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MONIA MACCAFERRI
TITOLARE DI BORSA DI STUDIO Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa
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Pubblicazioni
2024
- A comprehensive review on the role of mesenchymal stromal/stem cells in the management of rheumatoid arthritis
[Articolo su rivista]
Pignatti, Elisa; Maccaferri, Monia; Pisciotta, Alessandra; Carnevale, Gianluca; Salvarani, Carlo
abstract
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with systemic manifestations. Although the success of immune modulatory drug therapy is considerable, about 40% of patients do not respond to treatment. Mesenchymal stromal/stem cells (MSCs) have been demonstrated to have therapeutic potential for inflammatory diseases. Areas covered: This review provides an update on RA disease and on pre-clinical and clinical studies using MSCs from bone marrow, umbilical cord, adipose tissue, and dental pulp, to regulate the immune response. Moreover, the clinical use, safety, limitations, and future perspective of MSCs in RA are discussed. Using the PubMed database and ClincalTrials.gov, peer-reviewed full-text papers, abstracts and clinical trials were identified from 1985 through to April 2023. Expert opinion: MSCs demonstrated a satisfactory safety profile and potential for clinical efficacy. However, it is mandatory to deepen the investigations on how MSCs affect the proinflammatory deregulated RA patients' cells. MSCs are potentially good candidates for severe RA patients not responding to conventional therapies but a long-term follow-up after stem cells treatment and standardized protocols are needed. Future research should focus on well-designed multicenter randomized clinical trials with adequate sample sizes and properly selected patients satisfying RA criteria for a valid efficacy evaluation.
2023
- Assessing the Ability of Human Dental Pulp Stem Cells to Modulate the Macrophages Phenotype.
[Poster]
Maccaferri, M; Pisciotta, A; Carnevale, G; Salvarani, C; Pignatti, E.
abstract
2023
- EFFETTO DEL MICROAMBIENTE INFIAMMATORIO INDOTTO DAI MONOCITI SUI FIBROBLASTI E AZIONE MODULATORIA DELLE CELLULE STAMINALI DELLA POLPA DENTALE UMANA
[Poster]
Maccaferri, Monia; Corbelli, Tommaso; Lazzari, Giorgia; Pisciotta, Alessandra; Carnevale, Gianluca; Salvarani, Carlo; Pignatti, Elisa
abstract
2023
- Effect of the Inflammatory Microenvironment Induced by Monocytes on Fibroblasts and Modulatory Action of Human Dental Pulp Stem Cells.
[Poster]
Maccaferri, M; Pisciotta, A; Carnevale, G; Salvarani, C; Pignatti, E.
abstract
2023
- Studio in vitro dei tempi di risposta dei sinoviociti di tipo fibroblastico allo stimolo infiammatorio
[Poster]
Maccaferri, M.; Corbelli, T.; Lazzari, G.; Salvarani, C.; Pignatti, E.
abstract
2022
- MODULAZIONE DEI MONOCITI NEI PROCESSI INFIAMMATORI CON IL CONTRIBUTO DELLE CELLULE STAMINALI DELLA POLPA DENTALE UMANA (hDPSC)
[Poster]
Pignatti, E.; Maccaferri, M.; Pisciotta, A.; Di Tinco, R.; Bertani, G.; Bertoni, L.; Croci, S.; Bonacini, M.; Carnevale, G.; Salvarani, C.
abstract
2022
- RUOLO DEI MACROFAGI IN CONDIZIONI PRO- ED ANTI-INFIAMMATORIE E MECCANISMI DI REGOLAZIONE INDOTTI DALLE hDPSCs
[Poster]
Maccaferri, M.; Pisciotta, A.; Di Tinco, R.; Bertani, G.; Bertoni, L.; Carnevale, G.; Salvarani, C.; Pignatti, E.
abstract
2021
- Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
[Articolo su rivista]
Di Tinco, R.; Bertani, G.; Pisciotta, A.; Bertoni, L.; Pignatti, E.; Maccaferri, M.; Bertacchini, J.; Sena, P.; Vallarola, A.; Tupler, R.; Croci, S.; Bonacini, M.; Salvarani, C.; Carnevale, G.
abstract
Background: Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. Methods: Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. Results: Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. Conclusions: Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties.
2020
- Biomarkers associated with COVID-19 disease progression
[Articolo su rivista]
Ponti, Giovanni; Maccaferri, Monia; Ruini, Cristel; Tomasi, Aldo; Ozben, Tomris
abstract
The SARS-COVID 19 pandemic is a scientific, medical and social challenge. The complexity of the virus is centred on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: haematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte-ratio (NLR), and Hhemoglobin ), inflammatory (C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), procalcitonin(PCT )), immunological (IL-6 ) and biochemical (D-Dimer, Troponin, CK, AST ), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.
2020
- Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response
[Articolo su rivista]
Ponti, G.; Pellacani, G.; Tomasi, A.; Depenni, R.; Maccaferri, M.; Maiorana, A.; Orsi, G.; Giusti, F.; Cascinu, S.; Manfredini, M.
abstract
In difference to other solid malignancies, the identification of biomarkers for the prediction of malignant melanoma (MM) response to immunotherapy is limited. The aim of the current study was to evaluate the immunohistochemical (IHC) expression of MMR proteins in a cohort of MM metastatic patients receiving anti PD-1 treatments. The therapeutic response of patients was also retrospectively assessed. The cohort of the current study included 14 patients with advanced MM that had received anti PD-1 from January 2014 to December 2016 (12 males, 2 females; average age, 71 years; age range, 47-88 years). IHC analysis of MLH1, PMS2, MSH2 and MSH6 proteins was performed on paraffin-embedded primary tumor samples from each patient and on the 23 available metastasis specimens obtained from the Division of Pathology (University of Modena and Reggio Emilia). The results revealed that 7% of the primary melanoma tissue obtained from the patient cohort exhibited the loss of expression of at least one MMR protein. Three samples from one patient, including one primary melanoma and two metastases, exhibited no MSH6 expression and had the most successful response to anti PD-1 treatment, with a progression-free survival and overall survival of 956 and 2,546 days, respectively. In conclusion, the assessment of MMR protein expression represents a potential predictive marker that may have critical importance for patients with primary and metastatic MM, primarily as criterion for the adoption of immunotherapy treatments.
2020
- Liquid biopsy with cell free DNA: new horizons for prostate cancer
[Articolo su rivista]
Ponti, Giovanni; Maccaferri, Monia; Percesepe, Antonio; Tomasi, Aldo; Ozben, Tomris.
abstract
Although prostate cancer (PCa) is one of the most common tumors in European males, the only minimally invasive diagnostic tool in PCa setup is the determination of PSA in serum. Cell-free DNA (cfDNA) has been demonstrated to be helpful for PCa diagnosis but has not yet been integrated into the clinical setting. This review aims to provide a systematic update of cfDNA and its fragmentation patterns in PCa reported in literature published over the last twenty years. Due to the high variability of the scientific methods adopted and a lack of standardized median cfDNA levels, results fluctuate across different studies. These differences may be due to the cfDNA source, the quantification method, or the fragmentation pattern. Blood plasma is the most frequently analyzed biological fluid, but seminal plasma has been reported to contain higher cfDNA concentration due to its vicinity to the tumor origin. CfDNA has been shown to be composed of single-stranded (ssDNA) and double-stranded DNA (dsDNA), so the total cfDNA concentration should be preferred as it corresponds best to the tumor mass. Fluorometry and capillary electrophoresis (CE) may be quick and cost-effective tools for cfDNA assessment in a clinical setting. The greatest future challenge is the elaboration of common guidelines and standardized procedures for diagnostic laboratories performing cfDNA analysis. A multiparametric approach combining the analysis of total cfDNA (both ssDNA and dsDNA), cfDNA fragment length, and specific genetic mutations (ctDNA assessment) is required for optimal future applications of liquid biopsy.
2019
- Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis
[Articolo su rivista]
Ponti, Giovanni; Maccaferri, Monia; Manfredini, Marco; Micali, Salvatore; Torricelli, Federica; Milandri, Riccardo; Del Prete, Chiara; Ciarrocchi, Alessia; Ruini, Cristel; Benassi, Luisa; Bettelli, Stefania; Kaleci, Shaniko; Ozben, Tomris; Tomasi, Aldo
abstract
Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis.
2018
- PTCH1 germline mutations and the basaloid follicular hamartoma values in the tumor spectrum of basal cell carcinoma syndrome (NBCCS)
[Articolo su rivista]
Ponti, Giovanni; Manfredini, Marco; Pastorino, Lorenza; Maccaferri, Monia; Tomasi, Aldo; Pellacani, Giovanni
abstract
Background/Aim: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities. The aim of our single-institution study was the analysis of a cohort of PTCH1-mutated patients in order to define clinical and biomolecular relationship between NBCCS and BFHs. Materials and Methods: In our study we evaluated PTCH1 gene-carrier probands affected by NBCCS to detect the incidence of BFHs and their correlation with this rare syndrome. Results: Among probands we recognized 4 patients with BFHs. We found 15 germline PTCH1 mutations, uniformly distributed across the PTCH1 gene. Six of them had familial history of NBCCS, two of them were novel and have not been described previously. Conclusion: NBCCS and BFHS may be the same genetic entity and not two distinctive syndromes. The inclusion of BFH in the NBCCS cutaneous tumor spectrum might be useful for the recognition of misdiagnosed NBCCS cases that could benefit from tailored surveillance strategies.
2018
- Seminal cell free DNA concentration levels discriminate between prostate cancer and benign prostatic hyperplasia
[Articolo su rivista]
Ponti, Giovanni; Maccaferri, Monia; Micali, Salvatore; Manfredini, Marco; Milandri, Riccardo; Bianchi, Giampaolo; Pellacani, Giovanni; Kaleci, Shaniko; Chester, Johanna; Conti, Andrea; Prete, Chiara Del; Tomasi, Aldo
abstract
Background/Aim: Seminal plasma cfDNA (scfDNA) was recently proposed as a novel PCa biomarker. Our aim was to evaluate whether scfDNA could discriminate PCa from benign prostate hyperplasia (BPH) patients. Patients and Methods: A cohort of 43 patients (18 and 25 pathology proven PCa and BPH patients), and 13 healthy age-matched control subjects were enrolled. scfDNA quantification was performed. Data were analyzed through ANOVA testing. Results: Average scfDNA concentrations were 1,407.83 ng/μl, 128.13 ng/μl and 78.09 ng/μl for PCa patients, BPH patients and healthy subjects, respectively. Statistical analysis showed a significant difference among the groups, allowing for distinction of patients with optimal accuracy. A cut-off level of 450 ng/μl scfDNA was identified for the differentiation of PCa and BPH patients. Conclusion: scfDNA concentrations are significantly different between PCa patients and BPH patients. scfDNA is a promising biomarker with several applications in PCa diagnosis, screening programs and therapeutic monitoring.
2018
- Seminal cell-free DNA assessment as a novel prostate cancer biomarker
[Relazione in Atti di Convegno]
Ponti, Giovanni; Maccaferri, Monia; Mandrioli, Mauro; Ozbenc, Tomris; Manfredini, Marco; Micali, Salvatore; Cotugno, Michele; Bianchi, Giampaolo; Pellacani, Giovanni; Tomasi, Aldo
abstract
n.d.
2018
- Seminal cell-free DNA molecular profile as a novel diagnostic and prognostic prostate cancer biomarkers
[Articolo su rivista]
Ponti, Giovanni; Maccaferri, Monia; Manfredini, Marco; Cotugno, Michele; Pellacani, Giovanni; Conti, Andrea; Micali, Salvatore; Mandrioli, Mauro; Tomasi, Aldo
abstract
n.d.
2018
- The value of fluorimetry (Qubit) and spectrophotometry (NanoDrop) in the quantification of cell-free DNA (cfDNA) in malignant melanoma and prostate cancer patients
[Articolo su rivista]
Ponti, Giovanni; Maccaferri, Monia; Manfredini, Marco; Kaleci, Shaniko; Mandrioli, Mauro; Pellacani, Giovanni; Ozben, Tomris; Depenni, Roberta; Bianchi, Giampaolo; Pirola, Giacomo Maria; Tomasi, Aldo
abstract
Background
Circulating cell-free tumor DNA (cfDNA) is of crucial interest in oncology. cfDNA constitutes a potential prognostic and therapeutic marker for different solid tumors and can be used in the diagnostic and therapeutic management of cancer patients for which nowadays there are no valid laboratory markers. In the present study, the quality and quantity of the cfDNA were assessed by different quantification procedures, in order to identify the potential applications of these techniques in the preliminary cfDNA quantification.
Methods
Qubit with single (ss) and double strand (ds) DNA assay kits, NanoDrop and quantitative Real Time PCR (qPCR), were adopted to assess the cfDNA in the blood samples of 18 melanoma patients, 67 prostate cancer patients and 15 healthy controls.
Results
The quantification by NanoDrop (average value 8.48 ng/μl, 95% confidence limit (CL) = 7.23–9.73), Qubit ssDNA (average value 23.08 ng/μl, CL = 19.88–26.28), dsDNA (average value 4.32 ng/μl, CL = 3.52–5.12) assay kits and qPCR (average value 0.39 ng/μl, CL = 0.31–0.47) revealed differences among the four procedures. Qubit 2.0 ss-DNA kit gave higher cfDNA concentration values for all the samples analyzed. In detail, Qubit ssDNA assay revealed higher sensitivity in the quantification of small amounts of pure ss-DNA and ds-DNA, while NanoDrop allowed the assessment of the purity of cfDNA samples.
Conclusions
The NanoDrop and Qubit 2.0 measurements were analyzed in order to define their correlation with qPCR cfDNA assessment, showing good correlation values with the qPCR that should be considered the “gold standard”. In our proposal, the sequential combination of NanoDrop and Qubit ssDNA methods should be adopted for a cost-effective preliminary assessment of total circulating cfDNA in melanoma and prostate cancer patients, and only discordant values should undergo qPCR assessment.
2017
- BRAF
,NRASandC-KITAdvanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival
[Articolo su rivista]
Ponti, Giovanni; Manfredini, Marco; Greco, Stefano; Pellacani, Giovanni; Depenni, Roberta; Tomasi, Aldo; Maccaferri, Monia; Cascinu, Stefano
abstract
The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management.
2017
- Desmoplastic melanoma: a challenge for the oncologist
[Articolo su rivista]
Manfredini, Marco; Pellacani, Giovanni; Losi, Lorena; Maccaferri, Monia; Tomasi, Aldo; Ponti, Giovanni
abstract
To evaluate clinical, pathologic and genetic features of desmoplastic melanoma (DM).MATERIALS & METHODS:
Analysis of all DM records from 1991 to 2015.
RESULTS:
The most common location of DMs was the head and neck (69%); median age and follow-up were 60.5 and 7.3 years, respectively. A familial predisposition for DMs and others malignancies was analyzed. Thin Breslow thickness (<4.5 mm) was associated with an intraepidermal component or a previous lentigo maligna, whereas high Breslow thickness (>4.5 mm) was observed in 'pure' DM.
CONCLUSION:
DM could progress from an early phase, characterized by an intraepidermal component, to late phase, characterized by a dermal nodule. This hypothesis correlates with melanoma genetic and NF1 mutation, which could be an early event in the progression of DM.
2016
- BRAFp.V600E, p.V600K, and p.V600R Mutations in Malignant Melanoma: Do They Also Differ in Immunohistochemical Assessment and Clinical Features?
[Articolo su rivista]
Ponti, Giovanni; Tomasi, Aldo; Maiorana, Antonino; Ruini, Cristel; Maccaferri, Monia; Cesinaro, Anna M; Depenni, Roberta; Manni, Paola; Gelsomino, Fabio; Giusti, Francesca; Garagnani, Lorella; Pellacani, Giovanni
abstract
Although the detection of BRAF p.V600E mutation by immunohistochemistry was clearly described in melanoma, discordant evidences were reported for the detection of p.V600K and p.V600R mutations. The aim of the study was to evaluate the efficacy of BRAFp.V600E, p.V600K, and p.V600R detection by immunohistochemistry in melanoma.
2016
- M09Quantification of circulating cell-free DNA by fluorimetry (Qubit) and spectrophotometry (NanoDrop) in patients with malignant melanoma and prostate cancer
[Abstract in Atti di Convegno]
Ponti, G.; Maccaferri, M.; Depenni, R.; Mandrioli, M.; Pellacani, G.; Manfredini, M.; Ozben, T.; Ruini, C.; Iattoni, E.; Cerioli, D.; Cascinu, S.; Tomasi, A.
abstract
Quantification of circulating cell-free DNA by fluorimetry (Qubit) and spectrophotometry (NanoDrop) in patients with malignant melanoma and prostate cancer
2016
- Quantification of circulating cell-free DNA by fluorimetry (Qubit) and spectrophotometry (NanoDrop) in patients with malignant melanoma and prostate cancer
[Abstract in Rivista]
Ponti, Giovanni; Maccaferri, M; Depenni, Roberta; Mandrioli, Mauro; Pellacani, Giovanni; Manfredini, M; Ozben, T; Ruini, C; Iattoni, Elena; Cerioli, Davide; Cascinu, Stefano; Tomasi, Aldo
abstract
n.d.
2015
- BRAFV600E mutated and wild type melanomas: dermoscopy and reflectance confocal microscopy characterization
[Poster]
Manfredini, Marco; Ponti, Giovanni; Mandel, Victor Desmond; Persechino, Flavia; Ruini, Cristel; Maccaferri, Monia; Pellacani, Giovanni
abstract
The advent of modern molecular approaches was of crucial importance for the identification of melanoma genetic signatures, opening new horizons in the treatment of metastatic disease with molecular targeted therapies. Similarly the melanoma diagnosis is aided by reflectance confocal microscopy (RCM): a promising technique that allows non-invasive imaging from the skin surface to the upper dermis with quasi-histologic resolution. The most common melanoma mutation involves the gene BRAF and it is represented by the BRAFV600E, however, V600K, V600R and V600D mutations are also known. Because different genetic aberrations categorize melanoma subtypes with distinct clinical characteristics, it is reasonable to hypothesize that a distinctive molecular signature corresponds to specific morphologic patterns. A comparison between the dermoscopic patterns of BRAF p.V600E, BRAF p.V600K and wild-type BRAF primary melanomas was assessed from a collection of 12 lesions (4 primary melanomas per each BRAFV600 mutated status and 4 wt). In 9 cases the RCM images were available and the frequency of the RCM descriptors was examined. The RCM analysis showed that the presence of plump bright cells, collagen bundles and inflammatory cells in the dermis were frequently observed even when dermoscopy showed no regression features. Our study showed that regression phenomena and the associated dermoscopic and RCM descriptors could help the clinician to discriminate between the different BRAF mutated status, providing key information for patient screening, management and follow-up.
2014
- NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies
[Articolo su rivista]
Ponti, Giovanni; Martorana, Davide; Pellacani, Giovanni; Ruini, Cristel; Loschi, Pietro; Baccarani, Alessio; DE SANTIS, Giorgio; Pollio, Annamaria; Tauro, Maria Neri; Mandel, Victor Desmond; Maiorana, Antonio; Maccio, Livia; Maccaferri, Monia; Tomasi, Aldo
abstract
Background/aim: Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Patients and methods: Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Results: Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. Conclusion: This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1.