Molecularly-targeted therapy for the oral cancer stem cells

Ohnishi, Yozo; Yasui, Hirofumi; Nozaki, Masami; Nakajima, Masahiro

doi:10.1016/j.jdsr.2017.11.001

Cited by 20 publications

(17 citation statements)

References 58 publications

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“…In this study, we utilized live-cell imaging and time-lapse analysis, which revealed that cetuximab treatment significantly reduced cell motility. Previous investigators reached the same conclusion after performing cell-migration assays 25 , 42 , 43 . Thus, we conclude that reduced cell motility was associated with a high cell density.…”

Section: Discussionsupporting

confidence: 53%

Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma

Okuyama

Suzuki

Naruse

et al. 2021

Sci Rep

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Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is an efficient anti-tumor therapeutic agent that inhibits the activation of EGFR; however, data related to the cellular effects of prolonged cetuximab treatment are limited. In this study, the long-term cellular outcome of prolonged cetuximab treatment and the related molecular mechanism were explored in a head and neck squamous cell carcinoma cell line constitutively expressing a fluorescent ubiquitination-based cell cycle indicator. Fluorescent time-lapse imaging was used to assess clonal growth, cell motility, and cell-cycle progression. Western blot analysis was performed to measure the level of phosphorylation and protein-expression following cetuximab treatment. Over 5 days cetuximab treatment decreased cell motility and enhanced G1 phase cell arrest in the central region of the colonies. Significantly decreased phosphorylation of retinoblastoma, Skp2, and Akt-mTOR proteins, accumulation of p27Kip1, and induction of type II LC3B were observed over 8 days cetuximab treatment. Results of the present study elucidate the cetuximab-dependent inhibition of cell migration, resulting in high cell density-related stress and persistent cell-cycle arrest at G1 phase culminating in autophagy. These findings provide novel molecular insights related to the anti-tumor effects of prolonged cetuximab treatment with the potential to improve future therapeutic strategy.

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Section: Discussionsupporting

confidence: 53%

Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma

Okuyama

Suzuki

Naruse

et al. 2021

Sci Rep

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“… 2 In recent years, with the development of targeted drugs, the prognosis for patients with OSCC has been extended. 14 , 15 Immune checkpoint inhibitors have also shed light on the treatment of OSCC, and inflammation and immunity have been involved in the development of OSCC. 16 However, the immunological characteristics of OSCC are still largely uncovered.…”

Section: Discussionmentioning

confidence: 99%

<p>Inflammatory Marker Predicts Outcome of Oral Squamous Cell Carcinoma Receiving Chemo-Radiotherapy</p>

Sun

Gao

2020

CMAR

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Background: Inflammation is involved in the progression of oral squamous cell carcinoma. We therefore postulate that a blood-based inflammatory marker, the neutrophil-tolymphocyte ratio, could help to predict the prognosis in patients with oral squamous cell carcinoma receiving chemo-radiotherapy, and build a prognostic nomogram. Methods: In 111 cases of oral squamous cell carcinoma, several baseline variables, including inflammatory markers and lactate dehydrogenase, were measured within the week of chemoradiotherapy initiation as predictors of mortality and separate risk scores were developed. Results: Dichotomized neutrophil-to-lymphocyte ratio was found to be associated with AJCC stage (p<0.001). Patients with oral squamous cell carcinoma with a low neutrophil-tolymphocyte ratio survived longer than those with a high neutrophil-to-lymphocyte ratio (overall survival HR=2.39, 95% CI 1.24-4.61, p=0.009). The Harrell's concordance (C)-statistic of the nomogram was 0.74 and the calibration curve demonstrated the goodness of fit. Conclusion: The inflammatory marker neutrophil-to-lymphocyte ratio, obtained before chemo-radiotherapy, was an independent factor of survival prediction for oral squamous cell carcinoma. The nomogram incorporating immunological markers could more accurately predict individualized survival probability than the existing models. These findings are significant for the creation of personalized treatment strategies in the clinical setting.

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“…Previous studies on the pathogenesis of oral cancer have identified a considerable number of molecular pathways involved in the development and progression of this disease ( 8 , 9 ). In effect, some of the altered signaling pathways involved in oral cancer have been proven to be potential targets for the development of anti-cancer therapies ( 10 ). Long non-coding RNAs (lncRNAs, >200 nt) encode no proteins but participate in cancer biology by regulating cancer-related gene expression ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

lncRNA UASR1 is overexpressed in oral squamous cell carcinoma and regulates cancer cell proliferation by regulating miR‑375/JAK2 axis

2021

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Long non-coding RNAs (lncRNAs) have been confirmed to participate in cancer regulation, including oral squamous cell carcinoma (OSCC). The aim of the present study was to investigate the role of UASR1 in OSCC. The expression levels of UASR1, miR-375 and JAK2 were detected in OSCC tissues by reverse transcriptase quantitative PCR. The targets of UASR1 were predicted by IntaRNA. Colony formation and CCK-8 assays were conducted to estimate cell proliferation. Western blotting was used to detect the protein expression of JAK2. The results demonstrated that UASR1 was upregulated in OSCC tissues compared with non-tumor tissues, and the high level of UASR1 expression was associated with poor overall survival. UASR1 is predicted to interact with miR-375 and the interaction was confirmed by Dual-luciferase activity assay. However, overexpression of UASR1 and miR-375 did not affect the expression of each other. Instead, upregulation of JAK2, a target of miR-375, was observed after the overexpression of UASR1 in OSCC cells. Moreover, overexpression of UASR1 attenuated the inhibitory effects of miR-375 on the expression of JAK2 and cell proliferation. Therefore, UASR1 is overexpressed in OSCC and regulates cancer cell proliferation by regulating the miR-375/JAK2 axis.

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Molecularly-targeted therapy for the oral cancer stem cells

Cited by 20 publications

References 58 publications

Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma

Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma

<p>Inflammatory Marker Predicts Outcome of Oral Squamous Cell Carcinoma Receiving Chemo-Radiotherapy</p>

lncRNA UASR1 is overexpressed in oral squamous cell carcinoma and regulates cancer cell proliferation by regulating miR‑375/JAK2 axis

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