Mechanical study of PLA-PCL fibers during in vitro degradation

The aliphatic polyesters are widely used in biomedical applications since they are susceptible to hydrolytic and/or enzymatic chain cleavage, leading to alpha-hydroxyacids, generally metabolized in the human body. This is particularly useful for many biomedical applications, especially, for temporary mechanical supports in regenerative medical devices. Ideally, the degradation should be compatible with the tissue recovering. In this work, the evolution of mechanical properties during degradation is discussed based on experimental data. The decrease of tensile strength of PLA-PCL fibers follows the same trend as the decrease of molecular weight, and so it can also be modeled using a first order equation. For each degradation stage, hyperelastic models such as Neo-Hookean, Mooney-Rivlin and second reduced order, allow a reasonable approximation of the material behavior. Based on this knowledge, constitutive models that describe the mechanical behavior during degradation are proposed and experimentally validated. The proposed theoretical models and methods may be adapted and used in other biodegradable materials, and can be considered fundamental tools in the design of regenerative medical devices where strain energy is an important requirement, such as, for example, ligaments, cartilage and stents

Differential splicing using whole-transcript microarrays

<p>Abstract</p> <p>Background</p> <p>The latest generation of Affymetrix microarrays are designed to interrogate expression over the entire length of every locus, thus giving the opportunity to study alternative splicing genome-wide. The Exon 1.0 ST (sense target) platform, with versions for Human, Mouse and Rat, is designed primarily to probe every known or predicted exon. The smaller Gene 1.0 ST array is designed as an expression microarray but still interrogates expression with probes along the full length of each well-characterized transcript. We explore the possibility of using the Gene 1.0 ST platform to identify differential splicing events.</p> <p>Results</p> <p>We propose a strategy to score differential splicing by using the auxiliary information from fitting the statistical model, RMA (robust multichip analysis). RMA partitions the probe-level data into probe effects and expression levels, operating robustly so that if a small number of probes behave differently than the rest, they are downweighted in the fitting step. We argue that adjacent poorly fitting probes for a given sample can be evidence of <it>differential </it>splicing and have designed a statistic to search for this behaviour. Using a public tissue panel dataset, we show many examples of tissue-specific alternative splicing. Furthermore, we show that evidence for putative alternative splicing has a strong correspondence between the Gene 1.0 ST and Exon 1.0 ST platforms.</p> <p>Conclusion</p> <p>We propose a new approach, FIRMAGene, to search for differentially spliced genes using the Gene 1.0 ST platform. Such an analysis complements the search for differential expression. We validate the method by illustrating several known examples and we note some of the challenges in interpreting the probe-level data.</p> <p>Software implementing our methods is freely available as an <monospace>R</monospace> package.</p

Methylthioadenosine (MTA) inhibits melanoma cell proliferation and <it>in vivo </it>tumor growth

<p>Abstract</p> <p>Background</p> <p>Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment.</p> <p>Methods</p> <p>To investigate the therapeutic potential of MTA we performed <it>in vitro </it>proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities <it>in vivo </it>in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties.</p> <p>Results</p> <p><it>In vitro </it>experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting <it>in vivo </it>tumor growth. The molecular analysis of tumor samples and <it>in vitro </it>experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1.</p> <p>Conclusions</p> <p>MTA inhibits melanoma cell proliferation and <it>in vivo </it>tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment.</p

Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients

Purpose\ud The aim of this systematic review was to analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (RT) (morning versus late afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide.\ud \ud Methods\ud A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, no guideline possible.\ud \ud Results\ud A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and/or conflicting evidence.\ud \ud Conclusions\ud None of the agents reviewed was determined to be effective for the prevention or treatment of OM. Two agents, pilocarpine and pentoxifylline, were determined to be ineffective, in the populations listed above. Additional well-designed research is needed on other interventions