促红细胞生成素对腹膜透析患者红细胞免疫功能的影响

应用重组人类促红细胞生成素（rHuEPO）治疗终末期尿毒症腹膜透析（CAPD）患者28例，治疗16周，分别检测治疗前后红细胞C3b受体花环率（E·C3bR·R）和红细胞免疫复合物花环率（E·IC·R）。治疗后E·C3bR·R升高，E·IC·R降低，而对照组无变化．提示rHuEPO可改善患者红细胞免疫功能。     

红细胞生成素受体介导的白血病细胞5纱增殖信号传导的研究

目的 检测白血病细胞系红细胞生成素受体（ＥｐｏＲ）的表达并阐明ＥｐｏＲ介导的白血病细胞系ＫＯＣＬ－３３增殖信号传导途径。方法 用生物系酰基化Ｅｐｏ及流式细胞仪检测白血 纱ＫＯＣＬ－３３细胞中几种信号传导蛋白 酷氨酸磷酸化。结果 （１）除Ｔ淋巴细胞系外,其余细胞纱ＥｐｏＲ表达均为阳性,阳性率为１８％～９９％,均值５２％。不同类型的细胞系ＥｐｏＲ阳性率的差异没有统计学意义。（２）９株细胞中７株细胞因受     

重组人促红细胞生成素治疗结肠和直肠癌化疗相关贫血

目的 :观察重组人促红细胞生成素 (rhEPO)治疗结、直肠癌化疗相关贫血的疗效。方法 :选择 6 2例结、直肠癌采用以奥沙利铂为主联合方案化疗所致贫血患者 ,随机分为两组 :rhEPO治疗组 34例 ,给予皮下注射rhEPO 4 0 0 0 0U/周。对照组 2 8例 ,不给予rhEPO治疗 ,仅给予五参芪口服液。结果 :治疗后 4周起治疗组患者血红蛋白 (Hb) ,红细胞压积 (HCT)、红细胞总数 (RBC)均明显上升 ,与对照组相比差异有统计学意义 (P <0 .0 1)。rhEPO治疗组总有效率为 79.4 % ,对照组为 2 1.7% ,差异有统计学意义 (P <0 .0 1)。结论 :rhEPO 4 0 0 0 0U/周对晚期结、直肠癌联合方案化疗相关贫血有肯定的疗效     

Cutaneous allergic reaction correlates with anti‐erythropoietin antibodies in dialysis patient developing pure red cell aplasia

We describe a case of concomitant erythropoietin allergy and resistance with a possible IgE and IgG‐mediated immune response, in which the local allergic cutaneous symptoms preceded the antibody‐mediated anemia.     

促红细胞生成素后处理对大鼠再灌注损伤肺细胞凋亡的干预及机制

目的：探讨促红细胞生成素后处理对再灌注损伤肺细胞凋亡的干预作用及其机制。方法：健康雄性成年SD大鼠40只,随机分为假手术对照组（C组）、缺血/再灌注组（I/R组）、促红细胞生成素＋缺血/再灌注组（EPO组）、促红细胞生成素＋溶剂对照组1（0.4%DMSO的PBS溶液）（D组）和促红细胞生成素＋U0126（U组）。对比观察各组肺组织湿/干重比值（W/D）的变化;原位缺口末端标记法（TUNEL）检测肺组织细胞凋亡情况,计算凋亡指数（AI）;免疫组织化学方法测定肺组织Bcl-2、Bax蛋白的相对含量,RT-PCR法检测肺组织Bcl-2、Bax mRNA表达;光镜下观察肺组织的病理变化及测定肺泡损伤数（IQA）。结果：与C组比较,I/R组肺组织W/D显著升高,I/R组IQA显著升高,AI显著升高,Bcl-2蛋白和Bcl-2 mRNA表达明显下降,Bax蛋白和Bax mRNA表达明显上调,Bcl-2/Bax和Bcl-2 mRNA/Bax mRNA的比值降低（ P均〈 0.01）,肺组织形态学发生异常改变;与I/R组比较,EPO组、D组、U组的W/D显著降低,IQA显著降低,AI显著降低,Bcl-2蛋白和Bcl-2 mRNA表达增强,Bax蛋白和Bax mRNA表达减弱,Bcl-2/Bax和Bcl-2 mRNA/Bax mRNA的比值增高（P 〈0.05或P 〈0.01）,肺组织形态学结构异常改变有所减轻;与EPO组比较,D组的W/D、IQA、AI、Bcl-2蛋白和Bcl-2 mRNA、Bax蛋白和Bax mRNA及Bcl-2/Bax和Bcl-2 mRNA/Bax mRNA的比值均无明显差异（P〉0.05）,U组的W/D升高,IQA升高,AI显著升高,Bcl-2蛋白和Bcl-2 mRNA表达下降,Bax蛋白和Bax mRNA表达上调,Bcl-2/Bax和Bcl-2 mRNA/Bax mRNA的比值降低（P 〈0.05或P 〈0.01）,U组的肺组织形态学结构损伤较EPO组加重。结论：促红细胞生成素后处理能减轻肺缺血/再灌注损伤,其机制可能通过激活ERK1/2信号转导通路,上调凋亡抑制因子Bcl-2的表达,下调促凋亡基因Bax的表达,提高Bcl-2/Bax比值,使肺组织细胞凋亡减少。     

Advances in understanding iron metabolism and its crosstalk with erythropoiesis

Recent years have witnessed impressive advances in our understanding of iron metabolism. A number of studies of iron disorders and of their animal models have provided landmark insights into the mechanisms of iron trafficking, distribution and homeostatic regulation, the latter essential to prevent both iron deficiency and iron excess. Our perception of iron metabolism has been completely changed by an improved definition of cellular and systemic iron homeostasis, of the molecular pathogenesis of iron disorders, the fine tuning of the iron hormone hepcidin by activators and inhibitors and the dissection of the components of the hepcidin regulatory pathway. Important for haematology, the crosstalk of erythropoiesis, the most important iron consumer, and the hepcidin pathway has been at least partially clarified. Novel potential biomarkers are available and novel therapeutic targets for iron‐related disorders have been tested in murine models. These preclinical studies provided proofs of principle and are laying the ground for clinical trials. Understanding iron control in tissues other than erythropoiesis remains a challenge for the future.     

A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain

Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnatal brain, whereas EPO is abundant in embryonic brain and decreases postnatally. Upon hypoxia, EPO and its receptor are rapidly reexpressed, whereas neuronal TPO and its receptor are down-regulated. Unexpectedly, TPO is strongly proapoptotic in the brain, causing death of newly generated neurons through the Ras-extracellular signal-regulated kinase 1/2 pathway. This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired target-derived neurotrophic support.     

Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies

Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end-stage renal failure and cancer-related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was <6 months. All six patients were treated with rHuEpo for their anemia, either without any chemotherapy or very mild chemotherapy for a short time. Yet, surprisingly they lived for 45-133 months totally from MM diagnosis and 38-94 months with rHuEpo (with a good quality of life). In fact, one patient, is still alive and well, more than 8 yr after chemotherapy was discontinued because of a resistant aggressive disease. The course in these six MM patients led us to hypothesize that Epo might have an antineoplastic or antimyeloma effect. We proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with MOPC-315 myeloma cells. We then presented evidence that the mechanism is a new immune-mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Future trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.     

Detection and quantification of functionally defined hematopoietic progenitor cells and tissue specific mRNA within the peripheral blood of myeloma patients after administration of granulocyte colony-stimulating factor and erythropoietin

Objective:  Hematopoietic progenitor cells (HPC) as well as tissue committed stem cells expressing mRNA specific to various somatic tissues are thought to be part of the CD34⁺ bone marrow compartment. In this study, we explore and quantify their mobilization in patients with multiple myeloma undergoing chemotherapy upon administration of granulocyte colony-stimulating factor (G-CSF) plus/minus erythropoietin (EPO).
Patients and methods:  HPC were quantified by flow cytometry and functional assays within the blood of healthy donors and myeloma patients before and after chemotherapy followed by G-CSF or G-CSF + EPO given subcutaneously. The mRNA expression was studied by quantitative polymerase chain reaction (PCR). Cytokines and peripheral blood protease levels were measured by an enzyme-linked immunosorbent assay.
Results:  EPO did not significantly alter the number of HPC mobilized by G-CSF alone, and mRNA specific for liver, brain, muscle and kidney was detected in both treatment groups. Quantitative PCR analysis revealed a 2.7-fold increased expression of glial fibrillary acidic protein after G-CSF + EPO administration compared to G-CSF alone ( P  = 0.003). The concentration of G-CSF rose from 62 ± 22 pg/mL and 48 ± 10 pg/mL to 28 ± 9 ng/mL and 85 ± 10 ng/mL after 10 d of treatment with G-CSF and G-CSF + EPO, respectively. The concentration of neutrophil elastase (NE) rose only in the G-CSF group by a factor 1.5.
Conclusion:  The alteration of G-CSF and NE levels as well as the expression of tissue committed RNA after the administration of EPO in addition to G-CSF indicate that different growth factors mobilize different stem cells that might potentially be used for the support of tissue repair in future treatment protocols.