Interest of new alkylsulfonylhydrazide-type compound in the treatment of alcohol use disorders.

Rationale: Recent preclinical research suggested that histone deacetylase inhibitors (HDACIs) and specifically class I HDAC selective inhibitors might be useful to treat alcohol use disorders (AUDs).

Objective: The objective of this study was to find a new inhibitor of the HDAC-1 isoenzyme and to test its efficacy in an animal model of AUDs.

Methods: In the present study, we prepared new derivatives bearing sulfonylhydrazide-type zinc-binding group (ZBG) and evaluated these compounds in vitro on HDAC-1 isoenzyme.

Variation of the epidermal expression of glucocorticoid receptor-beta as potential predictive marker of bullous pemphigoid outcome.

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease in Western countries. Although topical and/or systemic glucocorticoids treatment efficacy is widely recognized, up to 30% of patients with BP may undergo a relapse during the first year of treatment. We investigated the protein expression of the total glucocorticoid receptor and GRβ isoform in the skin biopsy specimens from patients with BP and wondered whether such investigation at baseline provided a tool to predict disease outcome.

Histone deacetylases meet microRNA-associated MMP-9 expression regulation in glucocorticoid-sensitive and -resistant cell lines.

Glucocorticoids are largely used in the treatment of inflammatory pathologies and/or hematological malignancies and regulate the expression of a variety of genes involved in inflammation or metastasis such as matrix metalloproteinases (MMP). Long-term exposure to glucocorticoids can result in failure of responsiveness, which is often associated with an unwanted gene expression. Epigenetic mechanisms are involved in gene expression modulated after development of glucocorticoid resistance but how these mechanisms take place must be further studied.

The DNA hypomethylating agent, 5-aza-2'-deoxycytidine, enhances tumor cell invasion through a transcription-dependent modulation of MMP-1 expression in human fibrosarcoma cells.

In diseases such as cancer, cells need to degrade the extracellular matrix (ECM) and therefore require high protease levels. Thus, aberrant tissue degradation is associated to matrix metalloproteinases (MMPs) overexpression resulting from different mechanisms including epigenetic events. One of the most characterized epigenetic mechanisms is DNA methylation causing changes in chromatin conformation, thereby decreasing the accessibility to the transcriptional machinery and resulting in a robust gene silencing.

Regulation of MMPs during melanoma progression: from genetic to epigenetic.

Melanoma is the most severe skin cancer characterized by a bad prognosis at metastatic stages due to resistance to most classical chemotherapies. Invasion of melanoma cells into the surrounding microenvironment locally and at distance of the primary tumour, is facilitated by expression of proteases that degrade the extracellular matrix. Matrix metalloproteinases (MMP) have been long thought as potential therapeutic targets as they are involved in several steps of tumour progression.

Raman microspectroscopy detects epigenetic modifications in living Jurkat leukemic cells.

Aims: Classical biochemical and molecular methods for discerning cells with epigenetic modifications are often biologically perturbing or even destructive. We wondered whether the noninvasive laser tweezer Raman spectroscopy technique allowed the discrimination of single living human cells undergoing epigenetic modifications.

Materials & Methods: Human Jurkat leukemic cells were treated with inhibitors of histone deacetylases (trichostatin A and MS-275).

Epigenetic regulation of proMMP-1 expression in the HT1080 human fibrosarcoma cell line.

The matrix metalloproteinase (MMP) family members play an important role in various physiological and pathological processes. Although MMP-1 (collagenase-1) has been shown to be involved in tumor invasiveness, the regulation of its expression is still not fully elucidated and could implicate epigenetic mechanisms. The aim of this study was to analyze the effects of the Histone Deacetylase Inhibitor (HDI) trichostatin A (TSA) and the inhibitor of DNA methylation 5-aza-2'-deoxycytidine (5-azadC) on the proMMP-1 expression in the human HT1080 fibrosarcoma cell line.

Thalidomide alters nuclear architecture without ABCB1 gene modulation in drug-resistant myeloma cells.

ABCB1 gene overexpression has been described as an important mechanism for resistance to conventional chemotherapy in multiple myelomas. In the refractory multiple myelomas, other drug regimens have been successfully applied, including thalidomide treatments. Besides its well-documented anti-angiogenic effects, thalidomide therapy could result in a decrease in ABCB1 gene expression.

Detection of drug-resistance genes using single bronchoscopy biopsy specimens.

Expression of three major resistance genes MDR1, MRP1 and LRP was investigated in small cell lung cancer, non-small cell lung cancer and metastasis. Single biopsies of bronchoscopy from 73 patients were performed to investigate expression of these three resistance genes by reverse transcriptase-polymerase chain reaction. Relations between gene expression and patient age, smoking status, histology, and chemotherapy were evaluated.

Differential modulation of nuclear texture, histone acetylation, and MDR1 gene expression in human drug-sensitive and -resistant OV1 cell lines.

Image cytometric study of pathological specimens or cell lines has suggested that epigenetic mechanisms are likely to play a major role in determining chromatin patterns evaluable through nuclear texture analysis. We previously reported that nuclear textural changes observed in the OV1-VCR etoposide-resistant ovarian carcinoma cell line were associated with an increased acetylated histone H4 level. In this study we analyzed the effects of treatments with the HDAC inhibitor trichostatin A (TSA) or with nickel subsulfide on histone H4 acetylation, nuclear texture, and MDR1 gene expression in drug-sensitive IGROV1 and drug-resistant OV1-VCR cell lines.

Imaging of P-glycoprotein of H69/VP small-cell lung cancer lines by scanning near-field optical microscopy and confocal laser microspectrofluorometer.

Chemoresistance remains the major obstacle to successful therapy of the lung cancer. The multi-drug resistance (MDR) is generally associated with altered expression of drug transporter proteins, such as P-glycoprotein (P-gp). So the distribution of P-gp on the membrane is of great importance to further study the interaction between drug and P-gp.

Effects of the histone deacetylase inhibitor trichostatin A on nuclear texture and c-jun gene expression in drug-sensitive and drug-resistant human H69 lung carcinoma cells.

Background: Texture analysis of chromatin patterns by image cytometry can be used in the development and refinement of diagnosis and prognosis of cancers and in the follow-up of therapies. However, little is known about the biological mechanisms underlying these patterns. Epigenetic mechanisms as histone posttranslational modifications and particularly histone acetylation could play a major role in the determination of these chromatin patterns and then influence nuclear texture measurements.