Publications
134 results found
Misciali C, Tengattini V, Baraldi C, et al., 2013, Leg ulcers associated with giant cell arteritis relapse., Int J Low Extrem Wounds, Vol: 12, Pages: 69-70
Magnani L, Carroll J, Zwart W, et al., 2012, ChIPing away at breast cancer, LANCET ONCOLOGY, Vol: 13, Pages: 1185-1187, ISSN: 1470-2045
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- Citations: 2
Magnani L, Brunelle M, Gevry N, et al., 2012, Chromatin landscape and endocrine response in breast cancer, EPIGENOMICS, Vol: 4, Pages: 675-683, ISSN: 1750-1911
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- Citations: 12
Thiaville MM, Stoeck A, Chen L, et al., 2012, Identification of PBX1 target genes in cancer cells by global mapping of PBX1 binding sites, PLOS One, Vol: 7, ISSN: 1932-6203
PBX1 is a TALE homeodomain transcription factor involved in organogenesis and tumorigenesis. Although it has been shown that ovarian, breast, and melanoma cancer cells depend on PBX1 for cell growth and survival, the molecular mechanism of how PBX1 promotes tumorigenesis remains unclear. Here, we applied an integrated approach by overlapping PBX1 ChIP-chip targets with the PBX1-regulated transcriptome in ovarian cancer cells to identify genes whose transcription was directly regulated by PBX1. We further determined if PBX1 target genes identified in ovarian cancer cells were co-overexpressed with PBX1 in carcinoma tissues. By analyzing TCGA gene expression microarray datasets from ovarian serous carcinomas, we found co-upregulation of PBX1 and a significant number of its direct target genes. Among the PBX1 target genes, a homeodomain protein MEOX1 whose DNA binding motif was enriched in PBX1-immunoprecipicated DNA sequences was selected for functional analysis. We demonstrated that MEOX1 protein interacts with PBX1 protein and inhibition of MEOX1 yields a similar growth inhibitory phenotype as PBX1 suppression. Furthermore, ectopically expressed MEOX1 functionally rescued the PBX1-withdrawn effect, suggesting MEOX1 mediates the cellular growth signal of PBX1. These results demonstrate that MEOX1 is a critical target gene and cofactor of PBX1 in ovarian cancers.
Restuccia G, Cavazza A, Boiardi L, et al., 2012, Small-vessel vasculitis surrounding an uninflamed temporal artery and isolated vasa vasorum vasculitis of the temporal artery: two subsets of giant cell arteritis., Arthritis Rheum, Vol: 64, Pages: 549-556
OBJECTIVE: To evaluate the frequency and clinical characteristics of periadventitial small-vessel vasculitis (SVV) and isolated vasa vasorum vasculitis (VVV). METHODS: We identified 455 temporal artery biopsies performed in residents of Reggio Emilia, Italy between 1986 and 2003. Slides of temporal artery biopsy specimens were reviewed by a pathologist who was blinded with regard to clinical data. SVV was defined as inflammation of the small vessels external to the temporal artery adventitia, and VVV was defined as isolated inflammation of temporal artery vasa vasorum. Medical records of patients with SVV and/or VVV were reviewed, and demographic, clinical, laboratory, and followup data were collected. For comparison purposes, we collected the same data from an equal number of randomly selected patients with evidence of classic giant cell arteritis (GCA). RESULTS: Sixteen patients had SVV, 18 had isolated VVV, and 5 had both SVV and VVV. Compared with patients with classic GCA, the frequencies of headache, scalp tenderness, abnormalities of temporal arteries, jaw claudication, anorexia, and weight loss, the levels of acute-phase reactant at diagnosis, and the initial and cumulative doses prednisone were significantly lower and the frequency of peripheral synovitis was higher in the patients with SVV, and the frequency of cranial ischemic events was similar in the 2 groups. In contrast, the clinical characteristics and erythrocyte sedimentation rate at diagnosis of patients with isolated VVV were similar to those of patients with classic GCA. CONCLUSION: Our findings indicate that isolated VVV and SVV should be considered part of the histopathologic spectrum of GCA.
Salvarani C, Magnani L, Catanoso M, et al., 2012, Tocilizumab: a novel therapy for patients with large-vessel vasculitis., Rheumatology (Oxford), Vol: 51, Pages: 151-156
OBJECTIVE: Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV. METHODS: Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8 mg/kg bodyweight) for 6 consecutive months. Two patients were treatment naïve, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [(18)F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy. RESULTS: All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes. CONCLUSIONS: In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings.
Catanoso MG, Spaggiari L, Magnani L, et al., 2012, Efficacy of infliximab in a patient with refractory idiopathic retroperitoneal fibrosis., Clin Exp Rheumatol, Vol: 30, Pages: 776-778, ISSN: 0392-856X
Glucocorticoids are the mainstay of treatment of idiopathic retroperitoneal fibrosis (IRF). However, relapses are frequent upon tapering of the glucocorticoid dose. A variety of traditional immunosuppressants have been proposed as steroid-sparing agents, but some patients fail to adequately respond to combined glucocorticoid and immunosuppressive therapy. We report a patient with IRF refractory to combined glucocorticoid and methotrexate therapy treated with the anti-TNF-α monoclonal antibody infliximab. Infliximab was administered at 5 mg/kg/bodyweight at week 0, 2, 6 and 8-weekly thereafter for 3 consecutive years. Drug efficacy and safety were assessed clinically and by laboratory tests at treatment onset and subsequently before each infusion. In addition, 18FFluorodeoxyglucose (FDG) positron emission computerised tomography (PET/CT) and abdominal CT scans were used to monitor disease activity and response to treatment. Infliximab therapy resulted in a satisfactory clinical and laboratory response paralleled by an improvement in imaging findings. No serious adverse events were noted. Infliximab may be an effective and safe treatment for refractory IRF. A controlled study is required to confirm our findings.
Salvarani C, Magnani L, Catanoso MG, et al., 2012, Rescue treatment with tocilizumab for Takayasu arteritis resistant to TNF-α blockers., Clin Exp Rheumatol, Vol: 30, Pages: S90-S93, ISSN: 0392-856X
Anti-TNF-α therapy has successfully been used to treat Takayasu arteritis (TA) refractory to conventional immunosuppressive treatment. However, some patients fail to respond even to TNF-α blockers. Interleukin-6 (IL-6) is a key player in the pathogenesis of TA. Preliminary data also suggest efficacy of the IL-6 receptor inhibitor tocilizumab in patients with large-vessel vasculitis. We report a patient with TA refractory to multiple conventional immunosuppressive agents and two TNF-α blockers successfully treated with monthly tocilizumab infusions (8 mg/kg body weight) for 6 consecutive months. Clinical indices of disease activity, inflammatory markers, and 18Ffluorodeoxyglucose positron emission/computerised tomography findings normalised, while the prednisone dosage could be tapered. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels raised during tocilizumab treatment consistent with the mode of action of tocilizumab. Tocilizumab holds promise for patients with refractory TA. Larger studies are required to confirm our findings.
Wang X, Park K-E, Koser S, et al., 2012, <i>KPNA7</i>, an oocyte- and embryo-specific karyopherin α subtype, is required for porcine embryo development, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 24, Pages: 382-391, ISSN: 1031-3613
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- Citations: 32
Magnani L, Ballantyne EB, Zhang X, et al., 2011, PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer, PLOS GENETICS, Vol: 7, ISSN: 1553-7404
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- Citations: 144
Magnani L, Eeckhoute J, Lupien M, 2011, Pioneer factors: directing transcriptional regulators within the chromatin environment, TRENDS IN GENETICS, Vol: 27, Pages: 465-474, ISSN: 0168-9525
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- Citations: 109
Catanoso M, Pipitone N, Magnani L, et al., 2011, New indications for biological therapies., Intern Emerg Med, Vol: 6 Suppl 1, Pages: 1-9
Biological agents have originally been developed to treat refractory arthritis, but evidence has been accruing, supporting their use in vasculitis as well. In the large-vessel vasculitides giant cell arteritis and Takayasu arteritis, TNF-α inhibitors have shown some efficacy in patients with relapsing disease. In contrast, in patients with recent onset of giant cell arteritis, TNF-α inhibitors failed to provide a significant benefit over and above that conferred by glucocorticoids alone. More recent, preliminary data suggest a role for the interleukin-6 receptor antagonist tocilizumab in both resistant and treatment-naïve giant cell arteritis and Takayasu arteritis. Biological agents have also been proposed to treat difficult anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Uncontrolled observations suggest that the TNF-α inhibitor infliximab might be beneficial in resistant cases. On the contrary, a randomized controlled trial did not show superiority of the recombinant human soluble TNF-α p75 receptor fusion protein etanercept over placebo in maintaining remission in granulomatosis with polyangiitis. Two randomized controlled trials have demonstrated that the anti-CD20 monoclonal antibody rituximab was as effective as the standard-of-care agent cyclophosphamide in inducing remission. In addition, rituximab appeared to be superior to cyclophosphamide in inducing remission in the subset of patients with relapsing disease. These findings prove that biological therapy has a role in vasculitis. Research is investigating novel therapies as well as focusing on how to best use the available drugs.
Magnani L, Versari A, Salvo D, et al., 2011, Disease activity assessment in large vessel vasculitis, Reumatismo, Vol: 63, Pages: 86-90, ISSN: 0048-7449
Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.
Wang K, Sengupta S, Magnani L, et al., 2010, Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts, PLOS One, Vol: 5, ISSN: 1932-6203
During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates that suppression of Oct4 expression in the trophectoderm is mediated by Cdx2. Nonetheless, the underlying epigenetic modifiers required for Cdx2-dependent repression of Oct4 are largely unknown. Here we show that the chromatin remodeling protein Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts. By employing a combination of RNA interference (RNAi) and gene expression analysis we found that both Brg1 Knockdown (KD) and Cdx2 KD blastocysts exhibit widespread expression of Oct4 in the trophectoderm. Interestingly, in Brg1 KD blastocysts and Cdx2 KD blastocysts, the expression of Cdx2 and Brg1 is unchanged, respectively. To address whether Brg1 cooperates with Cdx2 to repress Oct4 transcription in the developing trophectoderm, we utilized preimplantation embryos, trophoblast stem (TS) cells and Cdx2-inducible embryonic stem (ES) cells as model systems. We found that: (1) combined knockdown (KD) of Brg1 and Cdx2 levels in blastocysts resulted in increased levels of Oct4 transcripts compared to KD of Brg1 or Cdx2 alone, (2) endogenous Brg1 co-immunoprecipitated with Cdx2 in TS cell extracts, (3) in blastocysts Brg1 and Cdx2 co-localize in trophectoderm nuclei and (4) in Cdx2-induced ES cells Brg1 and Cdx2 are recruited to the Oct4 promoter. Lastly, to determine how Brg1 may induce epigenetic silencing of the Oct4 gene, we evaluated CpG methylation at the Oct4 promoter in the trophectoderm of Brg1 KD blastocysts. This analysis revealed that Brg1-dependent repression of Oct4 expression is independent of DNA methylation at the blastocyst stage. In toto, these results demonstrate that Brg1 cooperates with Cdx2 to repress Oct4 expression in the developing trophectoderm to ensure normal development.
Park K-E, Johnson CM, Magnani L, et al., 2010, Global H3K9 Dimethylation Status Is Not Affected by Transcription, Translation, or DNA Replication in Porcine Zygotes, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 77, Pages: 420-429, ISSN: 1040-452X
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- Citations: 10
Dinelli BM, Arnone E, Brizzi G, et al., 2010, The MIPAS2D database of MIPAS/ENVISAT measurements retrieved with a multi-target 2-dimensional tomographic approach, ATMOSPHERIC MEASUREMENT TECHNIQUES, Vol: 3, Pages: 355-374, ISSN: 1867-1381
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- Citations: 33
Park K-E, Magnani L, Cabot RA, 2009, Differential Remodeling of Mono- and Trimethylated H3K27 During Porcine Embryo Development, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 76, Pages: 1033-1042, ISSN: 1040-452X
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- Citations: 43
Xing X, Magnani L, Lee K, et al., 2009, Gene Expression and Development of Early Pig Embryos Produced by Serial Nuclear Transfer, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 76, Pages: 555-563, ISSN: 1040-452X
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- Citations: 18
Carlotti M, Magnani L, 2009, Two-dimensional sensitivity analysis of MIPAS observations, OPTICS EXPRESS, Vol: 17, Pages: 5340-5357, ISSN: 1094-4087
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- Citations: 7
Magnani L, Cabot RA, 2009, Manipulation of <i>SMARCA2</i> and <i>SMARCA4</i> transcript levels in porcine embryos differentially alters development and expression of <i>SMARCA1</i>, <i>SOX2</i> <i>NANOG</i>, and <i>EIF1</i>, REPRODUCTION, Vol: 137, Pages: 23-33, ISSN: 1470-1626
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- Citations: 21
Wang X, Magnani L, Cabot R, 2009, KARYOPHERIN α EXPRESSION IN PORCINE OOCYTES AND EMBRYOS PRODUCED BY <i>IN VITRO</i> FERTILIZATION, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 21, Pages: 197-198, ISSN: 1031-3613
Biancardi MN, Magnani L, Johnson CM, et al., 2009, TRANSCRIPT ABUNDANCE OF METHYLTRANSFERASES SPECIFIC FOR H3K9 DIFFER AT DISCRETE STAGES OF PORCINE OOCYTE AND CLEAVAGE STAGE EMBRYO DEVELOPMENT, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 21, Pages: 188-188, ISSN: 1031-3613
Magnani L, Cabot RA, 2008, In Vitro and In Vivo Derived Porcine Embryos Possess Similar, but Not Identical, Patterns of Oct4, Nanog, and Sox2 mRNA Expression During Cleavage Development, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 75, Pages: 1726-1735, ISSN: 1040-452X
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- Citations: 53
Xing X, Magnani L, Lee K, et al., 2008, Gene expression in early porcine embryos following serial nuclear transfer, 16th International Congress on Animal Reproduction, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 7-7, ISSN: 0936-6768
Magnani L, Lee K, Fodor WL, et al., 2008, Developmental capacity of porcine nuclear transfer embryos correlate with levels of chromatin-remodeling transcripts in donor cells, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 75, Pages: 766-776, ISSN: 1040-452X
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- Citations: 5
Park K, Magnani L, Cabot R, 2008, Expression patterns of H3/K27 methylation mediating genes in porcine embryos, 41st Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 96-97, ISSN: 0006-3363
Magnani L, Cabot R, 2008, Relative abundance of Oct-4, Nanog, and Sox-2 transcripts in porcine oocytes and cleavage-stage embryos produced via fertilization <i>in vitro</i> or parthenogenesis, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 20, Pages: 168-169, ISSN: 1031-3613
Magnani L, Johnson CM, Cabot RA, 2008, Expression of eukaryotic elongation initiation factor 1A differentially marks zygotic genome activation in biparental and parthenogenetic porcine embryos and correlates with <i>in vitro</i> developmental potential, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 20, Pages: 818-825, ISSN: 1031-3613
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- Citations: 22
Magnani L, Cabot R, 2008, Ectopic expression of Brahma in porcine embryos induces developmental arrest and alters expression of SNF2L, 41st Annual Meeting of the Society-for-the-Study-of-Reproduction, Publisher: SOC STUDY REPRODUCTION, Pages: 72-72, ISSN: 0006-3363
Magnani L, Cabot RA, 2007, Developmental arrest induced in cleavage stage porcine embryos following microinjection of mRNA encoding <i>Brahma</i> (<i>Smarca 2</i>), a chromatin remodeling protein, MOLECULAR REPRODUCTION AND DEVELOPMENT, Vol: 74, Pages: 1262-1267, ISSN: 1040-452X
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- Citations: 11
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