Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

The maximum bit rates of soliton communication systems with lumpedamplifiers and filters in different distances

The maximum bit rate of a soliton communication system with lumped amplifiers and optical filters is considered. When the dispersion of the fiber varies from one amplifier spacing to another amplifier spacing, the maximum bit rate is significantly reduced. To overcome the effect, the amplitude of the soliton is amplified so that it is still the average soliton corresponding to the fiber dispersion for an amplifier spacing. Thus, the maximum bit rate is only slightly less than that without the dispersion variations. For a given distance, the maximum bit rate limited by the stability and soliton interaction is obtained. The result is compared with that limited by the Gordon-Haus effect. For shorter transmission distance, the maximum bit rate is limited by the stability and soliton interaction. For longer transmission distance, the maximum bit rate is limited by the Gordon-Haus effect     

我国聚甲醛工业的供需分析

从国内聚甲醛树脂的生产、贸易及消费状况出发 ,分析了国内聚甲醛工业的供需现状并提出短期预测。     

Surface localization of the sea urchin egg receptor for sperm

The sea urchin egg receptor for sperm is thought to be involved in species-specific sperm-egg interactions at the egg surface. Recent revisions in the deduced amino acid sequence of the cloned cDNAs indicate that the protein encoded does not possess the common structural hallmarks of a membrane protein. Thus, investigation of the localization and association of the protein with the egg surface is crucial. We describe and characterize a new monoclonal antibody raised against recombinant sperm receptor protein. This antibody, in conjunction with several polyclonal antibodies, was used to study the receptor protein in eggs. Immunoprecipitation studies indicated that the antibodies recognize the high Mr (ca. 350 K) sperm receptor protein which copurified with egg plasma membrane-vitelline layer complexes. The sperm receptor protein was solubilized only by detergents and not by treatments designed to solubilize peripherally associated or lipid-anchored membrane proteins, suggesting a tight association with the membrane fraction. Confocal immunofluorescence microscopy of live eggs indicated surface staining. Finally, lysylendoproteinase C treatment of live eggs resulted in a loss of the high Mr receptor protein epitopes, and the concomitant release of a 70-kDa proteolytic fragment, which correlated with a reduced ability of the eggs to be fertilized. Taken together, these data indicate that at least some fraction of the sperm receptor protein is present on the egg surface, a requisite locale for a sperm binding protein.     

Progress in the study of mechanism of fetal scarless wound healing

From January 1987 to December 1993, 426 patients with lung cancer were operated in our hospital, among which 159 patients were diagnosed postoperatively to be N2 disease by pathology including 81 central type and 78 peripheral type lung cancer. Radical operations were performed on 135 cases, palliative operations on 24 cases. Follow up study: one-year survival rate was 71.7%, three-year survival rate 29.0% and five-year survival rate 21.7%. The main factors affecting operative results are tumor cell type, the number and location of metastatic lymph nodes and the thoroughness of dissection. Tumor staging, except T4 tumor is not a main factor influencing prognosis. The indications of operation performed on N2 lung cancer and the necessity of extensive nodal exenteration are also discussed in this article. We consider extensive hilar and mediastinal nodal exenteration necessary in order to achieve radical resection and good prognosis.     

China＇s Electric Power Reform：Different Economics and Challenges

China＇s electric power reform has followed the western reform format, however, it doest not seem to have endorsed the liberalization ideology underlying the reform model. This raises the concern of whether and how a competitive power market may be established and reform objectives reached. The new market competition model is easy to build in theory. The experience of many countries suggests that the market reform is extremely difficult because of the interruptions by different interest groups. To transform a centrally planned power sector into a competitive power market is a daunting task. Policy makers need to take into consideration the transitional nature of the economy and power industry as they implement the competitive power market model.     

降低射频电路串扰噪声的布线方法

研究并解决了无障碍多层无网格射频电路的布线问题,主要包括三个部分:设计规则、串扰噪声限制和布线方法.首先通过设计规则计算连线参数,运用RLc模型估算串扰噪声,然后,按照需要连接的实节点个数进行归类并提出相应的布线算法.实验结果表明,该布线方法可有效地降低射频电路的串扰噪声.     

一种新型特级防火卷帘的研究与开发——3J特级防火卷帘

介绍3J特级防火卷帘的各种重要功能特点,讨论其实用性与易用性以及推广该产品的必要性与可行性。