Comparative Expression Profiling Reveals Molecular Markers Involved in the Progression of Cutaneous Melanoma towards Metastasis.

Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management.

The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy.

Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules in the fine tuning of melanoma progression. Here we review the contribution of microRNAs and lncRNAs to melanoma invasion, metastasis and acquired drug resistance, highlighting their potential for clinical applications as biomarkers and therapeutic targets.

Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment.

Cutaneous squamous cell carcinoma (cSCC) is a common type of neoplasia, representing a terrible burden on patients' life and clinical management. Although it seldom metastasizes, and most cases can be effectively treated with surgical intervention, once metastatic cSCC displays considerable aggressiveness leading to the death of affected individuals. No consensus has been reached as to which features better characterize the aggressive behavior of cSCC, an achievement hindered by the high mutational burden caused by chronic ultraviolet light exposure. Even though some subtypes have been recognized as high risk variants, depending on certain tumor features, cSCC that are normally thought of as low risk could pose an increased danger to the patients. In light of this, specific genetic and epigenetic markers for cutaneous SCC, which could serve as reliable diagnostic markers and possible targets for novel treatment development, have been searched for. This review aims to give an overview of the mutational landscape of cSCC, pointing out established biomarkers, as well as novel candidates, and future possible molecular therapies for cSCC.

Release of the Non-Steroidal Anti-Inflammatory Drug Flufenamic Acid by Multiparticulate Delivery Systems Promotes Adipogenic Differentiation of Adipose-Derived Stem Cells.

Engineered tissue-like structures often instigate an inflammatory response in the host that can inhibit wound healing and ultimately lead to the rejection of the implant. In our previous study, we have characterized the properties and biocompatibility of novel multiparticulate drug delivery systems (MDDS), based on collagen matrix with gradual release of anti-inflammatory drug flufenamic acid, we evaluated their anti-inflammatory potential and demonstrated their efficiency against burns and soft tissue lesions. In addition to these results, FA was previously described as a stimulant for adipogenesis, therefore we hypothesized that MDDS might also be appropriate for adipose tissue engineering. After the cell-scaffold constructs were obtained, cell morphology, adhesion and spreading on the systems were highlighted by scanning electron microscopy, immunostaining and confocal microscopy. The effect of FA-enriched materials on adipogenesis was evaluated at gene and protein level, by RT-qPCR, confocal microscopy and immunohistochemistry. Our current work indicates that flufenamic acid plays a beneficial role in adipocyte differentiation, with a direct effect upon the gene and protein expression of important early and late markers of adipogenesis, such as PPARγ2 and perilipin.

Nanocomposite foams based on flexible biobased thermoplastic polyurethane and ZnO nanoparticles as potential wound dressing materials.

In the present study biobased and soft thermoplastic polyurethane (TPU), obtained by polymerization from fatty acids, was used to produce TPU/ZnO nanocomposite foams by thermally induced phase separation method (TIPS). The produced foams were characterized and evaluated regarding their potential uses as wound dressing materials. The structure and morphology of the prepared flexible polymer foams with different content of ZnO nanofiller (1, 2, 5 and 10 wt% related to the polymer) were studied by Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). Highly porous nanocomposite structure made of interconnected pores with dimensions between 10 and 60 µm was created allowing water vapor transmission rate (WVTR) up to 8.9 mg/cm2·h. The TPU/ZnO foams, tested for their ability to support cells and their growth, showed highest cell proliferation for TPU nanocomposite foams with 2 and 5 wt% ZnO. Overall, the nanocomposite foams displayed a low cytotoxic potential (varied proportionally to the ZnO content) and good biocompatibility. All tested nanocomposite foams were found to be significantly active against biofilms formed by different Gram-positive (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Based on their behaviors, flexible TPU/ZnO nanocomposite foams can be considered for biomedical applications such as potential active wound dressing.