Molecular Tumorigenesis of Bladder Cancer

总结 膀胱癌由两种主要类型组成：低度乳头状肿瘤和高度肌层浸润性肿瘤。 肿瘤的虽然大多数低度恶性乳头状肿瘤生长缓慢，但其中约有五分之一的肿瘤生长缓慢。 肿瘤以目前不可预测的方式进展到肌肉侵入阶段。我是校长 低级别乳头状膀胱肿瘤需要终身警惕性随访并重复膀胱镜检查的原因 以及为什么膀胱癌是治疗费用最高的癌症。 从低级别乳头状膀胱肿瘤到高级别浸润性膀胱肿瘤的转变尚未被证实。 划定的在我们母公司P01资助的支持下，我们最近发现肿瘤抑制因子的消融 存在于人类染色体9p21上，常发生于人类肌肉浸润性膀胱肿瘤中， 小鼠加速了HRas诱导的低度乳头状膀胱肿瘤的形成，但未能触发 入侵我们的研究结果表明，9p21上额外的遗传成分的丢失是必要的，以使 入侵发生。本行政补充文件的目的是请求资金， 开发了一种新的转基因品系，除了我们最初提出的， 调查所要求的研究补充是在我们的父母P01赠款的一般范围内， 新的鼠标线将有助于加速母公司所有组成项目中的研究 P01格兰特。此外，小鼠系具有促进研究其他癌症类型的潜力， 9p21经常被删除。

Summary Bladder cancer is comprised of two major variants: low-grade papillary tumors and high-grade muscle-invasive tumors. Although the majority of the low-grade papillary tumors are slow-growing, approximately 1 in 5 of these tumors progresses to the stage of muscle invasion in a presently unpredictable manner. This is the principal reason of why low-grade papillary bladder tumors require lifelong, vigilant follow-up with repeated cystoscopy and biopsy and why bladder cancer is the most expensive cancer to treat. The genetic causes underlying the transition from low-grade papillary bladder tumors to high-grade invasive bladder tumors have not been delineated. Under the auspices of our parent P01 grant, we recently found that ablation of tumor suppressors residing on human chromosome 9p21, which occurs frequently in human muscle-invasive bladder tumors, in mice accelerates the formation of HRas-induced low-grade papillary bladder tumors, but failed to trigger invasion. Our results suggest that loss of additional genetic components on 9p21 is necessary in order for the invasion to take place. The objective of this administrative supplement is to request funds to support the development of a novel transgenic line that lacks gene components additional to what we initially proposed to investigate. The requested research supplement is well within the general scope of our parent P01 grant, and the new mouse line will serve to accelerate the research contained in all the component projects of the parent P01 grant. Additionally, the mouse line has the potential to facilitate the investigation of other cancer types in which 9p21 is frequently deleted.