Circulating tumor cells and their advances to promote cancer metastasis and relapse, with focus on glioblastoma multiforme.

In the late stages of their development, cancers can form metastases. Formation of metastases was found to be associated with the capacity of cancer cells to quit the tumor mass and journey through the circulation to distant organs. This cell population is called circulating tumor cells (CTCs).

Epigenetic Alterations in DNA and Histone Modifications Caused by Depression and Antidepressant Drugs: Lessons from the Rodent Models.

Epigenetic modifications regulate chromatin folding and function. Epigenetic mechanisms regulate transcription mediating effects of various stimuli on gene expression. These mechanisms are involved in transcriptional control in various physiological and pathological conditions including neuropsychiatric disorders and behavioral abnormalities such as depression.

Engineered Nanoparticles: Their Properties and Putative Applications for Therapeutic Approaches Utilizing Stem Cells for the Repair of Atherosclerotic Disease.

Background: Stem cell therapy was established as a promising approach for regenerative medicine applications such as cardiac repair. However, current stem cell-based therapeutic strategies have serious challenges such as low retention and viability of transplanted stem cells in the injured myocardium. This significantly limits efficiency of stem cell therapy.

The EGFR variant III mutant as a target for immunotherapy of glioblastoma multiforme.

In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand.

Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life.

Chemokines and Relevant microRNAs in the Atherogenic Process.

Chemokines play a significant role in initial and advanced steps of atherogenesis. In early steps, chemokines control the adhesion of leukocytes to endothelial cells (ECs) followed by transmigration of monocytes and their deposition in the intima where they differentiate to proinflammatory macrophages. Except for proinflammatory activity, chemokines are responsible for homeostasis and homing of progenitor cells.

Nanocarriers in Improving Chemotherapy of Multidrug Resistant Tumors: Key Developments and Perspectives.

The multidrug resistance (MDR) of tumor cells significantly reduces the efficiency of traditional anticancer therapy. Tumor MDR is complex and involves several mechanisms such as decreased drug uptake, increased drug efflux, enhanced drug exocytosis, increased drug detoxification and inactivation by drugmetabolizing enzymes, altered drug targets due to genetic and epigenetic modifications, altered DNA repair, and impaired apoptotic pathways. Implementation of nanoparticles can markedly improve drug delivery through increased stability in the plasma, prolonged half-life, enhanced specificity of transfer, and advanced drug accumulation and retention in the tumor cells.

The phenomenon of atherosclerosis reversal and regression: Lessons from animal models.

Studies in non-rodent and murine models showed that atherosclerosis can be reversed. Atherosclerosis progression induced by high-fat or cholesterol-rich diet can be reduced and reversed to plaque regression after switching to a normal diet or through administration of lipid-lowering agents. The similar process should exist in humans after implementation of lipid-lowering therapy and as a result of targeting of small rupture-prone plaques that are major contributors for acute atherosclerotic complications.

Role of Progenitor Cells in Liver Regeneration after Subtotal Resection.

In the liver of rats subjected to subtotal liver resection (80% organ weight), the expression of sox9 gene and SOX9 protein content increased and cells with hepatocyte morphology expressing SOX9 appeared; the proportion of cells expressing cytokeratin-19 also increased. Based on these data, we cannot completely exclude the involvement of resident progenitor cells and hepatocyte reprogramming in liver regeneration after subtotal resection, however, the contribution of these processes seems to be insignificant. The leading mechanism of liver mass recovery after subtotal resection is proliferation of hepatocytes.

Immune-inflammatory responses in atherosclerosis: Role of an adaptive immunity mainly driven by T and B cells.

Adaptive immune response plays an important role in atherogenesis. In atherosclerosis, the proinflammatory immune response driven by Th1 is predominant but the anti-inflammatory response mediated mainly by regulatory T cells is also present. The role of Th2 and Th17 cells in atherogenesis is still debated.

Effects of shear stress on endothelial cells: go with the flow.

Haemodynamic forces influence the functional properties of vascular endothelium. Endothelial cells (ECs) have a variety of receptors, which sense flow and transmit mechanical signals through mechanosensitive signalling pathways to recipient molecules that lead to phenotypic and functional changes. Arterial architecture varies greatly exhibiting bifurcations, branch points and curved regions, which are exposed to various flow patterns.

Temozolomide promotes genomic and phenotypic changes in glioblastoma cells.

Background: Temozolomide (TMZ) is a first-line drug for the treatment of glioblastoma. Long-term TMZ-treated tumour cells acquire TMZ resistance by profound reprogramming of the transcriptome, proteome, kinome, metabolism, and demonstrate versatile and opposite changes in proliferation, invasion, in vivo growth, and drug cross-resistance. We hypothesized that chromosomal instability (CIN) may be implicated in the generation of TMZ-driven molecular and phenotype diversity.

mTOR inhibitor temsirolimus and MEK1/2 inhibitor U0126 promote chromosomal instability and cell type-dependent phenotype changes of glioblastoma cells.

The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and the RAF/mitogen-activated and extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways are frequently deregulated in cancer. Temsirolimus (TEM) and its primary active metabolite rapamycin allosterically block mTOR complex 1 substrate recruitment. The context-/experimental setup-dependent opposite effects of rapamycin on the multiple centrosome formation, aneuploidy, DNA damage/repair, proliferation, and invasion were reported.

Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes.

Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of function, and there is a need for a unified knowledge repository designed to track, analyze and visualize the cause and effect relationships and interactions between the many elements and processes on all levels. Aging Chart (http://agingchart.

Blood-brain barrier permeability in healthy rats and rats with experimental C6 glioma after fractionated radiotherapy of the brain.

Objective: To evaluate the effect of fractionated radiotherapy on permeability of the blood-brain barrier in healthy rats and rats with C6 glioma in vivo.

Material And Methods: An increase in BBB permeability in C6 glioma was assessed by dynamic MRI monitoring (glioma size before and after radiation therapy in combination with immunotherapy, n=30) and confocal microscopy (fluorescence imaging of tumor invasion boundaries in a dose-dependent experiment for the amount of injected antibodies). In healthy rats, BBB permeability to macromolecular substances (MMS) was assessed by ELISA (n=23, 192 plasma samples) and confocal microscopy (n=7).

Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.

A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role.

Changes in transcriptome of macrophages in atherosclerosis.

Macrophages display significant phenotypic heterogeneity. Two growth factors, macrophage colony-stimulating factor and chemokine (C-X-C motif) ligand 4, drive terminal differentiation of monocytes to M0 and M4 macrophages respectively. Compared to M0 macrophages, M4 cells have a unique transcriptome, with expression of surface markers such as S100A8, mannose receptor CD206 and matrix metalloproteinase 7.

Versatile Conjugated Polymer Nanoparticles for High-Resolution O2 Imaging in Cells and 3D Tissue Models.

High brightness, chemical and photostability, tunable characteristics, and spectral and surface properties are important attributes for nanoparticle probes designed for live cell imaging. We describe a class of nanoparticles for high-resolution imaging of O2 that consists of a substituted conjugated polymer (polyfluorene or poly(fluorene-alt-benzothiadiazole)) acting as a FRET antenna and a fluorescent reference with covalently bound phosphorescent metalloporphyrin (PtTFPP, PtTPTBPF). The nanoparticles prepared from such copolymers by precipitation method display stability, enhanced (>5-10 times) brightness under one- and two-photon excitation, compatibility with ratiometric and lifetime-based imaging modes, and low toxicity for cells.

Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes.

Macrophages are essential players in induction and progression of atherosclerotic inflammation. The complexity of macrophage phenotypes was observed in human plaques and atherosclerotic lesions in mouse models of atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (pro-inflammatory) and M2 (anti-inflammatory).

Intestinal mucosal tolerance and impact of gut microbiota to mucosal tolerance.

The mucosal barriers are very sensitive to pathogenic infection, thereby assuming the capacity of the mucosal immune system to induce protective immunity to harmful antigens and tolerance against harmless substances. This review provides current information about mechanisms of induction of mucosal tolerance and about impact of gut microbiota to mucosal tolerance.

Myeloid dendritic cells: Development, functions, and role in atherosclerotic inflammation.

Myeloid dendritic cells (mDCs) comprise a heterogeneous population of professional antigen-presenting cells, which are responsible for capture, processing, and presentation of antigens on their surface to T cells. mDCs serve as a bridge linking adaptive and innate immune responses. To date, the development of DC lineage in bone marrow is better characterized in mice than in humans.

Contribution of neovascularization and intraplaque haemorrhage to atherosclerotic plaque progression and instability.

Atherosclerosis is a continuous pathological process that starts early in life and progresses frequently to unstable plaques. Plaque rupture leads to deleterious consequences such as acute coronary syndrome, stroke and atherothrombosis. The vulnerable lesion has several structural and functional hallmarks that distinguish it from the stable plaque.

Studying progression from glucose intolerance to type 2 diabetes in obese children.

Aim: Identification of metabolic and genetic factors capable to mediate progression from normal glucose tolerance (NGT) through impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in childhood obesity.

Patients And Methods: Three groups of obese children with NGT (n=54), IGT (n=35), and T2D (n=62) were evaluated. A control group of non-obese normal children (n=210) was also studied.