Profiling of the Predicted Circular RNAs in Ductal In Situ and Invasive Breast Cancer: A Pilot Study

The recent advantage obtained by next generation sequencing allows a depth investigation of a new "old" kind of noncoding transcript, the circular RNAs. Circular RNAs are nontranslated RNAs, typically nonpolyadenylated, with a resistance to exonucleases that gives them the ability to be more stable than the common linear RNA isoforms. We used a bioinformatic detection tool (CIRCexplorer) to research predictive circRNAs from the next generation sequenced data of five samples of ductal in situ carcinoma (DCIS) and matched adjacent invasive ductal carcinoma (IDC). Furthermore, we also investigated the circular RNAs expressed in MCF7, an invasive breast ductal carcinoma cell line. We described the genomic context of the predicted circular RNAs and we address the hypothetical possible functional roles. This study showed a perspective of a panel of predictive circRNAs identified and the function that circRNAs could exert

A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl) 121,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, obtained by conjugating the protein with the macrocyclic chelating agent DOTA through a one-pot reaction in aqueous medium. The product has been fully characterized and is stable to the thermal conditions adopted for labeling; after radiolabeling with longer half-life radionuclides such as 177 Lu or 111 In, it has shown radiochemical purity (RCP) >90% and resulted stable when stored in saline or plasma for 6 days at 37 \ub0C. A \u3bcPET/CT study, performed in vivo on adult female rats, showed that the radioactivity of HAC labeled with 64 Cu remained located in the mammary glands for at least 40 h, without diffusion or drainage in healthy tissues or in the lymphatic circulation. This new imaging agent might make the ROLL procedure more accessible, safe and flexible, promoting a significant time and cost reduction of this intervention. Moreover, HAC might also be used in other radio-guided surgical procedures in oncology

Heterogeneity in circulating tumor cells : the relevance of the stem-cell subset

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial⁻mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity

Distal motor neuropathy associated with novel EMILIN1 mutation

Abstract Elastin microfibril interface-located proteins (EMILINs) are extracellular matrix glycoproteins implicated in elastogenesis and cell proliferation. Recently, a missense mutation in the EMILIN1 gene has been associated with autosomal dominant connective tissue disorder and motor-sensory neuropathy in a single family. We identified by whole exome sequencing a novel heterozygous EMILIN1 mutation c.748C>T [p.R250C] located in the coiled coil forming region of the protein, in four affected members of an autosomal dominant family presenting a distal motor neuropathy phenotype. In affected patient a sensory nerve biopsy showed slight and unspecific changes in the number and morphology of myelinated fibers. Immunofluorescence study of a motor nerve within a muscle biopsy documented the presence of EMILIN-1 in nerve structures. Skin section and skin derived fibroblasts displayed a reduced extracellular deposition of EMILIN-1 protein with a disorganized network of poorly ramified fibers in comparison with controls. Downregulation of emilin1a in zebrafish displayed developmental delay, locomotion defects, and abnormal axonal arborization from spinal cord motor neurons. The phenotype was complemented by wild-type zebrafish emilin1a, and partially the human wild-type EMILIN1 cRNA, but not by the cRNA harboring the novel c.748C>T [p.R250C]. These data suggest a role of EMILIN-1 in the pathogenesis of diseases affecting the peripheral nervous system

Loss of miR-204 expression is a key event in melanoma

Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds − 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS

Flow boiling in microchannels and microgravity

A critical review of the state of the art of research on internal forced convection boiling in microchannels and in microgravity conditions is the main object of the present paper. In many industrial applications, two-phase flows are used for heavy-duty and reliable cooling and heating processes. The boiling phenomena are essential for evaporator heat exchangers, even in a very small scales, such as for PC cooling, refrigerators, HVAC systems. Even if the study of boiling is a standard research since a century, there are many aspects which are still under discussion, especially for forced convection boiling in small tubes. As the present review is pointing out, some literature results are still incongruous, giving critical uncertainties to the design engineers. The use of non-dimensional parameters is rather useful, but, especially in case of boiling, may provide an erroneous picture of the phenomena in quantitative and qualitative meaning. The idea to consider the channel microsize together with the microgravity effects in a single review is due to the fact that the transition between confined and unconfined bubble flows may be defined using dimensionless numbers, such as the Eötvös number Eo = g(ρL-ρV)L2/σ and its analogs, which are at the same time linked to the tube diameter and the gravity forces. In fact the Eötvös number tends to zero either when the gravity tends to zero or when the tube diameter tends to zero, but physical phenomena appear different considering separately either only the tube size or only the microgravity condition. Since the global picture of such physical process in flow boiling remains unclear, we claim the necessity to define in the most complete way the status-of-the-art of such an important research field and critically investigate the successes and the weaknesses of the current scientific literature. Noteworthy, the distinction between a macroscale and a microscale regime is misleading, since it could bring to consider a drastical variation of the physical phenomena, which is in fact not occurring until extremely low values of the channel dimension. Instead there is a typical flow pattern, the confined bubble flow, which is the dominant flow mechanism in small channels and in microgravity. Furthermore the vapor quality is a very important parameter, whose role is not well described in the present pattern classification. The values and combinations of the dimensionless numbers at which such pattern appears is the main issue of the present researches. Noteworthy, the meaning of "micro" is here used, as in the present literature, in a broad meaning, not strictly linked to the actual size of the channel, but to a change of patterns (and other physical characteristics) linked to a given dimensionless scale

Food-related family lifestyle associated with fruit and vegetable consumption among young adolescents in Belgium Flanders and the Veneto Region of Italy.

none5The present paper examined the relationship between fruit and vegetable consumption and food-related family lifestyle (dinner with parents, family food rules, and television viewing behaviors) in a sample of 14,407 adolescents from Belgium Flanders (N = 7,904) and the Veneto Region of Italy (N = 6,503) using multilevel binary logistic regression analyses. The data are part of the Health Behavior in School-aged Children cross-sectional survey. Daily dinner with parents, having more strict family food rules, and low television viewing behaviors were associated with daily fruit and vegetable intake. Watching television during meals was not associated with the outcome variables.mixedVERZELETTI C.; MAES L.; SANTINELLO M.; BALDASSARI D.; VEREECKEN C.A.Verzeletti, Chiara; Maes, L.; Santinello, Massimo; Baldassari, D.; Vereecken, C. A