Significant gaps are apparent in the literature addressing breast cancer survivorship and return to work. This is a complex problem and it will likely require interdisciplinary research teams to develop effective and feasible interventions for this population.
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity. Inhibition of glycolysis preferentially causes severe ATP depletion and massive cell death in FLT3/ITD leukemia cells. Glycolytic inhibitors significantly enhances the cytotoxicity induced by FLT3 tyrosine kinase inhibitor sorafenib. Importantly, such combination provides substantial therapeutic benefit in a murine model bearing FLT3/ITD leukemia. Our study suggests that FLT3/ITD mutation promotes Warburg effect, and such metabolic alteration can be exploited to develop effective therapeutic strategy for treatment of AML with FLT3/ITD mutation via metabolic intervention.
AimsRecovery after peripheral nerve injury (PNI) is often difficult, and there is no optimal treatment. Schwann cells (SCs) are important for peripheral nerve regeneration, so SC‐targeting treatments have gained importance. Adipose‐derived stem cells (ADSCs) and their exosomes can promote peripheral nerve repair, but their interactions with SCs are unclear.MethodsPurified SCs from sciatic nerve injury sites were harvested, and apoptosis and proliferation of SCs at post‐PNI 24 hours were analyzed. The effects of coculture with ADSCs and different concentrations of ADSC‐derived exosomes (ADSC‐Exo) were studied through in vitro experiments by flow cytometry, CCK8 assay, immunofluorescence staining, and histological analysis. The expression of the apoptosis‐related genes Bcl‐2 and Bax was also analyzed by qRT‐PCR.ResultsADSC‐Exo reduced the apoptosis of SCs after PNI by upregulating the anti‐apoptotic Bcl‐2 mRNA expression and downregulating the pro‐apoptotic Bax mRNA expression. Further, it also improved the proliferation rate of SCs. This effect was confirmed by the morphological and histological findings in PNI model rats.ConclusionOur results present a novel exosome‐mediated mechanism for ADSC‐SC cross talk that reduces the apoptosis and promotes the proliferation of SCs and may have therapeutic potential in the future.
Background: Lymphedema is one of the major treatment complications following breast cancer surgery and radiation. As the majority of women who develop breast cancer are at the age of employment, occupational functioning and employment are issues of concern. This study is novel in exploring the ways that lymphedema affects their work experience. Methods: A multiple-case study methodology drawn from Yin’s definition was employed. A total of 13 female survivors who developed breast cancer–related lymphedema participated by completing a survey and a 60-min semi-structured interview. Results: Four main themes emerged: (1) breast cancer–related lymphedema affects physical and emotional functioning associated with work; (2) ongoing treatment for breast cancer–related lymphedema creates challenges for work; (3) environmental factors affect the return-to-work experience; and (4) personal factors play a key role in adjusting to return-to-work. Conclusion: Both breast cancer–related lymphedema and its treatment have direct and indirect effects on work, with environmental and personal factors also shaping the work-return experience. This study suggests that breast cancer survivors with lymphedema who wish to return to work face potential barriers, and that gaps remain in the availability of supports.
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