肝癌单克隆抗体与氨甲喋呤交联物的制备及细胞毒的研究

在肝癌单克隆抗体Ｈｅｐａｍａ－１－人血清白蛋白－ＭＴＸ结合物的制备中，首先ＭＴＸ在二环己基碳二亚胺（Ｄｉｃｙｃｌｏｈｅｘｙｌｃａｒｂｏｄｉｍｉｄｅ，ＤＣＣ）作用下，与Ｎ－羟基琥珀酰亚胺（Ｎ－Ｈｙｄｒｏｘｙｓｕｃｃｉｎｉｍｉｄｅ，ＮＨＳ）反应，得到ＭＴＸ活性酯，中间载体ＨＳＡ与ＳＰＤＰ作用引入巯基，再与ＭＴＸ活性酯反应得到ＨＳ－ＨＳＡ－ＭＴＸ。然后与碘乙酰化单克隆抗体Ｈｅｐａｍａ－Ｉ反应，获得硫醚键连接的交联物。交联物中Ｈｅｐａｍａ－Ｉ：ＨＳＡ：ＭＴＸ克分子比为１１．６３０，对靶细胞ＢＥＬ－７４０５及对照细胞ＨｅＬａ的杀伤效率，以交联物按ＭＴＸ的克分子浓度计算，ＩＣ５０（５０％抑止率）分别为２．５×１０－８ｍｏｌ／Ｌ和６．４×１０－７ｍｏｌ／Ｌ。单独ＭＴＸ对上述二种细胞株不显示选择性杀伤，ＩＣ５０均为７．１×１０－８ｍｏｌ／Ｌ。     

胃癌单克隆抗体与丝裂霉素C交联物导向治疗研究—附3例临床初步试用报告

本文报告采用活性酯方法制备了胃癌单克隆抗体３Ｈ１１与ＭＭＣ直接交联物３Ｈ１１－ＭＭＣ，又以ＳＰＤＰ为交联剂，人血清白蛋白（ＨＳＡ）为中间载体制备了间接交联物３Ｈ１１－ＨＳＡ－ＭＭＣ。３Ｈ１１与ＭＭＣ克分子比，前者为１∶７，后者为１∶４０，两者抗体活性均近完全保留，ＢＧＣ８２３体外细胞毒实验ＩＣ５０分别为０．７μｇ／ｍｌ及０．９μｇ／ｍｌ，游离ＭＭＣＩＣ５０为４．３μｇ／ｍｌ。裸鼠胃癌移植瘤抑制率两种交联物均为７１．４％，明显优于游离ＭＭＣ（４６．９％）及非特导性抗体交联物（４％）（Ｐ＜０．０１）。３例晚期及手术后复发胃癌病人接受８、１６ｍｇＭＭＣ量的３Ｈ１１－ＨＳＡ－ＭＭＣ治疗，副反应包括寒战、轻至中度发热及恶心、呕吐；２例肿瘤稳定，１例进展。２例血中检出抗鼠抗体（ＨＡＭＡ）。     

双弹头组合单抗免疫导向治疗肝癌的实验研究

以肝癌单克隆抗体ＨＡｂ１８、ＨＡｂ２５为载体，以￣（１３１）Ｉ、阿霉素（ＡＤＭ）为“弹头”．应用间接交联方法及氯胺Ｔ法，制备出肝癌“双弹头组合单抗”免疫导向偶合物［￣（１３１）Ｉ－ＨＡｂ１８－ＡＤＭ］／［￣（１３１）Ｉ－ＨＡｂ２５－ＡＤＭ］，其标记率４９．８％，比放射性６．８８×１０４Ｂｑ／μｇ，免疫结合率４２．５％。细胞毒实验结果显示双弹头组合单抗偶合物杀伤力显著强于单弹头单抗体偶合物（Ｐ＜０．０５）。荷肝癌棵鼠导向治疗实验，１６８小时ＳＰＥＣＴ扫描清楚定位，瘤／肝比值３．７３５±０．１２０，治疗效果显著强于其它各组（Ｐ＜０．０５）。上述结果表明，“双弹头”集中了化疗与放疗优点，二者协同，明显提高了杀伤效应；组合单抗较好地消除了肿瘤异质性对导向治疗的影响。     

天花粉-5A(10)2免疫毒素的形成及其对人肺腺癌细胞SPC体外导向杀伤作用的研究

目的通过化学交联形成天花粉┐５Ａ（１０）２免疫毒素，对人肺腺癌细胞ＳＰＣ进行导向杀伤作用的研究。方法天花粉毒蛋白与２┐ＩＴ（ｉｍｉｎｏｔｈｉｏｌａｎｅ，２┐亚氨基四氢噻吩）作用、抗人肺腺癌单抗５Ａ（１０）２与ＳＰＤＰ（Ｎ┐ｓｕｃｃｉｎｉｍｉｄｙｌ┐３┐［２┐ｐｙｒｉｄｙｌｄｉｔｈｉｏ］ｐｒｏｐｉｏｎａｔｅ，Ｎ┐琥铂酰亚胺┐３┐［２┐吡啶二硫］┐丙酸酯）作用，分别导入巯基（┐ＳＨ）和２┐吡啶二硫丙酰（ＰＤＰ，２┐［ｐｙｒｉｄｙｌｄｉｔｈｉｏ］ｐｒｏｐｉｏｎａｔｅ）基，通过天花粉分子中引入的┐ＳＨ与５Ａ（１０）２分子中引入的ＰＤＰ作用将天花粉与５Ａ（１０）２单抗连接在一起，形成免疫毒素分子。结果体外细胞毒实验表明，天花粉┐５Ａ（１０）２免疫毒素对ＳＰＣ的杀伤作用比游离天花粉至少高６～７倍，而对肝癌细胞７７２１的杀伤作用与游离天花粉相近。结论证明天花粉┐５Ａ（１０）２免疫毒素在体外对靶细胞ＳＰＣ具有导向杀伤作用。天花粉┐５Ａ（１０）２免疫毒素的体内抑瘤（荷瘤裸鼠）实验在进行中     

抗人胰腺癌单克隆抗体介导LAK细胞体外体内抗胰腺癌作用的研究

体外４小时５１Ｃｒ释放试验表明，抗人胰腺癌单克隆抗体（ＹＰＣ３ＭｃＡｂ）能增强ＬＡＫ细胞对Ｃａｐａｎ－２人胰腺癌细胞的杀伤作用，这种ＬＡＫ细胞的抗体依赖性细胞介导的细胞毒作用（ＡＤＣＣ），随ＹＰＣ３ＭｃＡｂ的浓度增加而加强，５０μｇ／ｍｌ的ＹＰＣ３ＭｃＡｂ增加ＬＡＫ细胞的杀伤率约６０％。而对照抗体无此作用。裸鼠体内实验表明，ＹＰＣ３ＭｃＡｂ和ＬＡＫ细胞同时使用，能完全阻止Ｃａｐａｎ－２细胞的生长，优于ＬＡＫ细胞、脾细胞和ＹＰＣ３ＭｃＡｂ的分别作用。结果提示，ＹＰＣ３ＭｃＡｂ和ＬＡＫ细胞的联合应用，对胰腺癌治疗有一定价值。     

免疫导向药物B_（159）－Dex－EPI与B_（159）－Dex－ADR抗肿瘤活性研究

作者应用氧化葡聚糖Ｔ_（１０）作为交联剂，将抗Ｂ淋巴细胞白血病单抗Ｂ_（１５９）分别与抗癌药物表阿霉素（ＥＰＩ）和阿霉素（ＡＤＲ）连接，制成免疫导向药物Ｂ_（１５９）－Ｄｅｘ－ＥＰＩ和Ｂ_（１５９）－Ｄｅｘ－ＡＤＲ，Ｂ_（１５９）与ＥＰＩ或ＡＤＲ的克分子比均为１：１２～１４。经活细胞免疫荧光法和细胞ＥＬＩＳＡ法测定，免疫导向药物保持了抗体活性。ＭＴＴ试验证实，两种免疫导向药物均具有明显的选择性杀伤作用，对非靶细胞毒性小；两种免疫导向药物对靶细胞的杀伤作用明显强于游离药物和正常鼠抗体结合物；Ｂ_（１５９）－Ｄｅｘ－ＥＰＩ的靶细胞毒性作用强于Ｂ_（１５９）－Ｄｅｘ－ＡＤＲ。     

CD3AK细胞和LAK细胞治疗晚期恶性肿瘤的临床和实验研究

将５１例晚期恶性肿瘤患者（男性２３例，女性２８例）分成两组，其中一组（３１例）以ＣＤ３ＭｃＡｂ（ＣＤ３单克隆抗体）和小剂量ＩＬ－２（５００ｕ／ｍｌ）共同诱导的ＣＤ３ＡＫ细胞治疗，另一组（２０例）输注大剂量ＩＬ－２（１０００ｕ／ｍｌ）诱导的常规ＬＡＫ细胞治疗，以探讨降低ＩＬ－２用量、提高杀伤细胞细胞毒活性的可能性。结果显示ＣＤ３ＡＫ组患者生活质量改善、症状缓解均优于ＬＡＫ组。ＣＤ３ＡＫ组ＰＲ＋ＭＲ率较ＬＡＫ组高２９．０％，Ｓ＋Ｐ率和死亡率分别较ＬＡＫ组低１２．４％和９．６％。同时比较了ＣＤ３ＡＫ细胞与ＬＡＫ细胞的体外增殖和细胞毒活性，结果表明ＣＤ３ＡＫ细胞增殖率高于ＬＡＫ细胞（Ｐ＜０．０１），靶细胞抑制率二者在０．０５水平无显著差异。提示ＣＤ３ＭｃＡｂ在刺激杀伤细胞活性，尤其在提高其增殖能力方面，具有显著的作用，ＣＤ３ＡＫ／ＩＬ－２能更有效地治疗晚期恶性肿瘤。     

肺癌单克隆抗体3C9及其相关抗原的研究

用肺腺癌细胞系Ａ５４９免疫ＢＡＬＢ／Ｃ小鼠，常规细胞融合，获得一株ＩｇＭ型单抗３Ｃ９。Ｗｅｓｔｅｒｎｂｌｏｔ研究发现该抗体识别５６．４ＫＤ蛋白带。免疫组化研究发现，３Ｃ９相关抗原（３Ｃ９Ａｇ）在肺癌组织中表达阳性率高达９２．５％。３Ｃ９Ａｇ血清学研究发现，其诊断肺癌的敏感性为６４．７％，特异性为９３．０％，准确性为８２．５％。其血清水平与组织学分布相关，在高、中分化的肺癌病人阳性率高于低分化者（Ｐ     

经化疗药物作用的肿瘤细胞对LAK细胞敏感性研究

应用肺腺癌细胞株Ａ５４９作为靶细胞，探讨ＬＡＫ细胞与抗癌药物协同杀伤肿瘤细胞的作用。浓度为１０μｇ／ｍｌ～０．１５５μｇ／ｍｌ的丝裂霉Ｃ、阿霉素、顺铂３种抗瘤药物作用于Ａ５４９细胞２４或４小时以后，再加入ＬＡＫ细胞并用乳酸脱氢酶释放法测定细胞毒作用。结果显示，丝裂霉素不改变细细胞对ＬＡＫ细胞的敏感性、阿霉素的作用可随浓度增加使ＬＡＫ细胞对肿瘤细胞的杀伤作用增强。而顺铂则在特定浓度显示与ＬＡＫ细胞有协同作用。     

单克隆抗体导向平阳霉素对食管癌细胞的细胞毒特征

本文报道用葡聚糖为中介体制备抗胃癌单抗MGb_2与平阳霉素的结合物,经测算每克分子抗体可携带60～70克分子的药物。在结合物制备过程中抗体活性无明显丧失,结合物能与靶细胞特异结合。体外细胞毒试验证实,结合物对靶细胞(食管癌细胞ECA—109)具有较强的选择性杀伤作用,优于游离平阳霉素及无关抗体结合物;对非靶细胞则毒性明显减弱。提示该免疫结合物可能会成为一种较好的抗体导向化疗药物。     

E-钙粘蛋白及PTEN基因编码蛋白与胃癌浸润转移

目的:观察抑癌基因PTEN蛋白和ECD在胃癌组织中的表达,探讨其与胃癌生物学行为及预后的关系。方法:以兔抗人PTEN多克隆抗体、鼠抗人ECD单克隆抗体,采用SABC免疫组化法,检测100例胃癌手术切除标本中拟测指标的表达。以χ2和Logrank检验对结果做统计学分析。结果:ECD、PTEN蛋白在非癌胃粘膜中均见表达;在胃癌组织中表达下调或缺失。ECD异常表达率为42.0%;弥漫型胃癌异常表达率(48.57%),明显高于肠型胃癌(26.67%),(P<0.05);ECD异常表达与浸润深度有关(P<0.05)。胃癌组织中PTEN蛋白缺失率为59%;弥漫型胃癌缺失率(65.71%)明显高于肠型胃癌(43.33%),(P<0.05);伴淋巴结转移的胃癌缺失率(64.47%)明显高于无淋巴结转移者(41.67%),(P<0.05);PTEN蛋白缺失的患者比阳性表达者预后差(P=0.0066)。65.85%PTEN阳性表达者同时伴ECD正常表达。结论:两种标志物与胃癌浸润转移有关,PTEN表达与胃癌患者预后密切相关。将两种指标联合检测,可作为正确判断胃癌患者预后,指导临床治疗的分子生物学指标。     

Cytologic classification of precancer and cancer of the endometrium and esophagus and of malignant lymphomas

The paper discusses cytological classifications of precancer and cancer of the endometrium, esophagus and malignant lymphomas presented by cytologists from five Soviet research institutes of oncology. The classifications were based on the data of 4400 cases in conformity with WHO histologic classifications.     

世界卫生组织骨质疏松症防治工作报告和防治建议

引 言 作为对第51号综合处理非传染性疾病预防与控制的世界卫生组织决议的反应,1998年7月WHO成立了致力于不断完善对骨质疏松预防和治疗策略的工作小组。小组成员来自世界各国致力于骨质疏松研究的知名专家。Harry K.Genant为本届主席。这一项世界范围内的骨质疏松教育计划旨在通过世界范围的研究,不断改善对骨质疏松的诊断水平和发展并完善对骨质疏松病人的合理治疗。其重点将以发展中国家为主。并为各国政府及其卫生部门和病人群体提供世界性有关骨质疏松症的总体的、完整的指导性资料。该项研究、教育计划的实施将由世界各国的骨质疏松症研究和治疗机构共同完成,并经权威学术机构、政府和非政府组织进行有针对性的回顾研究,最终由WHO审议通过。     

Schwannomas of Head and Neck and Review of Literature

Benign nerve cell tumours have been given various names like schwannoma, neurilemmoma, neurinoma, neurofibroma, spindle cell tumours etc. Extra cranial head and neck schwannomas usually present as solitary and well-demarcated lesions. The lesion can cause secondary symptoms, such as nasal obstruction, dysphasia, and hoarseness, depending upon the location of the lesion. Fine needle aspiration cytology, CT scans, and MRI may be of limited help in the diagnosis of schwannomas. The treatment is complete surgical excision of the benign tumour and postoperative histopathological examination establishes the final diagnosis.     

Quality of life and care in leukemia,myeloma and non-malignant disease. Opinions of patients and relatives,and effects of geography and time

In a questionnaire study 140 subjects answered 4200 questions in 1980 and 1986. They consisted of patients with myeloma, acute leukemia, lung carcinoma, and non-malignant disease and their relatives. In 22 additional cases the questionnaire was not answered. The results show that myeloma patients are less content with the general care than leukemia patients (P < 0.05). Similarly, relatives of deceased myeloma patients are less satisfied with the information given to them than relatives of deceased leukemia patients (P < 0.001). The information has improved with time, however, since the patients were more satisfied in 1986 than in 1980 (P < 0.001) and relatives of myeloma patients still alive were more satisfied than relatives of patients who had died earlier (P < 0.001).     

A comparative study of knowledge and awareness of colorectal and breast cancerA comparative study of knowledge and awareness of colorectal and breast cancer

Aims: To assess and compare knowledge and awareness of colorectal cancer and breast cancer in a sample of the general population. Methods: Eleven hundred visitors to six different outpatient clinics, in a University Hospital, were given a study-specific questionnaire, based on educational material from the British Association of Cancer United Patients (CancerBACUP). The questionnaire consisted of 12 statements on the incidence, presentation, detection, treatment and prognosis of colorectal and breast cancer. Results: One thousand and sixty-eight individuals returned the questionnaire. One thousand and four completed questionnaires were analysed. The mean age (SD) of respondents was 50.1 (17.2) years, and the male to female ratio was 2:3. Respondents had read more about breast than about colorectal cancer (60.3%vs 32.4%,P <0.0001, McNemar's test). The proportion of correct answers for each statement on breast cancer was higher than for answers to corresponding items on colorectal cancer. Mean overall scores (95% CI) for breast and colorectal cancer were 88.1 (86.9, 89.2) and 64.4 (62.5, 66.3) respectively, the mean difference (95% CI) being 23.7 (22.0, 25.5). Scores were higher for breast cancer irrespective of age or gender. Conclusion: There is a low level of understanding of colorectal cancer in the general population when compared to breast cancer. This highlights the importance of public education in this common cancer.     

Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers

BACKGROUND: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. METHODS: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. RESULTS: With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. CONCLUSIONS: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.