An improved method to build lung cancer PDX models by surgical resection samples and its association with B7-H3 expression.

BACKGROUND: Patient-derived xenograft (PDX) models are biologically stable and can accurately reflect the primary tumor in histopathology and genetic expression in many cancers. In lung cancer, the models' engraftment rate by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and computed tomography (CT)-guided biopsy is exceptionally low, and this limits the development of PDX models in lung cancer research. In this study, we aimed to improve the traditional method, and explore the feasibility and convenience of establishing lung cancer PDX models using the samples directly from surgical resection. We also endeavored to explore the correlation between PDX formation and primary tumor B7-H3 protein expression. METHODS: From September 2017 to July 2018, 24 patients were enrolled in this study. The pathological diagnoses were as follows: 15 adenocarcinomas, 7 squamous cell carcinomas, 1 large cell carcinoma, and 1 small cell carcinoma. The tumor tissues were cut into sizes of 2×2×2 mm3/fragment and inoculated subcutaneously into immunodeficiency mice with a trocar needle. The engrafted tumors were passaged at least 3 generations, and B7-H3 IHC staining was performed on primary tumors. To explore the correlation between PDX formation and B7-H3 protein expression, we also performed H&E staining to evaluate whether the established PDX models could retain the histological features of the primary tumor. RESULTS: Xenograft formation success was achieved in 19 out of 24 cases (79.2%). The time between implantation to tumor formation was an average of 81.5 days (27-154 days) in P1, an average of 44.4 days (14-122 days) in P2, and an average of 26.9 days (12-75 days) in P3. The diameter of the tumor was associated with tumor engraftment: the longer the diameter, the easier engraftment formation was (P=0.0342). The data also suggests that lung cancers with B7-H3 expression greatly induced PDX formation (P=0.0375). The histological characters of each passage resembled the primary tumors. CONCLUSIONS: This study shows that the samples from carefully selected lung cancer by surgical resection can be used for the establishment of PDX models with a high success rate; this improved method is closer to actual clinical work. Compared with the same kind of research, the success rate of the xenograft indicates significant improvement, so this improved method is suitable for promotion and application. The results of H&E staining showed that the histological characters of each passage resembled the primary tumors. Furthermore, the diameter of the tumor was associated with tumor engraftment, and higher B7-H3 expression demonstrated a statistically significant difference compared with the PDX model formation.

[Analysis of correlation between serum thymidine kinase 1 and acute myeloid leukemia].

This study was purposed to investigate the clinical significance of serum thymidine kinase 1 (STK1) level change in acute myeloid leukemia (AML). Peripheral blood samples of 60 newly diagnosed AML patients were collected and the STK1 levels were determined by enhanced chemiluminescent dot-blot method before and at two weeks after start of inductive treatment and in consolidatory treatment. Using non-parametric test, the differences between groups were analyzed. Then the correlation between STK1 level and clinical characteristics was explored by a way of chi-square test. The results indicated that the serum TK1 level in complete remission (CR) or partial remission (PR) AML patients decreased in varying degree as compared to pretreatment (P < 0.05), while there was no significant difference of TK1 level in non-remission (NR) ones (P > 0.05). The serum TK1 level in CR patients remained low level but increased noticeably after relapse into progressive disease (P < 0.05). A significant correlation was found between STK1 level and chromosomal abnormalities, serum LDH level as well as whether had fever in de novo AML patients (P < 0.05). It is concluded that the serum TK1 level change may be applied for reflecting the aggressiveness of disease, monitoring the clinical response to chemotherapy, evaluating the prognosis and predicating the relapse risk. The decrease of TK1 level suggests effective treatment and tumor burden reduction, while its increase indicate poor prognosis and relapse risk.