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101.
Alice Guazzelli Parisa Meysami Emyr Bakker Ezio Bonanni Constantinos Demonacos Marija Krstic-Demonacos 《Expert opinion on investigational drugs》2013,22(8):719-732
Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival.Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy.Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment 相似文献
102.
103.
Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia 总被引:4,自引:2,他引:4
We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production. 相似文献
104.
de Haas M; Kerst JM; van der Schoot CE; Calafat J; Hack CE; Nuijens JH; Roos D; van Oers RH; von dem Borne AE 《Blood》1994,84(11):3885-3894
In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo. 相似文献
105.
106.
High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy 总被引:2,自引:1,他引:2
Brown RA; Herzig RH; Wolff SN; Frei-Lahr D; Pineiro L; Bolwell BJ; Lowder JN; Harden EA; Hande KR; Herzig GP 《Blood》1990,76(3):473-479
Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens. 相似文献
107.
Esmée A. Bakker Duck-chul Lee Xuemei Sui Thijs M.H. Eijsvogels Francisco B. Ortega I-Min Lee Carl J. Lavie Steven N. Blair 《Mayo Clinic proceedings. Mayo Clinic》2018,93(4):419-428
Objective
To examine the associations of resistance exercise, independent of and combined with aerobic exercise, with the risk of development of hypercholesterolemia in men.Patients and Methods
This study used data from the Aerobics Center Longitudinal Study, which is a cohort examining the associations of clinical and lifestyle factors with the development of chronic diseases and mortality. Participants received extensive preventive medical examinations at the Cooper Clinic in Dallas, Texas, between January 1, 1987, and December 31, 2006. A total of 7317 men aged 18 to 83 years (mean age, 46 years) without hypercholesterolemia at baseline were included. Frequency (times per week) and total amount (min/wk) of resistance and aerobic exercise were determined by self-report. Hypercholesterolemia was defined as a total cholesterol level of 240 mg/dL or higher or physician diagnosis.Results
During a median (interquartile range) follow-up of 4 (2 to 7) years, hypercholesterolemia developed in 1430 of the 7317 men (20%). Individuals meeting the resistance exercise guidelines (≥2 d/wk) had a 13% lower risk of development of hypercholesterolemia (hazard ratio [HR], 0.87; 95% CI, 0.76-0.99; P=.04) after adjustment for general characteristics, lifestyle factors, and aerobic exercise. In addition, less than 1 h/wk and 2 sessions per week of resistance exercise were associated with 32% and 31% lower risks of hypercholesterolemia (HR, 0.68; 95% CI, 0.54-0.86; P=.001; and HR, 0.69; 95% CI, 0.54-0.88; P=.003), respectively, compared with no resistance exercise. Higher levels of resistance exercise did not provide benefits. Meeting both resistance and aerobic exercise guidelines (≥500 metabolic equivalent task min/wk) lowered the risk of development of hypercholesterolemia by 21% (HR, 0.79; 95% CI, 0.68-0.91; P=.002). compared with meeting none of the guidelines.Conclusion
Compared with no resistance exercise, less than 1 h/wk of resistance exercise, independent of aerobic exercise, is associated with a significantly lower risk of development of hypercholesterolemia in men (P=.001). However, the lowest risk of hypercholesterolemia was found at 58 min/wk of resistance exercise. This finding suggests that resistance exercise should be encouraged to prevent hypercholesterolemia in men. However, future studies with a more rigorous analysis including major potential confounders (eg, diet, medications) are warranted. 相似文献108.
Correlations between plasma strontium concentration,components of calcium and phosphate metabolism and renal function in type 2 diabetes mellitus
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109.
Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open‐angle glaucoma
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