Correlation of Smac/DIABLO protein expression with the clinico-pathological features of breast cancer patients

Smac/DIABLO protein promotes caspase-dependent apoptosis by inhibition of inhibitor of apoptosis protein (IAP) family members. The role of Smac/DIABLO in breast cancer has not been yet established. Therefore, the aim of the study was to assess the expression of this protein in tumor cells from breast cancer patients. The expression of Smac/DIABLO was analyzed in 62 breast cancer patients by flow cytometry. The obtained results were compared with expression of this protein in benign breast tumor tissue, which served as the control (11 patients with fibroadenoma). Expression of caspase-3 proteins in breast cancer was also evaluated. Smac/DIABLO expression in breast cancer was correlated with clinical and pathological data. Although the expression of Smac/DIABLO protein was found in all examined samples of both the breast cancer and fibroadenoma patients, the median expression of Smac/Diablo in breast cancer was significantly lower than in the control (39.1% vs. 48.1%; p=0.0047). Smac/DIABLO expression correlated with expression of caspase-3 (p=0.000008). In pT1 breast cancer patients, expression of Smac/DIABLO protein was higher than in those with pT2-3 (p=0.02). Diffuse cancer infiltration significantly correlated with lower expression of Smac/DIABLO protein (p=0.02). Moreover, there was a loose correlation between low expression of Smac/DIABLO protein and cancer embolus in minor blood and lymphatic vessels (p=0.08). Our results indicate that expression of Smac/DIABLO inversely correlates with the tumor stage, which may suggest that this protein may play an important role in the breast cancer development.     

A learning-based wrapper method to correct systematic errors in automatic image segmentation: consistently improved performance in hippocampus, cortex and brain segmentation

We propose a simple but generally applicable approach to improving the accuracy of automatic image segmentation algorithms relative to manual segmentations. The approach is based on the hypothesis that a large fraction of the errors produced by automatic segmentation are systematic, i.e., occur consistently from subject to subject, and serves as a wrapper method around a given host segmentation method. The wrapper method attempts to learn the intensity, spatial and contextual patterns associated with systematic segmentation errors produced by the host method on training data for which manual segmentations are available. The method then attempts to correct such errors in segmentations produced by the host method on new images. One practical use of the proposed wrapper method is to adapt existing segmentation tools, without explicit modification, to imaging data and segmentation protocols that are different from those on which the tools were trained and tuned. An open-source implementation of the proposed wrapper method is provided, and can be applied to a wide range of image segmentation problems. The wrapper method is evaluated with four host brain MRI segmentation methods: hippocampus segmentation using FreeSurfer (Fischl et al., 2002); hippocampus segmentation using multi-atlas label fusion (Artaechevarria et al., 2009); brain extraction using BET (Smith, 2002); and brain tissue segmentation using FAST (Zhang et al., 2001). The wrapper method generates 72%, 14%, 29% and 21% fewer erroneously segmented voxels than the respective host segmentation methods. In the hippocampus segmentation experiment with multi-atlas label fusion as the host method, the average Dice overlap between reference segmentations and segmentations produced by the wrapper method is 0.908 for normal controls and 0.893 for patients with mild cognitive impairment. Average Dice overlaps of 0.964, 0.905 and 0.951 are obtained for brain extraction, white matter segmentation and gray matter segmentation, respectively.     

The kinetics of hematopoietic niche cytokines and their influence on mobilization efficacy and timing in patients with hematological malignancies

The bone marrow niche functions are modulated by complicated cytokines network. The aim of our study was to evaluate the levels of VCAM‐1, VEGF, MMP‐9 and SDF during mobilization of CD34+ cells in patients with hematological malignancies. Thirty four patients were enrolled to the study (19F, 15 M) at median age of 57 years. The group consisted of patients with multiple myeloma (26) and lymphoma (8). The mobilization procedures comprised chemotherapy and then G‐CSF. Blood samples were collected before chemotherapy (N = 34) and on the day of the first apheresis (N = 26). Cytokines were evaluated with ELISA assay. We observed significant increase in VCAM‐1 levels during mobilization. On contrary, VEGF and SDF levels decreased during mobilization procedure. The levels of MMP‐9 were stable during mobilization. We divided patients according to baseline cytokines levels below and above median into “low” and “high” expressors. The group of VEGF “low” expressors had longer median time of G‐CSF treatment before first apheresis than ‘high’ expressors. Baseline VEGF levels correlated adversely with duration of G‐CSF treatment before first apheresis. Patients were also divided according to median cytokines levels at apheresis into “low” and “high” expressors. “High” VCAM‐1 expressors had higher CD34+in peripheral blood as well as higher CD34+numbers collected during first apheresis than “low” expressors. In conclusion, the levels of niche cytokines change significantly during mobilization in patients with hematopoietic malignancies. Baseline VEGF can influence timing of mobilization. Higher VCAM‐1 corresponds with higher mobilization efficacy. J. Clin. Apheresis 30:247–251, 2015. © 2014 Wiley Periodicals, Inc.     

Late stent thrombosis thirteen months after drug-eluting stent implantation

We present a case of a very late stent thrombosis which occurred 13 months after drug-eluting stent (DES) implantation. The DES was off-label used in a high-risk patient and was followed by 12-month clopidogrel administration. One month after the drug discontinuation the stent thrombosis occurred, resulting in acute myocardial infarction. The patient was successfully treated with balloon coronary angioplasty and was advised to use clopidogrel indefinitely.     

Thermosensitive polymers in drug form technology. II. Possibilities of use of thermosensitive polymers as active substance carriers

Thermosensitive drug delivery can be used as substances carriers, which are applied in oral system, vaginal systems of release, applied on skin, the rectal, nasal, passed to eyes and parenteral. Sol-gel transition of the prepared formulations at physiological temperature ranges of the body makes possible their application in the liquid state and subsequent gelification in situ providing a prolonged release of the active substance at the application site.     

Estrogenicity of bisphenol A in a human endometrial carcinoma cell line

The ability of bisphenol A (BPA) to affect human estrogen receptor (ER) binding, expression of progesterone receptor (PR) mRNA and protein, and cell proliferation has been measured in the human endometrial cell line,ECC-1. Although less potent than 17β-estradiol, BPA was able to bind to the human uterine ER. BPA also induced both mRNA and protein to levels similar to E2. BPA-mediated PR mRNA induction was antagonized by ICI, suggesting an ER-mediated pathway. Finally, E2 produced a 2-fold increase in cell number, while BPA showed no difference compared with vehicle control. The increase by E2 was inhibited by treatment with the either ICI 182,780 (ICI) or BPA, suggesting similar binding sites. Although ER binding is similar, E2 affected both proliferation and PR expression, while BPA only affected PR gene expression. The results of this study provide evidence that two ER agonists can act differentially in vitro to affect the expression of genes involved in regulating cellular growth and development, though the human risk potential remains to be determined.     

Metallocene Catalyzed Polymerization of Ethylene in the Presence of Graphite, 1. Synthesis and Characterization of the Composites

Polyethylene/graphite composites have been prepared by two different methods. In a first approach, the ethylene polymerization has been catalyzed by metallocene in the presence of neat graphite particles (NGC composites). A second series of composites (TGC) has been prepared by the polymerization‐filling technique, which requires that the metallocene/methylalumoxane catalyst is fixed onto the graphite surface prior to the ethylene polymerization. The two series of composites exhibit significantly different morphology and thermal properties. The filler distribution is very heterogeneous in the NGC series. The morphology changes from an intimate mixture of PE and filler particles at low graphite content to graphite covered by patches of PE at high filler loading. The graphite distribution is much more homogeneous in the TGC samples, and the morphology consists of particles covered by a layer of PE in the whole composition range. Differences in the thermal properties are discussed in relation to the morphology.     

Quality of life in heart failure patients undergoing hybrid comprehensive telerehabilitation versus usual care – results of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) Randomized Clinical Trial

IntroductionHybrid comprehensive telerehabilitation (HCTR) consisting of telecare (with psychological telesupport), telerehabilitation and remote monitoring of implantable devices might be an innovative option improving heart failure (HF) patients’ quality of life (QoL) and emotional health. The aim of the study was to investigate the influence of HCTR on various facets of QoL in HF patients in comparison with usual care (UC) alone.Material and methodsThe present analysis formed part of a multicenter, randomized trial that enrolled 850 HF patients (NYHA I–III, LVEF ≤ 40%). Patients were randomized 1 : 1 to HCTR plus UC or UC only. Patients underwent either an HCTR program or UC with observation. The psychological intervention in the HCTR group included supportive psychological counseling via mobile phone. The Medical Outcome Survey Short Form 36 Questionnaire was used to assess QoL. Measurements were made before and after a 9-week intervention (HCTR group)/observation (UC group).ResultsAfter the intervention, the HCTR group showed significant improvement in overall QoL, physical domain (PD) of QoL, and 4 areas of QoL (physical functioning (PhF), role functioning related to physical state (RF), general health (GH), vitality (VI)). A significant positive change in QoL in the UC group was observed only in VI and social functioning. There were also significant differences in QoL after 9-week intervention/observation between the two groups. The results showed greater improvement in HCTR for overall QoL (p = 0.009), PD of QoL (p = 0.0003) and three specific areas of QoL: PhF (p = 0.001), RF (p = 0.003), bodily pain (BP) (p = 0.015).ConclusionsIn comparison to UC, HCTR resulted in improvement in overall QoL, PD of QoL and 3 specific areas of QoL: PhF, RF and BP.