Comparison of angiogenesis-related factor expression in primary tumor cultures under normal and hypoxic growth conditions

<p>Abstract</p> <p>Background</p> <p>A localized hypoxic environment occurs during tumor growth necessitating an angiogenic response or tumor necrosis results. Novel cancer treatment strategies take advantage of tumor-induced vascularisation by combining standard chemotherapeutic agents with angiogenesis-inhibiting agents. This has extended the progression-free interval and prolonged survival in patients with various types of cancer. We postulated that the expression levels of angiogenesis-related proteins from various primary tumor cultures would be greater under hypoxic conditions than under normoxia.</p> <p>Methods</p> <p>Fifty cell sources, including both immortalized cell lines and primary carcinoma cells, were incubated under normoxic conditions for 48 hours. Then, cells were either transferred to a hypoxic environment (1% O₂) or maintained at normoxic conditions for an additional 48 hours. Cell culture media from both conditions was collected and analyzed via an ELISA-based assay to determine expression levels of 11 angiogenesis-related factors: VEGF, PDGF-AA, PDGF-AA/BB, IL-8, bFGF/FGF-2, EGF, IP-10/CXCL10, Flt-3 ligand, TGF-β1, TGF-β2, and TGF-β3.</p> <p>Results</p> <p>A linear correlation between normoxic and hypoxic growth conditions exists for expression levels of eight of eleven angiogenesis-related proteins tested including: VEGF, IL-8, PDGF-AA, PDGF-AA/BB, TGF-β1, TGF-β2, EGF, and IP-10. For VEGF, the target of current therapies, this correlation between hypoxia and higher cytokine levels was greater in primary breast and lung carcinoma cells than in ovarian carcinoma cells or tumor cell lines. Of interest, patient cell isolates differed in the precise pattern of elevated cytokines.</p> <p>Conclusion</p> <p>As linear correlations exist between expression levels of angiogenic factors under normoxic and hypoxic conditions <it>in vitro</it>, we propose that explanted primary cells may be used to probe the <it>in vivo </it>hypoxic environment. Furthermore, differential expression levels for each sample across all proteins examined suggests it may be possible to build a predictor for angiogenesis-related anticancer agents, as each sample has a unique expression profile. Further studies should be performed to correlate <it>in vitro </it>protein expression levels of angiogenesis-related factors with <it>in vivo </it>patient response.</p

Magnetic phase diagram of the frustrated S=1/2 chain magnet LiCu_2O_2

We present the results of the magnetization and dielectric constant measurements on untwinned single crystal samples of the frustrated S=1/2 chain cuprate LiCu_2O_2. Novel magnetic phase transitions were observed. A spin flop transition of the spiral spin plane was observed for the field orientations H||a,b. The second magnetic transition was observed at H~15 T for all three principal field directions. This high field magnetic phase is discussed as a collinear spin-modulated phase which is expected for an S=1/2 nearest-neighbor ferromagnetic and next-nearest-neighbor antiferromagnetic chain system

Maternal Yolk Steroids: A Potential Compensatory Mechanism for Red-winged Blackbirds (Agelaius phoeniceus) In North Dakota

Many of the suggested management techniques directed at reducing blackbird breeding populations fail to incorporate the underlying mechanisms regulating populations. Theoretically, removal of individuals from the breeding population should lower the breeding densities and presumably reduce recruitment. However, compensatory responses might occur with decreased breeding densities, but no empirical data are available to test this hypothesis. Much of the underlying compensatory theory is based on differential allocation of resources to reproduction vs. self maintenance at different breeding densities, mainly in the form of depensatory effects of resource limitation on growth and survival. However, as the breeding density in an area changes, social interactions among individuals also change (Whittingham and Schwabl 2002; Pilz and Smith 2004). Recent research has shown maternally derived steroid hormones present in eggs offer a potential compensatory mechanism by which adult social interactions affect offspring growth and survival (Schwabl 1996a; Schwabl 1996b). Gaining insight into the underlying mechanisms regulating red-winged blackbird populations will allow for more effective and efficient management techniques. This study focuses on the effects of density and social interactions on nesting female red-winged blackbirds and the effects of maternally derived yolk steroids on offspring survival

NMR and LDA evidence for spiral magnetic order in the chain cuprate LiCu2O2

We report on {6,7}Li nuclear magnetic resonance measurements of the spin-chain compound LiCu2O2 in the paramagnetic and magnetically ordered states. Below T about 24 K the NMR lineshape presents a clear signature of incommensurate (IC) static modulation of the local magnetic field consistent with an IC spiral modulation of the magnetic moments. {7}Li NMR reveals strong phason-like dynamical fluctuations extending well below 24 K. We hypothesize that a series of phase transitions at 24.2, 22.5, and 9 K reflects a "Devil's staircase" type behavior generic for IC systems. LDA based calculations of exchange integrals reveal a large in-chain frustration leading to a magnetical spiral.Comment: 4 pages, 4 figure

Disparities in Quality of Life by Appalachian-Designation among Women with Breast Cancer

Introduction: Few studies have examined the association of geography and quality of life (QOL) among breast cancer patients, particularly differences between Appalachian and non-Appalachian Kentucky women, which is important given the cancer and socioeconomic disparities present in Appalachia. Purpose: The purpose of this study was to determine whether women with breast cancer residing in Appalachian Kentucky experience poorer health outcomes in regards to depression, stress, QOL, and spiritual wellbeing, relative to those living in non-Appalachian Kentucky after adjusting for demographic, socioeconomic, and health-related factors. Methods: Women, aged 18–79, recruited from the Kentucky Cancer Registry between 2009 and 2013 with an incident, primary breast cancer diagnosis completed a telephone interview within 12 months of diagnosis. In this cross-sectional study, sociodemographic characteristics and mental and physical health status were assessed, including number of comorbid conditions, symptoms of depression and stress, and QOL. Results: Among 1245 women with breast cancer, 334 lived in Appalachia and 911 in non-Appalachian counties of Kentucky. Appalachian breast cancer patients differed from non-Appalachian patients on race, education, income, health insurance status, rurality, smoking, and stage at diagnosis. In unadjusted analysis, Appalachian residence was associated with having significantly more comorbid conditions, more symptoms of stress in the past month, and lower Functional Assessment of Cancer Therapy-Breast scores compared to non-Appalachian residence. Implications: However, adjustment for sociodemographic and health-related differences by region appear to explain geographic differences in these poorer QOL indicators for women living in Appalachian Kentucky relative to non-Appalachian Kentucky. Policy-, provider-, and individual-level implications are discussed

Effects of a Mindfulness-Based Intervention on Distress, Weight Gain, and Glucose Control for Pregnant Low-Income Women: A Quasi-Experimental Trial Using the ORBIT Model.

BackgroundStress can lead to excessive weight gain. Mindfulness-based stress reduction that incorporates mindful eating shows promise for reducing stress, overeating, and improving glucose control. No interventions have tested mindfulness training with a focus on healthy eating and weight gain during pregnancy, a period of common excessive weight gain. Here, we test the effectiveness of such an intervention, the Mindful Moms Training (MMT), on perceived stress, eating behaviors, and gestational weight gain in a high-risk sample of low income women with overweight/obesity.MethodWe conducted a quasi-experimental study assigning 115 pregnant women to MMT for 8&nbsp;weeks and comparing them to 105 sociodemographically and weight equivalent pregnant women receiving treatment as usual. Our main outcomes included weight gain (primary outcome), perceived stress, and depression.ResultsWomen in MMT showed significant reductions in perceived stress (β&nbsp;= - 0.16) and depressive symptoms (β&nbsp;= - 0.21) compared to the treatment as usual (TAU) control group. Consistent with national norms, the majority of women (68%) gained excessive weight according to Institute of Medicine weight-gain categories, regardless of group. Slightly more women in the MMT group gained below the recommendation. Among secondary outcomes, women in MMT reported increased physical activity (β&nbsp;=&nbsp;0.26) and had lower glucose post-oral glucose tolerance test (β&nbsp;= - 0.23), being 66% less likely to have impaired glucose tolerance, compared to the TAU group.ConclusionA short-term intervention led to significant improvements in stress, and showed promise for preventing glucose intolerance. However, the majority of women gained excessive weight. A longer more intensive intervention may be needed for this high-risk population. Clinical Trials.gov #NCT01307683

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials &amp; methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans

Deployable-erectable trade study for space station truss structures

The results of a trade study on truss structures for constructing the space station are presented. Although this study was conducted for the reference gravity gradient space station, the results are generally applicable to other configurations. The four truss approaches for constructing the space station considered in this paper were the 9 foot single fold deployable, the 15 foot erectable, the 10 foot double fold tetrahedral, and the 15 foot PACTRUSS. The primary rational for considering a 9 foot single-fold deployable truss (9 foot is the largest uncollapsed cross-section that will fit in the Shuttle cargo bay) is that of ease of initial on-orbit construction and preintegration of utility lines and subsystems. The primary rational for considering the 15 foot erectable truss is that the truss bay size will accommodate Shuttle size payloads and growth of the initial station in any dimension is a simple extension of the initial construction process. The primary rational for considering the double-fold 10 foot tetrahedral truss is that a relatively large amount of truss structure can be deployed from a single Shuttle flight to provide a large number of nodal attachments which present a pegboard for attaching a wide variety of payloads. The 15 foot double-fold PACTRUSS was developed to incorporate the best features of the erectable truss and the tetrahedral truss