Modeling and cost-effectiveness analysis of etanercept in adults with rheumatoid arthritis in Japan: a preliminary analysis

The tumor necrosis factor (TNF) antagonist etanercept is an antirheumatic agent which was approved by Japanese regulatory authorities in January 2005. In Japan, the cost-effectiveness of this therapy for patients with rheumatoid arthritis (RA) has not previously been evaluated. This study models the cost-utility of etanercept in comparison with standard therapy with disease-modifying antirheumatic drugs (DMARDs) among adult Japanese RA patients who have failed a previous course of the DMARD bucillamine. A Markov model with 6-month cycles was constructed to compare two therapeutic strategies: etanercept versus standard therapy. For each cycle, one of three options was possible: a patient could (i) remain on current therapy if American College of Rheumatology criteria for 20% clinical improvement (ACR20) were achieved, (ii) switch to another drug in the therapeutic pathway if ACR20 was not achieved or if side effects severe enough to cause treatment discontinuation occurred, or (iii) they could die. The therapeutic pathway for the etanercept strategy was etanercept, methotrexate (MTX), sulfasalazine (SSZ), combination therapy (MTX + SSZ) and, finally, no DMARD. The pathway for standard therapy was identical except the initial therapy was MTX (etanercept was excluded). Results from clinical trials in U.S. and European patient populations were used to derive model probabilities for disease progression, response to drug therapy, and relationships between ACR20 response and functional improvement as measured by the Health Assessment Questionnaire (HAQ) disability index. An equation was developed to predict utility from HAQ scores of Japanese patients. Costs for drugs and medical services in Japan were obtained for April 2003. Analysis was conducted from a societal perspective, including lost productivity costs due to RA disability and premature mortality. Costs were discounted at 6% annually, and quality-adjusted life years (QALYs) at 1.5% annually. Model parameters were varied by 20% above and below base-case values in sensitivity analyses. Compared to standard therapy, the etanercept strategy was ￥6.39 million more costly per patient but yielded an additional 2.56 QALYs. The incremental cost-utility ratio was ￥2.50 million/QALY. Sensitivity analyses revealed that cost-utility was most strongly influenced by the acquisition cost of etanercept and the percentage of etanercept recipients who achieved ACR20. Using commonly applied thresholds for acceptable cost-effectiveness in the United States ($50 000 = ￥5.5 million/QALY) and the United Kingdom (￡30 000 = ￥5.7 million/QALY), etanercept therapy in Japan can be considered cost-effective. Cost-utility ratios did not exceed these thresholds in any sensitivity analysis. Further analyses should be conducted once clinical and epidemiologic data for Japanese patients become available.     

小分子靶向肽（RGD）2C与力达霉素的偶联物抗肿瘤作用研究

目的：考察小分子靶向肽（RGD）：C与力达霉素的偶联物的抗肿瘤作用。方法：MTr法观察偶联物和力达霉素在体外对人口腔鳞癌KB细胞、人乳腺癌MCF-7细胞以及人肝癌Bel7402细胞的细胞毒性。克隆形成法观察其对人肝癌Bel7402细胞克隆形成的抑制作用。采用C57BIM6小鼠Lewis肺癌移植瘤模型观察其实验治疗作用。结果：MrlT法结果表明,偶联物对人口腔鳞癌KB细胞、人肝癌Bel7402细胞和人乳腺癌MCF-7细胞的细胞毒性比力达霉素分别下降13倍、46倍和186倍。克隆形成法表明．偶联物对人肝癌Bel7402细胞的克隆形成抑制率比力达霉素下降10倍。0．2,0．1,O．05mg·kg-1偶联物对C57BL／6小鼠Lewis癌皮下原发瘤的生长抑制率分别为35．8％,25．6％和10．3％;0．05mg·kg-1素对肿瘤生长的抑制率为32．4％。0．2,0．1,0．05mg·kg-1偶联物对小鼠Lewis癌肺转移的抑制率分别为69．6％,50．5％和34．2％,0．05mg·kg-1达霉素、0．05mg·kg-1力达霉素＋1mg·kg-1（RGD）：C肽的抑制率分别为53．3％和54．9％。结论：按等细胞毒性剂量来计算,偶联物体内抗肿瘤活性和抗肿瘤转移活性比力达霉素强,提示小分子靶向肽RGD与力达霉素偶联后发挥了一定的导向作用。     

翡翠贻贝多糖对荷瘤小鼠的抗肿瘤和免疫功能调节作用

目的观察翡翠贻贝多糖（PVPS）对荷瘤小鼠肿瘤生长及免疫功能的影响。方法建立小鼠移植性S180实体瘤模型,观察PVPS对荷瘤小鼠的抑瘤率及对T淋巴细胞增殖能力、白介素2（IL-2）等指标的影响。结果PVPS可明显抑制荷瘤小鼠S180实体瘤的生长（P〈0．05orP〈0．01）,提高T淋巴细胞增殖能力和IL-2的产生（P〈0．01）。结论PVPS可显著抑制荷瘤小鼠肿瘤的生长,并能增强荷瘤小鼠的免疫功能。     

国内熊果酸衍生物相关专利结构修饰技术的研究进展

熊果酸衍生物可抑制多种肿瘤细胞的生长,并因其细胞低毒性而日益成为抗肿瘤药物领域的研究热点.本文对通过中国专利数据库进行检索获得的熊果酸衍生物在中国的相关专利申请进行了分析,总结了目前国内专利申请中熊果酸衍生物主要结构修饰位置及其活性,并结合目前国内雄果酸衍生物相关专利申请的现状给出了今后专利申请的建议.     

真菌植物提取物体内抗小鼠S180作用及与环磷酰胺联合作用

目的研究真菌植物提取物AMH-D的体内抗肿瘤作用,与环磷酰胺是否具有联合作用以及联合作用的形式和强度,为抗癌药物的开发提供科研基础.方法昆明种小鼠右腋皮下接种S-180肿瘤细胞,随机分组后,第2天开始腹腔注射给药,隔天给药1次,第11天处死小鼠,剥离并称重肿瘤,以肿瘤重量作为分析评价指标.结果提取物AMH-D能显著抑制S-180的生长,在剂量为150 mg/kg时抑瘤率达50.45%,其肿瘤抑制作用呈现剂量-效应关系.AMH-D对小鼠体重增长没有明显的影响.AMH-D与环磷酰胺具有体内协同抗肿瘤作用.结论真菌植物提取物AMH-D具有体内抑制S-180肿瘤作用,并与临床抗癌药物环磷酰胺具有体内联合抗癌作用.     

褪黑素抗肝癌作用及其机制的研究进展

褪黑素是一种由脊椎动物脑中松果腺体分泌的吲哚类激素,它可能通过对细胞周期的调节、通过调钙蛋白M与雌激素信号通路发生联系而发挥抑制人类肿瘤生长、扩散的作用.褪黑素已在乳腺癌、前列腺癌的发病及治疗方面取得一定的成果,但对肝癌的研究并不深入,可能与黑色素对肝细胞凋亡诱导、影响肝癌细胞周期以及调节免疫等作用有关,该文就褪黑素抗肝癌作用机制的研究新进展予以综述.     

中药抗肿瘤多药耐药机制的研究进展

肿瘤治疗中化疗药物的使用很大程度上抑制了肿瘤的生长,复发及转移,但肿瘤多药耐药现象的出现严重影响了化疗的疗效及肿瘤患者的生存期。多药耐药是肿瘤细胞在接触某种化疗药物之后,对其产生耐药性,同时对其他结构类似的化疗药物也产生交叉抗药性的一种肿瘤治疗进程中出现的难题。越来越多的中药制剂已表现出逆转肿瘤多药耐药的潜力,对其作用机制的研究也越发得到关注。本文将综述一下中药抗肿瘤多药耐药的广泛机制,并以胃癌为例进行较详细阐述,最后提出一些中药抗肿瘤多药耐药的研究新思路。     

浅析临从抗肿瘤药物的不良反应和防治措施、掌握药品说明书内容、监护整个用药过程及对患者的用药教育四个方面探讨临床药师对抗肿瘤药物的药学监护,促进抗肿瘤药物的合理使用.临床药师应关注和掌握抗肿瘤药物常见的不良反应及防治措施,掌握抗肿瘤药品说明书的内容,协助医生选择合理的用药方法,监护整个用药过程,做好药品的正确使用、患者的用药教育和健康教育,提高患者的依从性.临床药师只有通过临床实践,真正树立以病人为中心和团队合作共同为病人服务的理念,才能在实践中发现潜在的或实际存在的临床用药问题并正确预防或解决. 床药师对抗肿瘤药物的药学监护

从抗肿瘤药物的不良反应和防治措施、掌握药品说明书内容、监护整个用药过程及对患者的用药教育四个方面探讨临床药师对抗肿瘤药物的药学监护,促进抗肿瘤药物的合理使用.临床药师应关注和掌握抗肿瘤药物常见的不良反应及防治措施,掌握抗肿瘤药品说明书的内容,协助医生选择合理的用药方法,监护整个用药过程,做好药品的正确使用、患者的用药教育和健康教育,提高患者的依从性.临床药师只有通过临床实践,真正树立以病人为中心和团队合作共同为病人服务的理念,才能在实践中发现潜在的或实际存在的临床用药问题并正确预防或解决.     

Differentiation of bel-7402 human hepatocarcinoma cells induced by aqueous extracts of fresh gecko (AG) and its anti-tumor activity in vivo

Ethnopharmacological relevance

Gecko, a kind of reptile, has been widely used as a traditional Chinese medicine to treat various diseases including cancer in China for thousands of years. The aim of this study was to investigate the anti-tumor effect of AG (aqueous extracts of fresh gecko) on human hepatocellular carcinoma cell Bel-7402 in vitro and mouse H22 hepatocellular in vivo. Further to underlie the molecular mechanism of AG inducing the differentiation of Bel-7402 cells.

Materials and methods

AG was obtained by water extracting method and qualitatively analyzed through High Performance Liquid Chromatography. The total protein concentration of AG was measured by BCA (bicinchoninic acid disodium) assay. The anti-tumor activities in vivo were analyzed through H22 (mouse hepatocellular carcinoma cell line H22) tumor xenografts mice. The cytotoxic activity of AG on Bel-7402 cells was evaluated by MTT assays. AFP (alpha fetoprotein) was detected by radioimmunoassay. ALB (albumin), ALP (alkaline phosphatase) and γ-GT (γ-glutamyl transpeptidase) were detected by biochemical methods with commercial kits. While morphological changes were observed through an inverted microscope. Moreover, the expression level of the proteins involved in MAPK (mitogen-activated protein kinase) signal pathway which was closely related to cellular differentiation was assessed by Western blot.

Results

AG showed obviously anti-tumor activity in vivo and anti-proliferative activity on Bel-7402 cells in vitro both dose-dependently. The number of clones of Bel-7402 cells treated with AG reduced and the cells were displaying differentiation state such as relatively bigger size and dispersed growth. The biochemical function markers of the cells were significantly changed after being treated with AG. The data showed that AFP secretion of the cells decreased 42.5%, ALB secretion increased 58.9%, the activity of ALP and γ-GT markedly decreased 67.0% and 48.5% separately when the concentration of AG was 10 μl/ml, and those effects were all in a dose-dependent manner. The major original and phosphorylated signal proteins (ERK1/2 (extracellular sigal-regualted kinase 1/2), P38 (p38 MAPK) and JNK1/2 (c-Jun N-terminal kinase 1/2)) involved in MAPK signal pathway were measured and the results showed that AG activated the ERK1/2 of Bel-7402 cells.

Conclusions

AG has anti-tumor activity in vivo and inhibits Bel-7402 cell proliferation in vitro through inducing cell differentiation, and the mechanism involves the activation of ERK1/2.