非霍奇金淋巴瘤采用CHOP方案治疗与护理

目的探讨NHL采用CHOP方案治疗中护理的重要性.方法对115例NHL采用CTX,750mg/m2 静滴第1日,VCR 1.4g/m2静滴第1.8日,PDN100mg/m2PO第1～5日,每21天为1周期,本组病例用药4～6个周期.结果顺利地完成了115例NHL的化疗,无1例出现化疗作用.结论肿瘤专科护理的措施是顺利完成化疗,减轻副作用,提高生活质量的保证.     

Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100mg/m², IV_Y day 8), Adriamycin (30mg/m², IV_Y days 1,2), teniposide (75 mg/rn², IV, day 1), cyclophophamide (300 mg/m², po, days one to five), Oncovin (1.4 mg/m², IV: maximum 2 mg, days 8,15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m², IV, day 1), Adriamycin (50 mg/m², IV, day 1), Oncovin (1.4 mg/m² IV: maximum 2 mg, day 1) and prednisolone (100 mg, PO, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p 0.0001), mucositis (p= 0.002) and infections (p= 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification. (Aust NZ J Med 1992; 22: 123–128.)     

褪黑素对大鼠急性脊髓损伤内质网应激蛋白GADD153/CHOP表达的影响

目的探讨褪黑素（MT）对急性脊髓损伤（ASCI）大鼠模型脊髓组织GADD153/CHOP表达的影响。方法选取健康SD大鼠96只,随机分为生理盐水处理组（NS组）、乙醇处理组（ET组）及褪黑素治疗组（MT组）各32只。所有大鼠均以改良Allen法制备脊髓损伤模型;MT组在模型制备的基础上给予褪黑素治疗;ET组在模型制备的基础上给予5%乙醇处理;NS组在模型制备的基础上给予0.9%氯化钠溶液处理。分别于伤后3h、1d、3d、7d时各取8只应用改良Tarlov评分法评价其神经功能;Tarlov评分后处死,取受损节段脊髓行HE染色及免疫组化染色,观察形态学改变和CHOP表达的特点;并应用TUNEL方法检测神经细胞凋亡情况。其量的评定借助于麦克奥迪数码医学图像分析系统A（Motic.med6.0）软件,结果分别用累积光密度（IOD）及细胞凋亡指数（AI）来表示。结果所有实验大鼠脊髓组织均有不同程度出血、水肿、细胞凋亡及坏死。MT组Tarlov评分除3h时间点外,其他各时间点Tarlov评分明显高于ET组及NS组,且差异有统计学意义（P〈0.05或P〈0.01）。MT组与ET、NS组不同时间点CHOP表达、细胞凋亡差异有统计学意义,表现为除3h时间点外,其他各个时间点MT组CHOP表达及细胞凋亡均明显低于其余两组（P〈0.05）。而ET、NS组之间各时间点CHOP表达、细胞凋亡比较,差异无统计学意义（P〉0.05）。结论 MT可抑制CHOP表达,降低脊髓细胞凋亡指数,可能为其发挥急性脊髓损伤保护作用的重要机制之一。     

美罗华治疗32例弥漫型大B细胞性非何杰金氏淋巴瘤

目的 评价美罗华治疗弥漫型大B细胞性非何杰金氏淋巴瘤DLBCL的临床效果及不良反应。方法 用同期对照的前瞻性研究方法,将68例弥漫型大B细胞性NHL患者分为研究组(美罗华组)和对照组,前组32例用CHOP方案(环磷酰胺、阿霉素、长春新碱和强的松)联合美罗华治疗;后组36例单用CHOP方案。每4周循环1个疗程,3～6疗程后作评价。将两组患者按国际淋巴瘤预后因子指数(IPI)分为中低危组和高危组,分析其疗效与预后。全部患者6个疗程后停止治疗,随访观察生存情况。结果 美罗华组完全缓解率(CR)达56.3％,总有效率87.5%;对照组分别为13.9％、63.9%,两组疗效差异有统计学意义(P<0.001)。美罗华组6、12、24、36月总的生存率分别为96.9％、87.5％、71.9％和65.6％,对照组分别为91.7％、80.6％、58.3％和41.7％(P>0.05)。美罗华组中中低危组的CR及部分缓解率(PR)分别为68.4％、26.3％,高危组分别为38.5%、38.5％(P<0.01);对照组中低危组的CR及PR分别为15.8％、68,4％,高危组则分别为11.8％、29.4％(P<0.001)。结论 美罗华联合CHOP方案治疗DLBCL的疗效显著,3年生存率高,不良反应较单纯化疗少,可作为该病目前的首选方案。     

内质网应激介导的细胞凋亡途径及新靶点药物

 目的综述内质网应激介导的细胞凋亡信号转导途径,以及以各条途径中所涉及的关键酶为新靶点开发研制药物的进展情况。方法着重以近几年国外该领域有代表性的文献为依据,进行分析、归纳、总结。结果与结论Caspase,C/EBP homologous prote in(CHOP),Bc l-2,凋亡信号调节激酶(ASK1)等酶在内质网应激介导的细胞凋亡的信号转导途径中发挥着非常重要的作用,针对这些酶所设计的抑制剂或激活剂,可以抑制或促进细胞的凋亡,从而达到治疗相关疾病的目的。     

TP53 mutation and survival in aggressive B cell lymphoma

TP53 is mutated in 20–25% of aggressive B‐cell lymphoma (B‐NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B‐NHL, we investigated TP53 gene mutations within the RICOVER‐60 trial. Of 1,222 elderly patients (aged 61–80 years) enrolled in the study and randomized to six or eight cycles of CHOP‐14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index‐Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B‐symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event‐free (EFS), progression‐free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI‐factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed.     

PERK信号通路介导结肠癌细胞对5-氟尿嘧啶耐药机制的研究

目的:观察PERK蛋白对结肠癌细胞药物敏感性的影响,并进一步探讨其相关作用机制。方法:结肠癌细胞系HCT116分为三组:空白对照（Control）组、下调PERK表达（si-PERK）组、阴性对照（si-NC）组;采用免疫荧光及RT-PCR验证转染效率;利用CCK-8实验检测下调PERK表达后结肠癌细胞对化疗药物5-FU的敏感性变化;Annexin V-FITC凋亡实验检测下调PERK表达对结肠癌细胞凋亡的影响;利用RT-PCR及Western Blot实验检测PERK信号通路中关键分子eIF2α、ATF4、CHOP、XIAP的mRNA及蛋白表达变化。结果:RT-PCR实验表明:与正常对照组相比,si-PERK 组mRNA的表达显著下降（P＜0.05）,免疫荧光提示转染效率达80%以上;CCK-8实验发现与si-NC组相比,5-FU对 si-PERK组细胞的半数抑制浓度（IC50）明显降低（P＜0.01）;Annexin V-FITC凋亡实验发现与si-NC组相比,si-PERK组细胞的凋亡发生率显著升高（P＜0.05）;RT-PCR及Western Blot实验发现与si-NC组相比,si-PERK组细胞中PERK信号通路下游关键分子eIF2α、ATF4、CHOP的mRNA及蛋白表达均明显降低（P＜0.05）。结论:在结肠癌细胞中,抑制PERK表达后,其可能通过下调eIF2α、ATF4、CHOP的表达促进细胞发生凋亡,从而促进细胞对化疗药物5-FU的敏感性。     

CHOP和CHOEP方案治疗非霍奇金淋巴瘤的临床观察

观察2周CHOP（环磷酰胺＋阿霉素＋长春新碱＋强的松）方案和CHOEP方案治疗非霍奇金淋巴瘤（Non-Hodgkin’slymphoma,NHL）的有效性和毒副反应。将51例NHL患者随机分3组,分别采用标准CHOP、CHOEP和CHOP-14方案治疗并观察疗效和毒副反应。51例中CR29例,PR16例,总有效率（OR）88.2%（CR＋PR）,各组的CR和OR分别为50.0%和85.0%（CHOP）,56.0%和87.5%（CHOEP）,66.7%和93.3%（CHOP-14）。CHOEP和CHOP-14对NHL的疗效比标准CHOP有提高的趋势,但各组之间CR和OR差异无统计学意义,各组之间毒副反应相似。CHOEP和CHOP-14均可作为NHL安全有效的化疗方案。     

内质网应激相关蛋白与CXCL12蛋白在特发性肺纤维化中的表达及意义

目的 探讨内质网应激相关蛋白及CXCL12在特发性肺纤维化中的表达及意义.方法 收集荆州市中心医院2004～2014年诊断为特发性肺纤维化且存有活检或手术标本的患者共18例,并收集正常肺组织20例作为对照,通过蛋白免疫印迹法(Western blot)检测内质网应激相关蛋白(GRP78、CHOP)及CXCL12蛋白(SDF-1)的表达,通过逆转录PCR(RT-PCR)检测肺组织中GRP78 mRNA及CXCL12 mRNA的表达.结果 与对照相比,肺纤维化患者肺泡上皮中GRP78、CHOP、CXCL12蛋白表达均上调,且GRP78 mRNA及CXCL12 mRNA也表达上调.结论 内质网应激相关蛋白及CXCL12在特发性肺纤维化的发病过程中起重要作用,可能参与了特发性肺纤维化的发生与发展.