Nitric oxide and its production by iNOS is an established mechanism critical to tumor promotion or suppression. Macrophages have important roles in immunity, development, and progression of cancer and have a controversial role in pro- and antitumoral effects. The tumor microenvironment consists of tumor-associated macrophages (TAM), among other cell types that influence the fate of the growing tumor. Depending on the microenvironment and various cues, macrophages polarize into a continuum represented by the M1-like pro-inflammatory phenotype or the anti-inflammatory M2-like phenotype; these two are predominant, while there are subsets and intermediates. Manipulating their plasticity through programming or reprogramming of M2-like to M1-like phenotypes presents the opportunity to maximize tumoricidal defenses. The dual role of iNOS-derived NO also influences TAM activity by repolarization to tumoricidal M1-type phenotype. Regulatory pathways and immunomodulation achieve this through miRNA that may inhibit the immunosuppressive tumor microenvironment. This review summarizes the classical physiology of macrophages and polarization, iNOS activities, and evidence towards TAM reprogramming with current information in glioblastoma and melanoma models, and the immunomodulatory and therapeutic options using iNOS or NO-dependent strategies.
The Ancient Nubians have historically been renowned for their significant contributions to medicine. In spite of this, extremely poor oral health plagued this population. Paleopathological studies depict pronounced dental deterioration patterns far exceeding normal physiological progression. The advanced wear is popularly attributed to sand particle contamination of their daily diets. However, considering that individual wear mechanisms rarely act in isolation, we propose that adverse biochemical factors arising from regular consumption of tetracycline- fortified beer induced calcium malabsorption, and thus provided a synergistic diathesis in potentiating these effects. We examine these implications within the context of prevalent therapeutic remedies, bone fluorescence labeling data, and sociocultural attitudes when making the link between tetracycline and the compromised integrity of teeth, while citing the emergence of antibiotics actually predating formally-accepted convention.
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