Macrophages, IL-10, and nitric oxide increase, induced by hyperglycemic conditions, impact the development of murine melanoma B16F10-Nex2.

Epidemiological studies show a strong correlation between diabetes and the increased risk of developing different cancers, including melanoma. In the present study, we investigated the impact of a streptozotocin (STZ)-induced hyperglycemic environment on B16F10-Nex2 murine melanoma development. Hyperglycemic male C57Bl/6 mice showed increased subcutaneous tumor development, partially inhibited by metformin. Tumors showed increased infiltrating macrophages, and augmented IL-10 and nitric oxide (NO) concentrations. In vivo neutralization of IL-10, NO synthase inhibition, and depletion of macrophages reduced tumor development. STZ-treated TLR4 KO animals showed delayed tumor development; the transfer of hyperglycemic C57Bl/6 macrophages to TLR4 KO reversed this effect. Increased concentrations of IL-10 present in tumor homogenates of hyperglycemic mice induced a higher number of pre-angiogenic structures in vitro, and B16F10-Nex2 cells incubated with different glucose concentrations in vitro produced increased levels of IL-10. In summary, our findings show that a hyperglycemic environment stimulates murine melanoma B16F10-Nex2 primary tumor growth, and this effect is dependent on tumor cell stimulation, increased numbers of macrophages, and augmented IL-10 and NO concentrations. These findings show the involvement of tumor cells and other components of the tumor microenvironment in the development of subcutaneous melanoma under hyperglycemic conditions, defining novel targets for melanoma control in diabetic patients.

The kin17 Protein in Murine Melanoma Cells.

kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in the murine melanoma cell line B16F10-Nex2 and in two derived subclones with different metastatic potential, B16-8HR and B16-10CR. Nuclear and chromatin-associated protein fractions were analyzed, and kin17 was detected in all fractions, with an elevated concentration observed in the chromatin-associated fraction of the clone with low metastatic potential, suggesting that the kin17 expression level could be a marker of melanoma.

Comparison of Aß (1-40, 1-28, 11-22, and 29-40) aggregation processes and inhibition of toxic species generated in early stages of aggregation by a water-soluble ruthenium complex.

Neurotoxicity of amyloid beta (Aß) species generated in early stages of aggregation has been associated with development of Alzheimer's disease (AD). Consequently, the field of action of compounds that can identify and inhibit the formation of these species has enlarged considerably. This study investigates the effect and influence of the luminescent, water soluble metal complex cis-[Ru(phen)2(3,4Apy)2]2+ (RuApy, 3,4Apy = 3,4-diaminopyridine, phen = 1,10-phenanthroline) on the aggregation process and toxicity of Aß1-40 and its Aß1-28, Aß11-22 and Aß29-40 fragments since their early stages. The absence of correlation between the conformations generated by Aß fragments and the full length 1-40 peptide during aggregation and the absence of toxicity of Aß fragments to PC12 cells in all stages of aggregation indicated that the aggregation pathway and toxicity found to the full-length Aß1-40 depends on specific interactions between the three fragments. The toxicity of Aß1-40 was dependent on the aggregation step investigated: species generated at the beginning (15 min) of aggregation were toxic, whereas mature (120 min) fibrils were not. The RuApy complex is not toxic to PC12 cells up to 60 µM, and does not interfere with the aggregation pathway of the Aß fragments, but interferes with the aggregation of Aß1-40 and protects the PC12 cells, maintaining 100% of cell viability against the toxicity of Aß1-40 species generated in early stages of aggregation.