3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho; Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine; AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
Dr. Albino Martins
3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho; Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine; AvePark, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches.
Introduction: Receptor tyrosine kinases have been extensively studied owing to their frequently abnormal activation in the development and progression of human cancers. Platelet-derived growth factor receptors (PDGFRs) are receptors with intrinsic tyrosine kinase activity that regulate several functions in normal cells and are widely expressed in a variety of malignancies. After the demonstration that gastrointestinal stromal tumours without c-Kit mutations harbour PDGFR-α-activating mutations and that PDGFR-α is also a therapeutic target for imatinib mesylate, the interest for this receptor has increased considerably. Because breast cancer is one of the most frequent neoplasias in women worldwide, and only one study has reported PDGFR-α expression in breast carcinomas, the aim of this work was to investigate the potential significance of PDGFR-α expression in invasive mammary carcinomas. Methods: We used immunohistochemistry to detect PDGFR-α overexpression on a series of 181 formalin-fixed paraffin-embedded invasive ductal breast carcinomas and in two breast cancer cell lines: MCF-7 and HS578T. We associated its expression with known prognostic factors and we also performed polymerase chain reaction–single-stranded conformational polymorphism and direct sequencing to screen for PDGFR-α mutations. Results: PDGFR-α expression was observed in 39.2% of the breast carcinomas and showed an association with lymph node metastasis (P = 0.0079), HER-2 expression (P = 0.0265) and Bcl2 expression (P = 0.0121). A correlation was also found with the expression of platelet-derived growth factor A (PDGF-A; P = 0.0194). The two cell lines tested did not express PDGFR-α. Screening for mutations revealed alterations in the PDGFR-α gene at the following locations: 2500A→G, 2529T→A and 2472C→T in exon 18 and 1701G→A in exon 12. We also found an intronic insertion IVS17-50insA at exon 18 in all sequenced cases. None of these genetic alterations was correlated with PDGFR-α expression. The cell lines did not reveal any alterations in the PDGFR-α gene sequence. Conclusion: PDGFR-α is expressed in invasive breast carcinomas and is associated with biological aggressiveness. The genetic alterations described were not correlated with protein expression, but other mechanisms such as gene amplification or constitutive activation of a signalling pathway inducing this receptor could still sustain PDGFR-α as a potential therapeutic target.
19 November 2008 in Journal of Tissue Engineering and Regenerative Medicine
Despite being known for decades (since 1934), electrospinning has emerged recently as a very widespread technology to produce synthetic nanofibrous structures. These structures have morphologies and fiber diameters in a range comparable with those found in the extracellular matrix of human tissues. Therefore, nanofibrous scaffolds are intended to provide improved environments for cell attachment, migration, proliferation and differentiation when compared with traditional scaffolds. In addition, the process versatility and the highly specific surface area of nanofiber meshes may facilitate their use as local drug-release systems. Common electrospun nanofiber meshes are characterized by a random orientation. However, in some special cases, aligned distributions of the fibers can be obtained, with an interconnected microporous structure. The characteristic pore sizes and the inherent planar structure of the meshes can be detrimental for the desired cell infiltration into the inner regions, and eventually com...