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Maria Azrad,Robin T. Vollmer,John Madden,Mark Dewhirst,Thomas J. Polascik,Denise C. Snyder,Mack T. Ruffin,Judd W. Moul,Dean E. Brenner,Wendy Demark-Wahnefried 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.4
Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede tumor proliferation by inhibiting activation of nuclear factor kappa B (NFκB) and vascular endothelial growth factor (VEGF). We examined the associations between urinary enterolactone and enterodiol with prostatic tumor expression of NFκB, VEGF, and Ki67 among 147 patients with prostate cancer who participated in a presurgical trial of flaxseed supplementation (30 g/day) for 30 days. Urinary enterolignans and tissue biomarkers were determined by high-performance liquid chromatography and immunohistochemistry, respectively. After supplementation, we observed significant correlations between intakes of plant lignan and urinary concentrations of total enterolignans (ρ=0.677, P<.0001), enterolactone (ρ=0.676, P<.0001), and enterodiol (ρ=0.628, P<.0001). Importantly, we observed that total urinary enterolignans and enterolactone were significantly and inversely correlated with Ki67 in the tumor tissue (ρ=−0.217, P=.011, and ρ=−0.230, P=.007, respectively), and a near-significant inverse association was observed for enterodiol (ρ=−0.159, P=.064). An inverse association was observed between enterolactone and VEGF (ρ=−0.143, P=.141), although this did not reach statistical significance. We did not observe an association between enterolignans and NFκB. In conclusion, flaxseed-derived enterolignans may hinder cancer cell proliferation via VEGF-associated pathways.
Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer
( Roshni D Kalachand ),( Ciaran O’riain ),( Sinead Toomey ),( Aoife Carr¸ Bsc ),( Kirsten M Timms ),( Sharon O’toole ),( Stephen Madden ),( Mark Bates ),( John J O’leary ),( Noreen Gleeson ),( Dearbha 대한산부인과학회 2020 Obstetrics & Gynecology Science Vol.63 No.5
Objective The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progressionfree survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). Results We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43-0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22-1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51-1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. Conclusion We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.
Artificial Muscles from Fishing Line and Sewing Thread
Haines, Carter S.,Lima, Má,rcio D.,Li, Na,Spinks, Geoffrey M.,Foroughi, Javad,Madden, John D. W.,Kim, Shi Hyeong,Fang, Shaoli,Jung de Andrade, Mô,nica,Gö,ktepe, Fatma,Gö,ktepe, &Oum American Association for the Advancement of Scienc 2014 Science Vol.343 No.6173
<P><B>Toward an Artificial Muscle</B></P><P>In designing materials for artificial muscles, the goals are to find those that will combine high strokes, high efficiency, long cycle life, low hysteresis, and low cost. Now, <B>Haines <I>et al.</I></B> (p. 868; see the Perspective by <B>Yuan and Poulin</B>) show that this is possible. Twisting high-strength, readily available polymer fibers, such as those used for fishing lines or sewing thread, to the point where they coil up, allowed construction of highly efficient actuators that could be triggered by a number of stimuli.</P>