Head and Neck Squamous cell Carcinoma Targeted Chemosensitization

2009 ◽  
Vol 141 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Mindy R. Figures ◽  
Jessie Wobb ◽  
Koji Araki ◽  
Tingyan Liu ◽  
Lei Xu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Human Head ◽  
Neck Squamous Cell Carcinoma ◽  
Squamous Cell Carcinoma Tumor ◽  
Carcinoma Tumor

OBJECTIVE: The current treatment for advanced head and neck squamous cell carcinoma continues to result in poor outcomes. The purpose of this study is to investigate the benefit of fibroblast growth factor 2-targeted adenovirus-mediated mutant-Rad50 (FGF2-Ad-Rad50) gene transfer in enhancing chemosensitization for head and neck squamous cell carcinoma and reducing chemotoxicity. STUDY DESIGN: Randomized controlled laboratory study. SETTING: University of Pennsylvania, Philadelphia, PA. SUBJECTS AND METHODS: Human head and neck squamous cell carcinoma tumor cells and a mouse model with human head and neck squamous cell carcinoma were used for this study. There were five mice in each study group. FGF2-fab' molecule was conjugated with an adenoviral mutant-Rad50 construct. FGF2-targeted transgene expression efficiency was evaluated in vitro. Tumor cytotoxicity and growth inhibition were examined after combined FGF2-Ad-Rad50 with cisplatin treatment in vitro and in vivo. Anti-tumor mechanisms were investigated. RESULTS: FGF2-targeted gene transfer approach significantly improved transgene expression in head and neck squamous cell carcinoma tumor cells over a nontargeted approach (207.51 ± 33.62 vs 51.44 ± 8.28, respectively). FGF2-Ad-Rad50 with cisplatin demonstrated a superior tumor suppression effect (264.5 ± 124.1 mm 3 vs 567.1 ± 267.6 mm 3 ), increased DNA double-strand breaks (1349 ± 51.67 vs 774 ± 28.56), and anti-angiogenesis (%ROI: 0.76% ± 0.38% vs 2.10% ± 1.66%) in tumor cells over nontargeted adenovirus. CONCLUSION: Combination of FGF2-Ad-Rad50 with cisplatin significantly improves anti-tumor effect by targeting DNA repair systems and tumor angiogenesis. The great benefit of this strategy supports clinical trial for novel treatment of head and neck squamous cell carcinoma.

An Organ Culture System Designed to Study Interaction of Fetal Rat Calvaria with Human Head and Neck Squamous Cell Carcinoma

1988 ◽  
Vol 98 (3) ◽  
pp. 235-241 ◽  
Author(s):  
Barry L. Wenig ◽  
Bettie M. Steinberg ◽  
James J. Sciubba ◽  
Blasco C. Gomes ◽  
Allan L. Abramson
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tumor Cells ◽  
Cell Lines ◽  
Squamous Cell ◽  
Human Head ◽  
Chemotherapeutic Agents ◽  
Neck Squamous Cell Carcinoma ◽  
Fetal Rat

The development of permanent cell lines of human head and neck squamous cell carcinoma in culture has enabled these cell lines to be used to investigate the interaction of the tumor cells with bone. after the squamous carcinoma lines on fetal rat skulls were implanted the explants with their added tumor were maintained in longterm tissue culture by use of the procedures developed for growing these tumor cells. Results confirm direct interaction with the bone by the malignant cells. Specific surface and cytoplasmic markers have been demonstrated by use of monoclonal antibodies against the tumor cells. Furthermore, tumor angiogenesis without the addition of any endogenous endothelial components has been verified. Investigations into the degree of bone infiltration and susceptibility of these interacting tumor cells to various factors, radiation therapy, and chemotherapeutic agents have been carried out. The establishment of a model system for bony invasion by squamous cell carcinoma of the head and neck permits the investigation of the mechanism of tumor invasion and the study of various potential treatment modalities.

scholarly journals JAK Kinase Inhibition Abrogates STAT3 Activation and Head and Neck Squamous Cell Carcinoma Tumor Growth

Neoplasia ◽  
2015 ◽  
Vol 17 (3) ◽  
pp. 256-264 ◽  
Author(s):  
Malabika Sen ◽  
Netanya I. Pollock ◽  
John Black ◽  
Kara A. DeGrave ◽  
Sarah Wheeler ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Kinase Inhibition ◽  
Jak Kinase ◽  
Squamous Cell Carcinoma Tumor ◽  
Carcinoma Tumor

scholarly journals Evaluation of the immunogenicity of ALDHhigh human head and neck squamous cell carcinoma cancer stem cells in vitro

Oral Oncology ◽  
2016 ◽  
Vol 59 ◽  
pp. 30-42 ◽  
Author(s):  
Mark E.P. Prince ◽  
Li Zhou ◽  
Jeffrey S. Moyer ◽  
Huimin Tao ◽  
Lin Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Human Head ◽  
Neck Squamous Cell Carcinoma

scholarly journals CD137 Enhancement of HPV Positive Head and Neck Squamous Cell Carcinoma Tumor Clearance

Vaccines ◽  
2014 ◽  
Vol 2 (4) ◽  
pp. 841-853 ◽  
Author(s):  
Christopher Lucido ◽  
Paola Vermeer ◽  
Bryant Wieking ◽  
Daniel Vermeer ◽  
John Lee
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Squamous Cell Carcinoma Tumor ◽  
Tumor Clearance ◽  
Carcinoma Tumor

scholarly journals The AP-1 complex regulates AXL expression and determines sensitivity to PI3Kα inhibition in esophagus and head and neck squamous cell carcinoma

2018 ◽  
Author(s):  
Mai Bdarny ◽  
Manu Prasad ◽  
Noa Balaban ◽  
Joshua Ben-Zion ◽  
Anat Bahat Dinur ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Resistance Mechanism ◽  
Specific Inhibitor ◽  
Neck Squamous Cell Carcinoma

AbstractAXL overexpression is a common resistance mechanism to anti-cancer therapies, including the resistance to BYL719 (Alpelisib) – the p110α isoform specific inhibitor of phosphoinositide 3-kinase (PI3K) – in esophagus and head and neck squamous cell carcinoma (ESCC, HNSCC respectively). However, the mechanisms underlying AXL overexpression in resistance to BYL719 remain elusive. Here we demonstrated that the AP-1 transcription factors, c-JUN and c-FOS, regulate AXL overexpression in HNSCC and ESCC. The expression of AXL was correlated with that of c-JUN both in HNSCC patients and in HNSCC and ESCC cell lines. Silencing of c-JUN and c-FOS expression in tumor cells downregulated AXL expression and enhanced the sensitivity of human papilloma virus positive (HPVPos) and negative (HPVNeg) tumor cells to BYL719 in vitro. Blocking of the c-JUN N-terminal kinase (JNK) using SP600125 in combination with BYL719 showed a synergistic anti-proliferative effect in vitro, which was accompanied by AXL downregulation and potent inhibition of the mTOR pathway. In vivo, the BYL719-SP600125 drug combination led to the arrest of tumor growth in cell line-derived and patient-derived xenograft models, and in syngeneic head and neck murine cancer models. Collectively, our data suggests that JNK inhibition in combination with anti-PI3K therapy is a new therapeutic strategy that should be tested in HPVPosand HPVNegHNSCC and ESCC patients.

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

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