Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma

Yoshida, Ryoji; Nakayama, Hideki; Nagata, Masashi; Hirosue, Akiyuki; Tanaka, Takuya; Kawahara, Katsunobu; Nakagawa, Yoshihiro; Matsuoka, Yuichiro; Sakata, Junki; Arita, Hidetaka; Hiraki, Akimitsu; Shinohara, Masanori; Ito, Takaaki

doi:10.1038/bjc.2014.539

Cited by 24 publications

(17 citation statements)

References 31 publications

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“…All of the patients were preoperatively treated with a total dose of 30 Gy of concurrent chemoradiotherapy followed by curative surgery as a phase II study (Nagata et al , 2011; Yoshida et al , 2014). Radiotherapy was administered at a daily dose of 2 Gy five times a week for 15 days.…”

Section: Methodsmentioning

confidence: 99%

IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

et al. 2016

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Background:In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC.Methods:Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro. In addition, we investigated the involvement of the Nrf2-antioxidant pathway in IL-6-mediated radioresistant mechanisms using OSCC cell lines and tissues.Results:Increased levels of IL-6 suppressed radiation-induced cell death, and the blockade of IL-6 signalling by tocilizumab sensitised tumour cells to radiation. The radioresistant effect of IL-6 was associated with decreased DNA damage after radiation. We also found that IL-6 promotes the activation of not only the downstream molecule STAT3 but also the Nrf2-antioxidant pathway, leading to a significant decrease in oxidative stress by upregulating Mn-SOD.Conclusions:These results indicate that the blockade of IL-6 signalling combined with conventional radiotherapy could augment the treatment response and survival rate in patients with radioresistant OSCC.

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Section: Methodsmentioning

confidence: 99%

IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

et al. 2016

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“…In addition, blood plasma samples were obtained from 30 of the 52 patients; plasma was separated by centrifugation and stored at −80 • C until subsequent analysis. All patients were treated preoperatively with a total dose of 30 Gy of concurrent chemoradiotherapy, which was followed by curative surgery as a phase II study [38,39]. Radiotherapy was administered daily at 2 Gy five times per week for 15 days.…”

Section: Clinical Samplesmentioning

confidence: 99%

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

Sakata

Hirosue

Yoshida

et al. 2020

Cancers

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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.

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“…Kobayashi et al studied the prognostic effect of NS in invasive breast cancers and reported that cases with positive NS expression exhibited markedly shorter disease-free survival (16). The overexpression of NS in oral squamous cell carcinoma was correlated with advanced T and N stage, and worse prognosis (19). In these reports higher NS expression was associated with malignancy, aggressive behavior, and worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

High nucleostemin expression has a favorable prognostic effect on gastric carcinomas

2018

Turk J Med Sci

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Background/aim: Nucleostemin is a nuclear protein that maintains stem cell features and plays a role as a cell proliferation marker. It also participates in cell cycle regulation by interfering with other intracellular proteins. Recent reports have indicated that this protein plays a role in ribosomal biogenesis and genome protection. High expression level of nucleostemin has been reported in some cancer patients. However, the importance of nucleostemin in gastric cancer needs to be addressed. The aim of this study was to investigate nucleostemin expression in gastric cancer and the effects of this expression on prognosis. Materials and methods: Nucleostemin expression was assessed in 103 patients with gastric carcinomas via immunohistochemistry. Subsequently, relationships between nucleostemin expression and clinicopathological features and prognosis were evaluated. Results: In this study, there were 33 and 70 cases involving high and low nucleostemin expression, respectively. Nucleostemin expression was negatively correlated with lymphovascular invasion, the number of metastatic lymph nodes, extracapsular extension, and T stage. Disease-free survival and overall survival were markedly longer in patients with high nucleostemin expression. Conclusion: We suggest that nucleostemin is a favorable prognostic marker for gastric cancer patients. Our results are in conflict with prior studies. The prognostic effect of nucleostemin in gastric cancer remains to be solved.

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Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma

Cited by 24 publications

References 31 publications

IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

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

High nucleostemin expression has a favorable prognostic effect on gastric carcinomas

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