Detection and Diagnosis of Pancreatic Carcinoma

描述(申请人提供)：这项研究计划的目标是开发和评估具有临床实用价值的免疫分析方法，以“早期”发现和诊断胰腺癌。据估计，2009年美国将新增42,000例胰腺癌确诊病例。胰腺癌是当今男性和女性最常见的第十种癌症，但它是导致癌症死亡的第四大原因。该病最常见的症状，黄疸、腹痛、体重减轻，以及其他表现因素，本质上都是非特异性的。因此，在肿瘤生长的早期阶段诊断胰腺癌充其量是困难的，需要相当大的怀疑和广泛的诊断工作，直到并包括探查手术。我们实验室已经开发并鉴定了PAM4单抗(鼠源性、嵌合型和人源化版本)，为其在胰腺癌临床检测、成像和治疗方面的潜力提供了证据。我们的最新进展是采用体外酶免疫分析法定量患者血液中的PAM4反应抗原，在检测胰腺癌及其与胰腺炎以及其他癌症和正常人的鉴别方面似乎非常有希望。早期发现和诊断胰腺癌，以及对疾病进行适当的分期，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的免疫分析方法的能力，包括组织标本中的免疫组织化学检测和酶免疫分析，以检测和定量血清和胰液中的抗原，以便在治疗干预可能有更好的成功结果的时间点提供早期检测和诊断。本项目的具体目标是：1.评估PAM4-免疫分析的诊断准确性；2.评估PAM4-免疫分析对出现胰腺癌症状的患者进行准确诊断的临床应用；b-在无症状的胰腺癌高危人群中早期检测胰腺癌；c-评估肿瘤反应或早期检测复发；3.评估PAM4对抗原的反应性质。

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.