Iron Oxide Nanoparticles as Carriers for DOX and Magnetic Hyperthermia after Intratumoral Application into Breast Cancer in Mice: Impact and Future Perspectives.

There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.

Hyperthermia affects collagen fiber architecture and induces apoptosis in pancreatic and fibroblast tumor hetero-spheroids in vitro.

Desmoplasia, an aberrant production of extracellular matrix (ECM), is considered as one predictive marker of malignancy of pancreatic cancer. In this paper, we study the effect of mild hyperthermia on fibrillary collagen architecture in murine Achilles tendons and in a pancreatic cancer model, in vitro, i.e. 3D hetero-type tumor spheroids, consisting of pancreatic cancer (Panc-1) cells and fibroblasts (WI-38), producing collagen fibers. We clearly demonstrate that i) mild hyperthermia (40 °C, 42 °C) damages the collagen architecture in murine Achilles tendons. ii) Mild extrinsic (hot air) and iron oxide nanoparticle based magnetic hyperthermia reduce the level of collagen fiber architecture in the generated hetero-type tumor spheroids. iii) Mild magnetic hyperthermia reduces cell vitality mainly through apoptotic and necrotic processes in the generated tumor spheroids. In conclusion, hetero-type 3D tumor spheroids are suitable for studying the effect of hyperthermia on collagen fibers, in vitro.

Low DEFB4 copy number and high systemic hBD-2 and IL-22 levels are associated with dermatophytosis.

Dermatophytes initiate dermatophytosis, but susceptibility to infection is dictated by host genetic factors, although the role of some of these-such as human beta-defensin 2 (hBD-2) genomic (DEFB4) copy number (CN) variation and its induction by IL-22-remains unclear. This was investigated in this cross-sectional study in 442 unrelated Caucasian subjects, including 195 healthy controls and 247 dermatophytosis patients who were divided into five subgroups according to clinical presentation. DNA samples were evaluated for DEFB4 CN variation by relative quantification using the comparative CT method, and serum hBD-2 and IL-22 levels were determined by ELISA. DEFB4 CN in patients was significantly lower and, except in the tinea cruris subgroup, serum hBD-2 levels were higher than in controls. The positive correlation between hBD-2 levels and DEFB4 CN observed in controls was not detected in patients, who also had higher serum IL-22 levels that were positively correlated with hBD-2 levels. Moreover, unlike in control subjects, the serum IL-22 level was negatively correlated with DEFB4 CN in patients. Taken together, these findings suggest an association between decreased DEFB4 CN, elevated serum hBD-2 and IL-22 levels, and dermatophytosis, underscoring a gene/cytokine interaction in the occurrence of this infection.