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.     

国产重组人白细胞介素-11治疗恶性肿瘤患者化疗所致血小板减少的临床研究

目的评价rhIL-11(巨和粒)在化疗所致血小板减少治疗中的作用。方法将65例化疗后血小板减少的患者随机分为对照组(33例):予常规止血及对症、支持治疗;试验组(32例):除与对照组同样治疗外,加皮下注射巨和粒1.5mg/次,1次/d,比较两组治疗后外周血血小板计数变化及出血症状改善情况。结果试验组血小板计数回升、出血症状的改善较对照组快,血小板计数回升至100×109/L以上的平均时间比对照组短,分别为(5.5±0.5)d和(9.6±1.2)d,两组差异有显著性(P<0.01)。结论巨和粒对化疗所致血小板减少疗效显著,无明显副作用。     

重组人白细胞介素-11治疗化疗后血小板减少的临床研究

目的探讨重组人白细胞介素-11(rhIL-11)治疗化疗后血小板减少症的疗效和用药方法。方法回顾性分析该科2000年2月至2004年9月共38例化疗后出现Ⅲ～Ⅳ度血小板减少患者的治疗效果。对照组18例,用利血生、升血小板胶囊等药物;治疗组20例,用rhIL-11。结果治疗组Plt<50×109/L持续时间(2.5d)明显少于对照组(5.1d),差异有显著性(P<0.01);治疗组血小板恢复正常,既Plt>100×109/L所需时间(5.9d)明显少于对照组(13.5d),差异有显著性(P<0.01);停药后血小板数量并未明显回落,能稳定在正常水平。结论重组人白细胞介素-11(rhIL-11)是一种有效、安全的治疗化疗后血小板减少的药物。     

重组人白细胞介素-11治疗化疗所致血小板减少

[目的]观察重组人白细胞介素-11(rhIL-11)治疗恶性实体肿瘤患者化疗所致血小板减少的临床疗效与毒副作用.[方法]38例第1周期化疗后血小板减少的恶性肿瘤患者随机分为治疗组和对照组,第2周期化疗后血小板计数≤75.0×109/L时,治疗组即给予皮下注射rhIL-11 25μg/(kg·d),连续用药至血小板≥100×109/L时停药,对照组不予rhIL-11,以对症治疗为主.同一患者2周期的化疗方案及剂量强度相同.[结果]第2周期化疗后与对照组比较,治疗组血小板降低幅度较对照组小,而且血小板≤75.0×109/L持续的天数也短,其差异均有统计学意义,P＜0.05.治疗组患者在进行自身比较中也发现,使用rhIL-11的第2周期血小板降低的幅度较前明显缩短,P＜0.05.不良反应均为Ⅰ～Ⅱ度,主要是疲劳、头晕、肌肉关节疼痛等.[结论]对恶性实体肿瘤化疗所致的血小板减少,重组人白细胞介素-11的治疗性给药方法效果确切,毒副作用轻,患者耐受性好.     

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。     

白介素11在血小板减少疾病中的临床应用

目的观察国产重组人白介素11(rhIL-11)在治疗血小板减少疾病中的疗效.方法将55例血液肿瘤患者分为AB,BA 两组进行自身交叉对照;特发性(难治性)血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)组入选15例;血液肿瘤患者每例均化疗2个疗程(28 d为1个疗程).A疗程化疗结束后24 h加rhIL-11,剂量为25 μg/(kg*d),皮下注射,于化疗结束后24 h开始连用14 d,B疗程化疗后不使用rhIL-11,作为空白对照;自化疗开始隔日查血常规1次,观察各疗程外周血小板计数变化.ITP患者皮下注射rhIL-11 25 μg/(kg*d),连用14 d.结果血液肿瘤组:A疗程用rhIL-11后外周血小板数均值、最高值均大于 B疗程,A、B两疗程血小板数在用药前后差异有显著意义(P<0.05).A疗程血小板数低于50×109/L 的持续天数、恢复至75×109/L以上需要天数均有不同程度缩短;ITP组:rhIL-11治疗后患者血小板数均值逐渐升高,至第15天达(99±27)×109/L,用药前后血小板数差值为(80±16)×109/L.结论 rhIL-11对难治性血小板减少性紫癜及血液肿瘤化疗导致血小板减少有一定疗效,可耐受性好.     

全中枢照射所致血小板减少的临床研究

目的 评价重组人白细胞介素-11(rhIL-11)预防全中枢照射所致血小板减少的疗效和不良反应。 方法 采用随机对照研究方法,将 100例患者随机分为A组(rhIL-11预防治疗组 50例)和B组(对照组 50例)。A组患者放疗过程中血小板计数<100×10⁹/L时或血小板计数较放疗前基线水平下降>50%即开始按50 μg·kg^-1·d^-1剂量给予rhIL-11皮下注射,1 次/d,直至血小板数≥200×10⁹/L时停药。B组患者当血小板计数<50×10⁹/L时则按同样方案进行,直至血小板数≥100×10⁹/L时停药。 结果 92例可评价疗效,rhIL-11可升高全中枢照射中血小板最低值(P<0.01),缩短血小板减少症持续时间(P<0.01),缩短放疗所需时间(P<0.01)。主要不良反应为注射部位疼痛、硬结、红肿、乏力等,但程度较轻。 结论 rhIL-11 具有明显的促血小板生成作用,可显著减少全中枢照射过程中血小板减少的发生,保证放疗的顺利进行,不良反应较轻且较易处理。     

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.     

国产重组人白细胞介素-11治疗肺癌化疗所致血小板减少28例

[目的]观察国产重组人白细胞介素-11（rhIL—11）治疗肺癌化疗后所致血小板减少的疗效。[方法]48例肺癌化疗后血小板低于50-109／L的患者，随机分为两组，试验组28例，使用rhIL—11治疗，对照组20例，不接受rhIL—11治疗，观察两组治疗后外周血小板计数及出血症状改善情况。[结果]肺癌病人化疗后可致血小板计数降低，rhIL—11使用可使血小板计数回升，出血症状改善，血小板回升至100×10^9／L以上的平均时间比对照组短，分别为（7．6±0．5）d和（14．5±1．2）d，两组差异有显著性（P〈0.01）。[结论]国产rhIL-11可以促进肺癌化疗所致血小板减少的恢复。     

IL-11对中子辐射小鼠肠道IL-11受体表达的影响

目的探讨IL-11对4.0 Gy中子辐射小鼠肠道IL-11受体表达影响。方法136只BALB/C二级小鼠,经4.0Gy中子全身照射,于照前3 d或照后即刻注射600μg/kg rhIL-11,每日1次,连用3 d,并于照后6 h、1 d、2 d、5 d活杀取小肠,采用SP免疫组织化学和图像分析等技术,定量研究肠组织中IL-11、IL-11Rα和gp130表达变化。结果正常小鼠中,IL-11和gp130于肠绒毛上皮细胞和隐窝细胞浆呈强阳性,尤以绒毛顶端细胞为显著;IL-11Rα于肠绒毛全层上皮细胞和隐窝细胞浆呈强阳性,其强度高于IL-11。4.0 Gy中子照后2 d内,IL-11、IL-11Rα和gp130于肠绒毛和隐窝上皮细胞表达均明显减少;照前和照后应用IL-11,三者阳性强度均高于4.0 Gy照射组。结论4.0 Gy中子照射后,小鼠肠道IL-11、IL-11Rα和gp130表达减少,应用IL-11刺激肠上皮细胞IL-11受体表达上调,且该作用参与了中子辐射后肠道损伤与修复的病理生理过程。     

Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells

Previous investigations have shown that interleukin-11 (IL-11) and the IL-11 receptor (IL-11R) have been correlated with the regulation of tumor progression, cellular growth and differentiation in several malignant tumors. The objectives of this study were to clarify the role of IL-11 and IL-11Ralpha in human gastric carcinoma. IL-11 and IL-11Ralpha were studied in 73 cases of surgically resected human gastric adenocarcinomas by immunohistochemistry. The invasive activity and cell signaling pathway of gastric carcinoma cell lines were also examined. Among the 73 cases of adenocarcinoma, 53 (72.6%) and 47 cases (64.4%) showed positive staining in carcinoma cells for the IL-11 and IL-11Ralpha proteins, respectively. Histologically, IL-11 expression correlated only with Lauren's classification (p<0.05). The expression of IL-11Ralpha correlated with the grade of tumor invasion (p<0.05) and vessel infiltration (p<0.01). All of the four gastric carcinoma cell lines expressed both IL-11 and IL-11Ralpha proteins in western blot analysis. Recombinant human IL-11 (rhIL-11) promoted the migration of SCH cells by the activation of the phosphatidylinositol-3 kinase pathway. Wortmannin diminished the promotion of chemotactic motility and invasive activity by rhIL-11. These findings suggest that the IL-11/IL-11R pathway plays an important role in the progression and the differentiation of human gastric carcinomas.     

Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells

Liposarcoma is the second most common soft tissue sarcoma in adults, but treatment options have been quite limited thus far. In this study, we investigated the functional and therapeutic relevance of cyclin-dependent kinase 11 (CDK11) as a putative target in liposarcoma. CDK11 knockdown by synthetic siRNA or lentiviral shRNA decreased cell proliferation, and induced apoptosis in liposarcoma cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of doxorubicin to inhibit cell growth in liposarcoma cells. These findings suggest that CDK11 is critical for the growth and proliferation of liposarcoma cells. CDK11 may be a promising therapeutic target for the treatment of liposarcoma patients.     

脐尿管腺癌（附11例报告）

脐尿管癌临床少见，预后不良，发病机理一般认为是脐尿管的移行上皮化生所致。临床表现主要是无痛性肉眼血尿，伴尿频尿急，尿中含有粘液及耻骨上肿块。通过ＣＴ、Ｂ超和膀胱镜等多项检查再根据脐尿管癌的诊断标准，１１例中有７例患者术前作出正确诊断。２例有盆腔淋巴结转移，其中１例合并腹腔广泛转移。治疗以手术为主，采用扩大的膀胱切除术，即包括膀胱顶部、腹横筋膜和部分腹膜连同肿瘤整块切除，病理报告均为脐尿管粘液性腺癌。术后生存３例，２例术后１年，１例术后６年。５年存活率为９％。     

Interleukin 11

IL-11 is a pleiotropic cytokine originally isolated from a bone marrow stromal cell line. It has been shown to share many activities with IL-6, namely to stimulate T cell-dependent B cell maturation, megakaryopoiesis and various stages of myeloid differentiation, but to inhibit adipogenesis. However, the activity of IL-11 on different stages of erythropoiesis in vitro clearly sets it apart form IL-6.

IL-11 has little hematopoietic colony stimulatory activity of its own although it sustains terminal differentiation of the late erythroid progenitors CFU-E. In combination with IL-3, IL-11 has profound stimulatory effects on early multipotent hematopoietic progenitors (pre-CFC_multi), on multilineage colony-forming cells (CFC_multi), as well as on erythroid progenitors. The combination of IL-11 with the ligand for c-kit (KL) preferentially acts on early cells since it promotes the multiplication of pre-CFC_multi and stimulates highly proliferative erythroid progenitors that yields remarkable macroscopic erythroblast colonies in culture. The synergistic activity of IL-11 and KL, two stromal factors present in the bone marrow microenvironment, points to a pivotal role of IL-11 in early hematopoiesis.

In vivo administration of recombinant human IL-11 elevates the number of circulating neutrophils and platelets and increased megakaryopoiesis in normal mice and primates.     

Interleukin-11

Interleukin-11 (IL-11), a stromal cell-derived cytokine, has been known to act widely in hematopoietic and non-hematopoietic systems. IL-11 supports the growth of certain types of plasmacytoma and hybridoma cells, acts with interleukin-3 (IL-3) in shortening the Go period of early progenitors. IL-11 supports megakaryocyte colony formation and maturation, and acts as an autocrine growth factor in megakaryoblastic cell lines. In addition, IL-11 stimulates erythrocytopoiesis, enhances antigen-specific antibody responses, induces the synthesis of acute phase proteins, inhibits lipoprotein lipase activity and adipocyte differentiation, and promotes neuronal development. Administration of rhIL-11 to mice resulted in an increase of neutrophils and platelets. The human IL-11 gene is localized at 19q13.3-13.4, and codes 199 amino acids and 23 kDa with no N-glycosylation. Its receptor and signal transduction share partially those of interleukin-6 (IL-6). Further analysis of its role in normal and pathological state is necessary to determine the exact function and its application for clinical uses.     

新疆哈萨克族食管癌患者ALDH1L1基因甲基化及其与预后的关系

目的： 探讨新疆哈萨克族食管癌患者ALDH1L1基因甲基化状态及其与食管癌发生及预后之间的关系。方法：采用联合亚硫酸氢钠限制性内切酶分析(COBRA)法检测28例哈萨克族食管癌及癌旁组织标本中ALDH1L1基因启动子区甲基化状况,建立Cox回归模型分析临床病理指标、ALDH1L1基因甲基化水平等因素与预后的关系。结果：28例哈族食管癌患者癌组织和癌旁正常组织的ALDH1L1基因启动子甲基化率分别为71.43% 和39.28%,差异有统计学意义(P<0.05)。预后因素分析表明肿瘤浸润程度、TNM分期、淋巴结转移、癌组织ALDH1L1基因甲基化水平是影响哈萨克族食管癌预后的独立危险因素。癌组织ALDH1L1基因无甲基化患者术后生存时间长于完全甲基化患者(P<0.05)。结论：癌组织ALDH1L1基因启动子区甲基化状态与新疆哈萨克族食管癌的发生及预后有关。     

Proline-rich 11 (PRR11) promotes the progression of cutaneous squamous cell carcinoma by activating the EGFR signaling pathway

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignancies, and its incidence rate is increasing worldwide. Proline-rich 11 (PRR11) has been reported to be involved in the occurrence and development of various tumors. However, the role of PRR11 in cSCC remains unknown. In the present study, we observed upregulated expression of PRR11 in cSCC tissues and cell lines. Knockdown of PRR11 in the cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing cell cycle arrest during the G1/S phase transition, promoted cell apoptosis, and reduced cell migration and invasion in vitro. Conversely, overexpression of PRR11 promoted cell proliferation, decreased cell apoptosis, and enhanced cell migration and invasion. PRR11 knockdown also inhibited cSCC tumor growth in a mouse xenograft model. Mechanistic investigations by RNA sequencing revealed that 891 genes were differentially expressed genes between cells with PRR11 knockdown and control cells. Enrichment analysis of different genes showed that the epidermal growth factor receptor (EGFR) signaling pathway was the top enriched pathway. We further validated that PRR11 induced EGFR pathway activity, which contributed to cSCC progression. These data suggest that PRR11 may serve as a novel therapeutic target in cSCC.