scholarly journals Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 813
Author(s):  
Hao Lin ◽  
Lu Chen ◽  
Weizhong Li ◽  
Zihao Chen
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Squamous Cell ◽  
Data Sets ◽  
High Grade ◽  
Cycle Index ◽  
Hub Proteins ◽  
Mrna Expression Levels

Background: Tongue squamous cell carcinoma (TSCC) patients with high-grade tumors usually suffer from high occurrence and poor prognosis. The current study aimed at finding the biomarkers related to tumor grades and proposing potential therapies by these biomarkers. Methods: The mRNA expression matrix of TSCC samples from The Cancer Genome Atlas (TCGA) database was analyzed to identify hub proteins related to tumor grades. The mRNA expression patterns of these hub proteins between TSCC and adjacent control samples were validated in three independent TSCC data sets (i.e., GSE9844, GSE30784, and GSE13601). The correlation between cell cycle index and immunotherapy efficacy was tested on the IMvigor210 data set. Based on the structure of hub proteins, virtual screening was applied to compounds to find the potential inhibitors. Results: A total of six cell cycle biomarkers (i.e., BUB1, CCNB2, CDC6, CDC20, CDK1, and MCM2) were selected as hub proteins by protein–protein interaction (PPI) analysis. In the validation data sets, the mRNA expression levels of these hub proteins were higher in tumor samples versus normal controls. The cell cycle index was constructed by the mRNA expression levels of these hub proteins, and patients with a high cell cycle index demonstrated favorable drug response to the immunotherapy. Three small molecules (i.e., ZINC100052685, ZINC8214703, and ZINC85537014) were found to bind with hub proteins and selected as drug candidates. Conclusion: The cell cycle index might provide a novel reference for selecting appropriate cancer patient candidates for immunotherapy. The current research might contribute to the development of precision medicine and improve the prognosis of TSCC.

3-MA Enhanced Chemosensitivity in Cisplatin Resistant Hypopharyngeal Squamous Carcinoma Cells via Inhibiting Beclin -1 Mediated Autophagy

2020 ◽  
Vol 26 ◽  
Author(s):  
Jia Zhang ◽  
Wei Mao ◽  
Yuying Liu ◽  
Jian Ding ◽  
Jie Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Survival Rate ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cisplatin Resistance ◽  
Carcinoma Cells ◽  
Fadu Cell ◽  
Fadu Cells

Background: Hypopharyngeal carcinoma is characterized by high degree of malignancy. The most common pathological type is squamous cell carcinoma (HSCC). Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most widely used chemotherapeutic drugs nowadays and cisplatin resistance is a major problem in current treatment strategies. Clinical researches have reported that high autophagy level often caused insensitivity to chemotherapy, a common phenomenon that greatly reduces therapeutic effect in cisplatin-resistant tumor cell lines. 3-methyladenine (3-MA), an inhibitor of PI3K, plays a vital role in the formation and development of autophagosomes. Therefore, we speculate that the use of 3-MA may reduce cisplatin resistance in hypopharyngeal squamous cell carcinoma (HSCC). Methods: Part I: Cisplatin-resistant FaDu cell line (Human hypopharyngeal squamous cell carcinoma cells) was established and cultured. Cell counting kit-8 was used to detect drug resistance. Inverted microscope was used to observe the morphological changes at different concentrations, then the survival rate was calculated. After MDC staining, the autophagic vacuoles were observed by fluorescence microscopy. The expression of Beclin1 from each group was confirmed by RTPCR and Western blot method. Part II: 3-MA was applied for cisplatin-resistant cells intervention, Beclin1 was knocked down by plasmid transfection. Cell cycle was detected using flow cytometry assay, apoptosis with necrosis was detected by staining with propidium iodide (PI). CCK-8 was used to observe the cell survival rate in each group. The expression of autophagy-related protein Beclin1, LC3I, LC3II, Atg-5 and P62 in each group was verified by Western blot analysis. Results: Cisplatin-resistant FaDu cell line can be stably constructed by cisplatin intervention. Compared with normal group, autophagy and its related protein Beclin1 expression was enhanced in cisplatin resistant FaDu cells. Autophagy inhibition group showed significant cell cycle changes, mainly manifested by G1 arrest, increased apoptosis rate and significantly decreased survival rate at 24h level. The number of autophagy vacuoles were significantly reduced in the 3-MA group. Furthermore, Western blot showed that expression of Beclin1, lc3-I, lc3-II, atg-5 protein decreased significantly after 3-MA intervention, while the expression of p62 up-regulated, which also confirmed autophagy flow was blocked. Conclusion: Our work confirmed that enhanced autophagy is an important cause of cisplatin resistance in FaDu cells. The use of 3-MA can significantly reduce autophagy level and arresting its cell cycle, promote apoptosis and reverse the cisplatin resistance condition, this effect is partly mediated by inhibition of Beclin-1 expression. Our data provides a theoretical basis for the application of 3-MA in overcoming cisplatin resistance in hypopharyngeal cancer.

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

2019 ◽  
Vol 19 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Ling Gao ◽  
Jianwei Dong ◽  
Nanyang Zhang ◽  
Zhanxian Le ◽  
Wenhao Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cyclosporine A ◽  
Migration And Invasion ◽  
Signal Molecules ◽  
Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

scholarly journals MicroRNA-527 Induces Proliferation and Cell Cycle in Esophageal Squamous Cell Carcinoma Cells by Repressing PH Domain Leucine-Rich-Repeats Protein Phosphatase 2

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092868 ◽  
Author(s):  
Qingjie Xian ◽  
Ronglei Zhao ◽  
Juanjuan Fu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Protein Phosphatase ◽  
Ph Domain ◽  
Gene Reporter Assay ◽  
Protein Phosphatase 2

Increasing evidence indicated that microRNAs served dominant roles in carcinogenesis and cancer progression by targeting potential downstream genes. In our study, we found that miR-527 was an upregulated expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. Furthermore, overexpression of miR-527 promoted cell proliferation and colony formation, enhanced anchorage-independent growth ability, and contributed to cell cycle. In addition, protein phosphatase 2 (PHLPP2) was identified as the direct downstream target gene of miR-527 and was confirmed by luciferase gene reporter assay. In summary, we concluded that miR-527 acted as an oncogenic microRNA in ESCC development by directly targeting PHLPP2 might be a novel therapeutic target for the treatment of ESCC.

Hyperfractionated Radiation Therapy With or Without Concurrent Low-Dose Daily Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Prospective Randomized Trial

2000 ◽  
Vol 18 (7) ◽  
pp. 1458-1464 ◽  
Author(s):  
Branislav Jeremic ◽  
Yuta Shibamoto ◽  
Biljana Milicic ◽  
Nebojsa Nikolic ◽  
Aleksandar Dagovic ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Low Dose ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
High Grade ◽  
Free Survival

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.

scholarly journals FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest

2015 ◽  
Vol 12 (3) ◽  
pp. 3958-3964 ◽  
Author(s):  
WEI REN ◽  
PANFENG LIAN ◽  
LONG CHENG ◽  
PEIYUN DU ◽  
XIN GUAN ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Cycle Arrest ◽  
Squamous Cell ◽  
Carcinoma Cells ◽  
Tongue Squamous Cell Carcinoma ◽  
Cycle Arrest
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