Spontaneous regression of late-stage tumors in mice

小鼠晚期肿瘤的自发消退

• 批准号: 7006657
• 负责人: ZHENG CUI
• 金额: $ 24.94万
• 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/7006657
• 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(申请人提供)：肿瘤细胞的生长和存活受肿瘤细胞内部遗传控制和宿主因素的调节。在极少数癌症患者中，恶性肿瘤的进展可以被一种未知的宿主机制部分或完全逆转，这种机制被称为“自发消退”。缺乏自发消退的动物模型，阻碍了识别与肿瘤耐药机制有关的因素的努力。崔博士和他的同事们已经确定了一种独特的、由基因决定的小鼠特征，可以通过移植攻击性小鼠肉瘤180细胞而导致晚期腹水的自发消退。在携带突变的小鼠中，晚期腹水的自发消退是完全和永久性的。这一特征也保护小鼠免受小鼠白血病细胞移植后的肿瘤发展。免疫学研究表明，肿瘤细胞引发了免疫细胞向肿瘤部位的迁移。渗入的免疫细胞形成细胞-细胞聚集体，诱导肿瘤细胞坏死性破裂，在肿瘤移植后的几个小时内清除肿瘤细胞。遗传学研究表明，激活的免疫细胞对肿瘤细胞的这种独特反应可能是由这些小鼠中的一个显性突变引起的。初步的基因分型分析确定了该突变与小鼠4号染色体上两个相邻的微卫星标记之间的关联。在这项建议中，崔博士召集了一组来自基因组学、病理学、免疫学、癌症发生学和生物化学的专家，以确定这种强大的抗癌特性的遗传基础、细胞机制和抗肿瘤谱。这项建议的长期目标是确定类似的机制是否也可以有效地用于人类癌症的治疗和预防。这项建议有3个具体目标：1)鉴定肿瘤排斥反应的免疫学成分；2)确定肿瘤排斥反应的抗肿瘤谱；3)鉴定受突变影响的基因(S)。这些目标的完成将提供对这种独特的、强大的肿瘤耐药性的生物学机制的全面了解。将开发必要的工具来扩大这些研究，以在人类中寻找类似的基因，并设计更好、更有效的癌症治疗和预防策略。

项目成果

Mass spectrometry identification of circulating alpha-1-B glycoprotein, increased in aged female C57BL/6 mice.

老年雌性 C57BL/6 小鼠中循环 α-1-B 糖蛋白的质谱鉴定有所增加。

• DOI: 10.1016/j.bbagen.2006.06.020
• 发表时间: 2007
• 期刊: Biochimica et biophysica acta
• 作者: StehleJr,JohnR;Weeks,MarkE;Lin,Kai;Willingham,MarkC;Hicks,AmyM;Timms,JohnF;Cui,Zheng
• 通讯作者: Cui,Zheng