المؤلفون: Lavacchi, Daniele, Gelmini, Stefania, Calabri, Adele, Rossi, Gemma, Simi, Lisa, Caliman, Enrico, Mancini, Irene, Salvianti, Francesca, Petroni, Giulia, Guidolin, Alessia, Scolari, Federico, Messerini, Luca, Pillozzi, Serena, Pinzani, Pamela, Antonuzzo, Lorenzo

المساهمون: Regione Toscana

المصدر: Heliyon ; volume 9, issue 11, page e21853 ; ISSN 2405-8440

مصطلحات موضوعية: Multidisciplinary

الإتاحة: https://doi.org/10.1016/j.heliyon.2023.e21853Test
https://api.elsevier.com/content/article/PII:S2405844023090618?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2405844023090618?httpAccept=text/plainTest

المؤلفون: Salvianti, Francesca, Gelmini, Stefania, Costanza, Filomena, Mancini, Irene, Sonnati, Gemma, Simi, Lisa, Pazzagli, Mario, Pinzani, Pamela

المساهمون: Ministero della Salute, Horizon 2020, Horizon 2020 Framework Programme, Regione Toscana, Forskningsrådet för Arbetsliv och Socialvetenskap

المصدر: New Biotechnology ; volume 55, page 19-29 ; ISSN 1871-6784

مصطلحات موضوعية: Molecular Biology, General Medicine, Bioengineering, Biotechnology

الإتاحة: https://doi.org/10.1016/j.nbt.2019.09.006Test
https://api.elsevier.com/content/article/PII:S1871678418319629?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1871678418319629?httpAccept=text/plainTest

المؤلفون: Mini, Enrico, Lapucci, Andrea, Perrone, Gabriele, D'Aurizio, Romina, Napoli, Cristina, Brugia, Marco, Landini, Ida, Tassi, Renato, Picariello, Lucia, Simi, Lisa, Mancini, Irene, Messerini, Luca, Magi, Alberto, Pinzani, Pamela, Mazzei, Teresita, Tonelli, Francesco, Nobili, Stefania

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Fiveâ€year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach. From a series of CRC patients who received ACHT, two stage III extreme cohorts (unfavorable vs. favorable prognosis) were selected. RNAâ€sequencing was performed from fresh frozen explants. Tumors were characterized for somatic mutations. Validation was performed in stage III CRC patients extracted from two GEO datasets. According to diseaseâ€free survival (DFS), 108 differentially expressed genes (104/4 up/downregulated in the unfavorable prognosis group) were identified. Among 104 upregulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as pseudogenes (n = 17), uncharacterized noncoding RNA (n = 10), immune response genes (n = 4), microRNA (n = 1), cancerâ€related genes (n = 14) and cancerâ€unrelated genes (n = 16). Three out of four downâ€regulated genes were cancerâ€related. Mutational status (i.e., RAS, BRAF, PIK3CA) did not differ among the cohorts. In the validation cohort, multivariate analysis showed high PNN and KCNQ1OT1 expression predictive of shorter DFS in ACHT treated patients (p = 0.018 and p = 0.014, respectively); no difference was observed in untreated patients. This is the first study that identifies by a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers predictive of chemotherapy response in stage III CRC patients. After a further validation in an independent cohort, PNN and KCNQ1OT1 evaluation could be proposed to prospectively identify stage III CRC patients benefiting from ACHT.

العلاقة: url:https://www.openaccessrepository.it/communities/itmirrorTest; https://www.openaccessrepository.it/record/169198Test

الإتاحة: https://doi.org/10.1002/ijc.32326Test
https://www.openaccessrepository.it/record/169198Test

المؤلفون: Righi, Alberto, Mancini, Irene, Gambarotti, Marco, Picci, Piero, Gamberi, Gabriella, Marraccini, Cristina, Dei Tos, Angelo Paolo, Simi, Lisa, Pinzani, Pamela, Franchi, Alessandro

المساهمون: Righi, Alberto, Mancini, Irene, Gambarotti, Marco, Picci, Piero, Gamberi, Gabriella, Marraccini, Cristina, Dei Tos, Angelo Paolo, Simi, Lisa, Pinzani, Pamela, Franchi, Alessandro

مصطلحات موضوعية: COLD-PCR, Giant cell tumor of bone, Giant cellâ rich sarcoma, Histone 3.3 gene mutation, Malignant giant cell tumor, Adolescent, Adult, Aged, Biomarkers, Tumor, Bone Neoplasm, Child, Preschool, DNA Mutational Analysi, Diagnosis, Differential, Female, Histone, Human, Lung Neoplasm, Male, Middle Aged, Osteosarcoma, Predictive Value of Test, Young Adult, Mutation

الوقت: 2734

الوصف: Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. Although more than 90% of GCTBs present histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study, we examined a series of giant cellâ rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cellâ rich sarcomas. Sixteen cases of nonmetastatic GCTB, 9 GCTBs with lung metastases, and 35 giant cellâ rich sarcomas were selected from our institutional archives. Eight chondroblastomas were used as controls. Direct sequencing for the presence of H3F3A and H3F3B variants in coding region between codons 1 and 42, including the hotspot codons (28, 35, and 37), was performed on DNA extracted from formalin-fixed, paraffin-embedded tissue using conventional polymerase chain reaction and fast coamplification at lower denaturation temperatureâ polymerase chain reaction. Overall, 24 GCTBs (96%) presented a mutation in the H3F3A gene (15 of 16 nonmetastatic and 9 of 9 metastatic). Five sarcomas harbored an H3F3A mutation (3 p.G35W, 1 p.G35L, and 1 p.G35E), and these were all secondary malignant GCTBs. In conclusion, we confirm that H3F3A mutational testing may be a useful adjunct to differentiate GCTB from giant cellâ rich sarcomas. Although the presence of H3F3A mutations does not exclude with certainty a diagnosis of sarcoma, the possibility of a malignant evolution of GCTB should also be considered.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/28899740; info:eu-repo/semantics/altIdentifier/wos/WOS:000416883100018; volume:68; firstpage:128; lastpage:135; numberofpages:8; journal:HUMAN PATHOLOGY; https://hdl.handle.net/11568/884918Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85031121870; http://www.elsevier.com/inca/publications/store/6/2/3/1/3/9/index.httTest

الإتاحة: https://doi.org/10.1016/j.humpath.2017.08.033Test
https://hdl.handle.net/11568/884918Test
http://www.elsevier.com/inca/publications/store/6/2/3/1/3/9/index.httTest

المؤلفون: Prodan Žitnik, Irena, Černe, Darko, Mancini, Irene, Simi, Lisa, Pazzagli, Mario, Di Resta, Chiara, Podgornik, Helena, Repič Lampret, Barbka, Trebušak Podkrajšek, Katarina, Sipeky, Csilla, Van Schaik, Ron, Brandslund, Ivan, Vermeersch, Pieter, Schwab, Matthias, Marc, Janja

المصدر: Prodan Žitnik , I , Černe , D , Mancini , I , Simi , L , Pazzagli , M , Di Resta , C , Podgornik , H , Repič Lampret , B , Trebušak Podkrajšek , K , Sipeky , C , Van Schaik , R , Brandslund , I , Vermeersch , P , Schwab , M & Marc , J 2018 , ' Personalized laboratory medicine : A patient-centered future approach ' , Clinical Chemistry and Laboratory Medicine , vol. 56 , no. 12 , pp. 1981–1991 . https://doi.org/10.1515/cclm-2018-0181Test

مصطلحات موضوعية: advanced omics technologies, diagnostic marker, genome, metabolome, molecular profiling, proteome, transcriptome, Medical Laboratory Science, Humans, Patient-Centered Care, Precision Medicine

الوصف: In contrast to population-based medical decision making, which emphasizes the use of evidence-based treatment strategies for groups of patients, personalized medicine is based on optimizing treatment at the level of the individual patient. The creation of molecular profiles of individual patients was made possible by the advent of "omics" technologies, based on high throughput instrumental techniques in combination with biostatistics tools and artificial intelligence. The goal of personalized laboratory medicine is to use advanced technologies in the process of preventive, curative or palliative patient management. Personalized medicine does not rely on changes in concentration of a single molecular marker to make a therapeutic decision, but rather on changes of a profile of markers characterizing an individual patient's status, taking into account not only the expected response to treatment of the disease but also the expected response of the patient. Such medical approach promises a more effective diagnostics with more effective and safer treatment, as well as faster recovery and restoration of health and improved cost effectiveness. The laboratory medicine profession is aware of its key role in personalized medicine, but to empower the laboratories, at least an enhancement in cooperation between disciplines within laboratory medicine will be necessary.

وصف الملف: application/pdf

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/70ef319e-4538-4ecc-b246-c87a014059ffTest

الإتاحة: https://doi.org/10.1515/cclm-2018-0181Test
https://portal.findresearcher.sdu.dk/da/publications/70ef319e-4538-4ecc-b246-c87a014059ffTest
https://findresearcher.sdu.dk/ws/files/142932592/Personalized_laboratory_medicine.pdfTest

المؤلفون: Girolami, Ilaria, Mancini, Irene, Simoni, Antonella, Baldi, Giacomo Giulio, Simi, Lisa, Campanacci, Domenico, Beltrami, Giovanni, Scoccianti, Guido, D'Arienzo, Antonio, CAPANNA, RODOLFO, FRANCHI, ALESSANDRO

المساهمون: Girolami, Ilaria, Mancini, Irene, Simoni, Antonella, Baldi, Giacomo Giulio, Simi, Lisa, Campanacci, Domenico, Beltrami, Giovanni, Scoccianti, Guido, D'Arienzo, Antonio, Capanna, Rodolfo, Franchi, Alessandro

مصطلحات موضوعية: BONE TUMOURS, CANCER GENETICS, IMMUNOCYTOCHEMISTRY, Adolescent, Adult, Aged, Angiogenesis Inhibitor, Bone Density Conservation Agent, Bone Neoplasm, Cell Proliferation, Core Binding Factor Alpha 1 Subunit, Denosumab, Female, Giant Cell Tumor of Bone, Histone, Human, Male, Matrix Attachment Region Binding Protein, Middle Aged, Mutation, Neovascularization, Pathologic, Predictive Value of Test, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Transcription Factor, Treatment Outcome, Young Adult, Biomarkers, Tumor

الوقت: 2734

الوصف: Aims: Denosumab, a fully human monoclonal antibody directed against RANKL, has recently been introduced in the treatment strategy of giant cell tumour of bone (GCTB). Aim of this study was to investigate the phenotypical modifications induced by denosumab treatment in a series of 15 GCTB. Methods: The tumours were characterised for histone 3.3 mutations, and studied immunohistochemically for the modifications of RANKL, RANK, SATB2 and RUNX2 expression, as well as of tumour proliferative activity and angiogenesis. Results: Nine of 11 tumours investigated presented a histone 3.3 mutation in H3F3A, and 2 of these for which the analysis was carried out in pretreatment and post-treatment specimens showed the same mutation in both. Denosumab induced the disappearance of osteoclast-like giant cells, leaving residual spindle neoplastic cells arranged in a storiform pattern, with deposition of trabecular collagen matrix and osteoid, which tended to maturation in the peripheral portions of the lesion. RANK and RANKL expression was variable, with no significant variation after treatment. Moreover, we did not observe any significant modification of the expression of the osteoblastic markers SATB2 and RUNX2. Denosumab treatment determined a significant reduction of the proliferative index and of tumour angiogenesis (p=0.001, Wilcoxon rank-sum test). Conclusions: These results indicate that denosumab induces a partial maturation towards the osteoblastic phenotype of the neoplastic cells of GCTB, with production of fibrous and osteoid matrix, but with minor immunophenotypical changes. Finally, we first report an antiangiogenic activity of denosumab in GCTB, possibly mediated by a RANKL-dependent pathway.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26338802; info:eu-repo/semantics/altIdentifier/wos/WOS:000370829100008; volume:69; issue:3; firstpage:240; lastpage:247; numberofpages:8; journal:JOURNAL OF CLINICAL PATHOLOGY; http://hdl.handle.net/11568/804508Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84959345838; https://jcp.bmj.com/content/69/3/240lTest

الإتاحة: https://doi.org/10.1136/jclinpath-2015-203248Test
http://hdl.handle.net/11568/804508Test
https://jcp.bmj.com/content/69/3/240lTest

المؤلفون: PONTI, Giovanni, PELLACANI, Giovanni, SIMI, Lisa, DEPENNI, Roberta, SPALLANZANI, Andrea, GELSOMINO, Fabio, POLLIO, Annamaria, BORSARI, Stefania, FABIANO, Antonella, MANDEL, Victor Desmond, TOMASI, Aldo, LUPPI, Gabriele

المساهمون: Ponti, Giovanni, Pellacani, Giovanni, Simi, Lisa, Depenni, Roberta, Spallanzani, Andrea, Gelsomino, Fabio, Pollio, Annamaria, Borsari, Stefania, Fabiano, Antonella, Mandel, Victor Desmond, Tomasi, Aldo, Luppi, Gabriele

الوصف: L’introduzione di terapie a bersaglio molecolare ha rivoluzionato la prognosi dei pazienti affetti da melanoma in stadio avanzato. Attualmente è possibile determinare lo status molecolare del melanoma analizzando geni quali C-KIT, BRAF ed N-RAS per la scelta di strategie terapeutiche mirate. Mutazioni di BRAF si riscontrano in circa il 50% dei melanomi: tra queste la V600E e la V600K sono maggiormente frequenti e ben studiate nei pregressi protocolli di sperimentazione fase II/III con inibitori di BRAF. Questi ultimi (Dabrafenib e Vemurafenib) hanno dimostrato chiara efficacia nell’indurre risposte obiettive nel melanoma avanzato. Con il presente lavoro presentiamo le preliminari valutazioni delle correlazioni tra tipologie di mutazioni somatiche del gene BRAF riscontrate in una coorte di melanomi in stadio IV e le risposte cliniche a tale inibitori selettivi. A partire dal giugno 2011, 19 pazienti (10 M; 9F; età media 55 anni) affetti da melanoma stage IV BRAF+ sono stati arruolati in protocolli terapeutici con Dabrafenib (150 mg 2 volte/die) o Vemurafenib (960 mg 2volte/die) presso l’Università di Modena. Il restaging strumentale della malattia veniva eseguito a 8 settimane dall’inizio della terapia. Sono state riscontrate mutazione hot spot V600E (c.1799T>A) in 18 pazienti, in due differenti pazienti sono state individuate le rare mutazioni V600M (c.1798G>A) e V600R (c.1790T>G). In un melanoma è stata evidenziata una doppia mutazione (V600E; V600M) ed il relativo paziente, trattato con Dabrafenib, ha presentato una rapida regressione delle importati lesioni metastatiche. In due casi la ricerca mutazionale in BRAF, risultata inizialmente negativa, è stata poi riscontrata in una successiva analisi. I dati clinici preliminari evidenziano una risposta obiettiva già nelle primissime settimane di terapia, buona tolleranza con scarsi effetti collaterali sia nei pazienti con mutazioni V600E che in quelli con le rare mutazioni V600 M e V600R. Il periodo di sopravvivenza medio libero da progressione dei ...

العلاقة: ispartofbook:XV Congresso Nazionale SIGU (Società Italiana di Genetica Medica); XV Congresso Nazionale SIGU 2012 - Società Italiana di Genetica Umana; numberofpages:1; http://hdl.handle.net/11380/814701Test

الإتاحة: http://hdl.handle.net/11380/814701Test

المؤلفون: Massi, Daniela, Simi, Lisa, Sensi, Elisa, Baroni, Gianna, Xue, Gongda, Scatena, Cristian, Caldarella, Adele, Pinzani, Pamela, Fontanini, Gabriella, Carobbio, Alessandra, Urso, Carmelo, Mandalà, Mario

المصدر: Modern Pathology ; volume 28, issue 4, page 487-497 ; ISSN 0893-3952

مصطلحات موضوعية: Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1038/modpathol.2014.137Test
http://www.nature.com/articles/modpathol2014137.pdfTest
http://www.nature.com/articles/modpathol2014137Test
https://api.elsevier.com/content/article/PII:S0893395222014429?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0893395222014429?httpAccept=text/plainTest

المؤلفون: Malentacchi, Francesca, Pazzagli, Mario, Simi, Lisa, Orlando, Claudio, Wyrich, Ralf, Günther, Kalle, Verderio, Paolo, Pizzamiglio, Sara, Ciniselli, Chiara Maura, Zhang, Hui, Korenková, Vlasta, Rainen, Lynne, Bar, Tzachi, Kubista, Mikael, Gelmini, Stefania

المساهمون: Wang, Junwen

المصدر: PLoS ONE ; volume 9, issue 11, page e112293 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0112293Test

المؤلفون: Mannelli Massimo, Arvia Rosaria, Deledda Cristiana, Gelmini Stefania, Luciani Paola, Malentacchi Francesca, Simi Lisa, Peri Alessandro, Orlando Claudio

المصدر: BMC Cancer, Vol 10, Iss 1, p 201 (2010)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Seladin-1 overexpression exerts a protective mechanism against apoptosis. Seladin-1 mRNA is variably expressed in normal human tissues. Adrenal glands show the highest levels of seladin-1 expression, which are significantly reduced in adrenal carcinomas (ACC). Since up to now seladin-1 mutations were not described, we investigated whether promoter methylation could account for the down-regulation of seladin-1 expression in ACC. Methods A methylation sensitive site was identified in the seladin-1 gene. We treated DNA extracted from two ACC cell lines (H295R and SW13) with the demethylating agent 5-Aza-2-deoxycytidine (5-Aza). Furthermore, to evaluate the presence of an epigenetic regulation also 'in vivo', seladin-1 methylation and its mRNA expression were measured in 9 ACC and in 5 normal adrenal glands. Results The treatment of cell lines with 5-Aza induced a significant increase of seladin-1 mRNA expression in H295R (fold increase, F.I. = 1.8; p = 0.02) and SW13 (F.I. = 2.9; p = 0.03). In ACC, methylation density of seladin-1 promoter was higher (2682 ± 686) than in normal adrenal glands (362 ± 97; p = 0.02). Seladin-1 mRNA expression in ACC (1452 ± 196) was significantly lower than in normal adrenal glands (3614 ± 949; p = 0.01). Conclusion On this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.

العلاقة: http://www.biomedcentral.com/1471-2407/10/201Test; https://doaj.org/toc/1471-2407Test; https://doaj.org/article/b3a9cf1c078043c6a2abd6ad777a08a5Test

الإتاحة: https://doi.org/10.1186/1471-2407-10-201Test
https://doaj.org/article/b3a9cf1c078043c6a2abd6ad777a08a5Test