重组人白细胞介素11预防和治疗血小板降低的临床研究报告

背景与目的:肿瘤化疗可引起血小板下降,有必要研制预防和治疗血小板减少的药物。本文主要观察重组人白细胞介素11(rhIL-11)预防和治疗化疗引起的血小板减少的疗效和毒性。方法:研究分两部分,第一部分主要观察rhIL-11能否预防化疗引起的血小板下降。109例癌症患者进入对照研究组,随机分AB和BA两组,每例患者均化疗2个疗程。A疗程化疗后加rhIL-11,B疗程化疗后不用rhIL-11治疗。rhIL-11剂量为:50μg·(kg·d)-1于化疗结束后24h开始,臀部皮下注射,连用14天或直到血小板从最低点恢复至>400×109/L。第二部分主要观察rhIL-11能否治疗化疗引起的血小板下降。41例化疗后血小板<50×109/L的患者直接进入开放研究组,IL-1150μg·(kg·d)-1,连用14天或至血小板>400×109/L。结果:对照研究组107例患者可评价疗效,A疗程化疗后全组血小板平均数量为(246.49±88.64)×109/L;B疗程化疗后全组血小板平均数量为(180.24±83.34)×109/L(P=0.000)。A疗程Ⅲ/Ⅳ级血小板减少发生率为6.5%(7/107),B疗程Ⅲ/Ⅳ级血小板减少发生率为14%(15/107)(P=0.04)。A疗程化疗后血小板最低值:(136.46±74.64)×109/L,B疗程化疗后血小板最低值为(107.77±61.33)×109/L(P=0.000)。A疗程化疗后血小板最高值(381.28±150.39)×109/L,B疗程化疗后血     

基因重组人白细胞介素-11治疗恶性肿瘤化疗所致血小板减少症的临床探讨

目的观察基因重组人白细胞介素-11(rhIL-11)治疗恶性肿瘤化疗所致血小板减少症的临床疗效及不良反应。方法本组51例患者随机分为治疗组(27例)和对照组(24例)。治疗组病例化疗后外周血血小板计数≤50×109/L时,给予rhIL-11 1.5 mg皮下注射,1/d,连续用药5~14 d,平均9.2 d;当外周血血小板升至≥100×109/L时停用rhIL-11观察血像。对照组病例仅以输注血小板及对症治疗为主。结果治疗组患者应用rhIL-11前后自身比较血小板计数最低值显著升高,差异有显著性(P<0.01);治疗组患者化疗后应用rhIL-11血小板计数最低值较对照组化疗后的最低值显著升高,差异也有显著性(P<0.01);治疗组应用白介素-11后血小板计数低于5.0×109/L的天数比对照组明显缩短,两者比较差异也有显著性(P<0.01)。共治疗27例恶性肿瘤化疗所致的血小板减少症,显效9例(33.3%),有效18例(66.7%)。结论在恶性肿瘤化疗所致的血小板减少症的治疗中,rhIL-11的升血小板作用显著、安全、经济实用。     

重组人血小板生成素治疗化疗所致的血小板减少症的疗效分析

目的:观察重组人血小板生成素 (recombinant human-thrombopoietin,rhTPO)治疗肿瘤化疗所致血小板减少的有效性及安全性.方法:回顾性分析我院经化疗后血小板计数≤50×109/L的肿瘤患者87例,分为rhTPO组45例和国产组白介素11(rhIL-11)组42例.rhTPO组给予rhTPO 300u/kg,皮下注射每日1次,连续使用;rhIL-11组给予rhIL-11 1.5mg皮下注射,每日1次,连续使用;两组在用药过程中待血小板计数恢复至≥100×109/L以上或血小板计数绝对值升高≥50×109/L时即停用.结果:rhTPO组患者血小板计数恢复至100×109/L平均使用7天,有效率86.6%;rhIL-11组患者血小板计数恢复至100×109/L平均使用11天,有效率69%,两组疗效比较有统计学差异(P<0.05).rhTPO组和rhIL-11组因出现出血症状而采取输注血小板患者例数分别为1例和3例.结论:rhTPO对肿瘤化疗所致的血小板减少症有效率高,起效快,安全性高,值得进一步推广.     

重组人白细胞介素-11治疗实体瘤化疗所致的血小板减少症的随机对照研究

目的:观察重组人白细胞介素-11(rhIL-11)治疗实体瘤化疗所致的血小板减少症的客观疗效;观察rhIL-11在人体的不良反应及其安全性.方法:本研究采用随机对照试验,55例化疗后血小板低于50×109/L的患者,随机分为A组和B组,A组接受rhIL-11,B组不接受rhIL-11治疗.主要观察IL-11能否治疗化疗引起的血小板减少症.结果:A组血小板值在第2～21d均高于B组,第4～21天差别具有显著的统计学意义;A组Ⅱ°、Ⅲ°及Ⅳ°血小板减少的持续天数分别为3.0d、3.2d及0.4d,B组分别为5.1d、5.8d及2.2d,A组血小板减少持续天数短于B组,但无统计学差异.IL-11的不良反应主要包括:心悸、心律失常、水肿、发热、关节肌肉疼痛、注射局部疼痛、皮疹、头痛头晕、乏力等.大多较轻,可以耐受.结论:rhIL-11能刺激血小板增生,治疗化疗引起的血小板降低,是一种有效、安全的治疗血小板减少的药物,值得进一步研究.     

重组人白细胞介素-11在16例急性髓系白血病化疗中的应用

 目的　观察重组人白细胞介素-11（rhIL-11）对急性髓系白血病化疗所致血小板减少的疗效和患者不良反应。方法　新诊断的16例急性髓系白血病患者分别接受DA 或TA 化疗方案,采用随机空白对照、自身交叉的研究方法,观察rhIL-11对化疗后血小板下降恢复的影响。化疗结束后24 h开始使用rhIL-11,皮下注射,连用7～14 d,血小板稳定在30×109／L且无明显的出血倾向时停药。结果　rhIL-11明显提高患者化疗后血小板计数,减少输注血小板的次数,且rhIL-11注射后患者不良反应轻微,主要表现为乏力、肌肉酸胀或低热等。结论　rhIL-11可有效促进化疗后外周血小板恢复,缩短血小板减少持续时间,减少输血相关并发症的发生,患者耐受性好。     

重组人白细胞介素11治疗急性白血病化疗所致血小板减少的多中心研究

目的 探究重组人白细胞介素11(rhIL-11)治疗急性白血病化疗所致血小板减少症的效果及安全性.方法 纳入2016年2月至7月全国6个中心急性白血病化疗后血小板减少症[血小板计数(Plt)<50×109/L]患者,给予rhIL-11皮下注射治疗,2 mg/次,2次/d,连续使用7 d或至Plt经最低值后恢复到≥50×109/L时停用,观察受试者Plt恢复情况.结果 共入组患者112例,2例退出.110例有效病例中,rhIL-11治疗的总有效率为74.5％(82/110),治疗前后受试者Plt回升平均量为(70±54)×109/L,治疗有效者Plt恢复的平均时间为(8.7±3.0)d.在重度血小板减少症的治疗上,单药rhIL-11治疗与rhIL-11联合血小板输注治疗相比,受试者Plt恢复时间缩短,差异有统计学意义[(8.0±2.6)d比(9.6±3.5)d,t=2.17,P=0.03].结论 rhIL-112次/d皮下注射的给药方式可加速血小板恢复,降低血小板输注率,不良反应少,值得临床推广应用.     

重组人白细胞介素-11治疗急性髓系白血病化疗后血小板减少36例

目的 观察重组人白细胞介素-11(rhIL-11,商品名:巨和粒)防治急性髓系白血病化疗后血小板减少的疗效及患者不良反应.方法 两组均采用DA或TA方案化疗,治疗组在化疗结束48 h后应用rhIL-11 3 mg/d皮下注射,连用10～14 d,观察两组化疗前后血小板计数、化疗后血小板最低值、血小板恢复时间及输注血小板的情况.结果 治疗组与对照组化疗前血小板计数差异无统计学意义(P＞0.05),治疗组血小板最低均值[(21.72±8.64)×109/L]高于对照组[(14.67±5.18)×109/L](P＜0.05),血小板恢复时间较对照组明显缩短[(10.43±2.38)d比(12.13±2.17)d]及输注血小板的数量显著减少[(1.50±1.08)个比(2.33±1.05)个](P＜0.05).结论 rhIL-11对治疗急性髓系白血病化疗后血小板减少有明显疗效,且患者不良反应轻微.     

重组人白细胞介素-11在急性白血病患者中的临床应用

 目的 探讨重组人白细胞介素－11（rhIL-11）对急性白血病（AL）患者诱导缓解化疗后巨核细胞－血小板等恢复的影响和疗效。方法 rhIL-11 1.5～3.0 mg于急性髓性白血病（AML）患者在标准的DA方案或相似方案化疗结束24 h,急性淋巴细胞白血病（ALL）患者在蒽环类药物治疗后24 h,皮下注射,连用至血小板≥100×109／L,最多不超过14 d。结果 注射rhIL-11后血小板恢复至≥30×109／L、≥50×109／L、≥100×109／L的平均时间均早于未使用rhIL-11者,血小板输注量明显减少（P＜0.05）。结论 rhIL-11可以有效地促进AL患者诱导缓解治疗后外周血小板恢复,从而减少患者对血小板输注的要求。     

重组人白细胞介素-11对恶性肿瘤化疗后血小板减少治疗的临床分析

18例恶性肿瘤患者化疗后血小板减少(<50×109L-1)。按经济状况分为两组A组(治疗组)8例,使用白细胞介素-11(rhIL-11)皮下注射1·5mg/d,使用3~12d;B组(对照组)10例,为空白对照。每周观察rhIL-11对血小板计数及血小板体积的影响,连续3周。化疗可降低血小板计数和平均血小板体积,A组化疗后血小板计数和平均血小板体积分别降至(42·47±12·89)×109L-1和(9·21±1·87)fL,对照组化疗后血小板计数和平均血小板体积分别降至(44·54±11·71)×109L-1和(8·96±1·66)fL。rhIL-11开始使用1周后,平均血小板体积上升至正常(10·47±2·23)fL,2周后血小板计数上升至正常水平(110·78±52·27)×109L-1。     

重组人白介素-11对肿瘤患者化疗所致血小板减少的治疗作用

目的观察国产重组人白介素-11(迈格尔,rhIL-11)对恶性肿瘤患者化疗所致血小板减少的疗效及其不良反应。方法采用自身对照的方法,对33例曾因同一方案化疗引起血小板Ⅲ度以上减少的恶性肿瘤患者(外周血Plt<50×109/L),给予rhIL-11预防性治疗。第1周期单用化疗,第2周期化疗联合rhIL-11。rhIL-11用量为1.5mg,每日1次皮下注射,血小板升高至正常(100.00×109/L)时停止给药,连续5~20天。结果单用化疗的对照周期化疗后血小板最低均值为(25.03±15.49)×109/L,血小板低于50×109/L平均天数(9.25±3.78)天,需要输注血小板平均数为(0.91±1.04)单位。应用rhIL-11的研究周期化疗后血小板最低均值为(43.61±28.24)×109/L(P=0.002),血小板低于50×109/L平均天数(4.96±4.36)天(P<0.001),需要输注血小板平均数为(0.36±0.85)单位(P=0.024)。主要不良反应乏力、注射部位疼痛、恶心呕吐、关节肌肉疼痛、结膜充血。结论预防性应用国产重组人白介素-11可降低化疗引起的血小板下降的幅度及缩短血小板低下的持续时间;不良反应可耐受。     

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.