Alginate–lanthanide microspheres for MRI-guided embolotherapy

In cancer therapy, a promising treatment option to accomplish a high tumor-to-normal-tissue ratio is endovascular intervention with microsized particles, such as embolotherapy. In this study, alginate microspheres (ams) were prepared with the JetCutter technique, which is based on cutting a sodium alginate solution jet stream into small droplets of uniform size which are then cross-linked with different lanthanides or iron-III, resulting in microspheres of a predefined size which can be visualized by magnetic resonance imaging (MRI). The microspheres were investigated for their size and morphology (light microscopy and scanning electron microscopy analysis), cation content and MRI properties. The lanthanide-ams formulations, with a uniform size of 250 μm and a cation content between 0.72–0.94%, showed promising results for MR imaging. This was further demonstrated for Ho³⁺-cross-linked alginate microspheres (Ho³⁺-ams), the most potent microsphere formulation with respect to MR visualization, allowing single sphere detection and detailed microsphere distribution examination. Intravascular infusion of Ho³⁺-ams by catherization of ex vivo rabbit and porcine liver tissue and assessment of the procedure with MRI clearly showed accumulation and subsequently embolization of the targeted vessels, allowing accurate monitoring of the microsphere biodistribution throughout the tissue. Therefore, the different alginate–lanthanide microsphere formulations developed in this study show great potential for utilization as image-guided embolotherapy agents.     

Thermoresponsive Substrates used for the Expansion of Human Mesenchymal Stem Cells and the Preservation of Immunophenotype

The facile regeneration of undifferentiated human mesenchymal stem cells (hMSCs) from thermoresponsive surfaces facilitates the collection of stem cells avoiding the use of animal derived cell detachment agents commonly used in cell culture. This communication proposes a procedure to fabricate coatings from commercially available pNIPAm which is both affordable and a significant simplification on alternative approaches used elsewhere. Solvent casting was used to produce films in the micrometer range and successful cell adhesion and proliferation was highly dependent on the thickness of the coating produced with 1 μm thick coatings supporting cells to confluence. 3T3 cell sheets and hMSCs were successfully detached from the cast coatings upon temperature reduction. Furthermore, results indicate that the hMSCs remained undifferentiated as the surface receptor profile of hMSCs was not altered when cells were detached in this manner.     

Ageing and the small,non-coding RNA world

MicroRNAs, a class of small, non-coding RNAs, are now widely known for their importance in many aspects of biology. These small regulatory RNAs have critical functions in diverse biological events, including development and disease. Recent findings show that microRNAs are essential for lifespan determination in the model organisms, Caenorhabditis elegans and Drosophila, suggesting that microRNAs are also involved in the complex process of ageing. Further, short RNA fragments derived from longer parental RNAs, such as transfer RNA cleavage fragments, have now emerged as a novel class of regulatory RNAs that inhibit translation in response to stress. In addition, the RNA editing pathway is likely to act in the double-stranded RNA-mediated silencing machinery to suppress unfavorable RNA interference activity in the ageing process. These multiple, redundant layers in gene regulatory networks may make it possible to both stably and flexibly regulate genetic pathways in ensuring robustness of developmental and ageing processes.     

Regeneration of the periodontium using enamel matrix derivative in combination with an injectable bone cement

Objectives

Enamel matrix derivative (EMD) has proven to enhance periodontal regeneration; however, its effect is mainly restricted to the soft periodontal tissues. Therefore, to stimulate not only the soft tissues, but also the hard tissues, in this study EMD is combined with an injectable calcium phosphate cement (CaP; bone graft material). The aim was to evaluate histologically the healing of a macroporous CaP in combination with EMD.

Materials and methods

Intrabony, three-wall periodontal defects (2?×?2?×?1.7 mm) were created mesial of the first upper molar in 15 rats (30 defects). Defects were randomly treated according to one of the three following strategies: EMD, calcium phosphate cement and EMD, or left empty. The animals were killed after 12 weeks, and retrieved samples were processed for histology and histomorphometry.

Results

Empty defects showed a reparative type of healing without periodontal ligament or bone regeneration. As measured with on a histological grading scale for periodontal regeneration, the experimental groups (EMD and CaP/EMD) scored equally, both threefold higher compared with empty defects. However, most bone formation was measured in the CaP/EMD group; addition of CAP to EMD significantly enhanced bone formation with 50 % compared with EMD alone.

Conclusions

Within the limits of this animal study, the adjunctive use of EMD in combination with an injectable cement, although it did not affect epithelial downgrowth, appeared to be a promising treatment modality for regeneration of bone and ligament tissues in the periodontium.

Clinical relevance

The adjunctive use of EMD in combination with an injectable cement appears to be a promising treatment modality for regeneration of the bone and ligament tissues in the periodontium.     

Impact of preoperative radiation on survival of patients with T3N0 >7-cm non–small cell lung cancers treated with anatomic resection using the Surveillance,Epidemiology, and End Results database

Background

Very large non–small cell lung cancers (NSCLC) remain a therapeutic challenge. The objective of this study was to evaluate the effect of surgery in the presence and absence of neoadjuvant radiation (NRT) on survival of patients with T3N0 >7-cm NSCLCs.

Materials and methods

The Surveillance, Epidemiology, and End Results database was used to identify patients undergoing lobectomy or pneumonectomy for T3N0 NSCLC tumors >7 cm from 1999–2008. Patients were categorized into groups based on type of surgery performed and whether NRT was used. Five-year overall (OS) and lung cancer–specific survival (LCSS) were estimated by the Kaplan-Meier method and comparisons made using log-rank tests and Cox regression models.

Results

There were 1301 patients evaluated, including 1232 undergoing primary surgical therapy (PST) and 69 receiving NRT. NRT was not associated with improvements in 5-y OS (48% versus 41%, P = 0.062) or LCSS (59% versus 52%, P = 0.116) compared with PST. Lobectomies were associated with better 5-y OS (43% versus 33%; P = 0.006) and LCSS (54% versus 43%, P = 0.005) compared with pneumonectomies. On multivariate analysis, NRT did not produce any significant advantage in OS (P = 0.242) and LCSS (P = 0.208). Pneumonectomies were associated with significantly worse OS (hazard ratio, 1.32; P = 0.007) and LCSS (hazard ratio, 1.38; P = 0.005) when compared with lobectomies.

Conclusions

NRT, which most likely was a combination of chemotherapy and radiation, was not associated with improvements in OS or LCSS in patients with T3N0 >7-cm NSCLC compared with PST. When feasible, lobectomy appears more beneficial than pneumonectomy in terms of long-term survival for very large tumors.