Essential oils, chemical composition, and biological activities of Eucalyptus oleosa F. Muell. : A review

Many Eucalyptus species are growing in the border of oasis areas. Eucalyptus sp. are generally known for their richness in essential oils and their virtues and economic interests. However, the great taxonomic diversity affects the quantity and quality of these oils. This study is designed to summarize the chemical composition of Eucalyptus oleosa and their biological activities. The yield of essential oils in the leaves of this species varies from 0.45% to 6.7%. These oils contain many chemical compounds of which 1,8-cineole is the main component (15.31% – 89.4%) followed by α-pinene (1%– 24.7%).  Eucalyptus oleosa essential oils exhibited antioxidant, antibacterial, anti-fungal and insecticidal activities with high variability. This variability is associated to many factors such as subspecific diversity, geographical location, part of plant and essential oil’s extraction method

High AHR expression in breast tumors correlates with expression of genes from several signaling pathways namely inflammation and endogenous tryptophan metabolism.

Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP). The aim of this study was to identify the type of breast tumors (ERα-positive or ERα-negative) that express AHR and how AhR affects human tumorigenesis. The levels of AHR, AHR nuclear translocator (ARNT) and AHR repressor (AHRR) mRNA expression were analyzed in a cohort of 439 breast tumors, demonstrating a weak association between high AHR expression and age greater than fifty years and ERα-negative status, and HR-/ERBB2 breast cancer subtypes. AHRR mRNA expression was associated with metastasis-free survival, while AHR mRNA expression was not. Immunohistochemistry revealed the presence of AhR protein in both tumor cells (nucleus and/or cytoplasm) and the tumor microenvironment (including endothelial cells and lymphocytes). High AHR expression was correlated with high expression of several genes involved in signaling pathways related to inflammation (IL1B, IL6, TNF, IL8 and CXCR4), metabolism (IDO1 and TDO2 from the kynurenine pathway), invasion (MMP1, MMP2 and PLAU), and IGF signaling (IGF2R, IGF1R and TGFB1). Two well-known ligands for AHR (TCDD and BaP) induced mRNA expression of IL1B and IL6 in an ERα-negative breast tumor cell line. The breast cancer ER status likely influences AhR activity involved in these signaling pathways. The mechanisms involved in AhR activation and target gene expression in breast cancers are also discussed

Biopathological Significance of PIWI–piRNA Pathway Deregulation in Invasive Breast Carcinomas

International audienceSimple SummaryThe PIWI-piRNA ribonucleoproteic complexes are pivotal regulators of genome integrity, differentiation and homeostasis and their dysregulation has recently been implicated in carcinogenesis. The aim of this study was to analyze the four PIWILs gene expression in invasive breast carcinomas (IBC) at RNA level using quantitative RT-PCR and protein level using immunohistochemistry. In normal breast tissue, PIWILs 2 and 4 were solely expressed, whereas an abnormal emergence of PIWIL1 and 3 was observed in respectively 30% and 6% of IBCs. Conversely, PIWIL2 was underexpressed in 48.3% and PIWIL4 downregulated in 43.3% of IBCs. Similar patterns of PIWIL deregulation were observed in a multitumoral panel, suggesting a generic mechanism in most cancers. PIWIL2 underexpression was significantly associated with DNA methylation and strong cytotoxic immune response. Characterization of the newly recognized PIWIL-piRNA pathway in IBCs opens interesting therapeutic perspectives using piRNAs, hypomethylating drugs, checkpoints immunotherapies and anti-PIWIL 1–3 antibodies.AbstractThe PIWI proteins emerging in the development of human cancers, edify PIWI-piRNA ribonucleoproteic complexes acting as pivotal regulators of genome integrity, differentiation and homeostasis. The aim of this study is to analyze the four PIWILs gene expression in invasive breast carcinomas (IBCs): at RNA level using quantitative RT-PCR (n = 526) and protein level using immunohistochemistry (n = 150). In normal breast tissue, PIWILs 2 and 4 were solely expressed, whereas an abnormal emergence of PIWIL1 and 3 was observed in respectively 30% and 6% of IBCs. Conversely, PIWIL2 was underexpressed in 48.3% and PIWIL4 downregulated in 43.3% of IBCs. Significant positive associations were observed between PIWIL4 underexpression, HR+ status and HR+ ERBB2+ molecular subtype and PIWIL2 underexpression, PR- status, ERBB2- status and molecular subtype. Similar patterns of PIWIL deregulation were observed in a multitumoral panel, suggesting a generic mechanism in most cancers. PIWIL2-4 underexpression was mainly regulated at epigenetic or post-transcriptional levels. PIWIL2 underexpression was significantly associated with DNA methylation and strong cytotoxic immune response. PIWIL2-4 were mainly associated with genes implicated in cell proliferation. As a result of this study, characterization of the PIWIL-piRNA pathway in IBCs opens interesting therapeutic perspectives using piRNAs, hypomethylating drugs, checkpoints immunotherapies and anti-PIWIL 1–3 antibodies

Relationship between <i>AHR</i> mRNA expression and classical clinical and pathological parameters in a series of 439 breast cancers.

<p>Relationship between <i>AHR</i> mRNA expression and classical clinical and pathological parameters in a series of 439 breast cancers.</p

Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility

International audienceSperm cells are highly specialized mammalian cells, and their biogenesis requires unique intracellular structures. Perturbation of spermatogenesis often leads to male infertility. Here, we assess the role of a post-translational modification of tubulin, glutamylation, in spermatogenesis. We show that mice lacking the tubulin deglutamylase CCP5 (also known as AGBL5) do not form functional sperm. In these mice, spermatids accumulate polyglutamylated tubulin, accompanied by the occurrence of disorganized microtubule arrays, in particular in the sperm manchette. Spermatids further fail to rearrange their intracellular space and accumulate organelles and cytosol, while nuclei condense normally. Strikingly, spermatids lacking CCP5 show supernumerary centrioles, suggesting that glutamylation could control centriole duplication. We show that most of these observed defects are also present in mice in which CCP5 is deleted only in the male germ line, strongly suggesting that they are germ-cell autonomous. Our findings reveal that polyglutamylation is, beyond its known importance for sperm flagella, an essential regulator of several microtubule-based functions during spermatogenesis. This makes enzymes involved in glutamylation prime candidates for being genes involved in male sterility

Survival curves of two groups of patients according to <i>AHRR</i> mRNA expression level in the cohort of 439 breast tumors.

<p>AUC analysis was used to divide the population into two relevant <i>AHRR</i> expression subgroups.</p

mRNA expression levels of <i>AHR</i>, <i>AHRR</i> and <i>ARNT</i>, and of genes involved in inflammation, in MDA-MB-436 breast cancer cell line treated with two different <i>AHR</i> ligands.

<p>MDA-MB-436 cells were cultivated in absence (CTL) or in presence of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) (10^-9M) or BaP (benzo[a]pyrene) (10^-6M) for 16 h. Cells were then lysed and mRNA extracted. mRNA expression levels of <i>AHR</i>, <i>AHRR</i> and <i>ARNT</i> (A), and of <i>IL1B</i>, <i>IL6</i>, <i>IL8</i> and <i>CXCR4</i> (B) were determined by qRT-PCR. All experiments were performed in triplicate. Results were expressed as mean +/- s.e.m and normalized so that the mean of the control cells was 1. Three levels of statistical significance are distinguished: *p-value<0.05; **p-value<0.01; ***p-value<0.001.</p

ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas

ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening

Clinical and pathological characteristics of patients in relation to metastasis-free survival (MFS).

<p>Clinical and pathological characteristics of patients in relation to metastasis-free survival (MFS).</p

Prognostic value of a newly identified MALAT1 alternatively spliced transcript in breast cancer

International audienc