Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy

Pegylated liposomal doxorubicin (Doxil, Caelyx) is a formulation of doxorubicin in poly(ethylene glycol)-coated (stealth) liposomes with a prolonged circulation time and unique toxicity profile. We review the preclinical and clinical pharmacology as well as recent clinical data obtained in specific cancer types. Doxil liposomes retain the drug payload during circulation and accumulate preferentially in tissues with increased microvascular permeability, as often is the case of tumors. Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosupression, minimal alopecia, and no apparent cardiac toxicity. Although the single maximum tolerated dose (MTD) of Doxil is actually lower than that of conventionally administered doxorubicin, the cumulative MTD dose of Doxil may be substantially greater than that of free doxorubicin. Doxil is probably one of the most active agents in AIDS-related Kaposi's sarcoma and has a definite role in management of recurrent ovarian cancer. The potential of Doxil in the treatment of other cancer types and the opportunities it offers in combination with other drugs and therapeutic modalities are under active investigation.     

受体导向药物L-HAS-Ara-AMP抗HBV效应的临床研究

目的：观察去唾液酸糖蛋白受体导向药物LHASAra-AMP的抗HBv临床疗效。方法：应用5 d和28 d疗程治疗慢性乙型肝炎29例,以Ara-AMP治疗27例为对照。结果：L-HSA-Ara-AMP 5 d疗程,10例HBeAg阳性阴转3例,8例HBV-DNA阳性阴转4例。28 d疗程HBeAg阴转率31.6％,HBeAg滴度下降率47.4％,有治疗效应者79.0％;HBV-DNA阴转率31.6％。5 d疗程治疗结束1月时部分HBeAg和HBV-DNA已复阳。28 d疗程治疗结束3月时阴转的病例仍为阴性。LHSA-Ara-AMP组未发现任何不良反应。结论：LHSA-Ara-AMP组的Ara-AMP实际用量大大减少仍具有与单用Ara-AMP相似或略优的抗病毒效果,并且毒副作用减少。     

125I-抗AFP抗体放射免疫导向治疗原发性肝癌的初步临床观察

目的：观察＾１２５Ｉ－抗ＡＦＰ抗体导向治疗肝癌的毒副反应,药物体代谢及近期疗效。方法：采用氯胺－Ｔ氧化法制备＾１２５Ｉ－抗ＡＦＰ抗体,经静脉给药,治疗２１例不能手术切除的原发性肝癌,每例接受＾１２５Ｉ的中位剂量为２８９．３ＭＢｑ（１００．３～７０８．９ＭＢｑ）结果：药物在血浆清除缓慢,第１５天＾１２５Ｉ血浓度仍为５．２７５±１．０５３×１０＾－４％,药物毒性低,耐受好,治后总有效率（ＣＲ＋ＰＲ＋Ｍ     

Enhancing effect of cetylmannoside on targeting of liposomes to Kupffer cells in rats

In order to evaluate whether surface modification of liposomes by cetylmannoside (Man) could be useful for targeting to Kupffer cells, the effect of Man on disposition of liposomes was examined after intravenous administration to rats. In the case of small unilamellar vesicles (SUV), no difference in disposition was observed between control liposomes (PC-SUV) and modified liposomes (Man-SUV). On the other hand, in the case of multilamellar vesicles (MLV), modified liposomes (Man-MLV) were rapidly eliminated from the circulation, and showed higher accumulation (51.4% of dose) in the liver as compared with control liposomes (PC-MLV, 25.7% of dose). In the spleen, splenic clearance of Man-MLV (0.068 ml/min) was comparable to that of PC-MLV (0.068 ml/min), although Man-MLV showed lower accumulation (5.7% of dose) than PC-MLV (14.7% of dose). This lower accumulation in the spleen of Man-MLV might be due to the low blood concentration caused by the high accumulation in the liver. Thus, it is considered that liposomal size is important in revealing the effects of Man, and Man-MLV is able to enhance only the affinity for the liver. The cellular distribution in the liver of Man-MLV 2 h after intravenous administration to rats gave encouraging evidence that Kupffer cells might be involved in the enhanced hepatic uptake of the liposomes. These results suggest the usefulness of Man-MLV for targeting to Kupffer cells. Furthermore, the involvement of plasma protein(s) in the uptake of Man-MLV is suspected.     

Transcatheter arterial embolization in unresectable hepatocellular carcinoma

Seven hundred thirty-nine patients with unresectable hepatocellular carcinoma have been treated by transcatheter arterial chemoembolization using gelatin sponge particles soaked in a solution of Mitomycin C and Adriamycin. This therapy can be equal, or superior to surgical resection and serves both as embolic therapy and targeted chemotherapy.     

Being targeted: Young women's experience of being identified for a teenage pregnancy prevention programme

Research on the unintended consequences of targeting ‘high-risk’ young people for health interventions is limited. Using qualitative data from an evaluation of the Teens & Toddlers Pregnancy Prevention programme, we explored how young women experienced being identified as at risk for teenage pregnancy to understand the processes via which unintended consequences may occur. Schools' lack of transparency regarding the targeting strategy and criteria led to feelings of confusion and mistrust among some young women. Black and minority ethnic young women perceived that the assessment of their risk was based on stereotyping. Others felt their outgoing character was misinterpreted as signifying risk. To manage these imposed labels, stigma and reputational risks, young women responded to being targeted by adopting strategies, such as distancing, silence and refusal. To limit harmful consequences, programmes could involve prospective participants in determining their need for intervention or introduce programmes for young people at all levels of risk.     

NP-DA-Dextra-FA靶向纳米分子探针对人肝癌细胞的体外磁共振成像研究

目的利用叶酸受体(folate receptor,FR)阳性的Bel7402人肝癌细胞及磁共振成像系统来探讨超顺磁性氧化铁-多巴胺-葡聚糖-叶酸(NP-DA-Dextra-FA)靶向纳米复合物的细胞靶向性并监测其体外成像的可行性。材料与方法研制叶酸靶向纳米分子探针(NP-DA-Dextra-FA)及非靶向纳米分子探针(NP-DADextran)。将人肝癌细胞Bel7402与叶酸靶向纳米分子探针及非靶向探针分别孵育2h后,行普鲁士蓝染色实验及细胞MR成像扫描,分析其T2WI信号强度及信号强度变化率的改变,并行竞争抑制实验。结果不同Fe浓度NP-DA-DextraFA及NP-DA-Dextran纳米分子探针分别与Bel7402细胞孵育后,靶向分子探针组结果显示Bel7402细胞T2信号强度随着铁浓度的升高明显减低,普鲁士蓝染色实验表明大量蓝色铁颗粒沉积位于Bel7402细胞内;非靶向组结果表明Bel7402细胞信号强度减低相对不明显,普鲁士蓝染色示Bel7402细胞内仅见少量蓝色铁颗粒沉积。竞争抑制实验结果表明随着叶酸浓度的升高,T2信号强度逐渐升高。结论叶酸靶向磁性纳米分子探针对人肝癌细胞Bel7402有靶向性,体外磁共振成像可对其靶向性监测。     

聚酰胺-胺树状聚合物靶向修饰及放射性核素标记研究进展

纳米分子在体内具有药物载体的特性,与生物靶向分子结合,可实现药物的靶向传递;与放射性核素的结合,可实现在体内靶向分布与靶向聚集的可视化,从而达到对特定病变的显像或治疗作用。本文对近年来新型树状纳米分子聚乙酰胺-胺（PAMAM）的靶向分子修饰及核素标记的研究进展进行综述。     

肝素缓释系统抑制兔眼白内障术后后发性白内障的实验研究

目的 通过观察肝素缓释系统植入兔眼白内障超声乳化术后的角膜、前房、后囊膜的浑浊分级及其病理变化情况,探讨其对后发性白内障的抑制作用.方法 健康新西兰大白兔24只共48眼,随机分为4组,建立白内障动物模型,在行白内障超声乳化术后分别囊袋内注入200U/ml肝素0.1ml(第1组),后房内植入空白缓释剂(第2组),后房内植入肝素缓释系统(第3组)及生理盐水滴眼(对照组).术后不同时间应用裂隙灯显微镜观察角膜、前房及晶状体后囊膜等眼部组织的变化,光镜观察后囊膜组织病理学改变.结果 肝素缓释剂组前房反应小,后囊膜混浊程度及发生时间与其他三组的后囊膜混浊率有显著性差异(P<0.05).结论 肝素缓释剂能有效地抑制兔眼白内障术后后发性白内障的发生.     

利用噬菌体肽库序贯筛选组织因子靶向肽

目的: 建立一种高效的筛选跨膜受体靶向肽的噬菌体展示新方法,据此筛选出组织因子( TF) 高亲和力靶向肽。方法: 分别以纯化TF蛋白和具有TF高特异性表达的结直肠癌细胞株HT-29为靶标,用噬菌体七肽库进行序贯筛选(受体-细胞序贯筛选法,STRCA法),ELISA初步鉴定噬菌体克隆对HT-29亲和力。对噬菌体克隆进行测序,利用竞争抑制 ELISA比较各合成肽的TF结合力。重复实验检测筛选结果的可靠性。结果: 经过5轮筛选,与TF结合的噬菌体得到了富集,回收率由(2.25×10^-4)%增加到(1.32×10^-2)%;ELISA结果显示30个克隆中,阳性率为76.7%。噬菌体测序结果中,4种合成肽(分别命名为A、B、C、D肽)中A肽序列重复率为23.3%(7/30),B肽为23.3%(7/30),C肽为26.7%(8/30),D肽为10.0%(3/30);E肽为A、B肽合成的复合靶向肽。经竞争抑制 ELISA比较5种肽的TF亲和力,其IC₅₀分别为3.25 nmol/L、6.72 mol/L、3.24×10³ mol/L、2.08×10² mol/L和45.77 mol/L。重复实验所获得的阳性噬菌体克隆序列与第1次实验相比,重复率为33.3%。结论: STRCA法是一种理想的筛选跨膜受体靶向肽方法,采用该法获得的TF靶向肽对TF具有高度的亲和力。