Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Reaction Monitoring of Aliphatic Amines in Supercritical Carbon Dioxide by Proton Nuclear Magnetic Resonance Spectroscopy and Implications for Supercritical Fluid Chromatography

In the recent years, it has repeatedly been stated that amines react with CO2 and can therefore not be chromatographed under supercritical conditions with CO2. The aim of the present work is to elucidate the structural requirements and conditions that can lead to the reaction of an amine analyte with CO2 and, if this occurs, the structure of the formed product. The use of NMR spectroscopy with a flow probe for supercritical fluid chromatography enables the investigation of these unstable analytes in supercritical mediums. Several alkyl-substituted secondary benzylamines and some primary aromatic amines were dissolved in supercritical CO2 and investigated by employing on-line SFC-1H NMR spectroscopy. It was found that the condition of carbamic acid formation depends on the steric properties of the substituents of the amine. A 2-isopropylamino alcohol compound, metoprolol, was also investigated with the setup. No carbamic acid could be detected with the present conditions

Chiral supercritical fluid chromatography on porous graphitic carbon using commercial dimethyl β-cyclodextrins as mobile phase additive

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