OPIOID GROWTH FACTOR AND PANCREATIC CANCER--PHASE 1

胰腺癌是全世界与癌症相关的死亡的第四大原因。 美国，每年有超过28,000人死亡。从……开始 诊断：中位生存期为3至6个月，胰腺 癌症患者是所有恶性肿瘤中预后最差的。原因何在 因为这种糟糕的前景部分是由于#年癌症的性质。 它对放射治疗和化疗的抗药性是出了名的， 事实上，癌症在早期阶段没有被诊断出来，当 手术切除是一种选择。我们的课题组一直在研究 早期诊断和治疗的策略。在初步研究中，我们 发现内源性(天然)阿片肽与阿片类药物相互作用 与抑制人胰腺癌细胞生长相关的受体 在体外和体内。我们的调查记录了阿片类药物的增长 因子(OGF)。[MET/5]-脑啡肽参与胰腺生长 癌症，并对致癌事件具有可逆作用，从而有助于 抑制经济增长。OGF的作用是由阿片受体Zeta介导的。 这项拨款假设OGF的管理将改变这一进程 通过作为抑制剂在人类受试者中预防胰腺癌。 我们建议通过开放标记的阶段1来研究这一假设 建立最大耐受剂量的临床试验，并评估 OGF对人体的安全性、生物学效应和药物毒性 研究对象。提出了以下具体目标：1)确定 肿瘤患者静脉注射OGF的最大耐受量 皮下注射OGF对患者的影响 对于癌症，评估其影响，并开始调查 OGF长期应用治疗胰腺癌的疗效观察 5)阐明OGF血浆水平与癌症的关系。 胰腺癌患者的肿瘤进展。这些研究是 这是一个长期计划的一部分，目的是了解 胰腺癌的治疗，尤其是细胞癌和胰腺癌 作为生长因子的多肽的分子生物学。

Pancreatic cancer is the 4th leading cause of cancer-related deaths in the U.S., with over 28,000 fatalities occurring each year. From the time of diagnosis the median survival ranges from 3 to 6 months, giving pancreatic cancer patients the most dismal prognosis of all malignancies. The reasons for this poor outlook are partially due to the nature of the cancer in that it is notoriously resistant to radiation therapy and chemotherapy, and the fact that the cancer is not diagnosed in early stages when surgical resection is an option. Our research group has been studying strategies for early diagnosis and treatment. In preliminary studies we have found that endogenous (native) opioid peptides interact with opioid receptors associated with human pancreatic cancer cells to inhibit growth in vitro and in vivo. Our investigations have documented the opioid growth factor (OGF). [MET/5]-enkephalin, is involved in the growth of pancreatic cancer, and has a reversible action on tumorigenic events that serves to repress growth. OGF's action is mediated by the opioid receptor, zeta. This grant hypothesizes that administration of OGF will change the course of pancreatic cancer in human subjects by acting as an inhibitory agent. We propose to investigate this hypothesis by an open-labelled Phase 1 clinical trial to establish the maximum-tolerance dose, and evaluate the safety, biological effects, and drug-related toxicities of OGF in human subjects. The following specific aims are proposed: 1) Determine the maximum-tolerated dose of OGF in cancer patients after an intravenous infusion, the effects of subcutaneous administration of OGF in patients with cancer, 4) Evaluate the repercussions and begin to investigate efficacy of chronic administration of OGF on patients with pancreatic cancer, and 5) Elucidate the relationship between OGF plasma levels and tumor progression in patients with pancreatic cancer. These studies are part of a long-range program directed toward understand the mechanism and treatment of pancreatic oncogenesis, particularly the cellular and molecular biology of peptides that serve as growth factors.