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Healthy Cells (healthy + cell)
Selected AbstractsFlutamide inhibits nifedipine- and interleukin-1,-induced collagen overproduction in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2010H.-K. Lu Lu H-K, Tseng C-C, Lee Y-H, Li C-L, Wang L-F. Flutamide inhibits nifedipine- and interleukin-1,-induced collagen overproduction in gingival fibroblasts. J Periodont Res 2010; 45: 451,457. © 2010 John Wiley & Sons A/S Background and Objective:, To understand the role of the androgen receptor in gingival overgrowth, the effects of flutamide on interleukin-1,- and nifedipine-induced gene expression of connective tissue growth factor (CTGF/CCN2) and collagen production in gingival fibroblasts were examined. Material and Methods:, Gingival fibroblasts from healthy subjects and patients with dihydropyridine-induced gingival overgrowth (DIGO) were used. Confluent cells were treated with nifedipine, interleukin-1, or both. The mRNA expression was examined using real-time polymerase chain reaction, and the concentration of total soluble collagen in conditioned media was analysed by Sircol Collagen Assay. In addition, the protein expressions of androgen receptor, CTGF/CCN2 and type I collagen in gingival tissue were determined by western blot. Results:, Interleukin-1, was more potent than nifedipine in stimulating CTGF/CCN2 and procollagen ,1(I) mRNA expression, and there was an additive effect of the two drugs. Healthy cells exhibited an equal or stronger response of procollagen ,1(I) than those with DIGO, but DIGO cells displayed a stronger response in the secretion of soluble collagen in the same conditions. Flutamide, an androgen receptor antagonist, inhibited stimulation by nifedipine or interleukin-1,. Additionally, the protein expressions of androgen receptor and type I collagen were higher in DIGO gingival tissue than those in healthy gingival tissue. Conclusion:, The data suggest that both nifedipine and interleukin-1, play an important role in DIGO via androgen receptor upregulation and that gingival overgrowth is mainly due to collagen accumulation. Flutamide decreases the gene expression and protein production of collagen from dihydropyridine-induced overgrowth cells. [source] Multiparametric analysis of normal and postchemotherapy bone marrow: Implication for the detection of leukemia-associated immunophenotypes,CYTOMETRY, Issue 1 2008D. Olaru Abstract Background: The knowledge of normal marrow is mandatory to assess the malignant counterpart of normal cells and define leukemia-associated immunophenotypes (LAIPs). In this study, the expression of a variety of antigens expressed in normal and postchemotherapy bone marrow (BM) was analyzed to provide a frame of reference for the identification of myeloid LAIPs. Methods: Multiparameter four- and six-color flow cytometry was used to define antigen combinations totally absent or present at very minimal levels in marrow cells of normal individuals (n = 20) and patients receiving chemotherapy for acute lymphoblastic leukemia (n = 20). Immature (blast) cells were gated according to CD45/SSC properties. Fifty-three acute myeloid leukemia (AML) samples were studied in six-color combinations. Results: In six-color flow cytometry, 47 phenotypes were totally absent from blast gate in all normal samples. Forty-one other phenotypes were identified in less than 0.05% of blast cells. There was no difference between normal and postchemotherapy BMs. The four-color panel allowed to identify only 30 phenotypes present at a frequency <0.05%. Using the six-color panel, 58% of the absent or infrequent phenotypes in normal BM were found in at least one of 53 AML samples. All AML cases exhibited at least one LAIP. Conclusion: Our results show that the ability to distinguish leukemic from healthy cells is considerably increased by a six-color approach. Furthermore, these absent or infrequent phenotypes in normal BM are identified in AML and can be utilized for minimal residual disease study. © 2007 Clinical Cytometry Society [source] Hollow Mesoporous Zirconia Nanocapsules for Drug DeliveryADVANCED FUNCTIONAL MATERIALS, Issue 15 2010Shaoheng Tang Abstract Hollow mesoporous zirconia nanocapsules (hm -ZrO2) with a hollow core/porous shell structure are demonstrated as effective vehicles for anti-cancer drug delivery. While the highly porous feature of the shell allows the drug, doxorubicin(DOX), to easily pass through between the inner void space and surrounding environment of the particles, the void space in the core endows the nanocapsules with high drug loading capacity. The larger the inner hollow diameter, the higher their DOX loading capacity. A loading of 102% related to the weight of hm -ZrO2 is achieved by the nanocapsules with an inner diameter of 385,nm. Due to their pH-dependent charge nature, hm -ZrO2 loaded DOX exhibit pH-dependent drug releasing kinetics. A lower pH offers a faster DOX release rate from hm -ZrO2. Such a property makes the loaded DOX easily release from the nanocapsules when up-taken by living cells. Although the flow cytometry reveals more uptake of hm -ZrO2 particles by normal cells, hm -ZrO2 loaded DOX release more drugs in cancer cells than in normal cells, leading to more cytotoxicity toward tumor cells and less cytotoxicity to healthy cells than free DOX. [source] Role of the Bone Marrow Microenvironment in Multiple Myeloma,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002G. David Roodman M.D., Ph.D. Abstract On June 26,27, 2001, the Sixth Research Roundtable in Multiple Myeloma, entitled "The Role of the Bone Microenvironment in Multiple Myeloma," was held and focused on the biology of cell-to-cell interactions, the mediators of bone disease, and novel treatment strategies for myeloma. Studies on cell-cell interactions showed that vascular cell adhesion molecule 1, expressed by local endothelial and stromal cells, binds to tumor cell surface integrins in which expression may be increased by tumor cell-derived chemokines such as macrophage inflammatory protein (MIP) 1,. These adhesive interactions increase production and release of vascular endothelial growth factor (VEGF). Studies on myeloma bone disease showed the ligand for receptor activator of nuclear transcription factor-,B (RANKL) was expressed on tumor cells and stromal cells associated with myeloma cells and was critical for osteoclast-induced osteolysis. Blockade of RANKL suppressed osteoclast maturation, bone resorption, and tumor development. Bisphosphonates, in addition to reducing osteoclast mobility and inducing osteoclast apoptosis, also decreased tumor cell adhesion to stroma. Immunomodulatory drugs such as thalidomide analogues targeted these tumor cell-stromal cell interactions, blocking both secretion of cytokines and activation of intracellular signaling pathways required for tumor survival and growth. These agents induced tumor cell apoptosis, decreased neovascularization, and potentiated natural killer cell activity. The proteasome inhibitor PS-341 also prevented expression of adhesion molecules and cytokines and triggered tumor cell apoptosis, even in drug-resistant cell lines, while showing minimal activity in healthy cells. In addition, potential therapeutic agents under investigation, which included RANKL antagonists, protein prenylation inhibitors, and osteoblast growth factors, were discussed. [source] Identification of Biological Samples in a Case of Contamination of a Cytological Slide Preparation,JOURNAL OF FORENSIC SCIENCES, Issue 3 2008Anke Junge Ph.D. Abstract:, Here we report a case where a discrete section of the cytological slide preparation of a female individual was obviously contaminated with pleura liquid of a female tumor patient. Analysis of the cancerous pleura liquid and the healthy cells of the slide preparation showed different DNA profiles, indicating that the material originated from two different female individuals. The DNA profile of the cell mixture revealed a heterogenous pattern whereby the alleles could be assigned to the healthy and the tumor patient. Loss of heterozygosity (LOH) was observed in four of eight short tandem repeat systems for the pleura liquid and the cell mixture. Despite the low amount of DNA on the slide preparation and the occurrence of LOH, it was possible to clarify the case and to support the assumption that a drop of cancerous pleura liquid contaminated the cytological slide. [source] Poster Session BP07: Neurodegenerative DiseasesJOURNAL OF NEUROCHEMISTRY, Issue 2002F. Jayman Presynaptic terminals contain an abundant 140-amino acid phosphoprotein, dubbed ,-synuclein, which is accumulated in Lewy bodies typically observed in neurons in neurodegenerative diseases, such as Parkinson's disease. In this study, the role of ,-synuclein in regulating cycle, differentiation, and survival of neuronal cells was studied using a rat dopaminergic cell line ZN27D. To delineate specific effects of ,-synuclein the same cell line was engineered to express human ,-synuclein and a vector-transfected cell line RK27 was used as a second control. All three cell lines showed significant proliferation even in serum-free medium, and complete inhibition of cell division and differentiation could be achieved in the ZN27D cells only when both dibutyryl cAMP (dbcAMP) and retinoic acid were present. In contrast, the ,-synuclein expressing cells could be differentiated in the presence of only dbcAMP. Dose dependence of MPP+(1-methyl-4-phenylpyridinium iodide)-mediated caspase3 activation was studied in undifferentiated ZN27D cells. At 200 ,m MPP+ a significant cleavage of the caspase3 substrate PARP was observed and it was reversed in the presence of ,-synuclein. MPP+ also inhibited aminophospholipid translocase (APTL), a P-type ATPase that is responsible for inner plasma membrane localization of phophotidylserine in healthy cells. The role of ,-synuclein in regulating cell cycle, differentiation, APTL activity and cell death is being investigated further in the dopaminergic ZN27D cell line. [source] Determination of the Minimum Temperature Required for Selective Photothermal Destruction of Cancer Cells with the Use of Immunotargeted Gold NanoparticlesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006Xiaohua Huang ABSTRACT Laser photothermal therapy of cancer with the use of gold nanoparticles immunotargeted to molecular markers on the cell surface has been shown to he an effective modality to selectively kill cancer cells at much lower laser powers than those needed for healthy cells. To elucidate the minimum light dosimetry required to induce cell death, photothermal destruction of two cancerous cell lines and a noncancerous cell line treated with antiepidermal growth factor receptor (anti-EGFR) antibody-conjugated gold nanoparticles is studied, and a numerical heat transport model is used to estimate the local temperature rise within the cells as a result of the laser heating of the gold nanoparticles. It is found that cell samples with higher nanoparticle loading require a lower incident laser power to achieve a certain temperature rise. Numerically estimated temperatures of 70,80°C achieved by heating the gold particles agree well with the measured threshold temperature for destruction of the cell lines by oven heating and those measured in an earlier nanoshell method. Specific binding of anti-EGFR antibody to cancerous cells overexpressing EGFR selectively increases the gold nanoparticle loading within cancerous cells, thus allowing the cancerous cells to be destroyed at lower laser power thresholds than needed for the noncancerous cells. in addition, photothermal therapy using gold nanoparticles requires lower laser power thresholds than therapies using conventional dyes due to the much higher absorption coefficient of the gold nanoparticles. [source] Differences in lethality between cancer cells and human lymphocytes caused by LF-electromagnetic fieldsBIOELECTROMAGNETICS, Issue 7 2004Maria Radeva Abstract The lethal response of cultured cancer cells lines K-562, U-937, DG-75, and HL-60 were measured directly after a 4 h exposure to a pulsating electromagnetic field (PEMF, sinusoidal wave form, 35 mT peak, 50 Hz) [Traitcheva et al. (2003): Bioelectromagnetics 24:148,158] and 24 h later, to determine the post-exposure effect. The results were found to depend on the medium, pH value, conductivity, and temperature. From these experiments, suitable conditions were chosen to compare the vitality between K-562 cells and normal human lymphocytes after PEMF treatment and photodynamic action. Both agents enhance necrosis synergistically for diseased as well as for healthy cells, but the lymphocytes are more resistant. The efficacy of PEMF on the destruction of cancer cells is further increased by heating (hyperthermia) of the suspension up to 44 °C or by lowering the pH-value (hyperacidity) to pH 6.4. Similar apoptosis and necrosis can be obtained using moderate magnetic fields (B,,,15 mT 50/60 Hz), but this requires longer treatment of at least over a week. PEMF application combined with anticancer drugs and photodynamic therapy will be very effective. Bioelectromagnetics 25:503,507, 2004. © 2004 Wiley-Liss, Inc. [source] Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all- trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Adrian Britschgi Summary Acute promyelocytic leukaemia (APL) patients are successfully treated with all- trans retinoic acid (ATRA). However, concurrent chemotherapy is still necessary and less toxic therapeutic approaches are needed. Earlier studies suggested that in haematopoietic neoplasms, the green tea polyphenol epigallocatechin-3-gallate (EGCG) induces cell death without adversely affecting healthy cells. We aimed at deciphering the molecular mechanism of EGCG-induced cell death in acute myeloid leukaemia (AML). A significant increase of death-associated protein kinase 2 (DAPK2) levels was found in AML cells upon EGCG treatment paralleled by increased cell death that was significantly reduced upon silencing of DAPK2. Moreover, combined ATRA and EGCG treatment resulted in cooperative DAPK2 induction and potentiated differentiation. EGCG toxicity of primary AML blasts correlated with 67 kDa laminin receptor (67LR) expression. Pretreatment of AML cells with ATRA, causing downregulation of 67LR, rendered these cells resistant to EGCG-mediated cell death. In summary, it was found that (i) DAPK2 is essential for EGCG-induced cell death in AML cells, (ii) ATRA and EGCG cotreatment significantly boosted neutrophil differentiation, and 67LR expression correlates with susceptibility of AML cells to EGCG. We thus suggest that EGCG, by selectively targeting leukaemic cells, may improve differentiation therapies for APL and chemotherapy for other AML subtypes. [source] Cytomics, the human cytome project and systems biology: top-down resolution of the molecular biocomplexity of organisms by single cell analysisCELL PROLIFERATION, Issue 4 2005G. ValetArticle first published online: 11 AUG 200 In addition, differential molecular cell phenotypes between diseased and healthy cells provide molecular data patterns for (i) predictive medicine by cytomics or for (ii) drug discovery purposes using reverse engineering of the data patterns by biomedical cell systems biology. Molecular pathways can be explored in this way including the detection of suitable target molecules, without detailed a priori knowledge of specific disease mechanisms. This is useful during the analysis of complex diseases such as infections, allergies, rheumatoid diseases, diabetes or malignancies. The top-down approach reaching from single cell heterogeneity in cell systems and tissues down to the molecular level seems suitable for a human cytome project to systematically explore the molecular biocomplexity of human organisms. The analysis of already existing data from scientific studies or routine diagnostic procedures will be of immediate value in clinical medicine, for example as personalized therapy by cytomics. [source] Cell permeabilization by poliovirus 2B viroporin triggers bystander permeabilization in neighbouring cells through a mechanism involving gap junctionsCELLULAR MICROBIOLOGY, Issue 8 2010Vanesa Madan Summary Poliovirus 2B protein is a well-known viroporin implicated in plasma membrane permeabilization to ions and low-molecular-weight compounds during infection. Translation in mammalian cells expressing 2B protein is inhibited by hygromycin B (HB) but remains unaffected in mock cells, which are not permeable to the inhibitor. Here we describe a previously unreported bystander effect in which healthy baby hamster kidney (BHK) cells become sensitive to HB when co-cultured with a low proportion of cells expressing poliovirus 2B. Viroporins E from mouse hepatitis virus, 6K from Sindbis virus and NS4A protein from hepatitis C virus were also able to permeabilize neighbouring cells to different extents. Expression of 2B induced permeabilization of neighbouring cell lines other than BHK. We found that gap junctions are responsible mediating the observed bystander permeabilization. Gap junctional communication was confirmed in 2B-expressing co-cultures by fluorescent dye transfer. Moreover, the presence of connexin 43 was confirmed in both mock and 2B-transfected cells. Finally, inhibition of HB entry to neighbouring cells was observed with 18,-glycyrrhethinic acid, an inhibitor of gap junctions. Taken together, these findings support a mechanism involving gap junctional intercellular communication in the bystander permeabilization effect observed in healthy cells co-cultured with poliovirus 2B-expressing cells. [source] Selenium- and Tellurium-Containing Multifunctional Redox Agents as Biochemical Redox Modulators with Selective CytotoxicityCHEMISTRY - A EUROPEAN JOURNAL, Issue 36 2010Dr. Vincent Jamier Abstract Various human diseases, including different types of cancer, are associated with a disturbed intracellular redox balance and oxidative stress (OS). The past decade has witnessed the emergence of redox-modulating compounds able to utilize such pre-existing disturbances in the redox state of sick cells for therapeutic advantage. Selenium- and tellurium-based agents turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. This kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect. To further improve selectivity, multifunctional sensor/effector agents are now required that recognize the biochemical signature of OS in target cells. The synthesis of such compounds provides interesting challenges for chemistry in the future. [source] | ||||||||||||||||