MORPHOLOGICAL MECHANISMS OF ORGANELLE FUNCTION AND TRANSFORMATION IN CULTURE CELL

癌变后细胞的性质发生了许多变化。 转型。我们关注的是表达的变化 可能代表肿瘤特异性标志物的表面分子 可用于人类肿瘤的诊断和治疗。vbl.使用 杂交瘤技术和形态学方法，我们已经分离出了单抗 针对人类肿瘤细胞表面表位的抗体。这其中的一个 抗体B3最近得到了详细研究。这种抗体具有 已被证明与Lewis(Y)抗原的特定区域发生反应 结构。这种抗体与一些正常组织发生反应，例如 胃和膀胱上皮，以及人的结肠、卵巢肿瘤 和乳房起源。最近，一种B3与假单胞菌外毒素的结合物 (PE)已被证明能有效地杀伤小鼠体内的靶肿瘤细胞。 组织培养，以及在裸鼠动物模型中使用这两种方法 A431和MCF-7人肿瘤细胞株。缺乏严重的组织特异性 猴子临床前试验的毒性表明B3可能是有用的 用于治疗一些人类癌症。另一种抗体K1与 卵巢肿瘤和正常间皮细胞的特征已经明确。它会做出反应 使用与CA125抗原频繁共表达的抗原， 但它不与纯化的CA125反应。与KI反应的抗原 (CAK1)没有从细胞表面脱落，但它从细胞表面释放 用磷脂酶C.CAK1处理的细胞已部分纯化并 似乎是一种约40kD的蛋白质。一种制备的免疫毒素 在组织培养中使用K1可以有效地杀伤靶细胞。在……里面 其他研究，一种单体-四聚体转化的形态分析 在完整的细胞中形成了丙酮酸激酶m1；这种酶是一种主要的 细胞质中的甲状腺激素结合蛋白。另外， 利用人表皮生长因子培育的转基因小鼠系的其他研究 受体基因显示，这些小鼠的微管存在缺陷 纯合子动物精子轴丝的稳定性。

There are many changes in the properties of cells following malignant transformation. We have concentrated on changes in the expression of surface molecules that might represent tumor- specific markers that could be exploited both for diagnosis and therapy of human tumors. Using hybridoma technology and morphologic methods, we have isolated monoclonal antibodies to surface epitopes on human tumor cells. One of these antibodies, B3, has recently been studied in detail. This antibody has been shown to react with a specific area of the Lewis(Y) antigen structure. This antibody reacts with some normal tissues, such as gastric and bladder epithelium, as well as human tumors of colon, ovarian and breast origin. Recently, a conjugate of B3 with Pseudomonas exotoxin (PE) has been shown to be effective in killing target tumor cells in tissue culture, as well as in an animal model in nude mice using both A431 and MCF-7 human tumor cells. The absence of serious tissue-specific toxicity in preclinical testing in monkeys suggest that B3 may be useful for therapy of some human cancers. Another antibody, Kl, reactive with ovarian tumors and normal mesothelium has been characterized. It reacts with an antigen that is coexpressed frequently with the CA125 antigen, but it does not react with purified CA125. The antigen reactive with KI (CAK1) is not shed from the surface of cells, yet it is released from cells treated with phospholipase C. CAK1 has been partially purified and appears to be a protein of approximately 40 kD. An immunotoxin prepared using Kl is effective in killing target cells in tissue culture. In other studies, a morphologic assay for the monomer-tetramer conversion of pyruvate kinase Ml in intact cells was developed; this enzyme is a major binding protein for thyroid hormone in the cytoplasm of cells. Also, other studies of a transgenic mouse line developed using the human EGF receptor gene showed that these mice have a defect in microtubule stability in the axoneme of sperm in homozygous animals.