Clinical Studies and Molecular Pathology

7.2.3。临床研究和分子病理学 核心领导人：雅克·范·达姆 调查人员：James Crawford，Jay Pasricha，Shiro Urayama 临床研究.新探头的测试 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。安全性和有效性都将是 使用动物模型进行判断。因为小动物甚至大动物模型都不能完美地预测 人类的生物学行为，一旦在动物身上的安全性和有效性有了，我们将转移到人类研究 已经建立了。在常规内窥镜检查期间将局部注射多肽探头(Hsiung P.et) Al.，2008)。目标组织(息肉、炎症、相对正常的粘膜控制区)将 用水洗去多余的粘液。大约3-6毫升的多肽，浓度为100 UM将使用标准喷雾导管(奥林巴斯洗涤管，奥林巴斯)局部给药 美国公司；宾夕法尼亚州中央山谷)。多余的多肽将被冲洗掉并进行成像。 对于更深层的靶结构，如肿瘤性病变(食道癌、胃癌、直肠癌)和 不确定性质(良性、炎症性、转移性)的相关增大的淋巴结，多肽探针 需要非肠道给药。同样，安全性和有效性将在动物模型中进行判断，然后再进行 人类研究。由于循环时间的限制，预计多肽将需要在 先进的成像程序。信号最强的多肽的最佳定位时间- 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的胃肠道恶性肿瘤患者进行腔内超声检查。 分期程序，并作为对照，那些有炎症条件的患者(食管炎、结肠炎、 胃炎)，增大的淋巴结可能是炎症性的而不是肿瘤性的。许多癌症 然后，患者将被转介进行手术切除和淋巴结采集。切除的淋巴结会 评估转移性疾病(护理标准)，并将作为“黄金标准”。许多患者患有 良性疾病(暴发性结肠炎、慢性胰腺炎)也将接受手术切除， 采集的淋巴结行组织病理学评估。

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.