PDF(Pubmed)
Abstract：
UNASSIGNED: Lung tumor organoids (LTOs) have attracted attention as in vitro preclinical models; however, their clinical and experimental applications have not been fully established.
UNASSIGNED: We attempted to establish LTOs from resected specimens of patients with lung cancer who underwent lung resection. Clinicopathologic characteristics related to the establishment of LTOs were evaluated. Histologic assessment and genetic analysis were conducted for both LTOs and their parental tumors. Organoid-derived xenografts were generated in immunocompetent mice. Drug sensitivity was assessed using cell proliferation assays.
UNASSIGNED: We established 53 LTOs from 79 lung cancer samples, including 10 long-term culture models. The establishment rate was significantly lower in squamous cell carcinomas than in other histologic types (48% versus 75%, p = 0.034). Histologic similarities were confirmed among LTOs, the parental tumors, and organoid-derived xenografts. Seven mutations, including two EGFR L858R and one EGFR exon 20 H773delinsYNPY mutations, were detected in both LTO and parental tumors; the other four mutations were detected in either LTO or parental tumors. The extensive culture ability of LTO (passaged >10 times) correlated with poor patient prognosis. LTO9 cells harboring EGFR H773delinsYNPY were sensitive to osimertinib. The parental patient, who had new metastatic lesions, was treated with osimertinib and exhibited a remarkable response.
UNASSIGNED: The establishment and growth rates of LTOs were associated with the histologic subtype and tumor size. LTOs derived from resected specimens have become preclinical models that can be used to predict drug responses and accelerate the development of treatment strategies for patients with rare mutations.
UNASSIGNED: We attempted to establish LTOs from resected specimens of patients with lung cancer who underwent lung resection. Clinicopathologic characteristics related to the establishment of LTOs were evaluated. Histologic assessment and genetic analysis were conducted for both LTOs and their parental tumors. Organoid-derived xenografts were generated in immunocompetent mice. Drug sensitivity was assessed using cell proliferation assays.
UNASSIGNED: We established 53 LTOs from 79 lung cancer samples, including 10 long-term culture models. The establishment rate was significantly lower in squamous cell carcinomas than in other histologic types (48% versus 75%, p = 0.034). Histologic similarities were confirmed among LTOs, the parental tumors, and organoid-derived xenografts. Seven mutations, including two EGFR L858R and one EGFR exon 20 H773delinsYNPY mutations, were detected in both LTO and parental tumors; the other four mutations were detected in either LTO or parental tumors. The extensive culture ability of LTO (passaged >10 times) correlated with poor patient prognosis. LTO9 cells harboring EGFR H773delinsYNPY were sensitive to osimertinib. The parental patient, who had new metastatic lesions, was treated with osimertinib and exhibited a remarkable response.
UNASSIGNED: The establishment and growth rates of LTOs were associated with the histologic subtype and tumor size. LTOs derived from resected specimens have become preclinical models that can be used to predict drug responses and accelerate the development of treatment strategies for patients with rare mutations.
摘要：
■肺肿瘤类器官（LTO）作为体外临床前模型引起了人们的关注；然而，其临床和实验应用尚未完全确立。
■我们试图从接受肺切除术的肺癌患者的切除标本中建立LTO。评估了与LTO建立相关的临床病理特征。对LTO及其亲本肿瘤进行组织学评估和遗传分析。在免疫活性小鼠中产生类器官来源的异种移植物。使用细胞增殖试验评估药物敏感性。
■我们从79个肺癌样本中建立了53个LTO，包括10种长期文化模式。鳞状细胞癌的建立率显着低于其他组织学类型（48％对75％，p=0.034)。在LTO之间证实了组织学相似性，亲本肿瘤，和类器官来源的异种移植物。七个突变,包括两个EGFRL858R和一个EGFR外显子20H773delinsYNPY突变，在LTO和亲本肿瘤中均检测到;在LTO或亲本肿瘤中检测到其他四种突变。LTO的广泛培养能力（传代>10次）与患者预后不良相关。携带EGFRH773delinsYNPY的LTO9细胞对奥希替尼敏感。父母的病人,有新的转移性病变的人，接受奥希替尼治疗并表现出显著的反应。
■LTO的建立和生长速率与组织学亚型和肿瘤大小有关。来自切除标本的LTO已成为临床前模型，可用于预测药物反应并加速罕见突变患者治疗策略的开发。
■我们试图从接受肺切除术的肺癌患者的切除标本中建立LTO。评估了与LTO建立相关的临床病理特征。对LTO及其亲本肿瘤进行组织学评估和遗传分析。在免疫活性小鼠中产生类器官来源的异种移植物。使用细胞增殖试验评估药物敏感性。
■我们从79个肺癌样本中建立了53个LTO，包括10种长期文化模式。鳞状细胞癌的建立率显着低于其他组织学类型（48％对75％，p=0.034)。在LTO之间证实了组织学相似性，亲本肿瘤，和类器官来源的异种移植物。七个突变,包括两个EGFRL858R和一个EGFR外显子20H773delinsYNPY突变，在LTO和亲本肿瘤中均检测到;在LTO或亲本肿瘤中检测到其他四种突变。LTO的广泛培养能力（传代>10次）与患者预后不良相关。携带EGFRH773delinsYNPY的LTO9细胞对奥希替尼敏感。父母的病人,有新的转移性病变的人，接受奥希替尼治疗并表现出显著的反应。
■LTO的建立和生长速率与组织学亚型和肿瘤大小有关。来自切除标本的LTO已成为临床前模型，可用于预测药物反应并加速罕见突变患者治疗策略的开发。
