DNA methylation changes in ovarian cancer are cumulative with disease progression and identify tumor stage

<p>Abstract</p> <p>Background</p> <p>Hypermethylation of promoter CpG islands with associated loss of gene expression, and hypomethylation of CpG-rich repetitive elements that may destabilize the genome are common events in most, if not all, epithelial cancers.</p> <p>Methods</p> <p>The methylation of 6,502 CpG-rich sequences spanning the genome was analyzed in 137 ovarian samples (ten normal, 23 low malignant potential, 18 stage I, 16 stage II, 54 stage III, and 16 stage IV) ranging from normal tissue through to stage IV cancer using a sequence-validated human CpG island microarray. The microarray contained 5' promoter-associated CpG islands as well as CpG-rich satellite and Alu repetitive elements.</p> <p>Results</p> <p>Results showed a progressive de-evolution of normal CpG methylation patterns with disease progression; 659 CpG islands showed significant loss or gain of methylation. Satellite and Alu sequences were primarily associated with loss of methylation, while promoter CpG islands composed the majority of sequences with gains in methylation. Since the majority of ovarian tumors are late stage when diagnosed, we tested whether DNA methylation profiles could differentiate between normal and low malignant potential (LMP) compared to stage III ovarian samples. We developed a class predictor consisting of three CpG-rich sequences that was 100% sensitive and 89% specific when used to predict an independent set of normal and LMP samples versus stage III samples. Bisulfite sequencing confirmed the NKX-2-3 promoter CpG island was hypermethylated with disease progression. In addition, 5-aza-2'-deoxycytidine treatment of the ES2 and OVCAR ovarian cancer cell lines re-expressed NKX-2-3. Finally, we merged our CpG methylation results with previously published ovarian expression microarray data and identified correlated expression changes.</p> <p>Conclusion</p> <p>Our results show that changes in CpG methylation are cumulative with ovarian cancer progression in a sequence-type dependent manner, and that CpG island microarrays can rapidly discover novel genes affected by CpG methylation in clinical samples of ovarian cancer.</p

Visual Evoked Potentials Change as Heart Rate and Carotid Pressure Change

The relationship between cardiovascular activity and the brain was explored by recording visual evoked potentials from the occipital regions of the scalp during systolic and diastolic pressure (Experiment I) and during fast and slow heartbeats at systolic and diastolic pressure (Experiment II). Visual evoked potentials changed significantly as heart rate and carotid pressure fluctuated normally, and these changes were markedly different in the right and left cerebral hemispheres. Evoked potentials recorded from the right hemisphere during various cardiac events differed significantly, whereas those recorded from the left did not. In both experiments, differences in the right hemisphere were due primarily to the P1 component, which was larger at diastolic than at systolic pressure. The present findings are consistent with formulations from behavioral studies suggesting that baroreceptor activity can influence sensory intake, and suggest that hemispheric specialization may play an important role in the relationship between cardiac events, the brain and behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73146/1/j.1469-8986.1982.tb02579.x.pd

Physicochemical and Functional-Properties of Rye Nonstarch Polysaccharides .1. Colorimetric Analysis of Pentosans and their Relative Monosaccharide Compositions in Fractionated (Milled) Rye Products

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Can We Get Some Cooperation Around Here? The Mediating Role of Group Norms on the Relationship Between Team Personality and Individual Helping Behaviors

Drawing on the group-norms theory of organizational citizenship behaviors and person-environment fit theory, we introduce and test a multilevel model of the effects of additive and dispersion composition models of team members' personality characteristics on group norms and individual helping behaviors. Our model was tested using regression and random coefficients modeling on 102 research and development teams. Results indicated that high mean levels of extraversion are positively related to individual helping behaviors through the mediating effect of cooperative group norms. Further, low variance on agreeableness (supplementary fit) and high variance on extraversion (complementary fit) promote the enactment of individual helping behaviors, but only the effects of extraversion were mediated by cooperative group norms. Implications of these findings for theories of helping behaviors in teams are discussed.close

88. Psychological resilience is associated with markers of inflammation and angiogenesis in pre-surgical ovarian cancer patients

Although psychological distress has been linked to biological processes that may promote ovarian cancer, little is known about the role that psychological resilience plays in this context. To address this issue, we examined how scores on a multi-faceted index of psychological resilience related to biomarkers of inflammation (interleukin-6; IL-6) and angiogenesis (vascular endothelial growth factor; VEGF) in a sample of 200 ovarian cancer patients assessed prior to diagnostic surgery. Using confirmatory factor analysis, a psychological resilience factor with the best fit was determined (Chi-square=7.28, p=.20; RMSEA=0.05; CFI=0.99; TLI=0.98). Factors included in the measurement model as indicators of resilience include psychological well-being (Psychological Well-Being Scales), positive affect (CESD-D positive affect subscale), and the spiritual, emotional, and functional well-being subscales of the Functional Assessment of Cancer Therapy scale. This psychological resilience index was then used in a structural equation model with IL-6 and VEGF regressed on the latent variable, controlling for cancer stage and grade, age, BMI, and fatigue. Greater psychological resilience was significantly associated with lower levels of IL-6 (beta=−0.20, SE=.09, p=0.026) but was unrelated to levels of VEGF (beta=−0.11, SE=.09, p=.241). This suggests that protective psychological factors may be linked to inflammatory biology in ovarian cancer. Additional research is needed to examine how psychological risk and resilience factors interact to predict clinical outcomes in ovarian cancer patients