决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Acquired crizotinib-resistant pulmonary adenocarcinoma and subsequent primary gallbladder cancer: A case report.
Acquired crizotinib-resistant pulmonary adenocarcinoma and subsequent primary gallbladder cancer: A case report.
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在诊断方面,精准的生物信息学分析与重复活检具有同等价值。
研究依据:针对原癌基因的靶向治疗对患有多原发肿瘤的老年患者获益有限。患者关注:一名间变性淋巴瘤激酶阳性肺腺癌女性患者接受crizotinib靶向治疗3年后出现获得性耐药。诊断:意外发现随后发生的原发性胆囊肿瘤。干预:给予lenvatinib治疗。同时采用生物信息学方法比较crizotinib治疗前后的新一代测序结果,分析肿瘤驱动突变基因。结局:患者死于腹水和肝衰竭。此外,研究发现旁路激活是该患者获得性耐药的主要原因,而抑癌基因和衰老相关基因异常表达可能是第二原发肿瘤发生的原因。经验:对老年肿瘤患者治疗前后测序数据进行生物信息学比较具有研究价值。结论:在诊断方面,精准生物信息学分析和重复活检同等重要。在治疗方面,p53基因替代疗法和CAR-T 疗法等潜在治疗手段,需要在衰老相关疾病中加以实践。
RATIONALE: Proto-oncogene-oriented targeted therapy has limited benefits in elderly patients with multiple primary tumors. PATIENT CONCERNS: A woman with anaplastic lymphoma kinase-positive lung adenocarcinoma developed acquired resistance after 3 years of targeted therapy with crizotinib. DIAGNOSES: Diagnosis of unexpected subsequent primary gallbladder tumor. INTERVENTIONS: Lenvatinib was administered therapeutically. Meanwhile, next-generation sequencing results before and after crizotinib treatment were analyzed by comparing the tumor-driving mutation genes with bioinformatics methods. OUTCOMES: The patient died of ascites and liver failure. Furthermore, bypass activation was found to be the main reason for acquired drug resistance for this patient, and the abnormal expression of tumor suppressor genes and senescence-related genes was the likely cause of the second primary tumor. LESSONS: A bioinformatic comparison of pre- and post-treatment sequencing in elderly oncology patients is of interest. CONCLUSIONS: For diagnosing, precision bioinformatics analysis and repeat biopsy are equally valuable. For therapy, potential therapy such as p53 gene replacement therapy and CAR-T therapy need to be practiced for senescence-related conditions.
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