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Article: Circulating tumor cells and host immunity: A tricky liaison.

Muraro, Elena / Brisotto, Giulia

International review of cell and molecular biology

2023 Volume 381, Page(s) 131–157

Abstract: During their dissemination, circulating tumor cells (CTCs) steadily face the immune system, which is a key player in the whole metastatic cascade, from intravasation to the CTC colonization of distant sites. In this chapter, we will go through the ... ...

Abstract	During their dissemination, circulating tumor cells (CTCs) steadily face the immune system, which is a key player in the whole metastatic cascade, from intravasation to the CTC colonization of distant sites. In this chapter, we will go through the description of immune cells involved in this controversial dialogue encompassing both the anti-tumor activity and the tumor-promoting and immunosuppressive function mediated by several circulating immune effectors as natural killer (NK) cells, CD4
MeSH term(s)	Humans ; Neoplastic Cells, Circulating ; Immunosuppressive Agents ; Macrophages ; T-Lymphocytes, Regulatory
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2023-08-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2427220-6
ISSN	1937-6448 ; 0074-7696
ISSN	1937-6448 ; 0074-7696
DOI	10.1016/bs.ircmb.2023.07.002
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Article ; Online: Long Noncoding RNAs as Innovative Urinary Diagnostic Biomarkers.

Brisotto, Giulia / Guerrieri, Roberto / Colizzi, Francesca / Steffan, Agostino / Montico, Barbara / Fratta, Elisabetta

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2292, Page(s) 73–94

Abstract: The characterization of circulating tumor cells (CTCs) is now widely studied as a promising source of cancer-derived biomarkers because of their role in tumor formation and progression. However, CTCs analysis presents some limitations and no standardized ...

Abstract	The characterization of circulating tumor cells (CTCs) is now widely studied as a promising source of cancer-derived biomarkers because of their role in tumor formation and progression. However, CTCs analysis presents some limitations and no standardized method for CTCs isolation from urine has been defined so far. In fact, besides blood, urine represents an ideal source of noninvasive biomarkers, especially for the early detection of genitourinary tumors. Besides CTCs, long noncoding RNAs (lncRNAs) have also been proposed as potential noninvasive biomarkers, and the evaluation of the diagnostic accuracy of urinary lncRNAs has dramatically increased over the last years, with many studies being published. Therefore, this review provides an update on the clinical utility of urinary lncRNAs as novel biomarkers for the diagnosis of bladder and prostate cancers.
MeSH term(s)	Animals ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/urine ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/urine ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/urine ; Urinary Bladder Neoplasms/diagnosis ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/urine
Chemical Substances	Biomarkers, Tumor ; RNA, Long Noncoding
Language	English
Publishing date	2021-03-02
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1354-2_7
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Article: Preliminary Study of the Relationship between Osteopontin and Relapsed Hodgkin's Lymphoma.

De Re, Valli / Lopci, Egesta / Brisotto, Giulia / Elia, Caterina / Mussolin, Lara / Mascarin, Maurizio / d'Amore, Emanuele Stefano Giovanni / Aieop The Hodgkin's Lymphoma Research Network

Biomedicines

2023 Volume 12, Issue 1

Abstract: The primary objective of this study was to investigate the potential role of tissue osteopontin, also known as secreted phosphoprotein 1 ( ...

Abstract	The primary objective of this study was to investigate the potential role of tissue osteopontin, also known as secreted phosphoprotein 1 (
Language	English
Publishing date	2023-12-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12010031
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Article: Polymorphisms in Pepsinogen C and miRNA Genes Associate with High Serum Pepsinogen II in Gastric Cancer Patients.

Re, Valli De / Zorzi, Mariangela De / Caggiari, Laura / Repetto, Ombretta / Brisotto, Giulia / Magris, Raffaela / Zanussi, Stefania / Steffan, Agostino / Cannizzaro, Renato

Microorganisms

2021 Volume 9, Issue 1

Abstract: Background: Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the : Methods: Serum levels of PGI and ...

Abstract	Background: Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the Methods: Serum levels of PGI and PGII were determined in 80 patients with gastric cancer and persons at risk for gastric cancer (74 first-degree relatives of patients, 62 patients with autoimmune chronic atrophic gastritis, and 2 patients with dysplasia), with and without Results: PGII levels were significantly higher in patients with gastric cancer, and in those with Conclusions: Serum PGII levels depend in part on an interaction between
Language	English
Publishing date	2021-01-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9010126
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Article: Polymorphisms in Pepsinogen C and miRNA Genes Associate with High Serum Pepsinogen II in Gastric Cancer Patients

Re, Valli De / Zorzi, Mariangela De / Caggiari, Laura / Repetto, Ombretta / Brisotto, Giulia / Magris, Raffaela / Zanussi, Stefania / Steffan, Agostino / Cannizzaro, Renato

Microorganisms. 2021 Jan. 07, v. 9, no. 1

2021

Abstract	Background: Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the PGC (Progastricsin) gene, is regulated by microRNAs (miRNA), but how PGII levels vary with Helicobacter pylori (H. pylori) infection and miRNAs genotype remains unclear. Methods: Serum levels of PGI and PGII were determined in 80 patients with gastric cancer and persons at risk for gastric cancer (74 first-degree relatives of patients, 62 patients with autoimmune chronic atrophic gastritis, and 2 patients with dysplasia), with and without H. pylori infection. As control from the general population, 52 blood donors were added to the analyses. Associations between PGII levels and genetic variants in PGC and miRNA genes in these groups were explored based on H. pylori seropositivity and the risk for gastric cancer. The two-dimensional difference in gel electrophoresis (2D-DIGE) and the NanoString analysis of messenger RNA (mRNAs) from gastric cancer tissue were used to determine the pathways associated with increased PGII levels. Results: PGII levels were significantly higher in patients with gastric cancer, and in those with H. pylori infection, than in other patients or controls. A PGI/PGII ratio ≤ 3 was found better than PGI < 25 ng/mL to identify patients with gastric cancer (15.0% vs. 8.8%). For two genetic variants, namely rs8111742 in miR-Let-7e and rs121224 in miR-365b, there were significant differences in PGII levels between genotype groups among patients with gastric cancer (p = 0.02 and p = 0.01, respectively), but not among other study subjects. Moreover, a strict relation between rs9471643 C-allele with H. pylori infection and gastric cancer was underlined. Fold change in gene expression of mRNA isolated from gastric cancer tissue correlated well with polymorphism, H. pylori infection, increased PGII level, and pathway for bacteria cell entry into the host. Conclusions: Serum PGII levels depend in part on an interaction between H. pylori and host miRNA genotypes, which may interfere with the cut-off of PGI/PGII ratio used to identify persons at risk of gastric cancer. Results reported new findings regarding the relation among H. pylori, PGII-related host polymorphism, and genes involved in this interaction in the gastric cancer setting.
Keywords	Helicobacter pylori ; at-risk population ; bacteria ; blood donors ; blood serum ; gastritis ; gel electrophoresis ; gene expression regulation ; genes ; genetic variation ; genotype ; infection ; messenger RNA ; microRNA ; patients ; pepsinogen ; polymorphism ; risk ; seroprevalence ; stomach neoplasms
Language	English
Dates of publication	2021-0107
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9010126
Database	NAL-Catalogue (AGRICOLA)

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Article: HER2-CDH1

De Re, Valli / Alessandrini, Lara / Brisotto, Giulia / Caggiari, Laura / De Zorzi, Mariangela / Casarotto, Mariateresa / Miolo, Gianmaria / Puglisi, Fabio / Garattini, Silvio Ken / Lonardi, Sara / Cannizzaro, Renato / Canzonieri, Vincenzo / Fassan, Matteo / Steffan, Agostino

Cancers

2022 Volume 14, Issue 5

Abstract: Trastuzumab is a human epidermal growth factor receptor 2 (HER2) inhibitor used to treat HER2+ metastatic gastric cancer (mGC). The present study aims to investigate the relationship ... ...

Abstract	Trastuzumab is a human epidermal growth factor receptor 2 (HER2) inhibitor used to treat HER2+ metastatic gastric cancer (mGC). The present study aims to investigate the relationship between
Language	English
Publishing date	2022-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14051266
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Article: Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients.

Muraro, Elena / Del Ben, Fabio / Turetta, Matteo / Cesselli, Daniela / Bulfoni, Michela / Zamarchi, Rita / Rossi, Elisabetta / Spazzapan, Simon / Dolcetti, Riccardo / Steffan, Agostino / Brisotto, Giulia

Frontiers in oncology

2022 Volume 12, Page(s) 983887

Abstract: Background: Metastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a ... ...

Abstract	Background: Metastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC. Methods: A cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita's overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher's, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method. Results: Stratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p<0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up (p=0.03). Conclusion: These data, whether validated in a larger cohort of patients, suggest that the combined analysis of CTCs and circulating anti-tumor T-cell immunity could represent a valuable immune-oncological biomarker for the liquid biopsy field. The clinical application of this promising tool could improve the management of mBC patients, especially in the setting of immunotherapy, a rising approach for BC treatment requiring reliable predictive biomarkers.
Language	English
Publishing date	2022-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.983887
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Article: Promising drugs and treatment options for pediatric and adolescent patients with Hodgkin lymphoma.

De Re, Valli / Repetto, Ombretta / Mussolin, Lara / Brisotto, Giulia / Elia, Caterina / Lopci, Egesta / d'Amore, Emanuele S G / Burnelli, Roberta / Mascarin, Maurizio

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 965803

Abstract: Currently-available therapies for newly-diagnosed pediatric and adolescent patients with Hodgkin lymphoma result in >95% survival at 5 years. Long-term survivors may suffer from long-term treatment-related side effects, however, so the past 20 years have ...

Abstract	Currently-available therapies for newly-diagnosed pediatric and adolescent patients with Hodgkin lymphoma result in >95% survival at 5 years. Long-term survivors may suffer from long-term treatment-related side effects, however, so the past 20 years have seen clinical trials for children and adolescents with HL gradually abandon the regimens used in adults in an effort to improve this situation. Narrower-field radiotherapy can reduce long-term toxicity while maintaining good tumor control. Various risk-adapted chemo-radiotherapy strategies have been used. Early assessment of tumor response with interim positron emission tomography and/or measuring metabolic tumor volume has been used both to limit RT in patients with favorable characteristics and to adopt more aggressive therapies in patients with a poor response. Most classical Hodgkin's lymphoma relapses occur within 3 years of initial treatment, while relapses occurring 5 years or more after diagnosis are rare. As the outcome for patients with relapsed/refractory classical Hodgkin lymphoma remains unsatisfactory, new drugs have been proposed for its prevention or treatment. This review summarizes the important advances made in recent years in the management of pediatric and adolescent with classical Hodgkin lymphoma, and the novel targeted treatments for relapsed and refractory classical Hodgkin lymphoma.
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.965803
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Article ; Online: Radiation recall dermatitis induced by COVID-19 vaccination in breast cancer patients treated with postoperative radiation therapy.

Vinante, Lorenzo / Caroli, Angela / Revelant, Alberto / Bertini, Federica / Giroldi, Anna / Marson, Marta / Franchin, Giovanni / Muraro, Elena / Brisotto, Giulia / Steffan, Agostino / Baboci, Lorena

Breast (Edinburgh, Scotland)

2022 Volume 65, Page(s) 49–54

Abstract: Background: and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients ... ...

Abstract	Background: and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients. Methods: Patients that received at least one COVID-19 vaccination dose during the year after the end of postoperative breast radiation therapy were included in this observational monocentric study. Local symptoms occurring inside the radiation field after vaccination were patient-reported and scored according to the PRO-CTCAE questionnaire. Descriptive data of radiation recall dermatitis incidence and severity, and potential risk factors were evaluated. Results: A cohort of 361 patients with 756 administered COVID-19 vaccinations was analyzed. Breast symptoms were reported by 7.5% of patients, while radiation recall dermatitis was considered for 5.5%. The incidence of radiation recall dermatitis per single dose of vaccine was 2.6%, with a higher risk for the first dose compared to the second/third (4.4% vs 1%, p = 0.003), especially when administered within the first month after the end of irradiation (12.5% vs 2.2%, p = 0.0004). Local symptoms were generally self-limited and a few cases required anti-inflammatory drugs. Conclusions: Radiation recall dermatitis is an uncommon but not rare phenomenon in breast cancer patients that received COVID-19 vaccination within one year after breast irradiation. However, symptoms severity were generally low/mild and reversible. These findings can be useful for patient counseling.
MeSH term(s)	Breast Neoplasms/radiotherapy ; Breast Neoplasms/surgery ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Female ; Humans ; Radiodermatitis/epidemiology ; Radiodermatitis/etiology ; Vaccination/adverse effects
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-07-02
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	1143210-x
ISSN	1532-3080 ; 0960-9776
ISSN (online)	1532-3080
ISSN	0960-9776
DOI	10.1016/j.breast.2022.06.008
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Article ; Online: IgG antibodies against SARS-CoV-2 decay but persist 4 months after vaccination in a cohort of healthcare workers.

Brisotto, Giulia / Muraro, Elena / Montico, Marcella / Corso, Chiara / Evangelista, Chiara / Casarotto, Mariateresa / Caffau, Cristina / Vettori, Roberto / Cozzi, Maria Rita / Zanussi, Stefania / Turetta, Matteo / Ronchese, Federico / Steffan, Agostino

Clinica chimica acta; international journal of clinical chemistry

2021 Volume 523, Page(s) 476–482

Abstract: Background and aims: Monitoring the immune response against SARS-CoV-2 is pivotal in the evaluation of long-term vaccine efficacy. Immunoglobulin G (IgG) antibodies represent an advisable tool to reach this goal, especially for the still poorly defined ... ...

Abstract	Background and aims: Monitoring the immune response against SARS-CoV-2 is pivotal in the evaluation of long-term vaccine efficacy. Immunoglobulin G (IgG) antibodies represent an advisable tool to reach this goal, especially for the still poorly defined antibody trend induced by the new class of mRNA vaccines against SARS-CoV-2. Materials and methods: Anti-Spike RBD IgG antibodies were monitored in a cohort of healthcare workers at CRO Aviano, National Cancer Institute, through MAGLUMI® chemiluminescence assay, at 1 and 4 months after full-schedule of BNT162b2 or mRNA-1273 vaccination. Results: At 1 month after vaccination, 99.9% of 767 healthcare workers showed a reactive antibody response, which was inversely correlated with age, and positively associated with a previous history of COVID-19, and mRNA-1273 vaccination. Serological response was maintained in 99.6% of the 516 subjects monitored also at follow-up. An antibody decay from 559.8 AU/mL (IQR 359.7-845.7) to 92.7 AU/mL (IQR 65.1-148.6; p < 0.001) was observed, independently from age and sex. Conclusion: Our data supported the ability of SARS-CoV-2 mRNA vaccines to induce at least a 4 months-lasting IgG response, even outside the rules of clinical trials. The antibody decay observed at follow-up suggested to deepen the immune response characterization to identify subjects with low anti-SARS-CoV-2 immunity possibly requiring a vaccination boost.
MeSH term(s)	2019-nCoV Vaccine mRNA-1273 ; BNT162 Vaccine ; COVID-19 ; COVID-19 Vaccines ; Health Personnel ; Humans ; Immunoglobulin G ; SARS-CoV-2 ; Vaccination ; Vaccine Efficacy ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin G ; mRNA Vaccines ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-10-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2021.10.035
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