8 results on '"Borrelli S"'
Search Results
2. Unexpected worsening of progressive multifocal leucoencephalopathy following COVID-19 pneumonia.
- Author
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Borrelli, S., Dachy, B., Gazagnes, M-D., and Du Pasquier, R.
- Subjects
- *
COVID-19 , *NATALIZUMAB , *SARS-CoV-2 , *MONOCLONAL antibodies , *PNEUMONIA , *MULTIPLE sclerosis - Abstract
Progressive multifocal leucoencephalopathy is a serious side effect of natalizumab, a humanized monoclonal antibody approved for the treatment of multiple sclerosis. Here, we report a case of unexpected worsening of natalizumab-related progressive multifocal leucoencephalopathy following COVID-19. After natalizumab discontinuation, a slight neurological improvement was observed, but, two months later the patient was admitted to the hospital because of neurological deterioration and COVID-19 mild pneumonia. Except for SARS-CoV-2 infection, no other potential factors of neurological worsening were identified. Thus, we pose the hypothesis that SARS-CoV-2 was instrumental in the progressive multifocal leucoencephalopathy deterioration. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. Mutant p53 subverts p63 control over KLF4 expression in keratinocytes
- Author
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Cordani, N, Pozzi, S, Martynova, E, Fanoni, D, Borrelli, S, Alotto, D, Castagnoli, C, Berti, E, Viganò, M, Mantovani, R, CORDANI, NICOLETTA, BERTI, EMILIO, Viganò, MA, Mantovani, R., Cordani, N, Pozzi, S, Martynova, E, Fanoni, D, Borrelli, S, Alotto, D, Castagnoli, C, Berti, E, Viganò, M, Mantovani, R, CORDANI, NICOLETTA, BERTI, EMILIO, Viganò, MA, and Mantovani, R.
- Abstract
Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.
- Published
- 2011
4. miR-205 regulates basement membrane deposition in human prostate: implications for cancer development.
- Author
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Gandellini, P, Profumo, V, Casamichele, A, Fenderico, N, Borrelli, S, Petrovich, G, Santilli, G, Callari, M, Colecchia, M, Pozzi, S, De Cesare, M, Folini, M, Valdagni, R, Mantovani, R, and Zaffaroni, N
- Subjects
BASAL lamina ,CANCER invasiveness ,CANCER cells ,ANDROGEN receptors ,MESSENGER RNA ,PROTEASOME inhibitors ,EXTRACELLULAR matrix - Abstract
The basement membrane (BM) is a layer of specialized extracellular matrix that surrounds normal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM is a prerequisite for tumor cell invasion into interstitial spaces, thus favoring metastasis. Therefore, BM maintenance represents a barrier against cancer development and progression. In the study, we show that miR-205 participates in a network involving ΔNp63α, which is essential for maintenance of the BM in prostate epithelium. At the molecular level, ΔNp63α is able to enhance miR-205 transcription by binding to its promoter, whereas the microRNA can post-transcriptionally limit the amount of ΔNp63α protein, mostly by affecting ΔNp63α proteasomal degradation rather than through a canonical miRNA/target interaction. Functionally, miR-205 is able to control the deposition of laminin-332 and its receptor integrin-β4. Hence, pathological loss of miR-205, as widely observed in prostate cancer, may favor tumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
5. The p63 target HBP1 is required for skin differentiation and stratification.
- Author
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Borrelli, S., Candi, E., Hu, B., Dolfini, D., Ravo, M., Grober, O. M. V, Weisz, A., Dotto, G. P., Melino, G., Viganò, M. A., and Mantovani, R.
- Subjects
- *
TRANSCRIPTION factors , *EPITHELIAL cells , *DNA-binding proteins , *CELL differentiation , *CHROMATIN , *KERATINOCYTES , *CELL physiology - Abstract
Genetic experiments established that p63 is crucial for the development and maintenance of pluristratified epithelia. In the RNA interference (RNAi) screening for targets of p63 in keratinocytes, we identified the transcription factor, High Mobility Group (HMG) box protein 1 (HBP1). HBP1 is an HMG-containing repressor transiently induced during differentiation of several cell lineages. We investigated the relationship between the two factors: using RNAi, overexpression, chromatin immunoprecipitations and transient transfections with reporter constructs, we established that HBP1 is directly repressed by p63. This was further confirmed in vivo by evaluating expression in p63 knockout mice and in transgenics expressing p63 in basal keratinocytes. Consistent with these findings, expression of HBP1 increases upon differentiation of primary keratinocytes and HaCaT cells in culture, and it is higher in the upper layers of human skin. Inactivation of HBP1 by RNAi prevents differentiation of keratinocytes and stratification of organotypic skin cultures. Finally, we analyzed the keratinocyte transcriptomes after HBP1 RNAi; in addition to repression of growth-promoting genes, unexpected activation of differentiation genes was uncovered, coexisting with repression of other genes involved in epithelial cornification. Our data indicate that suppression of HBP1 is part of the growth-promoting strategy of p63 in the lower layers of epidermis and that HBP1 temporally coordinates expression of genes involved in stratification, leading to the formation of the skin barrier. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
6. p63 regulates the caspase-8-FLIP apoptotic pathway in epidermis.
- Author
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Borrelli, S., Candi, E., Alotto, D., Castagnoli, C., Melino, G., Viganò, M. A., and Mantovani, R.
- Subjects
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TRANSCRIPTION factors , *EPITHELIAL cells , *WESTERN immunoblotting , *PROMOTERS (Genetics) , *KERATINOCYTES , *TRANSGENIC mice , *LABORATORY mice - Abstract
The transcription factor p63, member of the p53 family, is crucial for epithelial development. An RNAi screening identified the apoptotic gene Procaspase-8 as a target activated by p63. The caspase-8 inhibitor FLIP is also under p63 control. We analysed and detailed the direct transactivation through the use of RNAi, reporter assays, ChIPs, western blots, confocal studies in HaCat, as well as in primary human keratinocytes. The direct ΔNp63 regulation of these targets was confirmed in vivo using transgenic ΔNp63 mice under the K5 promoter, as compared with p63 knockout mice, and in vitro in normal human primary keratinocytes following UV irradiation. Lowering the steady state of p63 protein levels changes the relative ratio of FLIP isoforms, causing the activation of the expressed, inactive Procaspase-8, into the active isoform thus triggering the proapoptotic cascade. Therefore, p63 fine-tunes the Procaspase-8-FLIP pro- and antiapoptotic pathway in keratinocytes.Cell Death and Differentiation (2009) 16, 253–263; doi:10.1038/cdd.2008.147; published online 17 October 2008 [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
7. Monoclonal antibodies against Haemophilus ducreyi lipooligosaccharide and their diagnostic usefulness.
- Author
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Ahmed, H., Borrelli, S., Jonasson, J., Eriksson, L., Hanson, S., Höjer, B., Sunkuntu, M., Musaba, E., Roggen, E., Lagergård, T., and Lindberg, A.
- Abstract
Monoclonal antibodies against the lipooligosaccharide of Haemophilus ducreyi were produced. Two of them, MAHD6 and MAHD7, were found to be relatively, although not absolutely, specific and reacted with nearly all strains of Haemophilus ducreyi tested: 59 of 60 and 60 of 60, respectively. The diagnostic usefulness of MAHD7 was assessed. Clinical specimens collected in Zambia from patients with genital ulcers were tested using indirect immunofluorescence (IF), enzyme immunoassay (EIA), the polymerase chain reaction (PCR) and bacterial culture. Compared with culture, IF had a sensitivity of 100 %; compared with PCR, sensitivity was 89 %. The corresponding figures for the EIA were 83 % and 74 %, respectively. The sensitivity of culture compared with PCR was 63 %. The results suggest that IF on genital smears using M AH D7 might be an excellent tool for the diagnosis of chancroid in high-prevalence populations. However, further evaluation of the specificity of this test is needed. [ABSTRACT FROM AUTHOR]
- Published
- 1995
- Full Text
- View/download PDF
8. Mutant p53 subverts p63 control over KLF4 expression in keratinocytes
- Author
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S. Borrelli, Emilio Berti, Daniela Alotto, Elena Martynova, Daniele Fanoni, Roberto Mantovani, Carlotta Castagnoli, M A Viganò, Silvia Pozzi, Nicoletta Cordani, Cordani, N, Pozzi, S, Martynova, E, Fanoni, D, Borrelli, S, Alotto, D, Castagnoli, C, Berti, E, Viganò, M, and Mantovani, R
- Subjects
Keratinocytes ,Cancer Research ,Chromatin Immunoprecipitation ,Skin Neoplasms ,Cellular differentiation ,Mutant ,Blotting, Western ,Kruppel-Like Transcription Factors ,Fluorescent Antibody Technique ,Gene Expression ,keratinocyte ,Biology ,Transfection ,Kruppel-Like Factor 4 ,stomatognathic system ,Gene expression ,MED/35 - MALATTIE CUTANEE E VENEREE ,Genetics ,medicine ,Humans ,Promoter Regions, Genetic ,Molecular Biology ,p63 ,Microscopy, Confocal ,integumentary system ,Activator (genetics) ,Reverse Transcriptase Polymerase Chain Reaction ,fungi ,mutant p53 ,Membrane Proteins ,Promoter ,Cell Differentiation ,Molecular biology ,Immunohistochemistry ,KLF4 ,HaCaT ,medicine.anatomical_structure ,Gene Expression Regulation ,Tissue Array Analysis ,embryonic structures ,Mutation ,Carcinoma, Squamous Cell ,RNA Interference ,sense organs ,Tumor Suppressor Protein p53 ,Keratinocyte ,Chromatin immunoprecipitation - Abstract
Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.
- Published
- 2011
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