Implanted adipose progenitor cells as physicochemical regulators of breast cancer

Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.     

Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure

BackgroundPrevalence, predictors, and prognostic value of right ventricular (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF) symptoms with a broad range of left ventricular ejection fraction (LVEF) are unknown.Methods and ResultsOf 1,547 patients, mean (±SD) age was 71 ± 11 years, 48% were women, median (interquartile range [IQR]) TAPSE was 18.5 (14.0–22.7) mm, mean LVEF was 47 ± 16%, 47% had LVEF ≤45% and 67% were diagnosed with CHF, defined as systolic (S-HF) if LVEF was ≤45% and as heart failure with preserved ejection fraction (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR) follow-up of 63 (41–75) months, mortality was 34%. In multivariable analysis, increasing age, N-terminal pro–B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, right atrial volume index, and transtricuspid pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and atrial fibrillation (AF) or COPD were associated with an adverse prognosis. Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT-proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction.ConclusionsIn patients with CHF, low values for TAPSE are common, especially in those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of outcome.     

Toxicity and biomedical imaging of layered nanohybrids in the mouse

Layered nanohybrids (LNH) are a promising nonviral system allowing controlled drug and DNA delivery. In order to test the toxicity of LNH consisting of a magnesium/aluminum core, mice were subjected to subcutaneous, intraperitoneal, and intravenous injections of these nanoparticles at three doses. Intravenous injections resulted in 8% (1 out of 12) lethality at doses 100 micro l and 200 micro l of 6.96 x 10(- 4) M solution, while all mice survived after LNH administration by any other routes. Histopathological alterations were limited to mild localized inflammatory lesions in the lungs and the dermis after intravenous and subcutaneous administration, respectively. LNH labeled with Lucifer Yellow were readily detectable in both locations by fluorescent microscopy. To test their potential for intravital imaging, LNH-Lucifer Yellow were injected into the ovarian bursa and successfully visualized by multiphoton microscopy within the ovarian surface epithelial cells. In similar experiments, the ovary and the ovarian bursa were readily detectable by magnetic resonance imaging after administration of modified LNH, where aluminum was substituted for gadolinium. Taken together, these results demonstrate minimal in vivo toxicity of LNH and illuminate their potential as multifunctional nanoscale particles suitable for combination of intravital biomedical imaging with controlled drug release.     

Longitudinal myocardial dysfunction in healthy older subjects as a manifestation of cardiac ageing

BACKGROUND: Abnormalities of longitudinal left ventricular (LV) contraction and relaxation may be early markers of cardiac disease. This study was designed to assess the relationship between long-axis LV function and age in healthy subjects. METHODS: 118 healthy individuals aged 57 +/-19 years (range 20-90 years) with no evidence of cardiovascular disease under-went echocardiography with Doppler examination of transmitral flow. To assess longitudinal LV function, systolic (S(m)), early diastolic (E(m)) and late diastolic (A(m)) mitral annular velocities were measured using colour-coded tissue Doppler imaging. RESULTS: The left atrium was enlarged (P<0.001) in subjects >/=60 years of age compared to those <60 years, but there were no differences in LV volumetric indices and ejection fraction. Peak E velocity was lower (P<0.001) and peak A velocity of transmitral flow was higher in older subjects (P<0.001) with a higher E/A ratio (P<0.001) and longer isovolumic relaxation time (P= 0.001) indicative of impaired ventricular relaxation. S m and E m mitral annular velocities decreased (P<0.001) and A m velocity increased (P=0.002) in the older group. E m velocity and E m /A m ratio showed a strong negative correlation with age (r= -0.80, P<0.001 and r=-0.78, P<0.001, respectively). CONCLUSIONS: Global LV systolic function is preserved but the velocity of long-axis systolic shortening is depressed in older individuals, indicating selective impairment of the longitudinal component of systolic contraction. The decline in the velocity of early diastolic long-axis LV lengthening and the changes in the pattern of transmitral flow suggest impaired ventricular relaxation. These measures of cardiac function may be a useful index of normal cardiac ageing.     

Atherosclerotic disease of the abdominal aorta and its branches: prognostic implications in patients with heart failure

Aortic atherosclerosis reduces compliance in the systemic circulation and increases peripheral resistance, afterload and left ventricular wall stress. In patients with heart failure, these changes can impair left ventricular systolic function and energy efficiency, which could reduce exercise capacity. Though the interaction and the impact of aortic atherosclerosis on left ventricular function have been investigated, its prognostic implications in patients with heart failure are unclear. We used cardiac magnetic resonance imaging and gadolinium-enhanced abdominal aortography to investigate the prevalence and prognostic impact of atherosclerotic disease of the abdominal aorta and its side branches in 355 patients with heart failure. Sclerotic abdominal aortic disease was defined as a luminal narrowing >50% of the aorta and its side branches or the presence of abdominal aortic aneurysm. Patients with disease of the aorta and its branches were older (P?相似文献   

Relations between several parameters of respiratory mechanics after radical correction of congenital heart defects

The results of this study are at variance with highly prevalent opinion that an increase in Vinsp leads to a parallel growth of Cst. A different degree of relationship between Vinsp and Cst was observed in the studied groups (from 0.33 to 0.92). These relationships in children with congenital heart disease are determined by the state of pulmonary circulation and lung parenchyma before surgery and after correction and depend on the form of the defect and patient's age. Such a variety of values is due to specificity of changes in the lungs depending on the pathomorphology of congenital heart disease and progress of these changes with age.