Acute respiratory distress syndrome is characterized by loss of lung tissue as a result of inflammation and fibrosis. Augmenting tissue repair by the use of mesenchymal stem cells may be an important advance in treating this condition. We evaluated the role of term human umbilical cord cells derived from Wharton's jelly with a phenotype consistent with mesenchymal stem cells (uMSCs) in the treatment of a bleomycininduced mouse model of lung injury. uMSCs were administered systemically, and lungs were harvested at 7, 14, and 28 days post-bleomycin. Injected uMSCs were located in the lung 2 weeks later only in areas of inflammation and fibrosis but not in healthy lung tissue. The administration of uMSCs reduced inflammation and inhibited the expression of transforming growth factor-, interferon-␥, and the proinflammatory cytokines macrophage migratory inhibitory factor and tumor necrosis factor-␣. Collagen concentration in the lung was significantly reduced by uMSC treatment, which may have been a consequence of the simultaneous reduction in Smad2 phosphorylation (transforming growth factor- activity). uMSCs also increased matrix metalloproteinase-2 levels and reduced their endogenous inhibitors, tissue inhibitors of matrix metalloproteinases, favoring a pro-degradative milieu following collagen deposition. Notably, injected human lung fibroblasts did not influence either collagen or matrix metalloproteinase levels in the lung. The results of this study suggest that uMSCs have antifibrotic properties and may augment lung repair if used to treat acute respiratory distress syndrome. (Am J
BackgroundIn colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown.MethodsWe assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models.ResultsPatients consuming ≥2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04–2.68), compared with those consuming <2 servings per month (P
trend = 0.02). The association of sugar-sweetened beverages on cancer recurrence or mortality appeared greater among patients who were both overweight (body mass index ≥25 kg/m2) and less physically active (metabolic equivalent task-hours per week <18) (HR = 2.22; 95% CI, 1.29–3.81, P
trend = 0.0025).ConclusionHigher sugar-sweetened beverage intake was associated with a significantly increased risk of cancer recurrence and mortality in stage III colon cancer patients.
Purpose Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. Patients and Methods During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. Results Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (Ptrend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; Ptrend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; Ptrend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. Conclusion Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer.
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