コウコウ ヘンペイ ジョウヒ ガン ノ ハツガン オヨビ チリョウ テイコウセイ ニ オケル SMAD4 ノ ヤクワリ

博士(医学)熊本大

Efficacy of adjuvant chemotherapy with S-1 in stage II oral squamous cell carcinoma patients: A comparative study using the propensity score matching method.

It has been reported that 20% of early-stage oral squamous cell carcinoma (OSCC) patients treated with surgery alone (SA) may exhibit postoperative relapse within 2-3 years and have poor prognoses. We aimed to determine the safety of S-1 adjuvant chemotherapy and the potential differences in the disease-free survival (DFS) between patients with T2N0 (stage II) OSCC treated with S-1 adjuvant therapy (S-1) and those treated with SA. This single-center retrospective cohort study was conducted at Kumamoto University, between April 2004 and March 2012, and included 95 patients with stage II OSCC. The overall cohort (OC), and propensity score-matched cohort (PSMC) were analyzed. In the OC, 71 and 24 patients received SA and S-1, respectively. The time to relapse (TTR), DFS, and overall survival were better in the S-1 group, but the difference was not significant. In the PSMC, 20 patients each received SA and S-1. The TTR was significantly lower in the S-1 group than in the SA group, while the DFS was significantly improved in the former. S-1 adjuvant chemotherapy may be more effective than SA in early-stage OSCC

HMGA2 Contributes to Distant Metastasis and Poor Prognosis by Promoting Angiogenesis in Oral Squamous Cell Carcinoma

The highly malignant phenotype of oral squamous cell carcinoma (OSCC), including the presence of nodal and distant metastasis, reduces patient survival. High-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor that is involved in advanced malignant phenotypes and poor prognosis in several human cancers. However, its biological role in OSCC remains to be elucidated. The purpose of this study was to determine the clinical significance and role of HMGA2 in the malignant potential of OSCC. We first investigated the expression pattern of HMGA2 and its clinical relevance in 110 OSCC specimens using immunohistochemical staining. In addition, we examined the effects HMGA2 on the regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, which are related to angiogenesis, in vitro. High expression of HMGA2 was significantly correlated with distant metastasis and poor prognosis. Further, HMGA2 depletion in OSCC cells reduced the expression of angiogenesis genes. In OSCC tissues with high HMGA2 expression, angiogenesis genes were increased and a high proportion of blood vessels was observed. These findings suggest that HMGA2 plays a significant role in the regulation of angiogenesis and might be a potential biomarker to predict distant metastasis and prognosis in OSCC

Additional file 2: Figure S2. of Pre-treatment neutrophil to lymphocyte ratio predicts the chemoradiotherapy outcome and survival in patients with oral squamous cell carcinoma: a retrospective study

The relationship between the NLR status and cancer-specific survival in patients with OSCC. In the Kaplan-Meier survival analysis of patients with oral squamous cell carcinoma (OSCC), the patients were divided into three groups based on their NLR status (Tertiles 1, 2 and 3). (A) The overall survival (OS) of the 124 OSCC patients stratified by their NLR status. (B) The disease-free survival (DFS) of the 124 OSCC patients stratified by their NLR status. (JPG 974 kb

Additional file 1: Figure S1. of Pre-treatment neutrophil to lymphocyte ratio predicts the chemoradiotherapy outcome and survival in patients with oral squamous cell carcinoma: a retrospective study

The relationships between the NLR status and cancer-specific survival in patients with OSCC. In the Kaplan-Meier survival analysis of patients with oral squamous cell carcinoma (OSCC), the patients were divided into two groups (low and high groups) based on the average NLR value (=2.7). (A) Overall survival (OS) of the 124 OSCC patients based on their NLR status. (B) Disease-free survival (DFS) of the 124 OSCC patients based on their NLR status. (JPG 867 kb

Enhanced Expression of IGFBP-3 Reduces Radiosensitivity and Is Associated with Poor Prognosis in Oral Squamous Cell Carcinoma

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) modulates various cell functions through IGF-dependent or independent mechanisms. However, its biological roles in the radiosensitivity of oral squamous cell carcinoma (OSCC) remain largely unknown. The purpose of this study was to determine the clinical significance and molecular mechanisms of the association between IGFBP-3 and OSCC radiosensitivity. We performed an immunohistochemical analysis of IGFBP-3 in 52 OSCC specimens from patients treated with preoperative chemoradiotherapy and surgery (phase II study). Associations between IGFBP-3 expression and clinicopathological features were also evaluated. In addition, we examined the effects of IGFBP-3 on post-X-ray irradiation radiosensitivity and DNA damage in vitro. High IGFBP-3 expression was significantly correlated with poor chemoradiotherapy responses and prognosis. With IGFBP-3 knockdown, irradiated OSCC cells exhibited significantly higher radiosensitivity compared with that of control cells. Moreover, IGFBP-3 depletion in OSCC cells reduced phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is required for DNA double-strand break repair during non-homologous end joining. These findings indicate that IGFBP-3 may have a significant role in regulating DNA repair and is be a potential biomarker for predicting clinical response to radiotherapy and prognosis in OSCC