Peritumoral tissue (PTT): increasing need for naming convention.

Various terms are used to describe non-malignant tissue located in the proximity of a tumor, belonging to the organ from which the tumor originated. Traditionally, these tissues, sometimes called "normal adjacent tissue" have been used as controls in cancer studies, and were considered representative of morphologically healthy, non-cancerous tissue. However, with the advancement of OMIC technologies, such tissues are increasingly recognized to be distinct from both tumor and healthy tissues.

Plakins are involved in the regulation of centrosome position in polarized epithelial cells.

Background Information: The control of epithelial cell polarity is key to their function. Its dysregulation is a major cause of tissue transformation. In polarized epithelial cells,the centrosome is off-centred toward the apical pole.

Patrilineal segmentary systems provide a peaceful explanation for the post-Neolithic Y-chromosome bottleneck.

Studies have found a pronounced decline in male effective population sizes worldwide around 3000-5000 years ago. This bottleneck was not observed for female effective population sizes, which continued to increase over time. Until now, this remarkable genetic pattern was interpreted as the result of an ancient structuring of human populations into patrilineal groups (gathering closely related males) violently competing with each other.

Influence of physico-chemical properties of two lipoxin emulsion-loaded hydrogels on pre-polarized macrophages: a comparative analysis.

Inflammation, a crucial defense mechanism, must be rigorously regulated to prevent the onset of chronic inflammation and subsequent tissue damage. Specialized pro resolving mediators (SPMs) such as lipoxin A4 (LXA4) have demonstrated their ability to facilitate the resolution of inflammation by orchestrating a transition of M1 pro-inflammatory macrophages towards an anti-inflammatory M2 phenotype. However, the hydrophobic and chemically labile nature of LXA4 necessitates the development of a delivery system capable of preserving its integrity for clinical applications.

COL7A1 Expression Improves Prognosis Prediction for Patients with Clear Cell Renal Cell Carcinoma Atop of Stage.

Clear-cell renal cell carcinoma (ccRCC) accounts for 75% of kidney cancers. Due to the high recurrence rate and treatment options that come with high costs and potential side effects, a correct prognosis of patient survival is essential for the successful and effective treatment of patients. Novel biomarkers could play an important role in the assessment of the overall survival of patients.

Optimal microRNA Sequencing Depth to Predict Cancer Patient Survival with Random Forest and Cox Models.

(1) Background: tumor profiling enables patient survival prediction. The two essential parameters to be calibrated when designing a study based on tumor profiles from a cohort are the sequencing depth of RNA-seq technology and the number of patients. This calibration is carried out under cost constraints, and a compromise has to be found.

Prognosis of lasso-like penalized Cox models with tumor profiling improves prediction over clinical data alone and benefits from bi-dimensional pre-screening.

Background: Prediction of patient survival from tumor molecular '-omics' data is a key step toward personalized medicine. Cox models performed on RNA profiling datasets are popular for clinical outcome predictions. But these models are applied in the context of "high dimension", as the number p of covariates (gene expressions) greatly exceeds the number n of patients and e of events.

Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer's Disease Treatment.

Background And Purpose: The activation of 5-HT receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer's disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood-brain barrier shuttle peptide.

MicroRNA Therapeutics in Cancer: Current Advances and Challenges.

The discovery of microRNAs (miRNAs) in 1993 has challenged the dogma of gene expression regulation. MiRNAs affect most of cellular processes from metabolism, through cell proliferation and differentiation, to cell death. In cancer, deregulated miRNA expression leads to tumor development and progression by promoting acquisition of cancer hallmark traits.

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction.

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau).

Relevant Physicochemical Methods to Functionalize, Purify, and Characterize Surface-Decorated Lipid-Based Nanocarriers.

Surface functionalization of lipid-based nanocarriers (LBNCs) with targeting ligands has attracted huge interest in the field of nanomedicines for their ability to overcome some physiological barriers and their potential to deliver an active molecule to a specific target without causing damage to healthy tissues. The principal objective of this review is to summarize the present knowledge on LBNC decoration used for biomedical applications, with an emphasis on the ligands used, the functionalization approaches, and the purification methods after ligand corona formation. The most potent experimental techniques for the LBNC surface characterization are described.

Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells.

Mycoplasma hyopneumoniae is the most costly pathogen for swine production. Although several studies have focused on the host-bacterium association, little is known about the changes in gene expression of swine cells upon infection. To improve our understanding of this interaction, we infected swine epithelial NPTr cells with M.

Comparison of Environmental and Culture-Derived Bacterial Communities through 16S Metabarcoding: A Powerful Tool to Assess Media Selectivity and Detect Rare Taxa.

To compare environmental and culture-derived microbial communities, we performed 16S metabarcoding of uncultured samples and their culture-derived bacterial lawns. Microbial communities were obtained from freshwater river samples representative of an anthropization gradient along a river stream. Their culture-derived bacterial lawns were obtained by growing aliquots of the samples on a broad range medium and on two different semi-selective media.

miRViz: a novel webserver application to visualize and interpret microRNA datasets.

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through their binding to and repression of multiple mRNAs. With high-throughput methodologies, various outcomes can be measured that produce long lists of miRNAs that are often difficult to interpret. A common question is: after differential expression or phenotypic screening of miRNA mimics, which miRNA should be chosen for further investigation? Here, we present miRViz (http://mirviz.

Early Postoperative Circulating miR-483-5p Is a Prognosis Marker for Adrenocortical Cancer.

We have previously identified serum miR-483-5p as a preoperative diagnosis and prognosis biomarker for adrenocortical cancer (ACC). Here, we aimed to determine whether circulating miR-483-5p levels measured 3 months post-operatively distinguished patients with good prognosis (no recurrence for at least 3 years; NR3yrs) from patients with poor prognosis (recurrence or death within 3 years after surgery; R < 3yrs). We conducted a single-center retrospective analysis using sera from 48 patients with ACC that were initially non-metastatic and treated by surgery.

Ex-Vivo Treatment of Tumor Tissue Slices as a Predictive Preclinical Method to Evaluate Targeted Therapies for Patients with Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response.

Importance of Combining Advanced Particle Size Analysis Techniques To Characterize Cell-Penetrating Peptide-Ferrocifen Self-Assemblies.

The design of a simple platform to target the delivery of notably hydrophobic drugs into cancer cells is an ultimate goal. Here, three strategies were combined in the same nanovector, in limiting the use of excipients: cell-penetrating peptides, an amphiphilic prodrug, and self-assembly. Light scattering and cryogenic transmission electron microscopy revealed one size population of objects around 100 nm with a narrow size distribution.

Targeting AU-rich element-mediated mRNA decay with a truncated active form of the zinc-finger protein TIS11b/BRF1 impairs major hallmarks of mammary tumorigenesis.

Altered expression of regulatory RNA-binding proteins (RBPs) in cancer leads to abnormal expression of mRNAs encoding many factors involved in cancer hallmarks. While conventional anticancer therapies usually target one pathway at a time, targeting key RBP would affect multiple genes and thus overcome drug resistance. Among the Tristetraprolin family of RBP, TIS11b/BRF1/ZFP36L1 mediates mRNA decay through binding to Adenylate/Uridylate (AU-rich elements) in mRNA 3'-untranslated region and recruitment of mRNA degradation enzymes.

Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension.

Rationale: Although many familial cases of pulmonary arterial hypertension exhibit an autosomal dominant mode of inheritance with the majority having mutations in essential constituents of the BMP (bone morphogenetic protein) signaling, the specific contribution of the long-term loss of signal transduction triggered by the BMPR2 (type 2 BMP receptor) remains poorly characterized.

Objective: To investigate the role of BMP9, the main ligand of ALK1 (Activin receptor-like kinase 1)/BMPR2 heterocomplexes, in pulmonary hypertension.

Method And Results: The absence of BMP9 in Bmp9 mice and its inhibition in C57BL/6 mice using neutralizing anti-BMP9 antibodies substantially prevent against chronic hypoxia-induced pulmonary hypertension judged by right ventricular systolic pressure measurement, right ventricular hypertrophy, and pulmonary distal arterial muscularization.

Bioinformatics Methods to Select Prognostic Biomarker Genes from Large Scale Datasets: A Review.

With the increased availability of survival datasets, that comprise both molecular information (e.g., gene expression), and clinical information (e.

Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma.

Potent inhibitors of PI3K (GDC-0941) and Src (Saracatinib) exhibit as individual agents, excellent oral anticancer activity in preclinical models and have entered phase II clinical trials in various cancers. We found that PI3K and Src kinases are dysregulated in clear cell renal carcinomas (ccRCCs), an aggressive disease without effective targeted therapies. In this study we addressed this challenge by testing GDC-0941 and Saracatinib as either single agents or in combination in ccRCC cell lines, as well as in mouse and PDX models.

Indolizine-Based Scaffolds as Efficient and Versatile Tools: Application to the Synthesis of Biotin-Tagged Antiangiogenic Drugs.

We describe the design and optimization of polyfunctional scaffolds based on a fluorescent indolizine core derivatized with various orthogonal groups (amines, esters, oximes, alkynes, etc.). To show one application as tools in biology, the scaffold was used to prepare drug-biotin conjugates that were then immobilized onto avidin-agarose for affinity chromatography.

MiR-483-5p and miR-139-5p promote aggressiveness by targeting N-myc downstream-regulated gene family members in adrenocortical cancer.

Adrenocortical carcinoma (ACC) is a tumor with poor prognosis in which overexpression of a panel of microRNAs has been associated with malignancy but a very limited number of investigations on their role in ACC pathogenesis have been conducted. We examined the involvement of miR-483-5p and miR-139-5p in adrenocortical cancer aggressiveness. Using bioinformatics predictions and mRNA/miRNA expression profiles, we performed an integrated analysis to identify inversely correlated miRNA-mRNA pairs in ACC.

TWJ-Screen: an isothermal screening assay to assess ligand/DNA junction interactions in vitro.

The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells.