Detection and Diagnosis of Pancreatic Carcinoma

描述（由申请人提供）：本研究提案的目的是开发和评价具有临床实用性的免疫测定法，用于胰腺癌的“早期”检测和诊断。在2009年，估计在美国将诊断出42，000例新的胰腺癌病例。胰腺癌是当今男性和女性中第十大最常见的癌症形式，但它是癌症死亡的第四大原因。该病最常见的症状是黄疸、腹痛和体重减轻，以及其他表现因素，这些症状在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，直到并包括探索性手术。我们的实验室已经开发并表征了PAM 4单克隆抗体（鼠，嵌合和人源化版本），为胰腺癌的临床检测，成像和治疗提供了证据。我们最近的发展，采用体外酶免疫测定定量PAM 4-反应性抗原在患者的血液中，似乎很有前途的胰腺癌的检测和胰腺炎，以及其他癌症和正常人的歧视。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PAM 4的免疫测定法的能力，包括组织标本中的免疫组织化学检测和酶免疫测定法，以检测和定量血清和胰液中的抗原，从而在治疗干预可能有更好机会获得成功结果的时间点提供“早期”检测和诊断。该项目的具体目标是：1。评价PAM 4-免疫测定的诊断准确性的性能特征; 2.评估PAM 4-免疫测定用于以下的临床效用：a-准确诊断表现出提示胰腺癌的症状的患者; B-在胰腺癌高风险的无症状个体中早期检测胰腺癌; c-评估肿瘤反应或早期检测复发; 3.评价PAM 4反应性抗原的性质。

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.