Early Detection of Pancreatic Cancer Cachexia

早期发现胰腺癌恶病质

• 批准号: 7290947
• 负责人: Denis C Guttridge
• 金额: $ 7.28万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-28 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7290947
• 关键词: Abdomen; Adenocarcinoma; Adipose tissue; Affect; Agreement; Animal Cancer Model; Animal Model; Animals; Anorexia; Appetite Stimulants; Area; Benchmarking; Biological; Biological Markers; Body Weight; Body Weight decreased; Cachexia; Cancer Etiology; Cancer Patient; Cause of Death; Cessation of life; Chemotherapy-Oncologic Procedure; Clinical; Complex; Cytotoxic Chemotherapy; Desire for food; Diagnosis; Disease; Dystrophin; Early Diagnosis; Early identification; Excision; Fatty acid glycerol esters; Functional disorder; Glycoproteins; Histologic; Human; Image; Incidence; Inflammatory; Intervention; Lead; Liquid substance; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of pancreas; Mediator of activation protein; Metabolic Diseases; Muscle; Muscular Dystrophies; NIH Program Announcements; Nutritional; Operative Surgical Procedures; Outcome; Pancreas; Pathway interactions; Patients; Perioperative; Pilot Projects; Process; Quality of life; Radiation; Rate; Recurrence; Research; Resistance; Risk; Skeletal Muscle; Solid Neoplasm; Staging; Standards of Weights and Measures; Starvation; Supplementation; Survival Rate; Syndrome; System; Techniques; Testing; Therapeutic; Time; Ubiquitin; United States; Validation; Weight; Weight Gain; anticancer research; chemotherapy; cytokine; fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; improved; mortality; multicatalytic endopeptidase complex; novel; outcome forecast; pancreatic neoplasm; response; tissue culture; transcription factor; tumor; wasting

DESCRIPTION (provided by applicant): Pancreatic cancer is currently the fourth most common cancer causing death in the United States, with mortality rates nearly equaling incidence rates. Adenocarcinoma histologically constitutes approximately 90% of pancreatic tumors with current 5-year survival rates of only 4%. Successful surgical resection can improve survival rates to 25%, but tumor recurrence is common. A compounding feature of pancreatic cancer is the high incidence of the cachexia syndrome, a complex metabolic disorder characterized by extreme weight loss due to the gross depletion of adipose and skeletal muscle tissues. Unlike starvation which reduces fat content but where skeletal muscle is preserved, in cachexia neither fat nor muscle is spared. This may partly explain why nutritional supplementation alone stimulates transient weight gain due to accumulation of fat, but is not sufficient to influence lean mass, quality of life and/or survival. Pancreatic cancer patients typically lose greater than 10% of their pre-illness body weight, which can decline to 25% near time of death. Although weight loss represents the current benchmark standard to diagnose cachexia, too often this occurs in advanced stages of pancreatic cancer where anti-cachexia intervention may already be limiting. Intervention prior to the onset of weight loss may have therapeutic benefits, but this strategy is currently hindered by the inability to sufficiently recognize prognosticators of the cachexia syndrome. Clinical and molecular markers have been identified, but their validation has mainly been restricted to tissue culture systems and animal models of cancer cachexia. Therefore, there is a clear need in pancreatic cancer research to validate these current markers as well as to identify novel markers that may lead to effective early anti-cachexia treatment. To make this determination, the following two specific aims will be performed: 1) to validate the current markers of cachexia in human pancreatic cancer; and 2) to screen for novel early markers of cachexia in pancreatic cancer. Completion of these aims should advance our understanding of pancreatic cancer cachexia and potentially also affect treatment options to improve quality of life and/or survival.

描述（由申请人提供）：胰腺癌目前是美国第四大最常见的死亡癌症，死亡率几乎等于发病率。从组织学角度来看，腺癌约占胰腺肿瘤的 90%，目前 5 年生存率仅为 4%。成功的手术切除可以将生存率提高至25%，但肿瘤复发很常见。胰腺癌的一个复杂特征是恶病质综合征的高发病率，这是一种复杂的代谢性疾病，其特征是由于脂肪和骨骼肌组织的严重消耗而导致体重极度减轻。与饥饿会减少脂肪含量但保留骨骼肌不同，在恶病质中，脂肪和肌肉都不能幸免。这可以部分解释为什么单独的营养补充会因脂肪积累而刺激短暂的体重增加，但不足以影响瘦体重、生活质量和/或生存。胰腺癌患者的体重通常会比病前减轻 10% 以上，在临近死亡时可能会下降至 25%。尽管体重减轻代表了当前诊断恶病质的基准标准，但这种情况常常发生在胰腺癌的晚期，此时抗恶病质干预可能已经受到限制。在减肥开始之前进行干预可能具有治疗益处，但目前该策略因无法充分识别恶病质综合征的预后因素而受到阻碍。临床和分子标志物已被鉴定，但其验证主要限于癌症恶病质的组织培养系统和动物模型。因此，胰腺癌研究显然需要验证这些现有标记物，并确定可能导致有效的早期抗恶病质治疗的新标记物。为了做出这一决定，将执行以下两个具体目标：1）验证人类胰腺癌中恶病质的当前标志物； 2) 筛选胰腺癌恶病质的新型早期标志物。这些目标的完成应该增进我们对胰腺癌恶病质的理解，并可能影响改善生活质量和/或生存的治疗选择。