Search

The "microenvironment" where a tumor develops plays a fundamental role in determining its progression, the onset of metastasis and, eventually, its resistance to therapies. Tumor cells can be considered more or less invasive depending both on the nature of the cells and on the site where they are located. Commonly adopted laboratory culture protocols for the investigation of tumor cells take usually place on standard two-dimensional supports. However, such cultures do not allow for reproduction of the biophysical properties of the tumor’s microenvironment, thus causing the cells to lose most of their relevant characteristics. In this work MDA-MB 231 breast cancer cells were cultivated within Poly- l -Lactic Acid (PLLA) scaffolds produced via Thermally Induced Phase Separation (TIPS). Starting from a ternary solution (polymer-solvent-nonsolvent) we produced scaffolds with different morphologies, porosities and pore architectures. The influence of porosity and average pore size upon cell adhesion and growth were investigated by using Cell Counting Kit-8 (CCK-8) as cell viability test, a fluorescence assay staining cell with DAPI and Scanning Electron Microscopy (SEM). Our study demonstrates that the average pore size of the polymeric scaffolds influences both the cell adhesion and resulting morphology of the growing breast cancer cells. In particular, the reported data corroborate the evidence that an average pore size ranging from 40 to 50 μm induces tumor cell aggregation and the formation of the irregular tumor masses typically observed in-vivo. In addition, TIPS proved to be a suitable manufacturing technique for finely tuning the scaffolds’ architecture, relevant to developing the most effective microenvironment for an in-vitro tumor cells growth closely mimicking in-vivo conditions.

Cognitive abilities have been extensively studied in children and adults with Duchenne muscular dystrophy (DMD) but less has been reported on younger children. This is not surprising as the diagnosis of DMD remains at a mean age of 4 and 6 months. The aim of this study was to assess neurodevelopmental abilities before the age of 4 years in a cohort of DMD patients in whom early diagnosis was possible because of incidental raised creatine kinase levels, family history or neonatal screenings. Sixty-six children with a diagnosis of DMD of age between 7 and 43 months (mean 27 months) were included in the study. All children were assessed using the Griffiths Mental Development Scales, establishing both total scores and subscores for each of the subscales. Thirty-six of the 66 children had a developmental quotient (DQ) > 85, 21 had a DQ between 70 and 84 and 9 below 70. The mean total DQ was 86 (SD 16.07) and the mean scores for each subscale were as follows: (A) locomotor: 79 (19.47), (B) personal social: 91 (18.48), (C) hearing and speech: 85 (23.59), (D) eye hand coordination: 87 (17.20), (E) performance: 88 (18.40), (F) practical reasoning: 95 (16.08). (Scale F only for patients older than 2 years.) Details of mutations were available in 58 of the 66 children included. Low DQ were found in five of the 26 (18.5 %) patients with mutations before exon 44, in 15 of the 29 with mutations between 44 and 55 (51.7 %) and in all three with mutations in the exons beyond exon 55. it Conclusions: The DQ found in our cohort was on average one SD below a DQ of 100 with approximately 45% of the children having a DQ below 85. The locomotor scale had the lowest scores but even when we excluded the locomotor scale, a DQ below 85 was found in 28 patients (43%).