Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Evaluation of a regional disease management programme for patients with asthma or chronic obstructive pulmonary disease\ud

Objectives. To assess the impact of a population-based disease management programme for adult patients with asthma or chronic obstructive pulmonary disease (COPD) on process measures, intermediate outcomes, and endpoints of care. \ud Design. Quasi-experimental design with 12-month follow-up. \ud Setting. Region of Maastricht (the Netherlands) including university hospital and 16 general practices. \ud Participants. Nine hundred and seventy-five patients of whom 658 have asthma and 317 COPD. \ud Intervention. Disease management programme. \ud Main outcome measure(s). Endpoints of care are respiratory health, health utility, patient satisfaction, and total health care costs related to asthma or COPD. \ud Results. Quality aspects of care, disease control, self-care behaviour, smoking status, disease-specific knowledge, and patients’ satisfaction improved after implementation of the programme. Lung function was not affected by implementation of the programme. For COPD patients, a significant improvement in health utility was found. For patients with asthma, significant cost savings were measured. \ud Conclusions. Organizing health care according to principles of disease management for adults with asthma or COPD is associated with significant improvements in several processes and outcomes of care, while costs of care do not exceed the existing budget\u

Beneficial effects of sitostanol on the attenuated immune function in asthma patients: results of an in vitro approach.

BACKGROUND: In vitro and animal studies have suggested that plant sterols and stanols increase cytokine production by T-helper-1 cells. This may be beneficial for patient groups characterized by a T-helper-2 dominant immune response, e.g. asthma patients. (1) to evaluate whether sitostanol induces a T-helper-1 shift in peripheral blood mononuclear cells (PBMCs) from asthma patients, and (2) to unravel the role of regulatory T-cells in this respect. METHODOLOGY/PRINCIPAL FINDINGS: PBMCs from 10 asthma patients and 10 healthy subjects were isolated and incubated with 1.2 µM sitostanol, while stimulated with 5 µg/ml PHA. Similar amounts of cholesterol were used to determine whether effects were specific for plant stanols or for sterols in general. Changes in cytokine production were measured using antibody arrays and ELISAs. Changes in regulatory T-cell population size were measured by flow cytometry, using intracellular Foxp3 staining. Sitostanol increased production of IFNγ by 6.5% and IL-2 by 6.0% compared to cholesterol (p<0.01). No changes in IL-4 and IL-13 were found. Interestingly, this effect was only present in PBMCs from asthma patients. The number of Foxp3+ cells tended to increase and their activity, measured by IL-10 production, increased after sitostanol treatment in PBMCs from asthma patients compared to controls by 32.3% (p = 0.077) and 13.3% (p<0.05), respectively. CONCLUSIONS/SIGNIFICANCE: Altogether, the sitostanol-induced Thelper-1 shift in PBMCs from asthma patients and the stimulating effects of sitostanol on Treg cell numbers and activity indicate a possible novel approach for plant stanol ester enriched functional foods in the amelioration of asthmatic symptoms. Functional effects, however, require further evaluation

Cytokine responses upon stimulation with a purified House Dust Mite extract.

<p>PBMCs from asthma patients tended to produce more IL-13 than cells from healthy controls (1632 pg/mL v 695 pg/mL, p = 0.096). Other cytokines did not differ between asthma patients and healthy controls. Data are presented as single values and medians. # p<0.10.</p

Baseline subject characteristics.

<p>Baseline subject characteristics.</p

Effects of sitostanol and cholesterol on NK cells, NKT cells and CD107a expression after exposure to K562 cells.

<p>Sitostanol significantly reduced the percentage of NK cells in asthma patients as well as in healthy controls (p<0.05). Cholesterol lowered the activity of NK cells in asthma patients (p<0.05) and sitostanol did not increase the activity of NKT cells in asthma patients, but only in healthy controls (p<0.05). a = p<0.05 v cyclodextrin; b = p<0.10 v cholesterol; c = p<0.05 v sitostanol; d = p<0.10 v asthma patients.</p

Based on the results of this pilot study we suggest the above pathway in which sitostanol induces IL-2 production in Th1 cells, which leads to the proliferation of Treg cells.

<p>These cells will produce higher amounts of IL-10, that can inhibit the activity of the dominant Th2 cells, which might ultimately lead to a relief of asthmatic symptoms.</p

Baseline cell counts and CD107a expression.

<p>Healthy controls and asthma patients did not differ at baseline, apart from the percentage of NK cells in the PBMC population where asthma patients had a significantly higher NK cell count (9.66% v 2.17%, p<0.05). Data are presented as mean ± SD or median (range).</p>*<p>p<0.05.</p

Effects of sitostanol and cholesterol on the percentage of Treg cells and the production of IL-10 and IL-17.

<p>Sitostanol tended to induce a higher percentage of Treg cells in the total PBMC population from asthma patients (p = 0.77), and significantly increased IL-10 production (p<0.05). Cholesterol significantly increased IL-17 production when compared to sitostanol (p<0.05). a = p<0.05 v cyclodextrin; b = p<0.05 v sitostanol; c = p<0.10 v healthy controls; d = p<0.10 v cyclodextrin.</p