Cytokines, chemokines and growth factors play an important role in the persistence of mucosal inflammation associated with nasal polyps. Metalloproteinases seem to be crucial in nasal tissue remodeling in these patients. Arachidonic acid metabolites seem to be particularly important in the pathogenesis of nasal polyps in patients with aspirin hypersensitivity. We discuss the contribution of each one for the polyp formation.

Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views—differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.

Endometriosis is a chronic gynecological disorder defined as the presence of endometrial tissue within extra‐uterine sites. The proliferation of topic and ectopic endometrial tissue was demonstrated in several trials. In endometriotic tissues and cultured endometriotic cells the expression profile of cell cycle and inflammatory proteins are modified, particularly p27 protein – reduced expression – and IL‐1β – increased expression –, both leading to an increased cell proliferation. The therapeutic use of an adenoviral p27 super‐expression vector (Adp27EGFP) in endometriotic cell cultures induces the cells back to normal proliferative levels. In order to improve the therapeutic potential of this gene therapy we combined it with cell therapy using human umbilical cord mesenchymal stem cells (hUCMSC). The levels of IL‐1β were evaluated in the culture medium of normal and endometriotic endometrial cells transfected or not with Adp27EGFP and Adnull, and treated with hUCMSC. Treatment with hUCMSC leads to increased IL‐1β expression reaching endometriotic levels after 14 days of treatment even in the normal endometrial cells. The therapeutic effects of Adp27EGFP were totally inhibited in the endometriotic cells treated with hUCMSC. These results suggest that the mesenchymal stem cells can have a role in the progression of the endometriosis and cannot be used to treat the disease.

Introduction: Breast cancer cell lines frequently contain a sub-population of stem cells (SC). MDA-MB-231 is a model of basal-like breast cancer triple negative (TN) lineage widespread used in laboratories across the world. It contains a stem cell subpopulation, however little is known about the molecular mechanisms underlying undifferentiated ground state regulation in this type of cell. Aberrations in epigenetic processes such as histone (de)methylation may cause cancer. The largest family of zinc-finger transcription factors is composed of the Krüpell-associated box (KRAB) domain containing proteins. They do not have intrinsic enzymatic activity, instead, this transcription factor family recruits chromatin remodelers and histone-modifying enzymes to regulate gene transcription, generally acting as repressor proteins. Underlying molecular mechanisms for aggressiveness of basal-like/TN breast cancer stem cell remains to be elucidated. Objective: To investigate the molecular basis of MDA-MB-231 sub-populations (progenitor and differentiated cells), in order to obtain and compare the genome expression profile of stem cell and of differentiated subpopulations and identify gene networks regulating distinct differentiation states. Experimental Procedures: Cells were cultured in T75 flasks, suspended in Aldefluor assay buffer and incubated for 30 minutes for staining. Heterogeneity of aldehyde dehydrogenase expression in MDA-MB-231 sub-populations was revealed by Aldefluor flow cytometry-based assay. Separated cell sub-populations were harvested, had their RNA extracted (TRIzol), purified (silica columns plus DNase), measured (Nanodrop) and analyzed (Bioanalyzer). RNA samples were submitted to Agilent whole genome (8X60K) microarray experiments (one-color), according to manufacturer's instructions. cDNA samples from each experimental group (Aldefluor-positive cells, Aldefluor-negative cells and overall population - control) were loaded into a genome array. Experiments were performed in triplicates. The analysis of differential expression profiles were performed by GX11.5 GeneSpring software. Results: Fluorescence activated cell sorting (FACS) assay detected 4% of the overall MDA-MB-231 cell population as Aldefluor positive and 50% as non-Aldefluor positive. Microarray results analyzed with GeneSpring software demonstrate that among 337 genes upregulated (fold change ≥ 2.0, p≤ 0.001) exclusively in the stem cell-like subpopulation. Gene Ontology (GO) terms allowed annotation of these 337 upregulated genes as, molecular function (61.7.0%), cellular component (46.2) and biological process (2.1%). Among sixty-four molecular function related genes, twety-two (34.4%) are zinc-finger proteins and eighteen of them are genes coding for KRAB domain-containing zinc-finger proteins (ZNF688, ZNF419, ZNF397, ZNF821, ZNF12, ZNF280C, ZNF821, ZNF239, ZNF468, ZNF702P, ZNF496, ZNF205, ZNF829, ZNF345, ZNF526, ZNF329, ZNF561 and ZNF562). HDAC5 is downregulated 3.13 times in stem cell-like subpopulation when compared to Aldefluor negative sub-population. Conclusions: Our results show that the upregulation of the Krüpell family of zinc finger proteins might be part of the genome signature that distincts MDA-MB-231 stem cell sub-population from its progeny. It is known that HDACs have an important role in mammary tumor cell growth control. KRAB-containing zinc-finger proteins are involved in transcriptional regulation by recruiting histone modifiers and chromatin remodelers like, DNMT3a, HDAC5, JARID2 and Activation Protein 1 (AP1), in order to repress gene transcription. This being the case, zinc-finger proteins are linked to epigenetic processes and can be selectively targeted to regulate gene expression and determine cell fate. Citation Format: Samuel Marcos Ribeiro de Noronha, Carlos Fernandes Baptista, Werica Bernardo, Ismael Dale Cotrim Guerreiro Silva, Silvana Aparecida Alves Correa-Noronha. MDA-MB-231 stem cell subpopulation upregulates KRAB domain-containing zinc-finger gene family to hold undifferentiated ground state. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A59.