Inside anticancer therapy resistance and metastasis. Focus on CD36.

Despite recent advances in targeted cancer therapies, drug resistance remains an important setback in tumor control. Understanding the complex mechanisms involved in both innate and acquired drug resistance represents the first step in discovering novel therapeutic agents. Because of its importance in tumorigenesis, progression, and metastasis, lipid metabolism is increasingly garnering attention. CD36 is a membrane receptor at the top of the signaling cascade that transports lipids. Its expression has been repeatedly presented as an unfavorable prognostic factor for various tumor types, raising the question: could CD36 be a critical factor in cancer treatment resistance? In our review, we set out to explore the most prominent studies on the implication of CD36 in resistance to platinum-based drugs and other adjuvant cancer therapies in solid and haematological neoplasia. Moreover, we provide an overview of the latest anti-CD36 cancer therapies, thus opening new perspectives for future personalized medicine.

Gene expression profile of adhesion and extracellular matrix molecules during early stages of skeletal muscle regeneration.

Skeletal muscle regeneration implies the coordination of myogenesis with the recruitment of myeloid cells and extracellular matrix (ECM) remodelling. Currently, there are no specific biomarkers to diagnose the severity and prognosis of muscle lesions. In order to investigate the gene expression profile of extracellular matrix and adhesion molecules, as premises of homo- or heterocellular cooperation and milestones for skeletal muscle regeneration, we performed a gene expression analysis for genes involved in cellular cooperation, migration and ECM remodelling in a mouse model of acute crush injury. The results obtained at two early time-points post-injury were compared to a GSE5413 data set from two other trauma models. Third day post-injury, when inflammatory cells invaded, genes associated with cell-matrix interactions and migration were up-regulated. After day 5, as myoblast migration and differentiation started, genes for basement membrane constituents were found down-regulated, whereas genes for ECM molecules, macrophage, myoblast adhesion, and migration receptors were up-regulated. However, the profile and the induction time varied according to the experimental model, with only few genes being constantly up-regulated. Gene up-regulation was higher, delayed and more diverse following more severe trauma. Moreover, one of the most up-regulated genes was periostin, suggestive for severe muscle damage and unfavourable architecture restoration.

Myokines as Possible Therapeutic Targets in Cancer Cachexia.

Cachexia is an extremely serious syndrome which occurs in most patients with different cancers, and it is characterized by systemic inflammation, a negative protein and energy balance, and involuntary loss of body mass. This syndrome has a dramatic impact on the patient's quality of life, and it is also associated with a low response to chemotherapy leading to a decrease in survival. Despite this, cachexia is still underestimated and often untreated. New research is needed in this area to understand this complex phenomenon and ultimately find treatment methods and therapeutic targets. The skeletal muscle can act as an endocrine organ. Signaling between muscles and other systems is done through myokines, cytokines, and proteins produced and released by myocytes. In this review, we would like to draw attention to some of the most important myokines that could have potential as biomarkers and therapeutic targets: myostatin, irisin, myonectin, decorin, fibroblast growth factor 21, interleukin-6, interleukin-8, and interleukin-15.

Keratinocyte Motility Is Affected by UVA Radiation-A Comparison between Normal and Dysplastic Cells.

UVA radiation induces multiple and complex changes in the skin, affecting epidermal cell behavior. This study reports the effects of UVA exposure on normal (HaCaT) and dysplastic (DOK) keratinocytes. The adherence, spreading and proliferation were investigated by time-lapse measurement of cell layer impedance on different matrix proteins. Prior to UVA exposure, the time required for adherence and spreading did not differ significantly for HaCaT and DOK cells, while spreading areas were larger for HaCaT cells. Under UVA exposure, HaCaT and DOK cells behavior differed in terms of movement and proliferation. The cells' ability to cover the denuded surface and individual cell trajectories were recorded by time-lapse videomicroscopy, during wound healing experiments. Dysplastic keratinocytes showed more sensitivity to UVA, exhibiting transient deficiencies in directionality of movement and a delay in re-coating the denuded area. The actin cytoskeleton displayed a cortical organization immediately after irradiation, in both cell lines, similar to mock-irradiated cells. Post-irradiation, DOK cells displayed a better organization of stress fibers, persistent filopodia, and new, stronger focal contacts. In conclusion, after UVA exposure HaCaT and DOK cells showed a different behavior in terms of adherence, spreading, motility, proliferation, and actin cytoskeleton dynamics, with the dyplastic keratinocytes being more sensitive.