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The abnormal extracellular matrix and tumor vasculature surrounding tumor cells result in uneven drug distribution within the tumor, thereby reducing the effective drug concentration ( CAFs play a critical role in tumor progression and drug resistance by secreting growth factors and cytokines that promote tumor cell proliferation and migration

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The absence of long-term safety studies for most NPs, some of which have been fully developed for years, corroborates this dilemma

was obtained from the Gene Expression Omnibus (GEO ID: GSE15653)

Interestingly, one of the studies showed that the use of antidepressants among depressed patients was protective of RA development [hazard ratio (HR) 0.74, 95% CI 0.710.76] (168), whereas another study found it to be associated with subsequent seronegative RA (HR 1.75, 95% CI 1.322.32) (169)

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