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单克隆抗体药物综述

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单克隆抗体药物综述单克隆抗体药物综述 guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. D...
单克隆抗体药物综述
单克隆抗体药物综述 guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation 单克隆抗体药物综述 摘 要: 通过淋巴细胞杂交瘤技术或基因工程技术制备单克隆抗体药物 ,已经成为生物制药领域的一个重要方面 ,由于单克隆抗体药物专一性强、 疗效显著 ,因此成为近年来研究的热点药物之一。此文就单抗药物的分类、应用进行了综述 ,并对其应用前景及存在的不足作了概述。 关键词:单克隆抗体 抗体药物 靶向 联用 自 1975 年Koeh ler 和M ilstein 首先报道利用小鼠杂交瘤细胞制备单克隆抗体以来, 经过近 30 年的发展, 单抗技术在生命科学研究及医学实践方面作出了杰出的贡献, 已经成为了现代生物技术产业的支柱之一。 然而, 尽管单抗推动了生物诊断技术的革命, 但是在将单抗应用于人体疾病的治疗方面, 却在长时间内迟迟没有进展。早期的临床试验结果都不尽人意, 这是因为鼠源单抗应用于人体有许多限制]. 现今上市的单抗药物, 治疗的领域主要集中在肿瘤、 自身免疫疾病、 器官移植排斥及病毒感染等领域。由于单抗具有明确的作用位点, 与靶位点亲和力高, 而且通过改造的抗体其免疫原性大大减弱, 这些因素使得单抗在临床治疗中具有特异性强、 见效快、 副作用较低等优点, 因而单抗治疗有着广阔的前景。目前, FDA 批准上市的 17 个单抗药物中即有 8 个是用于治疗淋巴细胞肿瘤、 乳腺癌及结直肠癌等, 而在开发阶段的单抗也有一半以上是与治疗各种癌症相关。可以预见, 在未来几年来将有更多的治疗性单抗药物上市, 其市场份额将进一步扩大。 目前, 单抗类药物的市场销售逐年提升的年均增长幅度在20%以上, 现强劲。 用于治疗非霍奇金淋巴瘤的单抗药物R ituxan 已成为世界第一的抗肿瘤药物, 2003 年销售为 14 . 89亿美元, 2002 年为 11 . 63 亿美元, 在 2002 年全球最畅销前 50位商标名处方药中排名 43 位。用于治疗关节炎的单抗药物Rem icade, 2002 年销售额为 12 . 97 亿美元, 当年全球药物销售排名第 37 位。2000 年世界单抗药物的销售额为 22 . 05 亿美元, 据F ro st&Sullivan 预测, 到 2003 年销售额将达到 47 亿美元。 下面就单克隆抗体药物的研究进展作一综述。 1 单克隆抗体药物的分类 单抗药物一般分为:治疗疾病(尤其是肿瘤)的单抗药剂、 抗肿瘤单抗偶联物、 治疗其他疾病的单抗。单抗药剂针对的靶点通常为细胞表面的疾病相关抗原或特定的受体。如:最早被美国 FDA批准用于治疗肿瘤的单抗药物利妥昔单抗;抗肿瘤单抗偶联物 ,或称免疫偶联物( Immunoconjugate) , 由单抗与有治疗作用的物质(如:放射性核素、 毒素和药物等)两部分构成 ,其中包括放射免疫偶联物、 免疫毒素、 化学免疫偶联物 ,此外还有酶结合单抗偶联物、 光敏剂结合单抗偶联物等。 2 作为肿瘤治疗药剂的单克隆抗体药物 表1概括了近年来美国 FDA 批准上市的 5 个治疗肿瘤的单克隆抗体药物的基本情况 ,下面具体加以介绍。 2. 1 利妥昔单抗 guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation 在自身免疫性疾病形成过程中 ,B 细胞起重要作用。CD20是前B细胞向成熟淋巴细胞分化过程中表达的表面抗原 ,参与调节B细胞的生长和分化。利妥昔单抗(美罗华)是一种针对 CD20抗原的人鼠嵌合型单克隆抗体 ,是第一个被FDA批准用于临床治疗的单抗。进入人体后可与 CD20 特异性结合导致 B 细胞溶解 ,从而抑制 B 细胞增殖 ,诱导成熟 B细胞凋亡 ,但不影响原始B细胞。它能通过介导抗体依赖的细胞毒性(ADCC) 、 补体依赖的细胞毒性(CDC)作用和抗体与CD20分子结合引起的直接效应 ,包括抑制细胞生长 ,改变细胞周期以及凋亡等方式杀死淋巴瘤细胞[1 ]。 由于利妥昔单抗药物可以提高肿瘤细胞对化疗的敏感性 ,所以利妥昔单抗药物的优势就在于与其他治疗药物及治疗方式配合使用。临床研究表明美罗华单药或联合化疗治疗肿瘤具有良好的疗效和安全性 ,但还是存在一定的毒副作用。夏忠军等[2 ]进行的临床研究:34例确诊惰性淋巴瘤的患者接受含利妥昔的化疗 ,结果总有效率为 92. 3 % ,完全缓解率为60. 0 %。主要不良反应为骨髓抑制 ,其它不良反应包括恶心呕吐、 轻度脱发和肝功能受损等。张晓艳等[3 ]对 4例 CD20阳性非霍奇金淋巴瘤(NHL) 病人进行了5次利妥昔单抗联合自体外周血干细胞移植(APBSCT)的治疗研究 ,结果显示所有病人均对利妥昔单抗耐受良好 ,植入后在 8,11 d内达造血重建 ,表明利妥昔单抗联合APBSCT治疗 CD20阳性NHL 是一种耐受及效果良好的方法。 2. 2 曲妥珠单抗 曲妥珠单抗为一种针对 HER22/ neu的重组人源化 IgG单克隆抗体 ,能特异性识别 Her22调控的细胞表面蛋白 HER22 ,使其通过内吞噬作用离开胞膜进入核体内 ,抑制其介导的信号转导 ,从而起到治疗肿瘤的作用。美国 FDA 于 1999 年批准其上市 ,2002年在我国上市。大量临床资料证实曲妥珠单用于乳腺癌的有效率为21 % ,而且它与化疗联合应用明显提高了生存时间[4 ]。据报道 ,欧洲曲妥珠单抗辅助治疗试验研究了曲妥珠单抗对 HER22 阳性伴有或不伴有淋巴结阳性的乳腺癌患者的疗效 ,其中 1 组给予 1 年的曲妥珠单抗治疗 ,另1组作为对照。曲妥珠单抗治疗 1 年组与对照组相比 ,复发风险减少了46 % ,两组的整体生存率无明显区别 ,说明曲妥珠单抗用于治疗辅助化疗后的 HER22阳性乳腺癌患者 ,明显延长了患者的无病生存期[5 ]。我国也对曲妥珠进行了临床研究 ,沈坤炜等[6 ]对 42 例 ?, ?A期浸润性乳腺癌患者紫杉醇联合曲妥珠单抗治疗 24 周 ,结果单用新辅助化疗组完全缓解率为 26. 3 % ,在新辅助化疗联用曲妥珠单抗组为65. 2 % ,可见 ,对于 HER22 过表达的乳腺癌化疗联用曲妥珠单抗能显著提高完全缓解率。 2. 3 阿伦珠单抗 阿伦珠单抗是人源化、 非结合型单抗 ,作用靶点为正常与异常B淋巴细胞的 CD52 抗原 ,CD52 广泛分布于正常的 B淋巴细胞、 T淋巴细胞、 单核细胞、 巨噬细胞和B 淋巴细胞及T淋巴细胞瘤细胞表面 ,在慢性淋巴细胞白血病细胞表面尤为丰富。它与带 CD52 的靶细胞结合后 ,通过宿主效应子的补体依赖性细胞毒性(CDC) 、 抗体依赖性细胞毒性(ADCC)和细胞凋亡等机制导致细胞死亡。阿伦珠单抗作为一种作用机制独特的单克隆抗体 ,对源于B和 T细胞的各种恶性肿瘤具有很好的治疗作用。 英国科学家应用阿伦珠单抗和利妥昔单抗治疗复发性淋巴瘤患者 ,结果总反应率为 52 % ,其中完全缓解 8 % ,表明联合使用阿伦珠单抗和利妥昔单抗是安全可行的。在其它 T细胞恶性肿瘤的治疗中:对 22 例 ?, ?期皮肤 T细胞淋巴瘤(蕈样肉芽肿病和 Sezary综合征)患者静脉输注阿伦珠 12周 ,结果显示阿伦珠具有非常好的疗效 ,总有效率达 55 %。其中 ,红皮病患者总有效率达 69 % ,片状斑或皮肤肿瘤患者达40 %[7 ]。阿伦珠单抗联合其他药物、 化疗等治疗肿瘤具有显著的效果。但临床研究表明 ,其还存在一些常见并发症 ,如低血压、 寒颤、 发热、 恶心、 呕吐、 气短、 支气管痉挛、 皮疹、疲乏、 呼吸困难、 头痛、 腹泻、 感染等。 the functions and priorities compared to the requirements of our gap is still very big. Main is daily in the passive meet of more, active research of less, service also has not timely, and not in place of problem; work in the meet Yu traditional of, and program of of work way, develop innovation spirit and service innovation capacity not strong; supervision information work and promoted decision implementation of contact enough close, feedback situation not active; research resources of using enough full, research results of into degree not high; some sector documents running not specification; Municipal Government Office on the County (district) and municipal government sector Office work of guide enough, No real form interaction and close collaboration, promote the implementation of the work. These problems, we must effectively be addressed in the future work. Second, serve the overall situation, carry out their duties, improve quality, and strive to create a new situation of system of government offices in the city since last season, meeting the Secretary-General of the State Council and the provincial government has held a government system, from a global and strategic height, scientifically analyzed the new situation and the newTasks on the system of government offices bring new situations and new problems and new challenges, profoundly expounded the work of government departments at all levels in the new era should be put in the situation to understand, to grasp, to deploy at any time and under any circumstances, should always focus on the big picture, firmly grasp the overall situation, increasing in the overall implementing in earnest the work of spontaneity, initiative and steadfastness. And explicitly put forward the "surrounding situation, pay attention to implementation" is the core of government offices, requiring government departments at all levels cannot be "Gramophone", "mail room" and "the Messenger" is not confined to paper communications, yinglaisongwang and upload issue. Must to has strongly of implementation guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation 2. 4 西妥昔单抗 西妥昔单抗为 IgG 1 单克隆抗体 ,是表皮生长因子受体拮抗剂 ,可与表达于正常细胞和多种肿瘤细胞表面的表皮生长因子受体( EGFR)特异性结合 ,并竞争性阻断 EGF和其他配体 ,如α 2转化生长因子(TGF 2 α)的结合。它通过增加细胞周期抑制因子 p27kip 使得细胞周期停留在 G 1 期;增加 Bax表达和减少 bcl22表达 ,诱导癌细胞的凋亡;它还可减少基质金属蛋白酶和血管内皮生长因子(VEGF)的产生。相关实验表明 ,西妥昔单抗可抑制过度表达 EGFR的肿瘤细胞的增殖 ,但是对缺乏 EGFR表达的肿瘤细胞则没有抗肿瘤效果 ,还发现西妥昔与化疗联用要优于单独化疗[8 ]。 在对西妥昔单抗联合化疗的研究中 ,BOAD 试验最为著名。576例晚期结直肠癌(ACRC)患者中 82 %的 EGFR 过表达。治疗采取两个方案 ,第1组用西妥昔单抗联合伊立替康治疗;第2组单独用西妥昔单抗单药治疗。西妥昔单抗联合伊立替康与单用西妥昔单抗相比 ,联用疗效优于单一使用 ,有效率分别为23 %和11 % ,疾病控制率为 56 %和 32 % ,疾病进展中位时间为4. 1和1. 5个月 ,中位生存时间为8. 6和6. 9个月 ,而且西妥昔单抗并没有增加化疗的副作用。以上临床实验显示:西妥昔单抗能够克服 ACRC患者对伊立替康的耐药性 ,生存质量明显提高[9 ]。西妥昔单抗的毒副作用包括:痤疮样皮疹、 虚弱、 腹痛、 恶心、 呕吐、 白细胞减少和过敏反应等。其中痤疮样皮疹是最常见的不良反应 ,皮疹主要分布在脸部和躯干上部 ,这可能是由于西妥昔单抗干扰了 EGF的表皮生理作用所致[10 ]。 2. 5 贝伐单抗 贝伐单抗是抗VEGF的人源化单抗 ,主要通过中和VEGF来阻断其与内皮细胞上的受体结合 ,使得肿瘤细胞不能得到养分和氧 ,起到治疗肿瘤的作用。Presta 等[11 ]将鼠抗人VEGF单克隆抗体(muMAB VEGF) A. 4. 6. 1 的互补决定区与人 IgG 1的恒定区框架嵌合 ,并对相应氨基酸残基加以修饰 ,最终形成了人鼠嵌合型 VEGF单抗 ,仍然有 7 %的氨基酸来源于鼠抗体。实验表明 ,贝伐单抗用于治疗肿瘤安全有效。郑航等[12 ]探究贝伐单抗联合伊立替康治疗转移性结肠癌的疗效 ,90例患者中给予贝伐单抗联合伊立替康治疗的一组有效率为43. 3 % ,血清肿瘤标志物的浓度治疗前后有显著变化。这说明贝伐联合伊立替康治疗转移性结肠癌具有更高的疾病控制率。2005 年美国临床肿瘤学会年会上报道了贝伐单抗的最新研究结果 ,采用贝伐单抗联合伊立替康和顺铂一线治疗转移性胃癌或者胃食管连接部腺癌的患者 ,治疗的不良反应除了原有伊立替康和顺铂引起的肾髓抑制、 胃肠道反应等 ,还有贝伐单抗造成的不良反应包括栓塞性疾病、胃穿孔等。 3 抗肿瘤单抗偶联物 3. 1 放射免疫偶联物 放射免疫治疗(RIT)是以单克隆抗体为载体 ,以放射性核素为弹头 ,通过抗体特异性结合肿瘤细胞相关抗原 ,将产生高能射线的放射性核素靶向到肿瘤细胞 ,实现对肿瘤的近距离内照射治疗。RIT利用携带放射性核素的单克隆抗体特异地结合到病灶部位 ,减少了对正常组织的损伤。90Y— ibri2tumomab是第1个被 FDA批准应用于临床的放射免疫制剂 ,主要用于复发的淋巴瘤患者或对单独应用利妥昔单抗疗效不佳的患者。 3. 2 免疫毒素 免疫毒素是用化学方法或基因工程方法将肿瘤选择性单抗与经修饰的多肽毒素共价连接而成的肿瘤治疗药物。免疫毒素可与肿瘤细胞表面受体或与细胞表面的靶抗原相结合后内化 ,继而在胞内抑制细胞蛋白质合成 ,导致肿瘤细胞死亡。毒素有很多种 ,如植物毒素、 细菌毒素、 动物毒素 , 其中引用最广泛的是植物毒素中的白喉毒素。美国 FDA已经批准了白喉毒素与白细胞介素 2 重组的免疫毒素 ONTAK(DAB3892I L2) ,用于治疗人皮肤 T细胞淋巴瘤[13214 ]。 3. 3 化学免疫偶联物 guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation 单抗是药物良好的靶向性载体 ,通过药物分子上特殊的功能基团如:羟基、 巯基、 氨 基等 ,将治疗药物与单抗相连接而组成化学免疫偶联物 ,避免了药物对其他正常组织的毒害 作用,选择性地发挥治疗作用。常与单抗进行偶联的药物有阿霉素、 柔红霉素、 平阳霉素、 博安霉素、 丝裂霉素、 新制癌菌素、 氨甲喋呤等。 4 单克隆抗体在其他疾病中的应用 单克隆抗体药物不只在肿瘤的治疗中取得了很好疗效 ,在其他疾病的治疗中也取得了 一些疗效 ,例如:奥马珠单抗(omalizumab)通过与游离 IgE结合而显著降低游离 IgE的水平 , 阻断 IgE与肥大细胞、 嗜碱粒细胞结合 ,防止炎症介质的释放。可显著改善哮喘病人的症 状、 肺功能及生活质量 ,减少哮喘恶化的发作次数 ,减少糖皮质激素的用量 ,使用安全 ,具 有很好的耐受性[15 ]。Mab03. 2C1C2 在体外能抑制白念珠菌芽管的形成 ,从而抑制白念珠菌 对上皮细胞、 内皮细胞的粘附 ,降低白念珠菌的侵袭力。利妥昔单抗对类风湿和系统性红 斑狼疮也有很好的治疗作用。英夫利昔单抗对类风湿性关节炎患者疼痛、 晨僵、 关节肿胀 等临床症状减轻程度就可达60 %。另有研究显示 ,输注英夫利昔单抗可快速、 显著缓解顽 固性银屑病、 关节炎病人的关节和皮损症状[16 ]。英利昔单抗对克罗恩病、 溃疡性结肠炎、 酒精性肝病等消化系统疾病都有较好疗效 ,且在推荐的治疗范围内安全性良好[17 ]。 参考文献 [1 ] 冯洁.介绍几种抗肿瘤的靶向新药[J ] . 中国药师,2006 ,9 (2) :1762178. [2 ] 夏忠军.含美罗华方案治疗B细胞性惰性淋巴瘤34例[J ] .癌症,2006 ,25 (4) :4902494. [3 ] 张晓艳.利妥昔单抗联合自体外周血干细胞移植治疗非霍奇金淋巴瘤[J ] .中国新 药与临床杂志,2006 ,7 (19) :5412544. [4 ] 吴凤霞. Herceptin—一种治疗乳腺癌的新药[J ] . 中国生化药物杂志,1999 ,20 (1) :47. [5 ] 董嵩,朱建权,吴一龙. 美国临床肿瘤学年度报告[J ] . 循证医学,2006 ,6 (2) :67273. [6 ] 沈坤炜.紫杉醇序贯表阿霉素新辅助化疗联合曲妥珠单抗显著提高病理完全缓 解率[J ] .循证医学,2006 ,4 (6) :84286. [7 ] 崔银珠,胡江宁. 慢性淋巴细胞白血病治行新药 alemtuzumab[J ] .世界临床药 物,2004 ,25 (5) :2922296. [8 ] Baselga J . The EGFR as a target for anticancer therapy 2 focus on cetux2imab[J ] . Eur J Cancer 2001 ,37 (4) :16222. [9 ] Nygren P ,S orbye H O ,Sterlund P ,et al . Targeted drugs in metastaticcolorectal cancer with special emphasis on guidelines for the use of be2vacizumab and cetuximab : an Acta Oncologica expert report [J ] . ActaOncol ,2005 ,44 (3) :2032217. [10 ] Busam KJ ,Capodieci P ,Motzer R ,et al . Cutaneous side2effects in can2cer patients treated with the anti epidermal growth factor receptor anti2body C225[J ] .Br J Dermatol ,2001 ,144 (6) :116921176. [11 ] Presta L G,Chen H ,C onnor S J ,et al . Humanization of an anti2vascularendothelial growth factor monoclonal antibody for the therapy of s olid tu2mors and other dis orders[J ] . Cancer Res ,1997 ,57 (20) :459324599. [12 ] 郑航,陈锦章,廖吐军,等.贝伐单抗联合伊立替康治疗转移性结直肠癌的近期疗效 观察[J ] . 南方医科大学学报,2006 ,2652269. [13 ] 冯仁田,何维.白细胞介素218 的研究进展[J ] .中国生化药物杂志,1999 ,20 (2) :1012103. [14 ] 裴瑾,杨成君,杨翰仪,等. 白细胞介素 2 脂质体的制备及其抗肿瘤作用的研究[J ] . the functions and priorities compared to the requirements of our gap is still very big. Main is daily in the passive meet of more, active research of less, service also has not timely, and not in place of problem; work in the meet Yu traditional of, and program of of work way, develop innovation spirit and service innovation capacity not strong; supervision information work and promoted decision implementation of contact enough close, feedback situation not active; research resources of using enough full, research results of into degree not high; some sector documents running not specification; Municipal Government Office on the County (district) and municipal government sector Office work of guide enough, No real form interaction and close collaboration, promote the implementation of the work. These problems, we must effectively be addressed in the future work. Second, serve the overall situation, carry out their duties, improve quality, and strive to create a new situation of system of government offices in the city since last season, meeting the Secretary-General of the State Council and the provincial government has held a government system, from a global and strategic height, scientifically analyzed the new situation and the newTasks on the system of government offices bring new situations and new problems and new challenges, profoundly expounded the work of government departments at all levels in the new era should be put in the situation to understand, to grasp, to deploy at any time and under any circumstances, should always focus on the big picture, firmly grasp the overall situation, increasing in the overall implementing in earnest the work of spontaneity, initiative and steadfastness. And explicitly put forward the "surrounding situation, pay attention to implementation" is the core of government offices, requiring government departments at all levels cannot be "Gramophone", "mail room" and "the Messenger" is not confined to paper communications, yinglaisongwang and upload issue. Must to has strongly of implementation guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation中国生化药物杂志,1997 ,18 (4) :1662169. [15 ] 赵云峰,吴学玲,罗永艾.奥马珠单抗对支气管哮喘的治疗作用[J ] .中国新药与临床 杂志,2005 ,24 (1) :68272. [16 ] 林金盈.生物制剂在风湿病治疗中的应用[J ] .广西医学,2006 ,28 (1) :528. [17 ] 陈垦.英利昔单抗在消化系统疾病中的应用状况及前景[J ] .中国医院用药评价与 ,2006 ,6 (3) :1512153. guide sex further enhanced, documents handle and running of speed obviously speed up, program gradually specification, conference service and Chief reception of quality and level has has new of improve, Logistics support capability further strengthened. Document management, confidential, confidentiality, duty, letters and other items have been significantly improved. 4, Office construction increased at all levels. City Government offices adhere to strengthen and improve the construction of the system as a breakthrough, has developed a series of code of conduct, continuous improvement of operational mechanism, sound and the implementation of the rules and regulations, and adhere to the system of managing people, according to the rules, the work gradually into the orbit of institutionalization and standardization. Focus on strengthening ideological and political construction of the contingent of cadres, and actively carried out various business training, knowledge of the Office team structure has been optimized, to broaden the range of knowledge and operational capacity grows, nurtured a political firm, sharp, professional and innovative staff, created solidarity, striving for the top, pragmatic, dedication, good image. However, with the State Council and the provincial Government of the national, the province's Secretary-General meeting of government offices under the new situation
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