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11.
Transforming growth factor beta (TGF-beta) is a potent and selective growth inhibitor of early hematopoietic progenitors and leukemic cells. The cellular mechanism(s) underlying this antiproliferative effect is, however, currently unknown. In the present study, we demonstrate that TGF-beta inhibits the expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3), and granulocyte-CSF (G-CSF) receptors on murine factor-dependent and independent hematopoietic progenitor cell lines without a significant change in receptor affinity. A maximum reduction in GM-CSF receptor numbers of 65% to 77% was observed by 96-hour incubation with TGF-beta. The TGF- beta induced trans-down-modulation of GM-CSF receptors was prolonged, noncytotoxic but reversible, and not due to endogenous production of GM- CSF. The TGF-beta induced reduction in CSF receptor numbers preceded TGF-beta's growth inhibitory action. In addition, the ED50 (1 to 10 pmol/L) for TGF-beta's CSF receptor modulatory and antiproliferative effect was similar. The effect of TGF-beta on cell surface CSF receptor expression was specific, because the expression of other cell surface proteins (Ly 5 and Ly 17) was not affected by TGF-beta treatment, and because other growth inhibitors (tumor necrosis factor and interferon) did not affect CSF receptor expression. These data suggest that the downregulation of the growth of hematopoietic progenitor cells by TGF- beta involves reducing the cell surface expression on growth factor receptors. 相似文献
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Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
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目的:探讨如达溃疡散对大鼠乙酸性胃溃疡的作用及对其血清促胃液素(gastrin)含量的影响.方法:采用乙酸法复制胃溃疡模型,将大鼠随机分为对照组、如达溃疡散组、雷尼替丁组,观察如达溃疡散对大鼠胃溃疡的作用,并检测其对大鼠血清中促胃液素含量的影响.结果:与对照组相比,如达溃疡散能明显抑制溃疡的发生,抑制血清促胃液素含量.结论:如达溃疡散具有抗胃溃疡的作用,其作用机理可能是通过抑制促胃液素释放,进一步减少胃酸分泌来实现的. 相似文献
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CJT De Amorim e Silva A Mackenzie LM Hallowell SE Stewart MR Ditchfield 《Journal of Medical Imaging and Radiation Oncology》2006,50(4):319-323
The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital. 相似文献
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SE Daley AD Pearson AW Craft J Kernahan RA Wyllie L Price C Brock C Hetherington D Halliday K Bartlett 《Archives of disease in childhood》1996,75(4):273-281
Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover. 相似文献
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