Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells

Introduction

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines.

Materials and methods

Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey′s post hoc tests were performed.

Results

Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs.

Conclusions

We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.     

In vitro efficacy of 5 antifungal agents against Candida parapsilosis,Candida orthopsilosis, and Candida metapsilosis as determined by time–kill methodology

Killing activity of amphotericin B, fluconazole, voriconazole, posaconazole, and 5-fluorocytosine was determined against 6 Candida parapsilosis, 3 Candida orthopsilosis, and 4 Candida metapsilosis clinical isolates. After 24 h, 1 of 6 C. parapsilosis, 1 of 3 C. orthopsilosis, and 3 of 4 C. metapsilosis isolates were killed at 1 to 4 μg/mL (1–8× MIC) amphotericin B. The remaining isolates were killed by 2 to 4 μg/mL amphotericin B after 48 h. Fluconazole was fungistatic at ≥1× MIC (0.5–2 μg/mL) against C. parapsilosis and at ≥2× MIC (4–8 μg/mL) against C. orthopsilosis and C. metapsilosis isolates. Voriconazole inhibited C. parapsilosis at ≥1× MIC (0.015–0.12 μg/mL), but the other 2 species were inhibited only at 4 to 8× MIC (0.25–0.5 μg/mL). Against C. orthopsilosis and C. metapsilosis, posaconazole was fungistatic close to the MIC (0.03–0.06 and 0.015–0.03 μg/mL, respectively). Against C. orthopsilosis and C. metapsilosis, fluconazole and voriconazole, but not posaconazole, seem to be less active in vitro than against C. parapsilosis.     

Classification of spatially unaligned fMRI scans

The analysis of fMRI data is challenging because they consist generally of a relatively modest signal contained in a high-dimensional space: a single scan can contain millions of voxel recordings over space and time. We present a method for classification and discrimination among fMRI that is based on modeling the scans as distance matrices, where each matrix measures the divergence of spatial network signals that fluctuate over time. We used single-subject independent components analysis (ICA), decomposing an fMRI scan into a set of statistically independent spatial networks, to extract spatial networks and time courses from each subject that have unique relationship with the other components within that subject. Mathematical properties of these relationships reveal information about the infrastructure of the brain by measuring the interaction between and strength of the components. Our technique is unique, in that it does not require spatial alignment of the scans across subjects. Instead, the classifications are made solely on the temporal activity taken by the subject's unique ICs. Multiple scans are not required and multivariate classification is implementable, and the algorithm is effectively blind to the subject-uniform underlying task paradigm. Classification accuracy of up to 90% was realized on a resting-scanned schizophrenia/normal dataset and a tasked multivariate Alzheimer's/old/young dataset. We propose that the ICs represent a plausible set of imaging basis functions consistent with network-driven theories of neural activity in which the observed signal is an aggregate of independent spatial networks having possibly dependent temporal activity.     

Differential β2-adrenergic receptor expression defines the phenotype of non-tumorigenic and malignant human breast cell lines

Breast cancer is the most frequent malignancy in women. Several reports demonstrated that adrenergic receptors (ARs) are involved in breast cancer. Here we observed that epinephrine (Epi), an endogenous AR agonist, caused opposite effects in non-tumorigenic (MCF-10A and HBL-100) and tumor cells (MCF-7 and MDA-MB-231). Thus, Epi, in non-tumor breast cells, as well as isoproterenol (β-agonist), in all cell lines, maintained a benign phenotype, decreasing cell proliferation and migration, and stimulating cell adhesion. β-AR expression and cAMP levels were higher in MCF-10A than in MCF-7 cells. β₂-AR knock-down caused a significant increase of cell proliferation and migration, and a decrease of cell adhesion both in basal and in Iso-stimulated conditions. Coincidently, β₂-AR over-expression induced a significant decrease of cell proliferation and migration, and an increase of cell adhesion. Therefore, β₂-AR is implied in cell phenotype and its agonists or antagonists could eventually complement cancer therapy.     

International trends in hepatocellular carcinoma incidence, 1978–2012

Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.     

Folate and Nutrients Involved in the 1-Carbon Cycle in the Pretreatment of Patients for Colorectal Cancer

To assess the ingestion of folate and nutrients involved in the 1-carbon cycle in non-treated patients with colorectal adenocarcinoma in a reference center for oncology in southeastern Brazil. In total, 195 new cases with colorectal adenocarcinoma completed a clinical evaluation questionnaire and a Food Frequency Questionnaire (FFQ). Blood samples from 161 patients were drawn for the assessment of serum folate. A moderate correlation was found between serum concentrations of folate, folate intake and the dietary folate equivalent (DFE) of synthetic supplements. Mulatto or black male patients with a primary educational level had a higher intake of dietary folate. Of patients obtaining folate from the diet alone or from dietary supplements, 11.00% and 0.10%, respectively, had intake below the recommended level. Of the patients using dietary supplements, 35% to 50% showed high levels of folic acid intake. There was a prevalence of inadequacy for vitamins B2, B6 and B12, ranging from 12.10% to 20.18%, while 13.76% to 22.55% of patients were likely to have adequate choline intake. The considerable percentage of patients with folate intake above the recommended levels deserves attention because of the harmful effects that this nutrient may have in the presence of established neoplastic lesions.