UASSIGNED:患者来源的异种移植(PDX)模型在临床前和转化应用中显示出很高的效率。胃肠道(GI)肿瘤具有很强的异质性,PDX模型的植入率显着变化。然而,影响植入率的临床病理和分子特征仍然难以捉摸。
未经证实:将来自患有GI癌的患者的总共312个新鲜肿瘤组织样品植入到免疫缺陷小鼠中。患者中位随访时间为37个月。在PDX生长和总生存期方面比较了患者的特征。使用3-6代的PDX模型进行药物评价。
未经批准:总共,171(54.8%,171/312)建立了PDX模型,包括85个结肠直肠癌的PDX模型,21个食管癌的PDX模型,和65个胃癌的PDX模型。除了肿瘤部位,组织学,分化程度,和血清甲胎蛋白(AFP)水平,异种移植和患者特征之间没有发现显着差异。对于接受新辅助治疗的患者,疾病进展(PD)或疾病稳定(SD)患者的肿瘤形成发生率较高.在胃癌中,结果显示缺陷错配修复(dMMR)肿瘤的移植率较高,Ki-67可能是影响植入率的重要因素。RAS和BRAF的基因突变状态,结直肠癌的两个重要分子标志物,在患者肿瘤和PDX之间显示出高度的一致性。然而,未观察到这两种突变对PDX植入率的显著影响.更重要的是,在这项研究中,尽管在两个临床病例中检测到KRAS突变,在PDX模型和患者中,西妥昔单抗治疗后仍观察到明显的肿瘤抑制.
UNASSIGNED:在我们中心成功建立了包括171例胃肠道肿瘤的大规模PDX模型。阐明了临床病理和分子特征与植入率之间的关系。此外,这一资源为我们提供了对肿瘤异质性的深刻见解,使这些模型对PDX指导的治疗决策有价值,并提供PDX模型作为个性化治疗和翻译研究的绝佳工具。
UNASSIGNED: Patient-derived xenograft (PDX) models have shown a great efficiency in preclinical and translational applications. Gastrointestinal (GI) tumors have a strong heterogeneity, and the engraftment rate of PDX models remarkably vary. However, the clinicopathological and molecular characteristics affecting the engraftment rate still remain elusive.
UNASSIGNED: A total of 312 fresh tumor tissue samples from patients with GI cancer were implanted into immunodeficient mice. The median follow-up time of patients was 37 months. Patients\' characteristics were compared in terms of PDX growth and overall survival. PDX models of 3-6 generations were used for drug evaluation.
UNASSIGNED: In total, 171 (54.8%, 171/312) PDX models were established, including 85 PDX models of colorectal cancer, 21 PDX models of esophageal cancer, and 65 PDX models of gastric cancer. Other than tumor site, histology, differentiation degree, and serum alpha-fetoprotein (AFP) level, no significant differences were found between transplantation of xenografts and patients\' characteristics. For patients who had undergone neoadjuvant therapy, the incidence of tumor formation was higher in those with progressive disease (PD) or stable disease (SD). In gastric cancer, the results showed a higher transplantation rate in deficient mismatch repair (dMMR) tumors, and Ki-67 could be an important factor affecting the engraftment rate. The gene mutation status of RAS and BRAF, two important molecular markers in colorectal cancer, showed a high degree of consistency between patients\' tumors and PDXs. However, no significant effects of these two mutations on PDX engraftment rate were observed. More importantly, in this
study although KRAS mutations were detected in two clinical cases, evident tumor inhibition was still observed after cetuximab treatment in both PDX models and patients.
UNASSIGNED: A large-scale PDX model including 171 cases was successfully established for GI tumors in our center. The relationship between clinicopathological and molecular features and engraftment rates were clarified. Furthermore, this resource provides us with profound insights into tumor heterogeneity, making these models valuable for PDX-guided treatment decisions, and offering the PDX model as a great tool for personalized treatment and translation research.