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Article ; Online: Molecular and Cellular Mechanisms of Human Astrocytoma Progression: Advances in Knowledge to Reach Therapeutic Horizons.

Comincini, Sergio

2020 Volume 9, Issue 10

Abstract: Human astrocytic tumors are primary central nervous system (CNS) tumors that arise either from astrocytes or from precursor cells. A growing number of epidemiological and incidence studies in different countries underlined that, in addition to increasing ...

Abstract	Human astrocytic tumors are primary central nervous system (CNS) tumors that arise either from astrocytes or from precursor cells. A growing number of epidemiological and incidence studies in different countries underlined that, in addition to increasing economic costs for health systems, these cancers are still representing one of the main hurdles in developing a successful therapeutic goal for patients. On the other hand, new-omics technologies are offering customized instruments and more and more advantageous results toward personalized medicine approaches, underlining the concept that each tumor mass undergoes a peculiar transformation process under the control of specific genes' and proteins' functional signatures. The main aim of this Special Issue was to collect novel contributions in the wide field of human tumor astrocytic basic and translational research, to suggest further potential therapeutic targets/strategies that might interfere, possibly at the earliest stage of transformation, with the tumor progression, and to increase the molecular-based arsenal to counteract the prognostic poverty of high-grade astrocytic tumors.
MeSH term(s)	Apoptosis/genetics ; Astrocytoma/metabolism ; Brain Neoplasms/physiopathology ; Genetic Therapy/methods ; Humans
Language	English
Publishing date	2020-09-30
Publishing country	Switzerland
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9102216
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Article ; Online: Extracellular vesicles in degenerative retinal diseases: A new therapeutic paradigm.

Manai, Federico / Smedowski, Adrian / Kaarniranta, Kai / Comincini, Sergio / Amadio, Marialaura

Journal of controlled release : official journal of the Controlled Release Society

2023 Volume 365, Page(s) 448–468

Abstract: Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although their biological role is still something of a mystery. EVs are involved in the transfer ...

Abstract	Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although their biological role is still something of a mystery. EVs are involved in the transfer of lipids, nucleic acids and proteins from donor to recipient cells or distant organs as well as regulating cell-cell communication and signaling. Thus, EVs are important in intercellular communication and this is not limited to sister cells, but may also mediate the crosstalk between different cell types even over long distances. EVs play crucial functions in both cellular homeostasis and the pathogenesis of diseases, and since their contents reflect the status of the donor cell, they represent an additional valuable source of information for characterizing complex biological processes. Recent advances in isolation and analytical methods have led to substantial improvements in both characterizing and engineering EVs, leading to their use either as novel biomarkers for disease diagnosis/prognosis or even as novel therapies. Due to their capacity to carry biomolecules, various EV-based therapeutic applications have been devised for several pathological conditions, including eye diseases. In the eye, EVs have been detected in the retina, aqueous humor, vitreous body and also in tears. Experiences with other forms of intraocular drug applications have opened new ways to use EVs in the treatment of retinal diseases. We here provide a comprehensive summary of the main in vitro, in vivo, and ex vivo literature-based studies on EVs' role in ocular physiological and pathological conditions. We have focused on age-related macular degeneration, diabetic retinopathy, glaucoma, which are common eye diseases leading to permanent blindness, if not treated properly. In addition, the putative use of EVs in retinitis pigmentosa and other retinopathies is discussed. Finally, we have reviewed the potential of EVs as therapeutic tools and/or biomarkers in the above-mentioned retinal disorders. Evidence emerging from experimental disease models and human material strongly suggests future diagnostic and/or therapeutic exploitation of these biological agents in various ocular disorders with a good possibility to improve the patient's quality of life.
MeSH term(s)	Humans ; Quality of Life ; Extracellular Vesicles/metabolism ; Biomarkers/metabolism ; Retina/metabolism ; Retinal Diseases/drug therapy ; Retinal Diseases/metabolism ; Eye Diseases/drug therapy ; Eye Diseases/metabolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-12-02
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2023.11.035
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Article ; Online: Fostering "Education": Do Extracellular Vesicles Exploit Their Own Delivery Code?

Paolillo, Mayra / Comincini, Sergio / Schinelli, Sergio

Cells

2021 Volume 10, Issue 7

Abstract: Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has ... ...

Abstract	Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV "delivery code" and on the combinations of the hypothesized EV surface membrane "sender" and "recipient" molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Extracellular Vesicles/metabolism ; Glycomics ; Humans ; Models, Biological ; Proteomics ; Vaccines/immunology
Chemical Substances	Biomarkers ; Vaccines
Language	English
Publishing date	2021-07-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10071741
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Article: In Vitro Glioblastoma Models: A Journey into the Third Dimension.

Paolillo, Mayra / Comincini, Sergio / Schinelli, Sergio

Cancers

2021 Volume 13, Issue 10

Abstract: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, with an average survival time of about one year from initial diagnosis. In the attempt to overcome the complexity and drawbacks associated with in vivo GBM models, together ... ...

Abstract	Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, with an average survival time of about one year from initial diagnosis. In the attempt to overcome the complexity and drawbacks associated with in vivo GBM models, together with the need of developing systems dedicated to screen new potential drugs, considerable efforts have been devoted to the implementation of reliable and affordable in vitro GBM models. Recent findings on GBM molecular features, revealing a high heterogeneity between GBM cells and also between other non-tumor cells belonging to the tumoral niche, have stressed the limitations of the classical 2D cell culture systems. Recently, several novel and innovative 3D cell cultures models for GBM have been proposed and implemented. In this review, we first describe the different populations and their functional role of GBM and niche non-tumor cells that could be used in 3D models. An overview of the current available 3D in vitro systems for modeling GBM, together with their major weaknesses and strengths, is presented. Lastly, we discuss the impact of groundbreaking technologies, such as bioprinting and multi-omics single cell analysis, on the future implementation of 3D in vitro GBM models.
Language	English
Publishing date	2021-05-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13102449
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Article: Development of Berberine-Loaded Nanoparticles for Astrocytoma Cells Administration and Photodynamic Therapy Stimulation.

Comincini, Sergio / Manai, Federico / Sorrenti, Milena / Perteghella, Sara / D'Amato, Camilla / Miele, Dalila / Catenacci, Laura / Bonferoni, Maria Cristina

Pharmaceutics

2023 Volume 15, Issue 4

Abstract: Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer photodynamic therapy (PDT), and it has previously been favorably assayed against glioblastoma multiforme (GBM)-derived cells. In this work, two BBR ... ...

Abstract	Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer photodynamic therapy (PDT), and it has previously been favorably assayed against glioblastoma multiforme (GBM)-derived cells. In this work, two BBR hydrophobic salts, dodecyl sulfate (S) and laurate (L), have been encapsulated in PLGA-based nanoparticles (NPs), chitosan-coated by the addition of chitosan oleate in the preparation. NPs were also further functionalized with folic acid. All the BBR-loaded NPs were efficiently internalized into T98G GBM established cells, and internalization increased in the presence of folic acid. However, the highest mitochondrial co-localization percentages were obtained with BBR-S NPs without folic acid content. In the T98G cells, BBR-S NPs appeared to be the most efficient in inducing cytotoxicity events and were therefore selected to assess the effect of photodynamic stimulation (PDT). As a result, PDT potentiated the viability reduction for the BBR-S NPs at all the studied concentrations, and a roughly 50% reduction of viability was obtained. No significant cytotoxic effect on normal rat primary astrocytes was observed. In GBM cells, a significant increase in early and late apoptotic events was scored by BBR NPs, with a further increase following the PDT scheme. Furthermore, a significantly increased depolarization of mitochondria was highlighted following BBR-S NPs' internalization and mostly after PDT stimulation, compared to untreated and PDT-only treated cells. In conclusion, these results highlighted the efficacy of the BBR-NPs-based strategy coupled with photoactivation approaches to induce favorable cytotoxic effects in GBM cells.
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15041078
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Article ; Online: Gluten Exorphins Promote Cell Proliferation through the Activation of Mitogenic and Pro-Survival Pathways.

Manai, Federico / Zanoletti, Lisa / Morra, Giulia / Mansoor, Samman / Carriero, Francesca / Bozzola, Elena / Muscianisi, Stella / Comincini, Sergio

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Celiac disease (CD) is a chronic and systemic autoimmune disorder that affects preferentially the small intestine of individuals with a genetic predisposition. CD is promoted by the ingestion of gluten, a storage protein contained in the endosperm of the ...

Abstract	Celiac disease (CD) is a chronic and systemic autoimmune disorder that affects preferentially the small intestine of individuals with a genetic predisposition. CD is promoted by the ingestion of gluten, a storage protein contained in the endosperm of the seeds of wheat, barley, rye, and related cereals. Once in the gastrointestinal (GI) tract, gluten is enzymatically digested with the consequent release of immunomodulatory and cytotoxic peptides, i.e., 33mer and p31-43. In the late 1970s a new group of biologically active peptides, called gluten exorphins (GEs), was discovered and characterized. In particular, these short peptides showed a morphine-like activity and high affinity for the δ-opioid receptor (DOR). The relevance of GEs in the pathogenesis of CD is still unknown. Recently, it has been proposed that GEs could contribute to asymptomatic CD, which is characterized by the absence of symptoms that are typical of this disorder. In the present work, GEs cellular and molecular effects were in vitro investigated in SUP-T1 and Caco-2 cells, also comparing viability effects with human normal primary lymphocytes. As a result, GEs treatments increased tumor cell proliferation by cell cycle and Cyclins activation as well as by induction of mitogenic and pro-survival pathways. Finally, a computational model of GEs interaction with DOR is provided. Altogether, the results might suggest a possible role of GEs in CD pathogenesis and on its associated cancer comorbidities.
MeSH term(s)	Humans ; Glutens/chemistry ; Caco-2 Cells ; Peptides/metabolism ; Celiac Disease ; Intercellular Signaling Peptides and Proteins ; Cell Proliferation
Chemical Substances	Glutens (8002-80-0) ; exorphins (69989-30-6) ; Peptides ; Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043912
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Article: Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors.

Magrassi, Lorenzo / Brambilla, Francesca / Viganò, Raffaello / Di Silvestre, Dario / Benazzi, Louise / Bellantoni, Giuseppe / Danesino, Gian Marco / Comincini, Sergio / Mauri, Pierluigi

Cancers

2023 Volume 15, Issue 16

Abstract: Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor ... ...

Abstract	Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor resection and no indications of the evolution of cystic content are available. We characterized the evolution of the proteome of cystic fluid using a bottom-up proteomic approach on sequential samples obtained from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). We identified 1008 different proteins; 74 of these proteins were found at least once in the cystic fluid of all tumors. The most abundant proteins common to all tumors studied derived from plasma, with the exception of prostaglandin D2 synthase, which is a marker of cerebrospinal fluid origin. Overall, the protein composition of cystic fluid obtained at different times from the same tumor remained stable. After the identification of differentially expressed proteins (DEPs) and the protein-protein interaction network analysis, we identified the presence of tumor-specific pathways that may help to characterize tumor-host interactions. Our results suggest that plasma proteins leaking from local blood-brain barrier disruption are important contributors to cyst fluid formation, but cerebrospinal fluid (CSF) and the tumor itself also contribute to the cystic fluid proteome and, in some cases, as with immunoglobulin G, shows tumor-specific variations that cannot be simply explained by differences in vessel permeability or blood contamination.
Language	English
Publishing date	2023-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15164070
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Article ; Online: Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders.

Manai, Federico / Zanoletti, Lisa / Arfini, Davide / Micco, Simone Giorgio De / Gjyzeli, Arolda / Comincini, Sergio / Amadio, Marialaura

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. Due to its Nrf2-dependent and ... ...

Abstract	Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. Due to its Nrf2-dependent and independent mechanisms of action, DMF has a therapeutic potential much broader than expected. In this comprehensive review, we discuss the state-of-the-art and future perspectives regarding the potential repurposing of DMF in the context of chronic inflammatory diseases of the intestine, such as inflammatory bowel disorders (i.e., Crohn's disease and ulcerative colitis) and celiac disease. DMF's mechanisms of action, as well as an exhaustive analysis of the in vitro/in vivo evidence of its beneficial effects on the intestine and the gut microbiota, together with observational studies on multiple sclerosis patients, are here reported. Based on the collected evidence, we highlight the new potential applications of this molecule in the context of inflammatory and immune-mediated intestinal diseases.
MeSH term(s)	Humans ; Dimethyl Fumarate/pharmacology ; Dimethyl Fumarate/therapeutic use ; Multiple Sclerosis/drug therapy ; Colitis, Ulcerative/drug therapy ; Anti-Inflammatory Agents/therapeutic use ; Intestines
Chemical Substances	Dimethyl Fumarate (FO2303MNI2) ; Anti-Inflammatory Agents
Language	English
Publishing date	2023-06-08
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/ijms24129912
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Article ; Online: Autophagy and ionizing radiation in tumors: the "survive or not survive" dilemma.

Palumbo, Silvia / Comincini, Sergio

Journal of cellular physiology

2013 Volume 228, Issue 1, Page(s) 1–8

Abstract: Autophagy is a so-called "self-eating" system responsible for degrading long-lived proteins and cytoplasmic organelles, whose products are recycled to maintain cellular homeostasis. This ability makes autophagy a good candidate for a survival mechanism ... ...

Abstract	Autophagy is a so-called "self-eating" system responsible for degrading long-lived proteins and cytoplasmic organelles, whose products are recycled to maintain cellular homeostasis. This ability makes autophagy a good candidate for a survival mechanism in response to several stresses, including the tumor cell transformation. In particular, recent studies suggested that autophagy functions as a pro-death mechanism within different tumor contexts. It is, however, widely reported that autophagy represents both a survival mechanism or contributes directly to cell death fate. This interplay of the autophagy functions has been observed in many types of cancers and, in some cases, autophagy has been demonstrated to both promote and inhibit antitumor drug resistance. From a therapeutical point of view, the effects of the modulation of the tumor cell autophagic status, in response to ionizing radiations, are presently of particular relevance in oncology. Accordingly, this review also provides a perspective view on future works for exploring the modulation of autophagic indices in tumor cells as a novel molecular-based adjuvant strategy, in order to improve radiotherapy and chemotherapy effects in cancer patients.
MeSH term(s)	Animals ; Autophagy/physiology ; Autophagy/radiation effects ; Brain Neoplasms/physiopathology ; Brain Neoplasms/radiotherapy ; Gene Expression Regulation, Neoplastic/physiology ; Glioblastoma/physiopathology ; Glioblastoma/radiotherapy ; Humans ; Neoplasms/physiopathology ; Neoplasms/radiotherapy ; Prognosis ; Radiation, Ionizing
Language	English
Publishing date	2013-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.24118
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Article: Cytological, molecular, cytogenetic, and physiological characterization of a novel immortalized human enteric glial cell line.

Zanoletti, Lisa / Valdata, Aurora / Nehlsen, Kristina / Faris, Pawan / Casali, Claudio / Cacciatore, Rosalia / Sbarsi, Ilaria / Carriero, Francesca / Arfini, Davide / van Baarle, Lies / De Simone, Veronica / Barbieri, Giulia / Raimondi, Elena / May, Tobias / Moccia, Francesco / Bozzola, Mauro / Matteoli, Gianluca / Comincini, Sergio / Manai, Federico

Frontiers in cellular neuroscience

2023 Volume 17, Page(s) 1170309

Abstract: Enteric glial cells (EGCs), the major components of the enteric nervous system (ENS), are implicated in the maintenance of gut homeostasis, thereby leading to severe pathological conditions when impaired. However, due to technical difficulties associated ...

Abstract	Enteric glial cells (EGCs), the major components of the enteric nervous system (ENS), are implicated in the maintenance of gut homeostasis, thereby leading to severe pathological conditions when impaired. However, due to technical difficulties associated with EGCs isolation and cell culture maintenance that results in a lack of valuable
Language	English
Publishing date	2023-04-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1170309
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