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521.
Allogeneic blood transfusions have been reported to induce immunomodulation in recipients of blood products. While the mechanism(s) of this immunomodulatory effect is unknown, it has been suggested that this effect of allogeneic blood transfusions could adversely affect patients with a malignant disorder. These concerns have been supported by a number of nonrandomized, mainly retrospective, clinical studies which indicate that allogeneic blood transfusions can adversely affect prognosis following the surgical treatment of oncology patients. Recently, we have shown that allogeneic blood transfusions enhance primary tumor growth and increase metastatic pulmonary nodule formation in inbred mice. The tumor growth-promoting activity of allogeneic blood transfusions was studied also using outbred rabbits. In this present study, we demonstrate that the tumor growth-promoting effect of allogeneic blood transfusions is mediated by donor leukocytes and that this effect can be abolished by their removal before transfusion. We show also that the allogeneic blood transfusion tumor growth-promoting effect can be passively transferred to naive animals (both mice and rabbits) using spleen cells from allogeneically transfused animals. In these experiments, numbers of metastatic pulmonary nodules were significantly increased in both mice and rabbits that had received spleen cells from allogeneically transfused animals compared with those that had received spleen cells from syngeneically transfused animals, or from animals that had been transfused with leukodepleted allogeneic blood. 相似文献
522.
The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells 总被引:2,自引:0,他引:2
Luqman M Klabunde S Lin K Georgakis GV Cherukuri A Holash J Goldbeck C Xu X Kadel EE Lee SH Aukerman SL Jallal B Aziz N Weng WK Wierda W O'Brien S Younes A 《Blood》2008,112(3):711-720
B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder characterized by the surface expression of CD20, CD5 antigens, as well as the receptor CD40. Activation of CD40 by its ligand (CD40L) induces proliferation and rescues the cells from spontaneous and chemotherapy-induced apoptosis. CD40 activation also induces secretion of cytokines, such as IL-6, IL-10, TNF-, IL-8, and GM-CSF, which are involved in tumor cell survival, migration, and interaction with cells in the tumor microenvironment. Here we demonstrate that in primary B-CLL tumor cells, the novel antagonist anti-CD40 monoclonal antibody, HCD122, inhibits CD40L-induced activation of signaling pathways, proliferation and survival, and secretion of cytokines. Furthermore, HCD122 is also a potent mediator of antibody-dependent cellular cytotoxicity (ADCC), lysing B-CLL cells more efficiently than rituximab in vitro, despite a significantly higher number of cell surface CD20 binding sites compared with CD40. Unlike rituximab, however, HCD122 (formerly CHIR-12.12) does not internalize upon binding to the cells. Our data suggest that HCD122 may inhibit B-CLL growth by blocking CD40 signaling and by ADCC-mediated cell lysis. 相似文献
523.
524.
目的:观察骨髓基质干细胞与异种脱蛋白松质骨复合修复尺骨缺损的可行性。方法:实验于2006-01在辽宁医学院附属第一医院外科实验室(省级重点实验室)完成。①实验材料:取12月龄健康杂种犬18只,体质量(15.0±2.2)kg。②实验方法:将所有动物的双侧尺骨制备成中断20mm骨-骨膜缺损模型,骨髓基质干细胞与脱蛋白松质骨于体外复合培养后,将其植入其中16只犬的右侧缺损处作为实验组,左侧植入单纯脱蛋白松质骨作为对照组,另2只犬不植入任何材料为空白组。③实验评估:在4,8,12周分别行大体标本、扫描电镜和组织学观察,比较3组骨缺损修复的能力。结果:纳入健康杂种犬18只,均进入结果分析。4周时实验组支架材料部分吸收,植入物表面有纤维骨痂形成,对照组支架材料少量吸收,植入物表面有少量骨样组织形成;8周时,大体标本及组织学观察,实验组中的支架材料已完全降解,骨缺损部分修复,对照组中植入物两端少量新骨形成,材料中为纤维骨样组织;12周时,实验组骨缺损完全修复,对照组植入物两端有新骨包绕,与骨端连接紧密。12周时空白组骨缺损未修复。结论:利用体外扩增培养的骨髓基质干细胞与异种骨组合,具有较强的骨传导和骨诱导活性。 相似文献
525.
R Condliffe DG Kiely JS Gibbs PA Corris AJ Peacock DP Jenkins K Goldsmith JG Coghlan J Pepke-Zaba 《The European respiratory journal》2009,33(2):332-338
Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength. 相似文献