39 results on '"Masciale, Valentina"'
Search Results
2. The importance of medical treatment before surgery in pleomorphic carcinoma of the lung: A case series study
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Tormen, Francesco, Banchelli, Federico, Masciale, Valentina, Maiorana, Antonino, Morandi, Uliano, and Aramini, Beatrice
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- 2021
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3. Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study.
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Samarelli, Anna Valeria, Tonelli, Roberto, Raineri, Giulia, Mastrolia, Ilenia, Costantini, Matteo, Fabbiani, Luca, Catani, Virginia, Petrachi, Tiziana, Bruzzi, Giulia, Andrisani, Dario, Gozzi, Filippo, Marchioni, Alessandro, Masciale, Valentina, Aramini, Beatrice, Ruggieri, Valentina, Grisendi, Giulia, Dominici, Massimo, Cerri, Stefania, and Clini, Enrico
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LUNGS ,PULMONARY fibrosis ,IDIOPATHIC pulmonary fibrosis ,PROOF of concept ,GENE families ,LUNG cancer ,INTERSTITIAL lung diseases - Abstract
Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Proteomic profiling of formalin-fixed paraffine-embedded tissue reveals key proteins related to lung dysfunction in idiopathic pulmonary fibrosis.
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Samarelli, Anna Valeria, Tonelli, Roberto, Raineri, Giulia, Bruzzi, Giulia, Andrisani, Dario, Gozzi, Filippo, Marchioni, Alessandro, Costantini, Matteo, Fabbiani, Luca, Genovese, Filippo, Pinetti, Diego, Manicardi, Linda, Castaniere, Ivana, Masciale, Valentina, Aramini, Beatrice, Tabbì, Luca, Rizzato, Simone, Bettelli, Stefania, Manfredini, Samantha, and Dominici, Massimo
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IDIOPATHIC pulmonary fibrosis ,PULMONARY fibrosis ,PROTEOMICS ,LIQUID chromatography-mass spectrometry ,TRANSFORMING growth factors ,LUNGS ,FOCAL adhesions - Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues. Methods: We further determined the protein expression according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins. Results: After the pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor b (TGF-b) signaling pathways strongly associated with IPF onset and progression. Five proteins were significantly over-expressed in the lung of IPF patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLCO<55) compared to controls; thesewere lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan (OGN) thatmight play a key role in the fibrogenic processes. Discussion: Our work showed that the analysis of FFPE samples was able to identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or involved in the immune landscape of lung cancer, thusmaking possible commonmechanisms between lung carcinogenesis and fibrosis progression, two pathological conditions at risk for each other in the real life. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Author Correction: A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
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Candini, Olivia, Grisendi, Giulia, Foppiani, Elisabetta Manuela, Brogli, Matteo, Aramini, Beatrice, Masciale, Valentina, Spano, Carlotta, Petrachi, Tiziana, Veronesi, Elena, Conte, Pierfranco, Mari, Giorgio, and Dominici, Massimo
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- 2020
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6. A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
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Candini, Olivia, Grisendi, Giulia, Foppiani, Elisabetta Manuela, Brogli, Matteo, Aramini, Beatrice, Masciale, Valentina, Spano, Carlotta, Petrachi, Tiziana, Veronesi, Elena, Conte, Pierfranco, Mari, Giorgio, and Dominici, Massimo
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- 2019
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7. Chasing the Role of miRNAs in RCC: From Free-Circulating to Extracellular-Vesicle-Derived Biomarkers.
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Mastrolia, Ilenia, Catani, Virginia, Oltrecolli, Marco, Pipitone, Stefania, Vitale, Maria Giuseppa, Masciale, Valentina, Chiavelli, Chiara, Bortolotti, Carlo Augusto, Nasso, Cecilia, Grisendi, Giulia, Sabbatini, Roberto, and Dominici, Massimo
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MICRORNA ,RENAL cell carcinoma ,MINIMALLY invasive procedures ,NON-coding RNA ,EXTRACELLULAR vesicles ,CIRCULATING tumor DNA ,PROGRAMMED cell death 1 receptors - Abstract
Simple Summary: Renal cell carcinoma (RCC) is the most common type of kidney cancer. The therapeutic strategies are based on surgery and/or specific therapies able to inhibit growth factors that have been shown to promote the growth and spread of tumors. Currently, there is no established biomarker which helps in early diagnosis and in better disease monitoring with a high sensitivity. Much information could be provided by body fluids, especially blood liquid biopsy (LB), that are increasingly interesting to researchers. LB is a non- or minimally invasive procedure that could allow clinicians to monitor cancer evolution, also thanks to the presence of small vesicles known as extracellular vesicles (EVs) secreted by tumor cells and containing useful information. In particular, growing interest is focused on small RNA molecules (miRNAs) that are involved in tumor growth and could represent potential diagnostic, prognostic, and predictive biomarkers in RCC, as we summarize in this review. Renal cell carcinoma (RCC) is the second most common cancer of the urinary system. The current therapeutic strategies are based on partial or total nephrectomy and/or targeted therapies based on immune checkpoint inhibitors to which patients are often refractory. Preventive and screening strategies do not exist and the few available biomarkers for RCC are characterized by a lack of sensitivity, outlining the need for novel noninvasive and sensitive biomarkers for early diagnosis and better disease monitoring. Blood liquid biopsy (LB) is a non- or minimally invasive procedure for a more representative view of tumor heterogeneity than a tissue biopsy, potentially allowing the real-time monitoring of cancer evolution. Growing interest is focused on the extracellular vesicles (EVs) secreted by either healthy or tumoral cells and recovered in a variety of biological matrices, blood included. EVs are involved in cell-to-cell crosstalk transferring their mRNAs, microRNAs (miRNAs), and protein content. In particular, transferred miRNAs may regulate tumorigenesis and proliferation also impacting resistance to apoptosis, thus representing potential useful biomarkers. Here, we present the latest efforts in the identification of circulating miRNAs in blood samples, focusing on the potential use of EV-derived miRNAs as RCC diagnostic and prognostic markers. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development
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Samarelli, Anna Valeria, Masciale, Valentina, Aramini, Beatrice, Coló, Georgina Pamela, Tonelli, Roberto, Marchioni, Alessandro, Bruzzi, Giulia, Gozzi, Filippo, Andrisani, Dario, Castaniere, Ivana, Manicardi, Linda, Moretti, Antonio, Tabbì, Luca, Guaitoli, Giorgia, Cerri, Stefania, Dominici, Massimo, and Clini, Enrico
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Lung Neoplasms ,cancer associated fibroblasts (CAFs) ,QH301-705.5 ,CAFs ,Review ,respiratory system ,idiopathic pulmonary fibrosis ,lung cancer ,myofibroblast ,mechanotrasduction ,Mechanotransduction, Cellular ,respiratory tract diseases ,Transforming Growth Factor beta1 ,Chemistry ,Animals ,Humans ,Biology (General) ,Myofibroblasts ,QD1-999 - Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2-4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.
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- 2021
9. Editorial: Innovations in surgical oncology.
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Aramini, Beatrice, Masciale, Valentina, and van Vugt, Jeroen L. A.
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ONCOLOGIC surgery ,MINIMALLY invasive procedures - Published
- 2023
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10. The sternum reconstruction: Present and future perspectives.
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Aramini, Beatrice, Masciale, Valentina, Radaelli, Lorenzo Federico Zini, Sgarzani, Rossella, Dominici, Massimo, and Stella, Franco
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STERNUM ,HOMOGRAFTS ,MESENCHYMAL stem cells - Abstract
Sternectomy is a procedure mainly used for removing tumor masses infiltrating the sternum or treating infections. Moreover, the removal of the sternum involves the additional challenge of performing a functional reconstruction. Fortunately, various approaches have been proposed for improving the operation and outcome of reconstruction, including allograft transplantation, using novel materials, and developing innovative surgical approaches, which promise to enhance the quality of life for the patient. This review will highlight the surgical approaches to sternum reconstruction and the new perspectives in the current literature. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Biological effects of COVID-19 on lung cancer: Can we drive our decisions.
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Aramini, Beatrice, Masciale, Valentina, Samarelli, Anna Valeria, Tonelli, Roberto, Cerri, Stefania, Clini, Enrico, Stella, Franco, and Dominici, Massimo
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COVID-19 ,CANCER cell proliferation ,LUNG cancer ,CANCER invasiveness ,COVID-19 treatment - Abstract
COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although the consequences of this infection are not fully clear, it causes damage to the lungs, the cardiovascular and nervous systems, and other organs, subsequently inducing organ failure. In particular, the effects of SARS-CoV-2-induced inflammation on cancer cells and the tumor microenvironment need to be investigated. COVID-19 may alter the tumor microenvironment, promoting cancer cell proliferation and dormant cancer cell (DCC) reawakening. DCCs reawakened upon infection with SARS-CoV-2 can populate the premetastatic niche in the lungs and other organs, leading to tumor dissemination. DCC reawakening and consequent neutrophil and monocyte/macrophage activation with an uncontrolled cascade of proinflammatory cytokines are the most severe clinical effects of COVID-19. Moreover, neutrophil extracellular traps have been demonstrated to activate the dissemination of premetastatic cells into the lungs. Further studies are warranted to better define the roles of COVID-19 in inflammation as well as in tumor development and tumor cell metastasis; the results of these studies will aid in the development of further targeted therapies, both for cancer prevention and the treatment of patients with COVID-19. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Use of Octreotide in association with talc poudrage for the management of a severe chylothorax: A case report
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Lovati, Eleonora, Ruggiero, Ciro, Masciale, Valentina, Stefani, Alessandro, Morandi, Uliano, Aramini, Beatrice, Eleonora Lovati, Ciro Ruggiero, Valentina Masciale, Alessandro Stefani, Uliano Morandi, and Beatrice Aramini
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Case report ,Octreotide, talc poudrage, management, chylothorax ,Surgery ,Octreotide ,Chylothorax ,Conservative treatment ,Talc poudrage - Abstract
Highlights • Chylothorax is an uncommon form of benign pleural effusion. • It may have poor prognosis if not properly treated. • Conservative measures are the first line of treatment for managing chylothorax. • Surgery is considered an option for recurrent chylothorax. • In our recurrent case, octreotide plus talc poudrage was effective., Introduction and importance Chylothorax is an uncommon form of pleural effusion characterized by the presence of chylomicrons, triglycerides and cholesterol in the physical and chemical examination of the pleural fluid. It may have poor prognosis if not properly treated. Currently, conservative measures are the first line of treatment for managing chylothorax. The aim of our study is to show and suggest the use of octreotide in association with talc poudrage as good option to manage post-operative a severe chylothorax. Case presentation A 59-year-old male patient who underwent a replacement of the ascending aorta, aortic hemiarch and surgery of the aortic valve for aortic dissection showed a severe pleural effusion three months after surgery. Because the physical and chemical examination of the pleural fluid revealed high levels of triglycerides and cholesterol, a conservative treatment with pleural drainage, TPN and nihil per os was attempted, with the introduction of 0.3 mg/die of octreotide on day thirty-four. With the application of talc poudrage, the chylothorax completely resolved. Clinical discussion Octreotide has been shown to significantly decrease chylous effusion in many studies, but the dose and duration of therapy have not yet been defined. Our patient responded partially to octreotide after two days of treatment, with the drainage leak reduced to less than 100 mL/day. Conclusion After octreotide treatment associated with talc poudrage, the drainage leak was drastically reduced, suggesting that this could be a useful approach in the management of severe chylous leaks.
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- 2021
13. Cancer stem cells and macrophages: molecular connections and future perspectives against cancer
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Aramini, Beatrice, Masciale, Valentina, Grisendi, Giulia, Banchelli, Federico, D'Amico, Roberto, Maiorana, Antonino, Morandi, Uliano, Dominici, Massimo, Khawaja Husnain Haider, Beatrice Aramini, Valentina Masciale, Giulia Grisendi, Federico Banchelli, Roberto D’Amico, Antonino Maiorana, Uliano Morandi, Massimo Dominici, and Khawaja Husnain Haider
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cancer stem cells ,future perspectives ,Cancer stem cells ,Macrophage ,Macrophages ,Cancer stem cell ,Cancer ,Future perspectives ,Target treatments ,Review ,macrophages ,Future perspective - Abstract
Cancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs between these two cell types. The aim of this review is to define the complex crosstalk between these two cell types and to highlight potential future anti-cancer strategies.
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- 2021
14. CRISPR-mediated genome editing to redirect T cells against Non-Small Cell Lung Cancer
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Benati, Daniela, Masciale, Valentina, Grisendi, Giulia, Ferrari, Tommaso, Cattin, Eleonora, Marchionni, Matteo, Aramini, Beatrice, Dominici, Massimo, and Recchia, Alessandra
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- 2021
15. Phenotypic, functional, and metabolic heterogeneity of immune cells infiltrating non-small cell lung cancer.
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Aramini, Beatrice, Masciale, Valentina, Samarelli, Anna Valeria, Dubini, Alessandra, Gaudio, Michele, Stella, Franco, Morandi, Uliano, Dominici, Massimo, De Biasi, Sara, Gibellini, Lara, and Cossarizza, Andrea
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NON-small-cell lung carcinoma ,CANCER stem cells ,MYELOID cells ,PHENOTYPES ,LUNG cancer - Abstract
Lung cancer is the leading cancer in the world, accounting for 1.2 million of new cases annually, being responsible for 17.8% of all cancer deaths. In particular, non-small cell lung cancer (NSCLC) is involved in approximately 85% of all lung cancers with a high lethality probably due to the asymptomatic evolution, leading patients to be diagnosed when the tumor has already spread to other organs. Despite the introduction of new therapies, which have improved the long-term survival of these patients, this disease is still not well cured and under controlled. Over the past two decades, single-cell technologies allowed to deeply profile both the phenotypic and metabolic aspects of the immune cells infiltrating the TME, thus fostering the identification of predictive biomarkers of prognosis and supporting the development of new therapeutic strategies. In this review, we discuss phenotypic and functional characteristics of the main subsets of tumorinfiltrating lymphocytes (TILs) and tumor-infiltrating myeloid cells (TIMs) that contribute to promote or suppress NSCLC development and progression. We also address two emerging aspects of TIL and TIM biology, i.e., their metabolism, which affects their effector functions, proliferation, and differentiation, and their capacity to interact with cancer stem cells. [ABSTRACT FROM AUTHOR]
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- 2022
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16. Cancer Stem Cells and Cell Cycle Genes as Independent Predictors of Relapse in Non-small Cell Lung Cancer: Secondary Analysis of a Prospective Study.
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Masciale, Valentina, Banchelli, Federico, Grisendi, Giulia, D'Amico, Roberto, Maiorana, Antonino, Stefani, Alessandro, Morandi, Uliano, Stella, Franco, Dominici, Massimo, and Aramini, Beatrice
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- 2022
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17. Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments.
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Aramini, Beatrice, Masciale, Valentina, Arienti, Chiara, Dominici, Massimo, Stella, Franco, Martinelli, Giovanni, and Fabbri, Francesco
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CANCER chemotherapy , *FIBROBLASTS , *METASTASIS , *CELLULAR signal transduction , *TREATMENT effectiveness , *CANCER patients , *STEM cells , *TUMOR markers , *DRUG resistance in cancer cells - Abstract
Simple Summary: The world of small molecules in solid tumors as cancer stem cells (CSCs), circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) continues to be under-debated, but not of minor interest in recent decades. One of the main problems in regard to cancer is the development of tumor recurrence, even in the early stages, in addition to drug resistance and, consequently, ineffective or an incomplete response against the tumor. The findings behind this resistance are probably justified by the presence of small molecules such as CSCs, CTCs and CAFs connected with the tumor microenvironment, which may influence the aggressiveness and the metastatic process. The mechanisms, connections, and molecular pathways behind them are still unknown. Our review would like to represent an important step forward to highlight the roles of these molecules and the possible connections among them. The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network among them and the tumor microenvironment. In particular, cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment with different functions, including matrix deposition and remodeling, extensive reciprocal signaling interactions with cancer cells and crosstalk with immunity. The settings of new markers and the definition of the molecular connections may present new avenues, not only for fighting cancer but also for the definition of more tailored therapies. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study.
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Masciale, Valentina, Banchelli, Federico, Grisendi, Giulia, D'Amico, Roberto, Maiorana, Antonino, Stefani, Alessandro, Morandi, Uliano, Stella, Franco, Dominici, Massimo, and Aramini, Beatrice
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- 2022
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19. Challenging the efficacy of checkpoint inhibitors: a new 3D model for a precision medicine approach
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Elisabetta Manuela Foppiani, Olivia Candini, Beatrice Aramini, MASCIALE, VALENTINA, Giulia Grisendi, Matteo Brogli, Giorgio Mari, Massimo Dominici., Elisabetta Manuela Foppiani, Olivia Candini, Beatrice Aramini, MASCIALE, VALENTINA, Giulia Grisendi, Matteo Brogli, Giorgio Mari, and Massimo Dominici.
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Checkpoint inhibitors, 3D model, precision medicine approach ,biological phenomena, cell phenomena, and immunity - Abstract
Challenging the efficacy of checkpoint inhibitors: a new 3D model for a precision medicine approach.
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- 2018
20. New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells.
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Masciale, Valentina, Banchelli, Federico, Grisendi, Giulia, D'Amico, Roberto, Maiorana, Antonino, Stefani, Alessandro, Morandi, Uliano, Dominici, Massimo, and Aramini, Beatrice
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NON-small-cell lung carcinoma ,CANCER stem cells ,GENE expression profiling ,GENETIC overexpression ,LUNG cancer ,OVERTREATMENT of cancer - Abstract
Introduction: Lung cancer is one of the most common cancers in the world, causing over 1.7 million deaths in 2018. Thus far, no effective treatments against lung cancer for advanced stages have been found. For early stages, although surgery is considered the gold standard treatment, 30–55% of patients develop recurrence within the first 5 years of surgery. Our aim is to assess whether cancer stem cells (CSC) display overexpression of a pool of genes that were previously identified for adenocarcinoma recurrence in patients with early and locally advanced stages of non-small cell lung cancer (NSCLC). Methods: This cross-sectional study was carried out by harvesting surgical tumor specimens obtained from patients harboring early (I-II) and locally advanced (IIIA) stages of NSCLC. For each patient, cell sorting was performed to identify and isolate the ALDH
high (CSC) and ALDHlow (cancer cells) populations. The mRNA expressions of 31 recurrence-related genes (target genes) in both ALDHhigh and ALDHlow populations were then assessed and compared. Results: Surgical specimens were obtained from 22 patients harboring NSCLC. Sixteen (51.6%) out of 31 recurrence-related genes were significantly overexpressed in ALDHhigh cells in the early stages and 9 (29.0%) were overexpressed in the locally advanced stages of NSCLC. Overall, the relative mRNA expressions for these recurrence-related genes were higher in early-stage patients. The average fold change, considering all 31 recurrence-related genes together, was 4.5 (95% CI = 3.1-6.3) in early-stage patients and 1.6 (95% CI = 1.2-2.2) in locally advanced-stage patients. Conclusions: Our study represents the first attempt toward identifying genes associated with recurrence that are overexpressed in cancer stem cells in patients with early and locally advanced stages of NSCLC. This finding may contribute to the identification of new target therapies tailored for NSCLC stages. [ABSTRACT FROM AUTHOR]- Published
- 2021
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21. Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?
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Golinelli, Giulia, Mastrolia, Ilenia, Aramini, Beatrice, Masciale, Valentina, Pinelli, Massimo, Pacchioni, Lucrezia, Casari, Giulia, Dall'Ora, Massimiliano, Soares, Milena Botelho Pereira, Damasceno, Patrícia Kauanna Fonseca, Silva, Daniela Nascimento, Dominici, Massimo, and Grisendi, Giulia
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CANCER stem cells ,BIOENGINEERING ,EXTRACELLULAR vesicles ,STEM cells - Abstract
Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation. [ABSTRACT FROM AUTHOR]
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- 2020
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22. Cancer Stem-Like Cells in a Case of an Inflammatory Myofibroblastic Tumor of the Lung.
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Masciale, Valentina, Grisendi, Giulia, Banchelli, Federico, D'Amico, Roberto, Maiorana, Antonino, Sighinolfi, Pamela, Brugioni, Lucio, Stefani, Alessandro, Morandi, Uliano, Dominici, Massimo, and Aramini, Beatrice
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CANCER cells ,CANCER stem cells ,LUNG cancer ,ALDEHYDE dehydrogenase ,BENIGN tumors - Abstract
Background: Inflammatory myofibroblast tumor (IMT) is a rare tumor with obscure etiopathogenesis in which different inflammatory cells and myofibroblastic spindle cells are seen histologically. Although the majority of these neoplasms have a benign clinical course, the malignant form has also been reported. The gold standard is surgical treatment for complete removal. Our report describes a 50-year-old woman who underwent surgery for IMT of the lung. The aim is to determine whether cancer stem cells may be present in IMT of the lung. Methods: In April 2018, the patient underwent surgery for tumor mass asportation through lateral thoracotomy. The histology of the tumor was consistent with IMT of the lung. The ALDEFLUOR assay, after tissue digestion, was used to identify and sort human lung cancer cells expressing high and low aldehyde dehydrogenase (ALDH) activity. SOX2, NANOG, OCT-4, and c-MYC positivity were additionally determined by immunohistochemistry. Results: The specimen contained 1.10% ALDH
high cells among all viable lung cancer cells, which indicates the population of cancer stem cells is not negligible. Immunohistochemically assessed cell positivity for ALDH1A1, SOX2, NANOG, OCT-4, and c-MYC, which are considered as lung cancer stem-like cells markers. Conclusion: For the first time, we demonstrated the presence of cancer stem cells in a case of IMT of the lung. This finding may provide a base for considering new pathological and molecular aspects of this tumor. This perspective suggests further studies to understand the possibility of developing recurrence depending on the presence of cancer stem cells. [ABSTRACT FROM AUTHOR]- Published
- 2020
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23. Isolation and Identification of Cancer Stem-Like Cells in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Pilot Study.
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Masciale, Valentina, Grisendi, Giulia, Banchelli, Federico, D'Amico, Roberto, Maiorana, Antonino, Sighinolfi, Pamela, Stefani, Alessandro, Morandi, Uliano, Dominici, Massimo, and Aramini, Beatrice
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SQUAMOUS cell carcinoma ,CANCER cells ,CARCINOMA ,NON-small-cell lung carcinoma ,EPITHELIAL cell tumors - Abstract
Background: Lung cancer stem cells (CSCs) share many characteristics with normal stem cells, such as self-renewal and multipotentiality. High expression of aldehyde dehydrogenase (ALDH) has been detected in many tumors, particularly in the CSC compartment, and it plays an important role in tumor proliferation, metastasis, and drug resistance. CD44 is commonly used as a cell surface marker of cancer stem-like cells in epithelial tumors. The aim of this study was to isolate and analyze cancer stem-like cells from surgically removed specimens to compare lung adenocarcinoma (ADENO) and squamous (SQUAMO) cell carcinoma. Methods: The ALDEFLUOR assay was used to identify and sort ALDH
high and ALDHlow human lung cancer cells following tissue digestion. Fluorescence-activated cell sorting analysis for CD44 was performed with tumor cells. Quantitative real-time PCR was performed to assess the expression of SOX2 and NANOG as stemness markers. ALDH1A1 expression was additionally determined by immunohistochemistry. Anchorage-independent ALDHhigh cell growth was also evaluated. ALDHhigh ADENO and SQUAMO cells were cultured to analyze spheroid formation. Results: All specimens contained 0.5–12.5% ALDHhigh cells with 3.8–18.9% CD44-positive cells. SOX2 and NANOG relative expression in ALDHhigh compared to ALDHlow cells in ADENO and SQUAMO was analyzed and compared between the histotypes. Immunohistochemistry confirmed the presence of ALDH1A1 in the sections. SOX2 and NANOG were expressed at higher levels in the ALDHhigh subpopulation than in the ALDHlow subpopulation only in ADENO cells, and the opposite result was seen in SQUAMO cells. In vitro functional assays demonstrated that ALDHhigh cells exhibited migration capacity with distinct behaviors between ALDHhigh spheres in ADENO vs. SQUAMO samples. Conclusions: Our results highlight the importance of a better characterization of cancer stem-like cells in ADENO and SQUAMO histotypes. This may suggest new differential approaches for prognostic and therapeutic purposes in patients with non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]- Published
- 2019
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24. Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence.
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Aramini, Beatrice, Masciale, Valentina, Grisendi, Giulia, Bertolini, Federica, Maur, Michela, Guaitoli, Giorgia, Chrystel, Isca, Morandi, Uliano, Stella, Franco, Dominici, Massimo, and Haider, Khawaja Husnain
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CANCER invasiveness , *PHENOMENOLOGICAL biology , *CELL physiology , *NEUROPLASTICITY , *WNT proteins , *DISEASE relapse , *CELLULAR signal transduction , *STEM cells , *HEDGEHOG signaling proteins , *TUMOR markers , *DRUG resistance in cancer cells - Abstract
Simple Summary: Cancer is one of the most debated problems all over the world. Cancer stem cells are considered responsible of tumor initiation, metastasis, drug resistance, and recurrence. This subpopulation of cells has been found into the tumor bulk and showed the capacity to self-renew, differentiate, up to generate a new tumor. In the last decades, several studies have been set on the molecular mechanisms behind their specific characteristics as the Wnt/β-catenin signaling, Notch signaling, Hedgehog signaling, transcription factors, etc. The most powerful part of CSCs is represented by the niches as "promoter" of their self-renewal and "protector" from the common oncological treatment as chemotherapy and radiotherapy. In our review article we highlighted the primary mechanisms involved in CSC tumorigenesis for the setting of further targets to control the metastatic process. Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs' self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process. [ABSTRACT FROM AUTHOR]
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- 2022
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25. Deepening the Knowledge of ROS1 Rearrangements in Non-Small Cell Lung Cancer: Diagnosis, Treatment, Resistance and Concomitant Alterations.
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Guaitoli, Giorgia, Bertolini, Federica, Bettelli, Stefania, Manfredini, Samantha, Maur, Michela, Trudu, Lucia, Aramini, Beatrice, Masciale, Valentina, Grisendi, Giulia, Dominici, Massimo, and Barbieri, Fausto
- Subjects
NON-small-cell lung carcinoma ,PROTEIN-tyrosine kinase inhibitors ,CANCER diagnosis ,GENE rearrangement - Abstract
ROS proto-oncogene 1 (ROS1) rearrangements are reported in about 1–2% of non-squamous non-small-cell lung cancer (NSCLC). After efficacy of crizotinib was demonstrated, identification of ROS1 translocations in advanced disease became fundamental to give patients the chance of specific and effective treatment. Different methods are available for detection of rearrangements, and probably the real prevalence of ROS1 rearrangements is higher than that reported in literature, as our capacity to detect gene rearrangements is improving. In particular, with next generation sequencing (NGS) techniques, we are currently able to assess multiple genes simultaneously with increasing sensitivity. This is leading to overcome the "single oncogenic driver" paradigm, and in the very near future, the co-existence of multiple drivers will probably emerge more frequently and represent a therapeutic issue. Since recently, crizotinib has been the only available therapy, but today, many other tyrosine kinase inhibitors (TKI) are emerging and seem promising both in first and subsequent lines of treatment. Indeed, novel inhibitors are also able to overcome resistance mutations to crizotinib, hypothesizing a possible sequential strategy also in ROS1-rearranged disease. In this review, we will focus on ROS1 rearrangements, dealing with diagnostic aspects, new therapeutic options, resistance issues and the coexistence of ROS1 translocations with other molecular alterations. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature.
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Isca, Chrystel, Piacentini, Federico, Mastrolia, Ilenia, Masciale, Valentina, Caggia, Federica, Toss, Angela, Piombino, Claudia, Moscetti, Luca, Barbolini, Monica, Maur, Michela, Dominici, Massimo, and Omarini, Claudia
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BREAST cancer prognosis ,BREAST tumor treatment ,EXOSOMES ,CARCINOGENESIS ,TRASTUZUMAB ,MICRORNA ,TUMOR classification ,GENE expression ,EXTRACELLULAR space ,COMBINED modality therapy ,TUMOR markers ,NUCLEIC acids - Abstract
Simple Summary: Breast cancer is a leading cause of female cancer-related death worldwide. Anti-HER2-targeted therapies dramatically improved prognosis for HER2-positive breast cancer patients. Despite that, growing drug resistance due to the pressure of therapy is relatively frequent. For that reason, it is necessary to find biomarkers able to predict treatment sensitivity and survival outcomes. Increasing research has shown how miRNAs, secreted by tumor cells, are strongly involved in cancer development. In this review, we will discuss the recent evidence on the predictive and prognostic value of miRNAs involved in HER2-positive early breast cancer progression. MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value. [ABSTRACT FROM AUTHOR]
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- 2021
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27. Impact of soluble tumor necrosis factor-related apoptosis-inducing ligand released by engineered adipose mesenchymal stromal cells on white blood cells.
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Casari, Giulia, Dall'Ora, Massimiliano, Melandri, Aurora, Masciale, Valentina, Chiavelli, Chiara, Prapa, Malvina, Neri, Giovanni, Spano, Maria Carlotta, Murgia, Alba, D'Esposito, Angela, Baschieri, Maria Cristina, Ceccherelli, Giovanni Battista, Dominici, Massimo, and Grisendi, Giulia
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LEUCOCYTES , *STROMAL cells , *T cells , *VASCULAR endothelial growth factors , *TUMOR necrosis factors , *ADIPOSE tissue physiology , *TUMOR proteins - Abstract
The proapoptotic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is physiologically expressed by immune cells and performs regulatory functions in infections, autoimmune diseases and cancer, where it acts as a tumor suppressor. Adipose-derived mesenchymal stromal cells (AD-MSCs) also may play immunomodulatory roles in both primary and acquired immune responses. We have previously demonstrated the efficacy of an anticancer gene therapy based on AD-MSC engineered to secrete a soluble TRAIL variant (sTRAIL) against pancreatic cancer. However, the impact of AD-MSC sTRAIL on leukocyte subsets has been not yet considered also to predict a possible immunotoxicity profile in the clinical translation of this cell-based anticancer strategy. Monocytes, polymorphonuclear cells and T lymphocytes were freshly isolated from the peripheral blood of healthy donors. Immunophenotype and functional (DR4 and DR5) and decoy (DcR1 and DcR2) TRAIL receptors were tested by flow cytometry. The viability of white blood cells treated with sTRAIL released by gene-modified AD-MSC or co-cultured with AD-MSC sTRAIL was then evaluated by both metabolic assays and flow cytometry. In addition, cytokine profile in co-cultures was analyzed by multiplex enzyme-linked immunosorbent assay. Monocytes and polymorphonuclear cells showed high positivity for DR5 and DcR2, respectively, whereas T cells revealed negligible expression of all TRAIL receptors. Irrespective of TRAIL receptors' presence on the cell membrane, white blood cells were refractory to the proapoptotic effect displayed by sTRAIL secreted by gene-modified AD-MSC, and direct cell-to-cell contact with AD-MSC sTRAIL had negligible impact on T-cell and monocyte viability. Cytokine crosstalk involving interleukin 10, tumor necrosis factor alpha, and interferon gamma secreted by T lymphocytes and vascular endothelial growth factor A and interleukin 6 released by AD-MSC was highlighted in T-cell and AD-MSC sTRAIL co-cultures. In summary, this study demonstrates the immunological safety and thus the clinical feasibility of an anticancer approach based on AD-MSC expressing the proapoptotic molecule sTRAIL. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Precision Medicine in Lung Cancer : Challenges and Opportunities in Diagnostic and Therapeutic Purposes
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Aramini, Beatrice, Haider, Khawaja Husnain, Dominici, Massimo, D´Amico, Roberto, Banchelli, Federico, and Masciale, Valentina
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Medical - Abstract
Lung cancer is one of the leading causes of cancer death among both men and women, making up almost 25% of all cancer deaths. Precision medicine shows promise for improving many aspects of health and healthcare, including tests, drugs, and other technologies that support innovation, with the possibility of new partnerships with scientists in a wide range of specialties. Non–small-cell lung cancer (NSCLC) has become a prominent example of the success of precision medicine in treating solid tumor malignancies. The first step in this process involves new blood-based diagnostics, which can now noninvasively provide clinically useful information. However, the identification of novel biomarkers that could be used in early diagnosis is urgently needed, especially for guiding initial therapy and predicting relapse or drug resistance following the administration of novel targeted therapies.
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- 2019
29. Editorial: Aldehyde dehydrogenase in clinical settings: Potential biomarker and therapeutic target in solid tumors.
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Aramini B and Masciale V
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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2023
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30. The Influence of Cancer Stem Cells on the Risk of Relapse in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Prospective Cohort Study.
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Masciale V, Banchelli F, Grisendi G, D'Amico R, Maiorana A, Stefani A, Morandi U, Stella F, Dominici M, and Aramini B
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- Humans, Lung pathology, Neoplasm Recurrence, Local pathology, Neoplastic Stem Cells pathology, Prospective Studies, Adenocarcinoma pathology, Adenocarcinoma surgery, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell surgery, Lung Neoplasms pathology, Lung Neoplasms surgery
- Abstract
Purpose: Lung cancer relapse may be associated with the presence of a small population of cancer stem cells (CSCs) with unlimited proliferative potential. Our study assessed the relationship between CSCs and the relapse rate in patients harboring adenocarcinoma (ADL) and squamous cell carcinoma of the lung (SCCL)., Experimental Design: This is an observational prospective cohort study (NCT04634630) assessing the influence of CSC frequency on relapse rate after major lung resection in 35 patients harboring early (I-II) (n = 21) and locally advanced (IIIA) (n = 14) ADL and SCCL. There was a 2-year enrollment period followed by a 1-year follow-up period. Surgical tumor specimens were processed, and CSCs were quantified by cytofluorimetric analysis., Results: Cancer stem cells were expressed in all patients with a median of 3.1% of the primary cell culture. Primary analysis showed no influence of CSC frequency on the risk of relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.85-1.30). At secondary analysis, patients with locally advanced disease with higher CSC frequency had an increased risk of relapse (HR = 1.26, 95% CI = 1.14-1.39), whereas this was not observed in early-stage patients (HR = 0.90, 95% CI = 0.65-1.25)., Conclusion: No association was found between CSC and relapse rates after major lung resection in patients harboring ACL and SCCL. However, in locally advanced-stage patients, a positive correlation was observed between CSC frequency and risk of relapse. These results indicate a need for further molecular investigations into the prognostic role of CSCs at different lung cancer stages., Clinical Trial Registration: NCT04634630., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2022
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31. Cancer stem cells and macrophages: molecular connections and future perspectives against cancer.
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Aramini B, Masciale V, Grisendi G, Banchelli F, D'Amico R, Maiorana A, Morandi U, Dominici M, and Haider KH
- Abstract
Cancer stem cells (CSCs) have been considered the key drivers of cancer initiation and progression due to their unlimited self-renewal capacity and their ability to induce tumor formation. Macrophages, particularly tumor-associated macrophages (TAMs), establish a tumor microenvironment to protect and induce CSCs development and dissemination. Many studies in the past decade have been performed to understand the molecular mediators of CSCs and TAMs, and several studies have elucidated the complex crosstalk that occurs between these two cell types. The aim of this review is to define the complex crosstalk between these two cell types and to highlight potential future anti-cancer strategies., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare., (Copyright: © 2021 Aramini et al.)
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- 2021
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32. Use of Octreotide in association with talc poudrage for the management of a severe chylothorax: A case report.
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Lovati E, Ruggiero C, Masciale V, Stefani A, Morandi U, and Aramini B
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Introduction and Importance: Chylothorax is an uncommon form of pleural effusion characterized by the presence of chylomicrons, triglycerides and cholesterol in the physical and chemical examination of the pleural fluid. It may have poor prognosis if not properly treated. Currently, conservative measures are the first line of treatment for managing chylothorax. The aim of our study is to show and suggest the use of octreotide in association with talc poudrage as good option to manage post-operative a severe chylothorax., Case Presentation: A 59-year-old male patient who underwent a replacement of the ascending aorta, aortic hemiarch and surgery of the aortic valve for aortic dissection showed a severe pleural effusion three months after surgery. Because the physical and chemical examination of the pleural fluid revealed high levels of triglycerides and cholesterol, a conservative treatment with pleural drainage, TPN and nihil per os was attempted, with the introduction of 0.3 mg/die of octreotide on day thirty-four. With the application of talc poudrage, the chylothorax completely resolved., Clinical Discussion: Octreotide has been shown to significantly decrease chylous effusion in many studies, but the dose and duration of therapy have not yet been defined. Our patient responded partially to octreotide after two days of treatment, with the drainage leak reduced to less than 100 mL/day., Conclusion: After octreotide treatment associated with talc poudrage, the drainage leak was drastically reduced, suggesting that this could be a useful approach in the management of severe chylous leaks., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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33. ALDH Expression in Angiosarcoma of the Lung: A Potential Marker of Aggressiveness?
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Aramini B, Masciale V, Bianchi D, Manfredini B, Banchelli F, D'Amico R, Bertolini F, Dominici M, Morandi U, and Maiorana A
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Background: Primary angiosarcoma of the lung is a very aggressive rare malignant disease resulting in a severe prognosis (1). This type of cancer represents about 2% of all soft tissue sarcomas and has a high rate of metastasis through the hematogenous route. For the rarity of this malignant vascular tumor it is still challenging to set a diagnosis (1). The diagnostic features that have thus far been considered include primarily clinical and radiological findings. In some cases, immunohistochemical characteristics based on the most common markers used in pathology have been described. The aim of this report is to present two cases of angiosarcoma of the lung in which the aldehyde dehydrogenase (ALDH) marker was analyzed by immunohistochemistry. Methods: We report two cases of angiosarcoma of the lung in patients underwent lung surgery at our Unit. In addition to the standard histopathological analysis for this disease, immunohistochemistry using an ALDH1A1 antibody was performed in both of the cases. For ALDH quantification, a semi-quantitative method based on the positivity of the tumor cells was used: 0 (<5%), 1 (5-25%), 2 (>25-50%), 3 (>50-75%), 4 (>75%). Results: One patient with recurrent lung disease survived, achieving complete remission after chemo- and radiotherapy. The second patient died of recurrent disease within 5 years of diagnosis. ALDH1A1 was evaluated in both of these cases using an immunohistochemistry scoring system based on the positivity for this marker. The scores were consistent with the patients' clinical outcomes, as the lower (score 1) was observed in the patient with the better clinical outcome, while the higher (score 3) was seen in the patient with the worse outcome. Conclusion: Our data suggest that ALDH may be an important clinical marker in angiosarcoma of the lung. Although further studies need to be performed in a larger cohort of patients, we believe that, if the results will be confirmed, ALDH1A1 may be used to stratify patients in terms of prognosis and for targeted therapy., (Copyright © 2020 Aramini, Masciale, Bianchi, Manfredini, Banchelli, D'Amico, Bertolini, Dominici, Morandi and Maiorana.)
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- 2020
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34. Expression of ALDH and SOX-2 in Pulmonary Sclerosing Pnemocytoma (PSP) of the Lung: Is There a Meaning Behind?
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Aramini B, Masciale V, Manfredini B, Bianchi D, Banchelli F, D'Amico R, Bertolini F, Dominici M, Morandi U, and Maiorana A
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Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare benign pulmonary tumor that derives from primitive respiratory epithelium of the pulmonary alveolus. The etiology and pathogenesis are still unclear. Histopathological diagnosis focuses on cells that are positive for TTF1, EMA, cytokeratin-7, and CAM 5.2. The aim of our study is to highlight the elevated expression of ALDH and the presence of SOX-2 in pulmonary sclerosing pneumocytoma. Methods: We report five cases of pulmonary sclerosing pneumocytoma undergone surgery at our Division of Thoracic Surgery, during a period between 1994 and 2011. ALDH and SOX-2 markers were also tested for positivity in all the patients. Results: Patients showed elevated expression of ALDH during immunohistochemistry and mild expression of SOX-2, although in two cases in which SOX-2 was highly expressed. Among these two patients, one presented with lymph node recurrence while the other had no recurrence with a PET-positive nodule. In particular, the patient who had developed recurrence had an ALDH score of 4 and a SOX-2 score of 3, whereas the patient with the PET-positive nodule showed an ALDH score of 4 with a mild SOX-2 expression of score 1. Conclusions: This is the first attempt demonstrating the elevated expression of ALDH in this disease. SOX-2 expression was noted in both the patient who developed recurrence and the patient with a PET-positive nodule. We believe that further investigation may be highly useful to better characterize these two markers as well as understand their function., (Copyright © 2020 Aramini, Masciale, Manfredini, Bianchi, Banchelli, D'Amico, Bertolini, Dominici, Morandi and Maiorana.)
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- 2020
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35. Defining lung cancer stem cells exosomal payload of miRNAs in clinical perspective.
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Aramini B, Masciale V, and Haider KH
- Abstract
Since the first publication regarding the existence of stem cells in cancer [cancer stem cells (CSCs)] in 1994, many studies have been published providing in-depth information about their biology and function. This research has paved the way in terms of appreciating the role of CSCs in tumour aggressiveness, progression, recurrence and resistance to cancer therapy. Targeting CSCs for cancer therapy has still not progressed to a sufficient degree, particularly in terms of exploring the mechanism of dynamic interconversion between CSCs and non-CSCs. Besides the CSC scenario, the problem of cancer dissemination has been analyzed in-depth with the identification and isolation of microRNAs (miRs), which are now considered to be compelling molecular markers in the diagnosis and prognosis of tumours in general and specifically in patients with non-small cell lung cancer. Paracrine release of miRs via "exosomes" (small membrane vesicles (30-100 nm), the derivation of which lies in the luminal membranes of multi-vesicular bodies) released by fusion with the cell membrane is gaining popularity. Whether exosomes play a significant role in maintaining a dynamic equilibrium state between CSCs and non-CSCs and their mechanism of activity is as yet unknown. Future studies on CSC-related exosomes will provide new perspectives for precision-targeted treatment strategies., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2020
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36. CD44+/EPCAM+ cells detect a subpopulation of ALDH high cells in human non-small cell lung cancer: A chance for targeting cancer stem cells?
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Masciale V, Grisendi G, Banchelli F, D'Amico R, Maiorana A, Sighinolfi P, Stefani A, Morandi U, Dominici M, and Aramini B
- Abstract
Objectives: Several studies demonstrated that aldehyde dehydrogenase (ALDH) and CD44 are the most considered cancer stem cells (CSC) markers. However, a comparison between ALDH high cells and CD44+ cells have been previously described with no significant correlation. Indeed, the aim of the present research is to identify a superficial marker able to match with ALDH high cells population in freshly isolated human lung cancer cells., Materials and Methods: This cross-sectional study analyzed the expression of ALDH
high/low cells and the positivity for CD44 and epithelium cell adhesion molecule (EPCAM) antigens in surgical lung cancer tissues. The main approach was a cytofluorimetric analysis of ALDH expression and positivity for CD44/EPCAM on primary cell population obtained from 23 patients harboring NSCLC., Results: There was a highly positive correlation between the expressions of ALDHhigh and CD44+/EPCAM+ cells, with a Pearson's correlation coefficient equal to 0.69 (95% CI 0.39-0.86; P = 0.0002), and Spearman's correlation coefficient equal to 0.52 ( P = 0.0124). The average paired difference between the expression of ALDHhigh and CD44+/EPCAM+ cells was very close to 0, being 0.1% (SD 2.5%); there was no difference between these subpopulations in terms of means (95% CI = -1.0; 1.2%, P = 0.8464). These results highlight a strong similarity between ALDHhigh and CD44+/EPCAM+ cells., Conclusions: Our study is the first attempt which identifies a high correlation between the ALDHhigh and the CD44+/EPCAM+ cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells., Competing Interests: CONFLICTS OF INTEREST None of the Authors have any competing interests.- Published
- 2020
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37. Overall survival in patients with lung adenocarcinoma harboring "niche" mutations: an observational study.
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Aramini B, Banchelli F, Bettelli S, Manfredini S, D'Amico R, Masciale V, Pinelli M, Moretti M, Stefani A, Bertolini F, Dominici M, Morandi U, and Maiorana A
- Abstract
Objective: In addition to the most common somatic lung cancer mutations (i. e., KRAS and EGFR mutations), other genes may harbor mutations that could be relevant for lung cancer. We defined BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations as "niche" mutations and analyzed. The aim of this retrospective cohort study was to assess the differences in the overall survival (OS) of patients with lung adenocarcinoma harboring niche somatic mutations. Results: Data were gathered for 252 patients. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that 1) niche mutations had a higher mortality than EGFR mutations (HR = 2.3; 95% CI = 1.2-4.4; p = 0.009); 2) KRAS mutations had a higher mortality than EGFR mutations (HR = 2.5; 95% CI = 1.4-4.5; p = 0.003); 3) niche mutations presented a similar mortality to KRAS mutations (HR = 0.9; 95% CI = 0.6-1.5; p = 0.797). Methods: Three cohorts of mutations were selected from patients with lung adenocarcinoma and their OS was compared. Mutations that were searched for, were 1) BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET; 2) K-RAS; and 3) EGFR. Differences in OS between these three cohorts were assessed by means of a multivariable Cox model that adjusted for age, sex, smoking habits, clinical stages, and treatments. Conclusions: Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest., (Copyright: © 2020 Aramini et al.)
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- 2020
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38. Cancer stem-neuroendocrine cells in an atypical carcinoid case report.
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Masciale V, Grisendi G, Banchelli F, D'Amico R, Maiorana A, Morandi U, Dominici M, and Aramini B
- Abstract
Lung neuroendocrine cells tumor (NET) classification and diagnosis, particularly for typical and atypical carcinoids, are complicated by a variable natural history and nonspecific symptoms. Mechanisms for the development and progression of well-differentiated lung NETs are still unclear. An accurate and timely diagnosis can ensure the implementation of appropriate treatment and impact on prognosis. One of the main unclear point is the definition of these cells' composition. In fact, it is known that carcinoids are mainly constituted by neuroendocrine cells. Aim of our report is to show for the first time the presence of a high percentage of cancer stem cells (CSCs) in an atypical carcinoid. The ALDEFLUOR assay was used to identify and sort ALDH
high and ALDHlow human lung cancer cells following tissue digestion. SOX2 was additionally determined by immunohistochemistry. All specimens contained the 53.10% of ALDHhigh cells among all viable lung cancer cells, which indicates that more than half of the entire tumor cell population was composed by CSCs. As expected also in immunohistochemistry, about a half of the nuclei of the cells were positive for SOX2. We strongly support the hypothesis of the presence of cancer stem-neuroendocrine cells (CSCs-NETs) as subpopulation in these types of tumors., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Translational Lung Cancer Research. All rights reserved.)- Published
- 2019
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39. Correlating tumor-infiltrating lymphocytes and lung cancer stem cells: a cross-sectional study.
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Masciale V, Grisendi G, Banchelli F, D'Amico R, Maiorana A, Sighinolfi P, Pinelli M, Lovati E, Stefani A, Morandi U, Dominici M, and Aramini B
- Abstract
Background: Lung cancer stem cells (LCSCs) are endowed with high aldehyde dehydrogenase (ALDH) expression and play roles in tumor proliferation, metastasis, and drug resistance. Their elusive nature may allow them to escape the immune response by tumor-infiltrating lymphocytes (TILs), which can positively affect the outcome in non-small cell lung cancer (NSCLC) patients. Despite independent investigations on both LCSCs and TILs, the relationship between the two has been very marginally considered. We analyzed whether these two cell types may be related as a prerequisite for novel diagnostic and therapeutic approaches., Methods: In this cross-sectional study, NSCLC human surgical specimens from 12 patients were tested by ALDEFLUOR assay to identify ALDH
high cells. Fluorescence-activated cell sorting (FACS) analyses for CD3+, CD4+, and CD8+ TILs were performed in combination with immunohistochemistry evaluation., Results: Statistically positive correlations were found between ALDH+ and CD8+, and between ALDH+ and CD3+ cells populations; no correlation was found between ALDH+ and CD4+ cells. The expression of CD3+ and CD8+ by cells accounted for 40.1% and 58.7%, respectively, of the variability of ALDH+ cell expression by an R-squared index, which highlights the strong correlation between TILs and LCSCs. Immunohistochemistry revealed 6-25% positive cells., Conclusions: We report a correlation between cytotoxic TILs and LCSCs, which may contribute to the future development of targeted therapies focusing on the different roles of lymphocytes against lung cancer., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)- Published
- 2019
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