Detection and Diagnosis of Pancreatic Carcinoma

胰腺癌的检测和诊断

• 批准号: 8257497
• 负责人: DAVID V GOLD
• 金额: $ 26.41万
• 依托单位: CTR FOR MOLECULAR MEDICINE/IMMUNOLOGY
• 依托单位国家: 美国
• 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/8257497
• 关键词: Abdominal Pain; Affinity; Antibodies; Antibody Specificity; Antigens; Benign; Biochemical; Biological Assay; Biological Markers; Blood; Body Weight decreased; Cancer Etiology; Carcinoma; 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; Histocompatibility Testing; 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

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）：该研究建议的目的是对具有临床实用性的免疫测定的开发和评估，以“早期”检测和诊断胰腺癌。在2009年，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的第十个最常见的癌症形式，但这是癌症死亡的第四个主要原因。这种疾病，黄疸，腹痛和体重减轻的最常见症状以及其他表现因素本质上是非特异性的。因此，诊断在肿瘤生长的早期阶段诊断胰腺癌充其量很难，需要相当多的怀疑和广泛的诊断检查，直到探索性手术。我们的实验室已经开发并表征了PAM4单克隆抗体（鼠，嵌合和人源化版本），提供了证据表明其胰腺癌的临床检测，成像和治疗的潜力。我们最近采用体外酶免疫测定法对患者血液中PAM4反应抗原进行定量的发展似乎很有希望，可检测胰腺癌及其与胰腺炎以及其他癌症和其他癌症和正常人的歧视。胰腺癌的早期检测和诊断以及疾病的适当分期几乎可以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，包括在组织标本中的免疫组织化学检测和酶免疫测定法检测和定量血清和胰液中的抗原均可在更早的时间内进行时间介绍和诊断，以便在更高的时间内进行次要介绍。该项目的具体目的是：1。评估PAM4-免疫测定的性能概况以诊断精度； 2。评估PAM4-免疫测定法的临床实用性，以诊断出患有胰腺癌症状的患者的诊断； b-早期发现胰腺癌高风险的无症状患者胰腺癌的早期检测； c-评估肿瘤反应或复发的早期检测； 3。评估PAM4反应性的抗原的性质。 公共卫生相关性：胰腺癌是一种阴险的疾病，死亡率特别高。在很大程度上，这是由于肿瘤的位置可以以静默的方式生长。可能表明患者寻求医疗救助的症状通常在肿瘤生长的高级阶段才显而易见。加重这一挑战的是，目前可用的治疗程序无法为绝大多数患者提供治疗方法。我们的目标是在治疗程序有更好的成功结局机会的时候提供一种抗体方法来早日检测和诊断该疾病。我们已经开发了单克隆抗体PAM4，与良性胰腺疾病，其他类型的恶性肿瘤和正常个体相比，对胰腺癌具有很高的特异性。因此，检测PAM4反应性抗原为诊断胰腺癌提供了很高的可能性。拟议的研究的目的是进一步定义抗体对其提供准确诊断能力的特异性，并在症状发展之前（在症状发展之前，在症状发育之前，在一组被认为是这种疾病发育的高风险中，对胰腺癌的“早期”检测的价值。