Phosphorylated Form of Activated IKKbeta and Pancreatic Cancer

磷酸化形式的活化 IKKbeta 与胰腺癌

基本信息

批准号：
8622788
负责人：
Amarnath Natarajan
金额：
$ 16.37万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8622788
关键词：
Address Adverse effects Animal Model Animals Antibodies Apoptosis Autopsy Blood capillaries Cancer Patient Cancer cell line Cessation of life Chronic Clinic Data Development Diagnosis Disease Drug Targeting Ductal Epithelial Cell Embryo Endotoxins Event Genetic Goals Growth Human Immune response Immunohistochemistry Infection Inflammatory Isoelectric Focusing Label Lipopolysaccharides Malignant neoplasm of pancreas Mediating Metastatic Neoplasm to the Liver Modeling Mus Mutate Mutation Normal Cell Normal tissue morphology Pancreas Pancreatic Ductal Adenocarcinoma Pathology Patients Pharmaceutical Preparations Pharmacologic Substance Phospho-Specific Antibodies Phosphorylation Phosphotransferases Post-Translational Protein Processing Predisposition Protein Dephosphorylation Proteins Research Project Grants Sampling Specimen Stimulus Survival Rate System TNF gene Technology Testing Therapeutic Therapeutic Intervention Tissues Toxic effect Tumor Cell Line base cancer therapy capillary inhibitor/antagonist innovation kidney cell kinase inhibitor mortality mutant neoplastic cell new technology novel overexpression pancreatic cancer cells pancreatic neoplasm pre-clinical programs public health relevance small molecule therapeutic target therapy resistant tumor tumor growth tumor microenvironment tumorigenesis

项目摘要

Project Summary / Abstract Kinases are attractive drug targets as evidenced by the number of recent FDA approvals of kinase inhibitors for cancer therapy. The drugs currently in the clinics are against either overexpressed kinases or mutated kinases that are implicated in the disease. However not all druggable kinases are mutated or overexpressed in many cases their activity altered through post-translational modifications. Others and we have identified elevated levels of phosphorylated IKK¿ in the tumor samples compared to the normal tissues suggesting that the diseased state of IKK¿ exists phosphorylated state. IKK¿ like other kinases is regulated by sequential phosphorylation-dephosphorylation events. The lack of phospho-specific antibodies against the various phosphorylated forms of IKK¿ makes defining the diseased state a challenging endeavor. In this application we will use a novel technology NanoPro 1000 to address this issue in pancreatic tumors and cell lines. This is an exploratory project as we seek to characterize the various post-translational modifications associated with a disease relevant kinase. Our focus on the specific forms of IKK¿, rather than IKK¿ in general, makes this bother novel and innovative.

项目摘要 /摘要激酶是有吸引力的药物靶标的，这是由最近的FDA批准的数量证明的癌症治疗的抑制剂。目前诊所中的药物反对过表达的激酶或疾病中隐含的突变激酶。但是，并非所有可吸毒激酶都突变或在许多情况下，它们的活性通过翻译后修改改变了。别人和我们与正常组织相比表明IKK的患病状态存在磷酸化状态。 ikk¿和其他激酶一样受顺序磷酸化 - 脱磷酸化事件。缺乏针对磷酸的特异性抗体 Ikk的各种磷酸化形式使定义患病状态成为挑战。在这个应用程序我们将使用一种新型的技术Nanopro 1000来解决胰腺肿瘤和细胞中的此问题线。这是一个探索性项目，因为我们试图表征各种翻译后修改与疾病相关激酶有关。我们专注于ikk？的特定形式，而不是一般的Ikk？使这个既新颖又创新。