BackgroundA shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of “Press-Pulse” disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred.MethodsThis general concept can be applied to the management of cancer by creating chronic metabolic stresses on tumor cell energy metabolism (press disturbance) that are coupled to a series of acute metabolic stressors that restrict glucose and glutamine availability while also stimulating cancer-specific oxidative stress (pulse disturbances). The elevation of non-fermentable ketone bodies protect normal cells from energy stress while further enhancing energy stress in tumor cells that lack the metabolic flexibility to use ketones as an efficient energy source. Mitochondrial abnormalities and genetic mutations make tumor cells vulnerable metabolic stress.ResultsThe press-pulse therapeutic strategy for cancer management is illustrated with calorie restricted ketogenic diets (KD-R) used together with drugs and procedures that create both chronic and intermittent acute stress on tumor cell energy metabolism, while protecting and enhancing the energy metabolism of normal cells.ConclusionsOptimization of dosing, timing, and scheduling of the press-pulse therapeutic strategy will facilitate the eradication of tumor cells with minimal patient toxicity. This therapeutic strategy can be used as a framework for the design of clinical trials for the non-toxic management of most cancers.
Background. Chemicals that store in lipid-rich compartments have the potential for long-term disruption of metabolic and endocrine processes. Given the evidence that persistent organic pollutants (POPs) also alter systemic metabolic, endocrine, and immune system functions, it follows that elevated chemical concentrations in intra-abdominal fat may alter function, through local chemical signaling, of visceral organs. Despite this potential, there has been little study defining POP concentrations in live human intra-abdominal fat. It is at present uncertain whether POPs distribute equally to all fat compartments, including fat in serum. Methods. Seven human subjects scheduled for elective surgery for benign lesions or cancer provided consent for removal of samples of subcutaneous and intra-abdominal fat and/or cancerous tissue. These samples were analyzed for 22 chlorinated pesticides and 10 polychlorinated biphenyl (PCB) congeners by GC/ECD plus GC/MS. Results. In only two subjects were the patterns and relative concentrations of PCBs and pesticides about the same in all fat compartments. In the other subjects, there were major differences in levels in subcutaneous as compared to other compartments, but with some higher and some lower. While the pattern of PCBs in the various compartments matched that of the pesticides in some, it was opposite in others. Interpretation. These results demonstrate a complicated distribution of PCB congeners and pesticides in various lipid compartments. The difference may reflect various Kows, different rates of metabolism, and/or different lengths of exposure. But the results suggest that contaminant levels in serum or even subcutaneous fat do not necessarily indicate concentrations and patterns in other kinds of adipose tissue.
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