Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment

Abstract Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard “one size fits all” treatment approach included intensive chemotherapy treatment with anthracyclines and cytarabine. The manuscript first traces the evolution of the understanding of the pathology from the 1970s to the present. The enormous strides made in its categorization prove to be crucial for risk stratification, enabling an increasingly personalized diagnosis and treatment approach. Subsequently, we highlight how, over the past 15 years, technological advances enabling single cell RNA sequencing and T-cell modification based on the genomic tools are affecting the classification and treatment of AML. At the dawn of the new millennium, the advent of high-throughput next-generation sequencing technologies has enabled the profiling of patients evidencing different facets of the same disease, stratifying risk, and identifying new possible therapeutic targets that have subsequently been validated. Currently, the possibility of investigating tumor heterogeneity at the single cell level, profiling the tumor at the time of diagnosis or after treatments exist. This would allow the identification of underrepresented cellular subclones or clones resistant to therapeutic approaches and thus responsible for post-treatment relapse that would otherwise be difficult to detect with bulk investigations on the tumor biopsy. Single-cell investigation will then allow even greater personalization of therapy to the genetic and transcriptional profile of the tumor, saving valuable time and dangerous side effects. The era of personalized medicine will take a huge step forward through the disclosure of each individual piece of the complex puzzle that is cancer pathology, to implement a “tailored” therapeutic approach based also on engineered CAR-T cells

Cultura del gesto e cultura della parola. Viaggio antropologico nel mondo dei sordi

Un libro che ha visto la luce nel 1997 (in ristampa nel 2023 con una nuova introduzione) , nato da un’iniziativa di studenti di antropologia della Sapienza di Roma, ripubblicato con una nuova introduzione che fa il punto degli studi sociali sulla sordità in Italia. Studi che in questi anni hanno preso meno piede rispetto alla ricerca linguistica sulla Lingua dei Segni Italiana (LIS), che vanta invece oggi una notevole letteratura. Una lingua che nel 2021 ha finalmente, dopo anni di battaglie da parte delle persone sorde, ottenuto il riconoscimento ufficiale della Repubblica con Legge 21 maggio 2021, n. 69. Una serie di riflessioni immaginate come un viaggio alla scoperta del mondo della sordità intesa “non come difetto fisico, una menomazione corporea da curare o mascherare, ma una risorsa umana generatrice di cultura”. Viaggio che come studenti ritenevamo fosse l’anima di ogni ricerca antropologica nel viaggio della conoscenza di noi stessi e dell’altro.A book published in 1997 (reprinted in 2023 with a new introduction), born from an initiative of anthropology students of the Sapienza University of Rome, republished with a new introduction that takes stock of social studies on deafness in Italy. Studies that in recent years have gained less ground than the linguistic research on Italian Sign Language (LIS), which today boasts a considerable literature. A language that in 2021 finally, after years of battles by deaf people, obtained official recognition from the State (Law 21 May 2021, n. 69). A series of reflections imagined as a journey to discover the world of deafness understood "not as a physical defect, a bodily impairment to be treated or masked, but a human resource that generates culture". A journey that as students we believed was the soul of every anthropological research on the path of knowledge of ourselves and of the other

Reduced Interleukin-17-Expressing Cells in Cutaneous Melanoma

Characterization of tumor associated lymphocytes (TILs) in tumor lesions is important to obtain a clear definition of their prognostic value and address novel therapeutic opportunities. In this work, we examined the presence of T helper (Th)17 lymphocytes in cutaneous melanoma. We performed an immunohistochemical analysis of a small cohort of primary melanomas, retrospectively selected. Thereafter, we isolated TILs from seven freshly surgically removed melanomas and from three basal cell carcinomas (BCC), as a comparison with a non-melanoma skin cancer known to retain a high amount of Th17 cells. In both studies, we found that, differently from BCC, melanoma samples showed a lower percentage of Th17 lymphocytes. Additionally, TIL clones could not be induced to differentiate towards the Th17 phenotype in vitro. The presence or absence of Th17 cells did not correlate with any patient characteristics. We only observed a lower amount of Th17 cells in samples from woman donors. We found a tendency towards an association between expression by melanoma cells of placenta growth factor, angiogenic factors able to induce Th17 differentiation, and presence of Th17 lymphocytes. Taken together, our data indicate the necessity of a deeper analysis of Th17 lymphocytes in cutaneous melanoma before correlating them with prognosis or proposing Th17-cell based therapeutic approaches

Il Silenzio: The First Renaissance Oil Painting on Canvas from the Uffizi Museum Restored with a Safe, Green Antimicrobial Emulsion Based on Citrus aurantium var. amara Hydrolate and Cinnamomum zeylanicum Essential Oil

Preserving artworks from the attacks of biodeteriogens is a primary duty of humanity. Nowadays, restorers use chemicals potentially dangerous for both artworks and human health. The purpose of this work was to find a green and safe formulation based on natural substances with fungicidal activity to restore ancient oil paintings, particularly “Il Silenzio” (by Jacopo Zucchi) preserved at the Uffizi Museum in Florence, Italy. The study was divided into two phases. First phase (in vitro study): three essential oils (EOs) and four hydrolates (Hys) were analysed by GC-mass spectrometry and in vitro tested against six ATCC strains of molds. An emulsion based on the more active natural compounds was tested on aged and unaged canvases samples to evaluate both their fungicidal activity and the impact on chemical-physical parameters. Finally, an in vivo toxicity test performed on the Galleria mellonella model assessed the safety for health. Second phase (in situ application): the emulsion was sprayed on the back of the painting and left to act for 24 h. Biodeteriogens present on the “Il Silenzio” painting were microbiologically identified before and after the treatment. The emulsion formulated with C. zeylanicum EO and C. aurantium var. amara Hy showed the best antifungal activity both in vitro and in situ without altering the chemical-physical characteristics of paintings. Furthermore, no in vivo toxicity was shown. For the first time, a green antimicrobial emulsion based on Hy and EO, safe for operators, was used to decontaminate an artwork colonised by fungi before the restoration practices

Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients

Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465-16 762); (2) TRF-L correlates to VH-MS (r(2)=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as 'discordant'; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence

Misure critiche. Nuova Serie. A. 13, n. 2 (2014)- A. 14, n. 1 (2015)

N.S. A. 13, n. 2 (2014)- A. 14, n. 1 (2015) : Falardo A., Giuseppe Maria Galanti tra ‘pensieri vari’, ultime volontà e documenti inediti, P. 5 ; Lamberti E., Foscolo: autoesegesi, P. 48 ; Accumulo L., Thomas James Mathias, arcade inglese nella Napoli di primo Ottocento. Prime ricognizioni bibliografiche e documentarie, P. 71 ; Zaganelli G., Dalle teorie dell’interpretazione alla esegesi dei testi letterari. Iser tra Collodi e Dickens, P. 116 ; Tuscano F., Aspetti del pensiero musicale dei “Canti Orfici”, P. 128 ; Cappelluti D., Un ‘corsaro’ all’attacco del Potere, P. 159 ; Di Biasio R., La notte nel Purgatorio, P. 195 ; Santoli C., Riscritture goldoniane: l’originalità dei libretti ‘seri’, P. 211 ; Zaganelli G., Le macchine del tempo in letteratura: Proust e Genette leggono Nerval e Flaubert, P. 219 ; Celentano S., “Gli Albigesi” di Giuseppe La Farina tra storia, romanzesco e impegno anticlericale nella nuova edizione di Ella Imbalzano, P. 233 ; Tirri L. C., Su un’antologia bilingue della diaspora italiana, P. 241 ; Lucia C., Le forme plurime della ‘rêverie’ del passato: “Gli Anni Piccoli” di Enzo Moscato, P. 248 ; Tassoni L., Il Medioevo contemporaneo di Giulio Angioni, P. 257 ; Rosato C., recensione a, Giulia Dell’Aquila, Il «severissimo censore». Paolo Beni tra antichi e moderni, Stony Brook (NY), Forum Italicum 2013, P. 269 ; Monzone C., recensione a, Francesco Giordano, Domenico Tempio, cantore della Libertà, Catania, Edizioni Akkuaria 2011, P. 271 ; Caputo V., recensione a, Valeria Giannantonio, Tra metafore e miti. Poesia e teatro in D’Annunzio, Napoli, Liguori 2011, P. 274 ; D’Astore F., recensione a, Antonio Lucio Giannone, Fra Sud ed Europa. Studi sul Novecento letterario italiano, Lecce, Milella 2013, P. 277 ; Ottieri A., recensione a, Antonio Pietropaoli, Fra retorica e metrica. Saggi sulla poesia italiana contemporanea, Napoli, Guida 2014, P. 280 ; Rosato C., recensione a, Dalila Colucci, Nessuno crede al merlo d’acqua. Le ultime poesie di Goffredo Parise, Isernia, Cosmo Iannone Editore 2011, P. 283 ; Laudiero S., recensione a, Le vie di Troisi sono infinite, a cura di Valerio Caprara, Pasquale Sabbatino, Giuseppina Scognamiglio, Napoli, Edizioni Scientifiche Italiane 2012, P. 289 ; Comparini A., recensione a, Stefano Carrai, Il tempo che non muore, Novara, Interlinea 2012, P. 287 ; Leone G., recensione a, Valeria Giannantonio, Il tempo che non dura, Pescara, Lanieri 2013, P. 291 ; Giordano E., recensione a, Mena De Luca, Canzoniere di diverse stagioni, Firenze, Edizioni Tassinari 2011, P. 293 ; Formato E., recensione a, Enzo Moscato, Tempo che fu di Scioscia, Napoli, Tullio Pironti Editore 2014, P. 294

I segni raccontano. La Lingua dei Segni Italiana tra esperienze, strumenti e metodologie

Il libro, nato dalle ricerche, esperienze, proposte e sperimentazioni presentate al 3° Convegno sulla Lingua dei Segni Italiana, racconta di una lingua che è parte della vita di molte persone sorde e udenti, e si dipana intorno a quattro tematiche: i profili professionali in evoluzione; la LIS come risorsa; le esperienze di bilinguismo e integrazione; i diritti, i servizi e l’accessibilità.The book, born from the research, experiences, proposals and experiments presented at the 3rd Conference on Italian Sign Language, tells of a language that is part of the life of many deaf and hearing people, and unfolds around four themes: professional profiles Evolving; the LIS as a resource; experiences of bilingualism and integration; rights, services and accessibility