榄香烯治疗中晚期原发性肝癌的临床疗效观察

目的:观察榄香烯注射液对中晚期原发性肝癌的的近期疗效。方法:59例病例均为原发性肝癌Ⅲ期患者,经肝动脉缓慢注射榄香烯600~1000mg,并常规超乳化碘油10~40m l栓塞,介入术后继续静脉滴注榄香烯注射液,每日600~800mg,2周为1个疗程,给予护肝、对症和支持治疗。结果:总有效率83.05%,甲胎蛋白明显下降,病情的恶化率22.03%;同时显著改善生活质量,对外周血白细胞、红细胞、血小板、肝肾功能无明显影响。结论:榄香烯注射液在一定程度上能够抑制癌瘤的生长,对中晚期不宜手术的原发性肝癌的患者有提高生存质量,延长生存期的作用。     

榄香烯乳联合顺铂治疗恶性腹腔积液疗效观察

对38例恶性腹腔积液患者随机分为3组，分别采取单用顺铂、单用榄香烯乳、顺铂与榄香烯乳联用进行治疗，结果顺铂组或榄香烯乳组有效率分别为58．3％、66．7％，均低于联合组的88．6ok（P〈0．05）；且联合应用中未发现榄香烯乳有增加化疗毒性的作用。认为若患者因肝。肾功能异常或体质过弱，难以接受腹腔灌注化疗毒药物的，以选单独应用榄香烯乳为佳，若患者能够耐受，应联合应用以提高疗效。     

榄香烯乳加联合化疗治疗难治性急性非淋巴细胞白血病疗效观察

目的：评价榄香烯乳联合化疗治疗难治性急性非淋巴细胞白血病（ANLL）的疗效。方法：将28例ANLL患者随机分为治疗组和对照组,治疗组使用榄香烯乳300mg加入5％GS500ml中静脉滴注,持续用药14d,同时加联合化疗：高三尖杉酯碱4－6mg静脉滴注,持续7d,阿糖胞苷100－200mg/m^2,第1－7天;对照组单用化疗,方案用量用法同治疗组。结果：治疗组总有效率为75．0％,对照组总有效率为41．7％,两组差异有显著性意义（P＜0．05）。结论：榄香烯乳对难治性ANLL有肯定疗效,比单用联合化疗效果好,且不良反应少,无血常规和骨髓抑制。     

榄香烯治疗白血病初步观察

榄香烯是从姜科植物莪术中提取的一种有效抗癌成分，是非细胞毒性药物，主要作用于肿瘤细胞周期的S期、G2期及M期，阻止S期细胞进入G2期及M期，降低肿瘤细胞的分裂能力，抑制其增殖，从而达到杀灭肿瘤细胞的作用。国内已有报道榄香烯治疗妇癌、脑癌、肺癌、实体瘤等取得了很好的疗效，多次应用该药均对骨髓无抑制作用。     

中药提取物榄香烯治疗原发性肝癌的研究进展

<正>原发性肝癌(PHC)是指发生于肝细胞或肝内胆管细胞的恶性肿瘤，起病隐匿，早期症状不明显，使得PHC临床治疗比较棘手^[1]。最新流行病学数据显示，2020年PHC在中国常见新发癌症中排名第5位，在我国有超过41万人新患PHC,有超过39万人死于PHC^[2]。目前PHC常用治疗手段包括手术治疗、局部治疗、放射治疗、化疗、分子靶向治疗、中医药治疗及免疫治疗。但是由于PHC早期诊断困难，发展迅速，大部分患者就诊时已是中晚期或出现转移，     

榄香烯体内外抑制小鼠肝癌H_（22）细胞增殖与诱导凋亡作用的研究

[目的]研究中药莪术提取物榄香烯制剂（Elemene）对小鼠肝癌H22细胞增殖的抑制及诱导凋亡的作用。[方法]体内实验,通过建立H22小鼠肝癌实体瘤模型,观察榄香烯对荷瘤小鼠肿瘤生长的抑制作用,TdT酶介导的原位缺口末端标记法（TUNEL）检测凋亡细胞。体外进行细胞培养,采用MTT法检测榄香烯对细胞增殖的影响,Annexin V-FITC/PI双染色法检测细胞的凋亡。[结果]不同实验组对荷瘤小鼠肿瘤生长的抑制作用程度不同,5-氟脲嘧啶组抑制肿瘤生长最明显,榄香烯高剂量组较低剂量组抑瘤效果明显;MTT检测到榄香烯对H22细胞株具有抑制作用,呈剂量和作用时间的依赖性;Annexin V-FITC/PI法检测到早期凋亡细胞;TUNEL法检测到凋亡细胞。[结论]榄香烯可有效抑制小鼠肝癌H22细胞的增殖,其抑制癌细胞增殖的途径是通过诱导细胞发生凋亡而完成的。     

榄香烯乳联合化疗治疗急性难治性白血病120例疗效观察

目的评价榄香烯乳加联合化疗治疗难治性急性非淋巴细胞白血病的疗效。方法随机将241例白血病患者分为治疗组和对照组:治疗组120例,用榄香烯乳300mg/m2/d加入5%GS 500ml中静脉滴注,持续用药14天,同时加联合化疗HAA方案:高三尖杉酯碱4mg/m2/d静滴,持续7天,阿克拉霉素20mg/m2/d静滴、qd×7天,阿糖胞苷100~200mg/m2/d,第1~7天;对照组121例,单用HAA化疗,方案用量用法同治疗组。结果治疗组120例中有85例CR,有12例PR,NR23例,CR率70.8%(85/120),总有效率80.8%(97/16)。对照组121例中CR53例,PR11例,NR57例,CR率为43.8%(53/121),总有效率52.9%(64/121)。差异有显著性(P<0.05)。结论榄香烯乳对难治性急性非淋巴细胞白血病(ANLL)有肯定疗效,比单用联合化疗效果好,且不良反应少,无血象和骨髓抑制。     

榄香烯乳联合顺铂治疗恶性胸腹水疗效

晚期恶性肿瘤胸腹水丧失手术、放疗及化疗机会 ,为减轻患者由于胸腹水造成的呼吸困难 ,腹胀、腹痛症状 ,提高患者的生存质量 ,延长生命。我院 1999年～ 2 0 0 0年对 2 8例恶性胸腹水患者 ,采用榄香烯乳联合顺铂治疗 ,取得了很好的疗效 ,现报告如下。1　资料与方法1.1　一般资料　 2 8例患者中男 18例 ,女 10例 ;年龄 4 5～ 6 8岁 ,平均 5 4 .5岁 ,全部病例均经病理学诊断或影像学检查 (X线、CT或超声等 )诊断 ,均为晚期肿瘤患者伴有胸腹水者 ,其中胸腔积液 12例 ,原发灶均来自肺癌 ;腹腔积液 16例 ,原发于胃癌 4例、肝癌 6例、肠癌 2例、…     

榄香烯联合肝动脉化疗栓塞术治疗原发性肝癌的Meta分析

目的评价榄香烯联合肝动脉化疗栓塞术(TACE)治疗原发性肝癌(PLC)的近期、远期疗效及不良反应。方法两位评价员按相同的检索策略检索Pubmed、EMBASE、Cochrane Library、中国期刊全文数据库、万方数据库、中国生物医学文献数据库、维普期刊全文数据库中关于榄香烯联合TACE治疗PLC的临床研究,用Jadad质量评分法评价纳入文献的质量,用Review Manager 5.2软件进行Meta分析。结果共纳入9篇文献,487例患者。Meta分析的结果提示:榄香烯联合常规TACE组与常规TACE组比较,其有效率、疾病控制率及12、24个月生存率均提高,差异有统计学意义[有效率:相对危险度(RR)=1.43,95%可信区间(95%CI):1.23~1.67,P0.001;疾病控制率:RR=1.22,95%CI:1.11~1.32,P0.001;12个月生存率:RR=1.68,95%CI:1.22~2.31,P=0.001;24个月生存率:RR=2.91,95%CI:1.44~5.87,P=0.003];在不良反应发生率方面,榄香烯联合常规TACE组治疗PLC可降低腹痛发生率且差异有统计学意义(RR=0.59,95%CI:0.36~0.98,P=0.04)。结论榄香烯联合TACE与单独TACE治疗PLC比较,有可能提高肝癌患者的有效率、疾病控制率及生存率,并降低一些不良反应的发生。     

榄香烯治疗恶性胸腔积液65例报告

我院自１９９２年９月至１９９５年９月应用大连金港制药有限公司研制的榄香烯乳注射液对６５例恶性肿瘤所致恶性胸腔积液治疗。     

重组腺病毒载体携带多药耐药基因1反义RNA靶向逆转肝癌细胞多药耐药

目的 探讨携带多药耐药基因1(multidrug resistance gene 1,mdr1)反义RNA的重组腺病毒载体靶向逆转甲胎蛋白阳性(AFP+)的肝癌多药耐药细胞HepG2R的疗效及作用机制.方法 分别构建携带AFP启动子和mdr1基因反义核苷酸片段的重组腺病毒载体Adeno-asmdr及携带AFP启动子和增强绿色荧光蛋白基因的重组腺病毒载体Adeno-EGFP,将Adeno-EGFP转染人正常肝细胞L02(AFP-),人官颈癌细胞HeLa(AFP-)及HepG2(AFP+)细胞,检测增强绿色荧光蛋白基因在各细胞的转录水平;将Adeno-asmdr转染HepG2R细胞,Western blot检测不同时间P-gp170的表达,末端脱氧核苷酸转移酶介导的脱氧三磷酸尿苷缺口末端标记法检测HepG2R细胞凋亡,流式细胞术检测HepG2R细胞在不同药物作用下细胞周期、凋亡率.结果 增强绿色荧光蛋白基因在AFP阳性的HepG2细胞可得到显著转录,而在L02细胞和HeLa细胞,其转录减少,显示了该载体的良好转录活性以及靶向特异性.Adeno-asmdr转染HepG2R细胞后,HepG2R细胞P-gp170表达明显减弱,HepG2R细胞凋亡增加,HepG2R细胞对多种化疗药物的耐受能力明显下降,细胞出现显著的周期阻滞,大量细胞被阻滞于S期和G0/M期,凋亡细胞比例增加.结论 实验构建的Adneo-asmdr重组腺病毒载体可在AFP阳性HepG2R细胞内特异靶向性表达目的 基因,并可有效降低mdrl基因产物P-gp170的表达,从而达到对HepG2R细胞多药耐药的逆转作用.     

Estrual cycle periodicity in hormone-independent tumor-bearing mice

Summary The periodicity of the estrual cycle in mice was studied by vaginal cytology during the growth of a hormone-independent mammary adenocarcinoma. A direct relationship between age progression and lengthening of estrual cycle was observed in control mice but not in tumor-bearing mice of the same age. These results suggest that hormone regulation of the estrual cycle may be affected in tumor-bearing hosts.     

Enhanced therapeutic effects of combined chemotherapeutic drugs and midkine antisense oligonucleotides for hepatocellular carcinoma

AIM： To evaluate the effect of combined antisense oligonucleotides targeting midkine （MK-AS） and chemotherapeutic drugs [cisplatin（DDP）, 5-fluorouracil （5-FU） and adriamycin （ADM）] on inhibition of HepG2 cell proliferation, and to analyze the efficacy of MK-AS used in combined ADM in in situ human hepatocellular carcinoma （HCC） model. METHODS： HepG2 cells were treated with MK-AS and/or chemotherapeutic drugs mediated by Lipofectin, and cell growth activity was determined by MTS assay. An in situ HCC model was used in this experiment. MK- AS, ADM and MK-AS ＋ ADM were given intravenously for 20 d, respectively. The animal body weight and their tumor weight were measured to assess the effect of the combined therapy in vivo. RESULTS： Combined treatment with MK-AS reduced the IC50 of DDP, 5-FU and ADM in HepG2 cells. MK-AS significantly increased the inhibition rate of DDP, 5-FU and ADM. Additionally, synergism （Q 1.15） occurred at a lower concentration of ADM, 5-FU and DDP with combined MK-AS. Combined treatment with MK-AS and ADM resulted in the more growth inhibition on in situ human HCC model compared with treatment with chemotherapeutic drugs alone. CONCLUSION： MK-AS increases the chemosensitivity in HepG2 cells and in situ human HCC model, and the combination of MK-AS and ADM has a much better in vitro and in vivo synergism.     

可溶性PD-1和4-1BB配体在体内联合表达对小鼠实验性肝癌的治疗作用

目的了解4-1BB配体(4-1BBL)治疗小鼠实验性肝癌时可能引起的负调控因素,以及可溶性PD-1(sPD 1)与4-1BBL协同治疗肿瘤的效应和机制。方法按照5×105／只的剂量将H22肝癌细胞接种于Balb／c小鼠右后腿肌肉内,建立小鼠实验性肝癌模型,随机分成5组,每组12只。空白对照组注射等渗盐水;pcDNA3．1组、p4-1BBL组和 pPD-1A组分别注射质粒pcDNA3．1、p4-1BBL和pPD-1A;p4-1BBL+pPD-1A组为联合治疗组,同时注射质粒p4- 1BBL和pPD-1A。观察小鼠肿瘤生长情况及存活率,检测两种基因在瘤周组织中的表达,对各组小鼠残存瘤细胞进行表型分析,检测肿瘤组织中的淋巴细胞。结果单独或联合转染4-1BBL基因和sPD-1基因均显示出抗肿瘤作用．尤以联合转染组小鼠肿瘤的生长抑制效果最为明显,该组有42％的小鼠肿瘤被完全抑制(其他各组完全抑制率为0);至实验第6周,联合转染组小鼠存活率达到100％,明显高于pcDNA3．1组(30％)、1)4-1BBL组(65％)、pPD-1A组(62％)。流式细胞术检测结果表明,p4-1BBL组残存瘤细胞上负调节性分子B7-H1和B7-DC的表达水平明显高于其他各组瘤细胞, 联合治疗组小鼠瘤周组织中CD8(?)T淋巴细胞数量明显增加。结论4-1BBL在促进抗肿瘤免疫应答的同时．也会引起负调节因素的上调,sPD-1可与4-1BBL产生协同治疗效应,增强机体抗肿瘤作用。     

Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter, double-blind, randomized controlled study

Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group), 200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 ± 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 ± 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.     

Therapeutic effects of the combination of methotrexate and bucillamine in early rheumatoid arthritis: a multicenter,double-blind,randomized controlled study

Abstract

Disease-modifying antirheumatic drug (DMARD) combination therapies are used widely, but there have been few reports clearly demonstrating that combination therapy is more effective than DMARD monotherapy. We conducted a multicenter, double-blind controlled trial in order to clarify that the combination of methotrexate and bucillamine is more effective than either alone. The subjects of this study were 71 patients with active rheumatoid arthritis within 2 years of onset. Dosages were 8?mg methotrexate with 5?mg folic acid per week (MTX group), 200?mg bucillamine per day (BUC group), or both MTX and BUC (combination group). Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20 response rate was 79.2% in the combination group, significantly higher than the rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P = 0.0178). The cumulative survival curve of maintaining the ACR 20 response was significantly higher in the combination group than in the MTX and BUC groups (P = 0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score over 96 weeks was 12.6 ± 9.0 in the combination group, significantly lower (P = 0.0468) than the value of 28.0 ± 28.3 for the single DMARD (combined MTX and BUC) group. The incidence of adverse reactions did not differ significantly between the three groups. It was concluded that the combination therapy with MTX and BUC showed significantly higher clinical efficacy than either of the single DMARD therapies.     

达肝素钠对肝癌生长转移抑制的实验研究

目的研究低分子肝素达肝素钠对肝癌生长转移的抑制作用。方法采用人肝癌裸鼠转移模型(LCI-D20)。40只模型鼠随机分成4组即对照组、化疗组(顺铂 氟尿嘧啶),达肝素钠组、联合组(顺铂、氟尿嘧啶与达肝素钠)。观察肿瘤大小和转移、抑瘤率、测血清甲胎蛋白(AFP)、肿瘤微血管密度(MVD)、CD31。结果对照组、化疗组、达肝素钠组、联合组的肿瘤体积分别为(25245±13367)mm3、(1610 ±1217)mm3、(5883±3131)mm3和(5556±2570)mm3;抑瘤率分别为0%、93.6%、76.7%和78.0%;MVD 分别为20.7±6.8、18.2±2.6、4.8±1.8和6.5±2.4;CD31分别为31.8±5.7、25.5±5.1、21.6±4.8和19.6±2.4;AFP分别为(121.8±31.4)ng/ml、(21.5±13.3)ng/ml、(75.6±29.7)ng/ml 和(55.8±38.0)mg/ml;肝转移率分别为80%、70%、20%和10%;肺转移率分别为70%、60%、20%和10%; 腹壁转移率分别为90%、60%、30%和30%;腹水形成率分别为20%、10%、0%和0%。化疗组、达肝素钠组、联合组分别与对照组比,对肝癌生长的抑制作用差异有统计学意义,F=9.191,P<0.01。达肝素钠对肝癌血管形成和转移有良好的抑制作用,与对照组及单纯化疗组比差异有统计学意义,F=4.937,P<0.01。结论低分子肝素达肝素钠通过抗肿瘤血管形成,对肝癌的生长与转移有抑制作用。     

小鼠肝癌树突状细胞融合瘤苗抗肿瘤作用的研究

目的 探讨小鼠肝癌树突状细胞(D C)融合瘤苗抗肿瘤作用及其机制。 方法 用聚乙二醇(P E G)法制备小鼠肝癌D C融合瘤苗;流式细胞仪检测融合细胞表型特征;体内预防试验观察融合瘤苗免疫小鼠抵抗肿瘤攻击能力,乳酸脱氢酶(L D H)法检测其诱导的杀伤性T淋巴细胞活性;体内治疗试验观察荷瘤小鼠生存期及肿瘤组织中肿瘤坏死因子(TNF-α)、γ干扰素(IFN-γ)表达。 结果 小鼠肝癌D C融合瘤苗具备D C及肝癌细胞表型特征,能抵抗H 22小鼠肝癌细胞的攻击及诱导较强的细胞毒性T淋巴细胞(CTL)活性,DC/H22、DC H22、DC、H22各组CTL活性(A值)分别为0.624±0.014、0.330±0.014、0.262±0.019、0.246±0.017,F=65.46,P<0.01,能显著促进肿瘤组织中TNF-α、IFN—γ表达(F值分别为47.84、37.23,P值均<0.01)及延长荷瘤小鼠生存期(x2=18.45,P<0.01)。 结论 小鼠肝癌DC融合瘤苗能有效地诱导抗肿瘤免疫反应,在预防和治疗肝癌的复发及转移中有广阔的应用前景。     

Expression of multidrug resistance-associated protein gene in Ewing's sarcoma and malignant peripheral neuroectodermal tumor of bone

The expression of multidrug resistance-associated protein (MRP) mRNA was examined in ten samples of Ewing's sarcoma of bone (ES) and in one nude mice transplantable ES and two malignant peripheral neuroectodermal tumor (MPNT) cell lines using an RT-PCR assay. MRP mRNA expression was recognized in eight of the ten clinical specimen and in all three cell lines. On the other hand, the expression of multidrug resistance gene (MDR1) was demonstrated in three of the ten clinical samples and all three cell lines. Our results may contribute to elucidation of the mechanism of anti-cancer-drug resistance in this tumor.