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Article ; Online: Alpha-2-macroglobulin is a novel anticancer agent.

Facchiano, Francesco / D'Arcangelo, Daniela / Facchiano, Antonio

2023

Abstract: Introduction - Melanoma is the most aggressive skin cancer, with an increasing occurrence. Despite the recent important improvements due to novel immunotherapy approaches, when late diagnosed, melanoma prognosis is poor due to the metastatic progression ... ...

Abstract	Introduction - Melanoma is the most aggressive skin cancer, with an increasing occurrence. Despite the recent important improvements due to novel immunotherapy approaches, when late diagnosed, melanoma prognosis is poor due to the metastatic progression and drug-resistance onset. Therefore, there is an urgent need to identify additional therapeutic targets. Melanoma invasive behavior is related to the activity of metalloproteases, able to degrade extracellular matrix leading to tumor dissemination. A recent study suggested that the most potent proteases inhibitor alpha-2-macroglobulin (A2MG) from plasma of hibernating fishes exerts potent anti-proliferative effects. Our previous studies showed significant reduction of A2MG in sera from mice/human melanoma models. Methods - Gene and protein expression studies have been performed by using platforms and databases available online containing expression data form thousands of patients and healthy controls. Results - We carried out an extensive bioinformatics analysis to evaluate the A2MG gene/protein expression on a large cohort of patients affected by many different cancer types, compared to healthy control subjects, and we found highly significant difference of A2MG expression in 20 out of 31 cancers types (including melanoma) compared to healthy controls. Similar results were also confirmed at proteomic level using another platform available online. Further, we found that higher A2MG expression is significantly related to overall survival in different cancers including melanoma. Conclusion - Our results strongly suggest A2MG as a novel molecular target in melanoma therapy, as well as in other cancer types.
Language	English
Publishing date	2023-12-29
Publishing country	Switzerland
Document type	News
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000536033
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Article ; Online: An investigation into the molecular basis of cancer comorbidities in coronavirus infection.

Facchiano, Antonio / Facchiano, Francesco / Facchiano, Angelo

FEBS open bio

2020 Volume 10, Issue 11, Page(s) 2363–2374

Abstract: Comorbidities in COVID-19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in ...

Abstract	Comorbidities in COVID-19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. Using expression data from GENT2 databases, we evaluated gene expression in all anatomical districts from 32 normal tissues in 3902 individuals. Functional relationships with body districts were analyzed by chilibot. We performed DisGeNet, genemania and DAVID analyses to identify human diseases associated with these genes. Transcriptomic expression levels were then analyzed in 31 cancer types and healthy controls from approximately 43 000 individuals, using GEPIA2 and GENT2 databases. By performing receiver operating characteristic analysis, the area under the curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the five genes were found to associate with acute respiratory syndrome, diabetes, cardiovascular diseases and cancer (i.e. the most frequent COVID-19 comorbidities). Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively. The five coronavirus receptors are related to all main COVID-19 comorbidities and three show significantly different expression in cancer versus control tissues. Further investigation into their role may help in monitoring other comorbidities, as well as for follow-up of patients who have recovered from SARS-CoV-2 infection.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/virology ; Cell Adhesion Molecules/genetics ; Comorbidity ; Databases, Genetic ; Dipeptidyl Peptidase 4/genetics ; Epidemics ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease/genetics ; Humans ; Lectins, C-Type/genetics ; Male ; Membrane Proteins/genetics ; Neoplasms/classification ; Neoplasms/epidemiology ; Neoplasms/genetics ; Receptors, Cell Surface/genetics ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/physiology ; Serine Endopeptidases/genetics ; Serine Proteases/genetics
Chemical Substances	CLEC4M protein, human ; Cell Adhesion Molecules ; Lectins, C-Type ; Membrane Proteins ; Receptors, Cell Surface ; Serine Proteases (EC 3.4.-) ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS11D protein, human (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-10-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12984
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: An investigation into the molecular basis of cancer comorbidities in coronavirus infection

Facchiano, Antonio / Facchiano, Francesco / Facchiano, Angelo

FEBS Open Bio. 2020 Nov., v. 10, no. 11

2020

Abstract: Comorbidities in COVID‐19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in ...

Abstract	Comorbidities in COVID‐19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. Using expression data from GENT2 databases, we evaluated gene expression in all anatomical districts from 32 normal tissues in 3902 individuals. Functional relationships with body districts were analyzed by chilibot. We performed DisGeNet, genemania and DAVID analyses to identify human diseases associated with these genes. Transcriptomic expression levels were then analyzed in 31 cancer types and healthy controls from approximately 43 000 individuals, using GEPIA2 and GENT2 databases. By performing receiver operating characteristic analysis, the area under the curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the five genes were found to associate with acute respiratory syndrome, diabetes, cardiovascular diseases and cancer (i.e. the most frequent COVID‐19 comorbidities). Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively. The five coronavirus receptors are related to all main COVID‐19 comorbidities and three show significantly different expression in cancer versus control tissues. Further investigation into their role may help in monitoring other comorbidities, as well as for follow‐up of patients who have recovered from SARS‐CoV‐2 infection.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; colon ; comorbidity ; death ; diabetes ; gene expression ; humans ; kidneys ; liver ; testes ; thyroid neoplasms ; transcriptomics
Language	English
Dates of publication	2020-11
Size	p. 2363-2374.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12984
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors.

Buccarelli, Mariachiara / Castellani, Giorgia / Fiorentino, Vincenzo / Pizzimenti, Cristina / Beninati, Simone / Ricci-Vitiani, Lucia / Scattoni, Maria Luisa / Mischiati, Carlo / Facchiano, Francesco / Tabolacci, Claudio

Cells

2024 Volume 13, Issue 8

Abstract: Transglutaminase type 2 (TG2) is the most ubiquitously expressed member of the transglutaminase family. TG2 catalyzes the transamidation reaction leading to several protein post-translational modifications and it is also implicated in signal transduction ...

Abstract	Transglutaminase type 2 (TG2) is the most ubiquitously expressed member of the transglutaminase family. TG2 catalyzes the transamidation reaction leading to several protein post-translational modifications and it is also implicated in signal transduction thanks to its GTP binding/hydrolyzing activity. In the nervous system, TG2 regulates multiple physiological processes, such as development, neuronal cell death and differentiation, and synaptic plasticity. Given its different enzymatic activities, aberrant expression or activity of TG2 can contribute to tumorigenesis, including in peripheral and central nervous system tumors. Indeed, TG2 dysregulation has been reported in meningiomas, medulloblastomas, neuroblastomas, glioblastomas, and other adult-type diffuse gliomas. The aim of this review is to provide an overview of the biological and functional relevance of TG2 in the pathogenesis of nervous system tumors, highlighting its involvement in survival, tumor inflammation, differentiation, and in the resistance to standard therapies.
MeSH term(s)	Humans ; Protein Glutamine gamma Glutamyltransferase 2 ; Transglutaminases/metabolism ; GTP-Binding Proteins/metabolism ; Nervous System Neoplasms/pathology ; Nervous System Neoplasms/enzymology ; Nervous System Neoplasms/metabolism ; Animals
Chemical Substances	Protein Glutamine gamma Glutamyltransferase 2 (EC 2.3.2.13) ; Transglutaminases (EC 2.3.2.13) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2024-04-11
Publishing country	Switzerland
Document type	Journal Article ; Review ; 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/cells13080667
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Article ; Online: Reply to Jakovac: About COVID-19 and vitamin D.

Facchiano, Angelo / Facchiano, Antonio / Bartoli, Manuela / Ricci, Alberto / Facchiano, Francesco

American journal of physiology. Endocrinology and metabolism

2020 Volume 318, Issue 6, Page(s) E838

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Vitamin D
Chemical Substances	Vitamin D (1406-16-2)
Keywords	covid19
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00185.2020
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Article ; Online: Natural Compounds against Cancer, Inflammation, and Oxidative Stress.

Tabolacci, Claudio / Forni, Cinzia / Jadeja, Ravirajsinh N / Facchiano, Francesco

BioMed research international

2019 Volume 2019, Page(s) 9495628

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Biological Products/therapeutic use ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Inflammation/pathology ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Oxidative Stress/drug effects
Chemical Substances	Antineoplastic Agents ; Biological Products
Language	English
Publishing date	2019-05-09
Publishing country	United States
Document type	Editorial
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2019/9495628
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Article ; Online: Phytochemicals as Immunomodulatory Agents in Melanoma.

Tabolacci, Claudio / De Vita, Daniela / Facchiano, Antonio / Bozzuto, Giuseppina / Beninati, Simone / Failla, Cristina Maria / Di Martile, Marta / Lintas, Carla / Mischiati, Carlo / Stringaro, Annarita / Del Bufalo, Donatella / Facchiano, Francesco

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Cutaneous melanoma is an immunogenic highly heterogenic tumor characterized by poor outcomes when it is diagnosed late. Therefore, immunotherapy in combination with other anti-proliferative approaches is among the most effective weapons to control its ... ...

Abstract	Cutaneous melanoma is an immunogenic highly heterogenic tumor characterized by poor outcomes when it is diagnosed late. Therefore, immunotherapy in combination with other anti-proliferative approaches is among the most effective weapons to control its growth and metastatic dissemination. Recently, a large amount of published reports indicate the interest of researchers and clinicians about plant secondary metabolites as potentially useful therapeutic tools due to their lower presence of side effects coupled with their high potency and efficacy. Published evidence was reported in most cases through in vitro studies but also, with a growing body of evidence, through in vivo investigations. Our aim was, therefore, to review the published studies focused on the most interesting phytochemicals whose immunomodulatory activities and/or mechanisms of actions were demonstrated and applied to melanoma models.
MeSH term(s)	Melanoma/pathology ; Skin Neoplasms/drug therapy ; Immunomodulating Agents ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Plants
Chemical Substances	Immunomodulating Agents ; Phytochemicals
Language	English
Publishing date	2023-01-31
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/ijms24032657
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Article ; Online: Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation.

Magliozzi, Roberta / Pezzini, Francesco / Pucci, Mairi / Rossi, Stefania / Facchiano, Francesco / Marastoni, Damiano / Montagnana, Martina / Lippi, Giuseppe / Reynolds, Richard / Calabrese, Massimiliano

Cells

2021 Volume 10, Issue 7

Abstract: An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this ...

Abstract	An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739;
MeSH term(s)	Adaptive Immunity ; Adult ; Antigens, CD/cerebrospinal fluid ; Antigens, CD/genetics ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/cerebrospinal fluid ; Antigens, Differentiation, Myelomonocytic/genetics ; Antigens, Differentiation, Myelomonocytic/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; C-Reactive Protein/cerebrospinal fluid ; C-Reactive Protein/genetics ; C-Reactive Protein/immunology ; Case-Control Studies ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/immunology ; Cerebral Cortex/pathology ; Chemokine CXCL13/cerebrospinal fluid ; Chemokine CXCL13/genetics ; Chemokine CXCL13/immunology ; Chitinase-3-Like Protein 1/cerebrospinal fluid ; Chitinase-3-Like Protein 1/genetics ; Chitinase-3-Like Protein 1/immunology ; Cytokine TWEAK/cerebrospinal fluid ; Cytokine TWEAK/genetics ; Cytokine TWEAK/immunology ; Early Diagnosis ; Female ; Gene Expression Regulation ; Humans ; Immunity, Innate ; Interleukins/cerebrospinal fluid ; Interleukins/genetics ; Interleukins/immunology ; Magnetic Resonance Imaging ; Male ; Meninges/diagnostic imaging ; Meninges/immunology ; Meninges/pathology ; Multiple Sclerosis/cerebrospinal fluid ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/genetics ; Multiple Sclerosis/pathology ; Osteopontin/cerebrospinal fluid ; Osteopontin/genetics ; Osteopontin/immunology ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/immunology ; Receptors, Tumor Necrosis Factor, Type I/cerebrospinal fluid ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Receptors, Tumor Necrosis Factor, Type I/immunology ; Receptors, Tumor Necrosis Factor, Type II/cerebrospinal fluid ; Receptors, Tumor Necrosis Factor, Type II/genetics ; Receptors, Tumor Necrosis Factor, Type II/immunology ; Serum Amyloid P-Component/cerebrospinal fluid ; Serum Amyloid P-Component/genetics ; Serum Amyloid P-Component/immunology ; Signal Transduction ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; Tumor Necrosis Factor Ligand Superfamily Member 14/cerebrospinal fluid ; Tumor Necrosis Factor Ligand Superfamily Member 14/genetics ; Tumor Necrosis Factor Ligand Superfamily Member 14/immunology ; Tumor Necrosis Factor-alpha/cerebrospinal fluid ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/immunology ; White Matter/diagnostic imaging ; White Matter/immunology ; White Matter/pathology
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD163 antigen ; CHI3L1 protein, human ; CXCL13 protein, human ; Chemokine CXCL13 ; Chitinase-3-Like Protein 1 ; Cytokine TWEAK ; Interleukins ; Receptors, Cell Surface ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; SPP1 protein, human ; Serum Amyloid P-Component ; TNFRSF1A protein, human ; TNFSF12 protein, human ; TNFSF14 protein, human ; Tumor Necrosis Factor Ligand Superfamily Member 14 ; Tumor Necrosis Factor-alpha ; interleukin-35, human ; Osteopontin (106441-73-0) ; PTX3 protein (148591-49-5) ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-07-06
Publishing country	Switzerland
Document type	Journal Article ; 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/cells10071712
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Article ; Online: Targeting Melanoma-Initiating Cells by Caffeine: In Silico and In Vitro Approaches.

Tabolacci, Claudio / Cordella, Martina / Rossi, Stefania / Bonaccio, Marialaura / Eramo, Adriana / Mischiati, Carlo / Beninati, Simone / Iacoviello, Licia / Facchiano, Antonio / Facchiano, Francesco

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 12

Abstract: The beneficial effects of coffee on human diseases are well documented, but the molecular mechanisms of its bioactive compounds on cancer are not completely elucidated. This is likely due to the large heterogeneity of coffee preparations and different ... ...

Abstract	The beneficial effects of coffee on human diseases are well documented, but the molecular mechanisms of its bioactive compounds on cancer are not completely elucidated. This is likely due to the large heterogeneity of coffee preparations and different coffee-based beverages, but also to the choice of experimental models where proliferation, differentiation and immune responses are differently affected. The aim of the present study was to investigate the effects of one of the most interesting bioactive compounds in coffee, i.e., caffeine, using a cellular model of melanoma at a defined differentiation level. A preliminary in silico analysis carried out on public gene-expression databases identified genes potentially involved in caffeine's effects and suggested some specific molecular targets, including tyrosinase. Proliferation was investigated in vitro on human melanoma initiating cells (MICs) and cytokine expression was measured in conditioned media. Tyrosinase was revealed as a key player in caffeine's mechanisms of action, suggesting a crucial role in immunomodulation through the reduction in IL-1β, IP-10, MIP-1α, MIP-1β and RANTES secretion onto MICs conditioned media. The potent antiproliferative effects of caffeine on MICs are likely to occur by promoting melanin production and reducing inflammatory signals' secretion. These data suggest tyrosinase as a key player mediating the effects of caffeine on melanoma.
MeSH term(s)	Caffeine/pharmacology ; Cell Differentiation ; Cell Line, Tumor ; Central Nervous System Stimulants/pharmacology ; Computational Biology/methods ; Computer Simulation/statistics & numerical data ; Databases, Genetic ; Gene Expression Regulation ; Humans ; Melanins/metabolism ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/metabolism ; Melanoma/pathology ; Monophenol Monooxygenase/metabolism
Chemical Substances	Central Nervous System Stimulants ; Melanins ; Caffeine (3G6A5W338E) ; Monophenol Monooxygenase (EC 1.14.18.1)
Language	English
Publishing date	2021-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26123619
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Article: Reply to Jakovac: About COVID-19 and vitamin D

Facchiano, Angelo / Facchiano, Antonio / Bartoli, Manuela / Ricci, Alberto / Facchiano, Francesco

Am J Physiol Endocrinol Metab

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #327222
Database	COVID19

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