To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC. K E Y W O R D S drug sensitivity test, organoid culture, orthotopic transplantation, patient-derived xenograft (PDX) model, salivary adenoid cystic carcinoma 1 | INTRODUCTION Adenoid cystic carcinomas (ACC) is one of the most common types of salivary gland malignancies, representing approximately 1% of all head and neck malignancies and about 10% to 15% of all salivary gland cancers. 1,2 Salivary ACC generally represents as slow growth tumor, however, also

F-NLR score was useful to stratify patients to extract poor prognostic characteristics in patients with advanced HPC.

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Background/Aim: We evaluated the impact of FosL1, a member of the activated protein-1 family, on the pathways leading to regional metastasis of head and neck squamous cell carcinoma (HNSCC). Materials and Methods: We examined the influence of small interfering RNA (siRNA) and short heparin RNA (shRNA) mediated knockdown of FosL1 on cell migration, invasion, and proliferation in vitro as well as on regional metastasis in vivo. The prognostic significance of FosL1 was also analyzed using the Kaplan-Meier plotter using data from an HNSCC patient database. Results: Down-regulation of FosL1 inhibited cell migration, invasion, and proliferation in vitro, decreased the incidence of regional metastases, and prolonged the survival of mice in vivo. We also determined that HNSCC patients with higher expression levels of FosL1 had a significantly shorter survival time than those with low expression of FosL1. Conclusion: FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in HNSCC.Head and neck squamous cell carcinoma (HNSCC) patients often have advanced disease with cervical lymph node metastases at the time of diagnosis (1), resulting in poor prognosis despite advances in treatment modalities. Furthermore, treatment failure is often associated with locoregional recurrence in HNSCC patients. The presence of cervical lymph node metastasis is reported as one of the reliable prognostic factors for the survival of patients with HNSCC (2). Therefore, it is necessary to elucidate the mechanisms of cervical lymph node metastases to develop new treatments to improve the survival outcomes of patients with HNSCC.We previously reported that JunB, a member of the AP-1 family, regulates metastatic pathways by promoting cell invasion and migration of HNSCC (3). Thus, AP-1, which forms heterodimers with proteins of the Fos family, the Jun family, musculoaponeurotic fibrosarcoma (Maf), and activating transcription factor (ATF) (4, 5), plays crucial roles in regulating cellular processes such as proliferation, differentiation, death, and survival induced by growth factors, cell-matrix interactions, infections, cytokines, and stresses (6, 7). The Fos family of proteins and c-Jun have also been reported to induce tumorigenesis and metastasis (3,4,(8)(9)(10).These studies led us to characterize the regional metastatic potential in vivo using 14 different HNSCC cell lines in an orthotopic nude mouse model. We performed an upstream and key node analysis using whole-gene microarray data of these lines to determine key molecules associated with the regional metastatic potential of HNSCC. As we identified FosL1 as one of the key molecules associated with the regional metastatic potential of HNSCC, we examined the impact of FosL1 knockdown on cell migration in vitro, as well as cervical lymph node metastasis in vivo, to test the hypothesis that FosL1 could be the key molecule regulating the pathways associated with neck lymph node metastasis in HNSCC.

Background/Aim: We previously presented the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This study aimed to evaluate the prognostic significance of pretreatment inflammatory biomarkers in patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy as a supplementary study of our previous retrospective cohort study. Patients and Methods: The treatment outcomes of 100 patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy were compared according to patient characteristics and pretreatment inflammatory biomarkers using a Cox proportional hazards regression model. Survival was evaluated using the Kaplan-Meier method. Results: In multivariate analysis, a lymphocyte-to-monocyte ratio (LMR) of <1.944 and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 were independent risk factors for poor overall and progression-free survival. Furthermore, we found that the PS-LMR score based on the ECOG PS and LMR could stratify patients to extract the poor prognostic characteristics of R/M-SCCHN patients treated with the EXTREME regimen as first-line therapy. Conclusion: Further evaluation is warranted to study the reliability and applicability of this novel scoring system in predicting the prognosis of R/M-SCCHN patients in the future.