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21.
J G Wall H A Burris D D Von Hoff G Rodriguez R Kneuper-Hall D Shaffer T O'Rourke T Brown G Weiss G Clark 《Anti-cancer drugs》1992,3(4):337-345
Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
22.
B Têtu R L Katz S P Kalter A C Von Eschenbach B Barlogie 《Seminars in diagnostic pathology》1987,4(3):243-250
A review of acridine-orange DNA and RNA flow cytometry (FCM) histograms of 249 bladder irrigation specimens from 129 patients with a previous history of transitional cell carcinoma (TCC) reveals that aneuploidy and tetraploidy (greater than 10% of total cell population) are reliable markers to detect the presence of bladder tumor in patients treated by surgical resection of tumor only. Tetraploidy is unreliable when the patient received intravesical chemotherapy or radiation therapy but aneuploidy remains accurate. A comparison of the reliability of FCM compared with cytology indicates an overall lower sensitivity and specificity for FCM (respectively, 52% and 73%) as opposed to cytology (respectively, 62% and 92%). Sensitivity is improved and raised to 77% if FCM and cytology are used in conjunction and reaches 82% in patients treated by surgery only and 88% in those who received radiation therapy. The lowest sensitivity and specificity obtained with FCM are in patients treated by intravesical chemotherapy (respectively, 44% and 58%) and the highest are in those treated by surgery without additional therapy (56% and 83%). This study demonstrates that FCM criteria for diagnosis of TCC of urinary bladder on bladder irrigation specimens depends on patient's treatment history. It also indicates that sensitivity and specificity of cytology to detect bladder tumor are superior to those obtained with FCM but both methods may be considerably improved if they are used in conjunction. 相似文献
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24.
The density of T3 nuclear receptors is known to vary with tissues and physiopathological conditions, but the factors involved in their regulation are still unknown. We have previously shown in the anterior pituitary gland that T3 modulates its own receptors; the density of T3 receptors in hypothyroid rats is half that in normal rats, and one injection of T3 is able to restore normal density of T3 receptors within 1-3 h. To determine whether T3 has a direct action on the synthesis of its nuclear receptor, the effect of cycloheximide (Cy) on T3-induced nuclear receptor was studied. In addition, the relationship between the density of pituitary T3 receptors and the secretion of TSH in different thyroid states was examined. In normal rats one injection of Cy (0.5-8 mg/100 mg BW) induced within 3 h a dose-dependent reduction in the density of pituitary T3 receptors as well as an important decrease in plasma TSH, with no changes in T4, T3, or pituitary TSH content. In hypothyroid rats the 50% decrease in the density of pituitary T3 receptors was not further reduced by 1 mg Cy. However, when the same dose of Cy was given 30 min before T3 it completely inhibited the induction by T3 of its receptors. When Cy was given 30 min or 1 h after T3 the inhibition was only partial. An inverse correlation was found between the density of T3 receptors in the pituitary gland and plasma TSH (r = -0.8128) in all experimental groups except those treated with Cy; this drug had an inhibitory effect on both TSH secretion and the density of receptors. The present data, therefore, support the view that T3 in the pituitary gland may induce the synthesis of its own nuclear receptors and that the density of T3 receptors is also involved in the control of TSH secretion. 相似文献
25.
26.
Induction of a stable hapten-specific immunosuppression by a hapten conjugated to poly(N-vinylpyrrolidone) (PVP). 总被引:1,自引:0,他引:1 下载免费PDF全文
The ability of a hapten coupled to a clinically permissive synthetic polymer (NIP-PVP) to induce suppression was investigated. NIP coupled to the low molecular weight non-immunogenic form of poly(N-vinylpyrrolidone) (PVP) was found to be capable of inducing a hapten-specific longlasting suppression of both primary and secondary responses. The previous use of PVP as a plasma expander in humans makes this polymer a potentially suitable tool for the induction of specific immunosuppression to a variety of clinically important drug and tissue specific epitopes. The possible use of low molecular weight PVP for that purpose will be investigated further, specifically with larger antigenic components. 相似文献
27.
Hermann Schtzl Gerhard Schwarzfischer Dietlinde Rose Birgit Gathof Wilhelm Weise Friedrich Deinhardt Klaus Von Der Helm 《Journal of medical virology》1994,43(2):159-160
The extent of human T-cell lymphotropic retorvirus HTLV-I and HTLV-II infections in the general population in central Europe has not been investigated fully. Two hundred forty-eight thousand blood donors from southern Germany were examined serologically for antibodies to the human lymphotropic retroviruses HTLV-I and HTLV-II: 0.021% were confirmed postive and 0.056% were “indeterminate”. A limited number of seropositives and “indeterminate” samples were analyzed by polymerase chain reaction (PCR): the seropositives were confirmed as positive and 43% of the “indeterminate” samples were PCR-positive. The range of 0.021% HTLV-positives in 248,000 donors, i.e. about two in 10,000 individuals, mirrors closely the published data for the United States. © 1994 Wiley-Liss, Inc. 相似文献
28.
Autoimmune haemolytic anaemias. V. Studies on the resistance against complement haemolysis of the red cells of patients with chronic cold agglutinin disease 总被引:2,自引:1,他引:2 下载免费PDF全文
C. P. Engelfriet A. E. G. Kr. Von Dem Borne Do Beckers E. Reynierse J. J. Van Loghem 《Clinical and experimental immunology》1972,11(2):255-264
Experiments are described the results of which sustain the hypothesis that resistance against complement haemolysis, which is a characteristic of the red cells of patients with chronic cold agglutinin disease, is due to the following mechanism: when red cells react with cold auto-agglutinins in vivo, they are either haemolysed immediately, or, due to an unknown factor, escape direct haemolysis. In the latter case β1E and β1A disappear from the cell membrane. To the sites where these proteins have been attached once, no new β1E or β1A molecules can be bound. Full complement activation thus becomes impossible. 相似文献
29.
Theresa L. Whiteside Sylvia Miescher H. R. MacDonald V. Von Fliedner 《Journal of immunological methods》1986,90(2):221-233
The separation of viable tumor-infiltrating lymphocytes (TIL) from surgical biopsies of human solid tumors was achieved by velocity sedimentation at unit gravity or by discontinuous density gradients. The two methods were adapted to small volumes and cell numbers not exceeding 1 × 108. The recovery, purity and composition of the TIL-enriched fractions were comparable in the two methods. Density gradients were more rapid, simpler and more practical for preparation under sterile conditions of TIL from clinical material than velocity sedimentation. Lymphocytes in the TIL-enriched fractions obtained by either of the methods were poorly responsive to mitogens. This poor responsiveness is a characteristic of the human TIL and seems to be related to effects exerted by tumor cells. 相似文献
30.
On the partial suppression of IL-2 receptor expression and the prevention of lectin-induced lymphoblast formation by cyclosporine A. 下载免费PDF全文
W Solbach K Heeg D U Von Steldern M Rllinghoff H Wagner 《Clinical and experimental immunology》1985,60(3):501-508
The effect of cyclosporine A (CyA) on the expression of the Tac-antigen (IL-2 receptor) on PHA-activated PBMNC was analysed by immunofluorescence. In the initial experiments we determined the number of Tac(+) cells, disregarding cell size; we found that CyA did not affect the number of cells expressing the Tac antigen after lectin stimulation (Fig. 1, Table 1). When we found that comparable numbers of Tac(+)-lymphocytes absorbed less IL-2 when grown in CyA as compared to solvent controls, we analysed in more detail the correlation between Tac-antigen expression and cell size of cell populations grown in CyA. It was found that CyA prevented a majority of PHA-activated PBMNC to undergo blastogenesis despite having expressed the IL-2 receptor. A minority of the cells, however, were refractory to the CyA-mediated suppression of blast formation. Studies analysing the Tac antigen expression semiquantitatively showed that CyA reduced the intensity of Tac antigen expression on cells of all sizes. 相似文献