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排序方式: 共有2466条查询结果,搜索用时 15 毫秒
1.
Mitsumasa Iwata Shunji Izuta Motoshi Suzuki Kiyohide Kojima Yoshihito Furuhashi Yutaka Tomoda Shonen Yoshida 《Cancer science》1991,82(4):433-439
We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP. 相似文献
2.
Yawata Ayumi; Kanzaki Akio; Gilsanz Florinda; Delaunay Jean; Yawata Yoshihito 《Blood》1997,90(6):2471-2481
3.
Motohiko Kimura Toshifumi Sugiura Yoshihito Fukui Morio Togawa Yukio Harada† 《Artificial organs》1990,14(5):390-391
Carbon fibers with fibrin glue were used as electrodes for diaphragm pacing. The electrodes were applied to three mongrel dogs and the effectiveness was tested. The carbon leads were glued to phrenic nerves by means of the fibrinogen and thrombin bilaterally. The tidal volumes and threshold current level for stimulation were measured at various time up to 9 weeks after implantation. Effective contraction of diaphragm were observed for 9 weeks. By using this electrode, the exfoliation of the nerve is not necessary, the nerve can be maintained in an intact state, and the risk of the implanting operation can be minimized. 相似文献
4.
Yasuaki Saijo Eiji Yoshioka Tomonori Fukui Mariko Kawaharada Reiko Kishi 《Hypertension research》2006,29(8):589-596
The aim of this study was to investigate whether the metabolic syndrome (MS) was associated with an elevated level of C-reactive protein (CRP) and increased arterial stiffness, and to clarify whether combined MS and CRP data had a stronger relation to arterial stiffness than did MS data alone. Brachial-ankle pulse wave velocity (baPWV), CRP, and conventional risk factors were evaluated in 3,412 men and 854 women. Adjusted mean values of baPWV in men with 0, 1, 2, and > or = 3 components were 1,309, 1,372, 1,422, and 1,462 cm/s, respectively (p for trend <0.001). Adjusted mean values of baPWV in women with 0, 1, 2, and > or =3 components were 1,212, 1,292, 1,357, and 1,391 cm/s, respectively (p for trend <0.001). Adjusted geometric mean concentrations of CRP in men with 0, 1, 2, and > or = 3 components were 0.036, 0.049, 0.059, and 0.076 mg/dI, respectively (p for trend <0.001). Adjusted geometric mean concentrations of CRP in women with 0, 1, 2, and > or = 3 components were 0.023, 0.030, 0.057, and 0.077 mg/dI, respectively (p for trend <0.001). In analyses of adjusted mean values of baPWV according to the number of MS components and according to CRP levels within or without top quartile levels, the p value for the trend was significant (<0.001) in both men and women but, in post hoc analyses, comparing high and low CRP levels in each MS component-number group, no significant difference was found. These results suggest that, for prediction of increased arterial stiffness, combining MS and CRP data has little additive effect compared to the use of MS data alone. 相似文献
5.
H Okamoto N Saijo T Shinkai K Eguchi Y Sasaki T Tamura Y Ohe A Kojima H Kunikane A Karato 《Annals of oncology》1992,3(10):819-824
To elucidate the factors which influence the value of hemoglobin, the nadir value of hemoglobin, frequency of blood transfusion and prognostic value of blood transfusion in patients with primary lung cancer during intensive chemotherapy, the hematological features of 124 patients entered into a randomized phase III study containing cisplatin were retrospectively analyzed. There was no difference in the percent nadir hemoglobin value of the first course of chemotherapy (% of pretreatment value) in any of the subgroups with respect to sex, body weight loss, performance status, age, stage, number of metastatic sites or treatment arms. The only predictive indicator for the nadir hemoglobin value in the first course of chemotherapy was the pretreatment value of hemoglobin. The equation for the regression line was y = 1.07 + 0.73x (R2 = 0.663, p < 0.001). The lowest nadir hemoglobin value (% of pretreatment value) during all chemotherapy courses was significantly lower in the subgroups older than 60 years and those with body weight loss. There was an inverse correlation between the accumulated dose of cisplatin and the lowest nadir hemoglobin value (p < 0.05). The frequency of blood transfusion in patients with more than two metastatic sites was significantly higher than in those with one or no metastatic sites (p < 0.05). Survival of patients who had required blood transfusion after chemotherapy was significantly shorter than that of patients who had not (p < 0.05). 相似文献
6.
Phase I Study of Paclitaxel by Three-hour Infusion: Hypotension Just after Infusion Is One of the Major Dose-limiting Toxicities 总被引:4,自引:0,他引:4
Tomohide Tamura Yasutsuna Sasaki Yutaka Nishiwaki Nagahiro Saijo 《Cancer science》1995,86(12):1203-1209
The primary objectives of this study were to determine the maximum tolerated dose (MTD) of paclitaxel administered by 3-h infusion to patients with solid tumors, and to characterize the pharmacokinetics of a 3-h infusion in comparison with those of a 24-h infusion. Twenty-seven patients each received one of six levels of paclitaxel, 105, 135, 180, 210, 240 and 270 mg/m2 , with premedication. Two patients given 240 mg/m2 and one patient given 270 mg/m2 unexpectedly had grade 3/4 hypotension just after finishing the paclitaxel infusion. Peripheral neuropathy was also dose-limiting at 270 mg/m2 . Although granulocytopenia was significantly less severe than with a 24-h infusion, more than half of the patients experienced grade 4 toxicity at doses of 240 or 270 mg/m2 . Severe hypersensitivity reactions (HSRs) were not observed. Pharmacokinetic studies using high performance liquid chromatography demonstrated proportionally greater increases in the peak plasma concentration and area under the curve, and decreases in clearance and volume of distribution with increasing dose, suggesting non-linear pharmacokinetics of paclitaxel when given by 3-h infusion. The MTD of paclitaxel given as a 3-h infusion was determined to be 240 mg/m2 with dose-limiting toxicities of granulocytopenia, peripheral neuropathy and hypotension. Hypotension just after infusion, induced by 3-h infusion of paclitaxel, is a new observation which has not been reported previously. The recommended dose for phase II study is 210 mg/m2 . Although hypotension was observed as an unexpected toxic effect, paclitaxel could be administered safely over 3 h with premedication and proper monitoring, resulting in reduced myelotoxicity and with no increase in the incidence of HSRs as compared with a 24-h infusion. 相似文献
7.
The increase in life-span (ILS) of tumor-bearing mice caused by recombinant interleukin-2 (RIL-2) was studied in the solid tumor adenocarcinoma 755 system. With long-term treatment (Days 5-12), RIL-2 (10(5) U/mouse) showed a weak effect (24% ILS), but short-term RIL-2 treatment (Days 5-8 or 9-12) had hardly any effect. Mitomycin, at 2 mg/kg (maximum nontoxic dose), caused 35% ILS with Days 5-8 treatment and only 12% ILS with Days 9-12 treatment. Sequential treatment with mitomycin (Days 5-8) and RIL-2 (Days 9-12) markedly enhanced antitumor activity (88% ILS). This value is significantly greater than that of mitomycin alone or RIL-2 alone (P less than 0.01). Furthermore, mitomycin followed by RIL-2 markedly augmented killing activity of spleen cells that are cytotoxic in vitro. These results indicate that RIL-2 markedly affects the inhibition of growth of a tumor treated with an antitumor agent. 相似文献
8.
Summary. Three non-sense mutants of varicella-zoster virus (VZV) thymidine kinase (TK) gene, VZTK325, VZTK278 and VZTK224, were isolated. The mutants had a single nucleotide substitution at codons 326, 279 and 225, which changed the codon of TGG
(tryptophan) to the stop codon TGA. The wild type (WT) and mutant TKs were expressed in E. coli cells and their characteristics were evaluated. VZTK224 lost TK activity, but VZTK325 and VZTK278 maintained 74.8% and 21.2% of the WT TK activity. On the other hand, all mutants lost the thymidylate kinase activity. Moreover,
VZTK325 and VZTK278 polypeptides were heat-labile. These data suggest that the carboxy-terminal portion of herpesvirus TK plays an important
role in the stable folding of TK and thymidylate kinase activity.
Received April 21, 1997 Accepted June 16, 1997 相似文献
9.
Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. 总被引:21,自引:0,他引:21
M Fukuoka K Furuse N Saijo Y Nishiwaki H Ikegami T Tamura M Shimoyama K Suemasu 《Journal of the National Cancer Institute》1991,83(12):855-861
Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic. 相似文献
10.