Alterations in lipid metabolism accompanied by changes in protein and carotenoid content as spectroscopic markers of human T cell activation.

This work aims to understand better the mechanism of cellular processes accompanying the activation of human T cells and to develop a novel, fast, label-free approach to identify molecular biomarkers for this process. The standard methodology for confirming the activation state of T cells is based on flow cytometry and using antibodies recognizing activation markers. The method provide high specificity detection but may be susceptible to background staining or non-specific secondary antibody reactions.

Raman Spectroscopy as a Research and Diagnostic Tool in Clinical Hematology and Hematooncology.

Raman spectroscopy is a molecular spectroscopic technique able to provide detailed information about the chemical structure, phase, crystallinity, and molecular interactions of virtually any analyzed sample. Although its medical applications have been studied for several decades, only recent advances in microscopy, lasers, detectors, and better understanding of the principles of the Raman effect have successfully expanded its applicability to clinical settings. The promise of a rapid, label-free diagnostic method able to evaluate the metabolic status of a cell in vivo makes Raman spectroscopy particularly attractive for hematology and oncology.

Automatic subtyping of Diffuse Large B-cell Lymphomas (DLBCL): Raman-based genetic and metabolic classification.

Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin's lymphoma in adults, is a genetically and metabolically heterogeneous group of aggressive malignancies. The complexity of their molecular composition and the variability in clinical presentation make clinical diagnosis and treatment selection a serious challenge. The challenge is therefore to quickly and correctly classify DLBCL cells.

Cytotoxic Potential of Bioactive Compounds from , an Endophytic Fungus Isolated from against Breast Cancer: Experimental and Computational Approach.

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of , an endophytic fungus isolated from the roots of the medicinal grass , for its anticancer potential.

l-Ornithine-N5-monooxygenase (PvdA) Substrate Analogue Inhibitors for Infections Treatment: Drug Repurposing Computational Studies.

is an opportunistic pathogen that can cause acute and severe infections. Increasing resistance to antibiotics has given rise to the urgent need for an alternative antimicrobial agent. A promising strategy is the inhibition of iron sequestration in the bacteria.

Dynamic Changes in the Ability to Release Neutrophil ExtraCellular Traps in the Course of Childhood Acute Leukemias.

Acute leukemias, the most common cancers in children, are characterized by excessive proliferation of malignant progenitor cells. As a consequence of impaired blood cell production, leukemia patients are susceptible to infectious complications-a major cause of non-relapse mortality. Neutrophil extracellular traps (NETs) are involved in various pathologies, from autoimmunity to cancer.

Permuted 2,4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells.

Cancer is a heterogeneous disease, and its treatment requires the identification of new ways to thwart tumor cells. Amongst such emerging targets are glucose transporters (GLUTs, SLC2 family), which are overexpressed by almost all types of cancer cells; their inhibition provides a strategy to disrupt tumor metabolism selectively, leading to antitumor effects. Here, novel thiazolidinedione (TZD) derivatives were designed, synthesized, characterized, and evaluated for their GLUT1, GLUT4, and GLUT5 inhibitory potential, followed by in-vitro cytotoxicity determination in leukemic cell lines.

Structure guided design and synthesis of furyl thiazolidinedione derivatives as inhibitors of GLUT 1 and GLUT 4, and evaluation of their anti-leukemic potential.

Cancer cells increase their glucose uptake and glycolytic activity to meet the high energy requirements of proliferation. Glucose transporters (GLUTs), which facilitate the transport of glucose and related hexoses across the cell membrane, play a vital role in tumor cell survival and are overexpressed in various cancers. GLUT1, the most overexpressed GLUT in many cancers, is emerging as a promising anti-cancer target.

Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation.

Epigenetics plays a fundamental role in cancer progression, and developing agents that regulate epigenetics is crucial for cancer management. Among Class I and Class II HDACs, HDAC8 is one of the essential epigenetic players in cancer progression. Therefore, we designed, synthesized, purified, and structurally characterized novel compounds containing N-substituted TZD (P1-P25).

Design and in vitro evaluation of electrospun shape memory polyurethanes for self-fitting tissue engineering grafts and drug delivery systems.

Integration of multiple features including shape memory, biodegradation, and sustained drug delivery in a single material offers the opportunity to significantly improve the abilities of implantable devices for cardiovascular system regeneration. Two types of shape memory polyurethanes (SMPUs): PU-PLGA and PU-PLLA/PEG differing in soft segments composition that comprising blends of various biodegradable polyols, i.e.

Discovery of 5-naphthylidene-2,4-thiazolidinedione derivatives as selective HDAC8 inhibitors and evaluation of their cytotoxic effects in leukemic cell lines.

Histone deacetylases (HDACs) are being explored as a therapeutic target for interventions in different types of cancer. HDAC8 is a class I HDAC that is implicated as a therapeutic target in various indication areas, including different types of cancer and particularly childhood neuroblastoma. Most previously described HDAC8-selective inhibitors contain a hydroxamate function as zinc binding group (ZBG) to confer potency.

PPARγ Agonists in Combination Cancer Therapies.

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. These unique properties constitute a strong therapeutic potential that place PPARγ agonists as one of the most interesting and widely studied anticancer molecules. Although PPARγ agonists exert significant, antiproliferative and tumoricidal activity in vitro, their anticancer efficacy in animal models is ambiguous, and their effectiveness in clinical trials in monotherapy is unsatisfactory.

α2β1 integrin-mediated mechanical signals during osteodifferentiation of stem cells from the Wharton's jelly of the umbilical cord.

Introduction: The formation and maintenance of tissues is regulated by various signals triggered by biological, chemical, and physical factors. Data increasingly confirm that matrix or tissue elasticity plays an influential role in regulating numerous cell functions. The aim of the present study was to better understand the regulation of cellular differentiation by mechanical cues.

Statins inhibit ABCB1 and ABCG2 drug transporter activity in chronic myeloid leukemia cells and potentiate antileukemic effects of imatinib.

Despite undisputed success of tyrosine kinase inhibitors in the therapy of chronic myeloid leukemia (CML), development of drug resistance and inability to cure the disease challenge clinicians and researchers. Additionally, recent reports regarding cardiovascular toxicities of second and third generation tyrosine kinase inhibitors prove that there is still a place for novel therapeutic combinations in CML. We have previously shown that statins are able to modulate activity of chemotherapeutics or antibodies used in oncology.

Effect of substrate stiffness on the osteogenic differentiation of bone marrow stem cells and bone-derived cells.

There is a profound dependence of cell behaviour on the stiffness of its microenvironment. To gain a better understanding of the regulation of cellular differentiation by mechanical cues, we investigated the influence of matrix stiffness (E = 1.46 kPa and E = 26.

[Selected, biochemical markers of hypoxia].

Although tissues may exist regardless of reduced oxygen pressure, this requires glycolytic ATP generation, which is very expensive from the energetic viewpoint. Hypoxia is defined as the condition in which oxygen pressure is reduced at the level of bodily tissues. There are many clinical situations during which decreased tissue oxygenation may occur.

Proteasome inhibition potentiates antitumor effects of photodynamic therapy in mice through induction of endoplasmic reticulum stress and unfolded protein response.

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by inducing production of reactive oxygen species such as singlet oxygen. PDT leads to oxidative damage of cellular macromolecules, including proteins that undergo multiple modifications such as fragmentation, cross-linking, and carbonylation that result in protein unfolding and aggregation. Because the major mechanism for elimination of carbonylated proteins is their degradation by proteasomes, we hypothesized that a combination of PDT with proteasome inhibitors might lead to accumulation of carbonylated proteins in endoplasmic reticulum (ER), aggravated ER stress, and potentiated cytotoxicity toward tumor cells.

Statins impair antitumor effects of rituximab by inducing conformational changes of CD20.

Background: Rituximab is used in the treatment of CD20+ B cell lymphomas and other B cell lymphoproliferative disorders. Its clinical efficacy might be further improved by combinations with other drugs such as statins that inhibit cholesterol synthesis and show promising antilymphoma effects. The objective of this study was to evaluate the influence of statins on rituximab-induced killing of B cell lymphomas.

Pioglitazone, a PPAR-gamma ligand, exerts cytostatic/cytotoxic effects against cancer cells, that do not result from inhibition of proteasome.

Thiazolidinediones are oral antidiabetic agents that activate peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and exert potent antioxidant and anti-inflammatory properties. It has also been shown that PPAR-gamma agonists induce G0/G1 arrest and apoptosis of malignant cells. Some of these effects have been suggested to result from inhibition of proteasome activity in target cells.

Ciglitazone, an agonist of peroxisome proliferator-activated receptor gamma, exerts potentiated cytostatic/cytotoxic effects against tumor cells when combined with lovastatin.

Thiazolidinediones are ligands of PPAR-gamma, a member of the nuclear receptor family. These drugs have shown promising pre-clinical activity in tumor models but clinical studies failed to confirm their beneficial effect. We have studied the in vitro antitumor effects of a combination of ciglitazone, a thiazolidinedione drug, and lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.

Purpose: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells.

Experimental Design: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells.