記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: It is difficult to accurately predict occult cervical lymph node metastasis, a major factor that significantly influences treatment outcomes in patients with clinical stage I/II tongue cancer. This study aimed to develop a predictive model for occult cervical lymph node metastasis in patients with stage I/II tongue cancer based on clinical and histopathological findings. METHODS: This multicenter cross-sectional study analyzed the archived pathological specimens and clinical records of patients diagnosed with stage I/II tongue cancer between January 2012 and March 2020 at seven institutions in Japan. All patients underwent transoral partial glossectomy with elective neck dissection, and the histological depth of invasion (DOI) was confirmed to be 3-10 mm. The clinicopathological features of the primary tumors were compared with those of occult cervical lymph node metastases. Predictive factors for occult cervical lymph node metastasis were identified using the least absolute shrinkage and selection operator (LASSO) regression model, and the model performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: In total, 106 patients were included in this study. The LASSO regression analysis identified three significant predictors of occult cervical lymph node metastasis: vascular invasion, poorly differentiated clusters (PDC), and DOI. The predictive model incorporating these factors achieved an area under the curve (AUC) of 0.713. CONCLUSION: Vascular invasion, PDC, and DOI are the key histopathological predictors of occult cervical lymph node metastasis in early-stage tongue cancer. External validation in larger cohorts is warranted to validate the utility of the predictive model developed in this study.

DOI： 10.1007/s10147-026-03033-y

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The AJCC cutoff value of 2 mm for the extranodal extension (ENE) distance was determined from an analysis of patients with or without adjuvant therapy. The purpose of this study was to find out the ENE distance that reflects prognosis only in patients with head and neck squamous cell carcinoma (SCC) who received adjuvant therapy. METHODS: The ENE distance was defined for 109 patients who underwent surgery for SCC of larynx or hypopharynx as a primary tumor. RESULTS: To standardize patient conditions, only 26 patients who received additional postoperative treatment were analyzed. Receiver operating characteristic analysis of the ENE distance for overall survival (OS) and recurrence-free survival (RFS) yielded a cutoff value of 4250 μm. Multivariate analysis showed that the ENE distance was an independent poor prognostic factor for OS and RFS. CONCLUSION: The optimal ENE distance cutoff for OS and RFS in postoperatively treated patients was 4250 μm.

DOI： 10.1002/hed.28090

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We previously established a patient-derived xenograft (PDX) model, patient-derived organoids (PDOs), and PDX-derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2-positive SDC. METHODS: The therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice. RESULTS: The siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice. CONCLUSION: For the first time, we demonstrated the efficacy of anti-HER2 therapy in HER2-positive SDC using preclinical models of SDC PDX and PDXO.

DOI： 10.1002/hed.27395

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This study aimed to identify key molecules associated with the survival of patients with hypopharyngeal squamous cell carcinoma (HpSCC) by combining in silico and in vitro analyses. MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened using the Gene Expression Omnibus database. For DEGs, we performed functional enrichment and protein-protein interaction network analyses to identify potential biological functions and hub genes. Functional analysis of HpSCC cell lines verified the critical roles of the hub genes. RESULTS: DEGs were associated with the extracellular matrix. Among the hub genes, high expression of prolyl 4-hydroxylase subunit alpha 1 (P4HA1) was significantly associated with shorter survival. In addition, P4HA1 knockdown inhibited cell migration and colonization. Suppression of cell proliferation was demonstrated using P4HA1-selective inhibitors. CONCLUSION: P4HA1 may be a useful therapeutic target for the treatment of HpSCC.

DOI： 10.21873/anticanres.16424

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study was to generate experimental human SGC models of multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. METHODS: Tumor specimens from surgically resected SGCs were processed for the preparation of PDXs and patient-derived organoids (PDOs). Specimens from SGC PDXs were also processed for PDX-derived organoid (PDXO) generation. In vivo tumorigenicity was assessed using orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumors using immunohistochemistry. RNA-seq was used to analyze the genetic traits of our models. RESULTS: Three series of PDOs, PDXs and PDXOs of salivary duct carcinomas, one series of PDOs, PDXs and PDXOs of mucoepidermoid carcinomas and PDXs of myoepithelial carcinomas were successfully generated. We found that PDXs and orthotopic transplants from PDOs/PDXOs showed similar histological features as the original tumors. Our models also retained their genetic traits, i.e., transcription profiles, genomic variants and fusion genes of the corresponding histological subtypes. CONCLUSION: We report the generation of SGC PDOs, PDXs and PDXOs of multiple histological subtypes, recapitulating the histological and genetical characteristics of the original tumors. These experimental SGC models may serve as a useful resource for the development of novel therapeutic strategies and for investigating the molecular mechanisms underlying the development of these malignancies.

DOI： 10.1007/s13402-022-00758-6

PubMed

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

J-GLOBAL

researchmap

記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

researchmap

記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

researchmap