Clinical Studies and Molecular Pathology

7.2.3.核心C。临床研究和分子病理学 核心领导人：雅克·货车·达姆 调查员：James Crawford、Jay Pasricha、Shiro Urayama 临床研究-新探头测试 新探针的测试将首先在小动物模型中进行（以确定 摄取），然后在大型动物中使用内窥镜成像技术。安全性和有效性将 用动物模型来判断。由于小动物甚至大型动物模型都不能完全预测 一旦在动物中的安全性和有效性得到证实，我们将转向人类研究。 确立了习肽探针将在常规内窥镜检查期间局部施用（Hsiung P. 例如，2008年）。靶组织（息肉、炎症、相对正常粘膜的对照区域）将被 用水洗涤以除去多余的粘液。约3-6 mL肽，浓度为100 使用标准喷雾导管（Olympus洗涤管，Olympus 美国公司Center Valley，PA）。将多余的肽冲洗掉并进行成像。 对于更深的靶结构，如肿瘤病变（食管癌、胃癌、直肠癌）和 性质不确定的相关淋巴结肿大（良性、炎症、转移性），肽探针 将需要肠胃外给药。同样，将在给药前在动物模型中判断安全性和有效性。 人类研究。由于循环时间，预期肽将需要在体内施用。 先进的成像技术。最大信号肽的最佳定位时间- 在人类研究之前，将在动物模型中确定噪声比。一旦被批准用于人体研究， 患者选择将包括那些已知胃肠道恶性肿瘤的患者， 分期程序，并且作为对照，那些患有炎性疾病（食管炎，结肠炎， 胃炎）其中增大的淋巴结可能是炎性的而不是肿瘤性的。许多癌症 病人会被转介接受手术切除及淋巴结收集。将切除淋巴结 评估转移性疾病（护理标准），并将作为“金标准”。“许多患者 良性疾病（暴发性结肠炎，慢性胰腺炎）也将经历手术切除， 将组织病理学评估收获的淋巴结。

7.2.3. Core C. Clinical studies and molecular pathology Core Leader: Jacques Van Dam Investigators: James Crawford, Jay Pasricha, Shiro Urayama Clinical studies - testing of new probes The testing of new probes will be undertaken first in small animal models (to determine the focality of the uptake) and then in large animals using endoscopic imaging techniques. Both safety and efficacy will be judged using animal models. As small animals and even large animal models do not perfectly predict biological behavior in humans, we will move to human studies once safety and efficacy in animals have been established. Peptide probes will be administered topically during routine endoscopy (Hsiung P. et al., 2008). Target tissue (polyps, inflammation, control regions of relatively normal mucosa) will be washed with water to remove excess mucus. Approximately 3-6 mL of peptide at a concentration of 100 uM will be topically administered using a standard spray catheter (Olympus washing pipe, Olympus America, Inc.; Center Valley, PA). Excess peptide will be rinsed away and imaging undertaken. For deeper target structures such as neoplastic lesions (esophageal, gastric, rectal cancers) and associated enlarged lymph nodes of uncertain nature (benign, inflammatory, metastatic), peptide probes will require parenteral administration. Again, safety and efficacy will be judged in animal models prior to human study. Due to the circulating time, it is anticipated that peptides will require administration in advanced of the imaging procedure. The optimal time of localization of peptide with the greatest signal- to-noise ratio will be determined in animal models prior to human study. Once approved for human study, patient selection will include those with known gastrointestinal malignancy referred for endosonographic staging procedures and, as controls, those patients with inflammatory conditions (esophagitis, colitis, gastritis) in which enlarged lymph nodes may be inflammatory rather than neoplastic. Many cancer patients will then be referred for surgical resection and lymph node harvest. Excised lymph nodes will be assess for metastatic disease (standard of care) and will serve as "gold standard." Many patients with benign disease (fulminant colitis, chronic pancreatitis) will also undergo surgical resection and again, harvested lymph nodes will be histopathologically assessed.