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Dive into the research topics where Massimo Papale is active.

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Featured researches published by Massimo Papale.


Diabetes Care | 2010

Urine Proteome Analysis May Allow Noninvasive Differential Diagnosis of Diabetic Nephropathy

Massimo Papale; Salvatore Di Paolo; Riccardo Magistroni; Anna Maria Di Palma; Angela De Mattia; Maria Teresa Rocchetti; Luciana Furci; Sonia Pasquali; Salvatore De Cosmo; Mauro Cignarelli; Loreto Gesualdo

OBJECTIVE Chronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy in more than one-third of patients. We interrogated urine proteomic profiles generated by surface-enhanced laser desorption/ionization-time of flight/mass spectrometry with the aim of isolating a set of biomarkers able to reliably identify biopsy-proven diabetic nephropathy and to establish a stringent correlation with the different patterns of renal injury. RESEARCH DESIGN AND METHODS Ten micrograms of urine proteins from 190 subjects (20 healthy subjects, 20 normoalbuminuric, and 18 microalbuminuric diabetic patients and 132 patients with biopsy-proven nephropathy: 65 diabetic nephropathy, 10 diabetic with nondiabetic CKD [nd-CKD], and 57 nondiabetic with CKD) were run using a CM10 ProteinChip array and analyzed by supervised learning methods (Classification and Regression Tree analysis). RESULTS The classification model correctly identified 75% of patients with normoalbuminuria, 87.5% of those with microalbuminuria, and 87.5% of those with diabetic nephropathy when applied to a blinded testing set. Most importantly, it was able to reliably differentiate diabetic nephropathy from nd-CKD in both diabetic and nondiabetic patients. Among the best predictors of the classification model, we identified and validated two proteins, ubiquitin and β2-microglobulin. CONCLUSIONS Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis.


Clinical Chemistry and Laboratory Medicine | 2008

Saliva analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF/MS): from sample collection to data analysis.

Massimo Papale; Maria Carmela Pedicillo; Salvatore Di Paolo; Bradley John Thatcher; Lorenzo Lo Muzio; Pantaleo Bufo; Maria Teresa Rocchetti; Marta Centra; Elena Ranieri; Loreto Gesualdo

Abstract Background: Saliva is one of the most promising and easy-to-collect source of potential biomarkers of oral and systemic disease. We standardized a protocol suitable for pre-analytical treatment and for the analysis of whole normal saliva by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF/MS). Methods: We evaluated the impact of storage time, freeze/thaw cycles, denaturing agents, glycoproteins depletion, centrifugation, type of matrix and ProteinChip® used on the quality of the SELDI protein profile. Moreover, we explored the inter-individual and between-sex differences and the changes in the sample composition over the day. Results: Saliva was qualitatively stable, in the absence of protease inhibitors, for up to 3 h from the collection at room temperature, although the intensity of a number of peaks slightly decreased between 0 and 3 h and the addition of protease inhibitors did not completely revert this trend. The saliva proteome changed during the day and showed relevant between-sex differences. The protein profile remained stable for up to five freeze/thaw cycles. The addition of denaturing solutions and the depletion of glycoproteins improved the quality of the spectra without affecting their reproducibility. Conclusions: We defined a protocol that improved the quality and the reproducibility of SELDI-TOF/MS analysis, thus potentially supporting the search for putative biomarkers of disease. Clin Chem Lab Med 2008;46:89–99.


Experimental Diabetes Research | 2016

A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications

Francesca Conserva; Loreto Gesualdo; Massimo Papale

Diabetic nephropathy (DN), a microvascular complication occurring in approximately 20–40% of patients with type 2 diabetes mellitus (T2DM), is characterized by the progressive impairment of glomerular filtration and the development of Kimmelstiel-Wilson lesions leading to end-stage renal failure (ESRD). The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed.


European Journal of Endocrinology | 2011

Altered urinary excretion of aquaporin 2 in IgA nephropathy

Maria Teresa Rocchetti; Grazia Tamma; Domenica Lasorsa; Ida Valentina Suriano; Annamaria D'Apollo; Massimo Papale; Lisa Mastrofrancesco; Giuseppe Grandaliano; Maria Svelto; Giovanna Valenti; Loreto Gesualdo; Salvatore Di Paolo

OBJECTIVE The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indirectly, via RAS activation. Our aim is to explore the intrarenal activity of AVP, its relationship with RAS activity, as well as its modulation by therapies in IgAN. DESIGN In this observational study, we measured plasma copeptin, a surrogate marker of AVP, the urine excretion of aquaporin 2 (AQP2), a protein reflecting renal AVP action, and angiotensinogen (AGT), a parameter of renal RAS activation, and their relationship with renal function in 44 IgAN patients at the time of renal biopsy, without any drug therapy, and after 6-month treatment with ACEi or steroid+ACEi. Twenty-one patients with other CKD and 40 healthy subjects were recruited as controls. METHODS ELISAs were used to measure all variables of interest. RESULTS At baseline, IgAN patients showed higher urinary levels of AQP2, compared with controls and patients with other CKD. Urinary AQP2 and AGT levels strongly correlated with the presence of arterial hypertension. Steroids+ACEi caused the decrease of all the variables examined. The fall of urinary AQP2 and AGT following drug treatments was associated with the decrease of daily proteinuria. CONCLUSION Our findings would support the involvement of AVP-AQP2 axis, interacting with the RAS, in the progression of IgAN and candidate AQP2 as a possible novel marker of the disease.


European Journal of Inflammation | 2012

Salivary proteomic signatures of oral squamous cell carcinoma

Lucio Lo Russo; Massimo Papale; Donatella Perrone; Elena Ranieri; Corrado Rubini; Giovanni Giannatempo; Andrea Santarelli; Giuseppe Colella; Lorenzo Lo Muzio

Delay in diagnosing oral squamous cell carcinoma (OSCC) can be still identified as a major cause of its high morbidity and mortality. To date, the early diagnosis for OSCC is mainly based on clinical oral examination and there is an urgent need for reliable markers; thus, advancements in molecular technologies has set the stage for investigating new markers, as well as new diagnostic matrices. The aim of the present study is to investigate the presence of proteomic signatures of OSCC in saliva and their use as potential biomarkers for early and non-invasive diagnosis. Saliva from 45 OSCC patients and 30 healthy controls was analysed by SELDI-TOF mass spectrometry and ProteinChip® technology. A supervised multivariate statistical analysis (Classification and Regression Tree - CART) was used to build models for discriminating between OSCC and controls, and between early (ES-OSCC) and late stage (LS-OSCC) cancers. The peptide with 8041 Da mass was 22-fold more expressed in OSCC, thus being a suitable potential biomarker. Classification and regression analysis allowed to build a model that was capable of correctly classifying all cancers and controls in an independent testing set, using the 8041 m/z peak as splitter. Eleven peaks were also differently expressed between ES-OSCCand LS-OSCC, but, basing on these differences, it was not possible to build an algorithm to predict tumour staging. These findings confirm that saliva proteome in OSCC patients is different from healthy controls and these variations might reflect different stages of disease progression and are worthy of further validation as diagnostic and prognostic biomarkers.


American Journal of Enology and Viticulture | 2010

Identification of Grapevine Cultivar Biomarkers Using Surface-Enhanced Laser Desorption and Ionization (SELDI-TOF-MS)

Giovanni Povero; Massimo Papale; Loreto Gesualdo; Amedeo Alpi; Pierdomenico Perata; Elena Loreti

Protein-based tools for identifying plant varieties have developed rapidly, parallel to the evolution of gene-based technologies. In this study, we used ProteinChip technology to analyze the protein profiles of four different varieties of grapevines. This technique incorporates surface-enhanced laser desorption/ionization with mass spectrometry for rapid profiling and a comparison of protein profiles. Results revealed that several protein signals were differentially expressed in the varieties used, suggesting that this technology could potentially be used to identify cultivar-specific biomarkers in grapevines.


Oncotarget | 2017

Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell renal cell carcinoma

Massimo Papale; Grazia Vocino; Giuseppe Lucarelli; Monica Rutigliano; Margherita Gigante; Maria Teresa Rocchetti; Francesco Pesce; Francesca Sanguedolce; Pantaleo Bufo; Michele Battaglia; Giovanni Stallone; Giuseppe Grandaliano; Giuseppe Carrieri; Loreto Gesualdo; Elena Ranieri

Clear cell Renal Cell Carcinoma (ccRCC) causes over 13,000 deaths each year, and about 20,000 new cases/year in Europe. In most cases, the causes are unknown and, most importantly, there are no reliable biomarkers for the diagnosis and prognosis of this disease. The search for sensitive biomarkers for early diagnosis and prognosis of clear cell Renal Cell Carcinoma (ccRCC) is currently a fast growing field. We carried out proteomics analysis of 93 urinary samples of healthy subjects (HS) and patients affected by ccRCC, prostate cancer (PCa) and chronic kidney disease (CKD), that was able to successfully distinguish each group. The most significant candidate biomarker was identified by mass spectrometry as Raf Kinase Inhibitor Protein (RKIP), a key regulator of cell signaling, already described in several cancer types as a metastasis suppressor. By combining ELISA, immunoblotting and tissue microarray, we demonstrated that, in ccRCC, urinary excretion of RKIP and its phosphorylated form (p-RKIP) reflected the tissue expression of these putative biomarkers. Baseline urinary RKIP, evaluated in an independent cohort of 56 ccRCC patients and 28 HS, successfully distinguished both groups and, most importantly, a cut-off value of 10 ng/mg/g Pr/uCr enabled a highly accurate prediction of Cancer-specific survival and Progression-free survival. Furthermore, p-RKIP was totally undetectable in both tissue and urine samples of ccRCC, showing a great potential for diagnostics purposes. Our data indicate that urinary RKIP encompasses both the unphosphorylated and the phosphorylated form and that their combined evaluation can help in the diagnosis and prognosis of ccRCC.


Proteome Science | 2014

Two dimensional gel phosphoproteome of peripheral blood mononuclear cells: comparison between two enrichment methods.

Maria Teresa Rocchetti; Michela Alfarano; Leonarda Varraso; Salvatore Di Paolo; Massimo Papale; Elena Ranieri; Giuseppe Grandaliano; Loreto Gesualdo

BackgroundProtein phosphorylation is considered a key event in signal transduction. Peripheral blood mononuclear cells (PBMCs) are a critical component of the immune system. The analysis of PBMCs phosphoproteome might help elucidate the signaling pathways essential to their biological role in health, immunological diseases and cancer. Enrichment of phosphoproteins becomes a prerequisite for phosphoproteome analysis and conventionally requires a multi-step procedure and sophisticated equipments. In this study, we standardized 2D-PAGE phosphoproteome analysis of PBMCs and compared two phosphoprotein enrichment methods, lanthanum chloride precipitation and affinity micro-column. Further, the different specificity for PBMCs phosphorylated proteins of each method was investigated.ResultsPBMCs were isolated from fresh whole blood of ten healthy donors. PBMCs phosphoproteins were enriched either by phosphoprotein precipitation using lanthanum chloride, with an overall yield of 8.9 ± 4.7%, or by using an affinity micro-column, with a lower yield of 3.2 ± 1.6% (p = 0.05). Image analysis of Sypro-stained analytical 2D-PAGE gels detected 554 ± 68 protein spots for the lanthanum pattern [inter-assay coefficient of variation (CV) = 27.0%, intra-assay CV = 10.7%] and 575 ± 35 protein spots for the micro-column pattern (inter-assay CV = 26.8%; intra-assay CV = 11.0%) (p = 0.6), with 57% match of the spots detected by the 2 approaches. 1D gel electrophoresis and western blot analyses of the supernatants suggested a better lanthanum ions capability to deplete phosphoproteins in a PBMCs protein lysate compared to the affinity micro-column. On the other hand, 1D gel electrophoresis analysis of dephosphorylated PBMCs protein lysate revealed a relatively higher unspecificity for the lanthanum ions compared to affinity micro-column. Filamin-A, coronin 1A, pyruvate kinase isozymes M1/M2 and ficolin-1 were considerably more expressed in the lanthanum phosphoprotein pattern. Interestingly, ficolin-1 had not been reported in 2DE-PBMCs proteome profiles so far.ConclusionOur results describe the differences and the validity of phosphoprotein enrichment methods and provide two successful and complementary approaches for the 2DE phosphoproteome analysis of PBMCs.


Methods of Molecular Biology | 2014

Proteomic Approaches by SELDI and MALDI-TOF/MS for CTL Analysis

Massimo Papale; Maria Teresa Rocchetti

Extracellular stimuli activate, on target cells, a number of signal transduction processes regulating gene expression and the function and/or synthesis of the proteins. In order to highlight the slight changes of the quantity and quality of the proteome it is essential to optimize preparative strategies able to improve the signals of the less expressed proteins and to standardize the use of high-throughput techniques useful to detect them. We describe a complete workflow useful to enrich, from PBMC protein extracts and extrapolated to their subpopulations, the low-molecular-weight proteins and peptides and to detect them by SELDI-TOF protein profiling. The described protocol can also be applied to MALDI-TOF/MS instruments in order to obtain fast, reproducible, and high-quality protein profiles.


Clinica Chimica Acta | 2017

Differential proteome profile in ischemic heart disease: Prognostic value in chronic angina versus myocardial infarction. A proof of concept

Francesca Scebba; Massimo Papale; Silvia Rocchiccioli; Nadia Ucciferri; Federico Bigazzi; T. Sampietro; Antonio L'Abbate; Flavio Coceani; Debora Angeloni

The initial clinical manifestation of ischemic heart disease (IHD) i.e. unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is statistically associated with adverse or mild disease progression respectively in the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic biomarkers of IHD manifestation. We found several differentially expressed peaks but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively) were most reliable. Two of them were identified; 14,158m/z peak was the double-charged form of Apolipoprotein A-I and its vasoprotective action accords with prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude that SELDI-TOF-MS analysis may yield a panel of molecular signals able to retrospectively classify patients according to their clinical and molecular features, exploitable for predicting the natural course of IHD.

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