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Article ; Online: Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy.

Belgiovine, Cristina / Mebelli, Kristiana / Raffaele, Alessandro / De Cicco, Marica / Rotella, Jessica / Pedrazzoli, Paolo / Zecca, Marco / Riccipetitoni, Giovanna / Comoli, Patrizia

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some ... ...

Abstract	Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.
MeSH term(s)	Humans ; Child ; Tumor Microenvironment ; Neoplasms/pathology ; Immunotherapy/methods ; T-Lymphocytes
Language	English
Publishing date	2024-03-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063225
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Article: Synthesis of Ion-Exchange Catalysts by Introduction of Fluorinated Ponytails into Novel Mesoporous Polymers.

Dalla Valle, Chiara / Sandri, Francesco / Zecca, Marco / Rastrelli, Federico / Campestrini, Sandro / Centomo, Paolo

Materials (Basel, Switzerland)

2023 Volume 16, Issue 10

Abstract: A novel synthetic procedure for the functionalisation of styrenic cross-linked polymers with perfluorinated acyl chains has been reported. The effective significant grafting of the fluorinated moieties is supported by { ...

Abstract	A novel synthetic procedure for the functionalisation of styrenic cross-linked polymers with perfluorinated acyl chains has been reported. The effective significant grafting of the fluorinated moieties is supported by {
Language	English
Publishing date	2023-05-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma16103808
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Article ; Online: Cross-Linked Polymers as Scaffolds for the Low-Temperature Preparation of Nanostructured Metal Oxides.

Centomo, Paolo / Zecca, Marco / Biffis, Andrea

Chemistry (Weinheim an der Bergstrasse, Germany)

2020 Volume 26, Issue 42, Page(s) 9243–9260

Abstract: The current state of the art of the use of cross-linked organic polymers, both insoluble (resins or gels) and soluble (micro- and nanogels), as aids for the low-temperature preparation of stable metal oxide nanoparticles or nanostructured metal oxides is ...

Abstract	The current state of the art of the use of cross-linked organic polymers, both insoluble (resins or gels) and soluble (micro- and nanogels), as aids for the low-temperature preparation of stable metal oxide nanoparticles or nanostructured metal oxides is reviewed herein. Synthetic strategies for inorganic oxide nanomaterials of this kind can greatly benefit from the use of cross-linked polymers, which may act as scaffolds/exotemplates during inorganic nanoparticle synthesis, or as stabilizers following post-synthetic modification of the nanoparticles. Furthermore, the peculiar properties of the organic cross-linked polymers add to those of the inorganic oxide nanoparticles, producing materials with combined properties. The potential applications of such highly promising composite nanomaterials will be also briefly sketched.
Language	English
Publishing date	2020-07-09
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202000815
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Article: Exploring the Effects of Cancer as a Traumatic Event on Italian Adolescents and Young Adults: Investigating Psychological Well-Being, Identity Construction and Coping Strategies.

Ionio, Chiara / Bigoni, Francesca / Sacchi, Maddalena / Zecca, Marco / Bergami, Elena / Landoni, Marta / Ciuffo, Giulia / Rovati, Anna / Rizzi, Damiano

Pediatric reports

2023 Volume 15, Issue 1, Page(s) 254–262

Abstract: Cancer in adolescence is considered a family disease that can have numerous negative psychological consequences for adolescents and the entire household. The aim of this study was to investigate the impact of oncological disease in adolescence, with ... ...

Abstract	Cancer in adolescence is considered a family disease that can have numerous negative psychological consequences for adolescents and the entire household. The aim of this study was to investigate the impact of oncological disease in adolescence, with particular reference to the psychological and post-traumatic consequences for the adolescents themselves and the family system. An explorative case-control study was conducted with 31 adolescents (mean age 18.03 ± 2.799) hospitalised for cancer at IRCCS San Matteo Hospital in Pavia and 47 healthy adolescents (mean age 16.17 ± 2.099). The two samples completed a survey that included sociodemographic information and questionnaires assessing psychological well-being, traumatic effects of the disease, and adequacy of the relationship with parents. 56.7% of oncology adolescents scored below average in psychological well-being, and a small proportion of them fell within the range of clinical concern for anger (9.7%), PTS (12.9%), and dissociation (12.9%). Compared with peers, there were no significant differences. However, in contrast to peers, oncology adolescents showed a strong influence of the traumatic event on the construction of their identity and life perspectives. A significantly positive correlation also emerged between adolescents' psychological well-being and the relationship with their parents (mothers: r = 0.796;
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article
ISSN	2036-749X
ISSN	2036-749X
DOI	10.3390/pediatric15010021
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Article: Patient Blood Management after Hematopoietic Stem Cell Transplantation in a Pediatric Setting: Starting Low and Going Lower.

Del Fante, Claudia / Mortellaro, Cristina / Recupero, Santina / Giorgiani, Giovanna / Agostini, Annalisa / Panigari, Arianna / Perotti, Cesare / Zecca, Marco

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 13

Abstract: Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) ... ...

Abstract	Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL;
Language	English
Publishing date	2023-07-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13132257
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Article ; Online: Efficacy and safety of azacitidine in pediatric patients with newly diagnosed advanced myelodysplastic syndromes before hematopoietic stem cell transplantation in the AZA-JMML-001 trial.

Locatelli, Franco / Strålin, Karin Belander / Schmid, Irene / Sevilla, Julián / Smith, Owen P / van den Heuvel-Eibrink, Marry M / Zecca, Marco / Zwaan, Christian M / Gaudy, Allison / Patturajan, Meera / Poon, Jennifer / Simcock, Mathew / Niemeyer, Charlotte M

Pediatric blood & cancer

2024 Volume 71, Issue 5, Page(s) e30931

Abstract: Here we report efficacy, pharmacokinetics, and safety data obtained in treatment-naive, pediatric patients with newly diagnosed advanced MDS receiving azacitidine in the AZA-JMML-001 study. The primary endpoint was response rate (proportion of patients ... ...

Abstract	Here we report efficacy, pharmacokinetics, and safety data obtained in treatment-naive, pediatric patients with newly diagnosed advanced MDS receiving azacitidine in the AZA-JMML-001 study. The primary endpoint was response rate (proportion of patients with complete response [CR], partial response [PR], or marrow CR, sustained for ≥4 weeks). Of the 10 patients enrolled, one had an unconfirmed marrow CR and none had confirmed responses after three cycles; the study was therefore closed after stage 1. Azacitidine was well tolerated. The lack of efficacy of azacitidine in pediatric patients with newly diagnosed advanced MDS highlights the need for effective new treatments in these patients.
MeSH term(s)	Humans ; Child ; Azacitidine/adverse effects ; Leukemia, Myeloid, Acute/drug therapy ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/diagnosis ; Treatment Outcome ; Hematopoietic Stem Cell Transplantation/adverse effects
Chemical Substances	Azacitidine (M801H13NRU)
Language	English
Publishing date	2024-03-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30931
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Zs.A 1131: Show issues

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Article ; Online: Long-Term Complications after Allogeneic Hematopoietic Stem Cell Transplantation with Treosulfan- or Busulfan-Based Conditioning in Pediatric Patients with Acute Leukemia or Myelodysplastic Syndrome: Results of an Associazione Italiana Ematologia Oncologia Pediatrica Retrospective Study.

Saglio, Francesco / Pagliara, Daria / Zecca, Marco / Balduzzi, Adriana / Cattoni, Alessandro / Prete, Arcangelo / Tambaro, Francesco Paolo / Faraci, Maura / Calore, Elisabetta / Locatelli, Franco / Fagioli, Franca

Transplantation and cellular therapy

2024 Volume 30, Issue 4, Page(s) 433.e1–433.e10

Abstract: Patients undergoing hematopoietic stem cell transplantation (HSCT) for hematologic malignancies during childhood have an increased risk of developing long-term sequelae that are in part attributable to the conditioning regimen. The present study aimed to ...

Abstract	Patients undergoing hematopoietic stem cell transplantation (HSCT) for hematologic malignancies during childhood have an increased risk of developing long-term sequelae that are in part attributable to the conditioning regimen. The present study aimed to assess the occurrence of long-term toxicities in a population of children who underwent HSCT for hematologic malignancies using either treosulfan or busulfan in the conditioning regimen. The cumulative incidences of growth impairment, altered gonadal function, altered thyroid function, cataracts, secondary malignant neoplasia, and altered pulmonary function were evaluated retrospectively by univariable and multivariable analyses in a population of 521 pediatric patients with acute leukemias or myelodysplastic syndromes treated in 20 Italian transplant centers affiliated with the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP). The median duration of follow-up for the entire study population was 7.1 years (range, 1 to 16 years). Overall, a larger proportion of patients given busulfan developed long-term toxicities compared to patients treated with treosulfan (34% versus 20%; P = .01). In univariable analysis, gonadal toxicity developed in 10% of patients who received treosulfan (95% confidence interval [CI], 3% to 15%), compared with 38% (95% CI, 24% to 39%) of busulfan-treated patients (P = .02), and this finding was confirmed by multivariable analysis (relative risk, .51; 95% CI, .34 to .76; P = .0009). We did not find any statistically significant associations between the occurrence of other long-term toxicities and the use of either busulfan or treosulfan. This study provides evidence that the use of treosulfan is correlated with a reduced incidence of gonadal toxicity in children undergoing HSCT for hematologic malignancies.
MeSH term(s)	Humans ; Child ; Busulfan/adverse effects ; Busulfan/analogs & derivatives ; Retrospective Studies ; Transplantation Conditioning/adverse effects ; Transplantation Conditioning/methods ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Leukemia, Myeloid, Acute/therapy ; Myelodysplastic Syndromes/therapy ; Hematologic Neoplasms
Chemical Substances	treosulfan (CO61ER3EPI) ; Busulfan (G1LN9045DK)
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2023.12.671
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Zs.A 5082: Show issues

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Article ; Online: Future perspectives of radiation therapy for Hodgkin Lymphoma: Risk-adapted, response-adapted, and safer than before.

Saddi, Jessica / Barcellini, Amelia / Gotti, Manuel / Mazzacane, Alessandro / Tolva, Alessandra / Lazic, Tanja / Arcaini, Luca / Zecca, Marco / Orlandi, Ester / Filippi, Andrea Riccardo

Hematological oncology

2024 Volume 42, Issue 3, Page(s) e3269

Abstract: Classical Hodgkin lymphoma is a lymphoproliferative disease with a good prognosis mainly seen in young people. Nevertheless secondary malignancy, cardiac disease and infertility may affect the long survivors with significant impact on quality of life, ... ...

Abstract	Classical Hodgkin lymphoma is a lymphoproliferative disease with a good prognosis mainly seen in young people. Nevertheless secondary malignancy, cardiac disease and infertility may affect the long survivors with significant impact on quality of life, morbidity and overall survival. In the last decades several treatment strategies were evaluated to reduce the toxicity of first line treatment such as avoiding radiotherapy or its reduction in terms of dosage and extension. Many trials including interim Positron Emission Tomography evaluation fail to compare efficacy between combined modality treatment versus chemotherapy alone in particular in early stage disease. In this review we analyze which subset of patients could take advantage from proton therapy in terms of toxicity and cost effectiveness.
MeSH term(s)	Humans ; Hodgkin Disease/radiotherapy ; Proton Therapy/adverse effects ; Proton Therapy/methods
Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.3269
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Zs.A 1816: Show issues

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Article ; Online: Production of donor-derived cytotoxic T lymphocytes with potent anti-leukemia activity for adoptive immunotherapy in high-risk pediatric patients given haploidentical hematopoietic stem cell transplantation.

Tanzi, Matteo / Montini, Enrica / Rumolo, Agnese / Moretta, Antonia / Comoli, Patrizia / Acquafredda, Gloria / Rotella, Jessica / Taurino, Gloria / Compagno, Francesca / Cave, Francesco Delle / Perotti, Cesare / Marseglia, Gian Luigi / Zecca, Marco / Montagna, Daniela

Cytotherapy

2024

Abstract: Background aims: Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this ... ...

Abstract	Background aims: Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this approach strongly depends on the ex vivo generation of high-quality donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practices (GMP). We previously described a procedure for generating large numbers of donor-derived anti-leukemia CTL through stimulation of CD8-enriched lymphocytes with dendritic cells (DCs) pulsed with apoptotic LB in the presence of interleukin (IL)-12, IL-7 and IL-15. Here we report that the use of IFN-DC and the addition of IFNα2b during the priming phase significantly improve the generation of an efficient anti-leukemia T cells response in vitro. Methods: Using this approach, 20 high-risk pediatric patients given haploidentical HSCT for high-risk acute leukemia were enrolled and 51 batches of advanced therapy medical products (ATMP), anti-leukemia CTL, were produced. Results: Quality controls demonstrated that all batches were sterile, free of mycoplasma and conformed to acceptable endotoxin levels. Genotype analysis confirmed the molecular identity of the ATMP based on the starting biological material used for their production. The majority of ATMP were CD3+/CD8+ cells, with a memory/terminal activated phenotype, including T-central memory populations. ATMP were viable after thawing, and most ATMP batches displayed efficient capacity to lyse patients' LB and to secrete interferon-γ and tumor necrosis factor-α. Conclusions: These results demonstrated that our protocol is highly reproducible and allows the generation of large numbers of immunologically safe and functional anti-leukemia CTL with a high level of standardization.
Language	English
Publishing date	2024-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2024.04.005
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Zs.A 5601: Show issues

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Article: FANCA, TP53, and del(5q)/RPS14 alterations in a patient with T-cell non-Hodgkin lymphoma and concomitant Fanconi anemia and Li-Fraumeni syndrome.

Errichiello, Edoardo / Mina, Tommaso / Morbini, Patrizia / Zecca, Marco / Zuffardi, Orsetta

Cancer genetics

2020 Volume 256-257, Page(s) 179–183

Abstract: We traced the neoplastic history (from 5 to 11 years of age) of a child with concomitant Fanconi anemia and Li-Fraumeni syndrome. Interestingly, the patient developed a highly malignant T-cell non-Hodgkin lymphoma (NHL), which does not represent the ... ...

Abstract	We traced the neoplastic history (from 5 to 11 years of age) of a child with concomitant Fanconi anemia and Li-Fraumeni syndrome. Interestingly, the patient developed a highly malignant T-cell non-Hodgkin lymphoma (NHL), which does not represent the typical tumor type in the two aforementioned syndromes, presumably due to the underlying genomic instability. By using a combination of molecular and immunohistochemical approaches, we characterized the accumulation of multiple genetic alterations in a single patient, with both germline (parentally inherited biallelic FANCA variants and a likely de novo nonsense variant in TP53) and somatic (TP53 loss of heterozygosity and 5q interstitial deletion) contributions. Our findings support the interplay of TP53 and FANC genes in DNA damage response pathways and further highlight the genetic heterogeneity of lymphomas as well as the contribution of genomic instability to lymphomagenesis.
MeSH term(s)	Base Sequence ; Child, Preschool ; Fanconi Anemia/complications ; Fanconi Anemia/immunology ; Fanconi Anemia Complementation Group A Protein/genetics ; Gene Deletion ; Humans ; Li-Fraumeni Syndrome/complications ; Li-Fraumeni Syndrome/immunology ; Loss of Heterozygosity/genetics ; Lymphoma, Non-Hodgkin/complications ; Lymphoma, Non-Hodgkin/immunology ; Ribosomal Proteins/genetics ; T-Lymphocytes/immunology ; Tumor Suppressor Protein p53/genetics
Chemical Substances	FANCA protein, human ; Fanconi Anemia Complementation Group A Protein ; RPS14 protein, human ; Ribosomal Proteins ; Tumor Suppressor Protein p53
Language	English
Publishing date	2020-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599227-2
ISSN	2210-7762
ISSN	2210-7762
DOI	10.1016/j.cancergen.2020.10.003
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Zs.A 1521: Show issues

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