Multiphase modelling of tumour growth and extracellular matrix interaction: mathematical tools and applications

Resorting to a multiphase modelling framework, tumours are described here as a mixture of tumour and host cells within a porous structure constituted by a remodelling extracellular matrix (ECM), which is wet by a physiological extracellular fluid. The model presented in this article focuses mainly on the description of mechanical interactions of the growing tumour with the host tissue, their influence on tumour growth, and the attachment/detachment mechanisms between cells and ECM. Starting from some recent experimental evidences, we propose to describe the interaction forces involving the extracellular matrix via some concepts coming from viscoplasticity. We then apply the model to the description of the growth of tumour cords and the formation of fibrosis

Apparent diffusion coefficient by diffusion-weighted magnetic resonance imaging as a sole biomarker for staging and prognosis of gastric cancer

Objective: To investigate the role of apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) when applied to the 7th TNM classification in the staging and prognosis of gastric cancer (GC). Methods: Between October 2009 and May 2014, a total of 89 patients with non-metastatic, biopsy proven GC underwent 1.5T DW-MRI, and then treated with radical surgery. Tumor ADC was measured retrospectively and compared with final histology following the 7th TNM staging (local invasion, nodal involvement and according to the different groups — stage I, II and III). Kaplan-Meier curves were also generated. The follow-up period is updated to May 2016. Results: Median follow-up period was 33 months and 45/89 (51%) deaths from GC were observed. ADC was significantly different both for local invasion and nodal involvement (P<0.001). Considering final histology as the reference standard, a preoperative ADC cut-off of 1.80×10–3 mm2 /s could distinguish between stages I and II and an ADC value of ≤1.36×10–3 mm2 /s was associated with stage III (P<0.001). Kaplan-Meier curves demonstrated that the survival rates for the three prognostic groups were significantly different according to final histology and ADC cut-offs (P<0.001). Conclusions: ADC is different according to local invasion, nodal involvement and the 7th TNM stage groups for GC, representing a potential, additional prognostic biomarker. The addition of DW-MRI could aid in the staging and risk stratification of GC

Percolation, Morphogenesis, and Burgers Dynamics in Blood Vessels Formation

Experiments of in vitro formation of blood vessels show that cells randomly spread on a gel matrix autonomously organize to form a connected vascular network. We propose a simple model which reproduces many features of the biological system. We show that both the model and the real system exhibit a fractal behavior at small scales, due to the process of migration and dynamical aggregation, followed at large scale by a random percolation behavior due to the coalescence of aggregates. The results are in good agreement with the analysis performed on the experimental data.Comment: 4 pages, 11 eps figure

Measurements and tests on FBK silicon sensors with an optimized electronic design for a CTA camera

In October 2013, the Italian Ministry approved the funding of a Research & Development (R&D) study, within the "Progetto Premiale TElescopi CHErenkov made in Italy (TECHE)", devoted to the development of a demonstrator for a camera for the Cherenkov Telescope Array (CTA) consortium. The demonstrator consists of a sensor plane based on the Silicon Photomultiplier (SiPM) technology and on an electronics designed for signal sampling. Preliminary tests on a matrix of sensors produced by the Fondazione Bruno Kessler (FBK-Trento, Italy) and on electronic prototypes produced by SITAEL S.p.A. will be presented. In particular, we used different designs of the electronics in order to optimize the output signals in terms of tail cancellation. This is crucial for applications where a high background is expected, as for the CTA experiment.Comment: 5 pages, 6 figures; Proceedings of the 10th Workshop on Science with the New Generation of High-Energy Gamma-ray experiments (SciNeGHE) - PoS(Scineghe2014)00

Initial/boundary-value problems of tumor growth within a host tissue

This paper concerns multiphase models of tumor growth in interaction with a surrounding tissue, taking into account also the interplay with diffusible nutrients feeding the cells. Models specialize in nonlinear systems of possibly degenerate parabolic equations, which include phenomenological terms related to specific cell functions. The paper discusses general modeling guidelines for such terms, as well as for initial and boundary conditions, aiming at both biological consistency and mathematical robustness of the resulting problems. Particularly, it addresses some qualitative properties such as a priori nonnegativity, boundedness, and uniqueness of the solutions. Existence of the solutions is studied in the one-dimensional time-independent case.Comment: 30 pages, 5 figure

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence

Background: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. Methods: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. Results: We identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. Conclusions: These findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations

Future treatment strategies of aggressive pituitary tumors

While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR5) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing’s disease, and the SSTR5 analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR5 and SSTR2 may help reduce adenoma recurrence in the future

The Italian version of the Reflective Functioning Questionnaire: validity data for adults and its association with severity of borderline personality disorder

INTRODUCTION: Impairments in the ability to understand others and the self in terms of internal mental states (reflective functioning [RF] or mentalizing) are thought to play a key role in the development of borderline personality disorder (BPD). The first aim of this study was to validate the Italian version of the Reflective Functioning Questionnaire (RFQ), a brief self-report measure of RF, by examining its factor structure with Principal Component Analyses (PCA), and correlations with constructs that should be theoretically related to RF. In addition, we investigated whether the RFQ could empirically distinguish between healthy controls and carefully diagnosed BPD patients using Research Operating Curve methods, and was related to severity of borderline pathology as measured with the Shedler–Westen Assessment Procedure (SWAP), an observer-rated measure of BPD pathology. // METHODS: An Italian translation of the RFQ was administered to a sample of 154 healthy controls and a clinical sample of 59 BPD patients diagnosed with the Structured Clinical Interview for DSM-IV Axis II disorders. Clinical severity of BPD was assessed with the SWAP. Normal controls completed self-report inventories of constructs related to RF (mindfulness, empathy, Theory of Mind, alexithymia, and autistic traits). // RESULTS: PCA confirmed the a priori factor structure in the Italian translation of the RFQ, showing two subscales that measure certainty and uncertainty about mental states, with satisfactory reliability and construct validity. These dimensions also distinguished BPD patients from healthy controls (p < 0.05). ROC analyses showed that the uncertainty subscale discriminated BPD patients from healthy individuals (area under the curve = 78%, cut of 4.5 points, sensitivity = 73%, specificity = 68%). Within the patient group, regression analyses showed uncertainty about mental states to have a significant unique contribution in predicting BPD severity (p < 0.05), explaining 12% of the variance. // CONCLUSIONS: Results largely supported the reliability and validity of the Italian version of the RFQ. These findings also provide further evidence for the role of impairments in mentalizing and reinforce the rationale for offering mentalization-based interventions to individuals with this disorder