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Article ; Online: Mycobacterium tuberculosis Antigen 85B modifies BCG-induced anti-tuberculosis immunity and favors pathogen survival.

Piccaro, Giovanni / Aquino, Gabriella / Gigantino, Vincenzo / Tirelli, Valentina / Sanchez, Massimo / Iorio, Egidio / Matarese, Giuseppe / Cassone, Antonio / Palma, Carla

Journal of leukocyte biology

2024

Abstract: Tuberculosis is one of the deadliest infectious diseases worldwide. Mycobacterium tuberculosis (Mtb) has developed strategies not only to evade from host immunity but also to manipulate it for its survival. We investigated whether Mtb exploited the ... ...

Abstract	Tuberculosis is one of the deadliest infectious diseases worldwide. Mycobacterium tuberculosis (Mtb) has developed strategies not only to evade from host immunity but also to manipulate it for its survival. We investigated whether Mtb exploited the immunogenicity of Ag85B, one of its major secretory proteins, to redirect host anti-TB immunity to its advantage. We found that administration of Ag85B protein to mice vaccinated with Bacillus Calmette-Guérin (BCG) impaired the protection elicited by vaccination causing a more severe infection when mice were challenged with Mtb. Ag85B administration reduced BCG-induced CD4 T cell activation and IFN-γ, CCL-4 and IL-22 production in response to Mtb-infected cells. On the other hand, it promoted robust Ag85B-responsive IFN-γ-producing CD4 T cells, expansion of a subset of IFN-γ/IL-10-producing CD4+FOXP3+Treg cells, differential activation of IL-17/IL-22 responses and activation of regulatory and exhaustion pathways, including programmed death-ligand 1 expression on macrophages. All this resulted in impaired intracellular Mtb growth control by systemic immunity, both at pre- and post-Mtb challenge. Interestingly, Mtb infection itself generated Ag85B-reactive inflammatory immune cells incapable of clearing Mtb in both unvaccinated and BCG-vaccinated mice. Our data suggest that Mtb can exploit the strong immunogenicity of Ag85B to promote its own survival and spread. Since Ag85B is normally secreted by replicating bacteria and it is commonly found in the lungs of the Mtb-infected host, our findings may advance the understanding on the mechanisms of Mtb pathogenesis and immune evasion.
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiae014
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Article ; Online: LncRNA

Botti, Gerardo / Scognamiglio, Giosuè / Aquino, Gabriella / Liguori, Giuseppina / Cantile, Monica

International journal of molecular sciences

2019 Volume 20, Issue 9

Abstract: lncRNAs participate in many cellular processes, including regulation of gene expression at the transcriptional and post-transcriptional levels. In addition, many lncRNAs can contribute to the development of different human diseases including cancer. The ... ...

Abstract	lncRNAs participate in many cellular processes, including regulation of gene expression at the transcriptional and post-transcriptional levels. In addition, many lncRNAs can contribute to the development of different human diseases including cancer. The tumor microenvironment (TME) plays an important role during tumor growth and metastatic progression, and most of these lncRNAs have a key function in TME intracellular signaling. Among the numerous identified lncRNAs, several experimental evidences have shown the fundamental role of the lncRNA
MeSH term(s)	Carcinogenesis/genetics ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms/genetics ; RNA, Long Noncoding/genetics ; Tumor Microenvironment/genetics
Chemical Substances	HOTAIR long untranslated RNA, human ; RNA, Long Noncoding
Language	English
Publishing date	2019-05-08
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/ijms20092279
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Article ; Online: Cytological diagnosis of Xp11 translocation renal cell carcinoma: An unusual suspect in bone metastases from unknown primary malignancies.

Montella, Marco / Franco, Renato / Aquino, Gabriella / Ronchi, Andrea / Zito Marino, Federica / Di Napoli, Marilena / Pignata, Sandro / Cozzolino, Immacolata

Diagnostic cytopathology

2020 Volume 49, Issue 1, Page(s) 11–17

Abstract: Background: Renal cell carcinoma (RCC) constitutes 3% of all cancers, with a higher incidence in patients with age between 60 and 70 years. RCC frequently present as a metastatic tumor at diagnosis, and bones represent one of the most frequent sites. ... ...

Abstract	Background: Renal cell carcinoma (RCC) constitutes 3% of all cancers, with a higher incidence in patients with age between 60 and 70 years. RCC frequently present as a metastatic tumor at diagnosis, and bones represent one of the most frequent sites. Many cases, mainly in young patients, includes the Xp11 translocation RCC. The cytological diagnosis of Xp11 translocation RCC in adult population it is rarely performed, likely for the morphological overlap with other adult renal cell carcinoma subtypes. Methods: We retrospectively analyze a series of 92 adult patients with metastatic bone tumors, diagnosed on fine-needle aspiration cytology (FNAC) samples, focusing mainly on the cytological, immunophenotypic and molecular features of Xp11 translocation RCC. Results: In our series 6 of 92 (6.5%) cases were metastatic RCC (mRCC), among them 2 cases were metastasis from Xp11translocation RCC. Those cases showed a bloody background, with several groups of atypical cells arranged in syncytial groups or in papillary groups composed by atypical cells with abundant cytoplasm, with scattered clear cells. TFE3 was positive on immunocytochemical analysis and specific translocation t(Xp11.23) was detected by FISH analysis. Conclusions: In adult patients with mRCC, it is necessary to consider also Xp11 translocation RCC among the diagnostic hypotheses. FNAC represents a valid tool to investigate bone lesions but cytological features of Xp11 translocation RCC are still poorly described and must necessarily be better defined.
MeSH term(s)	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Biopsy, Fine-Needle ; Bone Neoplasms/diagnosis ; Bone Neoplasms/pathology ; Bone and Bones/pathology ; Chromosomes, Human, X ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Metastasis/pathology ; Neoplasms, Unknown Primary/diagnosis ; Neoplasms, Unknown Primary/pathology ; Oncogene Proteins, Fusion/genetics ; Retrospective Studies ; Translocation, Genetic
Chemical Substances	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Oncogene Proteins, Fusion ; TFE3 protein, human
Language	English
Publishing date	2020-08-18
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	632710-2
ISSN	1097-0339 ; 8755-1039
ISSN (online)	1097-0339
ISSN	8755-1039
DOI	10.1002/dc.24587
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Article ; Online: Molecular characterization of a bladder pleomorphic rhabdomyosarcoma in an adult patient.

Feroce, Florinda / Cantile, Monica / Aquino, Gabriella / Collina, Francesca / Scognamiglio, Giosuè / Castaldo, Luigi / Perdonà, Sisto / Botti, Gerardo / De Chiara, Annarosaria

Pathology, research and practice

2020 Volume 216, Issue 8, Page(s) 153033

Abstract: Pleomorphic rhabdomyosarcoma (PRMS) is a rare but highly aggressive soft tissue tumor, accounting for 3% of soft tissue sarcomas. PRMS is the most frequent subtype of RMS in adulthood and it is mainly located in the large muscles of the extremities, ... ...

Abstract	Pleomorphic rhabdomyosarcoma (PRMS) is a rare but highly aggressive soft tissue tumor, accounting for 3% of soft tissue sarcomas. PRMS is the most frequent subtype of RMS in adulthood and it is mainly located in the large muscles of the extremities, particularly the lower limbs and the trunk, more rarely in other locations especially in the bladder. At our knowledge, only six cases of adult pleomorphic rhabdomyosarcoma of the bladder have been reported in the literature. In this study, we report a case of PRMS of bladder with a very poor prognosis. In fact, the patient died a month after surgery. The tumor was characterized by poorly differentiated, medium-sized sometimes rhabdoid cells, mixed with large-sized and pleomorphic elements with evident anisonucleosis, and with large areas of necrosis. We used an extensive immunohistochemical panel to exclude other tumors much more frequently reported at this site. The positivity for myogenic markers such as actin, desmin, myogenin and MyoD1 allowed the correct diagnosis. Furthermore, since preliminary studies highlighted a series of specific molecular alterations in PMRS cell lines, we analyzed a panel of specific mutations and gene rearrangements by RT-PCR and FISH methods. We showed a copy gains of CCND1 and MALT genes in our samples, suggesting an accurate molecular characterization of PRMS to establish a better management of patients and new therapeutic opportunities.
MeSH term(s)	Biomarkers, Tumor/analysis ; Cyclin D1/genetics ; DNA Mutational Analysis ; Fatal Outcome ; Humans ; Male ; Middle Aged ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/genetics ; Rhabdomyosarcoma/genetics ; Rhabdomyosarcoma/pathology ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology
Chemical Substances	Biomarkers, Tumor ; CCND1 protein, human ; Cyclin D1 (136601-57-5) ; MALT1 protein, human (EC 3.4.22.-) ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein (EC 3.4.22.-)
Language	English
Publishing date	2020-05-28
Publishing country	Germany
Document type	Case Reports
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2020.153033
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Article ; Online: Synovial sarcoma diagnosis on fine needle cytology sample confirmed by fluorescence in situ hybridisation.

Ronchi, Andrea / Panarese, Iacopo / Aquino, Gabriella / Gambardella, Antonio / Franco, Renato / Cozzolino, Immacolata

Cytopathology : official journal of the British Society for Clinical Cytology

2018 Volume 30, Issue 3, Page(s) 314–317

MeSH term(s)	Adult ; Biopsy, Fine-Needle/methods ; Diagnosis, Differential ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Sarcoma, Synovial/diagnosis ; Sarcoma, Synovial/genetics ; Sarcoma, Synovial/pathology ; Translocation, Genetic/genetics
Language	English
Publishing date	2018-12-06
Publishing country	England
Document type	Case Reports
ZDB-ID	1034190-0
ISSN	1365-2303 ; 0956-5507 ; 1350-4037
ISSN (online)	1365-2303
ISSN	0956-5507 ; 1350-4037
DOI	10.1111/cyt.12651
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Zs.A 2926: Show issues

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Article: LncRNA

Collina, Francesca / Aquino, Gabriella / Brogna, Marianna / Cipolletta, Sabrina / Buonfanti, Gaetano / De Laurentiis, Michelino / Di Bonito, Maurizio / Cantile, Monica / Botti, Gerardo

Journal of Cancer

2019 Volume 10, Issue 9, Page(s) 2018–2024

Abstract: Triple-negative breast cancers (TNBCs) represent a heterogeneous disease characterized by several molecular subtypes with different prognoses and responses to therapy. For a correct clinical management of TNBC patients the knowledge of the gene ... ...

Abstract	Triple-negative breast cancers (TNBCs) represent a heterogeneous disease characterized by several molecular subtypes with different prognoses and responses to therapy. For a correct clinical management of TNBC patients the knowledge of the gene regulation mechanisms related to tumor progression and drug response has become fundamental. LncRNAs regulate gene expression through various processes, including chromatin modification, transcription and post-transcription and they are emerging as important cancer biomarkers being involved in tumor pathogenesis, metastatic progression and drug resistance. In this study we aimed to analyze the expression of the lncRNA
Language	English
Publishing date	2019-05-12
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.29670
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Article ; Online: Aberrant Expression of Long Non Coding RNA HOTAIR and De-Regulation of the Paralogous 13 HOX Genes Are Strongly Associated with Aggressive Behavior of Gastro-Entero-Pancreatic Neuroendocrine Tumors.

Di Mauro, Annabella / Scognamiglio, Giosuè / Aquino, Gabriella / Cerrone, Margherita / Liguori, Giuseppina / Clemente, Ottavia / Di Bonito, Maurizio / Cantile, Monica / Botti, Gerardo / Tafuto, Salvatore / Tatangelo, Fabiana

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of ... ...

Abstract	Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Homeobox ; Humans ; Intestinal Neoplasms/genetics ; Intestinal Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; RNA, Long Noncoding/genetics ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Up-Regulation
Chemical Substances	HOTAIR long untranslated RNA, human ; RNA, Long Noncoding
Language	English
Publishing date	2021-06-30
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/ijms22137049
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Article ; Online: High performance of multiplex fluorescence in situ hybridization to simultaneous detection of BCL2 and BCL6 rearrangements: useful application in the characterization of DLBCLs.

Marino, Federica Zito / Aquino, Gabriella / Brunelli, Matteo / Scognamiglio, Giosuè / Pedron, Serena / Ronchi, Andrea / Cozzolino, Immacolata / Sparano, Lucianna / Botti, Gerardo / Panico, Luigi / De Chiara, Anna / Franco, Renato

Virchows Archiv : an international journal of pathology

2021 Volume 479, Issue 3, Page(s) 565–573

Abstract: Chromosomal rearrangements involving BCL2, BCL6 and MYC are commonly found in the most frequent B cell lymphomas, namely follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs). Particularly, BCL2-rearrangement represents a diagnostic ... ...

Abstract	Chromosomal rearrangements involving BCL2, BCL6 and MYC are commonly found in the most frequent B cell lymphomas, namely follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs). Particularly, BCL2-rearrangement represents a diagnostic hallmark in FLs, whereas MYC translocation can occur simultaneously with BCL2 and/or BCL6 rearrangements, defining a specific category of DLBCLs with a poorer prognosis. In this study, we aim to validate the diagnostic performance of multiplex BCL2/BCL6 FISH approach in formalin-fixed paraffin-embedded FLs and DBCLs and cytological samples of DLBCL comparing to the classic set of single break-apart probes. We collected a series of lymphomas, including 85 DLBCLs, 45 FLs and 36 other B-cell lymphoma histotypes and 16 cytological samples of DLBCLs. MYC, BCL2 and BCL6 rearrangements were previously assessed by a classic FISH test using single break-apart probes. All samples were analysed by a multiplex FISH assay. In the FL series, 38 cases showed BCL2-R; in the DLBCLs series, MYC-R was detected in 21 out of 85 DLBCL patients, BCL2-R in 10 out of 85 and BCL6-R in 33 out of 85. In the DLBCL cytological series, MYC-R was detected in 4 out of 16, BCL2-R in 4 out of 16 and BCL6-R in 1 out of 16. Notably, in FFPE, 13 double-hit lymphomas (DHLs) and 3 triple-hit lymphomas (THLs) were detected; in the cytological series, only 3 DHL cases were observed. The dual BCL2/BCL6 FISH probe test results were fully concordant with the results obtained using classic BCL2 and BCL6 single break apart. Particularly, multiplex FISH to simultaneously detect BCL2-R and BCL6-R on a single slide could find a wide application in the characterisation of double- and triple-hit DLBCLs.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Female ; Gene Rearrangement ; Genetic Predisposition to Disease ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Male ; Middle Aged ; Phenotype ; Predictive Value of Tests ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-6/genetics ; Reproducibility of Results
Chemical Substances	BCL2 protein, human ; BCL6 protein, human ; Biomarkers, Tumor ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-bcl-6
Language	English
Publishing date	2021-03-25
Publishing country	Germany
Document type	Journal Article ; Validation Study
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-021-03084-8
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Article ; Online: Oral and Oropharyngeal squamous cell carcinoma: prognostic and predictive parameters in the etiopathogenetic route.

Panarese, Iacopo / Aquino, Gabriella / Ronchi, Andrea / Longo, Francesco / Montella, Marco / Cozzolino, Immacolata / Roccuzzo, Giuseppe / Colella, Giuseppe / Caraglia, Michele / Franco, Renato

Expert review of anticancer therapy

2019 Volume 19, Issue 2, Page(s) 105–119

Abstract: Introduction: Oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC) represents an increasing problem in the global public health. Indeed, squamous cell carcinoma is the most frequent malignancy in oral cavity and 1 of the 10 most common ... ...

Abstract	Introduction: Oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC) represents an increasing problem in the global public health. Indeed, squamous cell carcinoma is the most frequent malignancy in oral cavity and 1 of the 10 most common cancers worldwide. According to the most recent GLOBOCAN estimate in Europe between 2012 and 2015, there was an overall increasing incidence and mortality for oral cancer, mostly HPV-related in the oropharyngeal region with evidence of significant differences from the prognostic and therapeutic point of view. Areas covered: Until now, the management of the patients is based on classical histologic parameters such as TNM and tumor grading, but new molecular and cell markers have been investigated to improve patients' treatment and survival. Therefore, there is a need for new biomarkers characterizing the cancer diversity, with the consequent possibility of patient stratification for specific treatment. Expert commentary: This review aims to discuss some of the most relevant and novel genetic, epigenetic, and histological prognostic biomarkers in oral cancer, highlighting the main differences between HPV-unrelated oral squamous cell carcinoma (OSCC) and HPV-related oropharyngeal squamous cell carcinoma (OPSCC) that may aid in stratifying prognostic subgroups and rationalizing treatment decisions.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/therapy ; Humans ; Mouth Neoplasms/pathology ; Mouth Neoplasms/therapy ; Neoplasm Grading ; Oropharyngeal Neoplasms/pathology ; Oropharyngeal Neoplasms/therapy ; Papillomavirus Infections/complications ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/pathology ; Squamous Cell Carcinoma of Head and Neck/therapy
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2019-01-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1080/14737140.2019.1561288
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Article ; Online: Pleomorphic adenoma of salivary gland and synchronous/metachronous invasive ductal breast cancer: a casual coincidence or a clinical presentation resulting from common genetic events?

Longo, Francesco / Sabatino, Rocco / Aquino, Gabriella / Losito, Nunzia Simona / Cantile, Monica / Ionna, Franco / Botti, Gerardo

International journal of clinical and experimental pathology

2018 Volume 11, Issue 3, Page(s) 1712–1714

Abstract: Breast and salivary glands have similar morphological and pathological features; however genetic relation between these lesions were not described. In this report we described a small series of biomarkers that developed synchronously or metachronous ... ...

Abstract	Breast and salivary glands have similar morphological and pathological features; however genetic relation between these lesions were not described. In this report we described a small series of biomarkers that developed synchronously or metachronous pleomorphic adenoma of the salivary glands and invasive breast cancer, on which we have tested, by immunohistochemistry, several of bio-markers that may be associated with the pathogenesis of both malignancies. In conclusion, we suggest to better investigate early genetic alterations that could underlie of the synchronous occurrence of these lesions.
Language	English
Publishing date	2018-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2418306-4
ISSN	1936-2625 ; 1936-2625
ISSN (online)	1936-2625
ISSN	1936-2625
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