5-aza-2’deoxycytidine联合trichostatin A抑制乳腺癌细胞增殖能力的研究

背景与目的:晚近报道应用DNA甲基转移酶抑制剂5-aza-2’deoxycytid ine(AZA)联合组蛋白去乙酰化酶抑制剂trichostatin A(TSA)作用于多种肿瘤,可以达到治疗肿瘤的目的。本文在此探讨通过AZA联合TSA作用,抑制乳腺癌细胞株增殖能力。方法:联合应用两种药物作用于肿瘤细胞,应用RT-PCR的方法检测MDA-MB-435细胞株p21和p27的mRNA转录水平的改变。通过W ST方法来检测乳腺癌细胞的增殖能力变化,将MDA-MB-435细胞根据药物处理共分四组:①对照组;②AZA+TSA组;③AZA+TSA+4-OH TAM组;④4-OH TAM组。并且采用流式细胞仪来分析肿瘤细胞周期分布的改变,将MDA-MB-435分成另外四组:①对照组;②AZA+TSA组;③AZA+TSA+E2组;④AZA+TSA+E2+4-OH TAM组。结果:TSA以及AZA联合应用能使肿瘤细胞MDA-MB-435的p27的mRNA水平增加,而p21mRNA水平略减弱。增殖分析的四个组中:AZA+TSA组细胞增殖能力减弱(P<0.01),同时出现细胞阻滞于S期,加入雌激素后细胞阻滞稍减弱。AZA+TSA+4-OH TAM组增殖能力进一步减弱(P<0.01)。4-OH TAM组增殖能力没有改变。细胞周期分析的四个组中:AZA+TSA组出现细胞阻滞于S期,AZA+TSA+E2组细胞阻滞稍减弱。AZA+TSA+E2+4-OH TAM组细胞阻滞再次提高。结论:两种药物联合应用能使得乳腺癌肿瘤细胞增殖能力下降,对于肿瘤细胞有一定抑制作用。

5-aza-2’-deoxycytidine重新激活MDA-MB-231乳腺癌细胞雌激素受体基因的表达

目的 探讨 5 AZA CdR重新激活MDA MB 2 3 1乳腺癌细胞雌激素受体基因的表达。方法 采用免疫组织化学的方法 ,对用浓度为 2mg/L的 5 AZA CdR处理MDA MB 2 3 1乳腺癌细胞前后和阳性对照MCF 7乳腺癌细胞雌激素受体基因的表达情况进行检测分析。结果 5 AZA CdR处理过的MDA MB 2 3 1乳腺癌细胞ER的阳性表达率明显增高 (P <0 .0 5 )。结论 5 AZA CdR可以重新激活MDA MB 2 3

Effect of 5-Aza-2’-deoxycytidine on immune-associated proteins in exosomes from hepatoma

AIM: To study the effect of 5-Aza-2’-deoxycytidine (5-Aza-CdR) on heat shock protein 70 (HSP70), human leucocyte antigen-Ⅰ (HLA-Ⅰ) and NY-ESO-1 proteins in exosomes produced by hepatoma cells, HepG2 and Hep3B. METHODS: Exosomes derived from HepG2 and Hep3B cells treated with or without 5-aza-CdR were isolated and purified by ultrafiltration centrifugation and sucrose gradient ultracentrifugation. The number of exosomes was counted under electron microscope. Concentration of proteins in exosomes was measured by bicinchoninic acid protein assay. Expression of HSP70, HLA-Ⅰ and NY-ESO-1 proteins in exosomes was detected by Western blotting and immunoelectron microscopy. mRNA expression of p53 gene was detected by reverse transcription polymerase chain reaction.RESULTS: The mRNA expression of p53 gene was increased in both hepatoma cell lines after treatment with 5-Aza-CdR. The number of exosomes and the concentration of total proteins in exosomes were increased signifi cantly after treatment with 5-aza-CdR (P < 0.05). After treatment with 5-Aza-CdR, immunoelectron microscopy and Western blotting showed that the HSP70, HLA-Ⅰ and NY-ESO-1 proteins were increased in exosomes produced by both hepatoma cell lines. CONCLUSION: 5-aza-CdR, an inhibitor of DNA methyltransferase, can increase exosomes produced by hepatoma cells and immune-associated protein component of exosomes, which may be mediated by p53 gene upregulation and 5-Aza-CdR demethylation.

5-Aza-2'-deoxycytidine inhibits retinoblastoma cell by reactivating epigenetically silenced RASSF1A gene

AIM: To investigate the effect of 5-Aza-2’-deoxycytidine(5-Aza-CdR),a DNA methyltransferase(DNMT) inhibitor,on the growth and survival of the Chinese retinoblastoma(RB) cell line HXO-RB44. ·METHODS: The DNA methylation status of the Ras association domain family(RASSF1A) promoter in the presence of 5-Aza-CdR at different concentrations was analyzed by methylation-specific polymerase chain reaction(MSP). RASSF1A mRNA and protein levels were measured by semiquantitative RT-PCR and immunohistochemistry staining,respectively,when cells were treated with 5.0μmol/L of 5-Aza-CdR. The effect of 5.0μmol/L 5-Aza-CdR on the proliferation and viability of HXO-RB44 cells was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and flow cytometry. ·RESULTS: 5-Aza-CdR efficiently induced cell cycle arrest at G0 /G1 and apoptotic death in HXO-RB44 cells. MSP analysis showed that unmethylated RASSF1A DNA increased and methylated RASSF1A decreased in a dose-dependent manner in a range of 0.5-5.0μmol/L 5-Aza-CdR. Accordingly,RASSF1A expression was reactivated at both mRNA and protein levels. Incubation time of 5-Aza-CdR treatment also functioned as a factor for the demethylation status of RASSF1A promoter DNA,with a plateau on day four. 5-Aza-CdR at 5.0μmol/L completely demethylated the RASSF1A promoter in HXORB44 cells on day four,and as a result,RASSF1A expression increased significantly from day 4 to day 7.·CONCLUSION: 5-Aza-CdR inhibits the growth of the HXO-RB44 RB cell line and induces apoptosis by demethylating the RASSF1A gene.

Inhibitory Effects of 5-Aza-2'-Deoxycytidine and Trichostatin A in Combination with p53-Expressing Adenovirus on Human Laryngocarcinoma Cells

Objective： To investigate the effects of 5-Aza-2＇-deoxycytidine （5-Aza-Cdr） and trichostatin A （TSA） combined with p53-expressing adenovirus （Ad-p53） on Hep-2 cell line in vivo and in vitro, in order to explore its possibility in biological treatment of laryngocarcinoma. Methods： Effects of 5-Aza-Cdr and TSA in combination with Ad-p53 on Hep-2 cell line in vivo were determined by Cell Counting Kit-8 （CCK-8） assay. The effect of drug combination was calculated by Jin＇s formula. Effects on the cell line in vitro were investigated by establishing the nude mice model. Results： 5-Aza-Cdr and TSA showed inhibitory effects on the proliferation of Hep-2 cells in dose- and time-dependent manner. Ad-p53 can inhibit the growth of Hep-2 cells in vivo and in vitro. However, the combination of epigenetic reagents （5-Aza-Cdr/TSA） and Ad-p53 was less effective than individual use of Ad-p53. 5-Aza-Cdr and Ad-p53 inhibited the growth of transplanted tumors and reduced the volume of tumors, and the tumor volume of Ad-p53 group was significantly smaller than that of the control group （P0.05）. Conclusion： Both epigenetic reagents （5-Aza-Cdr/TSA） and Ad-p53 can suppress cell proliferation on Hep-2 in vivo and in vitro and there may be some antagonistic mechanism between Ad-p53 and epigenetic reagents （5-Aza-Cdr/ TSA）.

Comparative Evaluation of the Effects of 5-Aza-2'-deoxycytidine and Trichostatin A on Reactivation of hMLH1 in COC1/DDP Ovarian Cancer Cell Line

Objective： hMLH1 protein serves to detect the DNA damage caused by cisplatin （DDP） and destroys the cell. The absence of hMLH1 expression has been correlated with acquired resistance of ovarian cancer cells to platinum. The aim of this study was to determine the possible role of DNA methylation and histone H3 lysine 9 （H3-K9） acetylation on the loss of hMLH1 expression, and to evaluate the reversal effects of 5-Aza-2＇-deoxycytidine （5-Aza-dC） and Trichostatin A （TSA） on DDP-resistance in ovarian cancer cell lines. Methods： Two human ovarian cancer cell lines, COC1 and its DDP-resistant subline, COCI/DDP were cultured. The two cancer cells were treated with 5-Aza-dC or TSA. Using COC1 cells as a control, we used methylation-specific PCR （MSP） to analyze DNA methylation at hMLHI gene promoter, hMLH1 mRNA and protein expressions were analyzed by reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blot. Chromatin immunoprecipitation assay （CHIP） was used to test the levels of histone H3-K9 acetylation at hMLH1 gene promoter. Results： In COC1 cells, there was no DNA methylation at hMLH1 gene promoter, while there were hMLH1 mRNA and protein expression. In COC1/DDP cells, there was DNA hypermethylation at hMLH1 gene promoter, while there was no hMLH1 mRNA or protein expression. The treatment with 5-Aza-dC resulted in DNA demethylation at the promoter region, as well as restoration of hMLH1 expression in COC1/DDP cells. The treatment with TSA had no effects on DNA demethylation or restoration of hMLH1 expression in COC1/DDP cells. Conclusion： Hypermethylation of DNA at the promoter is related to the silencing of hMLH1 in COC1/DDP ovarian cancer cells. DNA methylation at hMLH1 promoter could play a significant role in determining the sensitivity of ovarian cancer to DDP. The drug resistance mediated by methylation of hMLH1 could be overcome by 5-Aza-dC.

Effect of 5-Aza-2'-deoxycytidine on the expression of p16 in hepatocellular carcinoma cells in vitro

Objective: To study the effect of 5-Aza-2’ -deoxycytidine (5-Aza-cdR) on tumour suppressor gene p16 expres- sion in hepatocellular carcinoma cells. Method: Expression of pl6 mRNA and protein in hepatocellular carcinoma cell lines SMMC-7721 and HePG2 before and after treatment with 5-Aza-cdR were analyzed via reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemistrty Results: The expression levels of p16 mRNA and protein were increased dramatically after treatment with 5-Aza-cdR. Conclusion: Our data show that, 5-Aza-2’ -deoxycytidine can increase the expression of pl6 gene both at transcription and translation. The findings suggested that 5-Aza-cdR may reactivate the pl6 gene by demethylation.

Gene Expression Profiling of Human Myeloid Leukemic MV4-11 Cells Treated with 5-Aza-2’-deoxycytidine

The pyrimidine analog, 5-aza-2’-deoxycytidine (5-aza-dC) is a DNA methyltransferase inhibitor that triggers DNA demethylation leading to the reactivation of epigenetically silenced tumor suppressor genes. To understand the shift in gene expression which mediates the beneficial 5-aza-dC effects in leukemia, we have treated human myeloid derived leukemic cells with 5-aza-dC. Target genes were identified first in MV4-11 cells using a genome-wide gene expression profiling assay to detect differences in treated and untreated cells. From this analysis six genes were identified (HOXA4, HOXD4, HOXA8, HOXD12, CD9 and RGS2) as being significantly different expressed after treatment. To validate microarray data, we performed quantitative PCR on these genes from multiple leukemic cells. The results suggest that these genes are epigenetically regulated indicating that dysregulation of HOXA4, HOXD4, HOXA8, HOXD12, CD9 and RGS2 expression may play an important role in establishing the malignant phenotype in AML.

CAFs促进ADH1B甲基化对卵巢癌细胞增殖及侵袭的影响

目的 探讨肿瘤相关成纤维细胞(CAFs)分泌的IL-6对卵巢癌细胞增殖及侵袭的影响及机制。方法 收取新鲜离体上皮性卵巢癌及正常卵巢上皮组织,分离纯化获得CAFs及正常卵巢成纤维细胞(NFs);蛋白质印迹和免疫荧光实验检测上皮细胞和成纤维细胞标志物α-平滑肌动蛋白(α-SMA)、上皮型钙黏附素(E-cadherin)表达;收集CAFs和NFs培养上清液与卵巢癌SKOV3细胞建立间接共培养体系,细胞分为SKOV3单独培养(SKOV3)组、SKOV3与NFs上清液(NFs)组及SKOV3与CAFs上清液(CAFs)组;细胞免疫组化检测SKOV3细胞共CAFs及NFs上清液培养后乙醇脱氢酶1B(ADH1B)表达;甲基化特异性PCR (MSP)、逆转录实时荧光定量PCR(RT-qPCR)、酶联免疫吸附试验(ELISA)及蛋白质印迹实验分别检测甲基化抑制剂5-氮杂-2′-脱氧胞苷(5-Aza-dC)干预前后各组细胞ADH1B mRNA表达及甲基化状态、信号转导和激活因子3(STAT3)蛋白磷酸化水平;细胞计数试剂盒8(CCK-8)法及Transwell实验分别检测IL-6抑制剂LMT-286及重组IL-6 (rhIL-6)对细胞增殖及侵袭能力的影响。结果 肿瘤成纤维细胞中高表达α-SMA,极低表达E-cadherin;相比较SKOV3组及NFs组,CAFs组ADH1B mRNA及蛋白表达明显下调,同时CAFs组细胞上清液中IL-6水平较SKOV3组及NFs组明显升高;5-Aza-dC作用后,ADH1B甲基化部分逆转;三组细胞ADH1B mRNA和蛋白表达均增加,CAFs组STAT3磷酸化水平下降;LMT-286及rhIL-6干预均仅抑制或促进CAFs组细胞增殖和侵袭,而SKOV3组和NFs组无明显改变。结论 CAFs通过IL-6/STAT3信号通路增强ADH1B甲基化促进卵巢癌细胞增殖和侵袭。

奥西替尼联合吉西他滨治疗伴肾转移的老年晚期NSCLC患者的临床疗效

【目的】探讨奥西替尼联合吉西他滨治疗伴肾转移的老年晚期非小细胞肺癌(NSCLC)患者的临床疗效。【方法】本院收治的238例老年晚期NSCLC患者,随机分为对照组和观察组,每组119例。对照组给予奥西替尼治疗,观察组在此基础上另给予顺铂、吉西他滨治疗。比较两组治疗3个疗程后的疗效及治疗前后肿瘤标志物、肾功能指标的变化,药物安全性和1年生存情况。【结果】观察组临床控制率高于对照组(P<0.05)。两组治疗后癌胚抗原(CEA)、胃泌素释放肽前体(ProGRP)、鳞状细胞癌抗原(SCCA)水平较治疗前均降低(P<0.05),且观察组CEA、ProGRP、SCCA均低于对照组(P<0.05)。两组治疗前后的血尿素氮、血肌酐水平比较,差异均无统计学意义(P>0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。观察组1年总存活曲线优于对照组(P<0.05)。【结论】奥西替尼联合吉西他滨方案治疗伴肾转移的老年晚期NSCLC患者疗效显著,可降低肿瘤标志物水平,延长患者近期生存时间,且安全性良好。

5-氮杂-2’-脱氧胞苷对苯并[a]芘致海马神经元毒性的保护作用

目的探讨5-氮杂-2’-脱氧胞苷(5-Aza-cdR)对苯并[a]芘(B[a]P)致海马神经元毒性的保护作用。方法体外培养海马神经元至第5天,观察并鉴定细胞。实验设立对照组,B[a]P组(20μmol/L B[a]P)和B[a]P+5-Aza-cdR组(20μmol/L B[a]P+10μmol/L 5-Aza-cdR)。观察细胞形态;检测细胞活力、DNA甲基转移酶蛋白和基因表达水平;测定细胞中的总甲基化水平和细胞凋亡情况。结果与对照组比较,B[a]P组海马神经元活性降低(P<0.05);细胞凋亡率升高(P<0.05);DNMT3A、DNMT3B基因和DNMT1、DNMT3A蛋白表达水平上升(P<0.05);总甲基化水平升高(P<0.05)。与B[a]P组比较,B[a]P+5-Aza-cdR组提高了海马神经元活性(P<0.05);降低细胞凋亡率(P<0.01);DNMTs基因和蛋白表达水平明显下降(P<0.05);总甲基化水平下降(P<0.01)。结论5-Aza-cdR对B[a]P诱导的海马神经元损伤有保护作用。

DNA Methyltransferase Inhibitors Induce Cerebral Dopamine Neurotrophic Factor Expression in C6 Glioma Cells

Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are involved in neuroprotection and mitigating endoplasmic reticulum (ER) stress in the brain and peripheral organs. In earlier work, an increase in histone acetylation, following treatment with an epigenetic modulator, valproic acid, was associated with induction of CDNF and MANF in cultured cells and rat brain. These findings prompted an investigation of the effects of DNA methyltransferase (DNMT) inhibitors, which can alter epigenetic function, on the expression of CDNF and MANF. Rat C6 glioma cells were treated with a micromolar range of DNMT inhibitors: 5-aza-2’-deoxycytidine (DAC or decitabine), 5-azacytidine (AZA) or zebularine (ZEB) for 24 h. Subsequently, qPCR analysis was used to examine the mRNA expression of DNMT1, ten-eleven translocation methylcytosine dioxygenase 2 (TET-2), CDNF and MANF. A significant dose-dependent decrease in DNMT1 mRNA levels, together with a significant increase in TET-2 expression, was observed following treatment with AZA or DAC. Importantly, DAC, AZA and ZEB caused a significant dose-dependent increase in CDNF mRNA levels. In contrast, MANF mRNA expression decreased following treatment with AZA, with no significant effects observed with DAC or ZEB. Western analysis revealed no significant changes in CDNF protein levels following treatment with DAC for 24 h. The significant increase in CDNF expression, following treatment with DNMT1 inhibitors, suggests that DNA methylation is involved in the regulation of this neurotrophic factor. Clarification of the epigenetic or other mechanisms underlying the regulation of CDNF may provide novel therapeutic approaches in neurodegenerative and ER stress-related disorders.

DNA甲基化抑制鼻咽癌细胞系膜联蛋白A1基因表达

为了研究不同分化程度和转移潜能鼻咽癌(NPC)细胞系膜联蛋白A1(ANXA1)mRNA和蛋白质表达情况及其与基因甲基化的关系.培养NPC细胞系CNE1、CNE2、5-8F、6-10B和永生化非癌性人鼻咽黏膜上皮细胞NP69细胞用于实验,用甲基化特异性聚合酶链反应(MSP)方法检测ANXA1基因甲基化状态,同时利用逆转录-聚合酶链反应(RT-PCR)方法检测ANXA1基因的mRNA表达水平.然后用不同浓度的5-杂氮-2′-脱氧胞苷(5-aza-2dC)对NPC细胞进行去甲基化处理,MSP和RT-PCR方法检测处理组和对照组细胞ANXA1基因甲基化状况和mRNA表达水平,并用Western-blotting方法检测ANXA1基因蛋白质表达水平.结果发现,NP69细胞ANXA1基因无甲基化,4株NPC细胞系ANXA1基因都存在不同程度的甲基化,甲基化程度与细胞的分化程度和转移潜能相关.NPC细胞ANXA1基因mRNA表达水平降低,低于NP69细胞,其降低的程度与基因的甲基化程度相关.5-aza-2dC能够剂量依赖性地引起ANXA1基因去甲基化,经去甲基化处理后,NPC细胞系ANXA1基因的mRNA和蛋白质的表达水平相应提高.研究证明,NPC细胞系ANXA1基因的mRNA和蛋白质表达水平出现下调,甲基化是导致表达下调的主要原因,5-aza-2dC去甲基化处理能够恢复ANXA1基因的表达水平.

卡培他滨联合多西紫杉醇治疗转移性乳腺癌的临床观察

为了探讨卡培他滨和多西紫杉醇联合方案治疗转移性乳腺癌的疗效及不良反应，29例转移性乳腺癌患者接受卡培他滨和多西紫杉联合方案化疗。卡培他滨2．0g／m^2，d1～d14；多西紫杉醇35mg／m^2，d1、d8、d15。21d重复，化疗2个周期以上。结果示29例患者入选，2例出组，27例可供评价疗效，29例可评价不良反应。有效率为51．9％（14／27），获益率为88．9％（24／27）；主要不良反应为手足综合征、皮肤色素沉着、白细胞减少、血小板减少、血红蛋白降低、恶心呕吐、口腔炎、腹泻、肝功能损害、脱发、心脏毒性、末梢神经毒性、过敏反应等。初步研究结果提示，对蒽环类药物和（或）紫杉醇治疗失败的转移性乳腺癌，卡培他滨联合多西紫杉醇是一种新的选择方案。

晚期胃癌一线化疗后卡培他滨维持治疗的疗效和安全性

目的观察卡培他滨在晚期胃癌一线化疗后维持治疗的疗效和不良反应。方法 280例晚期胃癌患者经FOLFOX4方案(奥沙利铂+氟尿嘧啶+亚叶酸钙,6~9个周期)或XELOX方案(奥沙利铂+卡培他滨,4~6个周期)一线化疗后,疗效评价无疾病进展的172例患者,按照患者意愿分为维持组63例(卡培他滨维持治疗,1 000 mg/m2,每天2次,d1~14,每3周重复)和观察组109例。结果 FOLFOX4方案组和XELOX方案组的疾病控制率分别为64.4%(85/132)和65.5%(97/148),两者比较,差异无统计学意义(P=0.95)。XELOX方案的患者入维持组的比例高于FOLFOX4方案患者(P=0.009)。中位无进展生存期维持组为10.7个月(95%CI:9.6~11.8个月),观察组为7.3个月(95%CI:6.9~7.6个月,P<0.01)。中位生存期维持组优于观察组,分别为18.3个月(95%CI:17.5~19.0个月)和15.0个月(95%CI:14.5~15.5个月,P<0.01)。维持组常见不良反应为血液学和胃肠道毒性,以1~2级多见。结论卡培他滨作为晚期胃癌一线化疗后维持治疗延长PFS和OS,耐受性良好。

散发性结直肠癌组织p33ING1b启动子甲基化情况及其意义

目的检测散发性结直肠癌组织p33ING1b启动子甲基化情况,探讨p33ING1b在散发性结直肠癌中转录抑制的可能机制。方法选择2008年10月—2012年3月在广西医科大学第一附属医院结直肠肛门外科住院的散发性结直肠癌患者63例,收集其癌组织及相应癌旁组织切除标本;同时选择在我院行吻合器痔上黏膜环切术(PPH)患者13例,收集其术后痔上黏膜组织。采用巢式-甲基化特异性PCR(nMSP法)检测p33ING1b启动子甲基化情况,RT-PCR检测癌组织p33ING1b mRNA表达水平;采用5-氮-2-脱氧胞苷(5-aza-dC)对人结直肠癌细胞株DLD-1、Caco-2进行去甲基化干预实验。结果癌组织p33ING1b启动子甲基化阳性率为82.5%(52/63),癌旁组织为34.2%(27/63),痔上黏膜组织未检测出p33ING1b启动子甲基化,癌组织p33ING1b启动子甲基化阳性率高于癌旁组织和痔上黏膜组织(χ2=21.21,P<0.001;χ2=33.98,P<0.001)。不同性别、年龄、肿瘤位置、分化程度及有无淋巴结转移、远处转移患者癌组织p33ING1b启动子甲基化阳性率比较,差异均无统计学意义(P>0.05);不同Dukes分期患者癌组织p33ING1b启动子甲基化阳性率比较,差异有统计学意义(P<0.05)。p33ING1b启动子甲基化癌组织p33ING1b mRNA相对表达量为(0.62±0.15),低于p33ING1b启动子非甲基化癌组织的(0.75±0.17)(t=2.553,P<0.05)。5-aza-dC干预后,人结直肠癌细胞株DLD-1、Caco-2的p33ING1b启动子甲基化均被逆转,且p33ING1b mRNA相对表达量较干预前升高(P<0.05)。结论 p33ING1b启动子甲基化与散发性结直肠癌存在关联,并可能通过抑制p33ING1b mRNA的表达参与结直肠癌的发生和发展。

卡培他滨联合多西紫杉醇治疗蒽环类耐药的转移性乳腺癌31例

为了探讨卡培他滨联合多西紫杉醇（DTX）治疗蒽环类耐药的转移性乳腺癌的疗效及不良反应，将61例确诊蒽环类耐药的转移性乳腺癌分为两组，联合组31例卡培他滨1650mg／（m^2·d），口服，d1～d14，DTX75mg／（m^2·d），静脉滴入，d1。时照组30例DTX 100mg／（m^2·d），静脉滴入，d1。两组每3周为1个周期，连用4个周期，治疗结束2周后评价疗效。61例均可评价疗效，联合组有效率（CR＋PR）为45．2％（14／31），中位生存时间为14．3个月。Ⅱ～Ⅲ度反应占67．7％（21／31），Ⅳ度反应占29．0％（9／31），主要为手足综合征、骨谴抑制、脱发和消化道毒性。时照组有效率（CR＋PR）为30．0％（9／30），中位生存时间为10．9个月。Ⅱ～Ⅲ度反应占50．0％（15／30）。Ⅳ度反应占33．3％（10／30），主要为发热、肌痛、关节痛、嗜中性粒细胞减少症。初步研究结果提示，卡培他滨联合DTX时经吡柔比星治疗失败的乳腺癌较DTX’单药有优势，且不良反应可以耐受。

急性白血病细胞内dCK和CDA含量与临床疗效的关系

目的 了解急性白血病细胞内脱氧胞苷激酶 (dCK )、胞苷脱氨酶 (CDA)的含量与临床疗效的关系。方法 应用核素闪烁计数仪 ,对 7例ALL ,2 4例AML化疗前细胞内dCK、CDA进行检测。结果 AML细胞内dCK、CDA活性均高于ALL(P <0 .0 5 )。AML完全缓解者dCK活性 3倍于未缓解者 (P <0 .0 0 1) ,CDA/dCK比值明显降低 (P <0 .0 5 )。AML初发者dCK活性是复发者的 2 .5倍 (P <0 .0 1)。M 3细胞内dCK活性高于其他髓系白血病细胞 ,其CDA/dCK比值显著降低 (P <0 .0 1)。细胞内CDA活性在 5 0岁以上者明显升高 (P<0 .0 5 ) ,男性患者细胞内dCK显著高于女性患者 (P <0 .0 1)。结论 细胞内dCK活性高、CDA活性低 ,CDA/dCK比值小 ,临床对Ara C疗效佳 ,故可作为预测对Ara C是否敏感的一个监测指标。

康莱特注射液合并健择对移植于裸鼠的人胰腺癌的疗效初步研究

目的:探讨康莱特注射液合并健择对移植于裸鼠的人胰腺癌的作用。方法:24只裸鼠皮下接种人胰腺癌细胞PANC-1,10d后随机分成4组,每组6只裸鼠。对照组给予生理盐水;康莱特组自接种第10天起连续给药10次,给药剂量为5·0g/kg,静脉推注;健择组在接种第12天给药1次,给药剂量为60mg/kg;合并给药组剂量及给药时间同单独给药组。停药后1周脱颈处死动物,解剖裸鼠,称体质量、瘤质量,测量肿块大小并计算抑瘤率。结果:单独注射康莱特及健择组的抑瘤率分别为12·24%和13·26%;合并用药组抑瘤率为40·11%,明显高于单独用药组。结论:康莱特注射液与健择对移植于裸鼠的人胰腺癌的抑制作用具有协同效应。

胸腺肽α_1联合低剂量吉西他滨治疗老年晚期非小细胞肺癌临床研究

目的观察及评价胸腺肽α1联合低剂量吉西他滨(泽菲)对老年晚期非小细胞肺癌的临床疗效。方法 58例老年晚期非小细胞肺癌患者,随机分为对照组(化疗)和治疗组(化疗+胸腺肽α1),治疗组30例,对照组28例。治疗组在化疗的同时给予1.6 mg胸腺肽α1皮下注射,隔日1次,连续应用8周,对照组则在化疗的同时给予等剂量生理盐水,用法与治疗组相同。所有患者均采用低剂量泽菲化疗(800 mg/m2,d1,d8)并记录患者Kanofsky体力评分及体重变化。结果治疗后治疗组患者的Kanofsky评分明显高于对照组(P<0.05)。体重增加明显高于对照组,差异有统计学意义(P<0.05)。治疗组不良反应明显低于对照组,差异无统计学意义(P>0.05)。结论胸腺肽α1可改善老年晚期非小细胞肺癌患者生活质量,未增加化疗的不良反应。