Development and validation of an in-silico tool for the study of therapeutic agents in 3D cell cultures.

Computational models constitute a fundamental asset for cancer research and drug R&D, as they provide controlled environments for testing of hypotheses and are characterized by the total knowledge of the system. These features are particularly useful for 3D cell culture models where a complex interaction among cells and their environments ensues. In this work, we present a programmable simulator capable of reproducing the behavior of cells cultured in 3D scaffolds and their response to pharmacological treatment. This system will be shown to be able to accurately describe the temporal evolution of the density of a population of MDA-MB-231 cells following their treatment with different concentrations of doxorubicin, together with a newly described drug-resistance mechanism and potential re-sensitization strategy. An extensive technical description of this model will be coupled to its experimental validation and to an analysis aimed at identifying which variables and behaviors account for differences in the response to treatment. Comprehensively, this work contributes to the growing field of integrated in-silico/in-vitro analysis of biological processes which has great potential for both the increase of our scientific knowledge and the development of novel, more effective treatments.

Change in condylar and mandibular morphology in juvenile idiopathic arthritis: Cone Beam volumetric imaging.

AIM: The aim of this study was to show the importance of Cone Beam Computerized Tomography (CBCT) to volumetrically quantify temporomandibular joint (TMJ) damage in patients with juvenile idiopathic arthritis (JIA), measuring condylar and mandibular real volumes. Methods. Thirty-four children with temporomandibular involvement by JIA were observed by CBCT. Four were excluded because of several imaging noises. The mandible was isolated from others craniofacial structures; the whole mandibular volume and its components' volumes (condyle, ramus, emibody, emisymphysis on right side and on left side) has been calculated by a 3D volume rendering technique. Results. The results show a highly significant statistical difference between affected side volumetric values versus normal side volumetric values, above all on condyle region (P<0.01), while there was no statistical difference between right versus left side. Conclusion. The CBCT represents a huge improvement in understanding of the condyle and mandibular morphological changes, even in the early stages of the JIA. In children the JIA can lead to TMJ damage with facial development and growth alterations.

RT-PCR determination of maspin and mammaglobin B in peripheral blood of healthy donors and breast cancer patients.

BACKGROUND: The aim of the present study was to evaluate the accuracy of two markers, maspin and mammaglobin B, singly or in combination, to detect breast cancer. To define better the potential and limits of the two markers for diagnostic purposes, blood positivity was analyzed in relation to clinical, pathological and biological tumor characteristics. PATIENTS AND METHODS: The markers were determined in peripheral blood (PB) samples from 27 healthy donors and 140 previously untreated patients using nested reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Positivity for maspin in blood samples was observed in 24% of patients with an 89% specificity. For mammaglobin B, positivity was observed in 7% of patients and never in healthy donors. The presence of maspin was correlated with cell proliferation of the primary tumor (P = 0.015), whereas mammaglobin B positivity correlated with pathological stage (P = 0.013). The presence of either marker was significantly related to nodal status. CONCLUSIONS: Our results indicate that the two markers in association could represent a potentially useful non-invasive tool to detect breast cancer. The validation of these markers as indicators of high risk of relapse is ongoing in a series of patients with an adequate follow-up.