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- Meani, F, et al.
(författare)
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Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology
- 2010
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Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 2:4, s. 504-518
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Tidskriftsartikel (refereegranskat)abstract
- Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight "peptidome" is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology
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| 2. |
- Vezzoli, M, et al.
(författare)
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RERT: A Novel Regression Tree Approach to Predict Extrauterine Disease in Endometrial Carcinoma Patients
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 10528-
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Tidskriftsartikel (refereegranskat)abstract
- Some aspects of endometrial cancer (EC) preoperative work-up are still controversial, and debatable are the roles played by lymphadenectomy and radical surgery. Proper preoperative EC staging can help design a tailored surgical treatment, and this study aims to propose a new algorithm able to predict extrauterine disease diffusion. 293 EC patients were consecutively enrolled, and age, BMI, children’s number, menopausal status, contraception, hormone replacement therapy, hypertension, histological grading, clinical stage, and serum HE4 and CA125 values were preoperatively evaluated. In order to identify before surgery the most important variables able to classify EC patients based on FIGO stage, we adopted a new statistical approach consisting of two-steps: 1) Random Forest with its relative variable importance; 2) a novel algorithm able to select the most representative Regression Tree (RERT) from an ensemble method. RERT, built on the above mentioned variables, provided a sensitivity, specificity, NPV and PPV of 90%, 76%, 94% and 65% respectively, in predicting FIGO stage > I. Notably, RERT outperformed the prediction ability of HE4, CA125, Logistic Regression and single cross-validated Regression Tree. Such algorithm has great potential, since it better identifies the true early-stage patients, thus providing concrete support in the decisional process about therapeutic options to be performed.
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| 3. |
- Ardighieri, L, et al.
(författare)
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Infiltration by CXCL10 Secreting Macrophages Is Associated With Antitumor Immunity and Response to Therapy in Ovarian Cancer Subtypes
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 690201-
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3+ T-cells and CD163+ tumor-associated macrophages (TAMs) densities identify a subgroup of immune infiltrated high-grade serous carcinomas (HGSCs) with better outcomes and superior response to platinum-based therapies. On the contrary, in most clear cell carcinomas (CCCs) showing poor prognosis and refractory to platinum, a high TAM density is associated with low T cell frequency. Immune infiltrated HGSC are characterized by the 30-genes signature (OC-IS30) covering immune activation and IFNγ polarization and predicting good prognosis (n = 312, TCGA). Immune infiltrated HGSC contain CXCL10 producing M1-type TAM (IRF1+pSTAT1Y701+) in close proximity to T-cells. A fraction of these M1-type TAM also co-expresses TREM2. M1-polarized TAM were barely detectable in T-cell poor CCC, but identifiable across various immunogenic human cancers. Single cell RNA sequencing data confirm the existence of a tumor-infiltrating CXCL10+IRF1+STAT1+ M1-type TAM overexpressing antigen processing and presentation gene programs. Overall, this study highlights the clinical relevance of the CXCL10+IRF1+STAT1+ macrophage subset as biomarker for intratumoral T-cell activation and therefore offers a new tool to select patients more likely to respond to T-cell or macrophage-targeted immunotherapies.
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