Detection and Diagnosis of Pancreatic Carcinoma

胰腺癌的检测和诊断

基本信息

批准号：
7886032
负责人：
DAVID V GOLD
金额：
$ 27.22万
依托单位：
CTR FOR MOLECULAR MEDICINE/IMMUNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-09 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7886032
关键词：
Abdominal Pain Affinity Antibodies Antibody Specificity Antigens Benign Biochemical Biological Assay Biological Markers Blood Body Weight decreased Cancer Etiology Cessation of life Clinical Clinical Trials Data Data Correlations Detection Development Diagnosis Diagnostic Discrimination Disease Disease Progression Early Diagnosis Enzyme Immunoassay Epitopes Evaluation Funding Generations Glycoproteins Goals Grant Hepatobiliary Histologic Icterus Image Immunoassay In Vitro Individual Investigation Laboratories Lesion Liquid substance Location Malignant - descriptor Malignant Neoplasms Malignant neoplasm of pancreas Mass Spectrum Analysis Measures Medical Assistance Mind Modification Monoclonal Antibodies Mucins Mus Nature Normal tissue morphology Observational Study Operative Surgical Procedures Outcome Pancreas Pancreatic Diseases Pancreatic Intraepithelial Neoplasia Pancreatic carcinoma Pancreatitis Patients Peptides Performance Phage Display Population Predictive Value Procedures Property Publications Publishing Relapse Reporting Research Research Proposals Role Sampling Screening procedure Serum Specificity Specimen Staging Study Section Surveillance Program Symptoms Systemic Therapy Testing Therapeutic Intervention Time Tissues Translating United States Woman Work base cancer diagnosis cell type diagnostic accuracy disease diagnosis follow-up high risk improved men mortality outcome forecast pancreatic neoplasm programs prospective public health relevance response statistics tumor tumor growth

项目摘要

DESCRIPTION (provided by applicant): The objective of this research proposal is the development and evaluation of immunoassays having clinical utility for the "early" detection and diagnosis of pancreatic carcinoma. In the year 2009, an estimated 42,000 new cases of pancreatic carcinoma will be diagnosed in the United States. Pancreatic carcinoma is the tenth most common form of cancer in men and women today, yet it is the fourth leading cause of cancer deaths. The most common symptoms of the disease, jaundice, abdominal pain, and weight loss, together with other presenting factors are nonspecific in nature. Thus, diagnosing pancreatic carcinoma at an early stage of tumor growth is difficult at best, requiring considerable suspicion and extensive diagnostic work-up, up to and including exploratory surgery. Our laboratory has developed and characterized the PAM4 monoclonal antibody (murine, chimeric and humanized versions), providing evidence as to its potential for clinical detection, imaging and therapy of pancreatic carcinoma. Our recent developments employing an in vitro enzyme immunoassay to quantitate PAM4-reactive antigen in the blood of patients, appears quite promising for detection of pancreatic carcinoma and its discrimination from pancreatitis, as well as other cancers and normal individuals. Early detection and diagnosis of pancreatic carcinoma, as well as appropriate staging of the disease, would almost certainly provide a survival advantage. With this in mind, we intend to further develop and assess the ability of the PAM4-based immunoassays, both immunohistochemical detection in tissue specimens and enzyme immunoassay to detect and quantitate the antigen in both serum and pancreatic fluids, to provide "early" detection and diagnosis at a time-point when therapeutic intervention may have better opportunity for successful outcome. The specific aims of this project are: 1. To evaluate the performance profile of the PAM4-Immunoassay for diagnostic accuracy; 2. To evaluate the clinical utility of the PAM4-Immunoassay for a-accurate diagnosis of patients presenting with symptoms suggestive of pancreatic cancer; b- early detection of pancreatic carcinoma in asymptomatic individuals at high risk for pancreatic cancer; c- assessment of tumor response or early detection of relapse; 3. To evaluate the nature of the antigen to which PAM4 is reactive. PUBLIC HEALTH RELEVANCE: Pancreatic carcinoma is an insidious disease with a particularly high mortality rate. In large measure, this is due to the location of the tumor where it can grow in a silent fashion. Symptoms that might suggest the patient seek medical assistance are usually not evident until an advanced stage of tumor growth. Compounding this challenge is that currently available treatment procedures have not been able to provide a cure for the overwhelming majority of patients. Our goal is to provide an antibody approach for early detection and diagnosis of the disease at a time when curative procedures have a better opportunity for successful outcome. We have developed monoclonal antibody PAM4 that has a high specificity for pancreatic carcinoma as compared to benign pancreatic disease, other types of malignancies, and normal individuals. Thus, the detection of the PAM4-reactive antigen provides a high likelihood for the diagnosis of pancreatic cancer. The aims of the proposed research are to further define the specificity of the antibody as to its ability to provide accurate diagnoses, and to examine the value of the immunoassay for "early" detection of pancreatic carcinoma, prior to the development of symptoms, in a group of patients considered to be at high risk for development of the disease.

描述（由申请人提供）：本研究计划的目的是开发和评估具有临床实用性的免疫测定法，用于“早期”检测和诊断胰腺癌。 2009年，美国估计将诊断出42,000例新的胰腺癌病例。胰腺癌是当今男性和女性中第十常见的癌症，但它是癌症死亡的第四大原因。该疾病最常见的症状、黄疸、腹痛和体重减轻以及其他表现因素本质上是非特异性的。因此，在肿瘤生长的早期阶段诊断胰腺癌充其量是困难的，需要相当多的怀疑和广泛的诊断检查，直至并包括探查手术。我们的实验室开发并表征了 PAM4 单克隆抗体（鼠源、嵌合和人源化版本），为其用于胰腺癌临床检测、成像和治疗的潜力提供了证据。我们最近的发展采用体外酶免疫测定法来定量患者血液中的 PAM4 反应性抗原，对于检测胰腺癌及其与胰腺炎以及其他癌症和正常个体的区分似乎很有希望。胰腺癌的早期发现和诊断以及疾病的适当分期几乎肯定会提供生存优势。考虑到这一点，我们打算进一步开发和评估基于 PAM4 的免疫测定的能力，包括组织标本中的免疫组织化学检测和酶免疫测定来检测和定量血清和胰液中的抗原，以提供“早期”检测和在治疗干预可能有更好机会获得成功结果的时间点进行诊断。该项目的具体目标是： 1. 评估 PAM4-Immunoassay 的性能概况以实现诊断准确性； 2. 评估 PAM4 免疫测定法对出现胰腺癌症状的患者进行准确诊断的临床实用性； b- 在胰腺癌高危无症状个体中早期发现胰腺癌； c-评估肿瘤反应或早期检测复发； 3.评价与PAM4反应的抗原的性质。公共卫生相关性：胰腺癌是一种死亡率特别高的隐匿性疾病。在很大程度上，这是由于肿瘤可以以无声的方式生长的位置。可能建议患者寻求医疗帮助的症状通常直到肿瘤生长的晚期才明显。使这一挑战更加复杂的是，目前可用的治疗程序无法治愈绝大多数患者。我们的目标是提供一种抗体方法，以便在治疗程序有更好的机会获得成功结果时早期检测和诊断疾病。我们开发了单克隆抗体PAM4，与良性胰腺疾病、其他类型的恶性肿瘤和正常个体相比，它对胰腺癌具有高特异性。因此，PAM4反应抗原的检测为胰腺癌的诊断提供了很高的可能性。拟议研究的目的是进一步确定抗体提供准确诊断能力的特异性，并检查免疫测定在症状出现之前“早期”检测胰腺癌的价值。被认为处于该疾病发展高风险的患者群体。