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71.
Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia 总被引:5,自引:1,他引:5
Kantarjian HM; Beran M; Ellis A; Zwelling L; O'Brien S; Cazenave L; Koller C; Rios MB; Plunkett W; Keating MJ 《Blood》1993,81(5):1146-1151
The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to- moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan. 相似文献
72.
Interferon-alpha stimulates production of interleukin-10 in activated CD4+ T cells and monocytes 总被引:4,自引:1,他引:4
Aman MJ; Tretter T; Eisenbeis I; Bug G; Decker T; Aulitzky WE; Tilg H; Huber C; Peschel C 《Blood》1996,87(11):4731-4736
In the present study, we investigated the effect of interferon-alpha (IFN-alpha) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4+ T cells. In mononuclear cells, IFN-alpha induced expression of IL-10 mRNA and further enhanced lipopolysaccharide (LPS)-stimulated IL-10 expression. In purified monocytes, a strong expression of IL-10 mRNA induced by LPS was not further enhanced by IFN-alpha. In highly purified CD4+ T cells, IFN- alpha upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN- alpha on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-alpha was seen after prolonged incubation periods of 48 to 96 hours, whereas IFN-gamma reduced IL-10 production in the early incubation period. Similar effects of IFN-alpha were observed in CD4+ T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-alpha caused an increase of IL-10 in culture supernatants of activated T-helper cells of more than 100% after 96 hours of incubation. In contrast, other cytokines, including IFN-gamma and IL-4, had no influence on IL-10 secretion stimulated by CD3 and CD28 in CD4+ T cells. In serum samples of IFN-alpha-treated individuals, we failed to detect an influence of cytokine treatment on IL-10 serum levels, confirming the requirement of additional activating signals for IFN-alpha-mediated effects on IL-10 synthesis. In conclusion, IFN-alpha enhances the late induction of IL- 10, which physiologically occurs upon stimulation of monocytes and T cells. Biologically, this effect might enhance the negative-feedback mechanism ascribed to IL-10, which limits inflammatory reactions. 相似文献
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76.
Gabrielle Jongeneel Thomas Klausch Felice N. van Erning Geraldine R. Vink Miriam Koopman Cornelis J.A. Punt Marjolein J.E. Greuter Veerle M.H. Coupé 《International journal of cancer. Journal international du cancer》2020,146(11):2968-2978
There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease-free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real-world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient-level data from reported DFS data and (iii) estimating treatment effect in the patient-level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient-level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups. 相似文献
77.
目的 与开腹胆囊切除术相比,腹腔镜胆囊切除术(LC)有减少术后不适和较少的创作,但仍有改进的余地。方法:为进一步减轻手术创伤,我们引进了针式腹间胆囊切除术,共29例。结果 平均手术时间为75分钟,19例当天出院,10例隔天出院,其中1例是胆总管探查。结论 针式航空 镜胆囊切除术是一种可靠的技术。 相似文献
78.
Locally deranged joint anatomy can predispose to septic arthritis which can be managed by surgical debridement. We present a case of manubriosternal subluxation/dislocation caused by kyphoscoliosis leading to manubriosternal septic arthritis. 相似文献
79.
Wisnumurti Kristanto Peter M. van Ooijen Riksta Dikkers Marcel J. Greuter Felix Zijlstra Matthijs Oudkerk 《The international journal of cardiovascular imaging》2010,26(1):77-87
Multi detector-row CT (MDCT), the current preferred method for coronary artery disease assessment, is still affected by motion
artefacts. To rule out motion artefacts, qualitative image analysis is usually performed. Our study aimed to develop a quantitative
image analysis for motion artefacts detection as an added value to the qualitative analysis. An anthropomorphic moving heart
phantom with adjustable heart-rate was scanned on 64-MDCT and dual-source-CT. A new software technique was developed which
detected motion artefacts in the coronaries and also in the myocardium, where motion artefacts are more apparent; with direct
association to the qualitative analysis. The new quantitative analysis managed to detect motion artefacts in phantom scans
and relate them to artefact-induced vessel stenoses. Quantifying these artefacts at corresponding locations in the myocardium,
artefact-induced vessel stenosis findings could be avoided. In conclusion, the quantitative analysis together with the qualitative
analysis rules out artefact-induced stenosis. 相似文献
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