Enablers, Barriers and Strategies to Build Resilience Among Cancer Survivors: a Qualitative Study Protocol

Cancer is a life-threatening illness affecting all dimensions of a person's health. Cancer survivors must build resilience to face this adversity and continue their life projects. The present study explores the enablers, barriers, and strategies to build resilience among cancer survivors. This qualitative, descriptive exploratory study will use purposive sampling to recruit cancer survivors and healthcare professionals from two hospital centers in Lisbon and Tagus Valley. Interviews will be conducted until data saturation occurs. Data analysis will be performed using an inductive content analysis process with the help of the QDA Miner Lite database. The findings from this study will generate knowledge that may help stakeholders to identify effective strategies to build resilience among cancer survivors. By implementing strategies to foster resilience, healthcare professionals can potentially promote positive adaptations to cancer by strengthening resilience enablers and reducing the impact of barriers.info:eu-repo/semantics/publishedVersio

Mechanistic insights into transition metal-mediated bioorthogonal uncaging reactions.

Cleavage of C-O and C-N bonds mediated by transition metals is a promising bioorthogonal approach to rescue the activity of caged molecules, such as proteins and cytotoxic drugs, under biological conditions. However, the precise mechanism of such uncaging reactions remains elusive. This review provides mechanistic insights into metal-mediated bond-cleavage reactions, with the goals of understanding the main factors that influence the reaction and aiding the rational development of new caging groups/catalysts for chemical biology and drug-delivery applications

Mechanisms of nucleophilic substitution reactions of methylated Hydroxylamines with bis(2,4-dinitrophenyl)phosphate. Mass spectrometric identification of key intermediates

Mono- and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initial attack of NHMeOH and NMe2OH on bis(2,4-dinitrophenyl)phosphate (BDNPP), which is largely by oxygen phosphorylation. O-Methylation, however, blocks this reaction and NH2OMe then slowly reacts with BDNPP via N-attack at phosphorus and at the aryl group. With NHMeOH, the initial product of O-attack at phosphorus reacts further, either by reaction with a second NHMeOH or by a spontaneous shift of NHMe to the aryl group via a transient cyclic intermediate. There is a minor N-attack of NHMeOH on BDNPP in an S(N)2(Ar) reaction. Reactions occurring via N-attack are blocked by N-dimethylation, and reaction of NMe2OH with BDNPP occurs via O-attack, generating a long-lived product. Reaction mechanisms have been probed, and intermediates identified, by using both NMR and MS spectroscopy, with the novel interception of key reaction intermediates in the course of reaction by electrospray ionization mass and tandem mass spectrometry.69186024603

Reaction of bis(2,4-dinitrophenyl) phosphate with hydrazine and hydrogen peroxide. Comparison of O- and N-phosphorylation

Nonionic hydrazine reacts with anionic bis(2,4-dinitrophenyl) phosphate (BDNPP), giving 2,4dinitrophenyl hydrazine and dianionic 2,4-dinitrophenyl phosphate by an S(N)2(Ar) reaction, and at the phosphoryl center, giving 2,4-dinitrophenoxide ion and a transient phosphorylated hydrazine that rearranges intramolecularly to N-(2,4-dinitrophenyl)-N-phosphonohydrazine. Approximately 58% of the reaction at pD = 10 occurs by N-phosphorylation, as shown by P-31 NMR spectroscopy. Reaction of HO2- is wholly at phosphorus, and the intermediate peroxophosphate reacts intramolecularly, displacing a second 2,4-dinitrophenoxide ion, or with H2O2, giving 2,4-dinitrophenyl phosphate and O-2. Rate constants of O- and N-phosphorylation in reactions at phosphorus of NH2NH2, HO2-, and NH2OH and its methyl derivatives follow Bronsted relationships with similar slopes, but plots differ for oxygen and nitrogen nucleophiles. The reaction with NH2NH2 has been probed by using both NMR spectroscopy and electrospray ionization mass and tandem mass spectrometry, with the novel interception of key reaction intermediates in the course of reaction.69237898790

Platinum-triggered Bond-cleavage of Pentynoyl amide and N-propargyl handles for Drug-Activation

The ability to create ways to control drug activation at specific tissues while sparing healthy tissues remains a major challenge. The administration of exogenous target-specific triggers offers the potential for traceless release of active drugs on tumor sites from antibody-drug conjugates (ADCs) and caged prodrugs. We have developed a metal-mediated bond-cleavage reaction that uses platinum complexes[K2PtCl4 or Cisplatin (CisPt)] for drug activation. Key to the success of the reaction is a water-promoted activation process that triggers the reactivity of the platinum com-plexes. Under these conditions the decaging of pentynoyl tertiary amides and N-propargyls occurs rapidly in aqueous systems. In cells, the protected analogues of cytotoxic drugs 5-fluorouracil (5-FU) and monomethyl auristatin E (MMAE) are partially activated by non-toxic amounts of platinum salts. Additionally, a non-internalizing ADC built with a pentynoyl traceless linker that features a tertiary amide protected MMAE was also decaged in the presence of platinum salts for extracellular drug release in cancer cells. Finally, CisPt-mediated prodrug activation of a propargyl derivative of 5-FU was shown in a colorectal zebrafish xenograft model that led to significant reductions in tumor size. Overall, our results reveal a new metal-based cleavable reaction that expands the application of platinum complexes beyond those in catalysis and cancer therapy