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Article ; Online: Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix

Giovanni Barillari / Roberto Bei / Vittorio Manzari / Andrea Modesti

International Journal of Molecular Sciences, Vol 22, Iss 13543, p

A Series of Chained Events?

2021 Volume 13543

Abstract: Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally ... ...

Abstract	Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally activated when the epithelium is chronically exposed to pathogens: this event deeply alters the tissue and eventually contributes to the development of diseases. Among the many of them is uterine cervical squamous cell carcinoma (SCC), the most frequent malignancy of the female genital system. SCC, whose onset is associated with the persistent infection of the uterine cervix by high-risk human papillomaviruses (HR-HPVs), often relapses and/or metastasizes, being resistant to conventional chemo- or radiotherapy. Given that these fearsome clinical features may stem, at least in part, from the exacerbated and long-lasting EMT occurring in the HPV-infected cervix; here we have reviewed published studies concerning the impact that HPV oncoproteins, cellular tumor suppressors, regulators of gene expression, inflammatory cytokines or growth factors, and the interactions among these effectors have on EMT induction and cervical carcinogenesis. It is predictable and desirable that a broader comprehension of the role that EMT inducers play in SCC pathogenesis will provide indications to flourish new strategies directed against this aggressive tumor.
Keywords	HPV ; inflammation ; p53 ; hypoxia ; EMT ; uterine SIL ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: O Estado e as políticas públicas que tornaram a agricultura familiar uma agente importante do desenvolvimento

Giovanni Barillari de Freitas

Mediações: Revista de Ciências Sociais, Vol 23, Iss

2018 Volume 2

Abstract: Ao longo da segunda metade do século XX, a luta organizada pelos pequenos produtores rurais e trabalhadores do campo, por participação no orçamento do Estado, desencadeou a institucionalização da categoria “agricultura familiar”, abarcando variados ... ...

Abstract	Ao longo da segunda metade do século XX, a luta organizada pelos pequenos produtores rurais e trabalhadores do campo, por participação no orçamento do Estado, desencadeou a institucionalização da categoria “agricultura familiar”, abarcando variados grupos, tornando o desenvolvimento rural difuso. O objetivo deste artigo é mostrar como se deu essa institucionalização, suas características e desafios frente a implementação das políticas públicas orientadas a uma categoria de agentes tão distintos no âmbito cultural, social, econômico e territorial. Para isso, a pesquisa utiliza o arcabouço teórico da sociologia reflexiva de Pierre Bourdieu, no que tange seus estudos sobre o Estado, com a intenção de identificar as lutas simbólicas no campo do poder, tendo a institucionalização da categoria agricultura familiar como produto, colocando diversos grupos sociais na agenda desenvolvimento nacional. Os resultados mostram que, embora tenha formalizado um conjunto de regulamentações e políticas públicas voltadas à agricultura familiar, sua diversidade traz a necessidade da participação de outros fatores que não, unicamente, as políticas públicas federais, evidenciando a distribuição desigual de capital simbólico à heterogênea agricultura familiar.
Keywords	Agricultura Familiar ; Pronaf ; Desenvolvimento Rural ; Social Sciences ; H ; Social sciences (General) ; H1-99
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Universidade Estadual de Londrina
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: O Estado e as políticas públicas que tornaram a agricultura familiar uma agente importante do desenvolvimento

Giovanni Barillari de Freitas

Mediações: Revista de Ciências Sociais, Vol 23, Iss 2, Pp 366-

2018 Volume 389

Abstract: Este artigo parte da hipótese de que o Programa Nacional de Fortalecimento da Agricultura Familiar (Pronaf) foi um marco definitivo para os pequenos produtores rurais, até então excluídos das políticas públicas nacionais. Já que, após sua criação em 1995 ...

Abstract	Este artigo parte da hipótese de que o Programa Nacional de Fortalecimento da Agricultura Familiar (Pronaf) foi um marco definitivo para os pequenos produtores rurais, até então excluídos das políticas públicas nacionais. Já que, após sua criação em 1995 e, principalmente, após o ano de 2003, as conquistas das famílias agricultoras se expandiram na direção de leis e políticas públicas que permitissem apontá-las como indivíduos integrados à sociedade capitalista. Desta maneira, o objetivo do artigo é mostrar a inclusão dos pequenos produtores rurais como atores do desenvolvimento nacional. Para isso, a pesquisa se utiliza do arcabouço teórico da sociologia reflexiva de Pierre Bourdieu no que tange seus estudos sobre o Estado e a construção de mercados, com a intenção de identificar elementos para além do econômico, como os institucionais, que constroem os mercados da agricultura familiar.
Keywords	agricultura familiar ; pronaf ; desenvolvimento rural ; Social Sciences ; H ; Social sciences (General) ; H1-99
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Universidade Estadual de Londrina
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma

Giovanni Barillari / Ombretta Melaiu / Marco Gargari / Silvia Pomella / Roberto Bei / Vincenzo Campanella

International Journal of Molecular Sciences, Vol 23, Iss 8336, p

An Overview

2022 Volume 8336

Abstract: Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue ... ...

Abstract	Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC.
Keywords	CD147 ; oral keratinocytes ; inflammation ; EMT ; oral premalignant diseases ; oral squamous cell carcinoma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma

Silvia Pomella / Matteo Cassandri / Ombretta Melaiu / Francesco Marampon / Marco Gargari / Vincenzo Campanella / Rossella Rota / Giovanni Barillari

International Journal of Molecular Sciences, Vol 24, Iss 2673, p

2023 Volume 2673

Abstract: Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification ... ...

Abstract	Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson’s correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1 , CCNB2 , CDK2 , CDK4 , CHECK1 , E2F1 , FANCD2 , and PRKDC ) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy.
Keywords	oral squamous cell carcinoma ; DNA damage response ; The Cancer Genome Atlas ; DepMap ; bioinformatics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors

Giovanni Barillari / Paolo Monini / Cecilia Sgadari / Barbara Ensoli

International Journal of Molecular Sciences, Vol 19, Iss 5, p

A Review of Preclinical and Clinical Studies

2018 Volume 1418

Abstract: Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to ... ...

Abstract	Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC), a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV), as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI) have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s) of its development. This article reviews published work concerning: (i) the role of HPV proteins (including HPV-E5, E6 and E7) and of matrix-metalloproteinases (MMPs) in CIN evolution into invasive CC; and (ii) the effect of HIV-PI on events leading to CIN progression such as basement membrane and extracellular matrix invasion by HPV-positive CIN cells and the formation of new blood vessels. Results from the reviewed literature indicate that CIN clinical progression can be monitored by evaluating the expression of MMPs and HPV proteins and they suggest the use of HIV-PI or their derivatives for the block of CIN evolution into CC in both HIV-infected and uninfected women.
Keywords	HPV ; uterine CIN ; uterine cervical carcinoma ; MMP ; HIV-PI ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma

Silvia Pomella / Antonella Porrazzo / Matteo Cassandri / Simona Camero / Silvia Codenotti / Luisa Milazzo / Francesca Vulcano / Giovanni Barillari / Giovanni Cenci / Cinzia Marchese / Alessandro Fanzani / Francesca Megiorni / Rossella Rota / Francesco Marampon

International Journal of Molecular Sciences, Vol 23, Iss 13281, p

2022 Volume 13281

Abstract: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine ... ...

Abstract	Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine different prognostic groups and related therapeutic treatment. Current multimodal therapeutic strategies involve surgery, chemotherapy (CHT) and radiotherapy (RT), but despite the deeper knowledge of response mechanisms underpinning CHT treatment and the technological improvements that characterize RT, local failures and recurrence frequently occur. This review sums up the RMS classification and the management of RMS patients, with special attention to RT treatment and possible radiosensitizing strategies for RMS tumors. Indeed, RMS radioresistance is a clinical problem and further studies aimed at dissecting radioresistant molecular mechanisms are needed to identify specific targets to hit, thus improving RT-induced cytotoxicity.
Keywords	rhabdomyosarcoma ; radiotherapy ; radiation therapy ; radiosensitizers ; radioresistance ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HIV-1 Tat Protein Enters Dysfunctional Endothelial Cells via Integrins and Renders Them Permissive to Virus Replication

Aurelio Cafaro / Giovanni Barillari / Sonia Moretti / Clelia Palladino / Antonella Tripiciano / Mario Falchi / Orietta Picconi / Maria Rosaria Pavone Cossut / Massimo Campagna / Angela Arancio / Cecilia Sgadari / Claudia Andreini / Lucia Banci / Paolo Monini / Barbara Ensoli

International Journal of Molecular Sciences, Vol 22, Iss 317, p

2021 Volume 317

Abstract: Previous work has shown that the Tat protein of Human Immunodeficiency Virus (HIV)-1 is released by acutely infected cells in a biologically active form and enters dendritic cells upon the binding of its arginine-glycine-aspartic acid (RGD) domain to the ...

Abstract	Previous work has shown that the Tat protein of Human Immunodeficiency Virus (HIV)-1 is released by acutely infected cells in a biologically active form and enters dendritic cells upon the binding of its arginine-glycine-aspartic acid (RGD) domain to the α5β1, αvβ3, and αvβ5 integrins. The up-regulation/activation of these integrins occurs in endothelial cells exposed to inflammatory cytokines that are increased in HIV-infected individuals, leading to endothelial cell dysfunction. Here, we show that inflammatory cytokine-activated endothelial cells selectively bind and rapidly take up nano-micromolar concentrations of Tat, as determined by flow cytometry. Protein oxidation and low temperatures reduce Tat entry, suggesting a conformation- and energy-dependent process. Consistently, Tat entry is competed out by RGD-Tat peptides or integrin natural ligands, and it is blocked by anti-α5β1, -αvβ3, and -αvβ5 antibodies. Moreover, modelling–docking calculations identify a low-energy Tat-αvβ3 integrin complex in which Tat makes contacts with both the αv and β3 chains. It is noteworthy that internalized Tat induces HIV replication in inflammatory cytokine-treated, but not untreated, endothelial cells. Thus, endothelial cell dysfunction driven by inflammatory cytokines renders the vascular system a target of Tat, which makes endothelial cells permissive to HIV replication, adding a further layer of complexity to functionally cure and/or eradicate HIV infection.
Keywords	integrins ; endothelial cells ; inflammatory cytokines ; HIV-1 Tat protein ; cellular uptake ; HIV-1 target cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571 ; 570
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells

Monica Benvenuto / Sara Ciuffa / Chiara Focaccetti / Diego Sbardella / Sara Fazi / Manuel Scimeca / Grazia Raffaella Tundo / Giovanni Barillari / Maria Segni / Elena Bonanno / Vittorio Manzari / Andrea Modesti / Laura Masuelli / Massimo Coletta / Roberto Bei

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 23

Abstract: Abstract Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer ... ...

Abstract	Abstract Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, triggered apoptosis, modulated the expression and activation of pro-survival signaling transduction pathways proteins activated by ErbB receptors and inhibited proteasome activity in vitro. Intraperitoneal administration of Bortezomib delayed tumor growth of SALTO-5 cells transplanted in BALB-neuT mice, protracted mice survival and adjusted tumor microenvironment by increasing tumor-infiltrating immune cells (CD4+ and CD8+ T cells, B lymphocytes, macrophages, and Natural Killer cells) and by decreasing vessels density. In addition, Bortezomib modified the expression of proteasome structural subunits in transplanted SALTO-5 cells. Our findings further support the use of Bortezomib for the treatment of HNC and reveal its ineffectiveness in counteracting the activation of deregulated specific signaling pathways in HNC cell lines when resistance to proteasome inhibition is developed.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fibroblast Growth Factor-2 and the HIV-1 Tat Protein Synergize in Promoting Bcl-2 Expression and Preventing Endothelial Cell Apoptosis

Cecilia Sgadari / Giovanni Barillari / Clelia Palladino / Stefania Bellino / Brunella Taddeo / Elena Toschi / Barbara Ensoli

International Journal of Vascular Medicine , Vol

Implications for the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

2011 Volume 2011

Keywords	Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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