microenvironment of target organs (niche), etc. Therefore, MCSC is the foundation of cancer metastasis. Antimetastasis strategies include killing CSC, blocking EMT and MET of CSC, inhibiting MCSC adhesion to microvessels, and destroying MCSC dependentniche. This review introduces the possible sources, biological features of MCSC, the possible breakthrough in MCSC research, and MCSCtargeted antimetastasis strategy, hoping to provide reference for researches about tumor metastasis mechanisms and antimetastasis strategies.
HU Shou-you
,
ZHU Xue-jun
,
FAN Zhen-fang
,
KONG Xiang-tu
,
CHEN Yu-chao
,
CHEN Jian-yi
,
JI Jian-min
,
SUN Xue-mei
2009, 16(6):557-563.
DOI: 10.3872/j.issn.1007-385X.2009.6.002
Abstract:
Objective:To investigate the effect of gemcitabine on myeloid derived suppressor cells (MDSC) in the spleen of B lymphoma cellbearing mice, and the therapeutic effect of gemcitabine combined with intratumoral injection of dendritic cells (DCs) in treatment of large B lymphoma. Methods: BALB/c mice were inoculated subcutaneously with B lymphoma A20 cells; large tumors were formed 30 d after inoculation. Gr1+CD11b+ MDSC proportion in the spleen was analyzed by flow cytometry before and after gemcitabine treatment. Splenic MDSC sorted by immunomagnetic beads was further treated with gemcitabine, and then the apoptosis of MDSC was examined by AnnexinV/PI staining. Tumor growth and survival time of A20 tumorbearing mice were observed after treatment with gemcitabine and intratumoral injection of DCs. Results: Splenic Gr1+CD11b+MDSC ratio in A20 cellbearing mice was 10 times higher than that in the normal mice. Gemcitabine induced apoptosis and necrosis of purified MDSC in vitro in a timedependent manner. The percentage of MDSC in the spleen of A20 tumorbearing mice was decreased after injection of a single dose of gemcitabine. Gemcitabine or intratumoral injection of DCs alone inhibited growth of tumor to a certain degree, with the mean survival periods of mice in the gemcitabine, DCs, and untreated groups being (48.8±3.6) d, (47.2±7.4) d, and (38.8±2.2) d, respectively. Gemcitabine chemotherapy combined with intratumoral DC injection resulted in continuous shrink of the tumors, and 60% of the mice survived for more than 90 d. Conclusion: Gemcitabine can effectively eliminate splenic MDSC in tumorbearing mice. Gemcitabine chemotherapy and DCs immunotherapy can work synergistically in the treatment of huge lymphoma. These results provide an experimental basis for the comprehensive chemotherapy and immunotherapy of relapsed or refractory lymphoma.
Objective:To investigate the effect of gemcitabine on myeloid derived suppressor cells (MDSC) in the spleen of B lymphoma cellbearing mice, and the therapeutic effect of gemcitabine combined with intratumoral injection of dendritic cells (DCs) in treatment of large B lymphoma. Methods: BALB/c mice were inoculated subcutaneously with B lymphoma A20 cells; large tumors were formed 30 d after inoculation. Gr1+CD11b+ MDSC proportion in the spleen was analyzed by flow cytometry before and after gemcitabine treatment. Splenic MDSC sorted by immunomagnetic beads was further treated with gemcitabine, and then the apoptosis of MDSC was examined by AnnexinV/PI staining. Tumor growth and survival time of A20 tumorbearing mice were observed after treatment with gemcitabine and intratumoral injection of DCs. Results: Splenic Gr1+CD11b+MDSC ratio in A20 cellbearing mice was 10 times higher than that in the normal mice. Gemcitabine induced apoptosis and necrosis of purified MDSC in vitro in a timedependent manner. The percentage of MDSC in the spleen of A20 tumorbearing mice was decreased after injection of a single dose of gemcitabine. Gemcitabine or intratumoral injection of DCs alone inhibited growth of tumor to a certain degree, with the mean survival periods of mice in the gemcitabine, DCs, and untreated groups being (48.8±3.6) d, (47.2±7.4) d, and (38.8±2.2) d, respectively. Gemcitabine chemotherapy combined with intratumoral DC injection resulted in continuous shrink of the tumors, and 60% of the mice survived for more than 90 d. Conclusion: Gemcitabine can effectively eliminate splenic MDSC in tumorbearing mice. Gemcitabine chemotherapy and DCs immunotherapy can work synergistically in the treatment of huge lymphoma. These results provide an experimental basis for the comprehensive chemotherapy and immunotherapy of relapsed or refractory lymphoma.
2009, 16(6):564-569.
DOI: 10.3872/j.issn.1007-385X.2009.6.003
Abstract:
Objective:To construct Krastargeted siRNAs (Kras siRNA) and to investigate the inhibitory effects of Kras siRNAs on the growth and migration of lung cancer A549 cells (containing mutant Kras gene) and NCIH446 cells (containing wildtype Kras gene). :Methods: :Four Kras siRNAs (Kras siRNA1~Kras siRNA3 targeting wildtype Kras and Kras siRNA4 targeting mutant Kras) were designed and artificially synthesized; they were used to transfect A549 cells and NCIH446 cells. The expressions of Ras mRNA and protein were examined by RTPCR and Western blotting. The inhibitory effects of Kras siRNAs on the proliferations of A549 and NCIH446 cells were determined by MTT assay. The effects of Kras siRNAs on the cell migration and apoptosis were observed by Transwell assay and Hoechst 33258 staining, respectively. :Results: :Mutant Krastargeted siRNA (Kras siRNA4) specifically inhibited the Kras expression but had no influence on Hras and Nras expression in A549 cells. Kras siRNA4 inhibited the proliferation of A549 cells but did not inhibit that of NCIH446 cells, which contained wild type Kras gene. Kras siRNA4 also induced apoptosis and inhibited migration of A549 cells. :Conclusion: :Mutant Krastargeted siRNA4 can inhibit the proliferation, migration and induce apoptosis of A549 cells. It may be a potential and personalized drug for the treatment against lung cancer containing mutant Kras gene.
Objective:To construct Krastargeted siRNAs (Kras siRNA) and to investigate the inhibitory effects of Kras siRNAs on the growth and migration of lung cancer A549 cells (containing mutant Kras gene) and NCIH446 cells (containing wildtype Kras gene). :Methods: :Four Kras siRNAs (Kras siRNA1~Kras siRNA3 targeting wildtype Kras and Kras siRNA4 targeting mutant Kras) were designed and artificially synthesized; they were used to transfect A549 cells and NCIH446 cells. The expressions of Ras mRNA and protein were examined by RTPCR and Western blotting. The inhibitory effects of Kras siRNAs on the proliferations of A549 and NCIH446 cells were determined by MTT assay. The effects of Kras siRNAs on the cell migration and apoptosis were observed by Transwell assay and Hoechst 33258 staining, respectively. :Results: :Mutant Krastargeted siRNA (Kras siRNA4) specifically inhibited the Kras expression but had no influence on Hras and Nras expression in A549 cells. Kras siRNA4 inhibited the proliferation of A549 cells but did not inhibit that of NCIH446 cells, which contained wild type Kras gene. Kras siRNA4 also induced apoptosis and inhibited migration of A549 cells. :Conclusion: :Mutant Krastargeted siRNA4 can inhibit the proliferation, migration and induce apoptosis of A549 cells. It may be a potential and personalized drug for the treatment against lung cancer containing mutant Kras gene.
2009, 16(6):570-576.
DOI: 10.3872/j.issn.1007-385X.2009.6.004
Abstract:
Objective:To explore the inhibitory effects of gefitinib (epidermal growth factor receptor inhibitor) combined with celecoxib (cyclooxygenase2 inhibitor) against human lung cancer A549 cells and the possible mechanism. :Methods: :A549 cells were cultured in RPMI 1640 medium and were divided into 4 groups: normal control group, 5 μmol/L gefitinib group, 25 μmol/L celecoxib group, and 5 μmol/L gefitinib+25 μmol/L celecoxib group. The morphological changes of A549 cells were observed under inverted microscope 48 h after treatment; the effects of drugs on growth of A549 Cells were detected by MTT assay; the apoptosis and cell cycles of A549 cells were measured by Annexin V/PI and Hoechst 33258 staining, respectively; and the expression of EGFR protein, COX2 protein, and EGFR mRNA were determined by immunofluorescence and realtime PCR. :Results: :Compared with gefitinib and celecoxib groups, many granules and vacuoles were observed in the gefitinib and celecoxib combination group, and cells became round and there was defluxion. Both gefitinib and celecoxib inhibited the growth of A549 cells in a time and dosedependent manner. After treatment for 48 h, the inhibitory rate was (58.2±4.6)% in the combination group, which was significantly higher than those of the other two groups. Apoptosis rate in the combination group was also significantly higher than those in the other two groups (33.9% vs 6.0%, 8.8%）, and the cell proportion in S phase significantly decreased and in G0/G1 phases significantly increased（P<0.01）. EGFR protein, COX2 protein, and EGFR mRNA expression in A549 cells was significantly decreased in the combination treatment group compared with those in the other two groups（P<0.05）. :Conclusion: :Gefitinib and celecoxib can synergistically inhibit the growth of A549 cells, possibly through promoting apoptosis, G0/G1 arrest, and downregulating activated EGFR and COX2 expression.
Objective:To explore the inhibitory effects of gefitinib (epidermal growth factor receptor inhibitor) combined with celecoxib (cyclooxygenase2 inhibitor) against human lung cancer A549 cells and the possible mechanism. :Methods: :A549 cells were cultured in RPMI 1640 medium and were divided into 4 groups: normal control group, 5 μmol/L gefitinib group, 25 μmol/L celecoxib group, and 5 μmol/L gefitinib+25 μmol/L celecoxib group. The morphological changes of A549 cells were observed under inverted microscope 48 h after treatment; the effects of drugs on growth of A549 Cells were detected by MTT assay; the apoptosis and cell cycles of A549 cells were measured by Annexin V/PI and Hoechst 33258 staining, respectively; and the expression of EGFR protein, COX2 protein, and EGFR mRNA were determined by immunofluorescence and realtime PCR. :Results: :Compared with gefitinib and celecoxib groups, many granules and vacuoles were observed in the gefitinib and celecoxib combination group, and cells became round and there was defluxion. Both gefitinib and celecoxib inhibited the growth of A549 cells in a time and dosedependent manner. After treatment for 48 h, the inhibitory rate was (58.2±4.6)% in the combination group, which was significantly higher than those of the other two groups. Apoptosis rate in the combination group was also significantly higher than those in the other two groups (33.9% vs 6.0%, 8.8%）, and the cell proportion in S phase significantly decreased and in G0/G1 phases significantly increased（P<0.01）. EGFR protein, COX2 protein, and EGFR mRNA expression in A549 cells was significantly decreased in the combination treatment group compared with those in the other two groups（P<0.05）. :Conclusion: :Gefitinib and celecoxib can synergistically inhibit the growth of A549 cells, possibly through promoting apoptosis, G0/G1 arrest, and downregulating activated EGFR and COX2 expression.
MA Ling-di
,
WANG Yong
,
NI Cheng
,
WANG Shi-zhong
,
BAO Yongyi
,
GUAN Nai-fu
,
ZHANG Ke
,
Leif G. Salford
,
FAN Xiaolong
2009, 16(6):577-582.
DOI: 10.3872/j.issn.1007-385X.2009.6.005
Abstract:
Objective:To observe the effects of recombinant adenovirus TRAIL (Ad5TRAIL & Ad5F35TRAIL) on apoptosis of nonsmall cell lung (NSCLC) cells, so as to assess the value of AdTRAIL in gene therapy of NSCLC. :Methods: :CAR and CD46 expression levels in lung cancer cell lines (A549, Z793, QG56 and NCIH520) and the primary lung cancer cells from samples of 10 NSCLC patients were assayed by flow cytometry analysis. The lung cancer cell lines and primary lung cancer cells were infected with Ad5TRAIL & Ad5F35TRAIL adenoviral vectors at MOI 10 or 50, respectively; the percentage of apoptosis cells labeled by Annexin VFITC in different cells were measured by flow cytometry 48 h after transfection. :Results:: The expression of CD46 were higher than that of CAR in all the lung cancer lines (A549, Z793, QG56 and NCIH520) and the primary lung cancer cells. Significant apoptosis was observed in Z793 and QG56 cells transfected with Ad5TRAIL or Ad5F35TRAIL at MOI 10, with the apoptosis rate being (1.76±2.10)%（Ad5TRAIL）, (15.96±2.89)%（Ad5F35TRAIL）and (6.05±1.58)%（Ad5TRAIL）,(10.11±1.26)%（Ad5F35TRAIL）, respectively, compared to no adenovirustransfected cells （\[2.33±0.37\]% and \[5.95±1.89\]%, respectively, P<0.05）. Less than 10% of apoptosis cells were detected in NCIH520 cells transfected with Ad5 or Ad5F35TRAIL at MOI 50 (\[12.89±3.2\]% for Ad5TRAIL and \[9.08±1.35\]% for Ad5F35TRAIL, respectively）compared to no adenovirustransfected cells (\[7.04±2.17\]%, P>0.05）. Moreover, apoptosis induced by Ad5 or Ad5F35TRAIL transfection in A549 cells was not detected both at MOI 10 and 50. About half of the primary lung cancer cells from 10 patients induced apoptosis after transfected with Ad5TRAIL or Ad5F35TRAIL vector. A higher percentage of apoptotic cells were found in Ad5F35TRAIL group than those in Ad5TRAIL and control groups. :Conclusion: :Ad5TRAIL can induce apoptosis of NSCLC cells in vitro, and Ad5F35TRAIL is more potent than Ad5TRAIL, so Ad5F35TRAIL is more suitable for gene therapy of NSCLC.
Objective:To observe the effects of recombinant adenovirus TRAIL (Ad5TRAIL & Ad5F35TRAIL) on apoptosis of nonsmall cell lung (NSCLC) cells, so as to assess the value of AdTRAIL in gene therapy of NSCLC. :Methods: :CAR and CD46 expression levels in lung cancer cell lines (A549, Z793, QG56 and NCIH520) and the primary lung cancer cells from samples of 10 NSCLC patients were assayed by flow cytometry analysis. The lung cancer cell lines and primary lung cancer cells were infected with Ad5TRAIL & Ad5F35TRAIL adenoviral vectors at MOI 10 or 50, respectively; the percentage of apoptosis cells labeled by Annexin VFITC in different cells were measured by flow cytometry 48 h after transfection. :Results:: The expression of CD46 were higher than that of CAR in all the lung cancer lines (A549, Z793, QG56 and NCIH520) and the primary lung cancer cells. Significant apoptosis was observed in Z793 and QG56 cells transfected with Ad5TRAIL or Ad5F35TRAIL at MOI 10, with the apoptosis rate being (1.76±2.10)%（Ad5TRAIL）, (15.96±2.89)%（Ad5F35TRAIL）and (6.05±1.58)%（Ad5TRAIL）,(10.11±1.26)%（Ad5F35TRAIL）, respectively, compared to no adenovirustransfected cells （\[2.33±0.37\]% and \[5.95±1.89\]%, respectively, P<0.05）. Less than 10% of apoptosis cells were detected in NCIH520 cells transfected with Ad5 or Ad5F35TRAIL at MOI 50 (\[12.89±3.2\]% for Ad5TRAIL and \[9.08±1.35\]% for Ad5F35TRAIL, respectively）compared to no adenovirustransfected cells (\[7.04±2.17\]%, P>0.05）. Moreover, apoptosis induced by Ad5 or Ad5F35TRAIL transfection in A549 cells was not detected both at MOI 10 and 50. About half of the primary lung cancer cells from 10 patients induced apoptosis after transfected with Ad5TRAIL or Ad5F35TRAIL vector. A higher percentage of apoptotic cells were found in Ad5F35TRAIL group than those in Ad5TRAIL and control groups. :Conclusion: :Ad5TRAIL can induce apoptosis of NSCLC cells in vitro, and Ad5F35TRAIL is more potent than Ad5TRAIL, so Ad5F35TRAIL is more suitable for gene therapy of NSCLC.
2009, 16(6):583-587.
DOI: 10.3872/j.issn.1007-385X.2009.6.006
Abstract:
Objective:To investigate the effect of survivinsiRNA plasmid on survivin expression in human lung cancer cell line A549, and to observe its effect on the apoptosis, proliferation, and chemosensitivity of A549 cells. :Methods: :pSilencersurvivinsiRNA (survivinsiRNA) plasmid was constructed using pSilencerU6 plasmid and was transfected into A549 cells. Expression of survivin mRNA and protein was examined by RTPCR and Western blotting analysis, respectively. Apoptosis and proliferation of A549 cells were examined by DAPI staining and MTT, respectively. :Results: :SurvivinsiRNA plasmid was successfully constructed, and it significantly inhibited survivin mRNA and protein expression in A549 cells. SurvivinsiRNA transfection induced apoptosis, inhibited proliferation and increased chemosensitivity of A549 cells to cisplatin. :Conclusion: :pSilencersurvivinsiRNA can silence survivin expression in A549 cells and subsequently inhibit proliferation, promote apoptosis, and enhance chemosensitivity of A549 cells to cisplatin. Survivin may serve as a potential target for gene therapy of lung cancer.
Objective:To investigate the effect of survivinsiRNA plasmid on survivin expression in human lung cancer cell line A549, and to observe its effect on the apoptosis, proliferation, and chemosensitivity of A549 cells. :Methods: :pSilencersurvivinsiRNA (survivinsiRNA) plasmid was constructed using pSilencerU6 plasmid and was transfected into A549 cells. Expression of survivin mRNA and protein was examined by RTPCR and Western blotting analysis, respectively. Apoptosis and proliferation of A549 cells were examined by DAPI staining and MTT, respectively. :Results: :SurvivinsiRNA plasmid was successfully constructed, and it significantly inhibited survivin mRNA and protein expression in A549 cells. SurvivinsiRNA transfection induced apoptosis, inhibited proliferation and increased chemosensitivity of A549 cells to cisplatin. :Conclusion: :pSilencersurvivinsiRNA can silence survivin expression in A549 cells and subsequently inhibit proliferation, promote apoptosis, and enhance chemosensitivity of A549 cells to cisplatin. Survivin may serve as a potential target for gene therapy of lung cancer.
2009, 16(6):588-594.
DOI: 10.3872/j.issn.1007-385X.2009.6.007
Abstract:
Objective:To use in vivo fluorescence image analysis system for evaluating the efficacies of pVAX1Ag85A and pVAX1Ag85B DNA vaccines in treatment of bladder cancer cellimplanted tumors in mice. :Methods: :Discosomasp red fluorescent protein (DsRed) stably transfected bladder cancer BTT cell line (BTTDsRed) was established and BTTDsRed cellimplanted mouse model was constructed. Six days later, 24 BTTDsRedbearing mice were randomly divided into pVAX1Ag85A DNA vaccine group, pVAX1Ag85B DNA vaccine group, and saline group through injecting the pVAX1Ag85A, pVAX1Ag85B, and saline into the right hind limbs of mice, respectively. The growth and metastasis of implanted BTTDsRed tumors were examined by in vivo fluorescence image analysis system. :Results: :BTT cell line stably transfected with DsRed (BTTDsRed) was successfully established. Fluorescence visible mouse model was successfully established by inoculating BTTDsRed cells into hind limbs of mice. After treatment with pVAX1Ag85A or pVAX1Ag85B for 2 weeks, the in vivo tumor fluorescence intensity in pVAX1Ag85B group was significantly lower than that in the saline group (P<0.05). After 3 weeks, tumor fluorescence intensities in both pVAX1Ag85A and pVAX1Ag85B groups were significantly lower than that in the saline group (P<0.01). But the efficacies of pVAX1Ag85A and pVAX1Ag85B groups were similar (P>0.05). The distant lymphatic metastasis rate in pVAX1Ag85B group was significantly lower than those in the saline (25.0% vs 87.5%) and pVAX1Ag85A groups (25.0% vs 62.5%) (P＜0.05). :Conclusion:: In vivo fluorescence image analysis system can dynamically, sensitively and visually evaluate the antitumor effects of DNA vaccines against bladder cancer cellimplanted tumors. Both pVAX1Ag85A and pVAX1Ag85B DNA vaccines have antitumor effects for bladder cancers.
Objective:To use in vivo fluorescence image analysis system for evaluating the efficacies of pVAX1Ag85A and pVAX1Ag85B DNA vaccines in treatment of bladder cancer cellimplanted tumors in mice. :Methods: :Discosomasp red fluorescent protein (DsRed) stably transfected bladder cancer BTT cell line (BTTDsRed) was established and BTTDsRed cellimplanted mouse model was constructed. Six days later, 24 BTTDsRedbearing mice were randomly divided into pVAX1Ag85A DNA vaccine group, pVAX1Ag85B DNA vaccine group, and saline group through injecting the pVAX1Ag85A, pVAX1Ag85B, and saline into the right hind limbs of mice, respectively. The growth and metastasis of implanted BTTDsRed tumors were examined by in vivo fluorescence image analysis system. :Results: :BTT cell line stably transfected with DsRed (BTTDsRed) was successfully established. Fluorescence visible mouse model was successfully established by inoculating BTTDsRed cells into hind limbs of mice. After treatment with pVAX1Ag85A or pVAX1Ag85B for 2 weeks, the in vivo tumor fluorescence intensity in pVAX1Ag85B group was significantly lower than that in the saline group (P<0.05). After 3 weeks, tumor fluorescence intensities in both pVAX1Ag85A and pVAX1Ag85B groups were significantly lower than that in the saline group (P<0.01). But the efficacies of pVAX1Ag85A and pVAX1Ag85B groups were similar (P>0.05). The distant lymphatic metastasis rate in pVAX1Ag85B group was significantly lower than those in the saline (25.0% vs 87.5%) and pVAX1Ag85A groups (25.0% vs 62.5%) (P＜0.05). :Conclusion:: In vivo fluorescence image analysis system can dynamically, sensitively and visually evaluate the antitumor effects of DNA vaccines against bladder cancer cellimplanted tumors. Both pVAX1Ag85A and pVAX1Ag85B DNA vaccines have antitumor effects for bladder cancers.
2009, 16(6):595-599.
DOI: 10.3872/j.issn.1007-385X.2009.6.008
Abstract:
Objective:To construct a mutant :D314A: of Escherichia coli cytosine deaminase (ECCD, substitution of an alanine (A) for the aspartic acid (D) at position 314 of cytosine deaminase) and investigate its antitumor effect. :Methods: :Eukaryotic expression plasmid containing ECCD gene (pcDNA3.1CDwt) was constructed, and the mutant pcDNA3.1CDD314A plasmid, with aspartic acid (D) at position 314 of ECCD gene substituted by alanine (A) (ECCDD314A), was established by sitedirected mutation. ECCDwt and ECCDD314A were transfected into human colon cancer cell line LoVo via LipofectamineTM 2000, and positive LoVoCDwt and LoVoCDD314A cells stably expressing corresponding genes were selected by G418. The cytotoxicity and bystander effects of ECCD and ECCDD314A genes on LoVo cells were evaluated by MTT assay. :Results: :The mutant :D314A: was confirmed by sequence analysis. ECCD and ECCDD314A mRNA were expressed after transfected into LoVo cells. The IC50 of LovoCDD314A cells was (85.13±0.60) mmol/L, which was significantly lower than that of LoVoCDwt cells (\[689.76±0.45\] μmol/L, P=0.000). Bystander effect assay showed that, when at the ratio of 30%, the survival rates of LoVoCDwt cells and LovoCDD314A cells were (48.5±049)% and (17.3±0.40)% (P=0.000), respectively. :Conclusion：:Mutatant ECCD gene (ECCDD314A) has a significantly increased antitumor effect on LoVo cells compared with wild type EGCD gene, and it may become a new candidate gene for tumor gene therapy.
Objective:To construct a mutant :D314A: of Escherichia coli cytosine deaminase (ECCD, substitution of an alanine (A) for the aspartic acid (D) at position 314 of cytosine deaminase) and investigate its antitumor effect. :Methods: :Eukaryotic expression plasmid containing ECCD gene (pcDNA3.1CDwt) was constructed, and the mutant pcDNA3.1CDD314A plasmid, with aspartic acid (D) at position 314 of ECCD gene substituted by alanine (A) (ECCDD314A), was established by sitedirected mutation. ECCDwt and ECCDD314A were transfected into human colon cancer cell line LoVo via LipofectamineTM 2000, and positive LoVoCDwt and LoVoCDD314A cells stably expressing corresponding genes were selected by G418. The cytotoxicity and bystander effects of ECCD and ECCDD314A genes on LoVo cells were evaluated by MTT assay. :Results: :The mutant :D314A: was confirmed by sequence analysis. ECCD and ECCDD314A mRNA were expressed after transfected into LoVo cells. The IC50 of LovoCDD314A cells was (85.13±0.60) mmol/L, which was significantly lower than that of LoVoCDwt cells (\[689.76±0.45\] μmol/L, P=0.000). Bystander effect assay showed that, when at the ratio of 30%, the survival rates of LoVoCDwt cells and LovoCDD314A cells were (48.5±049)% and (17.3±0.40)% (P=0.000), respectively. :Conclusion：:Mutatant ECCD gene (ECCDD314A) has a significantly increased antitumor effect on LoVo cells compared with wild type EGCD gene, and it may become a new candidate gene for tumor gene therapy.
LIU Zhao-long
,
YAN Bo
,
LUO Yun-bao
,
WANG Yong-bing
,
HAN Ce-ran
,
SONG An
,
YU Shi-yong
,
HOU Kun
2009, 16(6):600-603.
DOI: 10.3872/j.issn.1007-385X.2009.6.009
Abstract:
Objective:To investigate the effect of rapamycin on cell growth and migration of gallbladder cancer GBCSD cells, and to discuss its potential in clinical therapy of gallbladder cancer. :Methods: :Proliferation of GBCSD cells treated with different concentrations of rapamycin （12.5, 25, and 50 mmol/L）was examined by MTT assay. Cell cycle distribution and apoptosis of GBCSD cells treated with different concentrations of rapamycin were determined by flow cytometry. Migration ability of GBCSD cells was assessed by Transwell assay. The expression of mTOR (mammalian target of rapamycin) and its phosphorylation in GBCSD cells were examined by Western blotting assay. :Results: :Rapamycin significantly inhibited the phosphorylation of mTOR, but had no influence on the expression of mTOR in GBCSD cells. Rapamycin significantly inhibited the growth of GBCSD cells in a dosedependent manner (P<0.01). Rapamycin induced apoptosis of GBCSD cells and arrested them at the G1/S phase. Furthermore, rapamycin also significantly suppressed migration of GBCSD cells as showed by Transwell assay (P<0.01). :Conclusion:: Rapamycin can remarkably inhibit the growth and migration of gallbladder cancer cells, probably by inhibition of pmTOR pathway, induction of apoptosis and cell cycle arrest of gallbladder cancer cells.
Objective:To investigate the effect of rapamycin on cell growth and migration of gallbladder cancer GBCSD cells, and to discuss its potential in clinical therapy of gallbladder cancer. :Methods: :Proliferation of GBCSD cells treated with different concentrations of rapamycin （12.5, 25, and 50 mmol/L）was examined by MTT assay. Cell cycle distribution and apoptosis of GBCSD cells treated with different concentrations of rapamycin were determined by flow cytometry. Migration ability of GBCSD cells was assessed by Transwell assay. The expression of mTOR (mammalian target of rapamycin) and its phosphorylation in GBCSD cells were examined by Western blotting assay. :Results: :Rapamycin significantly inhibited the phosphorylation of mTOR, but had no influence on the expression of mTOR in GBCSD cells. Rapamycin significantly inhibited the growth of GBCSD cells in a dosedependent manner (P<0.01). Rapamycin induced apoptosis of GBCSD cells and arrested them at the G1/S phase. Furthermore, rapamycin also significantly suppressed migration of GBCSD cells as showed by Transwell assay (P<0.01). :Conclusion:: Rapamycin can remarkably inhibit the growth and migration of gallbladder cancer cells, probably by inhibition of pmTOR pathway, induction of apoptosis and cell cycle arrest of gallbladder cancer cells.
2009, 16(6):604-608.
DOI: 10.3872/j.issn.1007-385X.2009.6.010
Abstract:
Objective:To elucidate the relationship between Notch3 expression and chemosensitivity of human colon carcinoma cell line SW620 to topotecan. :Methods: :Notch3 siRNA was transfected into SW620 cells, and the expression of Notch3 in SW620 cells was examined by Western blotting. After transfected with Notch3 siRNA for different time periods, SW620 cells were further treated with topotecan, and the proliferation of SW620 cells was detected by MTT assay; the apoptosis of SW620 cells was detected by Hoechst 33342 staining and flow cytometry. Caspase3 activation in SW620 cells was examined by caspase3 activation kit. :Results: :Notch3 siRNA transfection remarkably inhibited Notch3 protein expression in SW620 cells. The IC50 of topotecan in Notch3 siRNAtransfected group was significantly decreased compared with that in the Ctrl siRNA group (P<0.05). Silence of Notch3 expression in SW620 cells by Notch3 siRNA remarkably promoted apoptosis (P<0.05) and caspase3 activation (P<0.05) of SW620 cells induced by topotecan. :Conclusion: :Notch3 downregulation by siRNA in SW620 cells can enhance the chemosensitivity cells to topotecan.
Objective:To elucidate the relationship between Notch3 expression and chemosensitivity of human colon carcinoma cell line SW620 to topotecan. :Methods: :Notch3 siRNA was transfected into SW620 cells, and the expression of Notch3 in SW620 cells was examined by Western blotting. After transfected with Notch3 siRNA for different time periods, SW620 cells were further treated with topotecan, and the proliferation of SW620 cells was detected by MTT assay; the apoptosis of SW620 cells was detected by Hoechst 33342 staining and flow cytometry. Caspase3 activation in SW620 cells was examined by caspase3 activation kit. :Results: :Notch3 siRNA transfection remarkably inhibited Notch3 protein expression in SW620 cells. The IC50 of topotecan in Notch3 siRNAtransfected group was significantly decreased compared with that in the Ctrl siRNA group (P<0.05). Silence of Notch3 expression in SW620 cells by Notch3 siRNA remarkably promoted apoptosis (P<0.05) and caspase3 activation (P<0.05) of SW620 cells induced by topotecan. :Conclusion: :Notch3 downregulation by siRNA in SW620 cells can enhance the chemosensitivity cells to topotecan.
11 Preparation of PEI-RGD/125I(αV)ASODN and its inhibitory effect on invasive ability of HepG2 cells
2009, 16(6):609-613.
DOI: 10.3872/j.issn.1007-385X.2009.6.011
Abstract:
Objective:To study the effects of 125I(αV)ASODN on the in vitro invasive ability of heptocellular carcinoma cell line（HepG2）through PEIRGDmediated receptor process. :Methods: :Intergrin αVspecific antisense oligonucleotide was labeled with 125I, and PEIRGD/125I(αV)ASODN complex was prepared by combining 125I(αV)ASODN with polyethyleneimine derivative PEIRGD. PEIRGD/125I(αV)ASODN complex was transferred into HepG2 cells through the receptormediated process. The effect of PEIRGD/125I(αV)ASODN complex on the invasive ability of HepG2 cells was examined by Boyden chamber invasive assay. :Results: :(1) The labeling yield and radiochemical purity of 125I(αV)ASODN were（73.78±4.09）% and（96.68±1.38）%, respectively, and the labeled compound had a good stability in vitro after 48 h at 37 ℃; (2) The ability of HepG2 cells to uptake PEIRGD/125I(αV)ASODN reached its peek（\[1277±0.85\]%) when PEIRGD/125I(αV)ASODN was at 4 μl/2 μg（\[12.77±0.85\]%）, and then gredually decreased thereafter. So the dosage of PEIRGD/125I(αV)ASODN for the following experiment was chosen as 2 μl/1 μg; (3) The invasive capacity of HepG2 cells was significantly reduced in PEIRGD/125I(αV)ASODN group compared with those in other experiment and control groups (P<0.01). :Conclusion:: 125I(αV) ASODN mediated by PEIRGD can effectively inhibit the invasive capacity of HepG2 cells.
Objective:To study the effects of 125I(αV)ASODN on the in vitro invasive ability of heptocellular carcinoma cell line（HepG2）through PEIRGDmediated receptor process. :Methods: :Intergrin αVspecific antisense oligonucleotide was labeled with 125I, and PEIRGD/125I(αV)ASODN complex was prepared by combining 125I(αV)ASODN with polyethyleneimine derivative PEIRGD. PEIRGD/125I(αV)ASODN complex was transferred into HepG2 cells through the receptormediated process. The effect of PEIRGD/125I(αV)ASODN complex on the invasive ability of HepG2 cells was examined by Boyden chamber invasive assay. :Results: :(1) The labeling yield and radiochemical purity of 125I(αV)ASODN were（73.78±4.09）% and（96.68±1.38）%, respectively, and the labeled compound had a good stability in vitro after 48 h at 37 ℃; (2) The ability of HepG2 cells to uptake PEIRGD/125I(αV)ASODN reached its peek（\[1277±0.85\]%) when PEIRGD/125I(αV)ASODN was at 4 μl/2 μg（\[12.77±0.85\]%）, and then gredually decreased thereafter. So the dosage of PEIRGD/125I(αV)ASODN for the following experiment was chosen as 2 μl/1 μg; (3) The invasive capacity of HepG2 cells was significantly reduced in PEIRGD/125I(αV)ASODN group compared with those in other experiment and control groups (P<0.01). :Conclusion:: 125I(αV) ASODN mediated by PEIRGD can effectively inhibit the invasive capacity of HepG2 cells.
2009, 16(6):614-618.
DOI: 10.3872/j.issn.1007-385X.2009.6.012
Abstract:
Objective:To study the inhibitory effect of :E1A: gene on the growth of tumors in nude mice implanted with nasopharygeal carcinoma CNE2 cells and its promotion effect on the radiosensitivity of CNE2implanted tumors, and to investigate the related mechanism. :Methods: ::E1A: gene was transfected into CNE2 cells using adenovirus system, and stable :E1A: positive clones were established. The inhibitory effect of :E1A: on tumor formationability of CNE2 cells was observed in nude mice. The efficacy of :E1A: gene therapy with or without radiotherapy against CNE2 cellimplanted tumors was evaluated. The effect of :E1A: gene therapy on the expression of :P53: was detected by RTPCR. :Results: :CNE2 cells stably transfected with :E1A: gene (CNE2AdE1A）were successfully established. The tumor formation time was later and tumor size was smaller in CNE2AdE1A cellimplanted mice compared with those in CNE2 cell and CNE2Adβgal cellimplanted mice (CNE2 cells stably transfected with Adβgal). Radiotherapy, :E1A: gene therapy and :E1A: gene+radiotherapy all suppressed the growth of implanted tumors, with the tumor suppression rates being (60.32±5.34)%, (7053±6.12)%, and (97.15±4.87)%, respectively. :E1A: gene therapy significantly increased the expression of :P53 : gene in tumor tissues. :Conclusion: ::E1A: can inhibit the growth of tumors in mice implanted with nasopharygeal carcinoma cells, and enhance its sensitivity to radiotherapy, which may be related to the increased expression of :P53: gene in tumor tissues.
Objective:To study the inhibitory effect of :E1A: gene on the growth of tumors in nude mice implanted with nasopharygeal carcinoma CNE2 cells and its promotion effect on the radiosensitivity of CNE2implanted tumors, and to investigate the related mechanism. :Methods: ::E1A: gene was transfected into CNE2 cells using adenovirus system, and stable :E1A: positive clones were established. The inhibitory effect of :E1A: on tumor formationability of CNE2 cells was observed in nude mice. The efficacy of :E1A: gene therapy with or without radiotherapy against CNE2 cellimplanted tumors was evaluated. The effect of :E1A: gene therapy on the expression of :P53: was detected by RTPCR. :Results: :CNE2 cells stably transfected with :E1A: gene (CNE2AdE1A）were successfully established. The tumor formation time was later and tumor size was smaller in CNE2AdE1A cellimplanted mice compared with those in CNE2 cell and CNE2Adβgal cellimplanted mice (CNE2 cells stably transfected with Adβgal). Radiotherapy, :E1A: gene therapy and :E1A: gene+radiotherapy all suppressed the growth of implanted tumors, with the tumor suppression rates being (60.32±5.34)%, (7053±6.12)%, and (97.15±4.87)%, respectively. :E1A: gene therapy significantly increased the expression of :P53 : gene in tumor tissues. :Conclusion: ::E1A: can inhibit the growth of tumors in mice implanted with nasopharygeal carcinoma cells, and enhance its sensitivity to radiotherapy, which may be related to the increased expression of :P53: gene in tumor tissues.
13 Effect of EGFRtargeted interference RNA on apoptosis of multidrugresistant ovarian cancer cells
2009, 16(6):619-623.
DOI: 10.3872/j.issn.1007-385X.2009.6.013
Abstract:
Objective:To investigate the effect of RNAmediated interference EGFR (epidermal growth factor receptor) expression on the apoptosis of multidrugresisitant ovarian cancer cell line SKOV3/DDP. :Methods: :Small hairpin RNA (shRNA) targeting EGFR was synthesized and recombinant plasmid containing pEGFRshRNA was constructed. pEGFRshRNA was tansfected into SKOV3/DDP cells by liposome system, untransfected cells and SKOV3/DDP cells tansfected with nonspecificshRNA (CtrlshRNA) were used as control. Expression of EGFR mRNA and protein in SKOV3/DDP cells was examined by RTPCR and immunocytochemistry after transfection, respectively. The apopototic rates and cell cycles of SKOV3/DDP cells were detected by flow cytometry. :Results: :Compared with CtrlshRNAtransfected cells, the expression of EGFR mRNA and protein in pEGFRshRNAtransfected SKOV3/DDP cells was significantly inhibited. Flow cytometry results showed that cell cycle distribution in pEGFRshRNAtransfected SKOV3/DDP cells was dramatically changed, and the apoptosis rate was significantly increased after further treatment with cisplatin for 24 h. :Conclusion: :EGFRtargeted interference RNA can inhibit the expression of EGFR in SKOV3/DDP cells, thereby regulating the cell cycle and increasing apoptosis of multidrugresistant SKOV3/DDP cells.
Objective:To investigate the effect of RNAmediated interference EGFR (epidermal growth factor receptor) expression on the apoptosis of multidrugresisitant ovarian cancer cell line SKOV3/DDP. :Methods: :Small hairpin RNA (shRNA) targeting EGFR was synthesized and recombinant plasmid containing pEGFRshRNA was constructed. pEGFRshRNA was tansfected into SKOV3/DDP cells by liposome system, untransfected cells and SKOV3/DDP cells tansfected with nonspecificshRNA (CtrlshRNA) were used as control. Expression of EGFR mRNA and protein in SKOV3/DDP cells was examined by RTPCR and immunocytochemistry after transfection, respectively. The apopototic rates and cell cycles of SKOV3/DDP cells were detected by flow cytometry. :Results: :Compared with CtrlshRNAtransfected cells, the expression of EGFR mRNA and protein in pEGFRshRNAtransfected SKOV3/DDP cells was significantly inhibited. Flow cytometry results showed that cell cycle distribution in pEGFRshRNAtransfected SKOV3/DDP cells was dramatically changed, and the apoptosis rate was significantly increased after further treatment with cisplatin for 24 h. :Conclusion: :EGFRtargeted interference RNA can inhibit the expression of EGFR in SKOV3/DDP cells, thereby regulating the cell cycle and increasing apoptosis of multidrugresistant SKOV3/DDP cells.
2009, 16(6):624-628.
DOI: 10.3872/j.issn.1007-385X.2009.6.014
Abstract:
Objective:To prepare autotumorspecific cytotoxicity T lymphocytes (CTLs) of breast cancer patients and to observe their therapeutic effects on bone marrow micrometastasis (BMM) of breast cancer. :Methods: :BMM in 82 patients with primary breast cancer (stage Ⅰto Ⅲ) , who were treated in the Fourth Affiliated Hospital of Hebei Medical University from March to December in 2007 (all the patients signed paper of informed consent), was exmined by flow cytometry using CK18 and CK19 as marker. Twentythree patients with BMM were randomly divided into two groups: 17 patients were treated with tumorspecific CTLs (therapy group), and 6 patients were treated with IL2 (control group). Tumorspecific CTLs were induced in vitro from axillary lymph nodes and peripheral blood of breast cancer patients in therapy group, and were reinfused into the same patient 1014 days after operation. The therapeutic effects of tumorspecific CTLs on BMM of breast cancer patients were observed. :Results: :Twentythree cases (28.05%) in 82 breast cancer patients were BMM positive as detected by FCM. BMM positive rates increased with the increase of clinical TNM stages and histological grades of breast cancer, and decreased with the increase of ER and PR protein expression in cancer tissues. Dendritic cells (DCs) were successfully isolated and induced from the peripheral blood of breast cancer patients. Tumorspecific CTLs were induced by coculturing lymphocytes from axillarey lymph nodes with autotumor antigenimpulsed DCs. Fourteen cases in the therapy group became negative of BMM after treatment with tumorspecific CTLs (14/19, 8235%). Only one case in the control group became negative of BMM after treatment with IL2 (1/6, 16.67%,〖HTSS〗:P=000028).: :Conclusion: :Tumorspecific CTLs have been successfully prepared and they show a satisfactory therapeutic effect on bone marrow micrometastasis of breast cancer.
Objective:To prepare autotumorspecific cytotoxicity T lymphocytes (CTLs) of breast cancer patients and to observe their therapeutic effects on bone marrow micrometastasis (BMM) of breast cancer. :Methods: :BMM in 82 patients with primary breast cancer (stage Ⅰto Ⅲ) , who were treated in the Fourth Affiliated Hospital of Hebei Medical University from March to December in 2007 (all the patients signed paper of informed consent), was exmined by flow cytometry using CK18 and CK19 as marker. Twentythree patients with BMM were randomly divided into two groups: 17 patients were treated with tumorspecific CTLs (therapy group), and 6 patients were treated with IL2 (control group). Tumorspecific CTLs were induced in vitro from axillary lymph nodes and peripheral blood of breast cancer patients in therapy group, and were reinfused into the same patient 1014 days after operation. The therapeutic effects of tumorspecific CTLs on BMM of breast cancer patients were observed. :Results: :Twentythree cases (28.05%) in 82 breast cancer patients were BMM positive as detected by FCM. BMM positive rates increased with the increase of clinical TNM stages and histological grades of breast cancer, and decreased with the increase of ER and PR protein expression in cancer tissues. Dendritic cells (DCs) were successfully isolated and induced from the peripheral blood of breast cancer patients. Tumorspecific CTLs were induced by coculturing lymphocytes from axillarey lymph nodes with autotumor antigenimpulsed DCs. Fourteen cases in the therapy group became negative of BMM after treatment with tumorspecific CTLs (14/19, 8235%). Only one case in the control group became negative of BMM after treatment with IL2 (1/6, 16.67%,〖HTSS〗:P=000028).: :Conclusion: :Tumorspecific CTLs have been successfully prepared and they show a satisfactory therapeutic effect on bone marrow micrometastasis of breast cancer.
2009, 16(6):629-632.
DOI: 10.3872/j.issn.1007-385X.2009.6.015
Abstract:
Objective:To investigate the expression of Oct4 and Wnt2 in human glioma tissues and its relationship with the clinicopathological features of glioma. :Methods: :Fiftysix paraffin blocks were obtained from glioma patients receiving surgery. The diagnosis of these patients were confirmed by pathology in our hospital from 20062009. Immunohistochemical staining was used to examine Oct4 and Wnt2 expression in the brain tissues of 10 patients with acute brain injury and 56 glioma tissues (including 15 recurrent cases). :Results: :The normal brain tissues were negative of Oct4, with only one case showing weak Wnt2 expression. Thirtyfour of the 56 glioma tissues showed positive expression of Oct4 (60.7%), and 40 showed positive expression of Wnt2 (71.4%). Positive expression rates of Oct4 and Wnt2 in lowgrade and highgrade glioma tissues were 46.2 %, 73.3% and 57.7 %, 83.3%, respectively (P<0.05). Oct4 positive rates in the recrudescence and newly diagnosed glioma tissues were 86.7% and 51.2%, respectively (P<0.05). Oct4 expression in the glioma tissues was positively correlated with that of Wnt2 (r=0.537，P<0.01). :Conclusion: :Expression of Oct4 and Wnt2 is associated with the malignant degrees of glioma, and Oct4 expression is related to the recurrence of glioma. Oct4 might participate in the development and progression of brain glioma through Wnt signaling pathway.
Objective:To investigate the expression of Oct4 and Wnt2 in human glioma tissues and its relationship with the clinicopathological features of glioma. :Methods: :Fiftysix paraffin blocks were obtained from glioma patients receiving surgery. The diagnosis of these patients were confirmed by pathology in our hospital from 20062009. Immunohistochemical staining was used to examine Oct4 and Wnt2 expression in the brain tissues of 10 patients with acute brain injury and 56 glioma tissues (including 15 recurrent cases). :Results: :The normal brain tissues were negative of Oct4, with only one case showing weak Wnt2 expression. Thirtyfour of the 56 glioma tissues showed positive expression of Oct4 (60.7%), and 40 showed positive expression of Wnt2 (71.4%). Positive expression rates of Oct4 and Wnt2 in lowgrade and highgrade glioma tissues were 46.2 %, 73.3% and 57.7 %, 83.3%, respectively (P<0.05). Oct4 positive rates in the recrudescence and newly diagnosed glioma tissues were 86.7% and 51.2%, respectively (P<0.05). Oct4 expression in the glioma tissues was positively correlated with that of Wnt2 (r=0.537，P<0.01). :Conclusion: :Expression of Oct4 and Wnt2 is associated with the malignant degrees of glioma, and Oct4 expression is related to the recurrence of glioma. Oct4 might participate in the development and progression of brain glioma through Wnt signaling pathway.
2009, 16(6):633-636.
DOI: 10.3872/j.issn.1007-385X.2009.6.016
Abstract:
Objective: To study the expression of negative costimulatroy molecule B7H4 in nonsmall cell lung cancer (NSCLC) tissues and its relationship with the clinical features of NSCLC. :Methods: :Fiftytwo NSCLC specimens from patients who were pathologically diagnosed in our hospital during January 2008 to April 2009 were included in the present study. B7H4 expression and infiltration of CD3+T cells in NSCLC tissues were detected by immunohistochemistry. The correlation between B7H4 expression, CD3+T infiltration, and the clinical features of NSCLC was studied. :Results:: The positive rate of B7H4 in 52 NSCLC tissues was 48.08% (25/52), and B7H4 expression in normal lung tissues was negative or low (P<0.05). B7H4 expression was positively correlated with the clinical tumor stages and lymph node metastasis of NSCLC (P<0.05), and negatively correlated with tumor infiltration of CD3+T cells (P<0.05), but had no relationship with clinicopathologic parameters of NSCLC (P>0.05). :Conclusion: :Negative costimulatroy molecule B7H4 may play important roles in the development of NSCLC. Positive expression of B7H4 is correlated with the clinical tumor stages and lymph node metastasis of NSCLC, which provides a foundation for diagnosis and therapy of NSCLC.
Objective: To study the expression of negative costimulatroy molecule B7H4 in nonsmall cell lung cancer (NSCLC) tissues and its relationship with the clinical features of NSCLC. :Methods: :Fiftytwo NSCLC specimens from patients who were pathologically diagnosed in our hospital during January 2008 to April 2009 were included in the present study. B7H4 expression and infiltration of CD3+T cells in NSCLC tissues were detected by immunohistochemistry. The correlation between B7H4 expression, CD3+T infiltration, and the clinical features of NSCLC was studied. :Results:: The positive rate of B7H4 in 52 NSCLC tissues was 48.08% (25/52), and B7H4 expression in normal lung tissues was negative or low (P<0.05). B7H4 expression was positively correlated with the clinical tumor stages and lymph node metastasis of NSCLC (P<0.05), and negatively correlated with tumor infiltration of CD3+T cells (P<0.05), but had no relationship with clinicopathologic parameters of NSCLC (P>0.05). :Conclusion: :Negative costimulatroy molecule B7H4 may play important roles in the development of NSCLC. Positive expression of B7H4 is correlated with the clinical tumor stages and lymph node metastasis of NSCLC, which provides a foundation for diagnosis and therapy of NSCLC.
17 Therapeutic effect of local rmhTNF plus cisplatin inoculation on patients with malignant effusion
2009, 16(6):637-639.
DOI: 10.3872/j.issn.1007-385X.2009.6.017
Abstract:
目的：观察重组改构肿瘤坏死因子（recombinant mutant human tumor necrosis factor，rmhTNF）联合顺铂治疗恶性腹腔积液的疗效和不良反应。方法：回顾分析2005年至2008年上海长海医院肿瘤科54例大至中量恶性腹腔积水患者，在尽量排尽腹腔积液后用rmhTNF联合顺铂注入腹腔进行治疗，观察疗效；观察病例年龄、性别、癌症类别等因素对疗效的影响。结果：54例恶性腹腔积液患者中，明显疗效 23例，有效 28例，无效3例，总有效率为94.4%。生活质量提高并完成化疗者32例，2例因病期较晚死亡。在单因素分析中，rmhTNF联合顺铂治疗对不同年龄、性别等病例的疗效无明显差异，而肿瘤组织类型、KPS评分和腹水积液量对治疗效果影响明显。结论：rmhTNF联合顺铂腹腔注入治疗恶性腹腔积液疗效可靠，可使患者生活质量明显提高，无明显不良反应，是治疗恶性腹腔积液的有效手段之一，尤其适用于不能耐受全身静脉化疗的恶性腹腔积液患者。
目的：观察重组改构肿瘤坏死因子（recombinant mutant human tumor necrosis factor，rmhTNF）联合顺铂治疗恶性腹腔积液的疗效和不良反应。方法：回顾分析2005年至2008年上海长海医院肿瘤科54例大至中量恶性腹腔积水患者，在尽量排尽腹腔积液后用rmhTNF联合顺铂注入腹腔进行治疗，观察疗效；观察病例年龄、性别、癌症类别等因素对疗效的影响。结果：54例恶性腹腔积液患者中，明显疗效 23例，有效 28例，无效3例，总有效率为94.4%。生活质量提高并完成化疗者32例，2例因病期较晚死亡。在单因素分析中，rmhTNF联合顺铂治疗对不同年龄、性别等病例的疗效无明显差异，而肿瘤组织类型、KPS评分和腹水积液量对治疗效果影响明显。结论：rmhTNF联合顺铂腹腔注入治疗恶性腹腔积液疗效可靠，可使患者生活质量明显提高，无明显不良反应，是治疗恶性腹腔积液的有效手段之一，尤其适用于不能耐受全身静脉化疗的恶性腹腔积液患者。
2009, 16(6):640-643.
DOI: 10.3872/j.issn.1007-385X.2009.6.018
Abstract:
肿瘤干细胞是肿瘤治疗的重要途径，而其干细胞特性的维持机制还不明确。近来在多种肿瘤如白血病、肝癌、乳腺癌、大肠癌、皮肤癌、前列腺癌及精原细胞瘤的研究中发现，Wnt信号转导途径激活后，肿瘤干细胞数量增加，侵袭性、耐药性增强，自我更新及体内致瘤能力增强。而在恶性黑素瘤的研究中却发现Wnt信号转导途径的活化使肿瘤细胞的增殖能力降低，分化程度增高，体内成瘤能力降低。Wnt信号转导途径在维持肿瘤干细胞的干细胞特性方面有着重要作用，所以以Wnt信号转导途径为靶点，破坏肿瘤干细胞的干细胞特性，从而消灭肿瘤干细胞不失为治疗肿瘤的一个重要策略。
肿瘤干细胞是肿瘤治疗的重要途径，而其干细胞特性的维持机制还不明确。近来在多种肿瘤如白血病、肝癌、乳腺癌、大肠癌、皮肤癌、前列腺癌及精原细胞瘤的研究中发现，Wnt信号转导途径激活后，肿瘤干细胞数量增加，侵袭性、耐药性增强，自我更新及体内致瘤能力增强。而在恶性黑素瘤的研究中却发现Wnt信号转导途径的活化使肿瘤细胞的增殖能力降低，分化程度增高，体内成瘤能力降低。Wnt信号转导途径在维持肿瘤干细胞的干细胞特性方面有着重要作用，所以以Wnt信号转导途径为靶点，破坏肿瘤干细胞的干细胞特性，从而消灭肿瘤干细胞不失为治疗肿瘤的一个重要策略。
2009, 16(6):644-647.
DOI: 10.3872/j.issn.1007-385X.2009.6.019
Abstract:
随着肿瘤免疫学的不断发展，肿瘤疫苗已成为肿瘤免疫治疗研究的热点。目前，肿瘤细胞疫苗在多项临床试验中的效果较为明显，在患者体内可检测出有意义的免疫应答反应, 且患者有很好的耐受性；基因疫苗在动物实验和临床试验中显示出靶向性和充分激活抗肿瘤免疫等优点；肿瘤多肽疫苗，因其化学性质稳定、易于制备、无潜在致癌性等优点, 更是受到广泛关注；以现代分子生物学技术将肿瘤细胞、裂解的肿瘤细胞成分或肿瘤细胞的凋亡产物、肿瘤mRNA或DNA等修饰树突状细胞制成瘤苗, 则为肿瘤治疗开辟了一种新的途径；细胞毒性T淋巴细胞表位肽疫苗通过在体内、外激发特异性CTL抗肿瘤免疫应答, 部分多肽表位疫苗已进入临床Ⅰ期和Ⅱ期试验, 并取得较好的疗效。本文将对这些肿瘤疫苗的作用特点、研究进展及应用现状作一综述。
随着肿瘤免疫学的不断发展，肿瘤疫苗已成为肿瘤免疫治疗研究的热点。目前，肿瘤细胞疫苗在多项临床试验中的效果较为明显，在患者体内可检测出有意义的免疫应答反应, 且患者有很好的耐受性；基因疫苗在动物实验和临床试验中显示出靶向性和充分激活抗肿瘤免疫等优点；肿瘤多肽疫苗，因其化学性质稳定、易于制备、无潜在致癌性等优点, 更是受到广泛关注；以现代分子生物学技术将肿瘤细胞、裂解的肿瘤细胞成分或肿瘤细胞的凋亡产物、肿瘤mRNA或DNA等修饰树突状细胞制成瘤苗, 则为肿瘤治疗开辟了一种新的途径；细胞毒性T淋巴细胞表位肽疫苗通过在体内、外激发特异性CTL抗肿瘤免疫应答, 部分多肽表位疫苗已进入临床Ⅰ期和Ⅱ期试验, 并取得较好的疗效。本文将对这些肿瘤疫苗的作用特点、研究进展及应用现状作一综述。
2009, 16(6):648-651.
DOI: 10.3872/j.issn.1007-385X.2009.6.020
Abstract:
溶酶体组织蛋白酶参与细胞凋亡的功能日益受到重视。目前研究认为，组织蛋白酶参与细胞凋亡的机制可能涉及三个方面：第一，通过死亡受体途径和线粒体等经典途径参与细胞凋亡；第二，通过炎症介质，部分炎症细胞等炎症反应参与细胞凋亡；第三，通过反向阻止生存信号途径活化了凋亡信号通路，从而参与细胞的凋亡。不过有部分学者认为溶酶体介导的细胞损伤可能是一种新的死亡方式或新的机制。总之，对组织蛋白酶的抑制可以明显减少细胞的死亡和损伤，随着研究的深入，溶酶体可能为肿瘤等疾病的诊治提供新的靶点。
溶酶体组织蛋白酶参与细胞凋亡的功能日益受到重视。目前研究认为，组织蛋白酶参与细胞凋亡的机制可能涉及三个方面：第一，通过死亡受体途径和线粒体等经典途径参与细胞凋亡；第二，通过炎症介质，部分炎症细胞等炎症反应参与细胞凋亡；第三，通过反向阻止生存信号途径活化了凋亡信号通路，从而参与细胞的凋亡。不过有部分学者认为溶酶体介导的细胞损伤可能是一种新的死亡方式或新的机制。总之，对组织蛋白酶的抑制可以明显减少细胞的死亡和损伤，随着研究的深入，溶酶体可能为肿瘤等疾病的诊治提供新的靶点。
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- 《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
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- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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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.