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Article ; Online: Single-cell omics: a new perspective for early detection of pancreatic cancer?

Wang, Qi / Šabanović, Berina / Awada, Azhar / Reina, Chiara / Aicher, Alexandra / Tang, Jiajia / Heeschen, Christopher

European journal of cancer (Oxford, England : 1990)

2023 Volume 190, Page(s) 112940

Abstract: Pancreatic cancer is one of the most lethal cancers, mostly due to late diagnosis and limited treatment options. Early detection of pancreatic cancer in high-risk populations bears the potential to greatly improve outcomes, but current screening ... ...

Abstract	Pancreatic cancer is one of the most lethal cancers, mostly due to late diagnosis and limited treatment options. Early detection of pancreatic cancer in high-risk populations bears the potential to greatly improve outcomes, but current screening approaches remain of limited value despite recent technological advances. This review explores the possible advantages of liquid biopsies for this application, particularly focusing on circulating tumour cells (CTCs) and their subsequent single-cell omics analysis. Originating from both primary and metastatic tumour sites, CTCs provide important information for diagnosis, prognosis and tailoring of treatment strategies. Notably, CTCs have even been detected in the blood of subjects with pancreatic precursor lesions, suggesting their suitability as a non-invasive tool for the early detection of malignant transformation in the pancreas. As intact cells, CTCs offer comprehensive genomic, transcriptomic, epigenetic and proteomic information that can be explored using rapidly developing techniques for analysing individual cells at the molecular level. Studying CTCs during serial sampling and at single-cell resolution will help to dissect tumour heterogeneity for individual patients and among different patients, providing new insights into cancer evolution during disease progression and in response to treatment. Using CTCs for non-invasive tracking of cancer features, including stemness, metastatic potential and expression of immune targets, provides important and readily accessible molecular insights. Finally, the emerging technology of ex vivo culturing of CTCs could create new opportunities to study the functionality of individual cancers at any stage and develop personalised and more effective treatment approaches for this lethal disease.
MeSH term(s)	Humans ; Proteomics ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Neoplastic Cells, Circulating/pathology ; Prognosis ; Biomarkers, Tumor/metabolism ; Pancreatic Neoplasms
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-06-16
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2023.112940
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Promising Extracellular Vesicle-Based Vaccines against Viruses, Including SARS-CoV-2.

Sabanovic, Berina / Piva, Francesco / Cecati, Monia / Giulietti, Matteo

Biology

2021 Volume 10, Issue 2

Abstract: Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, ... ...

Abstract	Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants. Here, we review the state-of-the-art for antiviral EV-based vaccines, including the ongoing projects of some biotech companies in the development of EV-based vaccines for SARS-CoV-2. Finally, we discuss the limits for further development of this promising class of therapeutic agents.
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10020094
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Article ; Online: Promising Extracellular Vesicle-Based Vaccines against Viruses, Including SARS-CoV-2

Berina Sabanovic / Francesco Piva / Monia Cecati / Matteo Giulietti

Biology, Vol 10, Iss 2, p

2021 Volume 94

Abstract	Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants. Here, we review the state-of-the-art for antiviral EV-based vaccines, including the ongoing projects of some biotech companies in the development of EV-based vaccines for SARS-CoV-2. Finally, we discuss the limits for further development of this promising class of therapeutic agents.
Keywords	COVID-19 ; exosomes ; vaccine ; antigen presentation ; antigen display ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Promising Extracellular Vesicle-Based Vaccines against Viruses, Including SARS-CoV-2

Sabanovic, Berina / Piva, Francesco / Cecati, Monia / Giulietti, Matteo

Biology. 2021 Jan. 27, v. 10, no. 2

2021

Abstract	Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants. Here, we review the state-of-the-art for antiviral EV-based vaccines, including the ongoing projects of some biotech companies in the development of EV-based vaccines for SARS-CoV-2. Finally, we discuss the limits for further development of this promising class of therapeutic agents.
Keywords	B-lymphocytes ; COVID-19 infection ; DNA ; Severe acute respiratory syndrome coronavirus 2 ; T-lymphocytes ; biogenesis ; biosafety ; cell communication ; humans ; therapeutics ; vaccine development
Language	English
Dates of publication	2021-0127
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10020094
Database	NAL-Catalogue (AGRICOLA)

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Article: Effects of the Exposure of Human Non-Tumour Cells to Sera of Pancreatic Cancer Patients.

Sabanovic, Berina / Giulietti, Matteo / Cecati, Monia / Spolverato, Gaya / Benna, Clara / Pucciarelli, Salvatore / Piva, Francesco

Biomedicines

2022 Volume 10, Issue 10

Abstract: Pancreatic ductal adenocarcinoma (PDAC) has high metastatic potential. The "genometastasis" theory proposes that the blood of some cancer patients contains elements able to transform healthy cells by transferring oncogenes. Since findings on ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) has high metastatic potential. The "genometastasis" theory proposes that the blood of some cancer patients contains elements able to transform healthy cells by transferring oncogenes. Since findings on genometastasis in PDAC are still scarce, we sought supporting evidence by treating non-tumour HEK293T and hTERT-HPNE human cell lines with sera of PDAC patients. Here, we showed that HEK293T cells have undergone malignant transformation, increased the migration and invasion abilities, and acquired a partial chemoresistance, whereas hTERT-HPNE cells were almost refractory to transformation by patients' sera. Next-generation sequencing showed that transformed HEK293T cells gained and lost several genomic regions, harbouring genes involved in many cancer-associated processes. Our results support the genometastasis theory, but further studies are needed for the identification of the circulating transforming elements. Such elements could also be useful biomarkers in liquid biopsy assays.
Language	English
Publishing date	2022-10-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10102588
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Article ; Online: Expression and co-expression analyses of TMPRSS2, a key element in COVID-19.

Piva, Francesco / Sabanovic, Berina / Cecati, Monia / Giulietti, Matteo

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

2020 Volume 40, Issue 2, Page(s) 451–455

Abstract: The ACE2 receptor is, so far, the best-known host factor for SARS-CoV-2 entry, but another essential element, the TMPRSS2 protease, has recently been identified. Here, we have analysed TMPRSS2 expression data in the lung correlating them with age, sex, ... ...

Abstract	The ACE2 receptor is, so far, the best-known host factor for SARS-CoV-2 entry, but another essential element, the TMPRSS2 protease, has recently been identified. Here, we have analysed TMPRSS2 expression data in the lung correlating them with age, sex, diabetes, smoking habits, exposure to pollutant and other stimuli, in order to highlight which factors might alter TMPRSS2 expression, and thus impact the susceptibility to infection and COVID-19 prognosis. Moreover, we reported TMPRSS2 polymorphisms affecting its expression and suggested the ethnic groups more prone to COVID-19. Finally, we also highlighted a gender-specific co-expression between TMPRSS2 and other genes related to SARS-CoV-2 entry, maybe explaining the higher observed susceptibility of infection in men. Our results could be useful in designing potential prevention and treatment strategies regarding the COVID-19.
MeSH term(s)	Aged ; COVID-19/etiology ; Female ; Humans ; Lung/enzymology ; Male ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; SARS-CoV-2 ; Serine Endopeptidases/genetics ; Serine Endopeptidases/physiology ; Virus Internalization
Chemical Substances	Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Language	English
Publishing date	2020-11-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	603155-9
ISSN	1435-4373 ; 0934-9723 ; 0722-2211
ISSN (online)	1435-4373
ISSN	0934-9723 ; 0722-2211
DOI	10.1007/s10096-020-04089-y
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Zs.A 1732: Show issues

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Article ; Online: Role of primary cilium in pancreatic ductal adenocarcinoma (Review).

Sabanovic, Berina / Giulietti, Matteo / Piva, Francesco

International journal of oncology

2020 Volume 57, Issue 5, Page(s) 1095–1102

Abstract: The primary cilium is a non‑motile cellular structure extending from the apical membrane of epithelial cells that is involved in several processes due to its ability to receive and elaborate different signals. Ciliogenesis and its obliteration are ... ...

Abstract	The primary cilium is a non‑motile cellular structure extending from the apical membrane of epithelial cells that is involved in several processes due to its ability to receive and elaborate different signals. Ciliogenesis and its obliteration are essential for proliferating cells, and several signalling pathways are responsible for their regulation. In fact, the primary cilium is a central hub for numerous signalling pathways implicated in a variety of biological processes, such as the Hedgehog, mammalian target of rapamycin and Wnt pathways. Loss of primary cilia has been recently correlated with different types of tumours, including pancreatic ductal adenocarcinoma (PDAC). K‑Ras and HDAC2 were recently identified as possible ciliogenesis regulators in PDAC, likely acting through Aurora A kinase (AURKA) which, in turn, controls inositol polyphosphate‑5‑phosphatase E. However, the exact molecular mechanisms underlying this regulatory effect remain to be fully elucidated. In the present study, the regulation of the main genes involved in primary cilia assembly/resorption was reconstructed showing the links with the Hedgehog and phosphoinositide 3‑kinase/AKT pathways. Finally, by analysing gene expression databases, the regulatory genes that have high probability to be associated with prognosis, histological grade and pathological stage in patients with PDAC have been highlighted. However, further experimental studies are required to reach definitive conclusions on the roles of these genes. Improving our understating of ciliogenesis and its regulators may help develop ciliotherapies using histone deacetylase and AURKA inhibitors, which may induce re‑differentiation of tumour cells into normal cells by reducing tumour growth or inducing apoptosis of cancer cells.
MeSH term(s)	Aurora Kinase A/physiology ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Cilia/drug effects ; Cilia/physiology ; Gene Expression Regulation, Neoplastic ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Phosphatidylinositol 3-Kinases/physiology ; Signal Transduction
Chemical Substances	Histone Deacetylase Inhibitors ; Aurora Kinase A (EC 2.7.11.1)
Language	English
Publishing date	2020-09-14
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2020.5121
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Zs.A 3690: Show issues

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Article ; Online: Effects of CXCL12 isoforms in a pancreatic pre-tumour cellular model: Microarray analysis.

Cecati, Monia / Giulietti, Matteo / Righetti, Alessandra / Sabanovic, Berina / Piva, Francesco

World journal of gastroenterology

2021 Volume 27, Issue 15, Page(s) 1616–1629

Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death among cancers, it is characterized by poor prognosis and strong chemoresistance. In the PDAC microenvironment, stromal cells release different extracellular ... ...

Abstract	Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death among cancers, it is characterized by poor prognosis and strong chemoresistance. In the PDAC microenvironment, stromal cells release different extracellular components, including CXCL12. The CXCL12 is a chemokine promoting the communication between tumour and stromal cells. Six different splicing isoforms of CXCL12 are known (α, β, γ, δ, ε, θ) but their role in PDAC has not yet been characterized. Aim: To investigate the specific role of α, β, and γ CXCL12 isoforms in PDAC onset. Methods: We used hTERT-HPNE E6/E7/KRasG12D (Human Pancreatic Nestin-Expressing) cell line as a pancreatic pre-tumour model and exposed it to the α, β, and γ CXCL12 isoforms. The altered expression profiles were assessed by microarray analyses and confirmed by Real-Time polymerase chain reaction. The functional enrichment analyses have been performed by Enrichr tool to highlight Gene Ontology enriched terms. In addition, wound healing assays have been carried out to assess the phenotypic changes, in terms of migration ability, induced by the α, β, and γ CXCL12 isoforms. Results: Microarray analysis of hTERT-HPNE cells treated with the three different CXCL12 isoforms highlighted that the expression of only a few genes was altered. Moreover, the α and β isoforms showed an alteration in expression of different genes, whereas γ isoform affected the expression of genes also common with α and β isoforms. The β isoform altered the expression of genes mainly involved in cell cycle regulation. In addition, all isoforms affected the expression of genes associated to cell migration, adhesion and cytoskeleton. In vitro cell migration assay confirmed that CXCL12 enhanced the migration ability of hTERT-HPNE cells. Among the CXCL12 splicing isoforms, the γ isoform showed higher induction of migration than α and β isoforms. Conclusion: Our data suggests an involvement and different roles of CXCL12 isoforms in PDAC onset. However, more investigations are needed to confirm these preliminary observations.
MeSH term(s)	Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Chemokine CXCL12/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Microarray Analysis ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Protein Isoforms/metabolism ; Tumor Microenvironment
Chemical Substances	CXCL12 protein, human ; Chemokine CXCL12 ; Protein Isoforms
Language	English
Publishing date	2021-03-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v27.i15.1616
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Zs.A 6039: Show issues

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Article: CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?

Righetti, Alessandra / Giulietti, Matteo / Šabanović, Berina / Occhipinti, Giulia / Principato, Giovanni / Piva, Francesco

Journal of oncology

2019 Volume 2019, Page(s) 9681698

Abstract: CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and ... ...

Abstract	CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and alters the behavior of cancer cells. Many studies investigated the roles of CXCL12 in order to understand if it has an anti- or protumor role. In particular, it seems to promote tumor invasion, proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in pancreatic cancer. Nevertheless, some evidence shows opposite functions; therefore research on CXCL12 is still ongoing. These discrepancies could be due to the presence of at least six CXCL12 splicing isoforms, each with different roles. Interestingly, three out of six variants have the highest levels of expression in the pancreas. Here, we report the current knowledge about the functions of this chemokine and then focus on pancreatic cancer. Moreover, we discuss the methods applied in recent studies in order to understand if they took into account the existence of the CXCL12 isoforms.
Language	English
Publishing date	2019-06-02
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2461349-6
ISSN	1687-8469 ; 1687-8450
ISSN (online)	1687-8469
ISSN	1687-8450
DOI	10.1155/2019/9681698
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Article: The Role of Artificial Intelligence in the Diagnosis and Prognosis of Renal Cell Tumors.

Giulietti, Matteo / Cecati, Monia / Sabanovic, Berina / Scirè, Andrea / Cimadamore, Alessia / Santoni, Matteo / Montironi, Rodolfo / Piva, Francesco

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 2

Abstract: The increasing availability of molecular data provided by next-generation sequencing (NGS) techniques is allowing improvement in the possibilities of diagnosis and prognosis in renal cancer. Reliable and accurate predictors based on selected gene panels ... ...

Abstract	The increasing availability of molecular data provided by next-generation sequencing (NGS) techniques is allowing improvement in the possibilities of diagnosis and prognosis in renal cancer. Reliable and accurate predictors based on selected gene panels are urgently needed for better stratification of renal cell carcinoma (RCC) patients in order to define a personalized treatment plan. Artificial intelligence (AI) algorithms are currently in development for this purpose. Here, we reviewed studies that developed predictors based on AI algorithms for diagnosis and prognosis in renal cancer and we compared them with non-AI-based predictors. Comparing study results, it emerges that the AI prediction performance is good and slightly better than non-AI-based ones. However, there have been only minor improvements in AI predictors in terms of accuracy and the area under the receiver operating curve (AUC) over the last decade and the number of genes used had little influence on these indices. Furthermore, we highlight that different studies having the same goal obtain similar performance despite the fact they use different discriminating genes. This is surprising because genes related to the diagnosis or prognosis are expected to be tumor-specific and independent of selection methods and algorithms. The performance of these predictors will be better with the improvement in the learning methods, as the number of cases increases and by using different types of input data (e.g., non-coding RNAs, proteomic and metabolic). This will allow for more precise identification, classification and staging of cancerous lesions which will be less affected by interpathologist variability.
Language	English
Publishing date	2021-01-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11020206
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