Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab' fragments.

PURPOSE: Monoclonal antibody-mediated targeting of liposomal anticancer drugs to surface antigens expressed on malignant B cells can be an effective strategy for treating B-cell malignancies. In a murine model of human B-cell lymphoma, we have made in vitro and in vivo comparisons of long-circulating sterically stabilized (Stealth) immunoliposome (SIL) formulations of two anticancer drugs, vincristine (VCR) and doxorubicin (DXR), with different mechanisms of action and drug release rates. EXPERIMENTAL DESIGN: SIL formulations of VCR or DXR were conjugated to the monoclonal antibody anti-CD19 (SIL[alphaCD19]) or its Fab' fragments (SIL[Fab']). Specific binding of SILs to Namalwa cells was studied using radiolabeled liposomes, and cytotoxicities of DXR- or VCR-loaded SILs were quantitated by a tetrazolium assay. Pharmacokinetic and drug leakage experiments were performed in mice using dual-labeled liposomes, and the therapeutic responses of SILs were evaluated in a Namalwa (human B lymphoma) cell xenograft model. RESULTS: SIL[alphaCD19] or SIL[Fab'] had higher association with and cytotoxicity against Namalwa cells than nontargeted liposomes. SIL[Fab'] had longer circulation times than SIL[alphaCD19], and VCR had faster release rates from the liposomes than DXR. SIL formulations of either VCR or DXR had significantly better therapeutic outcomes than nontargeted liposomes or free drugs. SILs loaded with VCR were superior to those loaded with DXR. SIL[Fab'] had better therapeutic outcomes than SIL[alphaCD19] for the drug DXR but were equally efficacious for the drug VCR. CONCLUSIONS: Treatment of a B lymphoma model with single injections of anti-CD19-targeted liposomal formulations of VCR resulted in high levels of response and long-term survivors. Responses to anti-CD19-targeted liposomal DXR were more modest, although the longer circulation times of SIL[Fab'] versus SIL[alphaCD19] led to superior therapeutics for DXR-loaded immunoliposomes.     

基于Hilbert曲线的数字图像置乱方法研究

研究了基于Hilbert曲线的数字图像置乱方法 ,引入二个概念 :“重合度”和“Hilbert曲线的平移” ,利用Hilbert曲线平移 ,获得了更多新的置乱路径 ,并根据重合度变化图探讨了置乱变换的规律 ,以测试置乱变换的周期和拟周期。然后把基于Hilbert曲线的置乱方法推广到任意大小的图像。实验结果表明 :利用Hilbert路径进行置乱不仅具有非常大的置乱路径选择空间 ,而且具有很好的置乱效果和极大的置乱周期 ,具有较大的实用性。     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

银环蛇毒素对白血病K562细胞株凋亡诱导作用的研究

目的 探讨银环蛇毒素及其若干组分在体外对白血病K562细胞株的凋亡诱导作用。方法 采用阳离子交换层析法分离纯化银环蛇粗毒，应用MTT法、荧光显微镜和流式细胞术等研究毒素对K562细胞株的凋亡作用。结果 除Ⅳ峰毒素外，银环蛇粗毒及分离的部分组分IV峰、Ⅶ峰和Ⅷ峰等毒素的荧光显微图末见特征性的凋亡小体，DNA含量分布组方图中的二倍体峰前末见Gl细胞群。结论 银环蛇毒对K562细胞具有杀伤作用，但并非是细胞凋亡作用，而是致细胞坏死，而粗毒中的某些组分可能具有促K562细胞凋亡作用。     

Marimastat对裸鼠原位种植人胃癌生长和转移抑制的实验研究

目的 探讨基质金属蛋白酶抑制剂Marimastat对胃癌生长和转移的抑制作用。方法 采用人胃腺癌细胞株SGC—7901完整组织块棵鼠原位种植，建立胃癌转移模型。移植7天后开始腹腔内注射Marimastat，隔天1次，剂量为0mg/kg(对照组)、10mg/kg、30mg/kg、60mg/kg(治疗组)，共用8周，第9周处死动物，测量原位肿瘤大小、抑瘤率、肿瘤微血管密度(MVD)、MMP—9的高表达率、观察肿瘤转移情况。结果 治疗组原位肿瘤瘤重明显较对照组轻，肿瘤肝脏转移、腹膜转移、肿瘤组织微血管密度和肿瘤组织MMP—9高表达率与对照组比较，均有显著性差异(P＜0．05)，且与Marimastat剂量呈正相关。结论 Marimastat对体内胃癌的生长及转移均有抑制作用。     

大肠癌组织中Survivin表达与血管生成、细胞增殖的关系

目的　探讨大肠癌组织中Survivin表达与血管生成、细胞增殖的关系。方法　采用原位杂交方法和免疫组织化学方法 ,对 46例大肠癌、2 2例大肠腺瘤和 10例大肠正常组织进行SurvivinmRNA和PCNA检测 ,并计数微血管密度 (MVD)。结果　大肠癌组织中SurvivinmRNA、PCNA指数和MVD均显著高于大肠腺瘤和大肠正常组织 (P <0 .0 5 )。SurvivinmRNA表达阳性组中 ,MVD和PCNA指数均明显高于SurvivinmRNA阴性组 (P <0 .0 5 )。结论　Survivin在大肠癌组织中表达上调 ,并与血管生成和细胞增殖关系密切 ,提示Survivin对大肠癌的发生发展起重要作用     

PET在肺癌诊断和分期中的应用

本文介绍正电子发射断层显像(PET)在肺癌诊断和分期中的应用概况，肯定了其临床应用价值。并简要叙述我国PET目前现状及今后展望。PET系大型医疗设备，我国未纳入医疗保险，其发展要根据社会经济发展和病人承受能力，合理布局，有限量地增加。作者指出，加强核医学科人员培训与临床各科医师(包括放射科，肿瘤科，胸外科，放射治疗等)的合作是提高PET临床应用和研究水平的关键因素。     

306例肺癌的淋巴结转移规律

目的 探讨可切除性肺癌的胸内淋巴结转移规律。方法 从l992年1月至2000年l2月，对306例肺癌患者施行根治性切除术和系统性胸内淋巴结清扫，分别记录各区淋巴结的数量、大小、颜色和质地，并进行病理检查。结果 全组共清扫胸内2456个区的46l4个淋巴结，平均每例15.1个。经病理检查证实其中521个区的954个淋巴结存在转移癌。胸内淋巴结的转移率高达61．8％，纵隔淋巴结的转移率高达43．5％。围绕肺门或肺根部的11、10、7、5和4区淋巴结的转移频度比远离肺根部的9、6、3、2、l区淋巴结高。小细胞肺癌的淋巴结转移率明显高于非小细胞肺癌(P＜0.01)。淋巴结转移率与淋巴结的大小、颜色和质地均有密切关系(尸＜0.00l，P＜0.00l，P＜0.001)。结论 多数肺癌的淋巴结转移遵循由近及远、自下而上、由肺内经肺门再向纵隔的顺序转移规律，少数纵隔淋巴结转移呈“跳跃式”。肺切除术时施行系统性胸内淋巴结清扫是必要的。     

中药糖脉通片治疗糖尿病周围神经病临床研究

应用糖脉通片治疗糖尿病周围神经病中医辨证属气阴两虚、痰瘀阻络证患者103例，并与西药弥可保组99例进行随机对照。结果：糖脉通片在缓解患者肢痛、麻木症状，改善血流变，升高SOD活性，降低MDA含量，改善神经传导速度等方面均有较好作用，部分指标改善情况优于弥可保。     

广佛手主要病害及综合防治

目的　制定广佛手病害的综合防治措施 ,以降低病害 ,促进广佛手生产的发展。方法　文献查找和实地调查。结果　综述了广佛手主要病害衰退病、黄龙病、炭疽病及溃疡病的发病状况和防治措施 ,分析了其发病原因和传播方式 ,制定了广佛手病害的综合防治措施。结论　认为广佛手病害的防治应采取预防为主、综合防治的原则 ,将农业防治、生物防治和药剂防治相结合。