المؤلفون: Bueno, Carlos A., Salinas, Franco M., Vazquez, L., Alché, Laura E., Michelini, Flavia M.

المصدر: Heliyon ; volume 9, issue 10, page e20148 ; ISSN 2405-8440

مصطلحات موضوعية: Multidisciplinary

الإتاحة: https://doi.org/10.1016/j.heliyon.2023.e20148Test
https://api.elsevier.com/content/article/PII:S2405844023073565?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2405844023073565?httpAccept=text/plainTest

المؤلفون: Carro, Gabriela Verónica, Guerbi, Ximena, Berra, Mariano, Rodriguez, María Gabriela, Noli, María Laura, Fuentes, Mariana, Ticona, Miguel Angel, Michelini, Flavia, Berra, Alejandro

المصدر: Foot & Ankle International ; ISSN 1071-1007 1944-7876

الوصف: Background: Diabetic foot ulcers (DFUs) constitute a complication that occurs in 19% to 34% of patients with diabetes mellitus (DM). The aim of this study is to describe median days to healing, average velocity of wound closure, and percentage of wound surface closed at 3, 6, and 12 weeks through the use of homogenized and lyophilized amniotic membrane (hAMpe) dressings for the treatment of DFUs in ambulatory patients. Methods: An observational, descriptive, longitudinal study was performed. Patients presenting with granulation-based DFU, after proper debridement, were included from August 19, 2021, until July 14, 2023. hAMpe dressings placed every 3 days were used for the treatment of these ulcers. Results: Sixteen patients were included with a mean age of 52.38 (8.07) years. The analyzed lesions were postsurgical ulcers in 15 of the 16 included patients. Median ulcer size was 19.5 cm 2 (6.12-36). The median ABI was 1.10 (1-1.14). The median days to healing was 96 (71-170). The median percentage closure of the wound at 3 weeks was 41% (28.9%-55.3%), at 6 weeks it was 68.2% (48.6%-74.2%), and at 12 weeks it was 100% (81%-100%). The average velocity closure was 1.04% per day (95% CI 0.71%-1.31%). It was higher during the closure of the first 50% of the ulcer, 2.12% per day (95% CI 0.16%-4.09%), and decreased from 50% to 25% of the ulcer size to 0.67% per day (95% CI 0.23%-1.10%) and from 25% to closure to 0.47% per day (95% CI 0.14%-0.80%), P < .001. Conclusion: These results are difficult to compare to other studies given the higher surface area of the ulcers included in our sample. The development of hAMpe dressings enables patients to apply them without requiring assistance from health care teams and was not associated with any recognized complications. Level of Evidence: Level IV, case series.

الإتاحة: https://doi.org/10.1177/10711007241243373Test

المؤلفون: Li, Bob T, Meric-Bernstam, Funda, Bardia, Aditya, Naito, Yoichi, Siena, Salvatore, Aftimos, Philippe, Anderson, Ian, Curigliano, Giuseppe, de Miguel, Maria, Kalra, Maitri, Oh, Do-Youn, Park, Joon Oh, Postel-Vinay, Sophie, Rha, Sun Young, Satoh, Taroh, Spanggaard, Iben, Michelini, Flavia, Smith, Ann, Machado, Karime Kalil, Saura, Cristina

المصدر: Lancet Oncol ; ISSN:1474-5488 ; Volume:25 ; Issue:6

الوصف: Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate approved by the US Food and Drug Administration and the European Medicines Agency for HER2-mutant non-small-cell lung cancer. Few treatment options exist for patients with HER2-mutant solid tumours beyond lung cancers. We investigated trastuzumab deruxtecan in metastatic solid tumours with specific activating HER2 mutations.

العلاقة: https://doi.org/10.1016/S1470-2045Test(24)00140-2; https://pubmed.ncbi.nlm.nih.gov/38710187Test

الإتاحة: https://doi.org/10.1016/S1470-2045Test(24)00140-2
https://pubmed.ncbi.nlm.nih.gov/38710187Test

المؤلفون: Sharma, Sheetal, Anand, Roopesh, Zhang, Xuzhu, Francia, Sofia, Michelini, Flavia, Galbiati, Alessandro, Williams, Hannah, Ronato, Daryl A., Masson, Jean-Yves, Rothenberg, Eli, Čejka, Petr, d'Adda di Fagagna, Fabrizio

المصدر: Cell Reports, 34 (1)

مصطلحات موضوعية: DNA damage, DNA double-strand breaks, DNA-damage induced transcription, damage-induced long non-coding RNA, dilncRNA, MRE11-RAD50-NBS1 complex, RNA polymerase II, in vitro transcription, DNA melting, single-molecule FRET

الوصف: The MRE11-RAD50-NBS1 (MRN) complex supports the synthesis of damage-induced long non-coding RNA (dilncRNA) by RNA polymerase II (RNAPII) from DNA double-strand breaks (DSBs) by an unknown mechanism. Here, we show that recombinant human MRN and native RNAPII are sufficient to reconstitute a minimal functional transcriptional apparatus at DSBs. MRN recruits and stabilizes RNAPII at DSBs. Unexpectedly, transcription is promoted independently from MRN nuclease activities. Rather, transcription depends on the ability of MRN to melt DNA ends, as shown by the use of MRN mutants and specific allosteric inhibitors. Single-molecule FRET assays with wild-type and mutant MRN show a tight correlation between the ability to melt DNA ends and to promote transcription. The addition of RPA enhances MRN-mediated transcription, and unpaired DNA ends allow MRN-independent transcription by RNAPII. These results support a model in which MRN generates single-strand DNA ends that favor the initiation of transcription by RNAPII. ; ISSN:2666-3864 ; ISSN:2211-1247

وصف الملف: application/application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/wos/000605650500004; http://hdl.handle.net/20.500.11850/464014Test

الإتاحة: https://doi.org/20.500.11850/464014Test
https://doi.org/10.3929/ethz-b-000464014Test
https://doi.org/10.1016/j.celrep.2020.108565Test
https://hdl.handle.net/20.500.11850/464014Test

المؤلفون: Lee, Jung-Yun, Makker, Vicky, Manso, Luis, González-Martín, Antonio, Ługowska, Iwona, Lorusso, Domenica, Banerjee, Susana, Liao, John, Lu, Chien-Hsing, Prasongsook, Naiyarat, Melichar, Bohuslav, Chen, Kai, Mcewen, Robert, Michelini, Flavia, Puvvada, Soham, Meric-Bernstam, Funda, Oaknin, Ana

المصدر: Plenary 02: Changing the Landscape of Endometrial Cancer

الإتاحة: https://doi.org/10.1136/ijgc-2023-igcs.7Test

المؤلفون: Sendra, Victor, Berra, Alejandro, Michelini, Flavia, Guerbi, Maria Ximena, Rodriguez, Giselle, del Papa, Melina Sol, Passerini, María Silvia

المصدر: The Pan-American Journal of Ophthalmology ; volume 5, issue 1 ; ISSN 2666-4909 2666-4909

الوصف: Purpose: The purpose of this study was to study the osmoprotective and bioprotective effect of trehalose 3% + carboxymethylcellulose (CMC) 0.5% during desiccation conditions. Materials and Methods: Normal human conjunctival epithelial cells (IOBA) were exposed to (1) culture media (control); (2) CMC 0.5% + glycerin 0. 9% + polyethylene glycol 400 0.25% (vehicle); and (3) vehicle + trehalose 3% (trehalose). Cells were treated for 1 h and then exposed to desiccating conditions. Metabolic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell viability by trypan blue. Trehalose water retention capability was assessed by a gravimetric analysis. Results: Metabolic activity was maintained during the first 30 min under desiccating conditions with no differences found between groups. After 45 min, metabolic activity decreased both in the control group and the vehicle group, while the trehalose group maintained activity values. Cell viability of the trehalose group was maintained throughout time and was statistically superior to those of the control and the vehicle groups at all evaluated times ( P < 0.01). The retention time 20-RT20 - (20% of water retention) was reached at 8 min in the control group, 10 min in the vehicle group, and 15 min in the trehalose group. Conclusions: The addition of 3% trehalose prolonged cell viability and extended water retention time in high-dryness environmental conditions.

الإتاحة: https://doi.org/10.4103/pajo.pajo_80_23Test

المؤلفون: Gioia, Ubaldo, Francia, Sofia, Cabrini, Matteo, Brambillasca, Silvia, Michelini, Flavia, Jones-Weinert, Corey W., d’Adda di Fagagna, Fabrizio

المساهمون: Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica, Fondazione Cariplo, Fondazione Italiana per la Ricerca sul Cancro, Worldwide Cancer Research

المصدر: Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: A novel class of small non-coding RNAs called DNA damage response RNAs (DDRNAs) generated at DNA double-strand breaks (DSBs) in a DROSHA- and DICER-dependent manner has been shown to regulate the DNA damage response (DDR). Similar molecules were also reported to guide DNA repair. Here, we show that DDR activation and DNA repair can be pharmacologically boosted by acting on such non-coding RNAs. Cells treated with enoxacin, a compound previously demonstrated to augment DICER activity, show stronger DDR signalling and faster DNA repair upon exposure to ionizing radiations compared to vehicle-only treated cells. Enoxacin stimulates DDRNA production at chromosomal DSBs and at dysfunctional telomeres, which in turn promotes 53BP1 accumulation at damaged sites, therefore in a miRNA-independent manner. Increased 53BP1 occupancy at DNA lesions induced by enoxacin ultimately suppresses homologous recombination, channelling DNA repair towards faster and more accurate non-homologous end-joining, including in post-mitotic primary neurons. Notably, augmented DNA repair stimulated by enoxacin increases the survival also of cancer cells treated with chemotherapeutic agents.

الإتاحة: https://doi.org/10.1038/s41598-019-42892-6Test
https://www.nature.com/articles/s41598-019-42892-6.pdfTest
https://www.nature.com/articles/s41598-019-42892-6Test

المؤلفون: King, Daniel A., Smith, Amber R., Pineda, Gino, Nakano, Michitaka, Michelini, Flavia, Goedegebuure, S. Peter, Thyparambil, Sheeno, Liao, Wei-Li, McCormick, Aaron, Ju, Jihang, Cioffi, Michele, Zhang, Xiuli, Hundal, Jasreet, Griffith, Malachi, Grandori, Carla, Pollastro, Maddy, Rosati, Rachele, Margossian, Astrid, Chatterjee, Payel, Ainge, Trevor

المصدر: JCO Precision Oncology; 4/20/2023, Vol. 7, p1-10, 10p

مصطلحات موضوعية: EPIDERMAL growth factor receptors, METASTASIS

مستخلص: Complete remission of metastatic HER2+ pancreatic cancer following immune and targeted therapy. [ABSTRACT FROM AUTHOR]

: Copyright of JCO Precision Oncology is the property of American Society of Clinical Oncology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Iannelli, Fabio, Galbiati, Alessandro, Capozzo, Ilaria, Nguyen, Quan, Magnuson, Brian, Michelini, Flavia, D’Alessandro, Giuseppina, Cabrini, Matteo, Roncador, Marco, Francia, Sofia, Crosetto, Nicola, Ljungman, Mats, Carninci, Piero, d’Adda di Fagagna, Fabrizio

المصدر: Nature Communications ; volume 8, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Of the many types of DNA damage, DNA double-strand breaks (DSBs) are probably the most deleterious. Mounting evidence points to an intricate relationship between DSBs and transcription. A cell system in which the impact on transcription can be investigated at precisely mapped genomic DSBs is essential to study this relationship. Here in a human cell line, we map genome-wide and at high resolution the DSBs induced by a restriction enzyme, and we characterize their impact on gene expression by four independent approaches by monitoring steady-state RNA levels, rates of RNA synthesis, transcription initiation and RNA polymerase II elongation. We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and on the distance from the DSB. Our study couples for the first time, to the best of our knowledge, high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites.

الإتاحة: https://doi.org/10.1038/ncomms15656Test
https://www.nature.com/articles/ncomms15656.pdfTest
https://www.nature.com/articles/ncomms15656Test

المؤلفون: Giugliano, Federica, Corti, Chiara, Tarantino, Paolo, Michelini, Flavia, Curigliano, Giuseppe

المساهمون: F. Giugliano, C. Corti, P. Tarantino, F. Michelini, G. Curigliano

مصطلحات موضوعية: Antibody–drug conjugate, Bystander effect, Sacituzumab govitecan, Trastuzumab deruxtecan, Trastuzumab emtansine, Settore MED/06 - Oncologia Medica

الوصف: Purpose of review Summarizing the current preclinical and clinical evidence about bystander effect of antibody-drug conjugates (ADCs) in solid tumors. Recent findings One of the main challenges of treating solid tumors with ADCs is the heterogeneous expression of the target antigen (Ag), which however may be overcome by the so-called bystander killing effect. This unique, but still debated, feature of certain ADCs is represented by the unintentional payload diffusion from Ag-positive tumor cells to adjacent Ag-negative tumor cells. Some pharmacological characteristics, such as a hydrophobic payload or a cleavable linker, seem to play a major role in this effect. Abundant preclinical evidence of the bystander effect has emerged, and the clinical activity of ADCs in tumors with a heterogeneous Ag expression suggests the relevance of this feature. Additional studies are required to investigate if the bystander effect is necessary for achieving a solid activity with ADCs.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35305211; info:eu-repo/semantics/altIdentifier/wos/WOS:000770734300003; volume:24; issue:7; firstpage:809; lastpage:817; numberofpages:9; journal:CURRENT ONCOLOGY REPORTS; https://hdl.handle.net/2434/985552Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85126752257

الإتاحة: https://doi.org/10.1007/s11912-022-01266-4Test
https://hdl.handle.net/2434/985552Test