The emergent interest in cancer epigenetics stems from the fact that epigenetic modifications are implicated in virtually every step of tumorigenesis. More interestingly, epigenetic changes are reversible heritable changes that are not due to the alteration in DNA sequence but have potential to alter gene expression. Dietary agents consist of many bioactive ingredients which actively regulate various molecular targets involved in tumorigenesis. We present evidence that numerous bioactive dietary components can interfere with various epigenetic targets in cancer prevention and therapy. These agents include curcumin (turmeric), genistein (soybean), tea polyphenols (green tea), resveratrol (grapes), and sulforaphane (cruciferous vegetables). These bioactive components alter the DNA methylation and histone modifications required for gene activation or silencing in cancer prevention and therapy. Bioactive components mediate epigenetic modifications associated with the induction of tumor suppressor genes such as p21WAF1/CIP1 and inhibition of tumor promoting genes such as the human telomerase reverse transcriptase during tumorigenesis processes. Here, we present considerable evidence that bioactive components and their epigenetic targets are associated with cancer prevention and therapy which should facilitate novel drug discovery and development. In addition, remarkable advances in our understanding of basic epigenetic mechanisms as well as the rapid progress that is being made in developing powerful new technologies, such as those for sensitive and quantitative detection of epigenetic and epigenomic changes in cancer biology, hold great promise for novel epigenetic approaches to cancer prevention and therapy.

Background According to the 2004 Surgeon General’s Report on Health Consequences of Smoking, after >15 years of abstinence, the cardiovascular risk of former smokers becomes similar to that of never-smokers. Whether this health benefit of smoking cessation varies by amount and duration of prior smoking remains unclear. Methods and Results Of the 4482 adults ≥65 years without prevalent heart failure (HF) in the Cardiovascular Health Study (CHS), 2556 were never-smokers, 629 current smokers, and 1297 former smokers with >15 years of cessation, of whom 312 were heavy smokers (highest quartile; ≥32 pack-years). Age-sex-race-adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for centrally-adjudicated incident HF and mortality during 13 years of follow-up were estimated using Cox regression models. Compared to never-smokers, former smokers as a group had similar risk for incident HF (aHR, 0.99; 95% CI, 0.85–1.16) and all-cause mortality (aHR, 1.08; 95% CI, 0.96–1.20), but former heavy smokers had higher risk for both HF (aHR, 1.45; 95% CI, 1.15–1.83) and mortality (aHR, 1.38; 95% CI, 1.17–1.64). However, when compared to current smokers, former heavy smokers had lower risk of death (aHR, 0.64; 95% CI, 0.53–0.77), but not of HF (aHR, 0.97; 95% CI, 0.74–1.28). Conclusions After >15 years of smoking cessation, older adults who smoked <32 pack-years appear to achieve the health profile of never-smokers. Although former heavy (≥32 pack-years) smokers may not achieve this health benefit of prolonged smoking cessation, their risk is clearly lower relative to current smokers.

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Glioblastoma multiforme (GBM), the most common and aggressive form of primary brain tumor, presents a dismal prognosis. Current standard therapies are only able to improve patient survival by a few months. The search for alternative approaches in glioblastoma treatment, together with the recent discovery of a new class of small RNA molecules that are capable of regulating gene expression, prompted a race for a deeper and thorough understanding of how these molecules work. Today, it is known that microRNAs are involved in many cellular processes that are altered in GBM tumors, such as angiogenesis, invasion, cell proliferation and apoptosis. Research in this area is now gathering efforts to translate these findings into clinically relevant therapies that could improve the diagnosis and outcome of GBM patients. In this review, we discuss the use of microRNAs as potential diagnostic, prognostic and therapeutic tools against glioblastoma. We will also assess the current challenges and future perspectives of microRNA-based therapies, with a special focus on why this promising therapeutic approach is not yet in the clinic and how to overcome this limitation.

Objective-To determine the demographic and clinical predictors of in-hospital mortality among hospitalized nursing home (NH) residents. Design-Retrospective Measurements-In-hospital mortality.Methods-A multivariable logistic regression model was developed to determine independent predictors of in-hospital mortality using the 2005 dataset. The model was then applied to the 2006 dataset to determine the generalizability of the predictors.Results-Significant independent predictors of in-hospital mortality in 2005 included ≥85 years (adjusted odds ratio {OR}, 2.53; 95% confidence interval {CI}, 1.21-5.30; P=0.013), acute respiratory failure (adjusted OR, 5.67; 95% CI, 3.51-9.17; P<0.0001), septicemia (adjusted OR, 4.63; 95% CI, 3.08-6.96; P<0.0001) and acute renal failure (adjusted OR, 2.11; 95% CI, 1.30-3.41; P=0.002). These baseline characteristics also predicted in-hospital mortality in 2006: age ≥85 years (adjusted OR, 2.45; 95% CI, 1.31-4.59.30; P=0.005), acute respiratory failure (adjusted OR, 7.11; 95% CI, 4.46-11.33; P<0.0001), septicemia (adjusted OR, 3.91; 95% CI, 2.64-5.80; P<0.0001) and acute renal failure (adjusted OR, 2.75; 95% CI, 1.82-4.15; P<0.0001). Chronic morbidities were not associated with in-hospital mortality.* Correspondence and reprint request: Ali Ahmed, MD, MPH, UAB Center for Aging, 1530 3rd Ave South, CH-19, Ste-219, Birmingham AL 35294-2041, Tel.: 2059349632; Fax: 2059757099; aahmed@uab.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-In hospitalized NH residents, age ≥85 years and several acute conditions, but not chronic morbidities, predicted in-hospital mortality. Elderly NH residents at risk of developing these acute conditions may benefit from palliative care. NIH Public Access