scholarly journals Overexpression of the Orotate Phosphoribosyl-Transferase Gene Enhances the Effect of 5-Fluorouracil in Head and Neck Squamous Cell CarcinomaIn Vitro

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Ryuji Yasumatsu ◽  
Torahiko Nakashima ◽  
Shizuo Komune
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Head And Neck ◽  
Squamous Cell ◽  
Orotate Phosphoribosyltransferase ◽  
Anabolic Pathway ◽  
Hnscc Cell ◽  
Hnscc Cell Line

5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). In the anabolic pathway of 5-FU, the first step in activation of the drug is phosphorylation of 5-FU by orotate phosphoribosyltransferase (OPRT), which directly metabolizes 5-FU to 5-fluorouridine monophosphate (FUMP) in the presence of 5-phosphoribosyl-1-pyrophosphate. To date, OPRT expression in the tumors has been related to the clinical response or survival of cancer patients receiving 5-FU-based chemotherapy. In this study, we examined whether OPRT expression correlates with the chemosensitivity to 5-FU and cell proliferation in HNSCC. We constitutively expressed an OPRT cDNA in an HNSCC cell line. The effects of OPRT expression onin vitrocell growth and 5-FU cytotoxicity were examined. OPRT transfection increases the cytotoxicity of 5-FU without affecting cell proliferation of HNSCC cellsin vitro. These results indicate that OPRT expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy.

scholarly journals Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3046
Author(s):  
Ming-Huei Chou ◽  
Hui-Ching Chuang ◽  
Yu-Tsai Lin ◽  
Ming-Hsien Tsai ◽  
Ying-Hsien Kao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Xenograft Model ◽  
Mtor Inhibitors ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hnscc Cell ◽  
Proliferation And Migration

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

scholarly journals The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma

2020 ◽  
Vol 22 ◽  
Author(s):  
Chumin Zhou ◽  
Jason L. Parsons
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Survival Rates ◽  
Cell Cycle Checkpoint ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv Status ◽  
Hnscc Cell

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with reported incidences of ~800 000 cases each year. One of the critical determinants in patient response to radiotherapy, particularly for oropharyngeal cancers, is human papillomavirus (HPV) status where HPV-positive patients display improved survival rates and outcomes particularly because of increased responsiveness to radiotherapy. The increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and repair of DNA double-strand breaks. Therefore, strategies to further radiosensitise HPV-positive HNSCC, but also radioresistant HPV-negative HNSCC, have focussed on targeting key DNA repair proteins including PARP, DNA-Pk, ATM and ATR. However, inhibitors against CHK1 and WEE1 involved in cell-cycle checkpoint activation have also been investigated as targets for radiosensitisation in HNSCC. These studies, largely conducted using established HNSCC cell lines in vitro, have demonstrated variability in the response dependent on the specific inhibitors and cell models utilised. However, promising results are evident targeting specifically PARP, DNA-Pk, ATR and CHK1 in synergising with radiation in HNSCC cell killing. Nevertheless, these preclinical studies require further expansion and investigation for translational opportunities for the effective treatment of HNSCC in combination with radiotherapy.

scholarly journals Sprouty2 protein is downregulated in human squamous cell carcinoma of the head and neck and suppresses cell proliferation in vitro

2014 ◽  
Vol 11 (1) ◽  
pp. 547-554 ◽  
Author(s):  
CHIANG-LIANG LIN ◽  
WEI-FAN CHIANG ◽  
CHAO-LING TUNG ◽  
JENG-LONG HSIEH ◽  
JENN-REN HSIAO ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Human Squamous Cell Carcinoma ◽  
Proliferation In Vitro

scholarly journals Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib

2021 ◽  
Vol 27 ◽  
Author(s):  
Fangling Hu ◽  
Liang Guo ◽  
Jieqing Yu ◽  
Daofeng Dai ◽  
Yuanping Xiong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Nuclear Antigen ◽  
Tumor Tissues

Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end.Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo.Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis.Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.

scholarly journals Identification of CCT3 as a prognostic factor and correlates with cell survival and invasion of head and neck squamous-cell carcinoma

2021 ◽  
Author(s):  
Yan Wang ◽  
Peicheng Liu ◽  
Ziwei Zhang ◽  
Jiulong Wang ◽  
Zhigang Cheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Cell Survival ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Clinicopathological Parameters ◽  
Hnscc Cell

Background: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Chaperonin-containing TCP-1 3 (CCT3) folds cancer-related proteins to control carcinogenesis. The prognostic value and growth association of CCT3 and HNSCC remains unknown. Methods: The GEO, Oncomine and UALCAN databases were used to examine CCT3 expression in HNSCC. A few clinical HNSCC samples with normal tissues were used to detect CCT3 expression by using immunohistochemistry method. The TCGA-HNSC dataset was used to evaluate the association between expression of CCT3 and prognosis. The molecular mechanism was investigated with gene set enrichment analysis (GSEA). CCK-8 and wound healing assays were used to detect cell growth and invasion of HNSCC, respectively. Results: CCT3 expression was significantly upregulated in HNSCC in both mRNA and protein levels. In addition, upregulated CCT3 expression was associated with various clinicopathological parameters. High expression of CCT3 was significantly correlated with inferior survival of HNSCC patients. Knockdown of CCT3 significantly inhibited cell growth and invasion of HNSCC cell lines. GSEA analysis indicated that CCT3 was closely correlated with tumor-related signaling pathways and HNSCC cell survival. Conclusion: Our findings suggest that CCT3 is a biomarker of poor prognosis and related to the process of HNSCC.

scholarly journals Cisplatin exposure causes c-Myc-dependent resistance to CDK4/6 inhibition in HPV-negative head and neck squamous cell carcinoma

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Anthony M. Robinson ◽  
Richa Rathore ◽  
Nathan J. Redlich ◽  
Douglas R. Adkins ◽  
Todd VanArsdale ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Growth Effect ◽  
Intrinsic Resistance ◽  
Hnscc Cell

AbstractThe loss of p16 is a signature event in Human Papilloma Virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) that leads to increased Cyclin Dependent Kinase 4/6 (CDK) signaling. Palbociclib, a CDK4/6 inhibitor, is active for the treatment of a subset of HNSCC. In this study, we analyzed patient response data from a phase I clinical trial of palbociclib in HNSCC and observed an association between prior cisplatin exposure and CDK inhibitor resistance. We studied the effects of palbociclib on cisplatin-sensitive and -resistant HNSCC cell lines. We found that while palbociclib is highly effective against chemo-naive HNSCC cell lines and tumor xenografts, prior cisplatin exposure induces intrinsic resistance to palbociclib in vivo, a relationship that was not observed in vitro. Mechanistically, in the course of provoking a DNA damage-resistance phenotype, cisplatin exposure upregulates both c-Myc and cyclin E, and combination treatment with palbociclib and the c-Myc bromodomain inhibitor JQ1 exerts a synergistic anti-growth effect in cisplatin-resistant cells. These data show the benefit of exploiting the inherent resistance mechanisms of HNSCC to overcome cisplatin- and palbociclib resistance through the use of c-Myc inhibition.

Comparison of in vivo and in vitro prostaglandin E production by squamous cell carcinoma of the head and neck

1994 ◽  
Vol 111 (3) ◽  
pp. 189-196 ◽  
Author(s):  
C SNYDERMAN ◽  
I KLAPAN ◽  
M MILANOVICH ◽  
D HEO ◽  
R WAGNER ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prostaglandin E
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