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Biomedicines
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State-of-the-Art Cancer Biology and Therapeutics in Italy
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State-of-the-Art Cancer Biology and Therapeutics in Italy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 12096

Special Issue Editors

Dr. Luca Pacini

E-Mail Website
Guest Editor
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome “Sapienza”, Roma, Italy
Interests: cancer biology; molecular marker; pharmacology; oxidative stress
Dr. Umberto Malapelle

E-Mail Website
Guest Editor
Department of Public Health, University of Naples Federico II, Naples, Italy
Interests: predictive molecular pathology in solid tumors; next generation technologies in molecular biology; liquid biopsies; predictive oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer still represents one of the leading causes of death in the world and in Italy, there have been many advances in the treatment and care of cancer patients; new molecular targeted therapies and new knowledge in the molecular field represent an important step. Understanding the basic biological processes, new biomarkers and their clinical characteristics will be fundamental for new therapies based on evaluating the individual response to treatments. Together, these data will open the way for more personalized medicine.

This call for papers aims to collect high quality documents on the research areas in tumor diseases in Italy, with particular attention to studies on biological heterogeneity, their impact in the clinic, studies on molecular biology and studies on new molecular pathways. The use of multidisciplinary approaches is essential for the success of this field; therefore, contributions including interdisciplinary studies (epidemiology, genetics, molecular biology, cell biology, immunology and pharmacology) are strongly encouraged.

Dr. Luca Pacini
Dr. Umberto Malapelle
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapeutics
  • epidemiology
  • immunology
  • pathomechanisms
  • molecular biology
  • cell biology
  • disease heterogeneity
  • genetics
  • biomarkers
  • pharmacology

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Published Papers (6 papers)

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Research

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16 pages, 3264 KiB  
Article
PBMCs as Tool for Identification of Novel Immunotherapy Biomarkers in Lung Cancer
by Caterina De Rosa, Francesca Iommelli, Viviana De Rosa, Giuseppe Ercolano, Federica Sodano, Concetta Tuccillo, Luisa Amato, Virginia Tirino, Annalisa Ariano, Flora Cimmino, Gaetano di Guida, Gennaro Filosa, Alessandra di Liello, Davide Ciardiello, Erika Martinelli, Teresa Troiani, Stefania Napolitano, Giulia Martini, Fortunato Ciardiello, Federica Papaccio, Floriana Morgillo and Carminia Maria Della Corteadd Show full author list remove Hide full author list
Biomedicines 2024, 12(4), 809; https://doi.org/10.3390/biomedicines12040809 - 5 Apr 2024
Cited by 1 | Viewed by 3152
Abstract
Background: Lung cancer (LC), including both non-small (NSCLC) and small (SCLC) subtypes, is currently treated with a combination of chemo- and immunotherapy. However, predictive biomarkers to identify high-risk patients are needed. Here, we explore the role of peripheral blood mononuclear cells (PBMCs) as [...] Read more.
Background: Lung cancer (LC), including both non-small (NSCLC) and small (SCLC) subtypes, is currently treated with a combination of chemo- and immunotherapy. However, predictive biomarkers to identify high-risk patients are needed. Here, we explore the role of peripheral blood mononuclear cells (PBMCs) as a tool for novel biomarkers searching. Methods: We analyzed the expression of the cGAS-STING pathway, a key DNA sensor that activates during chemotherapy, in PBMCs from LC patients divided into best responders (BR), responders (R) and non-responders (NR). The PBMCs were whole exome sequenced (WES). Results: PBMCs from BR and R patients of LC cohorts showed the highest levels of STING (p < 0.0001) and CXCL10 (p < 0.0001). From WES, each subject had at least 1 germline/somatic alteration in a DDR gene and the presence of more DDR gene mutations correlated with clinical responses, suggesting novel biomarker implications. Thus, we tested the effect of the pharmacological DDR inhibitor (DDRi) in PBMCs and in three-dimensional spheroid co-culture of PBMCs and LC cell lines; we found that DDRi strongly increased cGAS-STING expression and tumor infiltration ability of immune cells in NR and R patients. Furthermore, we performed FACS analysis of PBMCs derived from LC patients from the BR, R and NR cohorts and we found that cytotoxic T cell subpopulations displayed the highest STING expression. Conclusions: cGAS-STING signaling activation in PBMCs may be a novel potential predictive biomarker for the response to immunotherapy and high levels are correlated with a better response to treatment along with an overall increased antitumor immune injury. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)
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13 pages, 2145 KiB  
Communication
Iron Bioavailability in the Extracellular Environment Is More Relevant Than the Intracellular One in Viability and Gene Expression: A Lesson from Oligodendroglioma Cells
by Stefania Braidotti, Debora Curci, Daniele Zampieri, Cesare Covino, Davide Zanon, Natalia Maximova and Roberto Sala
Biomedicines 2023, 11(11), 2940; https://doi.org/10.3390/biomedicines11112940 - 31 Oct 2023
Viewed by 1261
Abstract
Oligodendroglioma (OG) is a brain tumor that contributes to <1% of brain tumor diagnoses in the pediatric population. Unfortunately, pediatric OG remains without definitive molecular characteristics to aid in diagnosis, and little is known about the tumor microenvironment. Tumor cells’ metabolism and proliferation [...] Read more.
Oligodendroglioma (OG) is a brain tumor that contributes to <1% of brain tumor diagnoses in the pediatric population. Unfortunately, pediatric OG remains without definitive molecular characteristics to aid in diagnosis, and little is known about the tumor microenvironment. Tumor cells’ metabolism and proliferation rate are generally higher than those of healthy cells, so their iron demand is also significantly higher. This consideration underlines the great importance of iron for tumor development and progression. In this context, this study aims to evaluate the effect of iron in a cellular in vitro model of human oligodendroglioma brain tumor. Cell morphology, the effect of siderotic medium on cell growth, iron uptake, and the expression of iron-metabolism-related genes were evaluated via optic microscopy, ICP-MS, confocal microscopy, and real-time PCR, respectively. This study underlines the great importance of iron for tumor development and progression and also the possibility of reducing the available iron concentration to determine an antiproliferative effect on OG. Therefore, every attempt can be promising to defeat OG for which there are currently no long-term curative therapies. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)
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12 pages, 1202 KiB  
Article
Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE)
by Alice Laffi, Lorenzo Gervaso, Oriana D’Ecclesiis, Sara Gandini, Agostino Riva, Rita Passerini, Francesca Spada, Stefania Pellicori, Manila Rubino, Chiara Alessandra Cella, Paola Simona Ravenda, Maria Giulia Zampino and Nicola Fazio
Biomedicines 2023, 11(2), 336; https://doi.org/10.3390/biomedicines11020336 - 25 Jan 2023
Viewed by 2236
Abstract
The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients’ care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and [...] Read more.
The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients’ care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)
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12 pages, 751 KiB  
Article
High Incidence of Thyroid Cancer in Southern Tuscany (Grosseto Province, Italy): Potential Role of Environmental Heavy Metal Pollution
by Marco Capezzone, Massimo Tosti Balducci, Eugenia Maria Morabito, Cosimo Durante, Paolo Piacentini, Liborio Torregrossa, Gabriele Materazzi, Giacomo Giubbolini, Virginia Mancini, Maja Rossi, Massimo Alessandri and Alessandra Cartocci
Biomedicines 2023, 11(2), 298; https://doi.org/10.3390/biomedicines11020298 - 20 Jan 2023
Cited by 2 | Viewed by 1929
Abstract
The incidence of thyroid cancer (TC) in Italy is one of the highest in Europe, and the reason for this is unclear. The intra-country heterogeneity of TC incidence suggests the possibility of an overdiagnosis phenomenon, although environmental factors cannot be excluded. The aim [...] Read more.
The incidence of thyroid cancer (TC) in Italy is one of the highest in Europe, and the reason for this is unclear. The intra-country heterogeneity of TC incidence suggests the possibility of an overdiagnosis phenomenon, although environmental factors cannot be excluded. The aim of our study is to evaluate the TC incidence trend in southern Tuscany, Italy, an area with particular geological characteristics, where the pollution and subsequent deterioration of various environmental matrices with potentially toxic elements (heavy metals) introduced from either geological or anthropogenic (human activities) sources are documented. The Tuscany cancer registry (ISPRO) provided us with the number of cases and EU standardized incidence rates (IR) of TC patients for all three provinces of southeast Tuscany (Siena, Grosseto, Arezzo) during the period of 2013–2016. In addition, we examined the histological records of 226 TC patients. We observed that the TC incidence rates for both sexes observed in Grosseto Province were significantly higher than those observed in the other two provinces. The increase was mostly due to the papillary (PTC) histotype (92% of cases), which presented aggressive variants in 37% of PTCs and tumor diameters more than 1 cm in 71.3% of cases. We demonstrated a high incidence of TC in Grosseto province, especially among male patients, that could be influenced by the presence of environmental heavy metal pollution. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)
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11 pages, 809 KiB  
Article
Role of Prosaposin and Extracellular Sulfatase Sulf-1 Detection in Pleural Effusions as Diagnostic Biomarkers of Malignant Mesothelioma
by Lorenzo Zallocco, Roberto Silvestri, Federica Ciregia, Alessandra Bonotti, Riccardo Marino, Rudy Foddis, Antonio Lucacchini, Laura Giusti and Maria Rosa Mazzoni
Biomedicines 2022, 10(11), 2803; https://doi.org/10.3390/biomedicines10112803 - 3 Nov 2022
Cited by 1 | Viewed by 1849
Abstract
Malignant pleural mesothelioma is an aggressive malignancy with poor prognosis. Unilateral pleural effusion is frequently the initial clinical sign requiring therapeutic thoracentesis, which also offers a diagnostic opportunity. Detection of soluble biomarkers can support diagnosis, but few show good diagnostic accuracy. Here, we [...] Read more.
Malignant pleural mesothelioma is an aggressive malignancy with poor prognosis. Unilateral pleural effusion is frequently the initial clinical sign requiring therapeutic thoracentesis, which also offers a diagnostic opportunity. Detection of soluble biomarkers can support diagnosis, but few show good diagnostic accuracy. Here, we studied the expression levels and discriminative power of two putative biomarkers, prosaposin and extracellular sulfatase SULF-1, identified by proteomic and transcriptomic analysis, respectively. Pleural effusions from a total of 44 patients (23 with mesothelioma, 8 with lung cancer, and 13 with non-malignant disease) were analyzed for prosaposin and SULF-1 by enzyme-linked immunosorbent assay. Pleural effusions from mesothelioma patients had significantly higher levels of prosaposin and SULF-1 than those from non-malignant disease patients. Receiver-operating characteristic (ROC) analysis showed that both biomarkers have good discriminating power as pointed out by an AUC value of 0.853 (p = 0.0005) and 0.898 (p < 0.0001) for prosaposin and SULF-1, respectively. Combining data ensued a model predicting improvement of the diagnostic performance (AUC = 0.916, p < 0.0001). In contrast, prosaposin couldn’t discriminate mesothelioma patients from lung cancer patients while ROC analysis of SULF-1 data produced an AUC value of 0.821 (p = 0.0077) but with low sensitivity. In conclusion, prosaposin and SULF-1 levels determined in pleural effusion may be promising biomarkers for differential diagnosis between mesothelioma and non-malignant pleural disease. Instead, more patients need to be enrolled before granting the possible usefulness of these soluble proteins in differentiating mesothelioma pleural effusions from those linked to lung cancer. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)
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Review

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14 pages, 6089 KiB  
Review
Emerging Mechanisms of Physical Exercise Benefits in Adjuvant and Neoadjuvant Cancer Immunotherapy
by Fabio Casciano, Lorenzo Caruso, Enrico Zauli, Arianna Gonelli, Giorgio Zauli and Mauro Vaccarezza
Biomedicines 2024, 12(11), 2528; https://doi.org/10.3390/biomedicines12112528 - 5 Nov 2024
Viewed by 761
Abstract
The primary factors that can be modified in one’s lifestyle are the most influential determinants and significant preventable causes of various types of cancer. Exercise has demonstrated numerous advantages in preventing cancer and aiding in its treatment. However, the precise mechanisms behind these [...] Read more.
The primary factors that can be modified in one’s lifestyle are the most influential determinants and significant preventable causes of various types of cancer. Exercise has demonstrated numerous advantages in preventing cancer and aiding in its treatment. However, the precise mechanisms behind these effects are still not fully understood. To contribute to our comprehension of exercise’s impact on cancer immunotherapy and provide recommendations for future research in exercise oncology, we will examine the roles and underlying mechanisms of exercise on immune cells. In addition to reducing the likelihood of developing cancer, exercise can also improve the effectiveness of certain approved anticancer treatments, such as targeted therapy, immunotherapy, and radiotherapy. Exercise is a pivotal modulator of the immune response, and thus, it can play an emerging important role in new immunotherapies. The mechanisms responsible for these effects involve the regulation of intra-tumoral angiogenesis, myokines, adipokines, their associated pathways, cancer metabolism, and anticancer immunity. Our review assesses the potential of physical exercise as an adjuvant/neoadjuvant tool, reducing the burden of cancer relapse, and analyzes emerging molecular mechanisms predicting favorable adjuvanticity effects. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Italy)
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