Vineyard practices reduce the incidence of Aspergillus spp. and alter the composition of carposphere microbiome in grapes (Vitis vinifera L.).

Going through the new transitioning era of the "European Green Deal," the search for alternative, non-chemical, disease control methods is essential. Aspergillus bunch rot is considered one of the most important diseases of grapevines resulting in severe yield losses and, major qualitative deterioration of grape products due to the production of mycotoxins. We investigated, in a two-year field study, the impact of agronomic practices like defoliation to enhance grape microclimate (DF), pruning method to reduce grape bunch density (LBD), and irrigation cut-off (NIR), at three developmental stages of grapevine (Pea size berry, Veraison, and Harvest), on (i) grape composition (titratable acidity, pH, and total soluble solids), (ii) on the frequency of occurrence of Aspergillus on grape berries, and (iii) on the overall composition of grape carposphere microbiome. The density of Aspergillus on grape berries was significantly reduced by the applied management practices (DF, LBD, and NIR). Amplicon sequencing analysis showed that both the phenological stage and the agronomic practices employed (particularly NIR and DF) imposed significant changes in the α-diversity and ß-diversity of the grape carposphere bacterial and fungal communities. The NIR, LBD, and DF treatments which supported lower Aspergillus populations, network analysis revealed negative co-occurrence patterns between Aspergillus and several bacterial genera (Streptococcus, Rhodococcus, and Melitangium) reported to have antifungal properties suggesting potential natural attenuation mechanisms for the control of Aspergillus. Overall, our study (i) showed that the application of halting of irrigation and thinning of leaves and grape bunches, reduce the occurrence of Aspergillus and hence the incidence of Aspergillus Bunch rot disease and (ii) identified preliminary evidence for interactions of Aspergillus with members of the epiphytic grape bacterial communities that might be involved in the suppression of Aspergilli, an observation which will be further pursued in following studies in the quest for the discovery of novel biological control agents.

Management of difficult bile duct stones and indeterminate bile duct structures: Reduced ERCP radiation exposure with adjunct use of digital single-operator cholangioscopy.

INTRODUCTION: Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is an well-established endoscopic procedure for the management of biliary diseases. The use of fluoroscopy during ERCP has often raised concerns regarding potential risks from radiation exposure, particularly in complex cases. We investigated whether a new digital single-operator cholangioscopy (D-SOC) system, used adjunctively to ERCP, actually reduces patient radiation exposure. MATERIALS AND METHODS: We retrospectively analyzed a prospective database (April 2016 to October 2018) including consecutive patients who underwent successful management of difficult-to-treat biliary stones or indeterminate biliary strictures by using either conventional ERCP (ERCP cohort) or ERCP in conjunction with D-SOC (ERCP/D-SOC cohort). The overall patient radiation exposure outcomes were compared in terms of Kerma Area Product (KAP), Fluoroscopy time (T) and the total number of films (F). RESULTS: Overall, 47 patients (mean 71.8 years, 59.6% males) were included (ERCP cohort = 29, ERCP/D-SOC cohort = 18), referred either for difficult bile duct stones (n = 36) or indeterminate biliary strictures (n = 11). The median KAP, T and F in the ERCP/D-SOC cohort were 12.3 Gycm2, 3.7 min and 4 films respectively, compared with 52.1 Gycm2, 8.4 min, and 5 films respectively in the ERCP cohort. Statistically significant differences (P = 0.0001) were found for KAP and T. CONCLUSIONS: Adjunct use of a digital cholangioscopy platform appears to significantly reduce radiation exposure in patients undergoing ERCP for the management of difficult bile stones or indeterminate biliary strictures.

Neovascularization in Ewing's sarcoma.

Ewing's sarcoma is the second most common bone malignancy in adolescents and young adults after osteosarcoma. Similar to other solid tumors, Ewing's sarcomas require an adequate vascular supply to grow and survive. The development and maintenance of vascular supply is accomplished via three main mechanisms; angiogenesis, vasculogenesis, and tumor cell vasculogenic mimicry. In addition, growth factors, parallel biochemical pathways and the tumor microenvironment are implicated in the initiation and maintenance of neovascularization. This article summarizes the different mechanisms and factors that contribute to neovascularization in Ewing's sarcoma, and discusses the significance of this phenomenon for current treatment options.

High Farnesoid X Receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma.

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. FXR positivity was noted in 91 (79.1%) and high FXR expression in 51 (44.3%) out of 115 invasive breast carcinoma cases. High FXR expression was significantly associated with smaller tumor size (p=0.0318) and increased tumor cells' proliferative rate (p=0.0375). Invasive breast carcinoma patients presenting high FXR expression showed significantly longer overall and disease-free survival times compared to those with low FXR expression (log-rank test, p=0.0052 and p=0.0058). In multivariate analysis, FXR expression was identified as independent prognostic factor of overall and disease-free patients' survival (Cox-regression analysis, p=0.0023 and p=0.0049, respectively). The present data support evidence that FXR may be implicated at the earlier stage of breast malignant disease progression, being a strong and independent prognosticator of favorable overall and disease-free survival in invasive breast carcinoma.

Risk factors for elevated blood lead levels among children aged 6-36 months living in Greece.

BACKGROUND: Childhood lead poisoning remains a critical environmental health concern because even low blood lead levels (BLLs) can result in permanent adverse health effects. Social factors and living conditions have been correlated with BLLs. There is no recent survey about the prevalence of elevated BLLs among children in Greece. The purpose of this study was to assess BLLs among children aged 6-36 months born and living in Greece and to evaluate their association with demographic, socio-economic and housing conditions. METHODS: In a cross-sectional hospital-based study including 814 randomly selected children aged 6-36 months, BLLs and haematological parameters were evaluated. A questionnaire investigating demographic and socio-economic conditions was completed in all children. Statistical analysis was performed using STATA for Windows v.8.5, and P < 0.05 was considered statistically significant. RESULTS: The mean BLLs of the population were 2.78 (SD = 2.34) µg/dl, and the median was 2.02 µg/dl; 11.7% had BLLs above 5 µg/dl, while 15 children (1.8%) exceeded 10 µg/dl. Being a toddler, being Roma or Asian, living in an industrial/low-income neighbourhood or in an old house, using traditional herbs and/or spices and having a mother with a manual occupation were independent risk factors for elevated BLLs. CONCLUSION: Lead exposure remains a threat for optimal health especially for toddlers and children of socio-economically disadvantaged families living in Greece. A nationwide survey to assess lead exposure in children is necessary to guide prevention governmental policies.

Elevated Farnesoid X Receptor (FXR) and Retinoid X Receptors (RXRs) expression is associated with less tumor aggressiveness and favourable prognosis in patients with pancreatic adenocarcinoma.

UNLABELLED: Farnesoid X Receptor (FXR) and its co-partners Retinoid X Receptors (RXRs) are considered to participate in crucial biochemical and cellular processes, being involved in the pathogenesis of several diseases, including cancer. The present study aimed to evaluate the clinical significance of FXR alone and in conjunction with RXRs expression, in pancreatic adenocarcinoma. FXR, RXR-α, -ß and -γ protein expression was assessed immunohistochemically on tumoral samples of 55 pancreatic adenocarcinoma cases and was statistically analyzed with clinicopathological characteristics, tumor proliferative capacity and patients' survival. Enhanced FXR expression was borderline associated with earlier histopathological stage (p=0.054). Concomitant elevated FXR/RXR-α expression was significantly associated with decreased tumor histological grade (p=0.017), while concomitant enhanced FXR/RXR-ß and FXR/RXR-γ expression with earlier histopathological stage (p=0.017 and p=0.004, respectively) and smaller tumor size (p=0.037 and p=0.005, respectively). Concomitant enhanced FXR/RXR-γ expression was additionally significantly associated with the absence of lymph node metastases (p=0.018). Pancreatic adenocarcinoma patients with enhanced FXR, FXR/RXR-ß or -γ expression showed significantly longer survival times compared to those with low expression (p=0.013, p=0.021 and p<0.001, respectively). In multivariate analysis, FXR and FXR/RXR-γ expression were identified as independent prognostic factors (p=0.044 and p=0.001, respectively). CONCLUSION: The present study suggested that FXR and RXRs were implicated in pancreatic malignant disease progression, reinforcing their utility as clinical markers for patients' management and prognosis, as well as targets for potential therapeutic interventions. KEYWORDS: FXR, RXR, pancreatic adenocarcinoma, immunohistochemistry, clinicopathological parameters, patients' survival.

Platelet-activating factor (PAF) receptor expression is associated with histopathological stage and grade and patients' survival in gastric adenocarcinoma.

Platelet activating factor (PAF) has been considered as potent inflammatory lipid mediator that exerts its actions by binding to PAF receptor (PAFR). PAF/PAFR system has been implicated in several pathophysiological states, including tumor progression, angiogenesis and metastasis. The present study aimed to evaluate the clinical significance of PAFR expression in gastric adenocarcinoma. PAFR protein expression was assessed immunohistochemically on 54 gastric adenocarcinoma tissue samples and was analyzed in relation with clinicopathological parameters, tumor proliferative capacity and patients' survival. PAFR was abundantly expressed in all gastric adenocarcinoma cases examined. Increased PAFR expression was significantly more frequently observed in well/moderately compared to poorly differentiated gastric adenocarcinoma cases (p=0.011). PAFR expression was significantly increased in intestinal- compared to diffuse-type cases (p=0.020). Elevated PAFR expression was significantly associated with smaller tumor size, absence of lymph node and organ metastasis and low tumor histopathological stage (p=0.025, p<0.001, p=0.009 and p<0.001, respectively). Additionally, patients presenting elevated PAFR expression had significantly longer survival times compared to those with low PAFR expression (log-rank test, p<0.001). These results support an important potential role of PAFR signalling in gastric malignant disease progression and render further research in this field a necessity.

Clinical significance of Src expression and activity in human neoplasia.

Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the human genome and member of the Src protein tyrosine kinases family (SFK). As described by Martin and Rous, a genetic recombination between c-src and the RSV oncogene of Rous sarcoma virus results in a modified Src protein, with increased intrinsic activity and transforming potential in animal and human tissues. Several in vitro and in vivo studies supported this theory providing insight in the signalling pathways involved. Accumulating evidence from studies on clinical samples supported the role of Src in the process of carcinogenesis and disease progression in several human malignancies. Some studies have further reinforced the significance of the kinase in malignacy by correlating its expression and/or activity with important clinicopathological parameters, such as tumour stage, histopathological grade, proliferative capacity and most importantly patient's survival. This review is a comprehensive report of the published evidence on the expression and clinical significance of Src in human malignancy, which constitutes the background of the current studies and clinical trials on the use of Src inhibitors as novel potent antineoplastic strategy.

Atherosclerosis regression study in rabbits upon olive pomace polar lipid extract administration.

BACKGROUND AND AIMS: Virgin olive oil polar lipid extract (OOPL) and olive pomace polar lipid extract (PPL) have similar antiatherosclerotic effects in cholesterol-fed rabbits. Our aim was to compare the effect of PPL with that of simvastatin on the progression of atherogenesis. METHODS AND RESULTS: Rabbits were fed an atherogenic diet for 6 weeks in order to develop dyslipidemia and atheromatous lesions. Following documentation of these events in random animals (group A, n=6), the remaining were fed for 3 weeks with: standard chow alone (group B, n=6), chow supplemented with PPL (group C, n=6), and chow supplemented with simvastatin (group D, n=6). Blood was collected at 0, 6 and 9 weeks, to determine plasma lipid levels, plasma PAF-AH activity, platelet aggregation (PAF-EC(50)), resistance of plasma to oxidation (RPO) and extent of atheromatous lesions in aortas. The atherogenic diet induced dyslipidemia and increased PAF-AH activity. Dyslipidemia and PAF-activity reduced more effectively in groups C and D. RPO decreased in group B only. PAF-EC(50) values decreased in group C only. Atherogenesis progression in group C was prevented to an extent indistinguishable from that in group D. PAF-AH activity was positively correlated, whereas RPO was negatively correlated with the extent of atheromatous lesions. CONCLUSION: PPL, as a dietary supplement, is equipotent to simvastatin in preventing the progression of atherogenesis.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1): a novel biomarker in the diagnosis and prognosis of human neoplasia.

The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a novel tumor-associated antigen that induces cell-cycle arrest and/or apoptosis in RCAS1 receptor-bearing human cells. Current evidence has revealed enhanced RCAS1 expression in the tumor malignant stage of several organs, which may play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. In the last few years, tissue RCAS1 protein expression and circulating levels in biofluids have further been the focus of extensive research as a diagnostic and prognostic marker in several human malignancies. The present article aimed to review the available data so far concerning the clinical significance of RCAS1 in human neoplasia. Reviewing of English literature revealed that tissue RCAS1 expression was associated with important clinicopathological parameters for patients' management and prognosis, being considered as an informative biomarker in several types of human malignancy. In addition, the current evidence supported a crucial role for RCAS1 in tumor immune escape, which renders this receptor a promising target for future (gene) therapeutic approaches. However, the clinical application of circulating RCAS1 concentrations in biofluids as a marker in the management and prognosis of tumor malignancies needs to be further explored, since the data so far are still extremely limited.

Role of OPG/RANKL/RANK axis on the vasculature.

Vascular calcification, a degenerative process considered in the past to be a passive procedure, has now been suggested to be related to ossification. Many proteins responsible for bone formation have been identified on the arterial wall. The OPG/RANKL/RANK axis, responsible for ossification and bone mineralization, seems to play a major role in vasculature and atherosclerosis. Mice lacking OPG gene present osteoporosis and arterial calcification, while overexpression of OPG gene leads to osteopetrosis. In the present review the latest knowledge related to the effects of the OPG/RANKL/RANK axis on vasculature, including atherosclerosis, will be analyzed. The clinical significance of circulating OPG and RANKL levels in vascular diseases will also be referred.

Magnifying lenses assisted nerve-sparing radical hysterectomy and prevention of nerve plexus trauma.

The objectives of the study were to present a new approach for nerve-sparing radical hysterectomy (NSRH) with the assistance of magnifying lenses and to describe the differences in autonomic nerve plexus trauma between NSRH type III and conventional radical hysterectomy (RH) types II and III with the aid of immunohistochemistry. Eighteen women with FIGO stage IB(1)-IB(2) cervical cancer underwent loupes-assisted NSRH (n = 8), RH type II (n = 6), and RH type III (n = 4). Biopsies were taken intraoperatively from uterosacral ligament (USL) and cardinal ligament (CL), as well as from anterior vaginal wall (AVW) and posterior vaginal wall (PVW). Immunohistochemistry was approached with the use of S-100 protein, a general nerve marker. The percentage area of immunoreactivity (PAI) was used as an objective quantitative measure of nerve fibers within the ligaments. The PAI was greater in RH-III biopsies from both USL and CL (P < 0.001) when compared with RH-II and NSRH biopsies. For AVW and PVW, PAI differences were not statistically significant (AVW, P = 0.119; PVW, P = 0.067). Uterine-supporting ligaments represent a major pathway for autonomic nerves to the pelvic organs. As significantly more autonomic nerves are transected during the division of the uterine-supporting ligaments in RH type III, a more careful approach in the dissection of the ligaments through nerve-preserving techniques seems to be necessary in order to prevent iatrogenic intraoperative injury of the pelvic plexus and reduce or prevent postoperative complications.

Effect of platelet-activating factor (PAF) receptor antagonist (BN52021) on acetaminophen-induced acute liver injury and regeneration in rats.

BACKGROUND: Platelet-activating factor (PAF) is an endogenous lipid mediator that plays a key role in catalyzing various pro-inflammatory processes associated with acute liver injury. In the present study, the possible influence of PAF-R antagonist (BN52021) on the protection of liver injury after 4-hydroxyacetanilide, N-acetyl-p-aminophenol, paracetamol (APAP) intoxication was investigated. METHODS: Thereby, one group of rats was treated with a toxic dose of APAP (3.5 g/kg body weight (b.w.). The animals were killed at 56, 66, 72, 84 and 96 h after treatment. RESULTS: APAP was found to cause an acute hepatic injury, evident by alterations of biochemical (serum enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase) and liver histopathological (degree of necrosis and apoptosis) indices, which was followed by liver regeneration, evident by three independent indices ([3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index). The protective effects of BN52021 were qualified during post-treatment time by: (1) significant reduction of hepatic injury as showed by all biochemical and histological parameters, (2) high decrease of regenerating activity showed by three regenerative markers and (3) remarkable increase of PAF-acetylhydrolase (PAF-AH) activity. CONCLUSION: These results suggest that PAF may play an important role in APAP-induced liver injury and regeneration, and PAF-R antagonist (BN52021) attenuates liver damage.

Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration.

Acetaminophen-induced toxicity has been attributed to cytochrome P-450-generated metabolites, which covalently modify target proteins. However, the mechanism of liver injury pathogenesis needs to be further elucidated. Platelet-activating factor (PAF) is one of the mediators involved in inflammatory tissue alterations associated with acute liver failure. In this study, alterations in blood PAF levels and the serum activity of PAF-acetylhydrolase (PAF-AH) were investigated over the time course of liver injury and regeneration induced by acetaminophen treatment in rats. The administration of a toxic dose of acetaminophen (3.5 g/kg) in rats caused acute hepatic injury, as evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices between 20 and 40 h post-treatment. The hepatic damage was followed by liver regeneration, made evident by three independent indices ([3H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index), presenting a peak at 72 h. The PAF levels were elevated at 24 and 28 h, presenting a remarkable peak at 32 h post-treatment. PAF-AH activity presented different kinetics to that of PAF. The enzyme activity was relatively low at all time points examined before the rise in PAF activity, peaking later, at 72, 84 and 96 h. Our data demonstrate that PAF is involved in the pathogenesis of acute liver failure and in augmented compensatory liver tissue repair post-acetaminophen treatment. However, the putative role of PAF during liver toxicity and regeneration remains to be established.

Metallothionein expression in human neoplasia.

The metallothionein family is a class of low-molecular-weight, cysteine-rich proteins with high affinity for metal ions. Four major isoforms (metallothionein-1, -2, -3, and -4) have been identified in mammals, involved in many pathophysiological processes, including metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, drug and radiotherapy resistance and several aspects of the carcinogenic process. In the present review we examine the expression of metallothionein in different human tumours and its correlation with histopathological variables, tumour cell proliferation or apoptosis, resistance to radiation or chemotherapy, patient survival and prognosis. A variable profile of metallothionein and its isoforms' expression has been observed in different cancer types. Although metallothionein expression has been implicated in carcinogenic evolution, its use as a marker of tumour differentiation, cell proliferation and prognosis predictor remains unclear. Detailed studies focused on the expression of metallothionein isoforms and isotypes in different tumour types could elucidate the role of this group of proteins in the carcinogenic process, delineating its possible clinical significance for the management of patients.

Metallothionein: a multifunctional protein from toxicity to cancer.

The metallothionein (MT) family is a class of low molecular weight, intracellular and cysteine-rich proteins presenting high affinity for metal ions. Although the members of this family were discovered nearly 40 years ago, their functional significance remains obscure. Four major MT isoforms, MT-1, MT-2, MT-3 and MT-4, have been identified in mammals. MTs are involved in many pathophysiological processes such as metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, chemoresistance and radiotherapy resistance. MT isoforms have been shown to be involved in several aspects of the carcinogenic process, cancer development and progression. MT expression has been implicated as a transient response to any form of stress or injury providing cytoprotective action. Although MT participates in the carcinogenic process, its use as a potential marker of tumor differentiation or cell proliferation, or as a predictor of poor prognosis remains unclear. In the present review the involvement of MT in defense mechanisms to toxicity and in carcinogenicity is discussed.

Focal adhesion kinase expression is not a prognostic predictor in colon adenocarcinoma patients.

AIM: Focal adhesion kinase (FAK) is an enzyme of the tyrosine kinase group linked to signaling pathways between cells and their extracellular matrix. FAK expression in tumor cells in vitro may correlate with their ability for invasion and metastasis. METHODS: FAK protein expression was examined immunohistochemically in 80 cases of colon adenocarcinoma, and correlated with clinicopathological parameters; tumor proliferative capacity, reflected by Ki-67 antigen expression; and survival. RESULTS: All tumor samples were FAK positive compared to normal colonic mucosa. FAK protein overexpression was seen in 32 out of 80 cases. FAK protein overexpression did not correlated with tumor histological grade, stage, Ki-67 positivity or survival. CONCLUSIONS: Raised FAK protein expression was noted by immunohistochemistry in human colon carcinoma cases. The implication are discussed.

Peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands and angiogenesis.

The peroxisome proliferator activated receptor (PPAR)- gamma ligands have been initially described as important regulators of adipogenic differentiation and glucose homeostasis. Detailed studies in different tissues pointed to the roles of these ligands in cell proliferation and cancer, establishing their anticancer properties against a wide variety of neoplastic cells. The growth of any solid tumor depends on angiogenesis, as tumor vascularization is a vital process for tumor volume increase and its metastatic potential. Recently, the role of PPAR- gamma ligands as potent angiogenesis modulators in vitro and in vivo, has been referred. This review takes into consideration the latest data concerning the participation of PPAR- gamma ligands in the biological mechanisms underlying angiogenesis inhibition (important in anticancer therapy) and the controversy concerning angiogenesis induction (important in non-neoplastic diseases). As inhibition of angiogenesis represents one of the more promising, new approaches to anticancer therapy, PPAR- gamma ligands in addition to their established role as tumor cell cycle modulators could be implicated in future strategies for cancer treatment.

Expression of metallothionein in lung carcinoma: correlation with histological type and grade.

AIMS: Over-expression of cellular metallothionein occurs frequently in human tumours but the underlying mechanism remains unknown. The aim of this study was to assess metallothionein expression in cases of lung carcinoma and to correlate it with histopathological parameters. METHODS AND RESULTS: Tumour tissue samples from 89 patients with lung carcinoma were immunostained by the streptavidin-biotin-peroxidase technique, using a monoclonal antibody against both metallothionein-1 and -2 isoforms. Positive matallothionein immunostaining was prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung carcinoma examined. Metallothionein positivity was prominent in 32 out of 43 (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of adenocarcinoma, while it was negative in all 11 cases of small-cell lung carcinoma examined, presenting a statistically significant difference between the different histological types. The intensity of metallothionein staining revealed a statistically significant difference between the squamous cell and adenocarcinoma cases examined. The pattern and extent of metallothionein staining in tumour cells and the expression of metallothionein in stromal cells were not correlated with histopathological parameters (type and grade) in metallothionein-positive cases of lung carcinoma examined. No association was found between metallothionein expression and lymph node status in the examined cases of lung carcinoma. CONCLUSIONS: Our findings indicate that expression of metallothionein was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in small-cell lung carcinoma, supporting evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung.

Histone deacetylase inhibitors and anticancer therapy.

Recent reports have shown that pharmacological manipulation of chromatin remodeling by histone deacetylase (HDAC) inhibitors, might develop into a potent and specific strategy for the treatment of cancer. Alterations in histone acetylation may lead to changes in chromatin structure and transcriptional dysregulation of genes that are implicated in controlling either cell cycle progression or pathways regulating cell differentiation and/or apoptosis. Dimethyl sulphoxide was one of the first chemicals to be identified as an inducer of transformed cell differentiation. In the class of HDAC inhibitors, now included a short-chain fatty acids, such as 4-phenylbutyrate and valporic acid, hydroxamic acids, such as suberoylanilide hydroxamic acid (SAHA), pyroxamide, trichostatin A, oxamflatin and CHAPSs, cyclic tetrapeptides, such as trapoxin, apicidin and depsipeptide-also known as FK-228 or FR 901228, and benzamides, such as MS-275. First clinical studies have shown that histone hyperacetylation can be achieved safely in humans and that treatment of cancer with such agents seems to become possible. Thus, HDAC inhibitors remains one of the most promising class of new anticancer agents. Further studies are needed in order to delineate the optimal dosage, the duration of therapy and possibly the efficacy of other agents able to synergize with HDAC inhibitors in the fight against cancer.