Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival

Theocharis, Stamatios; Klijanienko, Jerzy; Giaginis, Constantinos; Rodriguez, José; Jouffroy, Thomas; Girod, Angélique; Alexandrou, Paraskevi; Sastre-Garau, Xavier

doi:10.1111/j.1600-0714.2011.01031.x

Cited by 45 publications

(40 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of HDAC1 (and not HDAC2) in tongue squamous cell carcinoma is associated with poor differentiation of stages and lymph node metastasis (47). The siRNA targeting HDAC1 in OSCC cell line led to a decrease in cell proliferation and an increase in cell apoptosis (48).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and influence of Notch signaling in oral squamous cell carcinoma

Osathanon

Nowwarote

Pavasant

2016

Journal of Oral Science

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…HDACs are involved in oral cancer formation and progression (47). Overexpression of HDAC1 (and not HDAC2) in tongue squamous cell carcinoma is associated with poor differentiation of stages and lymph node metastasis (47).…”

Section: Discussionmentioning

confidence: 99%

Expression and influence of Notch signaling in oral squamous cell carcinoma

Osathanon

Nowwarote

Pavasant

2016

Journal of Oral Science

View full text Add to dashboard Cite

“…In oral tongue cancer (generally HPV-negative) it has been demonstrated that HDAC1 and 2 are overexpressed and associated with significantly shorter progression-free survival (PFS) [30]. Moreover, in several clinical studies the measurement of histone acetylation on PBMC has been studied as a surrogate marker of HDACi activity; however, in most cases this measurement has not been successfully linked to clinical outcome.…”

Section: Rationalementioning

confidence: 99%

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial

et al. 2016

View full text Add to dashboard Cite

BackgroundRecurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR.Method/DesignV-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day −14 with a titration strategy in each patient (target serum level of 50–100 μg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety.Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment.DiscussionOverall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents.EudraCT Number2014-001523-69Trial registrationClinicalTrials.gov number, NCT02624128

show abstract

“…[29] [34] [30] In this environment, psoriatic keratinocytes produce high quantities of VEGF via HIF-1alpha that is not ubiquitinated by VHL due to the intervention of HDAC1 and LL-37. e same phenomenon could be occurring in squamous cell carcinoma (SCC) as HDAC1 overexpression has been observed in this cancer [35] and because in oral squamous cell cancinoma, VEGF is over-expressed and is reg ulate d by H I F-1a lpha under hyp oxic conditions. [36][37] In the same way, the dysfunction of VHL is also associated with the development of tongue cancer [39] as well as in psoriasis.…”

Section: Discussionmentioning

confidence: 97%

Vascular endothelial growth factor production is induced by histone deacetylase 1 and suppressed by von Hippel-Lindau protein in HaCaT cells

Reynoso-Roldán

Roldán

Cancino‐Díaz³

et al. 2012

CIM

View full text Add to dashboard Cite

Purpose: In hypoxic tumoral tissues, vascular endothelial growth factor (VEGF) expression is positively regulated by histone deacetylase 1 (HDAC1) and negatively regulated by the tumour suppressor protein von Hippel-Lindau (VHL) via hypoxia induced factor-1 alpha (HIF-1alpha). It has been reported that VEGF, HDAC1 and LL-37, but not VHL, are over-expressed in psoriatic skin. Although HIF-1alpha is constitutively expressed in normal keratinocytes, it is not known if HDAC1 and VHL can regulate VEGF production in these cells.Methods: e participation of HDAC1 and VHL in the regulation of VEGF expression in HDAC1-, VHL-and LL-37-transfected HaCaT cells, and in HaCaT cells treated with HDAC1 inhibitors, was studied.Results: e production of VEGF was increased in HDAC1-and LL-37-transfected HaCaT cells and maintained in VHL-transfected cells under hypoxic conditions; meanwhile, VEGF production decreased in HaCaT cells treated with TSA, in cells transfected with HDAC1-siRNA, in cells co-transfected with HIF-1alpha-siRNA and pHDAC-1 and in VHL-transfected HaCaT cells. e levels of cytoplasmic HIF-1alpha were high in pLL37-transfected cells and low in pVHL-and pHDAC1-transfected cells; however, HIF-1alpha was detected in the nucleus of the HDAC1-transfected cells. e expression of VEGF was high in cells co-transfected with pHDAC1-and pLL-37, and the expression decreased when pVHL was present.Conclusions: ese data demonstrate that HDAC1, LL-37 and VHL can modulate the production of VEGF via HIF-1alpha in HaCaT cells.

show abstract

Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival

Abstract: The present study supported evidence that HDACs may participate in the formation and progression of mobile tongue SCC, reinforcing their possible use as biomarkers as also the therapeutic utility of HDAC inhibitors in mobile tongue SCC chemoprevention and treatment.

Cited by 45 publications

References 55 publications

Expression and influence of Notch signaling in oral squamous cell carcinoma

Expression and influence of Notch signaling in oral squamous cell carcinoma

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial

Vascular endothelial growth factor production is induced by histone deacetylase 1 and suppressed by von Hippel-Lindau protein in HaCaT cells

Contact Info

Product

Resources

About