27 research outputs found
Carrageenan-based hydrogels for the controlled delivery of PDGF-BB in bone tissue engineering applications
One of the major drawbacks found in most bone tissue engineering approaches developed so far consists in the
lack of strategies to promote vascularisation. Some studies have addressed different issues that may enhance
vascularisation in tissue engineered constructs, most of them involving the use of growth factors (GFs) that are
involved in the restitution of the vascularity in a damaged zone. The use of sustained delivery systems might also
play an important role in the re-establishment of angiogenesis. In this study, !-carrageenan, a naturally occurring
polymer, was used to develop hydrogel beads with the ability to incorporate GFs with the purpose of establishing
an effective angiogenesis mechanism. Some processing parameters were studied and their influence on the final
bead properties was evaluated. Platelet derived growth factor (PDGF-BB) was selected as the angiogenic factor
to incorporate in the developed beads, and the results demonstrate the achievement of an efficient encapsulation
and controlled release profile matching those usually required for the development of a fully functional vascular
network. In general, the obtained results demonstrate the potential of these systems for bone tissue engineering
applications.This work was supported by the European NoE EXPERTISSUES (NMP3-CT-2004-500283), the European STREP HIPPOCRATES (NMP3-CT-2003-505758), and by the Portuguese Foundation for Science and Technology (FCT) through the project PTDC/FIS/68517/2006 and through the V. Espirito Santo's Ph.D. grant (SFRH/BD/39486/2007)
The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas
Inhibition of FLT3 in AML: A focus on sorafenib
FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ∼30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation. In this review, we summarize the clinical data on sorafenib and other FLT3 inhibitors in AML