scholarly journals Selective inhibition of PI3K110α as a novel therapeutic strategy for cetuximab‑resistant oral squamous cell carcinoma

2020 ◽  
Vol 44 (3) ◽  
pp. 863-872
Author(s):  
Hiroki Tsuchihashi ◽  
Tomofumi Naruse ◽  
Souichi Yanamoto ◽  
Kohei Okuyama ◽  
Kohei Furukawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Strategy ◽  
Selective Inhibition ◽  
Novel Therapeutic

Selective Inhibition of Cyclooxygenase 2 Induces p27kip1 and skp2 in Oral Squamous Cell Carcinoma

2003 ◽  
Vol 32 (04) ◽  
pp. 226 ◽  
Author(s):  
Antti A. Mäkitie ◽  
Monica Chau ◽  
Steve Lim ◽  
Mary-Anne Viani ◽  
Ralph Gilbert ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Selective Inhibition ◽  
Cyclooxygenase 2

Increased Phosphatidylserine on Blood Cells in Oral Squamous Cell Carcinoma

2019 ◽  
Vol 98 (7) ◽  
pp. 763-771 ◽  
Author(s):  
Y. Liu ◽  
B. Li ◽  
T.L. Hu ◽  
T. Li ◽  
Y. Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Confocal Microscopy ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Blood Cells ◽  
Therapeutic Strategy ◽  
Stage Iii ◽  
Healthy Controls ◽  
Rapid Coagulation

The specific function of phosphatidylserine (PS) in the context of the development of a hypercoagulable state among individuals with oral squamous cell carcinoma (OSCC) is uncertain. The goal of this study was therefore to assess the exposure of PS on microparticles (MPs) as well as on endothelial and blood cells and to assess procoagulant activity (PCA) as a function of the stage of OSCC progression. We recruited patients with OSCC ( n = 63) as well as healthy controls ( n = 26) to participate in this study. PS exposure was then assessed via confocal microscopy and flow cytometry, revealing that patients with stage III/IV OSCC exhibited higher frequencies of PS-exposing blood cells, MPs, and serum-cultured endothelial cells (ECs) than did patients with stage I/II OSCC or healthy controls. When we conducted functional coagulation assays, we discovered that PS+blood cells, MPs, and serum-cultured ECs from patients with stage III/IV OSCC mediated more rapid coagulation and more substantial production of FXa, thrombin, and fibrin as compared with controls. When samples were treated with the PS antagonist lactadherin, this resulted in an 80% disruption of PCA. Strikingly, when pre- and postoperative samples were compared from patients with stage III/IV OSCC undergoing resective surgery, PCA was significantly reduced in the postoperative samples. After stimulating ECs with inflammatory cytokines, we found by confocal microscopy that they expose PS on their cell membranes, thus generating FVa and FXa binding sites and mediating the formation of fibrin. Together our findings provide evidence that PS+blood cells and MPs are important mediators of the development of a hypercoagulable and prothrombotic state among individuals afflicted by advanced-stage OSCC. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.

scholarly journals Oncogenic role of MiR-130a in oral squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karthik Mallela ◽  
Swamy Shivananda ◽  
Kodaganur S. Gopinath ◽  
Arun Kumar
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Strategy ◽  
Inverse Correlation ◽  
Migration And Invasion ◽  
Cellular Functions

AbstractAberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3′UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3′UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but also the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC.

scholarly journals Oncogenic Role of miR-130a in Oral Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Karthik Mallela ◽  
Shivananda Swamy ◽  
K. Gopinath ◽  
Arun Kumar
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Strategy ◽  
Inverse Correlation ◽  
Migration And Invasion ◽  
Cellular Functions

Abstract Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3’UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3’UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC.

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