METALLOPROTEINASES AND NEUROBLASTOMA METASTASIS

神经母细胞瘤是儿童期最常见的实体瘤之一， 尽管化疗取得了进展，但晚期预后不良。 然而，开发替代的、新的治疗模式是可能的。 为了改善结果，在描述了 神经母细胞瘤行为 金属蛋白酶72和92-ketoDa IV型 胶原酶可能通过促进组织降解介导转移 和细胞入侵。 本研究探讨了这些因素的作用。 胶原酶在鼠和小鼠的转移和侵袭特性中的作用 人神经母细胞瘤 72和92-酮-Da IV型的内源性活性 胶原酶及其天然抑制剂， 金属蛋白酶（TIMP）将在各种培养的鼠和 人神经母细胞瘤细胞系。 它们在神经母细胞瘤侵袭中的作用 和转移将通过基因转移方法使用72- keto-Da和92-keto-Da胶原酶和TIMP。 转移性和 通过体内鼠实验评价侵袭潜力， 体外transwell测定。 金属蛋白酶的临床意义 活性将通过胶原酶的免疫组织化学测定来确定 在人类神经母细胞瘤的存档标本中的活性。 相关性 对肿瘤的临床和生化指标进行分析 侵略性胶原酶活性升高可能是一种有效的新的 用于识别哪些肿瘤有转移风险的标志物， 需要积极的治疗 使用胶原酶抑制剂的治疗， 因为TIMP可能能够抑制神经母细胞瘤转移。 候选人在医学院毕业后完成了12年的训练， 所有这些都是为了实现儿科手术培训， 1991年在贝勒医学院完成， 在她职业生涯的各个阶段积极进行研究培训 发展 她被招聘到目前的助理职位 肯塔基州大学的外科教授， 部门对研究的坚定承诺。 该奖项将提供 候选人有机会扩大她的基础研究 技能与监督扩展到分子的重要领域 生物学 她致力于学术外科的职业生涯，而这 奖励将增强她的知识基础，个人科学发展， 并确保她作为独立调查员和培训师的地位， 学生在研究。

Neuroblastoma, one of the most common solid tumors of childhood, has a poor prognosis in advanced stages despite advances in chemotherapy. However it may be possible to develop alternate, novel modes of therapy to improve the outcome after delineating the molecular mechanisms of neuroblastoma behavior. The metalloproteinases 72 and 92-ketoDa type IV collagenases, may mediate metastasis by facilitating tissue degradation and cellular invasion. This study examines the role of these collagenases in the metastatic and invasive properties of murine and human neuroblastoma. Endogenous activity of 72 and 92-keto-Da type IV collagenases and their natural inhibitor, tissue inhibitor of metalloproteinases (TIMP) will be assayed in various cultured murine and human neuroblastoma cell lines. Their role in neuroblastoma invasion and metastasis will be investigated by gene transfer methods using 72- keto-Da and 92-keto-Da collagenase, and TIMP. Changes in metastatic and invasive potential will be evaluated by in vivo murine experiments and in vitro transwell assay. The clinical relevance of metalloproteinase activity will be determined by immunohistochemical assays of collagenase activity in archival specimens of human neuroblastoma. Correlations will be made to clinical and biochemical parameters of tumor aggressiveness. Elevated collagenase activity may be an effective new marker by which to identify which tumors are at risk for metastasis and require aggressive therapy. Therapy using collagenase inhibitors such as TIMP may be able to inhibit neuroblastoma metastasis. The candidate has completed 12 years of training after medical school, all directed toward achieving Pediatric Surgery training, which was recently completed at Baylor College of Medicine in 1991 and has actively pursued research training at every level of her career development. She was recruited to her current position of Assistant Professor of Surgery at University of Kentucky because of the department~s strong commitment to research. This award will provide the candidate an opportunity to broaden her foundation of basic research skills with supervised expansion into the important field of molecular biology. She is dedicated to a career in academic Surgery, and this award will enhance her knowledge base, personal scientific development, and secure her position as an independent investigator and trainer of student in research.