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Article ; Online: Investigating pathological epigenetic aberrations by epi-proteomics.

Robusti, Giulia / Vai, Alessandro / Bonaldi, Tiziana / Noberini, Roberta

2022 Volume 14, Issue 1, Page(s) 145

Abstract: Epigenetics includes a complex set of processes that alter gene activity without modifying the DNA sequence, which ultimately determines how the genetic information common to all the cells of an organism is used to generate different cell types. ... ...

Abstract	Epigenetics includes a complex set of processes that alter gene activity without modifying the DNA sequence, which ultimately determines how the genetic information common to all the cells of an organism is used to generate different cell types. Dysregulation in the deposition and maintenance of epigenetic features, which include histone posttranslational modifications (PTMs) and histone variants, can result in the inappropriate expression or silencing of genes, often leading to diseased states, including cancer. The investigation of histone PTMs and variants in the context of clinical samples has highlighted their importance as biomarkers for patient stratification and as key players in aberrant epigenetic mechanisms potentially targetable for therapy. Mass spectrometry (MS) has emerged as the most powerful and versatile tool for the comprehensive, unbiased and quantitative analysis of histone proteoforms. In recent years, these approaches-which we refer to as "epi-proteomics"-have demonstrated their usefulness for the investigation of epigenetic mechanisms in pathological conditions, offering a number of advantages compared with the antibody-based methods traditionally used to profile clinical samples. In this review article, we will provide a critical overview of the MS-based approaches that can be employed to study histone PTMs and variants in clinical samples, with a strong focus on the latest advances in this area, such as the analysis of uncommon modifications and the integration of epi-proteomics data into multi-OMICs approaches, as well as the challenges to be addressed to fully exploit the potential of this novel field of research.
MeSH term(s)	Humans ; Histones/metabolism ; Proteomics/methods ; DNA Methylation ; Epigenomics ; Protein Processing, Post-Translational ; Epigenesis, Genetic
Chemical Substances	Histones
Language	English
Publishing date	2022-11-12
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-022-01371-y
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Article ; Online: Detection and quantification of the histone code in the fungal genus Aspergillus.

Zhang, Xin / Noberini, Roberta / Vai, Alessandro / Bonaldi, Tiziana / Seidl, Michael F / Collemare, Jérȏme

Fungal genetics and biology : FG & B

2023 Volume 167, Page(s) 103800

Abstract: In eukaryotes, the combination of different histone post-translational modifications (PTMs) - the histone code - impacts the chromatin organization as compact and transcriptionally silent heterochromatin or accessible and transcriptionally active ... ...

Abstract	In eukaryotes, the combination of different histone post-translational modifications (PTMs) - the histone code - impacts the chromatin organization as compact and transcriptionally silent heterochromatin or accessible and transcriptionally active euchromatin. Although specific histone PTMs have been studied in fungi, an overview of histone PTMs and their relative abundance is still lacking. Here, we used mass spectrometry to detect and quantify histone PTMs in three fungal species belonging to three distinct taxonomic sections of the genus Aspergillus (Aspergillus niger, Aspergillus nidulans (two strains), and Aspergillus fumigatus). We overall detected 23 different histone PTMs, including a majority of lysine methylations and acetylations, and 23 co-occurrence patterns of multiple histone PTMs. Among those, we report for the first time the detection of H3K79me1, H3K79me2, and H4K31ac in Aspergilli. Although all three species harbour the same PTMs, we found significant differences in the relative abundance of H3K9me1/2/3, H3K14ac, H3K36me1 and H3K79me1, as well as the co-occurrence of acetylation on both K18 and K23 of histone H3 in a strain-specific manner. Our results provide novel insights about the underexplored complexity of the histone code in filamentous fungi, and its functional implications on genome architecture and gene regulation.
MeSH term(s)	Histones/genetics ; Histones/metabolism ; Histone Code/genetics ; Protein Processing, Post-Translational ; Heterochromatin ; Aspergillus nidulans/genetics ; Aspergillus nidulans/metabolism
Chemical Substances	Histones ; Heterochromatin
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1319820-8
ISSN	1096-0937 ; 1087-1845 ; 0147-5975
ISSN (online)	1096-0937
ISSN	1087-1845 ; 0147-5975
DOI	10.1016/j.fgb.2023.103800
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Zs.A 2431: Show issues

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Article: Lower-Neck Sparing Using Proton Therapy in Patients with Uninvolved Neck Nasopharyngeal Carcinoma: Is It Safe?

De Felice, Francesca / Vai, Alessandro / Camarda, Anna Maria / Iacovelli, Nicola Alessandro / Orlandi, Ester

Journal of clinical medicine

2022 Volume 11, Issue 12

Abstract: Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. ... ...

Abstract	Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. However, cervical nodal metastasis commonly involves retropharyngeal nodes and level II nodes, followed by level III nodes. In recent years, innovations in terms of systemic treatments and radiotherapy techniques have improved oncological outcome and treatment-related toxicities. Therefore, there is a growing interest in de-intensification strategies of reducing volumes and treatment-related side effects, especially in patients with NPC with N0-N1-stage disease. Proton therapy could represent a valid alternative to Intensity Modulated Radiotherapy (IMRT) in the management of NPC in this setting. With this Commentary, we aim to explore the feasibility of Intensity Modulated Proton Therapy (IMPT) in upper-neck irradiation of NPC N1-stage disease. We selected an NPC patient with N1 disease and compared the original IMRT plan with the IMPT plan in terms of dosimetric parameters. IMPT offers a minimal dosimetric advantage over IMRT in the bilateral lower-neck sparing. Clinical trials are needed to evaluate the significance of these proposed suggestions and their applicability in non-endemic areas.
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11123297
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Article ; Online: Is motherhood still possible after pelvic carbon ion radiotherapy? A promising combined fertility-preservation approach.

Barcellini, Amelia / Cassani, Chiara / Orlandi, Ester / Nappi, Rossella E / Broglia, Federica / Delmonte, Maria Paola / Molinelli, Silvia / Vai, Alessandro / Vitolo, Viviana / Gronchi, Alessandro / D'Ambrosio, Gioacchino / Cobianchi, Lorenzo / Fiore, Maria Rosaria

Tumori

2024 Volume 110, Issue 2, Page(s) 132–138

Abstract: Introduction: Preserving the endocrine and reproductive function in young female cancer patients undergoing pelvic radiation is a significant challenge. While the photon beam radiation's adverse effects on the uterus and ovaries are well established, ... ...

Abstract	Introduction: Preserving the endocrine and reproductive function in young female cancer patients undergoing pelvic radiation is a significant challenge. While the photon beam radiation's adverse effects on the uterus and ovaries are well established, the impact of pelvic carbon ion radiotherapy on women's reproductive function is largely unexplored. Strategies such as oocyte cryopreservation and ovarian transposition are commonly recommended for safeguarding future fertility. Methods: This study presents a pioneering case of successful pregnancy after carbon ion radiotherapy for locally advanced sacral chondrosarcoma. Results: A multidisciplinary approach facilitated the displacement of ovaries and uterus before carbon ion radiotherapy, resulting in the preservation of endocrine and reproductive function. Conclusion: The patient achieved optimal oncological response and delivered a healthy infant following the completion of cancer treatment.
MeSH term(s)	Female ; Humans ; Pregnancy ; Cryopreservation/methods ; Fertility/physiology ; Fertility Preservation/methods ; Heavy Ion Radiotherapy/adverse effects ; Ovary ; Adult
Language	English
Publishing date	2024-01-05
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	280962-x
ISSN	2038-2529 ; 0300-8916
ISSN (online)	2038-2529
ISSN	0300-8916
DOI	10.1177/03008916231218794
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Article ; Online: Technical note: Radiological clinical equivalence for phantom materials in carbon ion therapy.

Taylor, Paige A / Mirandola, Alfredo / Ciocca, Mario / Hartzell, Shannon / Vai, Alessandro / Alvarez, Paola / Howell, Rebecca M / Koay, Eugene J / Peeler, Christopher R / Peterson, Christine B / Kry, Stephen F

Medical physics

2024

Abstract: Purpose: As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a ... ...

Abstract	Purpose: As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a therapeutic carbon ion beam. Methods: Eight materials were tested for radiological material-equivalence in a carbon ion beam. The materials were computed tomography (CT)-scanned to obtain Hounsfield unit (HU) values, then irradiated in a monoenergetic carbon ion beam to determine relative linear stopping power (RLSP). The corresponding HU and RLSP for each phantom material were compared to clinical carbon ion calibration curves. For absorbed dose comparison, ion chamber measurements were made in the center of a carbon ion spread-out Bragg peak (SOBP) in water and in the phantom material, evaluating whether the material perturbed the absorbed dose measurement beyond what was predicted by the HU-RLSP relationship. Results: Polyethylene, solid water (Gammex and Sun Nuclear), Blue Water (Standard Imaging), and Techtron HPV had measured RLSP values that agreed within ±4.2% of RLSP values predicted by the clinical calibration curve. Measured RLSP for acrylic was 7.2% different from predicted. The agreement for balsa wood and cork varied between samples. Ion chamber measurements in the phantom materials were within 0.1% of ion chamber measurements in water for most materials (solid water, Blue Water, polyethylene, and acrylic), and within 1.9% for the rest of the materials (balsa wood, cork, and Techtron HPV). Conclusions: Several phantom materials (Blue Water, polyethylene, solid water [Gammex and Sun Nuclear], and Techtron HPV) are suitable for heterogeneous phantom measurements for carbon ion therapy. Low density materials should be carefully characterized due to inconsistencies between samples.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.17056
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Zs.A 1210: Show issues

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Article ; Online: The role of multiple anatomical scenarios in plan optimization for carbon ion radiotherapy of pancreatic cancer.

Molinelli, Silvia / Vai, Alessandro / Russo, Stefania / Loap, Pierre / Meschini, Giorgia / Paganelli, Chiara / Barcellini, Amelia / Vitolo, Viviana / Orlandi, Ester / Ciocca, Mario

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2022 Volume 176, Page(s) 1–8

Abstract: Purpose /objective: To quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer.: Material/methods: For 10 previously treated ... ...

Abstract	Purpose /objective: To quantify benefits of robust optimization on multiple 4DCT acquisitions combined with off-line treatment adaptation for neoadjuvant carbon ion therapy (CIRT) of pancreatic cancer. Material/methods: For 10 previously treated patients, 4DCTs were acquired around -15 (CT Results: (A) No recalculation exceeded the D Conclusion: Anatomical variations highlighted at multiple RE
MeSH term(s)	Humans ; Radiotherapy Planning, Computer-Assisted/methods ; Radiotherapy Dosage ; Heavy Ion Radiotherapy ; Organs at Risk ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/radiotherapy ; Radiotherapy, Intensity-Modulated/methods ; Proton Therapy/methods ; Pancreatic Neoplasms
Language	English
Publishing date	2022-09-14
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2022.09.005
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Article: Synthetic CT in Carbon Ion Radiotherapy of the Abdominal Site.

Parrella, Giovanni / Vai, Alessandro / Nakas, Anestis / Garau, Noemi / Meschini, Giorgia / Camagni, Francesca / Molinelli, Silvia / Barcellini, Amelia / Pella, Andrea / Ciocca, Mario / Vitolo, Viviana / Orlandi, Ester / Paganelli, Chiara / Baroni, Guido

Bioengineering (Basel, Switzerland)

2023 Volume 10, Issue 2

Abstract: The generation of synthetic CT for carbon ion radiotherapy (CIRT) applications is challenging, since high accuracy is required in treatment planning and delivery, especially in an anatomical site as complex as the abdomen. Thirty-nine abdominal MRI-CT ... ...

Abstract	The generation of synthetic CT for carbon ion radiotherapy (CIRT) applications is challenging, since high accuracy is required in treatment planning and delivery, especially in an anatomical site as complex as the abdomen. Thirty-nine abdominal MRI-CT volume pairs were collected and a three-channel cGAN (accounting for air, bones, soft tissues) was used to generate sCTs. The network was tested on five held-out MRI volumes for two scenarios: (i) a CT-based segmentation of the MRI channels, to assess the quality of sCTs and (ii) an MRI manual segmentation, to simulate an MRI-only treatment scenario. The sCTs were evaluated by means of similarity metrics (e.g., mean absolute error, MAE) and geometrical criteria (e.g., dice coefficient). Recalculated CIRT plans were evaluated through dose volume histogram, gamma analysis and range shift analysis. The CT-based test set presented optimal MAE on bones (86.03 ± 10.76 HU), soft tissues (55.39 ± 3.41 HU) and air (54.42 ± 11.48 HU). Higher values were obtained from the MRI-only test set (MAE
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering10020250
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Article ; Online: Characterization of a flat-panel detector for 2D dosimetry in scanned proton and carbon ion beams.

Rossi, Eleonora / Russo, Stefania / Maestri, Davide / Magro, Giuseppe / Mirandola, Alfredo / Molinelli, Silvia / Vai, Alessandro / Grevillot, Loïc / Bolsa-Ferruz, Marta / Rossomme, Séverine / Ciocca, Mario

Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

2023 Volume 107, Page(s) 102561

Abstract: Purpose: To fully characterize the flat panel detector of the new Sphinx Compact device with scanned proton and carbon ion beams.: Materials and methods: The Sphinx Compact is designed for daily QA in particle therapy. We tested its repeatability and ...

Abstract	Purpose: To fully characterize the flat panel detector of the new Sphinx Compact device with scanned proton and carbon ion beams. Materials and methods: The Sphinx Compact is designed for daily QA in particle therapy. We tested its repeatability and dose rate dependence as well as its proportionality with an increasing number of particles and potential quenching effect. Potential radiation damage was evaluated. Finally, we compared the spot characterization (position and profile FWHM) with our radiochromic EBT3 film baseline. Results: The detector showed a repeatability of 1.7% and 0.9% for single spots of protons and carbon ions, respectively, while for small scanned fields it was inferior to 0.2% for both particles. The response was independent from the dose rate (difference from nominal value < 1.5%). We observed an under-response due to quenching effect for both particles, mostly for carbon ions. No radiation damage effects were observed after two months of weekly use and approximately 1350 Gy delivered to the detector. Good agreement was found between the Sphinx and EBT3 films for the spot position (central-axis deviation within 1 mm). The spot size measured with the Sphinx was larger compared to films. For protons, the average and maximum differences over different energies were 0.4 mm (3%) and 1 mm (7%); for carbon ions they were 0.2 mm (4%) and 0.4 mm (6%). Conclusions: Despite the quenching effect the Sphinx Compact fulfills the requirements needed for constancy checks and could represent a time-saving tool for daily QA in scanned particle beams.
MeSH term(s)	Protons ; Proton Therapy ; Radiometry ; Carbon ; Film Dosimetry
Chemical Substances	Protons ; Carbon (7440-44-0)
Language	English
Publishing date	2023-03-08
Publishing country	Italy
Document type	Journal Article
ZDB-ID	1122650-x
ISSN	1724-191X ; 1120-1797
ISSN (online)	1724-191X
ISSN	1120-1797
DOI	10.1016/j.ejmp.2023.102561
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Article ; Online: High-dose hypofractionated pencil beam scanning carbon ion radiotherapy for lung tumors: Dosimetric impact of different spot sizes and robustness to interfractional uncertainties.

Mastella, Edoardo / Mirandola, Alfredo / Russo, Stefania / Vai, Alessandro / Magro, Giuseppe / Molinelli, Silvia / Barcellini, Amelia / Vitolo, Viviana / Orlandi, Ester / Ciocca, Mario

Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

2021 Volume 85, Page(s) 79–86

Abstract: Purpose: The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors.: Methods: CIRT plans of 9 patients ... ...

Abstract	Purpose: The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors. Methods: CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions. Standard spots (SS) were compared to big spots (BS). Plans were recalculated on multiple 4DCTs acquired within 3 weeks from treatment simulation and rigidly registered with planning images using bone matching. Warped dose distributions were generated using deformable image registration and accumulated on the planning 4DCTs. Target coverage (D98%, D95% and V95%) and dose to lung were evaluated in the recalculated and accumulated dose distributions. Results: Comparable target coverage was obtained with both spot sizes (p = 0.53 for D95%). The mean lung dose increased of 0.6 Gy(RBE) with BS (p = 0.0078), still respecting the dose constraint of a 4-fraction stereotactic treatment for the risk of radiation pneumonitis. Statistically significant differences were found in the recalculated and accumulated D95% (p = 0.048 and p = 0.024), with BS showing to be more robust. Using BS, the average degradations of the D98%, D95% and V95% in the accumulated doses were -2.7%, -1.6% and -1.5%. Conclusions: Gated 4DRRO was highly robust against setup and motion uncertainties. BS increased the dose to healthy tissues but were more robust than SS. The selected optimization settings guaranteed adequate target coverage during the simulated treatment course with acceptable risk of toxicity.
MeSH term(s)	Carbon ; Heavy Ion Radiotherapy ; Humans ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/radiotherapy ; Organs at Risk ; Proton Therapy ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated
Chemical Substances	Carbon (7440-44-0)
Language	English
Publishing date	2021-05-10
Publishing country	Italy
Document type	Journal Article
ZDB-ID	1122650-x
ISSN	1724-191X ; 1120-1797
ISSN (online)	1724-191X
ISSN	1120-1797
DOI	10.1016/j.ejmp.2021.05.004
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Article ; Online: Consensus guide on CT-based prediction of stopping-power ratio using a Hounsfield look-up table for proton therapy.

Peters, Nils / Trier Taasti, Vicki / Ackermann, Benjamin / Bolsi, Alessandra / Vallhagen Dahlgren, Christina / Ellerbrock, Malte / Fracchiolla, Francesco / Gomà, Carles / Góra, Joanna / Cambraia Lopes, Patricia / Rinaldi, Ilaria / Salvo, Koen / Sojat Tarp, Ivanka / Vai, Alessandro / Bortfeld, Thomas / Lomax, Antony / Richter, Christian / Wohlfahrt, Patrick

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 184, Page(s) 109675

Abstract: Background and purpose: Studies have shown large variations in stopping-power ratio (SPR) prediction from computed tomography (CT) across European proton centres. To standardise this process, a step-by-step guide on specifying a Hounsfield look-up table ...

Abstract	Background and purpose: Studies have shown large variations in stopping-power ratio (SPR) prediction from computed tomography (CT) across European proton centres. To standardise this process, a step-by-step guide on specifying a Hounsfield look-up table (HLUT) is presented here. Materials and methods: The HLUT specification process is divided into six steps: Phantom setup, CT acquisition, CT number extraction, SPR determination, HLUT specification, and HLUT validation. Appropriate CT phantoms have a head- and body-sized part, with tissue-equivalent inserts in regard to X-ray and proton interactions. CT numbers are extracted from a region-of-interest covering the inner 70% of each insert in-plane and several axial CT slices in scan direction. For optimal HLUT specification, the SPR of phantom inserts is measured in a proton beam and the SPR of tabulated human tissues is computed stoichiometrically at 100 MeV. Including both phantom inserts and tabulated human tissues increases HLUT stability. Piecewise linear regressions are performed between CT numbers and SPRs for four tissue groups (lung, adipose, soft tissue, and bone) and then connected with straight lines. Finally, a thorough but simple validation is performed. Results: The best practices and individual challenges are explained comprehensively for each step. A well-defined strategy for specifying the connection points between the individual line segments of the HLUT is presented. The guide was tested exemplarily on three CT scanners from different vendors, proving its feasibility. Conclusion: The presented step-by-step guide for CT-based HLUT specification with recommendations and examples can contribute to reduce inter-centre variations in SPR prediction.
MeSH term(s)	Humans ; Proton Therapy/methods ; Protons ; Consensus ; Phantoms, Imaging ; Tomography, X-Ray Computed/methods ; Calibration
Chemical Substances	Protons
Language	English
Publishing date	2023-04-19
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.109675
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