Spontaneous regression of late-stage tumors in mice

小鼠晚期肿瘤的自发消退

• 批准号: 6696951
• 负责人: ZHENG CUI
• 金额: $ 20.59万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-15 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6696951
• 关键词: Spontaneous; regression; late; stage; tumors

DESCRIPTION (provided by applicant): The growth and survival of neoplastic cells is regulated both by internal genetic control within tumor cells and by host factors. In a very small population of cancer patients, progression of malignant tumors can be partially or completely reversed by an unknown host mechanism termed "spontaneous regression". Lack of animal models for spontaneous regression has hampered the efforts to identify the factors involved in this mechanism of tumor resistance. Dr. Cui and his colleagues have identified a unique, genetically-determined mouse trait conferring the spontaneous regression of late-stage ascites induced by the transplantation of aggressive mouse sarcoma 180 cells. The spontaneous regression of late-stage ascites is complete and permanent in the mice carrying the mutation. This trait also protects the mice against tumor development following transplantation of mouse leukemia cells. Immunological studies revealed that tumor cells elicited a migration of immune cells to the tumor site. The infiltrating immune cells form cell-cell aggregates and induced necrotic rupture of tumor cells, eliminating tumor cells in a few hours after tumor transplantation. Genetic studies suggest that this unique response of activated immune cells to tumor cells may be caused by a dominant mutation in these mice. Initial genotype analysis established a linkage of this mutation to two adjacent microsatellite markers on mouse chromosome 4. In this proposal Dr. Cui has assembled a group of experts from genomics, pathology, immunology, carcinogenesis and biochemistry to determine the genetic basis, cellular mechanism and anti-tumor spectrum of this powerful tumor resistance trait. The long-term objective of this proposal is to determine if a similar mechanism can be also effective in human cancer treatment and prevention. This proposal has 3 specific aims: 1) to identify the immunological components for tumor rejection; 2) to determine the anti-tumor spectrum of tumor rejection, 3) to identify the gene(s) affected by the mutation. Completion of these aims will provide a comprehensive understanding of the biological mechanism of this unique, powerful resistance to tumors. Necessary tools will be developed to extend these studies to search for similar genes in humans and to design better, more efficient strategies of cancer treatment and prevention.

描述（由申请人提供）：肿瘤细胞的生长和存活既受肿瘤细胞内的内部遗传控制和宿主因素来调节。在很少的癌症患者中，恶性肿瘤的进展可能会被称为“自发消退”的未知宿主机制部分或完全逆转。缺乏自发消退的动物模型阻碍了确定这种肿瘤抗性机制所涉及的因素的努力。 CUI博士及其同事已经确定了一种独特的，遗传确定的小鼠特质，该特质赋予了由侵袭性小鼠肉瘤180细胞移植引起的晚期腹水的自发回归。晚期腹水的自发回归是完整的，并且在带有突变的小鼠中永久性。在小鼠白血病细胞移植后，该特征还可以保护小鼠免受肿瘤发育。免疫学研究表明，肿瘤细胞引起免疫细胞向肿瘤部位的迁移。浸润的免疫细胞形成细胞 - 细胞聚集体并诱导肿瘤细胞坏死破裂，在肿瘤移植后几个小时内消除肿瘤细胞。遗传研究表明，激活的免疫细胞对肿瘤细胞的独特反应可能是由于这些小鼠的显性突变引起的。最初的基因型分析在小鼠染色体4上建立了该突变与两个相邻的微卫星标志物的联系。在这一建议中，CUI博士汇集了来自基因组学，病理学，免疫学，致癌和生物化学的一组专家，以确定这种遗传基础，细胞机械机制和抗肿瘤谱的景点的遗传基础，细胞机制和抗tumormor谱。该提案的长期目标是确定类似机制是否在人类癌症治疗和预防中也有效。该提议具有3个具体目标：1）确定肿瘤排斥的免疫学成分； 2）确定肿瘤排斥的抗肿瘤光谱，3）确定受突变影响的基因。这些目标的完成将为这种独特，强大的肿瘤耐药性的生物学机制提供全面的理解。将开发必要的工具来扩展这些研究，以搜索人类中的类似基因，并设计更好，更有效的癌症治疗和预防策略。