紫杉醇（Taxo1）是60年代美国肿瘤研究所（National Cancer Institute）用生物活性测试跟踪大量筛选抗癌活性成分的成就，对35000种植物的几万个化事物筛选结果，紫杉醇最有希望。虽然Wani等在1971年就公布了从短叶红豆杉（Taxusbrevifo...紫杉醇（Taxo1）是60年代美国肿瘤研究所（National Cancer Institute）用生物活性测试跟踪大量筛选抗癌活性成分的成就，对35000种植物的几万个化事物筛选结果，紫杉醇最有希望。虽然Wani等在1971年就公布了从短叶红豆杉（Taxusbrevifolia）树皮中分离紫杉醇，并发现其对P388和P1534白血病有很高活性，抑制W256肉瘤活性也很好。也许因其含量很低，分离纯化困难。展开更多
Anesthesia is widely used in several medical settings and accepted as safe. However, there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis. Although chrom...Anesthesia is widely used in several medical settings and accepted as safe. However, there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis. Although chromosomal changes have not been observed in vivo, this is most likely due to DNA repair mechanisms, apoptosis, or cellular senescence. Potential chromosomal alterations after exposure to common anesthetic agents may be relevant in patients with genomic instability syndromes or with aggressive treatment of malignancies. In this study, the P388 murine B cells were cultured in vitro, and spectral karyotyping （SKY） was utilized to uncover genomewide changes. Clinically relevant doses of cisatracurium and propofol increased structural and numerical chromosomal instability. These results may be relevant in patients with underlying chromosomal instability syndromes or concurrently being exposed to chemotherapeutic agents. Future studies may include utilization of stimulated peripheral blood lymphocytes to further confirm the significance of these results.展开更多
Objective: To investigate the therapeutic effect of a novel suicide gene system, yeast cytosine deaminase (YCD)/5-Fluorocytosine(5-FC), on P388/DBA murine leukemia model. Methods: P388-YCD-eGFP clone was selected afte...Objective: To investigate the therapeutic effect of a novel suicide gene system, yeast cytosine deaminase (YCD)/5-Fluorocytosine(5-FC), on P388/DBA murine leukemia model. Methods: P388-YCD-eGFP clone was selected after retrovirus transduction by limited dilution. P388-eGFP and wild type (wt) P388 cells were used as controls. (1) Tumorigenesis study: DBA mice were inoculated intravenously with P388-YCD-eGFP, P388-eGFP or wt P388 cells at a dosage of 5×10~6 per mouse (n=5). (2) Therapeutic effect study of 5-FC: After inoculation with P388-YCD-eGFP, P388-eGFP or wt P388 cells (n=5), 5-FC was administered at a dosage of 5 μmol/d in each mouse for 2 weeks. 20 μmol/d 5-FC were administered on the 8~ th day in case 5 μmol/d did not work. The percentage of eGFP^+ cells was detected by flow cytometry, frozen section or HE section. Results: Mice in YCD, eGFP and wt P388 group developed leukemia and survived (8.0±1.0) d, (7.6±0.89) d and (7.8±1.64) d (P>0.05), respectively. After being treated with 5-FC for 2 weeks, mice in YCD and eGFP^+ groups survived (13.2±1.79) d and (8.4±0.58) d (P<0.05). When 20 μmol/d 5-FC was administered, the percentage of eGFP^+ cells dropped from 21.9%±16.09% to 5.4%±5.6%, as well detected by FACS within 24h after treatment. Conclusion: 5-FC can eliminate YCD gene modified cells in vivo when cells are inoculated intravenously. YCD is an efficient suicide gene system in vivo.展开更多
Lunasia amara Blanco is a famous plant in South Sulawesi. It was used largely by local people as antibacteria and aphrodisiac. Quinoline alkaloid lunacridine was known as the active principle from Lunasia amara Blanco...Lunasia amara Blanco is a famous plant in South Sulawesi. It was used largely by local people as antibacteria and aphrodisiac. Quinoline alkaloid lunacridine was known as the active principle from Lunasia amara Blanco. Its activity was reported as a DNA Intercalating Topoisomerase II inhibitor. In this study, we have isolated and assayed the cytotoxic activity of lunacridine on P388 murine leukemia cells by MTT colorimetric assay （in vitro）. Lunacridine showed the less cytotoxic activity with the IC50 of 39.52 μg/mL. With the aim to explore the structural determinants responsible for this activity, molecular docking study have been carried out with DNA model using AutoDock 4.0 software with various total of energy evaluations （in silico）. The best docking reached at the total energy evaluations of 2.5 × 107 with the binding free energy of-6.63 kcal/mol. Analysis of the docking results was in accordance with the ability of lunacridine to intercalate between base pairs of DNA. Cytotoxic activity of lunacridine is less probably due to low affinity and molecular interaction. Therefore this study suggests to design and to develop lunacridine as a lead compound for anticancer drug.展开更多
文摘紫杉醇（Taxo1）是60年代美国肿瘤研究所（National Cancer Institute）用生物活性测试跟踪大量筛选抗癌活性成分的成就，对35000种植物的几万个化事物筛选结果，紫杉醇最有希望。虽然Wani等在1971年就公布了从短叶红豆杉（Taxusbrevifolia）树皮中分离紫杉醇，并发现其对P388和P1534白血病有很高活性，抑制W256肉瘤活性也很好。也许因其含量很低，分离纯化困难。
基金supported in part by the Intramural Research Program of the NIH,the National Cancer Institute and the National Institute of Allergy and Infectious Diseases
文摘Anesthesia is widely used in several medical settings and accepted as safe. However, there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis. Although chromosomal changes have not been observed in vivo, this is most likely due to DNA repair mechanisms, apoptosis, or cellular senescence. Potential chromosomal alterations after exposure to common anesthetic agents may be relevant in patients with genomic instability syndromes or with aggressive treatment of malignancies. In this study, the P388 murine B cells were cultured in vitro, and spectral karyotyping （SKY） was utilized to uncover genomewide changes. Clinically relevant doses of cisatracurium and propofol increased structural and numerical chromosomal instability. These results may be relevant in patients with underlying chromosomal instability syndromes or concurrently being exposed to chemotherapeutic agents. Future studies may include utilization of stimulated peripheral blood lymphocytes to further confirm the significance of these results.
基金Supported in part by grants from"Outstanding physicianProgram" of public Health Department of ShanghaiMunicipal Government,China(98BR0 2 9),National NaturalScience Foundation of China(30 170 379
文摘Objective: To investigate the therapeutic effect of a novel suicide gene system, yeast cytosine deaminase (YCD)/5-Fluorocytosine(5-FC), on P388/DBA murine leukemia model. Methods: P388-YCD-eGFP clone was selected after retrovirus transduction by limited dilution. P388-eGFP and wild type (wt) P388 cells were used as controls. (1) Tumorigenesis study: DBA mice were inoculated intravenously with P388-YCD-eGFP, P388-eGFP or wt P388 cells at a dosage of 5×10~6 per mouse (n=5). (2) Therapeutic effect study of 5-FC: After inoculation with P388-YCD-eGFP, P388-eGFP or wt P388 cells (n=5), 5-FC was administered at a dosage of 5 μmol/d in each mouse for 2 weeks. 20 μmol/d 5-FC were administered on the 8~ th day in case 5 μmol/d did not work. The percentage of eGFP^+ cells was detected by flow cytometry, frozen section or HE section. Results: Mice in YCD, eGFP and wt P388 group developed leukemia and survived (8.0±1.0) d, (7.6±0.89) d and (7.8±1.64) d (P>0.05), respectively. After being treated with 5-FC for 2 weeks, mice in YCD and eGFP^+ groups survived (13.2±1.79) d and (8.4±0.58) d (P<0.05). When 20 μmol/d 5-FC was administered, the percentage of eGFP^+ cells dropped from 21.9%±16.09% to 5.4%±5.6%, as well detected by FACS within 24h after treatment. Conclusion: 5-FC can eliminate YCD gene modified cells in vivo when cells are inoculated intravenously. YCD is an efficient suicide gene system in vivo.
文摘Lunasia amara Blanco is a famous plant in South Sulawesi. It was used largely by local people as antibacteria and aphrodisiac. Quinoline alkaloid lunacridine was known as the active principle from Lunasia amara Blanco. Its activity was reported as a DNA Intercalating Topoisomerase II inhibitor. In this study, we have isolated and assayed the cytotoxic activity of lunacridine on P388 murine leukemia cells by MTT colorimetric assay （in vitro）. Lunacridine showed the less cytotoxic activity with the IC50 of 39.52 μg/mL. With the aim to explore the structural determinants responsible for this activity, molecular docking study have been carried out with DNA model using AutoDock 4.0 software with various total of energy evaluations （in silico）. The best docking reached at the total energy evaluations of 2.5 × 107 with the binding free energy of-6.63 kcal/mol. Analysis of the docking results was in accordance with the ability of lunacridine to intercalate between base pairs of DNA. Cytotoxic activity of lunacridine is less probably due to low affinity and molecular interaction. Therefore this study suggests to design and to develop lunacridine as a lead compound for anticancer drug.
