14 results on '"Di Lisio, L."'
Search Results
2. EBV-Bart-6-3p induces cell proliferation and escape of immunosurveillance in BL cell lines and primary tumours
- Author
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Falco, G., Navari, M., Onnis, A., Di Lisio, L., Martinez, N., Leon, E. A., Montes-Moreno, S., Rogena, E., Bellan, C., Piris, M. A., and Lorenzo LEONCINI
- Published
- 2012
3. new insights into the pathogenesis of Burkitt lymphoma: EBV-encoded and human microRNA profiling
- Author
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Di Lisio, L., Onnis, A., Martinez, N., Falco, G., Andres Leon, E., Montes-Moreno, S., Bellan, C., Tumwine, L., Mawanda, M., Ogwang, M., Piris, M. A., and Lorenzo LEONCINI
- Published
- 2011
4. MicroRNA signatures in B-cell lymphomas
- Author
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Di Lisio, L, primary, Sánchez-Beato, M, additional, Gómez-López, G, additional, Rodríguez, M E, additional, Montes-Moreno, S, additional, Mollejo, M, additional, Menárguez, J, additional, Martínez, M A, additional, Alves, F J, additional, Pisano, D G, additional, Piris, M A, additional, and Martínez, N, additional
- Published
- 2012
- Full Text
- View/download PDF
5. EBV-Bart-6-3p induces cell proliferation and escape of immunosurveillance in BL cell lines and primary tumours
- Author
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Falco, G., Navari, M., Ambrosio, M. R., Di Lisio, L., Onnis, A., Martinez, N., Leon, E. A., Bellan, C., Piris, M. A., and Lorenzo LEONCINI
6. EBV-Bart-6-3p induces cell proliferation and escape of immunosurveillance in BL cell lines and primary tumours
- Author
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Rogena, E. A., Di Lisio, L., Navari, M., Onnis, A., Martinez, N., Falco, G., Leon, E. A., Montes-Moreno, S., Bellan, C., Piris, M. A., Mwanda, W., and Lorenzo LEONCINI
7. Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma.
- Author
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Dayimu A, Di Lisio L, Anand S, Roca-Carreras I, Qian W, Al-Mohammad A, Basu B, Valle JW, Jodrell D, Demiris N, and Corrie P
- Subjects
- Humans, Prospective Studies, Proto-Oncogene Proteins p21(ras) genetics, Paclitaxel, CA-19-9 Antigen, Albumins, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Adenocarcinoma drug therapy, Adenocarcinoma genetics, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Liver Neoplasms secondary
- Abstract
Background: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) offers limited benefits, but survival outcomes vary. Reliable predictive response biomarkers to guide patient management are lacking., Methods: Patient performance status, tumour burden (determined by the presence or absence of liver metastases), plasma protein biomarkers (CA19-9, albumin, C-reactive protein and neutrophils) and circulating tumour DNA (ctDNA) were assessed in 146 patients with metastatic PDAC prior to starting either concomitant or sequential nab-paclitaxel + gemcitabine chemotherapy in the SIEGE randomised prospective clinical trial, as well as during the first 8 weeks of treatment. Correlations were made with objective response, death within 1 year and overall survival (OS)., Results: Initial poor patient performance status, presence of liver metastases and detectable
mut KRAS ctDNA all correlated with worse OS after adjusting for the different biomarkers of interest. Objective response at 8 weeks also correlated with OS (P = 0.026). Plasma biomarkers measured during treatment and prior to the first response assessment identified ≥10% decrease in albumin at 4 weeks predicted for worse OS (HR 4.75, 95% CI 1.43-16.94, P = 0.012), while any association of longitudinal evaluation ofmut KRAS ctDNA with OS was unclear (β = 0.024, P = 0.057)., Conclusions: Readily measurable patient variables can aid the prediction of outcomes from combination chemotherapy used to treat metastatic PDAC. The role ofmut KRAS ctDNA as a tool to guide treatment warrants further exploration., Clinical Trial Registration: ISRCTN71070888; ClinialTrials.gov (NCT03529175)., (© 2023. The Author(s).)- Published
- 2023
- Full Text
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8. Glutaminolysis is a metabolic dependency in FLT3 ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition.
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Gallipoli P, Giotopoulos G, Tzelepis K, Costa ASH, Vohra S, Medina-Perez P, Basheer F, Marando L, Di Lisio L, Dias JML, Yun H, Sasca D, Horton SJ, Vassiliou G, Frezza C, and Huntly BJP
- Subjects
- CRISPR-Cas Systems, Enzyme Activation drug effects, Enzyme Activation genetics, Genome-Wide Association Study, Glutamine genetics, Humans, K562 Cells, THP-1 Cells, Glutamine metabolism, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute enzymology, Leukemia, Myeloid, Acute genetics, Mutation, Protein Kinase Inhibitors pharmacology, fms-Like Tyrosine Kinase 3 antagonists & inhibitors, fms-Like Tyrosine Kinase 3 genetics, fms-Like Tyrosine Kinase 3 metabolism
- Abstract
FLT3 internal tandem duplication (FLT3
ITD ) mutations are common in acute myeloid leukemia (AML) associated with poor patient prognosis. Although new-generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3ITD AML patients remains poor and demands the identification of novel, specific, and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screen, we identify GLS, the first enzyme in glutamine metabolism, as synthetically lethal with FLT3-TKI treatment. Using complementary metabolomic and gene-expression analysis, we demonstrate that glutamine metabolism, through its ability to support both mitochondrial function and cellular redox metabolism, becomes a metabolic dependency of FLT3ITD AML, specifically unmasked by FLT3-TKI treatment. We extend these findings to AML subtypes driven by other tyrosine kinase (TK) activating mutations and validate the role of GLS as a clinically actionable therapeutic target in both primary AML and in vivo models. Our work highlights the role of metabolic adaptations as a resistance mechanism to several TKI and suggests glutaminolysis as a therapeutically targetable vulnerability when combined with specific TKI in FLT3ITD and other TK activating mutation-driven leukemias., (© 2018 by The American Society of Hematology.)- Published
- 2018
- Full Text
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9. The Evx1/Evx1as gene locus regulates anterior-posterior patterning during gastrulation.
- Author
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Bell CC, Amaral PP, Kalsbeek A, Magor GW, Gillinder KR, Tangermann P, di Lisio L, Cheetham SW, Gruhl F, Frith J, Tallack MR, Ru KL, Crawford J, Mattick JS, Dinger ME, and Perkins AC
- Subjects
- Animals, Bone Morphogenetic Protein 4 genetics, Bone Morphogenetic Protein 4 metabolism, CRISPR-Cas Systems, Gene Editing, Homeodomain Proteins genetics, Mice, RNA, Long Noncoding genetics, Wnt3A Protein genetics, Wnt3A Protein metabolism, Body Patterning physiology, Clustered Regularly Interspaced Short Palindromic Repeats physiology, Embryo, Mammalian embryology, Gastrulation physiology, Gene Expression Regulation, Developmental physiology, Homeodomain Proteins biosynthesis, RNA, Long Noncoding biosynthesis
- Abstract
Thousands of sense-antisense mRNA-lncRNA gene pairs occur in the mammalian genome. While there is usually little doubt about the function of the coding transcript, the function of the lncRNA partner is mostly untested. Here we examine the function of the homeotic Evx1-Evx1as gene locus. Expression is tightly co-regulated in posterior mesoderm of mouse embryos and in embryoid bodies. Expression of both genes is enhanced by BMP4 and WNT3A, and reduced by Activin. We generated a suite of deletions in the locus by CRISPR-Cas9 editing. We show EVX1 is a critical downstream effector of BMP4 and WNT3A with respect to patterning of posterior mesoderm. The lncRNA, Evx1as arises from alternative promoters and is difficult to fully abrogate by gene editing or siRNA approaches. Nevertheless, we were able to generate a large 2.6 kb deletion encompassing the shared promoter with Evx1 and multiple additional exons of Evx1as. This led to an identical dorsal-ventral patterning defect to that generated by micro-deletion in the DNA-binding domain of EVX1. Thus, Evx1as has no function independent of EVX1, and is therefore unlikely to act in trans. We predict many antisense lncRNAs have no specific trans function, possibly only regulating the linked coding genes in cis.
- Published
- 2016
- Full Text
- View/download PDF
10. miR-217 is an oncogene that enhances the germinal center reaction.
- Author
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de Yébenes VG, Bartolomé-Izquierdo N, Nogales-Cadenas R, Pérez-Durán P, Mur SM, Martínez N, Di Lisio L, Robbiani DF, Pascual-Montano A, Cañamero M, Piris MA, and Ramiro AR
- Subjects
- Animals, B-Lymphocytes pathology, B-Lymphocytes physiology, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic pathology, Cells, Cultured, DNA Damage genetics, DNA Repair genetics, Gene Regulatory Networks, Lymphoma genetics, Lymphoma metabolism, Mice, Mice, Transgenic, Microarray Analysis, Proto-Oncogene Proteins c-bcl-6 genetics, Germinal Center physiology, MicroRNAs physiology, Oncogenes physiology
- Abstract
microRNAs are a class of regulators of gene expression that have been shown critical for a great number of biological processes; however, little is known of their role in germinal center (GC) B cells. Although the GC reaction is crucial to ensure a competent immune response, GC B cells are also the origin of most human lymphomas, presumably due to bystander effects of the immunoglobulin gene remodeling that takes place at these sites. Here we report that miR-217 is specifically upregulated in GC B cells. Gain- and loss-of-function mouse models reveal that miR-217 is a positive modulator of the GC response that increases the generation of class-switched antibodies and the frequency of somatic hypermutation. We find that miR-217 down-regulates the expression of a DNA damage response and repair gene network and in turn stabilizes Bcl-6 expression in GC B cells. Importantly, miR-217 overexpression also promotes mature B-cell lymphomagenesis; this is physiologically relevant as we find that miR-217 is overexpressed in aggressive human B-cell lymphomas. Therefore, miR-217 provides a novel molecular link between the normal GC response and B-cell transformation., (© 2014 by The American Society of Hematology.)
- Published
- 2014
- Full Text
- View/download PDF
11. The Epstein Barr-encoded BART-6-3p microRNA affects regulation of cell growth and immuno response in Burkitt lymphoma.
- Author
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Ambrosio MR, Navari M, Di Lisio L, Leon EA, Onnis A, Gazaneo S, Mundo L, Ulivieri C, Gomez G, Lazzi S, Piris MA, Leoncini L, and De Falco G
- Abstract
Background: Burkitt lymphoma is an aggressive B-cell lymphoma presenting in three clinical forms: endemic, sporadic and immunodeficiency-associated. More than 90% of endemic Burkitt lymphoma carry latent Epstein-Barr virus, whereas only 20% of sporadic Burkitt lymphoma are associated with Epstein-Barr infection. Although the Epstein-Barr virus is highly related with the endemic form, how and whether the virus participates in its pathogenesis remains to be fully elucidated. In particular, the virus may impair cellular gene expression by its own encoded microRNAs., Methods: Using microRNA profiling we compared Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases for both cellular and viral microRNAs. The array results were validated by qRT-PCR, and potential targets of viral microRNAs were then searched by bioinformatic predictions, and classified in functional categories, according to the Gene Ontology. Our findings were validated by in vitro functional studies and by immunohistochemistry on a larger series of cases., Results: We showed that a few cellular microRNAs are differentially expressed between Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases, and identified a subset of viral microRNAs expressed in Epstein-Barr-positive Burkitt lymphomas. Of these, we characterized the effects of viral BART6-3p on regulation of cellular genes. In particular, we analyzed the IL-6 receptor genes (IL-6Rα and IL-6ST), PTEN and WT1 expression for their possible relevance to Burkitt lymphoma. By means of immunohistochemistry, we observed a down-regulation of the IL-6 receptor and PTEN specifically in Epstein-Barr-positive Burkitt lymphoma cases, which may result in the impairment of key cellular pathways and may contribute to malignant transformation. On the contrary, no differences were observed between Epstein-Barr-positive and Epstein-Barr-negative Burkitt lymphoma cases for WT1 expression., Conclusions: Our preliminary results point at an active role for the Epstein-Barr virus in Burkitt lymphomagenesis and suggest new possible mechanisms used by the virus in determining dysregulation of the host cell physiology.
- Published
- 2014
- Full Text
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12. The role of miRNAs in the pathogenesis and diagnosis of B-cell lymphomas.
- Author
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Di Lisio L, Martinez N, Montes-Moreno S, Piris-Villaespesa M, Sanchez-Beato M, and Piris MA
- Subjects
- Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Prognosis, Survival Analysis, Genetic Predisposition to Disease genetics, Lymphoma, B-Cell diagnosis, Lymphoma, B-Cell genetics, MicroRNAs genetics
- Abstract
There is a demand to understand B-cell lymphoma pathogenesis better, to identify new markers, and to define multiple lymphoproliferative disorders more accurately. MicroRNAs (miRNAs) are regulators of protein translation, comprising a group of more than 1500 short noncoding single-strand RNA molecules of approximately 22 nucleotides in length. They are easily detectable in fresh or paraffin-embedded diagnostic tissue and serum. Expression of individual miRNAs and miRNA signatures allows specific cell-differentiation stages to be identified, and is a powerful diagnostic and prognostic method. Here we review what is known about the pathogenic relevance of miRNAs, and use of miRNAs for the diagnosis and prognosis of B-cell lymphomas. Most of the published data concern chronic lymphocytic lymphoma and diffuse large B-cell lymphoma, and implicate miRNAs in the pathogenesis of these diseases. They identify miRNAs that could be used for diagnosis, prognosis, or prediction of response to specific therapies.
- Published
- 2012
- Full Text
- View/download PDF
13. Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway.
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Bueno MJ, Gómez de Cedrón M, Gómez-López G, Pérez de Castro I, Di Lisio L, Montes-Moreno S, Martínez N, Guerrero M, Sánchez-Martínez R, Santos J, Pisano DG, Piris MA, Fernández-Piqueras J, and Malumbres M
- Subjects
- Animals, Burkitt Lymphoma genetics, Cell Line, Tumor, Female, Humans, Male, MicroRNAs genetics, Proto-Oncogene Proteins c-myc genetics, RNA, Neoplasm genetics, Burkitt Lymphoma metabolism, Gene Expression Regulation, Neoplastic, MicroRNAs metabolism, Proto-Oncogene Proteins c-myc biosynthesis, RNA, Neoplasm metabolism
- Abstract
Many mammalian transcripts contain target sites for multiple miRNAs, although it is not clear to what extent miRNAs may coordinately regulate single genes. We have mapped the interactions between down-regulated miRNAs and overexpressed target protein-coding genes in murine and human lymphomas. Myc, one of the hallmark oncogenes in these lymphomas, stands out as the up-regulated gene with the highest number of genetic interactions with down-regulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach identifies MYC and multiple Myc targets as a preferential target of down-regulated miRNAs in human Burkitt lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately down-regulated to enhance critical oncogenes, such as Myc. Some of these Myc-targeting miRNAs are repressed by Myc, suggesting that these tumors are a consequence of the unbalanced activity of Myc versus miRNAs.
- Published
- 2011
- Full Text
- View/download PDF
14. Deregulated expression of the polycomb-group protein SUZ12 target genes characterizes mantle cell lymphoma.
- Author
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Martín-Pérez D, Sánchez E, Maestre L, Suela J, Vargiu P, Di Lisio L, Martínez N, Alves J, Piris MA, and Sánchez-Beato M
- Subjects
- Apoptosis, Cell Differentiation genetics, Cell Line, DNA Repair, Gene Expression Profiling, Humans, Neoplasm Proteins, Oligonucleotide Array Sequence Analysis, Polycomb Repressive Complex 2, Transcription Factors, Carrier Proteins genetics, Carrier Proteins metabolism, Gene Expression Regulation, Neoplastic, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism
- Abstract
Polycomb proteins are known to be of great importance in human cancer pathogenesis. SUZ12 is a component of the Polycomb PRC2 complex that, along with EZH2, is involved in embryonic stem cell differentiation. EZH2 plays an essential role in many cancer types, but an equivalent involvement of SUZ12 has not been as thoroughly demonstrated. Here we show that SUZ12 is anomalously expressed in human primary tumors, especially in mantle cell lymphoma (MCL), pulmonary carcinomas and melanoma, and is associated with gene locus amplification in some cases. Using MCL as a model, functional and genomic studies demonstrate that SUZ12 loss compromises cell viability, increases apoptosis, and targets genes involved in central oncogenic pathways associated with MCL pathogenesis. Our results support the hypothesis that the abnormal expression of SUZ12 accounts for some of the unexplained features of MCL, such as abnormal DNA repair and increased resistance to apoptosis.
- Published
- 2010
- Full Text
- View/download PDF
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