血清EPO及sTfR水平与恶性肿瘤性贫血的相关性研究

目的探讨血清促红细胞生成素（erythropoietin,EPO）、可溶性转铁蛋白受体（soluble transferrin receptor,sTfR）水平和癌性贫血之间的关系,为临床合理使用重组人红细胞生成素（Recombinant Human Erythropietin,r-HuEPO）和铁剂治疗癌性贫血提供理论依据。方法采用酶联免疫分析方法（ELISA）测定60例癌性贫血患者血清EPO水平和sTfR水平,并将其与52例非癌性贫血患者的测定值及20例正常对照进行比较,以直线相关分析sTfR、EPO水平和Hb之间的关系。结果癌性贫血患者血清EPO、sTfR均较正常对照显著升高（P〈0.01）;癌性贫血患者血清EPO显著高于非癌性贫血患者（P〈0.05）;癌性贫血患者sTfR高于非癌性贫血患者,差异无显著性（P〉0.05）;癌性贫血患者血清EPO、sTfR升高的程度与贫血严重程度一致,与Hb值存在负相关,但与病期无明显相关性;EPO和sTfR之间无相关性。结论恶性肿瘤患者的血清EPO和sTfR水平能较好地反映其贫血病因,对贫血的治疗以及预后判断有一定的临床参考价值。     

癌性贫血患者血清促红细胞生成素的检测及其临床意义

促红细胞生成素（erythropoietin,EPO）主要由肾脏近曲小管附近的细胞合成和分泌,是调节红细胞生成和成熟的最重要的细胞因子,而且具有阻止红系祖细胞凋亡的功能。临床上很多癌症患者处于贫血状态,其血清EPO浓度的临床意义究竟如何目前尚有争议。为进一步明确血清EPO水平和癌性贫血水平之间的关系,以指导临床上对这类贫血患者的处理,     

老年血液系统恶性肿瘤合并贫血患者EPO和sTfR水平的测定及意义

目的 测定老年血液系统恶性肿瘤合并贫血患者红细胞生成素(EPO)、可溶性转铁蛋白受体(sTfR)的水平并对其临床意义进行研究.方法 选取贫血患者142例,根据疾病类型不同将患者分为血液肿瘤贫血组(n=41)、实体肿瘤贫血组(n=51)、缺铁性贫血组(n=50).比较3组患者的血清EPO、sTfR水平,并对EPO、sTfR与血红蛋白(Hb)的相关性进行分析.结果 3组患者的Hb水平比较,差异无统计学意义(P>0.05);血液肿瘤贫血组和缺铁性贫血组患者的EPO水平比较,差异无统计学意义(P>0.05);血液肿瘤贫血组和缺铁性贫血组患者的EPO水平均高于实体肿瘤贫血组(P<0.05);血液肿瘤贫血组和实体肿瘤贫血组患者的sTfR水平均低于缺铁性贫血组(P<0.05);缺铁性贫血组患者的Hb与EPO、sTfR均呈负相关(r=-0.861、-0.546,P<0.01).结论 血液肿瘤患者的贫血机制可能并非源于EPO生成不足,而是由于骨髓红系造血功能受到抑制.     

重组人红细胞生成素大剂量冲击维持疗法治疗30例肿瘤相关贫血的临床报告

背景与目的:贫血是癌症患者常见的并发症,重组人红细胞生成素(recombinanthumanerythropoietin,rhEPO)的应用能改善癌症贫血患者的症状,但其最佳使用方法仍在探讨之中。为探索rhEPO在肿瘤相关贫血患者中的最佳用药方案,本研究在同期接受化疗的癌症贫血患者中进行了rhEPO冲击维持疗法的临床应用研究。方法:采用开放性非随机的临床研究方法,选取2004年5月至2005年2月30例同期接受化疗且伴随贫血的恶性肿瘤患者,第1周采用rhEPO120000U冲击用药(40000U皮下d1,3,5),然后rhEPO每周40000U皮下维持用药,共3周(d8,15,22);比较治疗前及治疗开始后每2周的血红蛋白(Hb)水平和红细胞压积(Hct)值。结果:入组患者给予rhEPO后Hb水平呈持续上升趋势,在治疗后第2周及第4周Hb比基础值(79.56g/L)上升≥20g/L的患者分别占27.59%和61.90%;第2周(n=29)及第4周(n=21)Hb的平均值分别为90.26g/L和96.81g/L,与治疗前相比差异均具有显著性(P<0.05);第2周及第4周Hct的平均值分别为27.01%和30.17%,与治疗前(24.29%)相比也有所提高(P=0.062,P=0.001)。所有患者均耐受良好。结论:在恶性肿瘤贫血患者中使用rhEPO大剂量冲击维持疗法,可有效快速提高患者的血红蛋白水平,改善患者的贫血状况,该疗法耐受性较好,值得进一步扩大临床研究。     

癌性贫血与雄激素及其受体

癌性贫血是影响癌症患者生活质量和预后的重要因素.癌性贫血在实体瘤和血液系恶性肿瘤中的发病率很高,而放化疗进一步加重贫血的发生率和严重程度.癌性贫血的常规治疗方法主要包括输血、红细胞生成刺激因子疗法(如促红细胞生成素EPO)、补充铁剂以及更改放化疗方案.接受大剂量化疗的患者对EPO反应差,雄性激素可能通过改善骨髓对EPO的反应性而发挥疗效,本文综述了癌性贫血的原因,治疗及雄激素治疗贫血的机制.     

恶性肿瘤患者血清红细胞生成素的水平及化疗对其影响

目的:探讨恶性肿瘤患者血清红细胞生成素(EPO)水平的变化及化疗对其影响。方法:用化学发光法测定了49例血液肿瘤和45例非造血系统肿瘤贫血患者血清EPO水平,与正常对照进行比较,并对其中25例急性白血病和31例非造血系统肿瘤患者化疗前后血清EPO水平进行比较。结果:血液肿瘤和非造血系统肿瘤患者的血清EPO水平均显著高于正常对照组(P<0.001;P<0.01);血液肿瘤患者的血清EPO显著高于非造血肿瘤患者(P<0.001);急性白血病患者化疗后血清EPO水平显著高于化疗前(P<0.001);而非造血系统肿瘤患者化疗前后血清EPO水平无显著差异(P>0.05);HB与血清EPO之间存在显著负相关(r=-0.78,P<0.001)。结论:恶性肿瘤患者体内内源性EPO水平是增高的,化疗后EPO水平的变化与骨髓红系造血状况有关。     

癌症患者治疗前后血红蛋白变化及贫血发生情况的调查分析

目的:研究癌症患者初诊时和治疗前后的血红蛋白(Hb)变化、贫血发生情况及其与临床分期、年龄、消化道出血和化疗等方面的关系。方法:对我院近10年期间住院的3079例癌症癌患者进行回顾分析,研究治疗前后Hb值的变化和贫血的发生例数,并按临床分期、年龄、出血、性别和年龄分组进行分析。结果:1)3079例患者初诊时(治疗前)贫血发生率为45.0%(1386例),治疗后发生率为63.0%(1941例),P<0.001。Ⅰ级984例(50.7%),Ⅱ级615例(31.7%),Ⅲ级188例(9.7%),Ⅳ级154例(7.9%)。初诊时Hb值(110.3±22.9)g/L,治疗后为(104.8±23.8)g/L,P<0.001。2)单因素分析出血、临床分期、年龄、化疗和性别均是贫血的危险因素(均为P=0.000)。而Logistic多因素回归分析结果则为在P<0.05水平,出血、分期、年龄和化疗是贫血的危险因素(均为P=0.000),但性别则未能进入模型,P=0.777。3)胃癌、肺癌、肠癌、食管癌、淋巴瘤和泌尿生殖肿瘤的总贫血发生率均显著高于初诊时发生率,P<0.001;肺癌、淋巴瘤、食管癌、泌尿生殖肿瘤和头颈部癌治疗后的Hb值均明显低于初诊时,差异有统计学意义。4)各种类型肿瘤的贫血的发生率有所不同,但贫血程度的NCI分级则无统计学意义。结论:癌症患者有较高的贫血发生率;贫血的发生与临床分期、年龄、出血和化疗有密切关系,与患者性别无密切关系。高龄、出血、中晚期患者更易发生贫血。     

消化道肿瘤患者红细胞生成素水平的检测及其临床意义

目的 探讨消化道恶性肿瘤患者血清红细胞生成素（EPO）水平的变化,分析 EPO 与贫血和临床病理特征的关系。 方法 用化学免疫发光法检测 226 例 1293 人次的消化道恶性肿瘤患者血清 EPO 水平,分析 EPO 与临床病理特征的相关性。 结果 消化道肿瘤患者红细胞平均血红蛋白浓度（MCHC）为（0.29±0.01） g/L, E P O 水平为（52.25±129.64） IU/L。贫血和 不贫血的肿瘤患者 EPO 有显著性差异（Z=-27.80, P<0.05, 双侧）。不同程度贫血患者的 EPO 有显著性差异（X=126.26, P<0.01, 双侧）。 IV 期患者和其他分期患者 E P O 水平分别为（60.05±141.43） IU/L 和（21.80±28.69） IU/L,有显著性差异 （X=52.47, P<0.01,双侧）, 血红蛋白浓度分别为（122.24±19.66）g/L 和（130.98±16.95）g/L,有显著性差异（X=47.87, P<0.01,双侧）。消化道肿瘤患者化疗前后患者贫血程度及 EPO 水平无显著性差异。 结论 消化道恶性肿瘤贫血多为小细 胞低色素性贫血。贫血肿瘤患者血清 EPO 水平异常增高,且肿瘤晚期和转移患者 EPO 水平增高更明显。分析化疗和贫血 及 EPO 的关系还需要考虑更多相关因素。     

Hepcidin在恶性血液病贫血患者中的表达及临床意义

目的:探讨铁调素(hepcidin)在恶性血液病贫血患者中的表达,并对hepcidin与白细胞介素6 (interleukin-6,IL-6)、血红蛋白(hemoglobin,Hb)、血清铁和铁蛋白表达水平进行相关性分析。方法:收集80例恶性血液病贫血患者外周血,分别检测hepcidin、IL-6、Hb、血清铁和铁蛋白的表达水平,并以30例健康人群作为对照;使用SPSS 21.0软件对实验结果进行统计学分析。结果:恶性血液病贫血患者血清中hepcidin、IL-6、Hb、血清铁和铁蛋白的表达量分别为(61.93±19.98) μg/L、(5.56±1.17) ng/L、(96.68±12.35) g/L、(9.85±1.09) μmol/L和329.42(299.70~459.06) μg/L;健康对照组相对应的表达量分别为(21.35±7.38) μg/L、(2.52±1.28) ng/L、(140.07±7.71) g/L、(19.95±4.25) μmol/L和95.72(76.56~131.42) μg/L,两组差异均具有统计学意义(P<0.01)。恶性血液病男性贫血患者中hepcidin、IL-6和Hb的表达量均高于女性患者(P<0.05);中度贫血患者hepcidin、IL-6和铁蛋白的表达量均高于轻度贫血患者,Hb和血清铁表达量低于轻度贫血患者(P<0.01)。线性回归分析结果显示hepcidin与Hb、血清铁含量呈负相关,与IL-6、铁蛋白含量呈正相关(P<0.05)。结论:Hepcidin在恶性血液病贫血患者中高表达,并与贫血程度相关,提示hepcidin在恶性血液病贫血发生中具有重要作用。     

癌性贫血患者内源性促红细胞生成素水平的研究

 目的 研究癌性贫血患者血清促红细胞生成素（ＥＰＯ）水平及其与血红蛋白（Ｈｂ）含量之间的关系。方法 用放射免疫分析检测血清ＥＰＯ含量，以直线相关分析ＥＰＯ水平与Ｈｂ含量之间的关系。结果癌性贫血患者血清ＥＰＯ含量为２．６２±０．９５μｇ／Ｌ（ｎ＝４３），显著高于不伴有贫血的癌症患者（１．７０±０．４１μｇ／Ｌ，ｎ＝３９）和正常对照组（１．５９±０．６９μｇ／Ｌ，ｎ＝９４）。癌性贫血患者血清 ＥＰＯ含量与 Ｈｂ水平存在明显的负相关关系（ｒ＝－０．６８２９３，Ｐ＜０．０１）。结论 癌性贫血患者血清内源性 ＥＰＯ水平增高，提示对此类患者检测血清 ＥＰＯ水平有助于指导临床治疗。     

Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecularly targeted anti-cancer agents being used to attack malignancy in a rational manner. A large body of preclinical data indicates that FTase inhibitors block cancer cell proliferation through both cytostatic and cytotoxic effects. Interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they may target unique aspects of cancer cell pathophysiology. The development of FTase inhibitors was predicated on the discovery that the Ras oncoproteins must be post-translationally modified to transform cells. However, recent work indicates that the anti-neoplastic effects of FTase inhibitors depend on altering the post-translational modifications of non-Ras proteins as well. In particular, a critical target protein that responds to FTase inhibition by blocking tumor cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In this review, we survey the biological foundations for the clinical development of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.     

Targeting tumor vasculature with homing peptides from phage display

Tumor vasculature expresses a number of molecular markers at much lower levels than those seen in the blood vessels of normal tissues, and in some cases, such markers are undetectable. The presence of these markers relates to angiogenesis; the same markers are shared by all blood vessels undergoing angiogenesis. The endothelial cells, pericytes and smooth muscle cells, and the vascular extracellular matrix in angiogenic vessels can each express such markers. Molecularly, they represent vascular growth factor receptors, cell adhesion proteins and their receptors. Screening of phage display libraries for peptides that home to tumor vasculature when injected into mice has recently provided a new tool for analyzing the distinguishing features of tumor vasculature. Tumor-homing peptides isolated in this manner, as well as an antibody against a form of fibronectin expressed in tumor blood vessels, have been found to serve as targeting devices to concentrate drugs and other therapeutic materials to tumors in in vivo models. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.     

Identification of EBV transforming genes by recombinant EBV technology

Epstein-Barr virus (EBV) is able to infect primary B-lymphocytes but usually does not proceed to replicate more virions. Instead, EBV persists as an incomplete virus and expresses 12 gene products that transform the growth of these cells into continuously proliferating lymphoblastoid cell lines. Because EBV is associated with several human malignancies, there is intense interest in delineating the molecular functions of these EBV gene products in transformation. This review focuses on the recombinant EBV technologies that have been developed to introduce specific mutations into EBV and test the functions of these EBV genes in primary B-lymphocyte growth transformation.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

New aspects of integrin signaling in cancer

Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behavior, including motility and invasiveness, cell growth, and cell survival. Engagement of integrins with extracellular matrix (ECM) proteins can activate members of the Rho-family of small GTPases; conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands. These events impinge on the control of cell motility, and ultimately on invasive and metastatic behavior. Integrin engagement with ECM also has important effects on cell survival, particularly for cells of epithelial origin. In some cases, specific integrins have selective effects on the efficiency of signal transduction in cell survival pathways.     

Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.     

腹部压块对膈肌运动影响的研究

目的 :研究腹部压块对膈肌运动的影响。方法 :选择拟行立体适形放疗患有肺癌或肝脏肿瘤的患者 2 0例。按治疗体位仰卧于体部立体放疗定位负压袋内 ,待患者呼吸平稳后 ,将灯光野的中心点置于膈顶运动的最低点 ,在膈肌运动至最高位时拍摄照片 ,测量膈肌运动的最大幅度 ;然后 ,将心形腹部压块放置于患者剑突下 ,并用定位框架的腹带交叉固定 ,按压程度以不引起患者呼吸困难或其他不适为标准 ,5min后按上述方法再次测量膈肌运动的最大幅度。结果 :2 0例患者未加腹部压块的运动幅度为0 6 2～ 2 6 7cm ,平均 (1 4± 0 6 4)cm ,加腹部压块后的膈肌运动幅度为 0 2 8～ 2 0 8cm ,平均 (1 0±0 5 5 )cm ,加腹部压块后膈肌运动幅度平均减小 (0 4± 0 34)cm ,P =0 0 0 0。加腹部压块后 90 % (18/2 0 )的患者膈肌运动幅度受到不同程度的限制 ,但有 10 % (2 /2 0 )的患者膈肌运动幅度增加。结论 :腹部压块可使大部分患者膈肌运动的幅度减小 ,但少部分患者例外 ,即腹部压块并不能使所有膈肌周围肿瘤的照射容积减少。建议在制定放射治疗计划前应预先进行测量和评价     

ABCG2在肺癌中表达的定量研究

目的 观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义.方法 常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度.结果 ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜.在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P＜0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零.癌周肺组织表达的PU值高于各型肺癌(P＜0.05).ABCG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P＞0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P＞0.05),与肺癌分化程度有关(P＜0.001).分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P＞0.05).结论 ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一.     

Telomerase and human tumorigenesis

Human cancer cells, unlike their normal counterparts, have shed the molecular restraints to limited cell growth and are immortal. Exactly how cancer cells manage this at the molecular level is beginning to be understood. Human cells must overcome two barriers to cellular proliferation. The first barrier, referred to as senescence, minimally involves the p53 and Rb tumor-suppressor pathways. Inactivation of these pathways results in some extension of lifespan. However, inactivation of these pathways is insufficient for immortalization. As normal cells undergo repeated rounds of DNA replication, their telomeres shorten due to the inability of traditional DNA polymerases to completely replicate the end of the chromosomal DNA. This shortening continues until the cells reach a second proliferative block referred to as crisis, which is characterized by chromosomal instability, end-to-end fusions, and cell death. Stabilization of the telomeric DNA through either telomerase activation or the activation of the alternative mechanism of telomere maintenance (ALT) is essential if the cells are to survive and proliferate indefinitely. Conversely, loss of telomere stabilization by an already-immortalized cell results in loss of immortality and cell death. Together this indicates that telomere maintenance is a critical component of immortality. In this review we attempt to describe our current understanding of the role of telomere maintenance in senescence, crisis, and tumorigenesis.     

Post-translational regulation of COX2 activity by FYN in prostate cancer cells

While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.