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Volume 15,Issue 5,2008 Table of Contents
2008, 15(5):401-405.
DOI: 10.3872/j.issn.1007-385X.2008.5.001
Abstract:
Nanomaterials, endowed with unique properties, bring new chance for early diagnosis and therapy of tumors and show a bright future. In recent years, research in in vitro detection techniques of nanoparticlebased early tumor biomarkers, in vivo dynamic multimodel molecular imaging techniques, nanoscale effects of nanopartilcebased nanoimaging and treatment integrated technology, nanoscale slowrelease drugs, and nanoscale drug delivery devices has made great progress. However, the long term interaction between nanomaterials and human body still remains poorly understood, the application of nanoscale therapy technology in clinical medicine still faces new challenges. In this paper, we review the main advances of tumor nanoscale diagnosis and therapy, with the aim to improve the development of tumor nanoscale diagnosis and therapy technology in China.
Nanomaterials, endowed with unique properties, bring new chance for early diagnosis and therapy of tumors and show a bright future. In recent years, research in in vitro detection techniques of nanoparticlebased early tumor biomarkers, in vivo dynamic multimodel molecular imaging techniques, nanoscale effects of nanopartilcebased nanoimaging and treatment integrated technology, nanoscale slowrelease drugs, and nanoscale drug delivery devices has made great progress. However, the long term interaction between nanomaterials and human body still remains poorly understood, the application of nanoscale therapy technology in clinical medicine still faces new challenges. In this paper, we review the main advances of tumor nanoscale diagnosis and therapy, with the aim to improve the development of tumor nanoscale diagnosis and therapy technology in China.
HAN Yuedong
,
CUI Daxiang
,
HUAN Yi
,
LI Zhiming
,
LIU Heliang
,
SONG Hua
,
LIU Bing
,
DU Tong
,
GAO Feng
,
HE Rong
2008, 15(5):406-411.
DOI: 10.3872/j.issn.1007-385X.2008.5.002
Abstract:
Abstract Objective: To investigate the feasibility of targeted imaging and therapy of prostate cancer using nanocomposite probes composed of fluorescent magnetic nanoparticles (FMCNPs) and single chain Fv (ScFv) antibody specific for gamaseminoprotein. Methods: The nanocomposite probes (FMCNPsScFv) were prepared by conjugating fluorescent magnetic nanoparticles with singlegamachain Fv antibody specific gamaseminoprotein, and were characterized by high resolution transmission electron microscopy, fluorescent spectrum and magnetic spectrum. Nanocomposite probes were incubated with prostate cancer LNCaP cells, and the targeting results of nanocomposite probes were observed by fluorescent microscopy. The cytotoxicity effect of the nanocomposite probes was measured by MTT. Nude mice models of prostate cancer were established and identified by immunohistochemistry method. The nanocomposite probes were injected into nude mice via tail vein. The distribution of nanocomposite probes in the nude mice was observed by Microanimal imaging system, targeted imaging of the prostate cancer was observed by MR instrument. The nude mice with prostate cancer were irradiated with 100 W magnetic field for 30 min, and the changes of tumor sizes were observed. Results: The FMCNPsScFv nanocomposite probes were successfully prepared. Nanocomposite probes entered into the cytoplasm of cancer cells and exhibited low cytotoxicity effect. Nude mice model with prostate cancer were successfully fabricated; the nanocomposite probes distributed quickly in the main organs of mice, and gradually concentrated on the tumor tissues within 24 h. MR images showed that the tumor images were gradually enhanced from 6 h to 24 h after injection of the nanocomposite probe. Four days after magnetic irradiation, the tumors in the nude mice grew slower compared with the control nude mice (P<0.05).Conclusion:The nanocomposite probes composed of FMCNPs and ScFv antibody can be used for targeted imaging of prostate cancer by MRI instrument and for therapy under in vitro magnetic field.
Abstract Objective: To investigate the feasibility of targeted imaging and therapy of prostate cancer using nanocomposite probes composed of fluorescent magnetic nanoparticles (FMCNPs) and single chain Fv (ScFv) antibody specific for gamaseminoprotein. Methods: The nanocomposite probes (FMCNPsScFv) were prepared by conjugating fluorescent magnetic nanoparticles with singlegamachain Fv antibody specific gamaseminoprotein, and were characterized by high resolution transmission electron microscopy, fluorescent spectrum and magnetic spectrum. Nanocomposite probes were incubated with prostate cancer LNCaP cells, and the targeting results of nanocomposite probes were observed by fluorescent microscopy. The cytotoxicity effect of the nanocomposite probes was measured by MTT. Nude mice models of prostate cancer were established and identified by immunohistochemistry method. The nanocomposite probes were injected into nude mice via tail vein. The distribution of nanocomposite probes in the nude mice was observed by Microanimal imaging system, targeted imaging of the prostate cancer was observed by MR instrument. The nude mice with prostate cancer were irradiated with 100 W magnetic field for 30 min, and the changes of tumor sizes were observed. Results: The FMCNPsScFv nanocomposite probes were successfully prepared. Nanocomposite probes entered into the cytoplasm of cancer cells and exhibited low cytotoxicity effect. Nude mice model with prostate cancer were successfully fabricated; the nanocomposite probes distributed quickly in the main organs of mice, and gradually concentrated on the tumor tissues within 24 h. MR images showed that the tumor images were gradually enhanced from 6 h to 24 h after injection of the nanocomposite probe. Four days after magnetic irradiation, the tumors in the nude mice grew slower compared with the control nude mice (P<0.05).Conclusion:The nanocomposite probes composed of FMCNPs and ScFv antibody can be used for targeted imaging of prostate cancer by MRI instrument and for therapy under in vitro magnetic field.
2008, 15(5):412-416.
DOI: 10.3872/j.issn.1007-385X.2008.5.003
Abstract:
Abstract Objective: Previous genomewide microarray analysis found TTCATTCT motif （DNA binding site of Runx1）in the RPL4 promoter of childhood leukemia cells, suggesting that Runx1 may regulate the expression of RPL4. This study is to investigate the relationship between Runx1 and RPL4 so as to better understand the effects of Runx1 on RPL4 gene transcription, laying a foundation for further studying leukemogenesis of childhood leukemia. Methods: The luciferase plasmids containing RPL4 promoter and its mutant were constructed and were cotransfected into 293T cells with the expression plasmid of Runx1. The transactivity of RPL4 promoter was assayed by luminometer. Results: Runx1 significantly decreased the transcriptional activity of RPL4 promoter (P<0.01), and the decreasing degree was associated with the increase of Runx1 dose (P<0.01). Runx1 protein had no significant effect on the transcriptional activity of RPL4 promoter mutant (P>0.05). Conclusion: Runx1 can inhibit RPL4 gene transcription in a dosedependent manner through binding to the TTCATTCT motif.
Abstract Objective: Previous genomewide microarray analysis found TTCATTCT motif （DNA binding site of Runx1）in the RPL4 promoter of childhood leukemia cells, suggesting that Runx1 may regulate the expression of RPL4. This study is to investigate the relationship between Runx1 and RPL4 so as to better understand the effects of Runx1 on RPL4 gene transcription, laying a foundation for further studying leukemogenesis of childhood leukemia. Methods: The luciferase plasmids containing RPL4 promoter and its mutant were constructed and were cotransfected into 293T cells with the expression plasmid of Runx1. The transactivity of RPL4 promoter was assayed by luminometer. Results: Runx1 significantly decreased the transcriptional activity of RPL4 promoter (P<0.01), and the decreasing degree was associated with the increase of Runx1 dose (P<0.01). Runx1 protein had no significant effect on the transcriptional activity of RPL4 promoter mutant (P>0.05). Conclusion: Runx1 can inhibit RPL4 gene transcription in a dosedependent manner through binding to the TTCATTCT motif.
2008, 15(5):417-421.
DOI: 10.3872/j.issn.1007-385X.2008.5.004
Abstract:
Abstract Objective: To investigate the effect of human microRNA10a(miR10a) on the migration and invasion of gastric cancer cell line BGC823. Methods: The Transwell system was used to select highly invasive subcell lines from gastric cancer cell line BGC823. Using miRNA microchip, we compared the miRNA expression in paired cell lines with high and low invasive potentials. MiR10a was relatively overexpressed in the highly invasive cell lines when compared with its counterpart. The mature type human miR10a was synthesized chemically. The synthesized miR10a（25, 50, 100, and 150 nmol/L）was transfected into BGC823 cells via lipofectamin 2000. Cells were also transfected with empty vectors and unrelated fragment to serve as controls. The expression of mature type miR10a was detected by realtime PCR. Cell counting kit8 was used to study the effect of miR10a on the proliferation of BGC823 cells. Flow cytometry was performed to detect the effect of miR10a on the apoptosis of BGC823 cells. The migration and invasion of BGC823 cells were investigated by Transwell assay. Results: Realtime PCR showed that cells transfected with mature type miR10a had significantly higher expression of miR10a, with the optimal concentration of miR10a being 100 nmol/L; the associated miR10a expression was 2.06 folds that of unrelated group. miR10a (100 nmol/L) had no obvious influence on the proliferation and apoptosis of BGC823 cells; however, it promoted the migration and invasion of BGC823 cells, with the promoting rates being (88.34±0.61)% and (56.02±3.13)%, respectively. Conclusion: Synthesized mature type human miR10a can effectively enhance miR10a expression and promote the migration and invasion of the BGC823 cells.
Abstract Objective: To investigate the effect of human microRNA10a(miR10a) on the migration and invasion of gastric cancer cell line BGC823. Methods: The Transwell system was used to select highly invasive subcell lines from gastric cancer cell line BGC823. Using miRNA microchip, we compared the miRNA expression in paired cell lines with high and low invasive potentials. MiR10a was relatively overexpressed in the highly invasive cell lines when compared with its counterpart. The mature type human miR10a was synthesized chemically. The synthesized miR10a（25, 50, 100, and 150 nmol/L）was transfected into BGC823 cells via lipofectamin 2000. Cells were also transfected with empty vectors and unrelated fragment to serve as controls. The expression of mature type miR10a was detected by realtime PCR. Cell counting kit8 was used to study the effect of miR10a on the proliferation of BGC823 cells. Flow cytometry was performed to detect the effect of miR10a on the apoptosis of BGC823 cells. The migration and invasion of BGC823 cells were investigated by Transwell assay. Results: Realtime PCR showed that cells transfected with mature type miR10a had significantly higher expression of miR10a, with the optimal concentration of miR10a being 100 nmol/L; the associated miR10a expression was 2.06 folds that of unrelated group. miR10a (100 nmol/L) had no obvious influence on the proliferation and apoptosis of BGC823 cells; however, it promoted the migration and invasion of BGC823 cells, with the promoting rates being (88.34±0.61)% and (56.02±3.13)%, respectively. Conclusion: Synthesized mature type human miR10a can effectively enhance miR10a expression and promote the migration and invasion of the BGC823 cells.
2008, 15(5):422-427.
DOI: 10.3872/j.issn.1007-385X.2008.5.005
Abstract:
Abstract Objective: To explore the inhibitory effect of human melanoma differentiation associated gene7 (mda7/IL24) on chronic myelocytic leukemia cell line K562 in vitro and in vivo.Methods: The expression of mda7〖STBZ〗 receptor was examined in 11 malignant hematopoietic cell lines（NB4, HL60, CEM, Namalwa, Jurkat, KG1a, U937, K562, Ramos, J61, and HEL） by RTPCR. Then the constructed pTargetIL24 eukaryotic expression vector was transduced into K562 cells via Lipofectamine reagent. The expression of mda7 mRNA and protein was verified by RTPCR and Western blotting. MTT assay, colony forming assay, flow cytometry, AnnexinⅤ/PI and xenograft tumor models in nude mice were used to assess the effects of mda7 on tumor cells proliferation, colony forming, cell cycle, apoptosis, and tumorigenesis, respectively. Results: The expression of mda7 intact receptor was not detected in the 11 malignant hematopoietic cell lines. Significant expression of mda7 mRNA and protein was found in K562 cells stably transfected with mda7. Compared with control cells transfected with plasmid vector or untransfected cells, cells transfected with mda7had decreased tumor cells proliferation (P<0.05), inhibited colony formation (P<0.05), and more cells were arrested in G0/G1 stage (P<0.05). However, there was no significant difference in cells apoptosis between control cells and K562 cells transfected with mda7. Tumor xenograft models in BALB/c nude mice showed that mda7/IL24 significantly inhibited the growth of K562 transplantation tumor (P<0.01). Conclusion: Human mda7/IL24 can efficiently inhibit the proliferation of chronic myelocytic leukemia cell line K562 in vitro and in vivo, possibly by inducing K562 cell arrest in G0/G1 stage.
Abstract Objective: To explore the inhibitory effect of human melanoma differentiation associated gene7 (mda7/IL24) on chronic myelocytic leukemia cell line K562 in vitro and in vivo.Methods: The expression of mda7〖STBZ〗 receptor was examined in 11 malignant hematopoietic cell lines（NB4, HL60, CEM, Namalwa, Jurkat, KG1a, U937, K562, Ramos, J61, and HEL） by RTPCR. Then the constructed pTargetIL24 eukaryotic expression vector was transduced into K562 cells via Lipofectamine reagent. The expression of mda7 mRNA and protein was verified by RTPCR and Western blotting. MTT assay, colony forming assay, flow cytometry, AnnexinⅤ/PI and xenograft tumor models in nude mice were used to assess the effects of mda7 on tumor cells proliferation, colony forming, cell cycle, apoptosis, and tumorigenesis, respectively. Results: The expression of mda7 intact receptor was not detected in the 11 malignant hematopoietic cell lines. Significant expression of mda7 mRNA and protein was found in K562 cells stably transfected with mda7. Compared with control cells transfected with plasmid vector or untransfected cells, cells transfected with mda7had decreased tumor cells proliferation (P<0.05), inhibited colony formation (P<0.05), and more cells were arrested in G0/G1 stage (P<0.05). However, there was no significant difference in cells apoptosis between control cells and K562 cells transfected with mda7. Tumor xenograft models in BALB/c nude mice showed that mda7/IL24 significantly inhibited the growth of K562 transplantation tumor (P<0.01). Conclusion: Human mda7/IL24 can efficiently inhibit the proliferation of chronic myelocytic leukemia cell line K562 in vitro and in vivo, possibly by inducing K562 cell arrest in G0/G1 stage.
2008, 15(5):428-432.
DOI: 10.3872/j.issn.1007-385X.2008.5.006
Abstract:
Abstract Objective: To explore 5fluorouracilinduced regulating effect of Egr1 promoter on expression of granulocytemacrophage colonystimulating factor (GM-CSF) in human bone marrow stromal cells. Methods:The human GMCSF cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with IRES and then inserted into the expression vector pCIneo under control of the Egr1 promoter(Egr-EG). The vector was then transferred into human bone marrow stromal cell line HFCL by lipofection. The transfected cell clones (HFCL/EG) were selected by the addition of G418. The cells were exposed to the anticancer agent 5-fluorouracil (5-FU). The activity of EGFP in HFCL/EG cells were detected by FACS. The amounts of GMCSF in HFCL/EG postchemotherapy were determined with ELISA. The effects of GMCSF in HFCL/EG cultural supernatants on expansion of CFU-GM derived from cord blood were also studied. The effect of N-acetylcysteine (a free radical scavenger) on GM-CSF production was examined following exposure to 5FU. Results: We successfully constructed vector EgrEG with Egr-1 promoter, and its transfectant HFCL/EG was obtained. The results indicated that the activity of EGFP and the amounts of secreted GMCSF in HFCL/EG cells exposed to 5-FU were increased compared to non5-FU group. The content of GM-CSF in HFCL/EG cultural supernatants was significantly higher than that in the non5-FU group (P<0.01). N-acetylcysteine significantly decreased the content of GM-CSF produced by HFCL/EG treated with 5-FU (P<0.01). Conclusion: 5-FU can enhance Egr-1 upregulate GM-CSF expression in human bone marrow stromal cells, and thus contribute to the recovery of hematopoietic function after chemotherapy.
Abstract Objective: To explore 5fluorouracilinduced regulating effect of Egr1 promoter on expression of granulocytemacrophage colonystimulating factor (GM-CSF) in human bone marrow stromal cells. Methods:The human GMCSF cDNA and enhanced green fluorescent protein (EGFP) cDNA were linked together with IRES and then inserted into the expression vector pCIneo under control of the Egr1 promoter(Egr-EG). The vector was then transferred into human bone marrow stromal cell line HFCL by lipofection. The transfected cell clones (HFCL/EG) were selected by the addition of G418. The cells were exposed to the anticancer agent 5-fluorouracil (5-FU). The activity of EGFP in HFCL/EG cells were detected by FACS. The amounts of GMCSF in HFCL/EG postchemotherapy were determined with ELISA. The effects of GMCSF in HFCL/EG cultural supernatants on expansion of CFU-GM derived from cord blood were also studied. The effect of N-acetylcysteine (a free radical scavenger) on GM-CSF production was examined following exposure to 5FU. Results: We successfully constructed vector EgrEG with Egr-1 promoter, and its transfectant HFCL/EG was obtained. The results indicated that the activity of EGFP and the amounts of secreted GMCSF in HFCL/EG cells exposed to 5-FU were increased compared to non5-FU group. The content of GM-CSF in HFCL/EG cultural supernatants was significantly higher than that in the non5-FU group (P<0.01). N-acetylcysteine significantly decreased the content of GM-CSF produced by HFCL/EG treated with 5-FU (P<0.01). Conclusion: 5-FU can enhance Egr-1 upregulate GM-CSF expression in human bone marrow stromal cells, and thus contribute to the recovery of hematopoietic function after chemotherapy.
2008, 15(5):433-439.
DOI: 10.3872/j.issn.1007-385X.2008.5.007
Abstract:
Abstract Objective: To study the role of adenoviralmediated PTEN gene transfection in reversing drug resistance of trastuzumabresistant human breast cancer. Methods: Recombinant adenoviruses carrying PTEN gene (AdPTEN) were constructed and transfected into trastuzumabresistant human breast cancer cell line BT474. Proliferation and apoptosis of BT474 cells treated with AdPTEN and trastuzumab were measured by MTT assay and FCM. Time course of BT474 cells apoptosis induced by AdPTEN was analyzed by detection of DNA fragmentation. Western blotting was employed to measure phosphorylatedAkt expression levels in AdPTEN treated BT474 cells. The nude mice model of BT474 cells was employed to observe the effects of AdPTEN and trastuzumab on trastuzumabresistant human breast cancer in vivo. The expression of PTEN gene, cancer cells apoptosis and ultrastructural changes were evaluated after the mice were sacrificed. Results: We successfully constructed recombinant AdPTEN; and the titer of the recombinant adenovirus was about 4.2×1011TCID50/ml. PTEN gene expression was identified by PCR, RTPCR and Western blotting assay. Combinatorial AdPTEN and trastuzumab significantly suppressed the proliferation of BT474 cells and induced the apoptosis. The percentage of apopotosis cells treated with AdPTEN was （20.7±5.82）% , companied by cells cycle arrest in G1 phrase (P＜0.01）. DNA of AdPTEN treated BT474 showed a typical DNA ladder at 24-36 h after infection. An obvious downregulation of phosphorylatedAkt expression level in cancer cells was identified by Western blotting. Tumor growth was inhibited in nude mice receiving injection of the recombinant adenoviruses when compared to control mice treated with AdLacZ (P＜0.01）. PTEN protein expression was confirmed by immunohistochemistry. Tumor cell apopotosis was detected by TUNEL and electron microscopy scanning. Conclusion: Our result suggests that PTEN protein can downregulate phosphorylatedAkt and Akt kinase activity, and block the activation of PI3K/Akt pathway, and subsequently reverse trastuzumab resistance and induce cell apoptosis.
Abstract Objective: To study the role of adenoviralmediated PTEN gene transfection in reversing drug resistance of trastuzumabresistant human breast cancer. Methods: Recombinant adenoviruses carrying PTEN gene (AdPTEN) were constructed and transfected into trastuzumabresistant human breast cancer cell line BT474. Proliferation and apoptosis of BT474 cells treated with AdPTEN and trastuzumab were measured by MTT assay and FCM. Time course of BT474 cells apoptosis induced by AdPTEN was analyzed by detection of DNA fragmentation. Western blotting was employed to measure phosphorylatedAkt expression levels in AdPTEN treated BT474 cells. The nude mice model of BT474 cells was employed to observe the effects of AdPTEN and trastuzumab on trastuzumabresistant human breast cancer in vivo. The expression of PTEN gene, cancer cells apoptosis and ultrastructural changes were evaluated after the mice were sacrificed. Results: We successfully constructed recombinant AdPTEN; and the titer of the recombinant adenovirus was about 4.2×1011TCID50/ml. PTEN gene expression was identified by PCR, RTPCR and Western blotting assay. Combinatorial AdPTEN and trastuzumab significantly suppressed the proliferation of BT474 cells and induced the apoptosis. The percentage of apopotosis cells treated with AdPTEN was （20.7±5.82）% , companied by cells cycle arrest in G1 phrase (P＜0.01）. DNA of AdPTEN treated BT474 showed a typical DNA ladder at 24-36 h after infection. An obvious downregulation of phosphorylatedAkt expression level in cancer cells was identified by Western blotting. Tumor growth was inhibited in nude mice receiving injection of the recombinant adenoviruses when compared to control mice treated with AdLacZ (P＜0.01）. PTEN protein expression was confirmed by immunohistochemistry. Tumor cell apopotosis was detected by TUNEL and electron microscopy scanning. Conclusion: Our result suggests that PTEN protein can downregulate phosphorylatedAkt and Akt kinase activity, and block the activation of PI3K/Akt pathway, and subsequently reverse trastuzumab resistance and induce cell apoptosis.
2008, 15(5):440-443.
DOI: 10.3872/j.issn.1007-385X.2008.5.008
Abstract:
Abstract Objective: To analyze the differential protein expression between multidrugresistant human osteosarcoma MG63/DXR100 and its parental cell line by differential ingel electrophoresis, so as to lay a foundation for exploring the mechanism of multidrug resistance(MDR) of osteosarcoma. Methods: Multidrugresistant clone of human osteosarcoma MG63 was established by stepwise exposure to increasing doses of doxorubicin(DXR). The total proteins of the above two cell lines were separated with twodimensional electrophoresis. The proteins of differential expression (increased or decreased by more than 30%) were analyzed with image scanning and DeCyder software. Then they were identified in MALDITOF Pro and Mascot database. Results: Thirty proteins with differential expression were identified by proteomic analysis, and 18 of them were further identified by MALDITOF Pro. Five protein spots were successfully identified: matrix metalloproteinases 1 (MMP1) related with tumor cell metastasis, alcohol dehydrogenase (ADH6) with function of detoxication, FERM domain containing protein 3 (FRMD3) which belongs to antioncogenes and two agnoproteins composed of 128 and 300 amino acid residues. MMP1, ADH6 and the two agnoproteins were overexpressed in MG63/DXR100 group, and FRMD3 expression was lower than that in the MG63 group. Conclusion: Five proteins including MMP1, ADH6, FRMD3 and two agnoproteins have been found abnormally expressed in MDR osteosarcoma cells by differential ingel electrophoresis; they might participate in MDR of osteosarcoma.
Abstract Objective: To analyze the differential protein expression between multidrugresistant human osteosarcoma MG63/DXR100 and its parental cell line by differential ingel electrophoresis, so as to lay a foundation for exploring the mechanism of multidrug resistance(MDR) of osteosarcoma. Methods: Multidrugresistant clone of human osteosarcoma MG63 was established by stepwise exposure to increasing doses of doxorubicin(DXR). The total proteins of the above two cell lines were separated with twodimensional electrophoresis. The proteins of differential expression (increased or decreased by more than 30%) were analyzed with image scanning and DeCyder software. Then they were identified in MALDITOF Pro and Mascot database. Results: Thirty proteins with differential expression were identified by proteomic analysis, and 18 of them were further identified by MALDITOF Pro. Five protein spots were successfully identified: matrix metalloproteinases 1 (MMP1) related with tumor cell metastasis, alcohol dehydrogenase (ADH6) with function of detoxication, FERM domain containing protein 3 (FRMD3) which belongs to antioncogenes and two agnoproteins composed of 128 and 300 amino acid residues. MMP1, ADH6 and the two agnoproteins were overexpressed in MG63/DXR100 group, and FRMD3 expression was lower than that in the MG63 group. Conclusion: Five proteins including MMP1, ADH6, FRMD3 and two agnoproteins have been found abnormally expressed in MDR osteosarcoma cells by differential ingel electrophoresis; they might participate in MDR of osteosarcoma.
2008, 15(5):444-450.
DOI: 10.3872/j.issn.1007-385X.2008.5.009
Abstract:
Abstract Objective: To investigate the inhibitory effect of 4′methyletherscutellarein (4MS), an extract from Verbena officinalis, on human choriocarcinoma JAR cell line and the possible mechanism. Methods：JAR cells were exposed to 4′methyletherscutellarein of different concentrations for 48 h. MTT assay was used to examine the antiproliferative effect of 4′methyletherscutellarein. Flow cytometry was used to investigate the apoptosis and the changes of cell cycle. AO/EB double staining was applied to discriminate the apoptotic cells from dead ones. The changes of Survivin, p38MAPK and Caspase 3mRNA expressions were detected by RTPCR in JAR cells treated with 4MS. Furthermore, Western blotting assay was used to determine Survivin protein expression, phosphorylation level of p38 and Caspase 3 in JAR cells before and after 4MS treatment. Results：4MS inhibited the proliferation of JAR cells in a dose and timedependent manner (P<0.05,P<0.01). 4MS treatment also induced apoptosis in JAR cells in a concentrationdependent manner, and percentage of cell cycle progression in G2/M phase increased dramatically compared with the control group (P<0.05). The result of AO/EB double staining showed that there were more viable apoptotic cells in 4MS treated groups than in the control group and the number of nonviable apoptotic cells and dead cells increased with dose. Phosphorylated p38 and Caspase 3 expressions in 4MS treated cells were increased at both mRNA and protein levels according to RTPCR and Western blotting results, while Survivin expression was downregulated; there were significant differences between the 4MS group and the control group (P<0.05). Conclusion：4MS can inhibit proliferation of JAR cells and induce their apoptosis, which might be related to cell arrest at G2/M, downregulation of Survivin activity, and direct activation of p38 MAPK pathway and Caspase 3.
Abstract Objective: To investigate the inhibitory effect of 4′methyletherscutellarein (4MS), an extract from Verbena officinalis, on human choriocarcinoma JAR cell line and the possible mechanism. Methods：JAR cells were exposed to 4′methyletherscutellarein of different concentrations for 48 h. MTT assay was used to examine the antiproliferative effect of 4′methyletherscutellarein. Flow cytometry was used to investigate the apoptosis and the changes of cell cycle. AO/EB double staining was applied to discriminate the apoptotic cells from dead ones. The changes of Survivin, p38MAPK and Caspase 3mRNA expressions were detected by RTPCR in JAR cells treated with 4MS. Furthermore, Western blotting assay was used to determine Survivin protein expression, phosphorylation level of p38 and Caspase 3 in JAR cells before and after 4MS treatment. Results：4MS inhibited the proliferation of JAR cells in a dose and timedependent manner (P<0.05,P<0.01). 4MS treatment also induced apoptosis in JAR cells in a concentrationdependent manner, and percentage of cell cycle progression in G2/M phase increased dramatically compared with the control group (P<0.05). The result of AO/EB double staining showed that there were more viable apoptotic cells in 4MS treated groups than in the control group and the number of nonviable apoptotic cells and dead cells increased with dose. Phosphorylated p38 and Caspase 3 expressions in 4MS treated cells were increased at both mRNA and protein levels according to RTPCR and Western blotting results, while Survivin expression was downregulated; there were significant differences between the 4MS group and the control group (P<0.05). Conclusion：4MS can inhibit proliferation of JAR cells and induce their apoptosis, which might be related to cell arrest at G2/M, downregulation of Survivin activity, and direct activation of p38 MAPK pathway and Caspase 3.
2008, 15(5):451-457.
DOI: 10.3872/j.issn.1007-385X.2008.5.010
Abstract:
Abstract Objective: To explore the apoptosis inducing effect of matrine on C6 glioma cells and the related mechanisms. Methods: MTT assay was used to examine the inhibition of C6 glioma cell line by matrine at various concentrations and the IC50 was calculated. Inverted microscope and TEM (transmission electron microscope) were employed to observe the morphological alterations of C6 glioma cells after exposure to matrine; FCM (Flow cytometry) was used to detect the apoptosis rate of C6 glioma cells; and realtime PCR was used to examine the differential expression of related genes. ICC and Western blotting was used to detect the expression of caspase3. Results: MTT showed that the cell inhibition effect of matrine increased with its concentration（0.11.0 mg/ml）（P<0.05）, with the IC50 being 0.715 mg/ml. Inverted microscope and TEM showed that matrine induced apoptosis of C6 glioma cells. FCM showed that the apoptosis rate increased[(3.56±0.73)%-(27.55±1.92)%] with the increase of matrine concentration（0.2-1.0 mg/ml）（P<0.05）. Realtime PCR showed that matrine induced upregulation of 58 genes and downregulation of 11 genes, and 22 of them were related to apoptosisinducing death receptor, 15 of them to apoptosisinducing mitochondrial pathway. ICC and Western blotting showed that matrine induced upregulation of caspase3 expression（P<0.05）. Conclusion: Matrine can induce C6 glioma cell apoptosis and the mechanism might be related to a number of genes involved in death receptor pathway and mitochondrial pathway.
Abstract Objective: To explore the apoptosis inducing effect of matrine on C6 glioma cells and the related mechanisms. Methods: MTT assay was used to examine the inhibition of C6 glioma cell line by matrine at various concentrations and the IC50 was calculated. Inverted microscope and TEM (transmission electron microscope) were employed to observe the morphological alterations of C6 glioma cells after exposure to matrine; FCM (Flow cytometry) was used to detect the apoptosis rate of C6 glioma cells; and realtime PCR was used to examine the differential expression of related genes. ICC and Western blotting was used to detect the expression of caspase3. Results: MTT showed that the cell inhibition effect of matrine increased with its concentration（0.11.0 mg/ml）（P<0.05）, with the IC50 being 0.715 mg/ml. Inverted microscope and TEM showed that matrine induced apoptosis of C6 glioma cells. FCM showed that the apoptosis rate increased[(3.56±0.73)%-(27.55±1.92)%] with the increase of matrine concentration（0.2-1.0 mg/ml）（P<0.05）. Realtime PCR showed that matrine induced upregulation of 58 genes and downregulation of 11 genes, and 22 of them were related to apoptosisinducing death receptor, 15 of them to apoptosisinducing mitochondrial pathway. ICC and Western blotting showed that matrine induced upregulation of caspase3 expression（P<0.05）. Conclusion: Matrine can induce C6 glioma cell apoptosis and the mechanism might be related to a number of genes involved in death receptor pathway and mitochondrial pathway.
2008, 15(5):458-463.
DOI: 10.3872/j.issn.1007-385X.2008.5.011
Abstract:
Abstract Objective:To investigate the inhibitory effect of recombinant human adenovirus P53(rAdP53) against human hepatocellular carcinoma cell lines with different P53 statuses and its enhancing effect on radiosensitivity. Methods: 〖WTBZ〗Two human hepatocellular carcinoma cell lines with different P53 genetic statuses, PLC/PRF/5 (MT P53) and SMMC7721 (WT P53) were infected with recombinant adenovirus carrying wildtype P53 gene (rAdP53) with increasing multiplicities of infection (MOI). P53 protein expression was detected by Western blotting assay; cell survival was evaluated by MTT; radiosensitivity was evaluated using a clonogenic assay; and cell apoptosis was assayed by TUNEL. Results: Infection efficiency of 50 MOI values of rAdP53 to PLC/PRF/5 and SMMC7721 cells were 89.37% and 86.53%, respectively. The expression of P53 protein was significantly increased in both cell lines 48 h after infection, and cell survival rates of PLC/PRF/5 and SMMC7721 cells were 3.41% and 35.44%, respectively. Inhibitory rates of PLC/PRF/5 and SMMC7721 cells 5 d after infection were 41.91% and 17.03%, respectively. Cells were treated with rAdP53 at 20 MOI for 48 h and then cells were irradiated (4 Gy); the apoptotic rates in PLC/PRF/5 and SMMC7721 cells were (269±5.6)% and (16.4±2.9), respectively (P<0.01). Clone formation assay showed that rAdP53 enhanced sensitivity of PLC/PRF/5 and SMMC7721 cells to radiotherapy, and SER (sensitive enhancement ratio) of Dq were 1.30 and 1.16, respectively, and SER of D0 were 1.57 and 1.25, respectively. Conclusion: rAdP53 can greatly inhibit proliferation, induce l apoptosis and increase radiosensitivity of human hepatocellular carcinoma cells. But the aforesaid efficacy of rAdP53 in PLC/PRF/5 cells is stronger that in SMMC7721 cells, which suggests that hepatocellular carcinoma cells with different P53 statuses responds differently to treatment with rAd-P53 or combination of rAdP53 and irradiation.
Abstract Objective:To investigate the inhibitory effect of recombinant human adenovirus P53(rAdP53) against human hepatocellular carcinoma cell lines with different P53 statuses and its enhancing effect on radiosensitivity. Methods: 〖WTBZ〗Two human hepatocellular carcinoma cell lines with different P53 genetic statuses, PLC/PRF/5 (MT P53) and SMMC7721 (WT P53) were infected with recombinant adenovirus carrying wildtype P53 gene (rAdP53) with increasing multiplicities of infection (MOI). P53 protein expression was detected by Western blotting assay; cell survival was evaluated by MTT; radiosensitivity was evaluated using a clonogenic assay; and cell apoptosis was assayed by TUNEL. Results: Infection efficiency of 50 MOI values of rAdP53 to PLC/PRF/5 and SMMC7721 cells were 89.37% and 86.53%, respectively. The expression of P53 protein was significantly increased in both cell lines 48 h after infection, and cell survival rates of PLC/PRF/5 and SMMC7721 cells were 3.41% and 35.44%, respectively. Inhibitory rates of PLC/PRF/5 and SMMC7721 cells 5 d after infection were 41.91% and 17.03%, respectively. Cells were treated with rAdP53 at 20 MOI for 48 h and then cells were irradiated (4 Gy); the apoptotic rates in PLC/PRF/5 and SMMC7721 cells were (269±5.6)% and (16.4±2.9), respectively (P<0.01). Clone formation assay showed that rAdP53 enhanced sensitivity of PLC/PRF/5 and SMMC7721 cells to radiotherapy, and SER (sensitive enhancement ratio) of Dq were 1.30 and 1.16, respectively, and SER of D0 were 1.57 and 1.25, respectively. Conclusion: rAdP53 can greatly inhibit proliferation, induce l apoptosis and increase radiosensitivity of human hepatocellular carcinoma cells. But the aforesaid efficacy of rAdP53 in PLC/PRF/5 cells is stronger that in SMMC7721 cells, which suggests that hepatocellular carcinoma cells with different P53 statuses responds differently to treatment with rAd-P53 or combination of rAdP53 and irradiation.
12 Roles of roscovitine and minosine in Fasmediated leukemia cell apoptosis and the possible mechanism
2008, 15(5):464-469.
DOI: 10.3872/j.issn.1007-385X.2008.5.012
Abstract:
Abstract Objective: To assess the roles of roscovitine (an inhibitor of DCK) and mimosine (DNA synthesis inhibitor) in Fasmediated leukemia cell apoptosis and to understand the possible mechanism. Methods: The target leukemia cell lines Molt4 and Jurkat were incubated with rhFasL, roscovitine and mimosine separately or with rhFasL+roscovitine or rhFasL+minosine for 18 h （Jurkat 8 h）, 24 h, and 24 h. Apoptotic cells were examined by Annexin V method or modified API method; cyclins expression were detected by cyclin/DNA biparameter flow cytometry; CDK1 and CDK2 activities were detected by Western blotting. Results: Fasmediated cell apoptosis was at G1 phase. Both roscovitine and mimosine significantly promoted Fasmediated apoptosis (P<0.05). Moreover, mimosine increased the levels of cycline D3 and cyclin E at G1 phase and more cells were arrested at G1phase; roscovitine also lowered the phosphorylation of CDK2 Thr160. Minosine+rhFasl decreased the phosphorylation of CDK2 Thr160, and the target cells were completely arrested at G1 phase; it also decreased the levels of cyclin D3, E, A and B1 and the phosphorylation of CDK2 Thr160 and CDK1 Thr161. Conclusion: Both roscovitine and mimosine have synergistic effects with rhFasL in inducing apoptosis of leukemia cells, which is related to the G1 phase cell arrest, inhibition of CKD2 activity and influence of cyclin proteins.
Abstract Objective: To assess the roles of roscovitine (an inhibitor of DCK) and mimosine (DNA synthesis inhibitor) in Fasmediated leukemia cell apoptosis and to understand the possible mechanism. Methods: The target leukemia cell lines Molt4 and Jurkat were incubated with rhFasL, roscovitine and mimosine separately or with rhFasL+roscovitine or rhFasL+minosine for 18 h （Jurkat 8 h）, 24 h, and 24 h. Apoptotic cells were examined by Annexin V method or modified API method; cyclins expression were detected by cyclin/DNA biparameter flow cytometry; CDK1 and CDK2 activities were detected by Western blotting. Results: Fasmediated cell apoptosis was at G1 phase. Both roscovitine and mimosine significantly promoted Fasmediated apoptosis (P<0.05). Moreover, mimosine increased the levels of cycline D3 and cyclin E at G1 phase and more cells were arrested at G1phase; roscovitine also lowered the phosphorylation of CDK2 Thr160. Minosine+rhFasl decreased the phosphorylation of CDK2 Thr160, and the target cells were completely arrested at G1 phase; it also decreased the levels of cyclin D3, E, A and B1 and the phosphorylation of CDK2 Thr160 and CDK1 Thr161. Conclusion: Both roscovitine and mimosine have synergistic effects with rhFasL in inducing apoptosis of leukemia cells, which is related to the G1 phase cell arrest, inhibition of CKD2 activity and influence of cyclin proteins.
2008, 15(5):470-473.
DOI: 10.3872/j.issn.1007-385X.2008.5.013
Abstract:
Abstract Objective: To investigate the inhibitory effect of recombinant human endostatin （ES）combined with rAd P53 on transplanted human breast cancer cell MCF7 in nude mice. Methods: Animal breast cancer model was established by inoculating MCF7 cells in nude mice. The animals were randomized into control group, ES group, rAd/P53 group, and ES+ rAd/P53 group. The tumor growth was observed in each group and immunohistochemical method was employed to examine the microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF). Results: Tumor growth was significantly inhibited in all the 3 treatment groups (P<0.05), with the inhibitory rates being 51.67％，48.74％ and 75.54％ in ES, rAd/P53, and ES + rAd/P53 group, respectively. The value of MVD in control, ES , rAd/P53, and ES + rAd/P53 group were 31.17±2.48, 20.33±4.84, 22.33±3.88 and 12.50±2.74，respectively; and their VEGF Hscores were 45.33±5.89, 33.67±4.80, 40.17±4.74 and 22.33±4.41, respectively. The MVD value and VEGF expression in the ES+rAd/P53 group were significantly lower than those of the other groups (P<0.01).Conclusion:Recombinant human endostatin combined with rAd/P53 can greatly inhibit the growth of transplanted human breast tumor in nude mice and reduce the formation of capillary.
Abstract Objective: To investigate the inhibitory effect of recombinant human endostatin （ES）combined with rAd P53 on transplanted human breast cancer cell MCF7 in nude mice. Methods: Animal breast cancer model was established by inoculating MCF7 cells in nude mice. The animals were randomized into control group, ES group, rAd/P53 group, and ES+ rAd/P53 group. The tumor growth was observed in each group and immunohistochemical method was employed to examine the microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF). Results: Tumor growth was significantly inhibited in all the 3 treatment groups (P<0.05), with the inhibitory rates being 51.67％，48.74％ and 75.54％ in ES, rAd/P53, and ES + rAd/P53 group, respectively. The value of MVD in control, ES , rAd/P53, and ES + rAd/P53 group were 31.17±2.48, 20.33±4.84, 22.33±3.88 and 12.50±2.74，respectively; and their VEGF Hscores were 45.33±5.89, 33.67±4.80, 40.17±4.74 and 22.33±4.41, respectively. The MVD value and VEGF expression in the ES+rAd/P53 group were significantly lower than those of the other groups (P<0.01).Conclusion:Recombinant human endostatin combined with rAd/P53 can greatly inhibit the growth of transplanted human breast tumor in nude mice and reduce the formation of capillary.
2008, 15(5):474-477.
DOI: 10.3872/j.issn.1007-385X.2008.5.014
Abstract:
Abstract Objective: To study the influence of GPC3 gene on the proliferation, adhesion and invasion of hepatoma cell line SKHep1. Methods: SKHep1 cells were transfected with pEGFPN2GPC3 using Lipofectamine2000. RTPCR was used to examine the GPC3mRNA expression in GPC3SKHep1 cells. MTT assay was used to examine the proliferation and calculate the adhesion rate of SKHep1 cells. Transwell system was used to assess the migration and invasion of the cells. Results: SKHep1 cells were successfully transfected with pEGFPN2GPC palsmid. GPC3 mRNA was detected in SKHep1 cells. Transfection with CPC3 significantly suppressed the growth of SKHep1 cells（P<0.01）. The adhesion ability of GPC3transfected cells was significantly decreased compared with control group（ [10.21±0.62]% vs [15.51±0.95]%, P<0.01]. Transfection with GPC3 significantly enhanced migration and invasion capacity（[131.7±7.44] vs [69.6±5.25]，P<0.01; [220±12.8] vs [130±8.2]，P<0.01]. Conclusion: Transfection with GPC3 gene can greatly inhibit the proliferation and adhesion of hepatoma SKHep1 cells, but can enhance their migration and invasiveness. The present study provides an experimental basis for studying the invasion mechanism of liver cancer.
Abstract Objective: To study the influence of GPC3 gene on the proliferation, adhesion and invasion of hepatoma cell line SKHep1. Methods: SKHep1 cells were transfected with pEGFPN2GPC3 using Lipofectamine2000. RTPCR was used to examine the GPC3mRNA expression in GPC3SKHep1 cells. MTT assay was used to examine the proliferation and calculate the adhesion rate of SKHep1 cells. Transwell system was used to assess the migration and invasion of the cells. Results: SKHep1 cells were successfully transfected with pEGFPN2GPC palsmid. GPC3 mRNA was detected in SKHep1 cells. Transfection with CPC3 significantly suppressed the growth of SKHep1 cells（P<0.01）. The adhesion ability of GPC3transfected cells was significantly decreased compared with control group（ [10.21±0.62]% vs [15.51±0.95]%, P<0.01]. Transfection with GPC3 significantly enhanced migration and invasion capacity（[131.7±7.44] vs [69.6±5.25]，P<0.01; [220±12.8] vs [130±8.2]，P<0.01]. Conclusion: Transfection with GPC3 gene can greatly inhibit the proliferation and adhesion of hepatoma SKHep1 cells, but can enhance their migration and invasiveness. The present study provides an experimental basis for studying the invasion mechanism of liver cancer.
2008, 15(5):478-483.
DOI: 10.3872/j.issn.1007-385X.2008.5.015
Abstract:
Abstract Objective: To study the clinical significance of examining serum pyridinoline crosslinked Ntelopeptides of type I collagen (NTx) and serum bone sialoprotein (BSP) in diagnosing bone metastasis of lung cancer and breast cancer. Methods：A total of 105 patients treated in the Oncology Department of Changhai Hospital were included in this study. Patients were divided into 2 groups: bone metastasis (n=50) and nonbone metastasis groups (n=55). The levels of serum NTx and serum BSP were measured by ELISA. Results: The levels of serum NTx and serum BSP in patients with bone metastasis were significantly higher than in those without bone metastasis (P<0.01). The sensitivity and specificity of serum NTx in the diagnosis of bone metastasis were 90.0% and 67.3%, respectively; the sensitivity and specificity of serum BSP were 84.0% and 70.9%, respectively. Thirtytwo patients with bone metastases had skeletal related events (SRE) and they also had significantly higher levels of serum NTx (P<0.05). During the followup, 21 patients were diagnosed with newonset of bone metastasis. COX anlysis showed that the relative risk ratio for bone metastasis of higher serum NTx level was 1.127. Further analysis showed that serum BSP was the only risk factor for patients with breast cancer to develop bone metastasis (P<0.01), with the relative risk ratio being 1.058. During the followup 33 patients died. The cumulative survival rate of patients with higher serum BSP was lower than that with normal serum BSP level. Conclusion: The serum NTx and BSP were important biomarkers for diagnosis of bone metastasis. The two markers can be regarded as risk factors for bone metastasis. BSP might be an independent factor for predicting the prognosis of lung and breast cancer.
Abstract Objective: To study the clinical significance of examining serum pyridinoline crosslinked Ntelopeptides of type I collagen (NTx) and serum bone sialoprotein (BSP) in diagnosing bone metastasis of lung cancer and breast cancer. Methods：A total of 105 patients treated in the Oncology Department of Changhai Hospital were included in this study. Patients were divided into 2 groups: bone metastasis (n=50) and nonbone metastasis groups (n=55). The levels of serum NTx and serum BSP were measured by ELISA. Results: The levels of serum NTx and serum BSP in patients with bone metastasis were significantly higher than in those without bone metastasis (P<0.01). The sensitivity and specificity of serum NTx in the diagnosis of bone metastasis were 90.0% and 67.3%, respectively; the sensitivity and specificity of serum BSP were 84.0% and 70.9%, respectively. Thirtytwo patients with bone metastases had skeletal related events (SRE) and they also had significantly higher levels of serum NTx (P<0.05). During the followup, 21 patients were diagnosed with newonset of bone metastasis. COX anlysis showed that the relative risk ratio for bone metastasis of higher serum NTx level was 1.127. Further analysis showed that serum BSP was the only risk factor for patients with breast cancer to develop bone metastasis (P<0.01), with the relative risk ratio being 1.058. During the followup 33 patients died. The cumulative survival rate of patients with higher serum BSP was lower than that with normal serum BSP level. Conclusion: The serum NTx and BSP were important biomarkers for diagnosis of bone metastasis. The two markers can be regarded as risk factors for bone metastasis. BSP might be an independent factor for predicting the prognosis of lung and breast cancer.
2008, 15(5):484-488.
DOI: 10.3872/j.issn.1007-385X.2008.5.016
Abstract:
Abstract Objective: To investigate the clinical anticancer efficacy of cocultured dendritic cells with cytokineinduced killer cells (DCIK) in treating patients with acute myeloid leukemia (AML). Methods: Totally 10 patients, who were diagnosed as AML and completely remitted after chemical therapy in the First Affiliated Hospital of Suzhou University from Jan. 2006 to Dec. 2007, were included in this study. Peripheral blood mononuclear cells (PBMC) isolated from these patients were treated with standard protocol and were induced to DCIK cells, which were identified by flow cytometry. MTT assay was used to evaluate the cytotoxic effect of DCIK cells against K562 cells. The qualified DCIK cells were administered to the patients and the clinical anticancer efficacy, immunological activity and side effects were evaluated. Results: The cultured DCIK cells inhibited the K562 cells by (58.3±3.3) %. In DCIK cells administered to patients, the proportion of CD3+CD56+ cells was (38.4±9.42)%. Among the 10 patients received DCIK therapy, 7 had continuous complete remission (70%), 2 had recurrence and 1 had tumorbearing survival. The ratios of CD4+, CD8+, and CD56+ cells in patients′ peripheral blood obviously increased after DCIK infusion. No patients had serious adverse event. Conclusion: DCIK can induce specific immunoreaction in the immune system and has satisfactory clinical anticancer efficacy in treatment of AML.
Abstract Objective: To investigate the clinical anticancer efficacy of cocultured dendritic cells with cytokineinduced killer cells (DCIK) in treating patients with acute myeloid leukemia (AML). Methods: Totally 10 patients, who were diagnosed as AML and completely remitted after chemical therapy in the First Affiliated Hospital of Suzhou University from Jan. 2006 to Dec. 2007, were included in this study. Peripheral blood mononuclear cells (PBMC) isolated from these patients were treated with standard protocol and were induced to DCIK cells, which were identified by flow cytometry. MTT assay was used to evaluate the cytotoxic effect of DCIK cells against K562 cells. The qualified DCIK cells were administered to the patients and the clinical anticancer efficacy, immunological activity and side effects were evaluated. Results: The cultured DCIK cells inhibited the K562 cells by (58.3±3.3) %. In DCIK cells administered to patients, the proportion of CD3+CD56+ cells was (38.4±9.42)%. Among the 10 patients received DCIK therapy, 7 had continuous complete remission (70%), 2 had recurrence and 1 had tumorbearing survival. The ratios of CD4+, CD8+, and CD56+ cells in patients′ peripheral blood obviously increased after DCIK infusion. No patients had serious adverse event. Conclusion: DCIK can induce specific immunoreaction in the immune system and has satisfactory clinical anticancer efficacy in treatment of AML.
2008, 15(5):489-493.
DOI: 10.3872/j.issn.1007-385X.2008.5.017
Abstract:
Abstract Objective: Epidermal growth factor receptor（EGFR）is closesly related to nasopharyngeal carcinoma (NPC). Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We aimed to explore the efficacy and toxicity of intensity modulated radiation therapy (IMRT) combined with cetuximab and cisplatin in the treatment of patients with NPC. Methods: From July 2007 to December 2007, 8 patients, including 7 with primary NPC patients and one with reoccurred NPC were included in this study; all patients were at stage Ⅲ or Ⅳ. Treatment included IMRT, cisplatin and cetuximab (400 mg/m2 one week prior to radiotherapy, followed by 250 mg/m2 once a week during radiotherapy). Results: All eight patients completed the planned IMRT. The median treatment cycle of cetuximab was 6 (ranging 4 to 8 cycles). Three patients received no chemotherapy due to hepatic dysfunction; 3 were treated with 4-7 cycles of cisplatin (30 mg/ m2, once a week); one was treated with two cycles of cisplatin (100 mg/m2); and another was treated with one cycle of cisplatin (100 mg/m2). All eight patients were presented with acnelike rash. The acute side effects were mucositis and neutropenia. Mucositis occurred in all the 8 patients; neutropenia occurred in 3 patients. After combined therapy, all 8 patients achieved complete remission (CR). During a followup of 4-10 months, one patient was diagnosed as having leb metastasis. Conclusion: IMRT in combination with cetuximab and chemotherapy in treatment of acute mucositis in patients with advanced nasopharyngeal carcinoma is too much for the patients; two of patients in the present group are intolerable. We suggest dose decrease of cetuximab. The short term efficacy is encouraging, and the longterm outcomes need to be further investigated.
Abstract Objective: Epidermal growth factor receptor（EGFR）is closesly related to nasopharyngeal carcinoma (NPC). Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We aimed to explore the efficacy and toxicity of intensity modulated radiation therapy (IMRT) combined with cetuximab and cisplatin in the treatment of patients with NPC. Methods: From July 2007 to December 2007, 8 patients, including 7 with primary NPC patients and one with reoccurred NPC were included in this study; all patients were at stage Ⅲ or Ⅳ. Treatment included IMRT, cisplatin and cetuximab (400 mg/m2 one week prior to radiotherapy, followed by 250 mg/m2 once a week during radiotherapy). Results: All eight patients completed the planned IMRT. The median treatment cycle of cetuximab was 6 (ranging 4 to 8 cycles). Three patients received no chemotherapy due to hepatic dysfunction; 3 were treated with 4-7 cycles of cisplatin (30 mg/ m2, once a week); one was treated with two cycles of cisplatin (100 mg/m2); and another was treated with one cycle of cisplatin (100 mg/m2). All eight patients were presented with acnelike rash. The acute side effects were mucositis and neutropenia. Mucositis occurred in all the 8 patients; neutropenia occurred in 3 patients. After combined therapy, all 8 patients achieved complete remission (CR). During a followup of 4-10 months, one patient was diagnosed as having leb metastasis. Conclusion: IMRT in combination with cetuximab and chemotherapy in treatment of acute mucositis in patients with advanced nasopharyngeal carcinoma is too much for the patients; two of patients in the present group are intolerable. We suggest dose decrease of cetuximab. The short term efficacy is encouraging, and the longterm outcomes need to be further investigated.
2008, 15(5):494-496.
DOI: 10.3872/j.issn.1007-385X.2008.5.018
Abstract:
摘 要 大量研究表明，微环境中的多种间质细胞对肿瘤细胞的生长和转移具有多方面的影响，而在此过程中趋化因子及其受体则发挥着至关重要的作用。乳腺癌中的肿瘤相关性巨噬细胞在趋化因子CCL2及其受体CCR2作用下向肿瘤部位大量聚集，发挥促肿瘤血管形成的作用；癌症相关性成纤维细胞通过CXCL12/CXCR4生物轴作用于乳腺癌细胞，促进肿瘤生长和转移；间充质干细胞以旁分泌的方式分泌CCL5，作用于CCR5阳性的乳腺癌细胞，增强肿瘤细胞的运动、浸润和转移能力。除此之外，骨髓来源的细胞、造血前驱细胞、肿瘤浸润性树突状细胞、肿瘤浸润性淋巴细胞以及其他白细胞也能借助趋化因子及其受体在肿瘤微环境中发挥着重要作用。由此可见，对肿瘤微环境中间质细胞及趋化因子的深入研究，可能为肿瘤的生物学治疗提供新的靶点。
摘 要 大量研究表明，微环境中的多种间质细胞对肿瘤细胞的生长和转移具有多方面的影响，而在此过程中趋化因子及其受体则发挥着至关重要的作用。乳腺癌中的肿瘤相关性巨噬细胞在趋化因子CCL2及其受体CCR2作用下向肿瘤部位大量聚集，发挥促肿瘤血管形成的作用；癌症相关性成纤维细胞通过CXCL12/CXCR4生物轴作用于乳腺癌细胞，促进肿瘤生长和转移；间充质干细胞以旁分泌的方式分泌CCL5，作用于CCR5阳性的乳腺癌细胞，增强肿瘤细胞的运动、浸润和转移能力。除此之外，骨髓来源的细胞、造血前驱细胞、肿瘤浸润性树突状细胞、肿瘤浸润性淋巴细胞以及其他白细胞也能借助趋化因子及其受体在肿瘤微环境中发挥着重要作用。由此可见，对肿瘤微环境中间质细胞及趋化因子的深入研究，可能为肿瘤的生物学治疗提供新的靶点。
2008, 15(5):497-500.
DOI: 10.3872/j.issn.1007-385X.2008.5.019
Abstract:
摘 要 本文综述了免疫治疗急性髓系白血病（acute myeloid leukemia, AML）的树突状细胞（dendritic cells, DC）疫苗的近期研究进展，主要涉及各种类型的白血病肿瘤抗原的确认与制备，包括AML特异融合蛋白及相关多肽、癌症睾丸抗原、酸洗脱多肽、白血病细胞冻融抗原/凋亡细胞、AMLDC融合细胞、白血病细胞来源的DC等；DC的制备与特性以及优化方法；临床试验研究的初步结果等，还对今后的研究方向进行了分析和展望。
摘 要 本文综述了免疫治疗急性髓系白血病（acute myeloid leukemia, AML）的树突状细胞（dendritic cells, DC）疫苗的近期研究进展，主要涉及各种类型的白血病肿瘤抗原的确认与制备，包括AML特异融合蛋白及相关多肽、癌症睾丸抗原、酸洗脱多肽、白血病细胞冻融抗原/凋亡细胞、AMLDC融合细胞、白血病细胞来源的DC等；DC的制备与特性以及优化方法；临床试验研究的初步结果等，还对今后的研究方向进行了分析和展望。
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Supported by:Beijing E-Tiller Technology Development Co., Ltd.