Molecular Biotechnology Center
Molecular Biotechnology Center
Penna E.,Molecular Biotechnology Center |
Orso F.,Molecular Biotechnology Center |
Orso F.,University of Turin |
Taverna D.,Molecular Biotechnology Center |
Taverna D.,University of Turin
Journal of Investigative Dermatology | Year: 2015
MicroRNAs are short regulatory RNAs that are able to post-transcriptionally modulate gene expression and that have crucial roles in the control of physiological and pathological processes including cancer onset, growth, and progression. miR-214, located inside the sequence of the long noncoding Dmn3os transcript, contributes to the regulation of normal and cancer cell biology, even if it operates in a context-dependent and sometimes contradictory manner. miR-214 is deregulated in several human tumors including melanoma, breast, ovarian, gastric, and hepatocellular carcinomas. miR-214's pleiotropic and tumor-specific contribution to various cancer formation and progression hallmarks is achieved via its several target genes. In fact, miR-214 behaves as a key hub by coordinating fundamental signaling networks such as PTEN/AKT, β-catenin, and tyrosine kinase receptor pathways. Interestingly, miR-214 also regulates the levels of crucial gene expression modulators: the epigenetic repressor Ezh2, "genome guardian" p53, transcription factors TFAP2, and another microRNA, miR-148b. Thus, miR-214 seems to have essential roles in coordinating tumor proliferation, stemness, angiogenesis, invasiveness, extravasation, metastasis, resistance to chemotherapy, and microenvironment. The sum of current literature reports suggests that miR-214 is a molecular hub involved in the control of cancer networks and, as such, could be a potential diagnostic/prognostic biomarker and target for therapeutic intervention. © 2015 The Society for Investigative Dermatology.
Arigoni M.,University of Turin |
Barutello G.,University of Turin |
Lanzardo S.,University of Turin |
Longo D.,University of Turin |
And 8 more authors.
Angiogenesis | Year: 2012
Angiomotin (Amot) is one of several identified angiostatin receptors expressed by the endothelia of angiogenic tissues. We have shown that a DNA vaccine targeting Amot overcome immune tolerance and induce an antibody response that hampers the progression of incipient tumors. Following our observation of increased Amot expression on tumor endothelia concomitant with the progression from pre-neoplastic lesions to full-fledged carcinoma, we evaluated the effect of anti-Amot vaccination on clinically evident tumors. Electroporation of plasmid coding for the human Amot (pAmot) significantly delayed the progression both of autochthonous tumors in cancer prone BALB-neuT and PyMT genetically engineered mice and transplantable TUBO tumor in wild-type BALB/c mice. The intensity of the inhibition directly correlated with the titer of anti-Amot antibodies induced by the vaccine. Tumor inhibition was associated with an increase of vessels diameter with the formation of lacunar spaces, increase in vessel permeability, massive tumor perivascular necrosis and an effective epitope spreading that induces an immune response against other tumor associated antigens. Greater tumor vessel permeability also markedly enhances the antitumor effect of doxorubicin. These data provide a rationale for the development of novel anticancer treatments based on anti-Amot vaccination in conjunction with chemotherapy regimens. © The Author(s) 2012.
Perino A.,Molecular Biotechnology Center |
Perino A.,University of Turin |
Ghigo A.,Molecular Biotechnology Center |
Ghigo A.,University of Turin |
And 4 more authors.
Circulation Research | Year: 2012
Spatial and temporal organization of signal transduction is coordinated through the segregation of signaling enzymes in selected cellular compartments. This highly evolved regulatory mechanism ensures the activation of selected enzymes only in the vicinity of their target proteins. In this context, CaMP-responsive triggering of protein kinase A is modulated by a family of sCaffold proteins referred to as A-kinase anchoring proteins. A-kinase anchoring proteins form the core of multiprotein complexes and enable simultaneous but segregated CaMP signaling events to occur in defined cellular compartments. In this review we will focus on the description of A-kinase anchoring protein function in the regulation of Cardiac physiopathology. ©2012 AmeriCan Heart Association, Inc.
De Chiara L.,Molecular Biotechnology Center |
Fagoonee S.,Molecular Biotechnology Center |
Ranghino A.,University of Turin |
Bruno S.,Molecular Biotechnology Center |
And 5 more authors.
Journal of the American Society of Nephrology | Year: 2014
Spermatogonial stem cells reside in specific niches within seminiferous tubules and continuously generate differentiating daughter cells for production of spermatozoa. Although spermatogonial stem cells are unipotent, these cells are able to spontaneously convert to germline cell-derived pluripotent stem cells (GPSCs) in vitro. GPSCs have many properties of embryonic stem cells and are highly plastic, but their therapeutic potential in tissue regeneration has not been fully explored. Using a novel renal epithelial differentiation protocol, we obtained GPSC-derived tubular-like cells (GTCs) that were functional in vitro, as demonstrated through transepithelial electrical resistance analysis. In mice, GTCs injected after ischemic renal injury homed to the renal parenchyma, and GTC-treated mice showed reduced renal oxidative stress, tubular apoptosis, and cortical damage and upregulated tubular expression of the antioxidant enzyme hemeoxygenase-1. Six weeks after ischemic injury, kidneys of GTC-treated mice had less fibrosis and inflammatory infiltrate than kidneys of vehicle-treated mice. In conclusion, we show that GPSCs can be differentiated into functionally active renal tubular-like cells that therapeutically prevent chronic ischemic damage in vivo, introducing the potential utility of GPSCs in regenerative cell therapy. Copyright © 2014 by the American Society of Nephrology.
Camussi G.,Molecular Biotechnology Center |
Deregibus M.C.,Molecular Biotechnology Center |
Tetta C.,Sis Ter
Current Molecular Medicine | Year: 2013
Tumor cells release microvesicles (MVs) that may remain in the extracellular space in proximity to the cell of origin, or that may migrate to distant sites by entering biological fluids. Increasing evidence indicates that MVs are mediators of cell-to-cell communication which are able to deliver specific signals, both within the tumor microenvironment and in the long-range. MVs are able to transfer bioactive lipids and proteins, including oncogene products and receptors, from the cell of origin to recipient cell. In addition, MVs may induce epigenetic changes in recipient cells by transferring genetic information in the form of mRNA, microRNA and oncogenes. Several changes in the phenotype and function that occur in stromal cells within the cancer microenvironment have been ascribed to tumor cell-derived MVs. In this review we discuss the various biological actions of tumor-derived MVs and their potential role in tumor biology. © 2013 Bentham Science Publishers.
Grassi E.,Molecular Biotechnology Center |
Gregorio F.D.,DNDG Srl |
Molineris I.,Molecular Biotechnology Center
IEEE/ACM Transactions on Computational Biology and Bioinformatics | Year: 2012
Nowadays storing data derived from deep sequencing experiments has become pivotal and standard compression algorithms do not exploit in a satisfying manner their structure. A number of reference-based compression algorithms have been developed but they are less adequate when approaching new species without fully sequenced genomes or nongenomic data. We developed a tool that takes advantages of fastq characteristics and encodes them in a binary format optimized in order to be further compressed with standard tools (such as gzip or lzma). The algorithm is straightforward and does not need any external reference file, it scans the fastq only once and has a constant memory requirement. Moreover, we added the possibility to perform lossy compression, losing some of the original information (IDs and/or qualities) but resulting in smaller files; it is also possible to define a quality cutoff under which corresponding base calls are converted to N. We achieve 2.82 to 7.77 compression ratios on various fastq files without losing information and 5.37 to 8.77 losing IDs, which are often not used in common analysis pipelines. In this paper, we compare the algorithm performance with known tools, usually obtaining higher compression levels. © 2013 IEEE.
Biancone L.,Molecular Biotechnology Center |
Bruno S.,Molecular Biotechnology Center |
Deregibus M.C.,Molecular Biotechnology Center |
Tetta C.,Fresenius Medical Care |
Camussi G.,Molecular Biotechnology Center
Nephrology Dialysis Transplantation | Year: 2012
Several studies have demonstrated that mesenchymal stem cells have the capacity to reverse acute and chronic kidney injury in different experimental models by paracrine mechanisms. This paracrine action may be accounted for, at least in part, by microvesicles (MVs) released from mesenchymal stem cells, resulting in a horizontal transfer of mRNA, microRNA and proteins. MVs, released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, are now recognized as being an integral component of the intercellular microenvironment. By acting as vehicles for information transfer, MVs play a pivotal role in cell-to-cell communication. This exchange of information between the injured cells and stem cells has the potential to be bi-directional. Thus, MVs may either transfer transcripts from injured cells to stem cells, resulting in reprogramming of their phenotype to acquire specific features of the tissue, or conversely, transcripts could be transferred from stem cells to injured cells, restraining tissue injury and inducing cell cycle re-entry of resident cells, leading to tissue self-repair. Upon administration with a therapeutic regimen, MVs mimic the effect of mesenchymal stem cells in various experimental models by inhibiting apoptosis and stimulating cell proliferation. In this review, we discuss whether MVs released from mesenchymal stem cells have the potential to be exploited in novel therapeutic approaches in regenerative medicine to repair damaged tissues, as an alternative to stem cell-based therapy. © The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Ellena S.,Molecular Biotechnology Center |
Viale A.,Molecular Biotechnology Center |
Gobetto R.,Molecular Biotechnology Center |
Aime S.,Molecular Biotechnology Center
Magnetic Resonance in Chemistry | Year: 2012
Para-hydrogen-induced polarization effects have been observed in the 29Si NMR spectra of trimethylsilyl para-hydrogenated molecules. The high signal enhancements and the long T1 values observed for the 29Si hyperpolarized resonances point toward the possibility of using 29Si for hyperpolarization applications. A method for the discrimination of multiple compounds and/or complex mixtures of hydroxylic compounds (such as steroids), consisting of the silylization of alcoholic functionalities with an unsaturated silylalkyl moiety and subsequent reaction with para-H2, is proposed. Copyright © 2012 John Wiley & Sons, Ltd.
Martini M.,Molecular Biotechnology Center |
De Santis M.C.,Molecular Biotechnology Center |
Braccini L.,Molecular Biotechnology Center |
Gulluni F.,Molecular Biotechnology Center |
Hirsch E.,Molecular Biotechnology Center
Annals of Medicine | Year: 2014
Despite development of novel agents targeting oncogenic pathways, matching targeted therapies to the genetic status of individual tumors is proving to be a daunting task for clinicians. To improve the clinical efficacy and to reduce the toxic side effects of treatments, a deep characterization of genetic alterations in different tumors is required. The mutational profile often evidences a gain of function or hyperactivity of phosphoinositide 3-kinases (PI3Ks) in tumors. These enzymes are activated downstream tyrosine kinase receptors (RTKs) and/or G proteins coupled receptors (GPCRs) and, via AKT, are able to induce mammalian target of rapamycin (mTOR) stimulation. Here, we elucidate the impact of class I (p110α, β, γ, and δ) catalytic subunit mutations on AKT-mediated cellular processes that control crucial mechanisms in tumor development. Moreover, the interrelation of PI3K signaling with mTOR, ERK, and RAS pathways will be discussed, exploiting the potential benefits of PI3K signaling inhibitors in clinical use. © 2014 Informa UK, Ltd.
Vinchi F.,Molecular Biotechnology Center |
Ingoglia G.,Molecular Biotechnology Center |
Chiabrando D.,Molecular Biotechnology Center |
Mercurio S.,Molecular Biotechnology Center |
And 4 more authors.
Gastroenterology | Year: 2014
Background & Aims The liver has one of the highest rates of heme synthesis of any organ. More than 50% of the heme synthesized in the liver is used for synthesis of P450 enzymes, which metabolize exogenous and endogenous compounds that include natural products, hormones, drugs, and carcinogens. Feline leukemia virus subgroup C cellular receptor 1a (FLVCR1a) is plasma membrane heme exporter that is ubiquitously expressed and controls intracellular heme content in hematopoietic lineages. We investigated the role of Flvcr1a in liver function in mice. Methods We created mice with conditional disruption of Mfsd7b, which encodes Flvcr1a, in hepatocytes (Flvcr1a fl/fl;alb-cre mice). Mice were analyzed under basal conditions, after phenylhydrazine-induced hemolysis, and after induction of cytochromes P450 synthesis. Livers were collected and analyzed by histologic, quantitative real-time polymerase chain reaction, and immunoblot analyses. Hepatic P450 enzymatic activities were measured. Results Flvcr1afl/fl;alb-cre mice accumulated heme and iron in liver despite up-regulation of heme oxygenase 1, ferroportin, and ferritins. Hepatic heme export activity of Flvcr1a was closely associated with heme biosynthesis, which is required to sustain cytochrome induction. Upon cytochromes P450 stimulation, Flvcr1afl/fl;alb-cre mice had reduced cytochrome activity, associated with accumulation of heme in hepatocytes. The expansion of the cytosolic heme pool in these mice was likely responsible for the early inhibition of heme synthesis and increased degradation of heme, which reduced expression and activity of cytochromes P450. Conclusions In livers of mice, Flvcr1a maintains a free heme pool that regulates heme synthesis and degradation as well as cytochromes P450 expression and activity. These findings have important implications for drug metabolism.