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41.
Leukemic cell growth in SCID mice as a predictor of relapse in high- risk B-lineage acute lymphoblastic leukemia 总被引:3,自引:2,他引:3
Uckun FM; Sather H; Reaman G; Shuster J; Land V; Trigg M; Gunther R; Chelstrom L; Bleyer A; Gaynon P 《Blood》1995,85(4):873-878
Mice with severe combined immunodeficiency (SCID) provide a model system to examine the in vivo homing, engraftment, and growth patterns of normal and malignant human hematopoietic cells. The relation between leukemic cell growth in this model and the treatment outcome in patients from whom cells were derived has not been established. Leukemic cells from 42 children with newly diagnosed high-risk B- lineage acute lymphoblastic leukemia were inoculated intravenously into CB.17 SCID mice. Mice were killed at 12 weeks or when they became moribund as a result of disseminated leukemia. All mice were necropsied and subjected to a series of laboratory studies to assess their burden of human leukemic cells. Twenty-three patients whose leukemic cells caused histopathologically detectable leukemia in SCID mice had a significantly higher relapse rate than the 19 patients whose leukemic cells did not (estimated 5-year event-free survival: 29.5% v 94.7%; 95% confidence intervals, 11.2% to 50.7% v 68.1% to 99.2%; P < .0001 by log- rank test). The occurrence of overt leukemia in SCID mice was was a highly significant predictor of patient relapse. The estimated instantaneous risk of relapse for patients whose leukemic cells caused overt leukemia in SCID mice was 21.5-fold greater than that for the remaining patients. Thus, growth of human leukemic cells in SCID mice is a strong and independent predictor of relapse in patients with newly diagnosed high-risk B-lineage acute lymphoblastic leukemia. 相似文献
42.
Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation 总被引:2,自引:0,他引:2
Bertram JH; Gill PS; Levine AM; Boquiren D; Hoffman FM; Meyer P; Mitchell MS 《Blood》1986,68(3):752-761
Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101. 相似文献
43.
Brennan FM; Browne KA; Green PA; Jaspar JM; Maini RN; Feldmann M 《Rheumatology (Oxford, England)》1997,36(6):643-650
Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum
samples from rheumatoid arthritis (RA) patients undergoing a double-blinded
placebo-controlled trial with the chimaeric anti-tumour necrosis factor
(TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent
MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the
commencement of the trial compared with normal control sera. Following cA2
therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10
mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10
mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at
all time points was observed, reducing maximally to 41% of pre-infusion
values at day 7. MMP-1 levels were also reduced, but less dramatically than
MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2
treated group. In a separate non-placebo-controlled study, we also
evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in
plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the
normal control range, but were significantly reduced (P < 0.035) 14 days
after infusion to 72% of pre-infusion values. This study confirms previous
reports that MMP-3 levels are elevated and correlate with measures of
inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1
levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst
serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to
and following anti-TNF-alpha antibody therapy, it remains to be
demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and
bone resorptive processes which are evident in this disease.
相似文献
44.
Mahmoud Alhosiny Fayed Hesham El-Sayed Abdel-Hady Mona Mohammed Hafez Osama Saad Salama Youssef Abdelhalim Al-Tonbary 《Hematology/oncology and stem cell therapy》2018,11(2):65-74
Background
The increased survival rate of thalassemic patients has led to unmasking of management related complications which were infrequently encountered.Objective
Study the increased coagulation and platelet activation in children with β-thalassemia, to analyze the factors that lead to such hypercoagulable state and to study pulmonary hypertension (PH) in conjunction with platelet activation and hypercoagulable state in children with β-thalassemia.Methods
36 Egyptian children with β-thalassemia with a mean age of 9.9 years (±4.7 SD). In addition, 20 healthy Egyptian children matched for age and sex were enrolled as a control group. Both were subjected to clinical and laboratory assessments. Echocardiography was done to the patient group and PH was diagnosed based on calculated mean pulmonary artery pressure [MPAP] >25 mmHg.Results
We found that, mean ± SD serum P-selectin level (platelet activator marker) was significantly higher in thalassemic patients (2337 ± 566 pg/ml) in comparison to controls (1467 ± 247 pg/ml) (P < 0.001). Mean serum protein-C and antithrombin-III levels were significantly lower in thalassemic patients (1.2 ± 1.3 µg/ml, 27.3 ± 7.5 mg/dl) in comparison to controls (2.3 ± 1.3 µg/ml, 35.1 ± 4.1 mg/dl) (P = 0.003 and <0.001) respectively. PH was detected in 17 (47.2%) patients and it was significantly associated with splenectomy (P = 0.01) and non-transfusion dependent thalassemia (NTDT) (P = 0.04). PH was positively correlated with serum levels of P-selectin (r = 0.38, P = 0.02), fibrinogen (r = 0.41, P = 0.01) and negatively correlated with serum protein-C level (r = ?0.48, P = 0.003).Conclusion
A chronic hypercoagulable state and platelet activation is present in children with β-thalassemia. Splenectomy and transfusion infrequency are the main risk factors noted to be associated with such hypercoagulable state and platelet activation and consequently the PH among our thalassemic patients. 相似文献45.
Hatem A. Tawfik Ahmed Abdelhalim Mamdouh H. Elkafrawy 《Saudi Journal of Ophthalmology》2012,26(4):409-418
Computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit have been competing for the hearts and minds of health care providers for well over 2 decades. While several drawbacks pertaining to CT have been outlined since the introduction of MRI, CT remains the standard diagnostic test for evaluating cross-sectional, 2 or 3-dimensional images of the body. 相似文献
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Transition metal complexes containing vanadium IV have been shown to
modulate the cellular redox potential and catalyse the generation of
reactive oxygen intermediates (ROI). Since sperm function is exquisitely
susceptible to ROI, we examined the effects of stable chelate complexes of
vanadocenes on human sperm motility. We synthesized seven structurally
distinct chelate complexes of bis(cyclopentadienyl)vanadium(IV) with
bidentate ligands [i.e. vanadocene acetylacetonato monotriflate (VDacac),
vanadocene hexafluoro acetylacetonato monotriflate (VDHfacac), vanadocene
N-phenyl benzohydroxamato monotriflate (VDPH), vanadocene acethydroxamato
monotriflate (VDH), vanadocene catecholate (VDCAT), vanadocene bipyridino
ditriflate (VDBPY), and vanadocene dithiocarbamate monotriflate (VDDTC)],
and evaluated their spermicidal activity using computer-assisted sperm
analysis (CASA; Hamilton-Thorne). All seven chelate complexes of vanadocene
elicited potent spermicidal activity at micromolar concentrations (EC50
values: 3.9-106 microM) without affecting the sperm acrosome integrity. The
catecholate and acetylacetonate complexes of vanadocene were the most
active and the bipyridyl complex the least active with an order of efficacy
VDCAT > VDacac > VDDTC > VDPH > VDH > VDHfacac > VDBPY.
The spermicidal activity of chelate complexes of vanadocenes was rapid and
irreversible since the treated spermatozoa underwent apoptosis, as
determined by the flow cytometric analysis of mitochondrial membrane
potential, surface annexin V binding assay, in-situ nick-end labelling of
sperm nuclei, and confocal laser scanning microscopy. These results provide
unprecedented evidence that chelate complexes of vanadocene with bidentate
ligands have spermicidal and apoptosis inducing properties. These
vanadocene complexes, especially VDacac, may be useful as contraceptive
agents.
相似文献
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