76 results on '"Collina, Francesca"'
Search Results
52. Aspetti di sicurezza nel Cloud Computing
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Collina, Francesca, thesis supervisor: Omicini, Andrea, Collina, Francesca, and thesis supervisor: Omicini, Andrea
53. Aspetti di sicurezza nel Cloud Computing
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Collina, Francesca, thesis supervisor: Omicini, Andrea, Collina, Francesca, and thesis supervisor: Omicini, Andrea
54. Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer
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Maurizio Di Bonito, Monica Fedele, Simona Camorani, Silvia Esposito, Margherita Passariello, Claudia De Lorenzo, Lisa Agnello, Laura Cerchia, Monica Cantile, Ilya V. Ulasov, Antonella Zannetti, Francesca Collina, Camorani, Simona, Passariello, Margherita, Agnello, Lisa, Esposito, Silvia, Collina, Francesca, Cantile, Monica, Di Bonito, Maurizio, Ulasov, Ilya V, Fedele, Monica, Zannetti, Antonella, De Lorenzo, Claudia, and Cerchia, Laura
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,PDGFRβ ,Metastase ,Apoptosis ,Triple Negative Breast Neoplasms ,Metastases ,Metastasis ,Targeted therapy ,Mice ,0302 clinical medicine ,Tumor Cells, Cultured ,Molecular Targeted Therapy ,Immune Checkpoint Inhibitors ,Triple-negative breast cancer ,Mice, Inbred BALB C ,Chemistry ,Aptamers, Nucleotide ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Oncology ,Tumor microenvironment ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Female ,TNBC ,PD-L1 monoclonal antibody ,Aptamer ,medicine.drug_class ,Mice, Nude ,Monoclonal antibody ,lcsh:RC254-282 ,Receptor, Platelet-Derived Growth Factor beta ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Growth factor receptor ,medicine ,Animals ,Humans ,Cell Proliferation ,Research ,Immunotherapy ,medicine.disease ,Xenograft Model Antitumor Assays ,Immune checkpoint ,030104 developmental biology ,Antitumor immunity ,PDGFR? ,Cancer research - Abstract
Abstract Background Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC. Methods The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4 T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4 T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAb-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in mice. It acts on both tumor cells, inhibiting Akt and ERK1/2 signaling pathways, and immune populations, increasing intratumoral CD8 + T cells and reducing FOXP3 + Treg cells. Conclusion Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first time an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.
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- 2020
55. AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer
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Luciano Pezzullo, Nella Prevete, Maria Grazia Chiofalo, Nunzia Simona Losito, Giuseppina Liguori, Francesca Collina, Laura Arenare, Elvira La Mantia, Francesca Di Gennaro, Monica Cantile, Rosa Marina Melillo, Giancarlo Vecchio, Renato Franco, Gerardo Botti, Lucia La Sala, Gabriella Aquino, Federica Liotti, Collina, F, La Sala, L, Liotti, F, Prevete, N, La Mantia, E, Chiofalo, Mg, Aquino, G, Arenare, L, Cantile, M, Liguori, G, Di Gennaro, F, Pezzullo, L, Losito, N, Vecchio, G, Botti, G, Melillo, Rm, Franco, R., Collina, Francesca, La Sala, Lucia, Liotti, Federica, Prevete, Nella, La Mantia, Elvira, Chiofalo, Maria Grazia, Aquino, Gabriella, Arenare, Laura, Cantile, Monica, Liguori, Giuseppina, Di Gennaro, Francesca, Pezzullo, Luciano, Losito, Nunzia Simona, Vecchio, Giancarlo, Botti, Gerardo, Melillo, Rosa Marina, and Franco, Renato
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0301 basic medicine ,Cancer Research ,Thymoma ,endocrine system diseases ,AKT1 ,P65 NF-kB activation ,Radioactive iodine (RAI)-refractorine ,lcsh:RC254-282 ,Article ,Receptor tyrosine kinase ,Thyroid cancer ,Thyroid carcinoma ,03 medical and health sciences ,0302 clinical medicine ,radioactive iodine (RAI)-refractoriness ,hemic and lymphatic diseases ,medicine ,biology ,GAS6 ,business.industry ,AXL ,disease persistence/recurrence ,p65 NF-kB activation ,thyroid cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Immunohistochemistry ,business ,Disease persistence/recurrence ,V600E - Abstract
Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs. Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs.
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- 2019
56. Interleukin-8, but Not the Related Chemokine CXCL1, Sustains an Autocrine Circuit Necessary for the Properties and Functions of Thyroid Cancer Stem Cells
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Lucia La Sala, Nella Prevete, Renato Franco, Rosa Marina Melillo, Francesca Collina, Federica Liotti, Emanuela Pone, Liotti, Federica, Collina, F, Pone, Emanuela, La Sala, L, Franco, R, Prevete, Nella, Melillo, ROSA MARINA, Collina, Francesca, La Sala, Lucia, Franco, Renato, and Melillo, Rosa Marina
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0301 basic medicine ,medicine.medical_specialty ,Chemokine ,Epithelial-Mesenchymal Transition ,Chemokine CXCL1 ,Mice, Nude ,Antigens, CD34 ,Biology ,Thyroid cancer ,Receptors, Interleukin-8B ,Receptors, Interleukin-8A ,03 medical and health sciences ,0302 clinical medicine ,Cancer stem cell ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Thyroid Neoplasms ,Interleukin 8 ,CXC chemokine receptors ,Autocrine signalling ,CXCR2 ,IL-8 ,CXCR1 ,Cancer stem cells ,Interleukin-8 ,Cell Biology ,respiratory system ,CXCL1 ,Autocrine Communication ,030104 developmental biology ,Endocrinology ,Cell culture ,030220 oncology & carcinogenesis ,Thyroid cancer, stem cell, IL-8 ,Neoplastic Stem Cells ,Cancer research ,biology.protein ,Molecular Medicine ,Female ,Snail Family Transcription Factors ,Stem cell ,Signal Transduction ,Developmental Biology - Abstract
Interleukin-8 (IL-8/CXCL8) mediates its biological effects through two receptors, CXCR1 and CXCR2. While CXCR1 recognizes IL-8 and granulocyte chemotactic protein-2, CXCR2 binds to multiple chemokines including IL-8, CXCL1, 2 and 3. Both IL-8 and CXCL1 have been implicated in the neoplastic features of thyroid cancer (TC). Here, we assessed the role of the autocrine circuits sustained by IL-8 and CXCL1 in determining TC stem cell (TC SC) features. Using immunohistochemistry, we found that thyroid epithelial cancerous, but not normal, cells stained positive for IL-8, whose levels correlated with lymph-nodal metastases. We assessed the expression of endogenous IL-8 and CXCL1, by ELISA assays, and of their receptors CXCR1 and CXCR2, by flow cytometry, in a panel of TC cell lines. These molecules were expressed in TC cell lines grown in adherence, and at higher levels also in thyrospheres enriched in stem-like cells. RNA interference demonstrated that IL-8/CXCR1, but not CXCL1/CXCR2, is crucial for the sphere-forming, self-renewal and tumor-initiating ability of TC cells. Accordingly, treatment of TC cells with IL-8, but not with CXCL1, potentiated cell stemness. We identified CD34 as an IL-8-induced gene and as a TC SC marker, since it was overexpressed in thyrospheres compared to adherent cells. Moreover, CD34 is required for the efficient sphere-forming ability and tumorigenicity of TC cells. Our data indicate that IL-8, but not the CXCL1 circuit, is critical for the regulation of TC SCs, and unveils novel potential targets for the therapy of as yet untreatable forms of TC.
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- 2016
57. Atypical amplification of chromosome region 22q12 in melanoma: A case report
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Mirella D'Andrea, Francesca Collina, Michele Caraglia, Laura Marra, Monica Cantile, Giuseppina Liguori, Gerardo Botti, Giovanni Francesco Nicoletti, Anna De Chiara, Renato Franco, Liguori, Giuseppina, Cantile, Monica, Collina, Francesca, Marra, Laura, de Chiara, Anna, Franco, Renato, Caraglia, Michele, Botti, Gerardo, D'Andrea, Mirella, and Nicoletti, Giovanni Francesco
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Cancer Research ,Pathology ,medicine.medical_specialty ,ATF1 ,medicine.diagnostic_test ,EWSR1 gene ,Fluorescence in situ hybridization ,Melanoma ,Differential diagnosi ,Chromosome ,Chromosomal translocation ,Articles ,Biology ,medicine.disease ,Oncology ,Chromosome regions ,medicine ,Clear-cell sarcoma ,Differential diagnosis ,Clear cell sarcoma - Abstract
Morphological, ultrastructural and immunohistochemical characteristics of clear cell sarcoma (CCS) of the soft tissue frequently overlap with those of malignant melanoma. Thus, the differential diagnosis between the two lesions represents an important diagnostic dilemma. However, a number of genetic factors can be used to differentiate the two tumors; in particular, the t(12;22)(q13;q12) chromosomal translocation is typical of CCS, resulting in fusion of the EWSR1 gene on chromosome 22q12 and the ATF1 gene on chromosome 12q13. The detection of this molecular alteration has proved useful in the differential diagnosis of the two lesions. The present study reports the case of a 71-year-old male patient with a suspicious lymph node mass. Immunohistochemical analysis of the lesion indicated a diagnosis of metastatic melanoma, however, cytogenetic analysis using fluorescence in situ hybridization was additionally performed to investigate the chromosomal rearrangements of the 22q12 region and completely exclude the possibility of CCS. The current case did not demonstrate the presence of the translocation, supporting the diagnosis of melanoma. However, a clear orange amplification signal was observed relative to an ~500-kb region adjacent to the EWSR1 gene in the centromeric direction of chromosome 22q12. To the best of our knowledge, this is the first description of a 22q12 chromosomal alteration in melanoma. Furthermore, despite the presence of numerous genes in this region, their amplification has not previously been associated with the pathogenesis of melanoma.
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- 2015
58. Hedgehog signalling pathway orchestrates angiogenesis in triple-negative breast cancers
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Paola Ciciola, Angela Chambery, Roberta Clara Orsini, Sabino De Placido, Concetta Di Mauro, Roberta Marciano, Roberto Bianco, Bianca Maria Veneziani, Monica Cantile, Luigi Formisano, Valeria Cicatiello, Roberta Di Rosa, Maurizio Di Bonito, Alberto Servetto, Francesca Collina, Valentina D’Amato, Sandro De Falco, Di Mauro, Concetta, Rosa, Roberta, D'Amato, Valentina, Ciciola, Paola, Servetto, Alberto, Marciano, Roberta, Orsini, Roberta Clara, Formisano, Luigi, De Falco, Sandro, Cicatiello, Valeria, Di Bonito, Maurizio, Cantile, Monica, Collina, Francesca, Chambery, Angela, Veneziani, Bianca Maria, De Placido, Sabino, Bianco, Roberto, and Veneziani, BIANCA MARIA
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Vascular Endothelial Growth Factor A ,0301 basic medicine ,Cancer Research ,Pyridines ,Angiogenesis ,GLI1 ,Triple Negative Breast Neoplasms ,Thrombospondin 1 ,Mice ,angiogenesis ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Aged, 80 and over ,Neovascularization, Pathologic ,Middle Aged ,Bevacizumab ,Angiogenesi ,Oncology ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Female ,TNBC ,Signal Transduction ,Adult ,medicine.medical_specialty ,Paclitaxel ,Mice, Nude ,NVP-LDE225 ,Biology ,Transfection ,Zinc Finger Protein GLI1 ,Young Adult ,03 medical and health sciences ,Paracrine signalling ,Internal medicine ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,Hedgehog Proteins ,Gene Silencing ,RNA, Messenger ,Autocrine signalling ,Hedgehog ,Aged ,Cell Proliferation ,Oncogene ,Biphenyl Compounds ,Endothelial Cells ,Membrane Proteins ,Kinase insert domain receptor ,Vascular Endothelial Growth Factor Receptor-2 ,Coculture Techniques ,030104 developmental biology ,Endocrinology ,Tissue Array Analysis ,Cancer cell ,biology.protein ,Cancer research ,Translational Therapeutics ,Neoplasm Transplantation - Abstract
Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in regulating TNBC-dependent angiogenesis was investigated. Background: Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in regulating TNBC-dependent angiogenesis was investigated.Methods: Expression and regulation of the Hh pathway transcription factor glioma-associated oncogene homolog1 protein (GLI1) were studied on the endothelial compartment and on TNBC-initiated angiogenesis. To evaluate the translational relevance of our findings, the combination of paclitaxel with the Smo inhibitor NVP-LDE225 was tested in TNBC xenografted mice.Results: Tissue microarray analysis on 200 TNBC patients showed GLI1 overexpression paired with vascular endothelial growth factor receptor 2 (VEGFR2) expression. In vitro, Hh pathway promotes TNBC progression in an autocrine manner, regulating the VEGF/VEGFR2 loop on cancer cell surface, and in a paracrine manner, orchestrating tumour vascularisation. These effects were counteracted by Smo pharmacological inhibition. In TNBC xenografted mice, scheduling NVP-LDE225 rather than bevacizumab provided a better sustained inhibition of TNBC cells proliferation and endothelial cells organisation.Conclusions: This study identifies the Hh pathway as one of the main regulators of tumour angiogenesis in TNBC, thus suggesting Hh inhibition as a potential new anti-angiogenic therapeutic option to be clinically investigated in GLI1 overexpressing TNBC patients.
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- 2017
59. Molecular strategies for detecting chromosomal translocations in soft tissue tumors (Review)
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Francesca Collina, Giuseppina Liguori, Gerardo Botti, Renato Franco, Laura Marra, Margherita Cerrone, Monica Cantile, Annarosaria De Chiara, Cerrone, Margherita, Cantile, Monica, Collina, Francesca, Marra, Laura, Liguori, Giuseppina, Franco, Renato, De Chiara, Annarosaria, and Botti, Gerardo
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Soft Tissue Neoplasm ,Chromosomal translocation ,Soft Tissue Neoplasms ,Computational biology ,Biology ,soft tissue tumors ,Translocation, Genetic ,chromosomal translocations ,Genetic ,molecular analyses ,Genetics ,medicine ,Humans ,Gene ,Medicine (all) ,Molecular analyse ,Soft tissue tumor ,Cancer ,General Medicine ,Articles ,Cell cycle ,medicine.disease ,Fusion protein ,Molecular medicine ,Real-time polymerase chain reaction ,Human - Abstract
Approximately one third of soft tissue tumors are characterized by chromosomal aberrations, in particular, translocations and amplifications, which appear to be highly specific. The identification of fusion transcripts not only supports the diagnosis, but provides the basis for the development of novel therapeutic strategies aimed at blocking the aberrant activity of chimeric proteins. Molecular biology, and in particular, cytogenetic and qualitative and quantitative polymerase chain reaction technologies, allow with high efficiency and specificity, the determination of specific fusion transcripts resulting from chromosomal translocations, as well as the analysis of gene amplifications. In this review, various molecular techniques that allow the identification of translocations and consequent fusion transcripts generated are discussed in the broad spectrum of soft tissue tumors.
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- 2014
60. Expression Analysis of SPARC/Osteonectin in Oral Squamous Cell Carcinoma Patients: From Saliva to Surgical Specimen
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Francesca Collina, Francesco Longo, Gabriella Malzone, Monica Cantile, Giuseppe Pannone, Nunzia Simona Losito, Corrado Aversa, Renato Franco, Rocco Sabatino, Franco Ionna, Gabriella Aquino, Gerardo Botti, Elvira La Mantia, Aquino, Gabriella, Sabatino, Rocco, Cantile, Monica, Aversa, Corrado, Ionna, Franco, Botti, Gerardo, La Mantia, Elvira, Collina, Francesca, Malzone, Gabriella, Pannone, Giuseppe, Losito, Nunzia Simona, Franco, Renato, and Longo, Francesco
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Adult ,Male ,Salivary Proteins and Peptide ,Saliva ,Pathology ,medicine.medical_specialty ,Stromal cell ,Article Subject ,Immunology and Microbiology (all) ,lcsh:Medicine ,General Biochemistry, Genetics and Molecular Biology ,Neoplasm Protein ,Pathogenesis ,Stroma ,Retrospective Studie ,medicine ,Humans ,Osteonectin ,Neoplastic transformation ,Salivary Proteins and Peptides ,Retrospective Studies ,Aged ,Aged, 80 and over ,Mouth neoplasm ,Biochemistry, Genetics and Molecular Biology (all) ,General Immunology and Microbiology ,biology ,lcsh:R ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Mouth Neoplasm ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,Carcinoma, Squamous Cell ,biology.protein ,Mouth Neoplasms ,Female ,Research Article ,Human - Abstract
Oral squamous cell carcinoma (OSCC) remains a significant cause of morbidity and mortality, with approximately 540,000 new cases annually worldwide. The molecular mechanisms related to the pathogenesis of this disease are still poorly understood. The discovery of a molecular marker that allows the early detection of this cancer, which can be easily identified in biological samples, such as saliva, without intervening in advanced stages, is a challenge. Numerous studies have identified a panel of molecular markers differently expressed in OSCC and normal oral mucosa. In particular, it was found an aberrant expression of matricellular glycoprotein SPARC. SPARC is involved in normal tissue remodeling, regulating the deposition of extracellular matrix, but also in neoplastic transformation. In fact, aberrant SPARC expression was detected both in stromal cells associated with cancer and in tumor cells. The aim of our study was the evaluation of SPARC on a retrospective series of 119 OSCC cases and the validation of the obtained data on a prospective series of 27 patients with OSCC, of whom we have previously collected saliva, and smeared material. The obtained results were correlated with each other and with clinical pathological parameters at our disposal. The study demonstrated a prognostic value of SPARC, especially with regard to its expression in the stroma surrounding OSCC (P< 0.05).
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- 2013
61. Power Capping in High Performance Computing Systems
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Michela Milano, Michele Lombardi, Luca Benini, Francesca Collina, Andrea Borghesi, Pesant G., Borghesi, Andrea, Collina, Francesca, Lombardi, Michele, Milano, Michela, and Benini, Luca
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business.industry ,Computer science ,Heuristic (computer science) ,Computer Science (all) ,Big data ,Cloud computing ,Supercomputer ,Power budget ,Theoretical Computer Science ,Portable Batch System ,Embedded system ,Component (UML) ,business ,Efficient energy use - Abstract
Power consumption is a key factor in modern ICT infrastructure, especially in the expanding world of High Performance Computing, Cloud Computing and Big Data. Such consumption is bound to become an even greater issue as supercomputers are envisioned to enter the Exascale by 2020, granted that they obtain an order of magnitude energy efficiency gain. An important component in many strategies devised to decrease energy usage is “power capping”, i.e., the possibility to constrain the system power consumption within certain power budget. In this paper we propose two novel approaches for power capped workload dispatching and we demonstrate them on a real-life high-performance machine: the Eurora supercomputer hosted at CINECA computing center in Bologna. Power capping is a feature not included in the commercial Portable Batch System (PBS) dispatcher currently in use on Eurora. The first method is based on a heuristic technique while the second one relies on a hybrid strategy which combines a CP and a heuristic approach. Both systems are evaluated and compared on simulated job traces.
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- 2015
62. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer
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Margherita Cerrone, Maurizio Di Bonito, Monica Cantile, Valeria Li Bergolis, Francesca Collina, Gerardo Botti, Francesco Nuzzo, Michelino De Laurentiis, Carlo Vitagliano, Collina, Francesca, Di Bonito, Maurizio, Li Bergolis, Valeria, DE LAURENTIIS, Michelino, Vitagliano, Carlo, Cerrone, Margherita, Nuzzo, Francesco, Cantile, Monica, and Botti, Gerardo
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Pathology ,lcsh:Medicine ,Triple Negative Breast Neoplasms ,medicine.disease_cause ,Prevalence ,Triple-negative breast cancer ,Aged, 80 and over ,biology ,General Medicine ,Middle Aged ,Prognosis ,Italy ,Neoplastic Stem Cells ,Cytokines ,Female ,Survival Analysi ,Stem cell ,Research Article ,Human ,Adult ,medicine.medical_specialty ,Article Subject ,Prognosi ,Triple Negative Breast Neoplasm ,Reproducibility of Result ,Risk Assessment ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,Breast cancer ,Cancer stem cell ,medicine ,Biomarkers, Tumor ,Humans ,Cytokine ,Aged ,General Immunology and Microbiology ,business.industry ,CD44 ,lcsh:R ,Reproducibility of Results ,medicine.disease ,Survival Analysis ,Tumor progression ,biology.protein ,Cancer research ,Neoplastic Stem Cell ,Carcinogenesis ,business - Abstract
Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.
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- 2015
63. SPARC/osteonectin is involved in metastatic process to the lung during melanoma progression
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Margherita Cerrone, Franco Fulciniti, Annamaria Anniciello, Bruna Grilli, Giosuè Scognamiglio, Paolo A. Ascierto, Laura Marra, Francesca Collina, Gerardo Botti, Maurizio Di Bonito, Renato Franco, Monica Cantile, Botti, Gerardo, Scognamiglio, Giosuè, Marra, Laura, Collina, Francesca, Di Bonito, Maurizio, Cerrone, Margherita, Grilli, Bruna, Anniciello, Annamaria, Franco, Renato, Fulciniti, Franco, Ascierto, Paolo Antonio, and Cantile, Monica
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Biology ,Pathology and Forensic Medicine ,Metastasis ,Melanoma progression ,medicine ,Humans ,Neoplastic transformation ,Osteonectin ,Molecular Biology ,Melanoma ,Aged ,Tissue microarray ,Medicine (all) ,SPARC expression ,Cancer ,Lung metastase ,General Medicine ,Cell Biology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Metastasis Gene ,Lung Neoplasm ,Cancer cell ,biology.protein ,Disease Progression ,Female ,Human - Abstract
The existence of a "metastasis gene signature" that predisposes primary breast cancer cells to metastasize to the lungs has been recently highlighted by gene expression profiling studies. The combination of genes responsible for this process includes genes encoding several metalloproteinases as well as the gene encoding SPARC (secreted protein acidic and rich in cysteine)/osteonectin. SPARC is involved in normal tissue remodeling as it regulates the deposition of extracellular matrix, but also plays a role in neoplastic transformation. Aberrant SPARC expression has been detected both in stromal cells associated with cancer and in cancer cells. The main aim of this study was to investigate whether or not SPARC might be involved in directing metastasis of other types of cancer to the lung. We constructed a tissue microarray containing lung metastases from a variety of primary tumors in different organs and used immunohistochemistry to assess SPARC expression. We found SPARC overexpressed mainly in lung metastases from melanoma. We then assessed the expression of SPARC mRNA and protein in metastatic melanoma from different anatomic sites and in their corresponding primary tumors, and found that it is overexpressed in lung metastases. Our data strongly support the hypothesis that SPARC is involved in directing melanoma metastases specifically to the lung, which underpins its potential as prognostic marker and novel target for specific therapy.
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- 2014
64. Tissue micro arrays for immunohistochemical detection of inflammatory infiltrates in renal cell carcinoma
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Scognamiglio, G., Cantile, M., Scala, S., Cecere, S., Russo, F., Collina, F., LAURA MARRA, Sabbatino, F., Botti, G., Franco, R., Scognamiglio, Giosuè, Cantile, Monica, Scala, Stefania, Cecere, Sabrina, Russo, Federica, Collina, Francesca, Marra, Laura, Sabbatino, Francesco, Botti, Gerardo, and Franco, Renato
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Genetics and Molecular Biology (all) ,Histology ,Medicine (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Biochemistry - Published
- 2014
65. Inadequacy of tissue microarrays for the immunohistochemical detection of cancer stem cells in solid tumors: a viewpoint
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Gerardo Botti, Giosuè Scognamiglio, Monica Cantile, Renato Franco, Francesca Collina, Maurizio Di Bonito, Cantile, Monica, Collina, Francesca, Scognamiglio, Giosuè, Di Bonito, Maurizio, Franco, Renato, and Botti, Gerardo
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Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Biology ,medicine.disease_cause ,Antineoplastic Agent ,Cancer stem cell ,Neoplasms ,medicine ,Humans ,Pharmacology (medical) ,Chemotherapy ,Tissue microarray ,Immunohistochemistry ,Treatment Outcome ,Oncology ,Drug Resistance, Neoplasm ,Tissue Array Analysis ,Neoplastic Stem Cells ,Tumor Stem Cells ,Neoplasm ,Neoplastic Stem Cell ,Carcinogenesis ,Tissue Array Analysi ,Human - Abstract
Pathology Unit, Istituto Nazionale Tumori Fondazione “G. Pascale”, via Mariano Semmola 80131, Napoli, Italy “Recent acquisitions on human carcinogenesis suggest that small populations of tumor stem cells can influence and modify neoplastic cells behavior and aggressiveness, as well as therapeutic response. In fact, the presence of cancer stem cells niches results in a poor sensitivity to current chemotherapy treatments.”
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- 2013
66. Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5
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Claudia Miele, Gerardo Botti, Pietro Campiglia, Maurizio Di Bonito, Rossella Valentino, Maria Rosaria Ambrosio, Domenico Liguoro, Francesco Beguinot, Rosa Spinelli, Renato Franco, Monica Cantile, Vittoria D'Esposito, Pietro Formisano, Francesca Collina, Gregory Alexander Raciti, Michelino De Laurentiis, D'Esposito, V, Liguoro, D, Ambrosio, Mr, Collina, Anna, Cantile, M, Spinelli, R, Raciti, Ga, Miele, C, Valentino, R, Campiglia, P, De Laurentiis, M, Di Bonito, M, Botti, G, Franco, R, Beguinot, F, Formisano, P, D'Esposito, Vittoria D., Liguoro, Domenico, Ambrosio, Maria Rosaria, Collina, Francesca, Cantile, Monica, Spinelli, Rosa, Raciti, Gregory Alexander, Miele, Claudia, Valentino, Rossella, Campiglia, Pietro, De Laurentiis, Michelino, Bonito, Maurizio Di, Botti, Gerardo, Franco, Renato, Beguinot, Francesco, and Formisano, Pietro
- Subjects
0301 basic medicine ,Adult ,Pathology ,medicine.medical_specialty ,Breast surgery ,medicine.medical_treatment ,Adipose tissue ,Triple Negative Breast Neoplasms ,Kaplan-Meier Estimate ,Diabete ,CCL5 ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Adipocytes ,Humans ,Neoplasm Invasiveness ,Triple negative breast cancer ,Obesity ,Lymph node ,Chemokine CCL5 ,Cytokine ,Triple-negative breast cancer ,Cancer prevention ,business.industry ,Diabetes ,Middle Aged ,medicine.disease ,Coculture Techniques ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Cellular Microenvironment ,Oncology ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Cancer cell ,Cancer research ,MCF-7 Cells ,Cytokines ,Female ,business ,Research Paper - Abstract
// Vittoria D'Esposito 1 , Domenico Liguoro 1 , Maria Rosaria Ambrosio 1 , Francesca Collina 2 , Monica Cantile 2 , Rosa Spinelli 1 , Gregory Alexander Raciti 1 , Claudia Miele 1 , Rossella Valentino 1 , Pietro Campiglia 3 , Michelino De Laurentiis 4 , Maurizio Di Bonito 2 , Gerardo Botti 2 , Renato Franco 2 , Francesco Beguinot 1 , Pietro Formisano 1 1 Department of Translational Medicine, Federico II University of Naples and URT “Genomic of Diabetes” of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy 2 Pathology Unit, National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy 3 Department of Pharmacy, University of Salerno, Salerno, Italy 4 Department of Breast Surgery and Cancer Prevention; National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy Correspondence to: Pietro Formisano, e-mail: fpietro@unina.it Keywords: triple negative breast cancer, adipose tissue, cytokines, diabetes, obesity Received: August 05, 2015 Accepted: February 28, 2016 Published: March 24, 2016 ABSTRACT Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination. Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node ( p -value = 0.04) and distant metastases ( p -value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients ( p -value = 0.039). Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC.
67. BCL10 expression and localization in Ocular Adnexa MALT lymphomas: A comparative cytogenetic and immunohistochemical study
- Author
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Margherita Cerrone, Collina, F., Chiara, A., Corazzelli, G., Pia Curcio, M., Renzo, A., Russo, F., Cantile, M., Staibano, S., Strianese, D., Tranfa, F., Botti, G., Rosa, G., Franco, R., Cerrone, Margherita, Collina, Francesca, De Chiara, Anna, Corazzelli, Gaetano, Pia Curcio, Maria, De Renzo, Amalia, Russo, Filippo, Cantile, Monica, Staibano, Stefania, Strianese, Diego, Tranfa, Fausto, Botti, Gerardo, De Rosa, Gaetano, Franco, Renato, Cerrone, M, Collina, F, De Chiara, A, Corazzelli, G, Curcio, Mp, De Renzo, A, Russo, F, Cantile, M, Strianese, D, Botti, G, De Rosa, G, and Franco, R.
- Subjects
Ocular adnexal B-cell lymphoma ,Histology ,6 - Ciencias aplicadas::61 - Medicina [CDU] ,Genetic aberration ,immune system diseases ,hemic and lymphatic diseases ,MALT lymphoma ,BCL10 - Abstract
Summary. T(1;14) (p22;q32) involving BCL10 and IGH genes is a rare but recurrent chromosomal aberration in MALT-type lymphoma. It is rarely described in ocular adnexa B cell lymphomas, although nuclear BCL10 shuttling seems to be critical for disease progression in this district. We have evaluated the translocations MALT lymphoma-related in a series of 45 ocular adnexa cases, focusing in particular on their relation with BCL10 expression and its cellular topographic distribution. A prognostic tissue microarray (TMA) with ocular adnexa MALT lymphomas was designed. A study of BCL10 expression and its topographic distribution was performed through immunohistochemistry. In addition the assessment of t(14;18) (q32;q21), t(1;14) (p22;q32) and t(11;18) (q21;q21) was determined by Fluorescent In Situ Hybridization (FISH). Our series revealed t(14;18) (q32;q21) in 6/43 cases (14,3%). t(1;14) (p22;q32), never described in ocular adnexa MALT lymphomas, was observed in 3/31 (9,7%), two of which exhibited the gain of 3’ upstream BCL10 gene signal (4%), whereas no case showed t(11;18) (q21;q21). Moreover, BCL10 expression was observed in 18/45 cases. In particular its nuclear expression was revealed in 12/45 cases, cytoplasmic expression in 5/45 and both cytoplasmic and nuclear expression in 1/45. Statistical analysis demonstrated that while BCL10 cytoplasmic expression is significantly related to the presence of the investigated chromosomal aberrations, in particular with t(14;18) (q32;q21), BCL10 nuclear shuttling does not show any correlation with these translocations. Our data support that BCL10 nuclear distribution is neither related to BCL10 rearrangement nor to other known translocations.
68. Case report & review: Bilateral NIFTP harboring concomitant HRAS and KRAS mutation: Report of an unusual case and literature review.
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Brogna MR, Collina F, Chiofalo MG, De Bartolo D, Montone A, Schiano MR, Del Sesto M, Pizza N, and Ferrara G
- Abstract
Diagnosis and treatment of thyroid disease are affected by the wide range of thyroid cancer subtypes and their varying degrees of aggressiveness. To better describe the indolent nature of thyroid neoplasms previously classified as noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC), the Endocrine Pathology Society working group has recently coined the term "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). The purpose of this nomenclature change is to avoid patients the distress of cancer diagnosis and to decrease the overtreatment of thyroid nodules with a RAS-LIKE molecular profile similar to follicular adenoma. Consequently, the reclassification has a significant impact on thyroid nodule clinical care as well as histopathologic and cytopathologic diagnosis. This paper will focus on a unique case of Bilateral NIFTP harboring concomitant HRAS and KRAS mutation; we will also review the background, molecular features, and clinical implications of NIFTP as well as the factors behind the nomenclature update. It also seemed helpful to emphasize the impact of NIFTP on clinical practice to avoid overtreating nodules that could be safely managed with lobectomy alone. Actually, despite the diagnosis is postsurgery, a comprehensive preoperative evaluation may raise a suspicion of NIFTP and suggest a more careful plan for treatment. Here, we present a unique case of bilateral NIFTP after total thyroidectomy; subsequent molecular analysis revealed that the patient's right nodule harbored an isolated p.(Q61K) HRAS mutation, while the left a p.(Q61K) KRAS mutation. To the best of our knowledge, this is the first case report of this nature. The existence of simultaneous mutations highlights the occurrence of intratumoral heterogeneity (ITH) also in the context of FVPTC, which requires comprehensive investigation. The available information shows that NIFTP, identified in accordance with stringent inclusion and exclusion criteria, exhibits a very latent clinical behavior even in the face of conservative lobectomy, lacking of radioactive iodine therapy. However, it cannot be regarded as a benign lesion because there is a small but significant incidence of adverse events, such as lymph nodes and distant metastases. Currently, NIFTP can only be suspected before surgery: several efforts could be explored to identify key molecular, cytological, and ultrasonographic traits that may be helpful in raising the possibility of NIFTP in the preoperative context. Additionally, our discovery of simultaneous mutations within the same lesion strengthens the evidence of ITH even in FVPTC. Although the extent and biological impact of this phenomenon in NIFTP are still debated, a deeper understanding is essential to ensure appropriate clinical management., (© 2024 The Author(s). Molecular Carcinogenesis published by Wiley Periodicals LLC.)
- Published
- 2024
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69. Concomitant BRAF V600E and NRAS Q61R mutations in the same thyroid nodule: a case report.
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Brogna M, Collina F, Losito S, Clery E, Montone A, DelSesto M, and Ferrara G
- Abstract
Background: Papillary thyroid cancer (PTC) is the most common type of well-differentiated endocrine malignancy. Generally, thyroid nodules with multiple oncogenic mutations are uncommon with an occurrence which may be related to more aggressive biological behavior of tumors. RET/PTC rearrangement, RAS, and BRAF mutations are considered to be mutually exclusive in PTC. Concomitant RET/PTC, RAS, or BRAF mutations have been documented, although the impact of these mutations for tumor growth and survival is debated., Case Description: Here we present a rare case of woman 46 years old with a neck mass and thyroid nodule classified as TIR5 on cytological examination. We found contemporary BRAF p.(Val600Glu) [p.(V600E); c.1799T>A] and NRAS p.(Gln61Arg) [p.(Q61R); c.182A>G] mutations in morphologically different areas within the same lobe (the right one); The two lesions show different morphology. The mutated BRAF lesion showed morphological characteristics compatible with classic papillary carcinoma. The mutant NRAS lesion shows morphological features compatible with follicular variant papillary carcinoma. To the best of our knowledges, this is the first time that such mutations, which are normally mutually exclusive, have been detected at the same time., Conclusions: The finding of synchronous mutations is a rare occurrence suggesting for intratumoral heterogeneity (ITH) even in PTC. Patients with multiple mutations have a clinical worse prognosis, generally characterized by an aggressive thyroid cancer, which may influence the surgical treatment, chemotherapy, and BRAF V600E mutation-targeting therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-83/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)
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- 2024
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70. Prune-1 drives polarization of tumor-associated macrophages (TAMs) within the lung metastatic niche in triple-negative breast cancer.
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Ferrucci V, Asadzadeh F, Collina F, Siciliano R, Boccia A, Marrone L, Spano D, Carotenuto M, Chiarolla CM, De Martino D, De Vita G, Macrì A, Dassi L, Vandenbussche J, Marino N, Cantile M, Paolella G, D'Andrea F, di Bonito M, Gevaert K, and Zollo M
- Abstract
M2-tumor-associated macrophages (M2-TAMs) in the tumor microenvironment represent a prognostic indicator for poor outcome in triple-negative breast cancer (TNBC). Here we show that Prune-1 overexpression in human TNBC patients has positive correlation to lung metastasis and infiltrating M2-TAMs. Thus, we demonstrate that Prune-1 promotes lung metastasis in a genetically engineered mouse model of metastatic TNBC augmenting M2-polarization of TAMs within the tumor microenvironment. Thus, this occurs through TGF-β enhancement, IL-17F secretion, and extracellular vesicle protein content modulation. We also find murine inactivating gene variants in human TNBC patient cohorts that are involved in activation of the innate immune response, cell adhesion, apoptotic pathways, and DNA repair. Altogether, we indicate that the overexpression of Prune-1, IL-10, COL4A1, ILR1, and PDGFB, together with inactivating mutations of PDE9A, CD244, Sirpb1b, SV140, Iqca1, and PIP5K1B genes, might represent a route of metastatic lung dissemination that need future prognostic validations., Competing Interests: All the authors declare no competing financial interests., (© 2020 The Author(s).)
- Published
- 2020
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71. Molecular characterization of a bladder pleomorphic rhabdomyosarcoma in an adult patient.
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Feroce F, Cantile M, Aquino G, Collina F, Scognamiglio G, Castaldo L, Perdonà S, Botti G, and De Chiara A
- Subjects
- 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
- 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2020
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72. Downregulation of androgen receptor is strongly associated with diabetes in triple negative breast cancer patients.
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Collina F, Cerrone M, Peluso V, Laurentiis MD, Caputo R, Cecio RD, Liguori G, Botti G, Cantile M, and Bonito MD
- Abstract
Developing of personalized therapies for Triple Negative Breast Cancer (TNBC) requires a more detailed knowledge of its biology and a correct stratification of molecular subtypes. Androgen Receptor (AR) is expressed in a large part of TNBCs but its prognostic role in this Breast Cancer (BC) subtype is highly debated. In this study, we analyzed AR expression in a series of 238 TNBCs and correlated its expression with clinical-pathological features, survival, and metabolic profile. We showed a consistent association between AR expression and a better prognosis of TNBC patients, while its downregulation appeared strongly associated with diabetic disease. Since a recent prospective study reported a lower BC risk in diabetic women treated with drugs able to reduce circulating levels of glucose compared with non-diabetic woman, and in vitro studies showed that AR level are regulated directly by hyperglycemia, we speculate on the perspective of new integrated therapies for TNBC.
- Published
- 2016
73. Deregulation of paralogous 13 HOX genes in oral squamous cell carcinoma.
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Aquino G, Franco R, Sabatino R, Mantia EL, Scognamiglio G, Collina F, Longo F, Ionna F, Losito NS, Liguori G, Botti G, and Cantile M
- Abstract
Many oncogenic drivers related to the pathogenesis of OSCC have identified, but the discovery of new molecular markers for early detection of this cancer, remains one the main goals of clinical research. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have demonstrated that the deregulation of HOX genes play a significant role in cancer development and progression. In this study, we built a prognostic TMA with 119 OSCC samples, representative of deep and superficial part of the tumour, to investigate, the paralogous 13 HOX proteins expression, correlating them with clinicpathological parameters, outcomes and therapy information. Our results show an aberrant expression of HOX A13 and HOX D13 in OSCC pathogenesis and tumour progression. HOX A13 overexpression is related to an OSCC better prognosis (P=0.029) and better therapy response in patients treated with both radiotherapy and chemotherapy (P=0.015). HOX D13 overexpression is inversely related to an overall survival (P=0.004). These data highlight the potential prognostic role of HOX paralogous group 13 genes in OSCC.
- Published
- 2015
74. HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer.
- Author
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Franco R, Collina F, Di Bonito M, Botti G, Montanaro D, Di Maio L, Vincenzi B, Landi G, D'Aiuto M, Caraglia M, and Baldi A
- Subjects
- Adult, Aged, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Female, High-Temperature Requirement A Serine Peptidase 1, Humans, Lymph Nodes pathology, Lymphatic Metastasis pathology, Middle Aged, Prognosis, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Sentinel Lymph Node Biopsy, Breast Neoplasms metabolism, Carcinoma, Ductal, Breast metabolism, Lymph Nodes metabolism, Neoplasm Invasiveness pathology, Serine Endopeptidases metabolism
- Abstract
Aim: HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients., Subjects and Methods: We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology., Results: HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001)., Conclusions: Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.
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- 2015
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75. Tissue micro arrays for immunohistochemical detection of inflammatory infiltrates in renal cell carcinoma.
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Scognamiglio G, Cantile M, Scala S, Cecere S, Russo F, Collina F, Marra L, Sabbatino F, Botti G, and Franco R
- Published
- 2014
76. BCL10 expression and localization in ocular adnexa MALT lymphomas: a comparative cytogenetic and immunohistochemical study.
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Cerrone M, Collina F, De Chiara A, Corazzelli G, Curcio MP, De Renzo A, Russo F, Cantile M, Staibano S, Strianese D, Tranfa F, Botti G, De Rosa G, and Franco R
- Subjects
- Adaptor Proteins, Signal Transducing biosynthesis, Adult, Aged, B-Cell CLL-Lymphoma 10 Protein, Biomarkers, Tumor analysis, Cytogenetic Analysis, Eye Neoplasms pathology, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Lymphoma, B-Cell, Marginal Zone pathology, Male, Middle Aged, Tissue Array Analysis, Translocation, Genetic, Eye Neoplasms genetics, Eye Neoplasms metabolism, Lymphoma, B-Cell, Marginal Zone genetics, Lymphoma, B-Cell, Marginal Zone metabolism
- Abstract
T(1;14) (p22;q32) involving BCL10 and IGH genes is a rare but recurrent chromosomal aberration in MALT-type lymphoma. It is rarely described in ocular adnexa B cell lymphomas, although nuclear BCL10 shuttling seems to be critical for disease progression in this district. We have evaluated the translocations MALT lymphoma-related in a series of 45 ocular adnexa cases, focusing in particular on their relation with BCL10 expression and its cellular topographic distribution. A prognostic tissue microarray (TMA) with ocular adnexa MALT lymphomas was designed. A study of BCL10 expression and its topographic distribution was performed through immunohistochemistry. In addition the assessment of t(14;18) (q32;q21), t(1;14) (p22;q32) and t(11;18) (q21;q21) was determined by Fluorescent In Situ Hybridization (FISH). Our series revealed t(14;18) (q32;q21) in 6/43 cases (14,3%). t(1;14) (p22;q32), never described in ocular adnexa MALT lymphomas, was observed in 3/31 (9,7%), two of which exhibited the gain of 3' upstream BCL10 gene signal (4%), whereas no case showed t(11;18) (q21;q21). Moreover, BCL10 expression was observed in 18/45 cases. In particular its nuclear expression was revealed in 12/45 cases, cytoplasmic expression in 5/45 and both cytoplasmic and nuclear expression in 1/45. Statistical analysis demonstrated that while BCL10 cytoplasmic expression is significantly related to the presence of the investigated chromosomal aberrations, in particular with t(14;18) (q32;q21), BCL10 nuclear shuttling does not show any correlation with these translocations. Our data support that BCL10 nuclear distribution is neither related to BCL10 rearrangement nor to other known translocations.
- Published
- 2014
- Full Text
- View/download PDF
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