IU Indianapolis ScholarWorks :: Browsing by Author "Battelli, Nicola"

Browsing by Author "Battelli, Nicola"

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Circulating Tumor Cells in Renal Cell Carcinoma: Recent Findings and Future Challenges
(Frontiers, 2019-04-05) Santoni, Matteo; Cimadamore, Alessia; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Massari, Francesco; Scarpelli, Marina; Galosi, Andrea Benedetto; Bracarda, Sergio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Emerging immunotherapeutic strategies targeting telomerases in genitourinary tumors
(Elsevier, 2018) Carrozza, Francesco; Santoni, Matteo; Piva, Francesco; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Montironi, Rodolfo; Battelli, Nicola; Tamberi, Stefano; Pathology and Laboratory Medicine, School of Medicine
Telomerase activity and telomere length are essential for the pathogenesis of several human diseases, including genitourinary tumors. Telomerase constitutes a complex system that includes human telomerase reverse transcriptase (hTERT), human telomerase RNA component (hTR) and telomerase associated protein 1 (TEP1), which are overexpressed in tumor cells compared to normal cells and are involved in the carcinogenesis and progression of renal cell carcinoma (RCC), bladder (BC) and prostate cancer (PCa). In addition, telomerase degraded peptide fragments expressed on the surface of tumor cells lead to their recognition by immune cells. On this scenario, in vitro and in vivo studies have shown effective anti-tumor activity of hTERT-tailored strategies in genitourinary tumors, including active immunotherapy with hTERT-peptide vaccines and passive immunotherapy with hTERT-transduced T cell infusion. This review emphasizes the role of telomerase in the carcinogenesis and progression of genitourinary tumors, thus underlying the potential of emerging telomerase-tailored immunotherapies in these patients.
Exploring Small Extracellular Vesicles for Precision Medicine in Prostate Cancer
(Frontiers Media, 2018-06-13) Giulietti, Matteo; Santoni, Matteo; Cimadamore, Alessia; Carrozza, Francesco; Piva, Francesco; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Battelli, Nicola; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Tumor microenvironment constitutes a complex network in which tumor cells communicate among them and with stromal and immune cells. It has been shown that cancer cells are able to exchange genetic materials through small extracellular vesicles (EVs), a heterogeneous group of vesicles with different size and shape, cargo content, and function. The importance to investigate populations of circulating EVs would be of great importance as prostate cancer (PCa) biomarkers. In several neoplasms as well as in PCa, nanometer-sized EVs of endosomal origin are implicated in supporting tumor growth and metastatic spread by both altering local stroma cells and creating a protumor environment that favors the formation of pre-metastatic niches. Several techniques are applicable for the isolation and analysis of PCa-derived small EVs and are illustrated in this article. Due to the high sensitivity and specificity of these techniques, small EVs have become ideal candidates for early diagnosis. Moreover, we discuss the role of small EVs during PCa carcinogenesis, as well as in modulating the development of drug resistance to hormonal therapy and chemotherapy, thus underlining the potential of EV-tailored strategies in PCa patients.
The Human Microbiota and Prostate Cancer: Friend or Foe?
(MDPI, 2019-03-31) Massari, Francesco; Mollica, Veronica; Di Nunno, Vincenzo; Gatto, Lidia; Santoni, Matteo; Scarpelli, Marina; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Battelli, Nicola; Montironi, Rodolfo; Brandi, Giovanni; Pathology and Laboratory Medicine, School of Medicine
The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer.
Immune checkpoint inhibitors for metastatic bladder cancer
(Elsevier, 2018-03) Massari, Francesco; Di Nunno, Vincenzo; Cubelli, Marta; Santoni, Matteo; Fiorentino, Michelangelo; Montironi, Rodolfo; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Ardizzoni, Andrea; Pathology and Laboratory Medicine, School of Medicine
Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors.
Immunotherapy in renal cell carcinoma: latest evidence and clinical implications
(Just Medical Media, 2018-06-05) Santoni, Matteo; Massari, Francesco; Di Nunno, Vincenzo; Conti, Alessandro; Cimadamore, Alessia; Scarpelli, Marina; Montironi, Rodolfo; Cheng, Liang; Battelli, Nicola; Lopez-Beltran, Antonio; Pathology and Laboratory Medicine, School of Medicine
Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC). The optimal combination between immunotherapy and targeted agents (as well as the possible favourable sequential therapy of these two classes of drugs) remains an open question at this moment. Several trials are currently underway to assess the combination of anti-programmed-death 1 (PD-1) or anti-PD-ligand(L)1 agents with other immunotherapies or with anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). In this editorial, we described the results of the most recent clinical trials on the use of immunotherapies in RCC and the emerging data on the research for reliable biomarkers of tumour response in this setting. In addition, we have focused on the role of the gut microbiome and tumour microenvironment in the development of future therapeutic strategies for RCC patients.
Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers
(MDPI, 2019-08-22) Santoni, Matteo; Cimadamore, Alessia; Massari, Francesco; Piva, Francesco; Aurilio, Gaetano; Martignetti, Angelo; Scarpelli, Marina; Di Nunno, Vincenzo; Gatto, Lidia; Battelli, Nicola; Cheng, Liang; Lopez-Beltran, Antonio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Background: In human populations, a certain amount of data correlate obesity/body mass index (BMI) with urothelial cancer (UC) and prostate cancer (PCa) occurrence, however this is not fully elucidated at all stages of disease. In an attempt to shed light on uncertain areas in such field, in the present review we illustrate the main molecular mechanisms linking obesity and cancer, focusing on the correlation between obesity and tumor risk, disease progression and response to chemo- and immunotherapy in patients with UC and the predictive/prognostic role of obesity in PCa patients treated with the currently available therapeutic approaches. Methods: We did a large-scale literature search on existing scientific websites focusing on keywords "obesity", "body mass index (BMI)", "urothelial cancer", "prostate cancer", "docetaxel", "cabazitaxel", "abiraterone acetate", "enzalutamide", and "radium223". Results: Many adipocytes-induced molecules support tumor proliferation through activation of various cellular pathways. The available evidence in the postoperative setting do the role of BMI in oncological outcomes prediction still not completely clear. Likewise, in metastatic UC patients controversial results link the role of obesity/BMI with clinical outcomes of tumor response to chemotherapy. Adipose stromal cells recruitment, induced by PCa cells, from white adipose tissue to the tumor sites inducing cell invasiveness was associated with poor survival. Conflicting data, although more oriented towards a better survival outcome, resulted in obese patients treated with docetaxel. In PCa cell-lines a certain cabazitaxel chemo resistance adipose stromal cells (ASC)-mediated was demonstrated. In metastatic castration-resistant PCa patients with high BMI (>25 kg/m2) receiving abiraterone acetate there were significant worse survival outcomes, while in enzalutamide patients BMI did not affect survival outcome. In radium 223 patients higher BMI significantly correlated with favorable overall survival. Conclusions: The main focus of this review was to understand the interplay between obesity/BMI and UC/PCa. Several pathogenic cellular pathways exploring the issue are discussed, opening the way to challenging tailored treatments on the basis of BMI. Improving the knowledge of molecular connections between obesity and UC and PCa could favor the development of new therapies likely reducing chemo- and immunotherapy drug resistance.
Narrative review: predicting future molecular and clinical profiles of prostate cancer in the United States
(AME Publishing, 2021-03) Santoni, Matteo; Cimadamore, Alessia; Massari, Francesco; Sorgentoni, Giulia; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Prostate cancer represents the most frequent tumor in men, accounting for the 21% of all diagnosed tumors, with 191,930 new cases and 33,330 deaths estimated in 2020. Advanced prostate cancer represents a heterogeneous disease, ranging from hormone naive or hormone sensitive to castration resistant. The therapeutic armamentarium for this disease has been implemented in the last years by novel hormonal therapies and chemotherapies. However, the percentage of patients who achieve complete responses still results negligible. On this scenario, the design of clinical trials investigating new therapeutic approaches represent a dramatic medical need. Predicting cancer incidence may be fundamental to design specific clinical trials, to optimize the allocation of economic resources, and to plan future cancer control programs. ERG, SPOP and DDR genes alterations can act as therapeutic targets in prostate cancer patients and can be tested to identify a gene-selected patient population to enrol in specific trials. According to our predictions, ERG gene fusions will be the most predominant molecular subtype, accounting for 69,050 new cases in 2030. Mutation in SPOP gene will be diagnosed in 16,512 tumors, corresponding to the number of cases associated with alterations in DDR genes (including 7,956 BRCA2 mutated tumors). In this article, we analyzed and discussed the future molecular and clinical profiles of prostate cancer in the United States, aimed to describe a series of distinct subpopulations and to quantify potential clinical trial candidates in the next years.
New Prostate Cancer Targets for Diagnosis, Imaging, and Therapy: Focus on Prostate-Specific Membrane Antigen
(Frontiers, 2018-12-21) Cimadamore, Alessia; Cheng, Monica; Santoni, Matteo; Lopez-Beltran, Antonio; Battelli, Nicola; Massari, Francesco; Galosi, Andrea B.; Scarpelli, Marina; Montironi, Rodolfo; Radiology and Imaging Sciences, School of Medicine
The rising incidence rate of the cancer in the prostate gland has increased the demand for improved diagnostic, imaging, and therapeutic approaches. Prostate-specific membrane antigen (PSMA), with folate hydrolase and carboxypeptidase and, internalization activities, is highly expressed in the epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with, metastasis, progression, and androgen independence. Recently, PSMA has been an active target of investigation by several approaches, including the successful utilization of small molecule inhibitors, RNA aptamer conjugates, PSMA-based immunotherapy, and PSMA-targeted prodrug therapy. Future investigations of PSMA in prostate cancer (PCa) should focus in particular on its intracellular activities and functions. The objective of this contribution is to review the current role of PSMA as a marker for PCa diagnosis, imaging, and therapy.
Predicting future cancer burden in the United States by artificial neural networks
(Taylor & Francis, 2021) Piva, Francesco; Tartari, Francesca; Giulietti, Matteo; Aiello, Marco Maria; Cheng, Liang; Lopez-Beltran, Antonio; Mazzucchelli, Roberta; Cimadamore, Alessia; Cerqueti, Roy; Battelli, Nicola; Montironi, Rodolfo; Santoni, Matteo; Pathology and Laboratory Medicine, School of Medicine
Aims: To capture the complex relationships between risk factors and cancer incidences in the US and predict future cancer burden. Materials & methods: Two artificial neural network (ANN) algorithms were adopted: a multilayer feed-forward network (MLFFNN) and a nonlinear autoregressive network with eXogenous inputs (NARX). Data on the incidence of the four most common tumors (breast, colorectal, lung and prostate) from 1992 to 2016 (available from National Cancer Institute online datasets) were used for training and validation, and data until 2050 were predicted. Results: The rapid decreasing trend of prostate cancer incidence started in 2010 will continue until 2018-2019; it will then slow down and reach a plateau after 2050, with several differences among ethnicities. The incidence of breast cancer will reach a plateau in 2030, whereas colorectal cancer incidence will reach a minimum value of 35 per 100,000 in 2030. As for lung cancer, the incidence will decrease from 50 per 100,000 (2017) to 31 per 100,000 in 2030 and 26 per 100,000 in 2050. Conclusion: This up-to-date prediction of cancer burden in the US could be a crucial resource for planning and evaluation of cancer-control programs.

Browsing by Author "Battelli, Nicola"

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