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Sample records for cancer cells exposed

  1. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

    OpenAIRE

    CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

    2010-01-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27O...

  2. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

    Science.gov (United States)

    Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2010-05-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

  3. The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

    International Nuclear Information System (INIS)

    Zhang, Li; Gong, Aimin; Ji, Jun; Wu, Yuanyuan; Zhu, Xiaoyu; Lv, Suqing; Lv, Hongzhu; Sun, Xizhuo

    2007-01-01

    This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells. The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions in vitro. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect. Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration. Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner

  4. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

    International Nuclear Information System (INIS)

    Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

    2008-01-01

    Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

  5. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    International Nuclear Information System (INIS)

    Bedia, Carmen; Dalmau, Núria; Jaumot, Joaquim; Tauler, Romà

    2015-01-01

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  6. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es; Tauler, Romà, E-mail: roma.tauler@idaea.csic.es

    2015-07-15

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  7. Sulindac enhances the killing of cancer cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Maria Marchetti

    2009-06-01

    Full Text Available Sulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID that affects prostaglandin production by inhibiting cyclooxygenases (COX 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer.Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP or hydrogen peroxide. This effect does not involve cyclooxygenase (COX inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells.These results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value.

  8. Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Sollewijn Gelpke, M.D.; Boeren, S.; Ström, A.; Gustafsson, J.A.; Murk, A.J.; Rietjens, I.M.C.M.; Vervoort, J.J.M.

    2011-01-01

    The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line

  9. BAG3 sensitizes cancer cells exposed to DNA damaging agents via direct interaction with GRP78.

    Science.gov (United States)

    Kong, De-Hui; Zhang, Qiang; Meng, Xin; Zong, Zhi-Hong; Li, Chao; Liu, Bao-Qin; Guan, Yifu; Wang, Hua-Qin

    2013-12-01

    Bcl-2 associated athanogene 3 (BAG3) has a modular structure that contains a BAG domain, a WW domain, a proline-rich (PxxP) domain to mediate potential interactions with chaperons and other proteins that participate in more than one signal transduction. In search for novel interacting partners, the current study identified that 78kDa glucose-regulated protein (GRP78) was a novel partner interacting with BAG3. Interaction between GRP78 and BAG3 was confirmed by coimmunoprecipitation and glutathione S-transferase (GST) pulldown. We also identified that the ATPase domain of GRP78 and BAG domain of BAG3 mediated their interaction. Counterintuitive for a prosurvival protein, BAG3 was found to promote the cytotoxicity of breast cancer MCF7, thyroid cancer FRO and glioma U87 cells subjected to genotoxic stress. In addition, the current study demonstrated that BAG3 interfered with the formation of the antiapoptotic GRP78-procaspase-7 complex, which resulted in an increased genotoxic stress-induced cytotoxicity in cancer cells. Furthermore, overexpression of GRP78 significantly blocked the enhancing effects of BAG3 on activation of caspase-7 and induction of apoptosis by genotoxic stress. Overall, these results suggested that through direct interaction BAG3 could prevent the antiapoptotic effect of GRP78 upon genotoxic stress. © 2013.

  10. Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

    International Nuclear Information System (INIS)

    Seyyedi, S. S.; Mozdarani, H.; Rezaei Tavirani, M.; Heydari, S.

    2010-01-01

    Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to extremely low-frequency electromagnetic fields may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Materials and Methods: Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields (3, 50 and 60 Hz, sinusoidal, 3h, and 4 m T). Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous extremely low-frequency electromagnetic fields (50 Hz, sinusoidal, 3 h, 4 m T). Metaphase plates Were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of extremely low-frequency electromagnetic fields on primary or established cell lines. Results: Results indicate that by increasing the frequency of extremely low-frequency electromagnetic fields, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Conclusion: Results obtained indicate that extremely low-frequency electromagnetic fields has the potential for induction of chromosomal aberrations in all cell types.

  11. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to 60Co at single fraction

    International Nuclear Information System (INIS)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de; Leite, M.F.; Goes, A.M.

    2005-01-01

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to 60 Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min -1 rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by 60 Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  12. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to {sup 60}Co at single fraction

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear]. E-mail: lidia.andrade@unifenas.br; Leite, M.F. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Fisiologia e Biofisica; Goes, A.M. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia

    2005-10-15

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to {sup 60} Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min{sup -1} rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by {sup 60} Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  13. Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins.

    Science.gov (United States)

    Bao, Peng; Chen, Song-Can; Xiao, Ke-Qing

    2015-12-01

    Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance.

  14. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin and celeco......Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin...... and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN EliSpot. Secondary objec- tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten...

  15. Asymptotic analysis and optimal control of an integro-differential system modelling healthy and cancer cells exposed to chemotherapy

    KAUST Repository

    Pouchol, Camille

    2017-10-27

    We consider a system of two coupled integro-differential equations modelling populations of healthy and cancer cells under chemotherapy. Both populations are structured by a phenotypic variable, representing their level of resistance to the treatment. We analyse the asymptotic behaviour of the model under constant infusion of drugs. By designing an appropriate Lyapunov function, we prove that both cell densities converge to Dirac masses. We then define an optimal control problem, by considering all possible infusion protocols and minimising the number of cancer cells over a prescribed time frame. We provide a quasi-optimal strategy and prove that it solves this problem for large final times. For this modelling framework, we illustrate our results with numerical simulations, and compare our optimal strategy with periodic treatment schedules.

  16. Multiple, disparate roles for calcium signaling in apoptosis of human prostate and cervical cancer cells exposed to diindolylmethane.

    Science.gov (United States)

    Savino, John A; Evans, Jodi F; Rabinowitz, Dorianne; Auborn, Karen J; Carter, Timothy H

    2006-03-01

    Diindolylmethane (DIM), derived from indole-3-carbinol in cruciferous vegetables, causes growth arrest and apoptosis of cancer cells in vitro. DIM also induces endoplasmic reticulum (ER) stress, and thapsigargin, a specific inhibitor of the sarcoplasmic reticulum/ER calcium-dependent ATPase, enhances this effect. We asked whether elevated cytosolic free calcium [Ca2+]i is required for cytotoxicity of DIM and thapsigargin in two cancer cells lines (C33A, from cervix, and DU145, from prostate). [Ca2+]i was measured in real-time by FURA-2 fluorescence. We tested whether DIM, thapsigargin, and DIM + thapsigargin cause apoptosis, measured by nucleosome release, under conditions that prevented elevation of [Ca2+]i, using both cell-permeable and cell-impermeable forms of the specific calcium chelator BAPTA. DIM, like thapsigargin, rapidly mobilized ER calcium. C33A and DU145 responded differently to perturbations in Ca2+ homeostasis, suggesting that DIM induces apoptosis by different mechanisms in these two cell lines and/or that calcium mobilization also activates different survival pathways in C33A and DU145. Apoptosis in C33A was independent of increased [Ca2+]i, suggesting that depletion of ER Ca2+ stores may be sufficient for cell killing, whereas apoptosis in DU145 required elevated [Ca2+]i for full response. Inhibitor studies using cyclosporin A and KN93 showed that Ca2+ signaling is important for cell survival but the characteristics of this response also differed in the two cell lines. Our results underscore the complex and variable nature of cellular responses to disrupted Ca2+ homeostasis and suggest that alteration Ca2+ homeostasis in the ER can induce cellular apoptosis by both calcium-dependent and calcium-independent mechanisms.

  17. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to 60Co at single fraction

    Directory of Open Access Journals (Sweden)

    Lídia Maria Andrade

    2005-10-01

    Full Text Available Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC exposed in vitro to 60 Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min-1 rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by 60Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nuclus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.Radioterapia utilizando radiação gama é uma modalidade comum no tratamento do câncer de mama. A proposta deste estudo é investigar a resposta biológica in vitro da linhagem celular MDAMB-231 de câncer de mama humano e células do sangue periférico humano (PBMC expostas à irradiação pelo Co60 em frações simples de 10Gy, 25Gy e 50Gy e 136,4cGy min-1 rate. As células foram irradiadas a temperatura ambiente usando o equipamento de radioterapia Theratron 80 radiotherapy system. A resposta biológica, após irradiação gama, foi avaliada através do ensaio do MTT para viabilidade celular e o do ensaio com Iodeto de Propídio para visualização do dano nuclear, além da eletroforese em gel de agarose. Os danos nucleares induzidos pelo Co60 foram comparados aos danos causados pela exposição das células à solução de metanol a 10%. Nós observamos que a dose de 50Gy não estimulou a mesma quantidade de danos nucleares que a solução de metanol a 10% nas c

  18. A generalised age- and phase-structured model of human tumour cell populations both unperturbed and exposed to a range of cancer therapies.

    Science.gov (United States)

    Basse, Britta; Ubezio, Paolo

    2007-07-01

    We develop a general mathematical model for a population of cells differentiated by their position within the cell division cycle. A system of partial differential equations governs the kinetics of cell densities in certain phases of the cell division cycle dependent on time t (hours) and an age-like variable tau (hours) describing the time since arrival in a particular phase of the cell division cycle. Transition rate functions control the transfer of cells between phases. We first obtain a theoretical solution on the infinite domain -infinity infinity. We then assume that age distributions at time t=0 are known and write our solution in terms of these age distributions on t=0. In practice, of course, these age distributions are unknown. All is not lost, however, because a cell line before treatment usually lies in a state of asynchronous balanced growth where the proportion of cells in each phase of the cell cycle remain constant. We assume that an unperturbed cell line has four distinct phases and that the rate of transition between phases is constant within a short period of observation ('short' relative to the whole history of the tumour growth) and we show that under certain conditions, this is equivalent to exponential growth or decline. We can then gain expressions for the age distributions. So, in short, our approach is to assume that we have an unperturbed cell line on t cell line is exposed to cancer therapy. This corresponds to a change in the transition rate functions and perhaps incorporation of additional phases of the cell cycle. We discuss a number of these cancer therapies and applications of the model.

  19. DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

    Science.gov (United States)

    Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

  20. Asymptotic analysis and optimal control of an integro-differential system modelling healthy and cancer cells exposed to chemotherapy

    KAUST Repository

    Pouchol, Camille; Clairambault, Jean; Lorz, Alexander; Tré lat, Emmanuel

    2017-01-01

    to the treatment. We analyse the asymptotic behaviour of the model under constant infusion of drugs. By designing an appropriate Lyapunov function, we prove that both cell densities converge to Dirac masses. We then define an optimal control problem, by considering

  1. WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Held, K. [Massachusetts General Hospital (United States)

    2016-06-15

    The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

  2. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  3. Role of Reactive Oxygen Species and Nitric Oxide in Mediating Chemotherapeutic Drug Induced Bystander Response in Human Cancer Cells Exposed In-Vitro

    Science.gov (United States)

    Chinnadurai, Mani; Rao, Bhavna S; Deepika, Ramasamy; Paul, Solomon F.D.; Venkatachalam, Perumal

    2012-01-01

    Background The intention of cancer chemotherapy is to control the growth of cancer cells using chemical agents. However, the occurrence of second malignancies has raised concerns, leading to re-evaluation of the current strategy in use for chemotherapeutic agents. Although the mechanisms involved in second malignancy remain ambiguous, therapeutic-agent-induced non-DNA targeted effects like bystander response and genomic instability cannot be eliminated completely. Hence, Bleomycin (BLM) and Neocarzinostatin (NCS), chemotherapeutic drugs with a mode of action similar to ionizing radiation, were used to study the mechanism of bystander response in human cancer cells (A549, CCRF-CEM and HL-60) by employing co-culture methodology. Methods Bystander effect was quantified using micronucleus (MN) assay and in-situ immunofluorescence(γH2AX assay).The role of reactive oxygen species (ROS) and nitric oxide (NO) in mediating the bystander response was explored by pre-treating bystander cells with dimethylsulphoxide (DMSO) and C-PTIO respectively. Results Bystander response was observed only in CCRF-CEM and A549 cells (P bystander response on treatment with DMSO, suggests that ROS has a more significant role in mediating the bystander response.Since the possibility of the ROS and NO in mediating these bystander effect was confirmed, mechanistic control of these signaling molecules could either reduce radiation damage and potential carcinogenicity of normal tissues (by reducing bystander signaling) or maximize cell sterilization during chemotherapy (by amplifying bystander responses in tumors). PMID:29147282

  4. Squamous cell cancer (image)

    Science.gov (United States)

    Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

  5. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  6. Cancer risk in men exposed in utero to diethylstilbestrol.

    Science.gov (United States)

    Strohsnitter, W C; Noller, K L; Hoover, R N; Robboy, S J; Palmer, J R; Titus-Ernstoff, L; Kaufman, R H; Adam, E; Herbst, A L; Hatch, E E

    2001-04-04

    An association between prenatal diethylstilbestrol (DES) exposure and cancer in men, especially testicular cancer, has been suspected, but findings from case-control studies have been inconsistent. This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospective follow-up. A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994. The overall and site-specific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population-based rates. The relative rate (RR) was used to assess the strength of the association between prenatal DES exposure and cancer development. All statistical tests were two-sided. Overall cancer rates among DES-exposed men were similar to those among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be elevated among DES-exposed men, since the RRs for testicular cancer were 3.05 (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95% CI = 0.82 to 4.20) times those of males in the population-based rates. The higher rate of testicular cancer in the DES-exposed men is, however, also compatible with a chance observation. To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer.

  7. Cancer incidence among workers exposed to softwood dust in Lithuania.

    Science.gov (United States)

    Smailyte, Giedre

    2012-06-01

    The aim of this study was to assess cancer incidence in a cohort of woodworkers exposed to softwood dust in a Lithuanian wooden joinery products factory. The study population consisted of 1518 workers (1080 men and 438 women) employed in the factory for at least 1 year between 1947 and 1996 and living in Lithuania on 1 January 1978, when the follow-up for cancer incidence began. The follow-up period for cancer was 1978-2007. Cancer risk was assessed by standardised incidence ratios (SIR) with reference to the national population. Overall cancer incidence was not increased among woodworkers. However, the number of mouth and pharynx cancer cases among male woodworkers was significantly increased compared with expected numbers (SIR 2.19, 95% CI 1.17 to 3.74). A higher risk was found for cancer of the buccal cavity than for pharyngeal cancer (SIRs 2.83 and 1.45, respectively). The SIR for larynx cancer was also elevated (SIR 1.39, 95% CI 0.64 to 2.64) among men, while the number of lung cancer cases was higher than expected only among women (SIR 2.07, 95% CI 00.57 to 5.31). This results of this study support the hypothesis that exposure to softwood dust may increase the risk of oral and pharyngeal cancer. No support was found for an increased risk of other respiratory cancers among workers exposed to softwood dust.

  8. Life-Time Dosimetric Assessment for Mice and Rats Exposed in Reverberation Chambers of the 2-Year NTP Cancer Bioassay Study on Cell Phone Radiation.

    Science.gov (United States)

    Gong, Yijian; Capstick, Myles; Kuehn, Sven; Wilson, Perry; Ladbury, John; Koepke, Galen; McCormick, David L; Melnick, Ronald L; Kuster, Niels

    2017-12-01

    In this paper, we present the detailed life-time dosimetry analysis for rodents exposed in the reverberation exposure system designed for the two-year cancer bioassay study conducted by the National Toxicology Program of the National Institute of Environmental Health Sciences. The study required the well-controlled and characterized exposure of individually housed, unrestrained mice at 1900 MHz and rats at 900 MHz, frequencies chosen to give best uniformity exposure of organs and tissues. The wbSAR, the peak spatial SAR and the organ specific SAR as well as the uncertainty and variation due to the exposure environment, differences in the growth rates, and animal posture were assessed. Compared to the wbSAR, the average exposure of the high-water-content tissues (blood, heart, lung) were higher by ~4 dB, while the low-loss tissues (bone and fat) were less by ~9 dB. The maximum uncertainty over the exposure period for the SAR was estimated to be <49% (k=2) for the rodents whereas the relative uncertainty between the group was <14% (k=1). The instantaneous variation (averaged over 1 min) was <13% (k=1), which is small compared to other long term exposure research projects. These detailed dosimetric results empowers comparison with other studies and provides a reference for studies of long-term biological effects of exposure of rodents to RF energy.

  9. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.

    Science.gov (United States)

    Munson, Phillip; Lam, Ying-Wai; Dragon, Julie; MacPherson, Maximilian; Shukla, Arti

    2018-03-19

    Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma. In the present study using lung epithelial cells (BEAS2B) and macrophages (THP-1), we first show that asbestos exposure causes changes in abundance of some proteins in the exosomes secreted from these cells. Furthermore, exposure of human mesothelial cells (HPM3) to these exosomes resulted in gene expression changes related to epithelial-to-mesenchymal transition and other cancer-related genes. This is the first report to indicate that asbestos-exposed cells secrete exosomes with differentially abundant proteins and that those exosomes have a gene-altering effect on mesothelial cells.-Munson, P., Lam, Y.-W., Dragon, J. MacPherson, M., Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.

  10. Cell phones and cancer

    Science.gov (United States)

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of ...

  11. Mammalian cells exposed to ionizing radiation: structural and biochemical aspects

    International Nuclear Information System (INIS)

    Sabanero, M.; Flores V, L. L.; Azorin V, J. C.; Vallejo, M. A.; Cordova F, T.; Sosa A, M.; Castruita D, J. P.; Barbosa S, G.

    2015-10-01

    Acute or chronic exposure to ionizing radiation is a factor that may be hazardous to health. It has been reported that exposure to low doses of radiation (less than 50 mSv / year) and subsequently exposure to high doses have greater effects in people. However, it is unknown molecular and biochemical level alteration. This study, analyzes the susceptibility of a biological system (HeLa Atcc CCL-2 human cervix cancer cell line) to ionizing radiation (6 and 60 mSv/ 90). Our evaluate multiple variables such as: total protein profile, mitochondrial metabolic activity (XTT assay), cell viability (Trypan blue exclusion assay), cytoskeleton (actin micro filaments), nuclei (D API), genomic DNA. The results indicate, that cells exposed to ionizing radiation structurally show alterations in nuclear phenotype and aneuploidy, further disruption in the tight junctions and consequently on the distribution of actin micro filaments. Similar alterations were observed in cells treated with a genotoxic agent (200μM H 2 O 2 /1 h). In conclusion, this multi-criteria assessment enables precise comparisons of the effects of radiation between any biological systems. However, it is necessary to determine stress markers for integration of the effects of ionizing radiation. (Author)

  12. Mammalian cells exposed to ionizing radiation: structural and biochemical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Sabanero, M.; Flores V, L. L. [Universidad de Guanajuato, Departamento de Biologia, DCNE, Noria Alta s/n, 36250 Guanajuato, Gto. (Mexico); Azorin V, J. C.; Vallejo, M. A.; Cordova F, T.; Sosa A, M. [Universidad de Guanajuato, Departamento de Ingenieria Fisica, DCI, Loma del Bosque 103, Col. Lomas del Campestre, 37150 Leon, Guanajuato (Mexico); Castruita D, J. P. [Universidad de Guadalajara, Departamento de Ecologia, CUCBA, Las Agujas, 45100 Zapopan, Jalisco (Mexico); Barbosa S, G., E-mail: myrna.sabanero@gmail.com [Universidad de Guanajuato, Departamento de Ciencias Medicas, DCS, 20 de Enero No. 929, Col. Obregon, 37000 Leon, Guanajuato (Mexico)

    2015-10-15

    Acute or chronic exposure to ionizing radiation is a factor that may be hazardous to health. It has been reported that exposure to low doses of radiation (less than 50 mSv / year) and subsequently exposure to high doses have greater effects in people. However, it is unknown molecular and biochemical level alteration. This study, analyzes the susceptibility of a biological system (HeLa Atcc CCL-2 human cervix cancer cell line) to ionizing radiation (6 and 60 mSv/ 90). Our evaluate multiple variables such as: total protein profile, mitochondrial metabolic activity (XTT assay), cell viability (Trypan blue exclusion assay), cytoskeleton (actin micro filaments), nuclei (D API), genomic DNA. The results indicate, that cells exposed to ionizing radiation structurally show alterations in nuclear phenotype and aneuploidy, further disruption in the tight junctions and consequently on the distribution of actin micro filaments. Similar alterations were observed in cells treated with a genotoxic agent (200μM H{sub 2}O{sub 2}/1 h). In conclusion, this multi-criteria assessment enables precise comparisons of the effects of radiation between any biological systems. However, it is necessary to determine stress markers for integration of the effects of ionizing radiation. (Author)

  13. A prototype methodology combining surface-enhanced laser desorption/ionization protein chip technology and artificial neural network algorithms to predict the chemoresponsiveness of breast cancer cell lines exposed to Paclitaxel and Doxorubicin under in vitro conditions.

    Science.gov (United States)

    Mian, Shahid; Ball, Graham; Hornbuckle, Jo; Holding, Finn; Carmichael, James; Ellis, Ian; Ali, Selman; Li, Geng; McArdle, Stephanie; Creaser, Colin; Rees, Robert

    2003-09-01

    An ability to predict the likelihood of cellular response towards particular chemotherapeutic agents based upon protein expression patterns could facilitate the identification of biological molecules with previously undefined roles in the process of chemoresistance/chemosensitivity, and if robust enough these patterns might also be exploited towards the development of novel predictive assays. To ascertain whether proteomic based molecular profiling in conjunction with artificial neural network (ANN) algorithms could be applied towards the specific recognition of phenotypic patterns between either control or drug treated and chemosensitive or chemoresistant cellular populations, a combined approach involving MALDI-TOF matrix-assisted laser desorption/ionization-time of flight mass spectrometry, Ciphergen protein chip technology and ANN algorithms have been applied to specifically identify proteomic 'fingerprints' indicative of treatment regimen for chemosensitive (MCF-7, T47D) and chemoresistant (MCF-7/ADR) breast cancer cell lines following exposure to Doxorubicin or Paclitaxel. The results indicate that proteomic patterns can be identified by ANN algorithms to correctly assign 'class' for treatment regimen (e.g. control/drug treated or chemosensitive/chemoresistant) with a high degree of accuracy using boot-strap statistical validation techniques and that biomarker ion patterns indicative of response/non-response phenotypes are associated with MCF-7 and MCF-7/ADR cells exposed to Doxorubicin. We have also examined the predictive capability of this approach towards MCF-7 and T47D cells to ascertain whether prediction could be made based upon treatment regimen irrespective of cell lineage. Models were identified that could correctly assign class (control or Paclitaxel treatment) for 35/38 samples of an independent dataset. A similar level of predictive capability was also found (> 92%; n = 28) when proteomic patterns derived from the drug resistant cell line MCF-7

  14. Inhibition of Mammary Cancer Progression in Fetal Alcohol Exposed Rats by β-Endorphin Neurons.

    Science.gov (United States)

    Zhang, Changqing; Franklin, Tina; Sarkar, Dipak K

    2016-01-01

    Fetal alcohol exposure (FAE) increases the susceptibility to carcinogen-induced mammary cancer progression in rodent models. FAE also decreases β-endorphin (β-EP) level and causes hyperstress response, which leads to inhibition of immune function against cancer. Previous studies have shown that injection of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) into the third ventricle increases the number of β-EP neurons in the hypothalamus. In this study, we assessed the therapeutic potential of stress regulation using methods to increase hypothalamic levels of β-EP, a neuropeptide that inhibits stress axis activity, in treatment of carcinogen-induced mammary cancer in fetal alcohol exposed rats. Fetal alcohol exposed and control Sprague Dawley rats were given a dose of N-Nitroso-N-methylurea (MNU) at postnatal day 50 to induce mammary cancer growth. Upon detection of mammary tumors, the animals were either transplanted with β-EP neurons or injected with dbcAMP-delivering nanospheres into the hypothalamus to increase β-EP peptide production. Spleen cytokines were detected using reverse transcription polymerase chain reaction assays. Metastasis study was done by injecting mammary cancer cells MADB106 into jugular vein of β-EP-activated or control fetal alcohol exposed animals. Both transplantation of β-EP neurons and injection of dbcAMP-delivering nanospheres inhibited MNU-induced mammary cancer growth in control rats, and reversed the effect of FAE on the susceptibility to mammary cancer. Similar to the previously reported immune-enhancing and stress-suppressive effects of β-EP transplantation, injection of dbcAMP-delivering nanospheres increased the levels of interferon-γ and granzyme B and decreased the levels of epinephrine and norepinephrine in fetal alcohol exposed rats. Mammary cancer cell metastasis study also showed that FAE increased incidence of lung tumor retention, while β-EP transplantation inhibited lung tumor growth in

  15. Exposing the cancer genome atlas as a SPARQL endpoint

    Science.gov (United States)

    Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

    2011-01-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

  16. Biological behaviour of buccal cells exposed to blue light

    International Nuclear Information System (INIS)

    Gritsch, Kerstin; Ponsonnet, Laurence; Schembri, Catherine; Farge, Pierre; Pourreyron, Laurence; Grosgogeat, Brigitte

    2008-01-01

    Blue light is used in dental practise to cure resin-based materials, but the path of the light often includes oral tissues such as gingival tissues. While adverse effects of blue light exposure on cells - such as retina cells - are well known, few studies have investigated the impact of blue light exposure on oral cells. The aim of the present in vitro study was to assess the biological effects of blue light emitted by two dental curing devices (a plasma-arc and a light-emitting diode curing unit) on human gingival fibroblasts. Light intensities and light-induced temperature rise were respectively measured with a radiometer and a thermocouple. Cellular response to blue light exposure was assessed by the observation of cell morphology (scanning electron microscopy) and the estimation of cell mitochondrial activity (MTT assay). Light intensities measured at the clinical distance were 488 ± 42 mW/cm 2 for the plasma-arc unit and ranged from 61 ± 5 to 140 ± 16 mW/cm 2 for the light-emitting diodes unit, according to the curing program used. The highest temperature rise was 0.5 and 3.5 deg. C for exposure to the plasma-arc light and to the light-emitting diodes light, respectively. Results showed no differences between exposed- and non-exposed cells in regards to cell morphology. However, cells exposed to blue light presented an increased mitochondrial activity compared to control cells (non-exposed), and mostly those exposed to plasma-arc light

  17. An immunosurveillance mechanism controls cancer cell ploidy.

    Science.gov (United States)

    Senovilla, Laura; Vitale, Ilio; Martins, Isabelle; Tailler, Maximilien; Pailleret, Claire; Michaud, Mickaël; Galluzzi, Lorenzo; Adjemian, Sandy; Kepp, Oliver; Niso-Santano, Mireia; Shen, Shensi; Mariño, Guillermo; Criollo, Alfredo; Boilève, Alice; Job, Bastien; Ladoire, Sylvain; Ghiringhelli, François; Sistigu, Antonella; Yamazaki, Takahiro; Rello-Varona, Santiago; Locher, Clara; Poirier-Colame, Vichnou; Talbot, Monique; Valent, Alexander; Berardinelli, Francesco; Antoccia, Antonio; Ciccosanti, Fabiola; Fimia, Gian Maria; Piacentini, Mauro; Fueyo, Antonio; Messina, Nicole L; Li, Ming; Chan, Christopher J; Sigl, Verena; Pourcher, Guillaume; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Lazar, Vladimir; Penninger, Josef M; Madeo, Frank; López-Otín, Carlos; Smyth, Mark J; Zitvogel, Laurence; Castedo, Maria; Kroemer, Guido

    2012-09-28

    Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers.

  18. Colorectal cancer stem cells.

    Science.gov (United States)

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  19. Exposing the cancer genome atlas as a SPARQL endpoint.

    Science.gov (United States)

    Deus, Helena F; Veiga, Diogo F; Freire, Pablo R; Weinstein, John N; Mills, Gordon B; Almeida, Jonas S

    2010-12-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  1. Detection of genomic instability in normal human bronchial epithelial cells exposed to 238Pu

    International Nuclear Information System (INIS)

    Kennedy, C.H.; Fukushima, N.H.; Neft, R.E.; Lechner, J.F.

    1994-01-01

    Alpha particle-emitting radon daughters constitute a risk for development of lung cancer in humans. The development of this disease involves multiple genetic alterations. These changes and the time course they follow are not yet defined despite numerous in vitro endeavors to transform human lung cells with various physical or chemical agents. However, genomic instability, characterized both by structural and numerical chromosomal aberrations and by elevated rates of point mutations, is a common feature of tumor cells. Further, both types of genomic instability have been reported in the noncancerous progeny of normal murine hemopoietic cells exposed in vitro to α-particles. The purpose of this investigation was to determine if genomic instability is also a prominent feature of normal human bronchial epithelial cells exposed to α-particle irradiation from the decay of inhaled radon daughters

  2. Fingerprints in cancer cells

    International Nuclear Information System (INIS)

    Servomaa, K.

    1994-01-01

    Gene research has shown that factors causing cancer, or carcinogens, may leave marks typical of each particular carcinogen (fingerprints) in the genotype of the cell. Radiation, for instance, may leave such fingerprints in a cancer cell. In particular, the discovery of a gene called p53 has yielded much new information on fingerprints. It has been discovered, for example, that toxic fungus and UV-radiation each leave fingerprints in the p53 gene. Based on the detection of fingerprints, it may be possible in the future to tell a cancer patient what factor had trigged the maglinancy

  3. Action spectra in mammalian cells exposed to ultraviolet radiation

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    A review is given of the literature published since 1977 on action spectra in mammalian cells exposed to ultraviolet radiation in the wavelength region above 220 nm. Action spectra for lethal events are discussed for cell inactivation in normal cells, growth arrested cells and photosensitive cells. Action spectra for non-lethal events are also discussed in relation to pyrimidine dimer formation, photoreactivation and the use of photosensitisers. It was concluded from these studies that damage to the DNA, and the extent of the repair of this damage, seems to determine a cell's response to such parameters as inactivation, mutation, transformation, latent viral activation, cellular viral capacity and ultraviolet enhanced viral reactivation. In addition to the direct effects of UV on DNA, photosensitization of cellular responses with chemicals such as 8-MOP extend the wavelength range at which damage can be demonstrated. (U.K.)

  4. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    The Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell tumors. That is, the tumors originate in the sperm forming cells in the testicles ( ...

  5. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  6. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  7. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  8. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  9. The efficiency of photovoltaic cells exposed to pulsed laser light

    Science.gov (United States)

    Lowe, R. A.; Landis, G. A.; Jenkins, P.

    1993-01-01

    Future space missions may use laser power beaming systems with a free electron laser (FEL) to transmit light to a photovoltaic array receiver. To investigate the efficiency of solar cells with pulsed laser light, several types of GaAs, Si, CuInSe2, and GaSb cells were tested with the simulated pulse format of the induction and radio frequency (RF) FEL. The induction pulse format was simulated with an 800-watt average power copper vapor laser and the RF format with a frequency-doubled mode-locked Nd:YAG laser. Averaged current vs bias voltage measurements for each cell were taken at various optical power levels and the efficiency measured at the maximum power point. Experimental results show that the conversion efficiency for the cells tested is highly dependent on cell minority carrier lifetime, the width and frequency of the pulses, load impedance, and the average incident power. Three main effects were found to decrease the efficiency of solar cells exposed to simulated FEL illumination: cell series resistance, LC 'ringing', and output inductance. Improvements in efficiency were achieved by modifying the frequency response of the cell to match the spectral energy content of the laser pulse with external passive components.

  10. Evaluation of selenium in biological sample of arsenic exposed female skin lesions and skin cancer patients with related to non-exposed skin cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Kolachi, Nida F.; Kazi, Tasneem G., E-mail: tgkazi@yahoo.com; Wadhwa, Sham K.; Afridi, Hassan I.; Baig, Jameel A.; Khan, Sumaira; Shah, Faheem

    2011-08-01

    The antagonistic effects between selenium (Se) and arsenic (As) suggest that low Se status plays an important role in arsenism development. The objective of present study was to assess Se contents in biological samples of As exposed females have skin lesions and cancer with related to non-exposed skin cancer patients. The biological samples (blood and scalp hair) of As exposed group comprises, female skin cancer (ESC) patients admitted in cancer hospitals have skin lesions (ESL) and exposed referents have not both diseases (ER), belongs to As exposed area of Pakistan. For comparative purposes, age matched female skin cancerous patient (RP) and non-cancerous females (NER) belong to non-exposed areas were also selected. The As and Se in acid digests of biological samples were pre-concentrated by complexing with chelating agent (ammonium pyrrolidinedithiocarbamate), and resulted complexes were extracted into non-ionic extractant (Triton X-114), prior to analysis by electrothermal atomic absorption spectrometry. The enhancement factor of about 25 was obtained by pre-concentrating 10 mL of sample solutions. The accuracy of the optimized procedure was evaluated by using certified reference material (BCR 397) with certified values for Se and As and standard addition method at three concentration levels in real samples. No significant differences was observed (p > 0.05) when comparing the values obtained by the proposed method, added and certified values of both elements. The biological samples of ESC patients had 2-3 folds higher As and lower Se levels as compared to RP (p < 0.001). Understudied exposed referents have high level of As and lower Se contents as compared to referents subjects of non-exposed area (p < 0.01). The higher concentration of As and lower levels of Se in biological samples of cancerous patients are consisted with reported studies. - Research Highlights: {yields} Advance extraction method for the enrichment of arsenic and selenium in biological

  11. Evaluation of selenium in biological sample of arsenic exposed female skin lesions and skin cancer patients with related to non-exposed skin cancer patients

    International Nuclear Information System (INIS)

    Kolachi, Nida F.; Kazi, Tasneem G.; Wadhwa, Sham K.; Afridi, Hassan I.; Baig, Jameel A.; Khan, Sumaira; Shah, Faheem

    2011-01-01

    The antagonistic effects between selenium (Se) and arsenic (As) suggest that low Se status plays an important role in arsenism development. The objective of present study was to assess Se contents in biological samples of As exposed females have skin lesions and cancer with related to non-exposed skin cancer patients. The biological samples (blood and scalp hair) of As exposed group comprises, female skin cancer (ESC) patients admitted in cancer hospitals have skin lesions (ESL) and exposed referents have not both diseases (ER), belongs to As exposed area of Pakistan. For comparative purposes, age matched female skin cancerous patient (RP) and non-cancerous females (NER) belong to non-exposed areas were also selected. The As and Se in acid digests of biological samples were pre-concentrated by complexing with chelating agent (ammonium pyrrolidinedithiocarbamate), and resulted complexes were extracted into non-ionic extractant (Triton X-114), prior to analysis by electrothermal atomic absorption spectrometry. The enhancement factor of about 25 was obtained by pre-concentrating 10 mL of sample solutions. The accuracy of the optimized procedure was evaluated by using certified reference material (BCR 397) with certified values for Se and As and standard addition method at three concentration levels in real samples. No significant differences was observed (p > 0.05) when comparing the values obtained by the proposed method, added and certified values of both elements. The biological samples of ESC patients had 2-3 folds higher As and lower Se levels as compared to RP (p < 0.001). Understudied exposed referents have high level of As and lower Se contents as compared to referents subjects of non-exposed area (p < 0.01). The higher concentration of As and lower levels of Se in biological samples of cancerous patients are consisted with reported studies. - Research Highlights: → Advance extraction method for the enrichment of arsenic and selenium in biological matrices

  12. Synthesis of protein in intestinal cells exposed to cholera toxin

    International Nuclear Information System (INIS)

    Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.

    1987-01-01

    The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells and Chinese hamster ovary cells exposed to cholera toxin. An increase in [ 3 H] leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of [ 35 S] methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed

  13. Polyamines and polyamine biosynthesis in cells exposed to hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Gerner, E.W.; Stickney, D.G.; Herman, T.S.; Fuller, D.J.

    1983-02-01

    The issue of how polyamines act to sensitize cultured cells to the lethal effects of hyperthermia was investigated using Chinese hamster cells which were induced to express thermotolerance. Intracellular levels of these naturally occurring polycations were manipulated in certain situations by treating whole cells with methylglyoxal bis-(guanylhydrazone), an inhibitor of the S-adenosyl-L-methionine decarboxylases. Exogenous spermine as low as 100 ..mu..M in the culture media dramatically sensitized cells expressing thermotolerance to the lethal effects of subsequent 42/sup 0/C exposures. When thermotolerance was differentially induced in cultures exposed to 42.4/sup 0/C by varying the rate of heating from 37 to 42.4/sup 0/C, the most resistant cells and the highest levels of intracellular spermidine and spermine. This finding was explainable in part by the observation that the putrescine-dependent S-adenosyl-L-methionine decarboxylase activity was minimally affected in cells expressng the greatest degree of thermotolerance. When this enzyme activity was inhibited by drug, lowered intracellular polyamine levels did not correspond with subsequent survival responses to heat. Interestingly, cultures treated with methylglyoxal bis-(guanylhydrazone) 24 hr previous to heat exposure showed a reduced capacity to express rate of heating-induced thermotolerance. Together, these results demonstrate that the polyamines, especially spermidine and spermine, enhance hyperthermia-induced cell killing by some mechanism involving the plasma membrane. Further, our data suggest that methylglyoxal bis-(guanylhydrazone) can act to affect thermal responses by a mechanism(s) other than modification of intracellular polyamine levels.

  14. Modeling lung cancer risks in laboratory dogs exposed to inhaled plutonium

    International Nuclear Information System (INIS)

    Gilbert, E.S.; Park, J.F.; Buschbom, R.L.

    1990-06-01

    These analyses are based on data from a lifespan study of beagle dogs exposed to inhaled plutonium being conducted at Pacific Northwest Laboratory. An important goal of this study is to increase understanding of health risk resulting from this exposure, with particular attention to lung cancer risks. Data on humans exposed to plutonium are inadequate for achieving this goal

  15. Adenine nucleotide depletion from endothelial cells exposed to xanthine oxidase

    International Nuclear Information System (INIS)

    Aalto, T.K.; Raivio, K.O.

    1990-01-01

    Hypoxia causes breakdown of cellular nucleotides, accumulation of hypoxanthine (HX), and conversion of xanthine dehydrogenase into xanthine oxidase (XO). Upon reoxygenation, the HX-XO reaction generates free radicals, one potential mechanism of tissue damage. Because endothelial cells contain XO and are exposed to circulating HX, they are a likely target for damage. We studied the effect of XO and/or HX at physiologically relevant concentrations on nucleotide metabolism of cultured endothelial cells from human umbilical veins. Cells were labeled with [14C]adenine and incubated for up to 6 h with HX, XO, or both, in the absence or presence of serum. Adenine nucleotides from cell extracts and nucleotide breakdown products (HX, xanthine, and urate) from the medium were separated and counted. HX alone had no effect. XO (80 mU/ml) alone caused a 70% (no serum) or 40% (with serum) fall in adenine nucleotides and an equivalent increase of xanthine and urate. The combination of HX and XO caused a 90% (no serum) or 70% (with serum) decrease in nucleotides, decrease in energy charge, and detachment of cells from the culture plate. Nucleotide depletion was not accounted for by proteolytic activity in the XO preparation. Albumin was only half as effective as serum in preventing nucleotide loss. Thus exogenous XO, in the presence of endogenous HX, triggers adenine nucleotide catabolism, but endogenous XO activity is too low to influence nucleotide levels even at high exogenous HX concentrations. Serum limits the catabolic effect of XO and thus protects cells from free radical damage

  16. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

  17. Cancer stem cells and personalized cancer nanomedicine.

    Science.gov (United States)

    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2016-02-01

    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  18. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  20. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  1. Local advanced transitional cell cancer and squamous cell cancer of ...

    African Journals Online (AJOL)

    Case report: A 51-year-old man presented with a locally advanced squamous cell cancer of the periurethral tissues as well as an underlying isolated transitional cell cancer of the urethra. Chemotherapy with Gemcitabin and Cisplatinum together with local radiation to the pelvis and the perineum was given. There was ...

  2. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.

    Science.gov (United States)

    Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

    2012-12-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.

  3. Modification of cell volume and proliferative capacity of Pseudokirchneriella subcapitata cells exposed to metal stress

    International Nuclear Information System (INIS)

    Machado, Manuela D.; Soares, Eduardo V.

    2014-01-01

    Highlights: •Metals induce morphological alterations on P. subcapitata. •Algal cell cycle consists: mother cell growth; cell division, with two nucleus divisions; release of four autospores. •Cu(II) and Cr(VI) arrest cell growth before the first nuclear division. •Cd(II) arrests cell growth after the second nuclear division but before the cytokinesis. •The approach used can be useful in the elucidation of different modes of action of pollutants. -- Abstract: The impact of metals (Cd, Cr, Cu and Zn) on growth, cell volume and cell division of the freshwater alga Pseudokirchneriella subcapitata exposed over a period of 72 h was investigated. The algal cells were exposed to three nominal concentrations of each metal: low (closed to 72 h-EC 10 values), intermediate (closed to 72 h-EC 50 values) and high (upper than 72 h-EC 90 values). The exposure to low metal concentrations resulted in a decrease of cell volume. On the contrary, for the highest metal concentrations an increase of cell volume was observed; this effect was particularly notorious for Cd and less pronounced for Zn. Two behaviours were found when algal cells were exposed to intermediate concentrations of metals: Cu(II) and Cr(VI) induced a reduction of cell volume, while Cd(II) and Zn(II) provoked an opposite effect. The simultaneous nucleus staining and cell image analysis, allowed distinguishing three phases in P. subcapitata cell cycle: growth of mother cell; cell division, which includes two divisions of the nucleus; and, release of four autospores. The exposure of P. subcapitata cells to the highest metal concentrations resulted in the arrest of cell growth before the first nucleus division [for Cr(VI) and Cu(II)] or after the second nucleus division but before the cytokinesis (release of autospores) when exposed to Cd(II). The different impact of metals on algal cell volume and cell-cycle progression, suggests that different toxicity mechanisms underlie the action of different metals

  4. Epigenetics in cancer stem cells.

    Science.gov (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  5. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  6. Studies on the hazard of leukaemia and cancer in persons occupationally exposed to radiation

    International Nuclear Information System (INIS)

    Streffer, C.

    1988-01-01

    The mortality rates of British radiologists in dependence of the duration of their radiation work are compared with the general mortality rate in England and Wales, the mortality rates of men of the social class 1 and the mortality rates of practicing physicians. It turns out that the mortality by malignant diseases (leukemia and cancer) of persons exposed to radiation at work in nuclear plants is not considerably higher than it is for comparable groups of persons not exposed to radiation. Tumour entities of the GI tract have not been found either in the British radiologists exposed to radiation. (DG) [de

  7. Cell growth, intracellular calcium concentration and metabolic cooperation measured in cells exposed to 50 Hz electromagnetic fields

    International Nuclear Information System (INIS)

    Skauli, K.S.

    1996-08-01

    Colony-forming efficiency, DNA/protein and DNA/cell were measured in cells exposed to magnetic fields of 0.2 and 1 mT at a frequency of 50 Hz. Intracellular calcium concentrations were measured in cells exposed to 0.3 and 1 mT at 50 Hz. Metabolic cooperation was measured in cells exposed to 1 mT at 50 Hz. No significant effects of the fields were observed. 20 refs., 10 figs

  8. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues...

  9. Potassium ion influx measurements on cultured Chinese hamster cells exposed to 60-hertz electromagnetic fields

    International Nuclear Information System (INIS)

    Stevenson, A.P.; Tobey, R.A.

    1985-01-01

    Potassium ion influx was measured by monitoring 42 KCl uptake by Chinese hamster ovary (CHO) cells grown in suspension culture and exposed in the culture medium to 60-Hz electromagnetic fields up to 2.85 V/m. In the presence of the field CHO cells exhibited two components of uptake, the same as previously observed for those grown under normal conditions; both these components of influx were decreased when compared to sham-exposed cells. Although decreases were consistently observed in exposed cells when plotted as loge of uptake, the differences between the means of the calculated fluxes of exposed and sham-exposed cells were quite small (on the order of 4-7%). When standard deviations were calculated, there was no significant difference between these means; however, when time-paired uptake data were analyzed, the differences were found to be statistically significant. Cells exposed only to the magnetic field exhibited similar small decreases in influx rates when compared to sham-exposed cells, suggesting that the reduction in K+ uptake could be attributed to the magnetic field. Additionally, intracellular K+ levels were measured over a prolonged exposure period (96 h), and no apparent differences in intracellular K+ levels were observed between field-exposed and sham-exposed cultures. These results indicate that high-strength electric fields have a small effect on the rate of transport of potassium ions but no effect on long-term maintenance of intracellular K+

  10. Cancer mortality among women frequently exposed to radiographic examinations for spinal disorders

    NARCIS (Netherlands)

    Ronckers, Cécile M.; Land, Charles E.; Miller, Jeremy S.; Stovall, Marilyn; Lonstein, John E.; Doody, Michele M.

    2010-01-01

    We studied cancer mortality in a cohort of 5,573 women with scoliosis and other spine disorders who were diagnosed between 1912 and 1965 and were exposed to frequent diagnostic X-ray procedures. Patients were identified from medical records in 14 orthopedic medical centers in the United States and

  11. Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts.

    Directory of Open Access Journals (Sweden)

    Simona Catalani

    Full Text Available Essential oils from the aerial parts (leaves, twigs and berries of Pistacia lentiscus (PLEO have been well characterized for their antibacterial and anti-inflammatory properties; however, poor information exists on their potential anticancer activity.Increasing concentrations of PLEO (0.01-0.1% v/v, 80-800 μg/ml were administered to a wide variety of cultured cancer cells from breast, cervix, colon, liver, lung, prostate, and thyroid carcinomas. Fibroblasts were also included as healthy control cells. Cell viability was monitored by WST-8 assay up to 72 hours after PLEO administration. The intracellular formation of reactive oxygen species (ROS, the induction of apoptosis, and the enhancement of chemotherapeutic drug cytotoxicity by PLEO were further investigated in the most responsive cancer cell line.A dose-dependent reduction of tumor cell viability was observed upon PLEO exposure; while no cytotoxic effect was revealed in healthy fibroblasts. FTC-133 thyroid cancer cells were found to be the most sensitive cells to PLEO treatment; accordingly, an intracellular accumulation of ROS and an activation of both the extrinsic and intrinsic apoptotic pathways were evidenced in FTC-133 cells after PLEO administration. Furthermore, the cytotoxic effect of the antineoplastic drugs cisplatin, 5-fluorouracil and etoposide was enhanced in PLEO-exposed FTC-133 cells.Taking into account its mode of action, PLEO might be considered as a promising source of natural antitumor agents which might have therapeutic potential in integrated oncology.

  12. Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts.

    Science.gov (United States)

    Catalani, Simona; Palma, Francesco; Battistelli, Serafina; Benedetti, Serena

    2017-01-01

    Essential oils from the aerial parts (leaves, twigs and berries) of Pistacia lentiscus (PLEO) have been well characterized for their antibacterial and anti-inflammatory properties; however, poor information exists on their potential anticancer activity. Increasing concentrations of PLEO (0.01-0.1% v/v, 80-800 μg/ml) were administered to a wide variety of cultured cancer cells from breast, cervix, colon, liver, lung, prostate, and thyroid carcinomas. Fibroblasts were also included as healthy control cells. Cell viability was monitored by WST-8 assay up to 72 hours after PLEO administration. The intracellular formation of reactive oxygen species (ROS), the induction of apoptosis, and the enhancement of chemotherapeutic drug cytotoxicity by PLEO were further investigated in the most responsive cancer cell line. A dose-dependent reduction of tumor cell viability was observed upon PLEO exposure; while no cytotoxic effect was revealed in healthy fibroblasts. FTC-133 thyroid cancer cells were found to be the most sensitive cells to PLEO treatment; accordingly, an intracellular accumulation of ROS and an activation of both the extrinsic and intrinsic apoptotic pathways were evidenced in FTC-133 cells after PLEO administration. Furthermore, the cytotoxic effect of the antineoplastic drugs cisplatin, 5-fluorouracil and etoposide was enhanced in PLEO-exposed FTC-133 cells. Taking into account its mode of action, PLEO might be considered as a promising source of natural antitumor agents which might have therapeutic potential in integrated oncology.

  13. Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Naylor, Paul H; Egan, James E; Berinstein, Neil L; Kast, W Martin

    2016-05-01

    Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

  14. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  15. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  16. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  17. Cancer incidence and risk in Alaskan natives exposed to radioactive fallout

    International Nuclear Information System (INIS)

    Stutzman, C.D.; Nelson, D.M.

    1986-01-01

    Cancer incidence in northern Alaskan villages exposed to radioactive fallout from nuclear weapons testing in the late 1950s and early 1960s was assessed using data from the Alaskan Native Tumor Registry. Previous studies have shown that cancer incidence in Alaskan natives differs from that in residents of the rest of the United States: rates of cancer of the nasopharynx and liver are higher in Alaskan native men and rates of cancer of the nasopharynx, gallbladder, cervix, and kidney are higher in Alaskan native women. Leukemia, breast cancer and bone sarcoma are the cancers most likely to result from fallout exposure in the Arctic, but the incidence of these cancers in the North Slope villages appeared to be lower than in either the entire Inuit population or the US population. The fallout radionuclides of potential health concern are cesium-137 and strontium-90, because of their abundance, long half-life, and chemical characteristics that facilitate transport through and concentration in the food chain and accumulation in sensitive tissues of the body. Radionuclide body burdens were determined in North Slope Inuit 25 years ago, because of their possible exposure to radioactive fallout via the lichen-caribou-man pathway. Cancer risk estimates have been calculated using highest average dose measurements from residents of Anaktuvuk Pass, under the assumption that peak exposure levels of the mid 1960s remained steady over the following 20 years. Worst-case estimates of expected cancer excess were calculated for leukemia, breast cancer and bone sarcoma

  18. EVALUATION OF CELL CYCLE OF Aspergillus nidulans EXPOSED TO THE EXTRACT OF Copaifera officinalis L PLANT

    Directory of Open Access Journals (Sweden)

    Simone Jurema Ruggeri Chiuchetta, Uériton Dias de Oliveira e Josy Fraccaro de Marins

    2006-12-01

    Full Text Available The oil extracted from the Copaifera officinalis L plant has been used in popular medicine to the treatment of several diseases, like cancer. In eukaryotic cells, the process of cellular proliferation follows a standard cycle, named cellular cycle. The transformation of a normal cell in a malignant one requires several steps, in which genes that control normal cellular division or cellular death are modified. Aspergillus nidulans fungus is an excellent system for the study of the cellular differentiation. Its asexual cycle results in the formation of conidia, which are disposed like chains, constituting a structure named conidiophore. This structure consists in an aerial hifae, multinucleate vesicle and uninucleate cells. Current research evaluated the capacity of the C. officinalis L plant extract in promoting alterations in the cellular cycle of A. nidulans diploid strains, by observing macroscopic and microscopic alterations in cellular growth of this fungus. Results shown that no macroscopic alterations were observed in cellular growth of strains exposed to the extract, however, microscopic alterations of conidiophore have been observed in the different extract concentrations analyzed. In this way, the study of the action of C. officinalis L plant extract becomes important considering the fact that this substance is capable to promote alterations in cellular cycle of eukaryotic cells.

  19. [Clinico-morphological peculiarities of thyroid cancer among children exposed to the Chernobyl disaster radiation].

    Science.gov (United States)

    Iakovleva, I N; Shishkov, R V; Poliakov, V G; Pankova, P A

    2008-01-01

    The paper deals with a comparison of clinico-morphological patterns of sporadic thyroid cancer and that in pediatric patients exposed to radiation during the Chernobyl disaster. The latter are highly prone to both local and regional metastatic spread to the lymph nodes (intrathyroid distribution--61%; extension through capsule--42%, and metastases to the neck lymph nodes--66%). However, these data do not differ significantly from those for intact areas. Yet, cancer occurs in exposed cohorts at an earlier stage: its incidence at age 4-6 is 2-3.5 higher and that of relapse such as presentation of latent metastases to the lymph nodes and tumor foci development in residual tumor tissue is 1.6 times the average. Also, morphological patterns have changed: typical papillary cancer incidence has dropped by half while the diffuse follicular variety has grown 1.8-fold.

  20. Risk of cancer among in utero children exposed to A-bomb radiation, 1950-84

    International Nuclear Information System (INIS)

    Yoshimoto, Yasuhiko; Kato, Hiroo; Schull, W.J.

    1990-01-01

    This study examines the risk of cancer (incidence) over a period of 40 years among the inutero exposed survivors of the atomic bombing of Hiroshima and Nagasaki, and adds eight years of follow-up to a previous report which was confined to mortality. Only two cases of childhood cancer were observed among these survivors in the first 14 years of life; both had been heavily exposed. Subsequent cancers have all been of the adult type. Not only did the observed cancers occur earlier in the ≥ 0.30 Gy dose group than in the 0 Gy dose group but the incidence continues to increase and the crude cumulative incidence rate, 40 years after the A-bombing, is 3.9-fold greater in the ≥ 0.30 Gy group. In the observation period 1950-84, based on the absorbed dose to the mother's uterus, as estimated by the Dosimetry System 1986 (DS86), the relative risk of cancer at 1 Gy is 3.77 with a 95% confidence interval of 1.14-13.48. For the entire ≥ 0.01 Gy dose group the average excess risk per 10 4 person-year-gray is 6.57 (0.07-14.49) and the estimated attributable risk is 40.9% (2.9%-90.2%). These results, when viewed in the perspective of fetus doses, suggest that susceptibility to radiation-induced cancers is higher in pre- than in postnatally exposed survivors (at least those exposed as adults). However, definitive conclusions must await further follow-up studies. (author)

  1. Multifaceted Interpretation of Colon Cancer Stem Cells.

    Science.gov (United States)

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-07-05

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

  2. CNT Nanobombs for Specific Eradication of Cancer Cells: A New Concept in Cancer Theranosticss

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2011-11-01

    Full Text Available Whole extermination of cancerous cells/tissue seems no longer to be a dream. Exploiting advanced photoactive nanomaterials such as functionalized fullerenes and carbon nanotubes (CNTs can act as CNT nanobombs (CNT-NBs when exposed to the near infrared (NIR radiation. PEGylated CNTs tagged with an antibody/aptamer can target cancer cells. Once attached to cancer cells, the NIR emission (700-1100 nm, in which body tissues are mostly transparent, can be applied to CNT-NBs which can absorb the light and get heated up. The resultant enhanced temperature can abolish the cancer. Once stealth CNT-NBs are tagged with imaging moieties, it would be a matter of computer gaming for physician who can inject it for real time visualization and destruction of cancer by activation of the NIR laser. While, many nanosystems (NSs are still in waiting list for clinical translation, our dreams may come true by applying stealth CNT-NBs against cancer.

  3. Risk of cancer among children exposed in utero to A-bomb radiations, 1950-84

    International Nuclear Information System (INIS)

    Yoshimoto, Yasuhiko; Kato, Hiroo; Schull, W.J.; Texas Univ., Houston

    1988-01-01

    This study examines the risk of cancer (incidence) over 40 years among in-utero exposed survivors of atomic bombing of Hiroshima and Nagasaki, and adds eight years of follow-up to a previous report confined to mortality. Only two cases of childhood cancer were observed among these survivors in the first 14 years of life; both had been heavily exposed. Subsequent cancers have all been of the adult type. Not only did the observed cancers occur earlier in the 0.30+ Gy dose group than in the 0 Gy dose group but incidence continues to increase, and crude cumulative incidence rate, 40 years after A-bombing, is 3.9-fold greater in the 0.3+ Gy group. In the observation period 1950-84, based on the absorbed dose to the mother's uterus as estimated by the 1986 dosimetry system (DS86), the relative risk of cancer at 1 Gy is 3.77 with a 95% confidence interval of 1.14-13.48. For the entire 0.01 + Gy dose group the average excess risk per 10 4 person-year-gray is 6.57 (0.07-14.49) and the estimated attributable risk is 40.9% (2.9-90.2%). (author)

  4. Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up.

    Science.gov (United States)

    Pira, Enrico; Piolatto, Giorgio; Negri, Eva; Romano, Canzio; Boffetta, Paolo; Lipworth, Loren; McLaughlin, Joseph K; La Vecchia, Carlo

    2010-07-21

    We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure.

  5. Phytochemicals radiosensitize cancer cells by inhibiting DNA repair

    International Nuclear Information System (INIS)

    Singh, Rana P.

    2017-01-01

    Solid tumors are mostly treated with radiotherapy. Radiotherapy is toxic to normal tissues and also promote the invasiveness and radioresistance in cancer cells. The resistance against radiotherapy and adverse effects to normal cells reduce the overall therapeutic effects of the treatment. Radiosensitizing agents usually show limited success during clinical trials. Therefore, the search and development of new radiosensitizers showing selective response to only cancer cells is desirable. We analyzed the radiosensitizing effects including cell death effect of silibinin, a phytochemical on prostate cancer cells. Silibinin enhanced gamma radiation (2.5-10 Gy) induced inhibition in colony formation selectively in prostate cancer cells. In cell cycle progression, G2/M phase is the most sensitive phase for radiation-induced damage which was delayed by the compound treatment in radiation exposed cells. The lower concentrations of silibinin substantially enhanced radiation-induced apoptosis. A prolonged reactive oxygen species production was also observed in these treatments EGFR signaling pathway can contribute to radiation-induced pro-survival mechanisms and to the therapeutic resistance. Agent treatment reduced the IR-induced EGFR phosphorylation and consequently reversed the resistance mediating mechanisms within the cancer cell. Thus, inhibiting DNA repair in cancer cells would enhance therapeutic response of radiation in cancer cells. Silibinin affected the localization of EGFR and DNA-dependent protein kinase, the DNA-PK is known to be an important mediator of DSB repair in human cells, and showed increased number of pH2AX (ser139) foci, and thus indicating lower DNA repair in these cancer cells. This was also confirmed in the tumor xenograft study. Our findings suggest that a combination of silibinin with radiation could be an effective treatment of radioresistant human prostate cancer and warrants further investigation. (author)

  6. Metabolism during ECM Detachment: Achilles Heel of Cancer Cells?

    Science.gov (United States)

    Mason, Joshua A; Hagel, Kimberly R; Hawk, Mark A; Schafer, Zachary T

    2017-07-01

    Integrin-mediated attachment to the extracellular matrix (ECM) is required to combat the induction of programmed cell death in a variety of distinct cell types. If cells fail to maintain proper ECM attachment, they become subject to elimination via an apoptotic cell death program known as anoikis. However, anoikis inhibition is not sufficient to promote the long-term survival of ECM-detached cells. Several recent studies have unveiled the profound (anoikis-independent) impact of cell metabolism on the viability of ECM-detached cells. Thus, we posit that, during metastatic dissemination (when cancer cells are exposed to periods of ECM detachment), cancer cells must alter their metabolism in a fashion that promotes survival and ultimately contributes to metastatic outgrowth. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Evidence for alteration of the membrane-bound ribosomes in Micrococcus luteus cells exposed to lead

    Energy Technology Data Exchange (ETDEWEB)

    Barrow, W; Himmel, M; Squire, P G; Tornabene, T G

    1978-01-01

    Micrococcus luteus cells exposed to Pb(NO/sub 3/)/sub 2/ contained cytosol ribosomal particles and disaggregated membranal ribosomal particles as determined by ultracentrifugation and spectral studies. Approximately 60% of the membrane ribosome fraction from lead exposed cells had a sedimentation value of 8.4S. Cytosol ribosome from lead exposed cells as well as membranal and cytosol ribosomes from control cells were comparable by their contents of predominantly the 70S type with the 50S and 100S present in relatively small amounts. The lead content of the 8.4S components was more than 200 times higher than the components with higher sedimentation coefficients from lead exposed cells and approximately 650 times more than that of control cell ribosomes. The cells exposed to lead, however, showed no adverse effects from the lead in respect to their growth rates and cellular yields. These results indicate that lead is interacting only at specific sites of the membrane and is inducing events initiated only in strategic cellular regions. These data further substantiate that subtle changes do occur in lead exposed cells that show no obvious effects. It is assumed that these minor alterations are, in toto, biologically significant. 24 references, 2 figures, 1 table.

  8. B cells exposed to enterobacterial components suppress development of experimental colitis

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

    2012-01-01

    ). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

  9. Reprogramming to developmental plasticity in cancer stem cells.

    Science.gov (United States)

    O'Brien-Ball, Caitlin; Biddle, Adrian

    2017-10-15

    During development and throughout adult life, sub-populations of cells exist that exhibit phenotypic plasticity - the ability to differentiate into multiple lineages. This behaviour is important in embryogenesis, is exhibited in a more limited context by adult stem cells, and can be re-activated in cancer cells to drive important processes underlying tumour progression. A well-studied mechanism of phenotypic plasticity is the epithelial-to-mesenchymal transition (EMT), a process which has been observed in both normal and cancerous cells. The epigenetic and metabolic modifications necessary to facilitate phenotypic plasticity are first seen in development and can be re-activated both in normal regeneration and in cancer. In cancer, the re-activation of these mechanisms enables tumour cells to acquire a cancer stem cell (CSC) phenotype with enhanced ability to survive in hostile environments, resist therapeutic interventions, and undergo metastasis. However, recent research has suggested that plasticity may also expose weaknesses in cancer cells that could be exploited for future therapeutic development. More research is needed to identify developmental mechanisms that are active in cancer, so that these may be targeted to reduce tumour growth and metastasis and overcome therapeutic resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Radiosensitizing effect of Chitosan on HeLa and LN 18 brain tumor cells exposed to electron beam radiation

    International Nuclear Information System (INIS)

    Rao, Shama; Shetty, Sukanya; Suchetha Kumari, N.; Madhu, L.N.

    2014-01-01

    Chitosan has been widely used for multiple applications because it is a non-toxic biocompatible, biodegradable, and adsorptive material. A previous study has shown that low-molecular-weight chitosan (LMWC) exerts a cytotoxic effect on oral cancer cells. Although a higher concentration of LMWC in comparison to cisplatin was needed in order to kill cancer cells, it was relatively less cytotoxic to non-cancer cells. Some of the well known anticancer drugs have the property of sensitizing the cell to radiation, which will be more applicable during combination therapy of cancer. The present study was undertaken to find the radiosensitizing effect of chitosan on Hela and Brain tumor (LN18) cells against electron beam radiation (EBR). Both the cancer cell lines, Hela and LN 18 were treated with different concentration of chitosan (50 and 100 μg/ml) pre and post exposure to 4 Gy EBR. The percentage of cell viability, percentage of apoptosis and ssDNA damage in the treated cells were assessed by MTT assay, DNA diffusion assay and comet assay respectively. The obtained results showed 62.13 1 5.08 and 65.24 1 2.45 percent Hela and LN 18 viable cells at 24 hour after the exposure to 4 Gy EBR. The percentage of viability was found to be decreased in cells exposed to EBR in the presence of chitosan. Supporting to this, percentage of apoptotic cells was found to be more in treated groups (28.13 1 4.34 and 25.13 1 3.76) when compared with control (23.19 1 1.07 and 20.79 1 4.86). Treatment of HeLa and LN18 before and after the exposure of EBR showed significantly (P<0.05) more frequency of micronucleus and % of DNA damage than the 4 Gy EBR control group. These results conclude the sensitizing effect of chitosan on cancer cell line against EBR exposure. (author)

  11. Mitochondrial DNA damage and oxidative damage in HL-60 cells exposed to 900 MHz radiofrequency fields

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yulong; Zong, Lin; Gao, Zhen [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Zhu, Shunxing [Laboratory Animal Center, Nantong University, Nantong, Jiangsu Province (China); Tong, Jian [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Cao, Yi, E-mail: yicao@suda.edu.cn [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China)

    2017-03-15

    Highlights: • Increased reactive oxygen species. • Decreased mitochondrial transcription Factor A and polymerase gamma. • Decreased mitochondrial transcripts (ND1 and 16S) and mtDNA copy number. • Increased 8-hydroxy-2′deoxyguanosine. • Decreased adenosine triphosphate. - Abstract: HL-60 cells, derived from human promyelocytic leukemia, were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm{sup 2} power intensity for 4 h/day for 5 consecutive days to examine whether such exposure is capable damaging the mitochondrial DNA (mtDNA) mediated through the production of reactive oxygen species (ROS). In addition, the effect of RF exposure was examined on 8-hydroxy-2′-dexoyguanosine (8-OHdG) which is a biomarker for oxidative damage and on the mitochondrial synthesis of adenosine triphosphate (ATP) which is the energy required for cellular functions. The results indicated a significant increase in ROS and significant decreases in mitochondrial transcription factor A, mtDNA polymerase gamma, mtDNA transcripts and mtDNA copy number in RF-exposed cells compared with those in sham-exposed control cells. In addition, there was a significant increase in 8-OHdG and a significant decrease in ATP in RF-exposed cells. The response in positive control cells exposed to gamma radiation (GR, which is also known to induce ROS) was similar to those in RF-exposed cells. Thus, the overall data indicated that RF exposure was capable of inducing mtDNA damage mediated through ROS pathway which also induced oxidative damage. Prior-treatment of RF- and GR-exposed the cells with melatonin, a well-known free radical scavenger, reversed the effects observed in RF-exposed cells.

  12. Lung cancer mortality among nonsmoking uranium miners exposed to radon daughters

    International Nuclear Information System (INIS)

    Roscoe, R.J.; Steenland, K.; Halperin, W.E.; Beaumont, J.J.; Waxweiler, R.J.

    1989-01-01

    Radon daughters, both in the workplace and in the household, are a continuing cause for concern because of the well-documented association between exposure to radon daughters and lung cancer. To estimate the risk of lung cancer mortality among nonsmokers exposed to varying levels of radon daughters, 516 white men who never smoked cigarettes, pipes, or cigars were selected from the US Public Health Service cohort of Colorado Plateau uranium miners and followed up from 1950 through 1984. Age-specific mortality rates for nonsmokers from a study of US veterans were used for comparison. Fourteen deaths from lung cancer were observed among the nonsmoking miners, while 1.1 deaths were expected, yielding a standardized mortality ratio of 12.7 with 95% confidence limits of 8.0 and 20.1. These results confirm that exposure to radon daughters in the absence of cigarette smoking is a potent carcinogen that should be strictly controlled

  13. small Cell Lung Cancer

    African Journals Online (AJOL)

    Blood samples were analyzed for CTC count before and after chemotherapy. Clinical relevance of. CTCs with ... reduction (p < 0.001) in CTC count was also observed after one cycle of chemotherapy. Conclusion: Patients with low CTC ... type of cancer in China with 21.7 % of males and. 14.3 % of females. The incidence of ...

  14. 5-Fluorouracil-induced apoptosis in cultured oral cancer cells.

    Science.gov (United States)

    Tong, D; Poot, M; Hu, D; Oda, D

    2000-03-01

    Chemotherapy is commonly used to treat advanced oral squamous cell carcinoma (SCC) and is known to kill cancer cells through apoptosis. Our hypothesis states that 5-fluorouracil (5FU) also kills cultured oral epithelial cells through programmed cell death or apoptosis. Cultured oral cancer cells were exposed to an optimum dose of 20 mg/ml of 5FU. Cells were analyzed for changes in cell cycle distribution and induction of cell death including apoptosis. Normal control, human papilloma virus-immortalized (PP), ATCC SCC cell line (CA1) and two primary oral SCC cell lines (CA3 and -4) were studied. Inhibition of apoptosis by a pan-caspase inhibitor was used. SYTO 11 flow cytometry showed increased apoptosis in all 5FU-treated cell cultures compared to untreated controls. The results show biological variation in apoptotic response. CA1 had the lowest apoptotic rate of the cancer cell lines at 1.5%. Next lowest was CA3, followed by CA4 and PP. In addition, alteration in the G1 and S phase fractions were found. Untreated CA1 showed 28% G1, 53% S compared to 43% G1, and 40% S of treated. We investigated the pathway of apoptosis using the pan-caspase inhibitor IDN-1529 by methylthiazolyl diphenyl tetrazolium bromide (MTT) colorimetric analysis. Results showed mild inhibition of cell death when cells were incubated with 50 microM IDN-1529 for 24 h. This suggests a probable caspase-dependent apoptotic pathway. In conclusion, our data suggest that 5FU induces oral cancer cell death through apoptosis and that biological variation exists between normal and cancer cells and between different types of cancer cells themselves. Our data indicate that cultures of a useful in vitro model for chemosensitivity assays are possible. Our results also suggest a caspase-dependent pathway for chemocytotoxicity in oral SCC.

  15. Targeting cancer cells using 3-bromopyruvate for selective cancer treatment

    Directory of Open Access Journals (Sweden)

    Hussam H Baghdadi

    2017-01-01

    Full Text Available Cancer treatment deserves more research efforts despite intensive conventional treatment modalities for many types of malignancies. Metastasis and resistance to chemotherapy and radiotherapy receive a lot of global research efforts. The current advances in cancer biology may improve targeting the critical metabolic differences that distinguish cancer cells from normal cells. Cancer cells are highly glycolytic for energy production, exhibit the Warburg effect, establish aggressive acidic microenvironment, maintain cancer stem cells, exhibit resistance to chemotherapy, have low antioxidant systems but different ΔΨm (delta psi, mitochondrial transmembrane potential, express P-glycoprotein for multidrug resistance, upregulate glucose transporters and monocarboxylate transporters and are under high steady-state reactive oxygen species conditions. Normal cells differ in all these aspects. Lactate produced through the Warburg effect helps cancer metastasis. Targeting glycolysis reactions for energy production in cancer cells seems promising in decreasing the proliferation and metastasis of cancer cells. 3-bromopyruvate makes use of cancer biology in treating cancer cells, cancer stem cells and preventing metastasis in human cancer as discussed in this review. Updated advances are analyzed here, which include research analysis of background, experience, readings in the field of cancer biology, oncology and biochemistry.

  16. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  17. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  18. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  19. General Information about Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  20. How Can We Treat Cancer Disease Not Cancer Cells?

    Science.gov (United States)

    Kim, Kyu-Won; Lee, Su-Jae; Kim, Woo-Young; Seo, Ji Hae; Lee, Ho-Young

    2017-01-01

    Since molecular biology studies began, researches in biological science have centered on proteins and genes at molecular level of a single cell. Cancer research has also focused on various functions of proteins and genes that distinguish cancer cells from normal cells. Accordingly, most contemporary anticancer drugs have been developed to target abnormal characteristics of cancer cells. Despite the great advances in the development of anticancer drugs, vast majority of patients with advanced cancer have shown grim prognosis and high rate of relapse. To resolve this problem, we must reevaluate our focuses in current cancer research. Cancer should be considered as a systemic disease because cancer cells undergo a complex interaction with various surrounding cells in cancer tissue and spread to whole body through metastasis under the control of the systemic modulation. Human body relies on the cooperative interaction between various tissues and organs, and each organ performs its specialized function through tissue-specific cell networks. Therefore, investigation of the tumor-specific cell networks can provide novel strategy to overcome the limitation of current cancer research. This review presents the limitations of the current cancer research, emphasizing the necessity of studying tissue-specific cell network which could be a new perspective on treating cancer disease, not cancer cells.

  1. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  2. Adoptive T cell cancer therapy

    Science.gov (United States)

    Dzhandzhugazyan, Karine N.; Guldberg, Per; Kirkin, Alexei F.

    2018-06-01

    Tumour heterogeneity and off-target toxicity are current challenges of cancer immunotherapy. Karine Dzhandzhugazyan, Per Guldberg and Alexei Kirkin discuss how epigenetic induction of tumour antigens in antigen-presenting cells may form the basis for multi-target therapies.

  3. Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines

    Directory of Open Access Journals (Sweden)

    Kaski Samuel

    2007-03-01

    Full Text Available Abstract Background Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes. Results We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L, GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files. Conclusion This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.

  4. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  5. Gastric stem cells and gastric cancer stem cells

    OpenAIRE

    Han, Myoung-Eun; Oh, Sae-Ock

    2013-01-01

    The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal ev...

  6. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties which

  7. Prostate Cancer Stem-Like Cells | Center for Cancer Research

    Science.gov (United States)

    Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation

  8. Glutathione in Cancer Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

    2011-03-11

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

  9. Cancer stem cells and differentiation therapy.

    Science.gov (United States)

    Jin, Xiong; Jin, Xun; Kim, Hyunggee

    2017-10-01

    Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

  10. Cell damage of hepatoma-22 cells exposed to continuous wave ultrasound.

    Science.gov (United States)

    Wang, Pan; Wang, Xiaobing; Liu, Quanhong

    2012-01-01

    processes. Moreover the mechanical effect might also be involved in inducing cell damage because there was significant mitochondria membrane potential loss and no visible ROS detection when cells were exposed to ultrasound for 30 s.

  11. Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine

    International Nuclear Information System (INIS)

    Velsor, Leonard W.; Kovacevic, Miro; Goldstein, Mark; Leitner, Heather M.; Lewis, William; Day, Brian J.

    2004-01-01

    The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use

  12. Cerebrospinal fluid cells and proteins in patients occupationally exposed to organic solvents

    Energy Technology Data Exchange (ETDEWEB)

    Juntunen, J; Taskinen, E; Luisto, M; Iivanainen, M; Nurminen, M

    1982-06-01

    Cerebrospinal fluid (CSF) cells and proteins were determined for 33 patients exposed to industrial organic solvents. A lymphoid reaction, i.e., a pathologically elevated number or percentage of enlarged lymphoid cells was observed in one-third of the patients, more often in patients with chronic intoxication (40%) than in those currently exposed to organic solvents (32%). An almost significant decrease of small lymphocytes in the CSF was observed among patients who had a past history of chronic solvent intoxication but no recent exposure. No cytological evidence of tissue destruction was found. Signs of slight blood--CSF barrier damage occurred in 5 (23%) of the currently exposed patients, but intrathecal IgG synthesis was not observed. Increased cellular activity in the CSF was also accentuated in principal component analysis. The results suggest slight nonspecific immunoactivation in the central nervous system of subjects exposed to organic solvents.

  13. Endothelial dysfunction in rectal cancer patients chronically exposed to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rakhypbekov, Tolebay; Pak, Laura; Chaizhunusova, Nailya; Manambayeva, Zukhra; Tokanova, Sholpan; Madiyeva, Madina [Semey State Medical University, Semey (Kazakhstan); Inoue, Ken [Kochi University, Health Service Center, Kochi (Japan); Kawano, Noriyuki; Hoshi, Masaharu [Hiroshima University, Hiroshima (Japan); Takeichi, Nobuo [Takeichi Clinic, Hiroshima (Japan); Noso, Yoshihiro [Shimane University, Department of General Surgery, Faculty of Medicine, Shimane (Japan); Khozhayev, Arman; Molgazhdarov, Maulen [The Kazakh National Medical University of S.D.Asfendiyarov, Department of Oncology, Almaty (Kazakhstan); Olzhaev, Sayakhat [Almaty Regional Oncologic Hospital, Department of Oncology, Almaty (Kazakhstan)

    2017-08-15

    We sought to identify the features of endothelial function in rectal cancer patients who were exposed to chronic ionizing radiation from a nuclear test site in Kazakhstan. We examined 146 individuals, 76 of whom were rectal cancer patients. The existence of a complex of disturbances of the endothelium and hemostasis systems in patients vs non-patients was revealed. Endothelial dysfunction was expressed as an increase of nitric oxide (NO) production along with decreases in vasodilatation function, and increased levels of von Willebrand factor in blood, along with an increase in the number of circulating endotheliocytes. Significant correlations between indicators of endothelial function and vascular-platelet hemostasis were observed. These changes and their interrelations were expressed more strongly in the patients who lived in the contaminated area around the nuclear test site. Such patients could have an increased risk of thrombosis and other complications after the treatment of a malignant neoplasm. (orig.)

  14. Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.

    Science.gov (United States)

    Vivanti, Alexandre; Soheili, Tayebeh S; Cuccuini, Wendy; Luce, Sonia; Mandelbrot, Laurent; Lechenadec, Jerome; Cordier, Anne-Gael; Azria, Elie; Soulier, Jean; Cavazzana, Marina; Blanche, Stéphane; André-Schmutz, Isabelle

    2015-07-17

    Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero. We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively). The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs. Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups. Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.

  15. B-cell infiltration in the respiratory mucosa of turkeys exposed to subtype C avian metapneumovirus.

    Science.gov (United States)

    Cha, Ra Mi; Khatri, Mahesh; Sharma, Jagdev M

    2007-09-01

    Turkeys exposed to avian metapneumovirus (aMPV) subtype C showed extensive lymphoid cell infiltrations in the nasal turbinates of the upper respiratory tract. The cellular infiltration occurred after the first virus exposure but not after re-exposure. Quantitation of the relative proportions of mucosal immunoglobulin (Ig)A+, IgG+, and IgM+ cells in controls and virus-exposed turkeys revealed that at 7 days after the first virus exposure, when mucosal infiltration was well pronounced, there was a significant increase (P < 0.05) in the numbers of infiltrating IgA+ but not of IgG+ and IgM+ cells. After the second virus exposure, although the overall numbers of mucosal lymphoid cells were similar in the virus-exposed and control turkeys, the relative proportions of IgA+ and IgG+ cells were significantly higher in the virus-exposed turkeys (P < 0.05) than in controls. Furthermore, elevated levels of aMPV-specific IgA were detected in the nasal secretions and the bile of virus-exposed birds after the second but not after the first virus exposure. These results suggest, for the first time, the possible involvement of local mucosal immunoglobulins in the pathogenesis of aMPV in turkeys.

  16. In vitro cell-mediated immunity studies of plutonium-exposed beagle dogs

    International Nuclear Information System (INIS)

    Morris, J.E.; Graham, T.; Park, J.F.

    1980-01-01

    Mitogen-induced activation was measured in spleen and mesenteric lymph node cell preparations from dogs exposed to a single inhalation exposure of plutonium oxide ( 238 Pu or 239 Pu). Reduced stimulation indices of splenic lymphocytes from exposed animals suggest that a reduction in lymphocyte function has occurred in this tissue. No apparent reduction in mitogen stimulation indices was observed in mesenteric lymph node cultures

  17. Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

    Directory of Open Access Journals (Sweden)

    Priscilla Ludovico da Silva

    2015-12-01

    Full Text Available The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

  18. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  19. Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

    Science.gov (United States)

    Smerhovsky, Z; Landa, K; Rössner, P; Brabec, M; Zudova, Z; Hola, N; Pokorna, Z; Mareckova, J; Hurychova, D

    2001-01-01

    We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals. PMID:11171523

  20. A DRD1 polymorphism predisposes to lung cancer among those exposed to secondhand smoke during childhood.

    Science.gov (United States)

    Robles, Ana I; Yang, Ping; Jen, Jin; McClary, Andrew C; Calhoun, Kara; Bowman, Elise D; Vähäkangas, Kirsi; Greathouse, K Leigh; Wang, Yi; Olivo-Marston, Susan; Wenzlaff, Angela S; Deng, Bo; Schwartz, Ann G; Ryan, Bríd M

    2014-12-01

    Lung cancer has a familial component which suggests a genetic contribution to its etiology. Given the strong evidence linking smoking with lung cancer, we studied miRNA-related loci in genes associated with smoking behavior. CHRNA, CHRNB gene families, CYP2A6, and DRD1 (dopamine receptor D1) were mined for SNPs that fell within the seed region of miRNA binding sites and then tested for associations with risk in a three-stage validation approach. A 3'UTR (untranslated region) SNP in DRD1 was associated with a lower risk of lung cancer among individuals exposed to secondhand smoke during childhood [OR, 0.69; 95% confidence interval (CI), 0.60-0.79; P secondhand smoke and heterogeneity between individuals in regard to their susceptibility to the effects of secondhand smoke, our data show an interaction between an SNP in the 3'UTR of DRD1 and exposure to secondhand smoke during childhood. Further work is needed to explore the mechanistic underpinnings of this SNP and the nature of the interaction between DRD1 and exposure to secondhand smoke during childhood. ©2014 American Association for Cancer Research.

  1. Exercise recommendations for childhood cancer survivors exposed to cardiotoxic therapies: an institutional clinical practice initiative.

    Science.gov (United States)

    Okada, Maki; Meeske, Kathleen A; Menteer, Jondavid; Freyer, David R

    2012-01-01

    Childhood cancer survivors who have received treatment with anthracyclines are at risk for developing cardiomyopathy in dose-dependent fashion. Historically, restrictions on certain types of physical activity that were intended to preserve cardiac function have been recommended, based on a mixture of evidence-based and consensus-based recommendations. In the LIFE Cancer Survivorship & Transition Program at Children's Hospital Los Angeles, the authors reevaluated their recommendations for exercise in survivors who were exposed to anthracyclines, with or without irradiation in proximity to the myocardium. The primary goal was to develop consistent, specific, practical, safe, and (where possible) evidence-based recommendations for at-risk survivors in the program. To accomplish this, the authors referred to current exercise guidelines for childhood cancer survivors, consulted recent literature for relevant populations, and obtained input from the program's pediatric cardiology consultant. The resulting risk-based exercise recommendations are designed to complement current published guidelines, maximize safe exercise, and help childhood cancer survivors return to a normal life that emphasizes overall wellness and physical activity. This article describes a single institution's experience in modifying exercise recommendations for at-risk childhood survivors and includes the methods, findings, and current institutional practice recommendations along with sample education materials.

  2. Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds.

    Science.gov (United States)

    Rennix, Christopher P; Quinn, Margaret M; Amoroso, Paul J; Eisen, Ellen A; Wegman, David H

    2005-09-01

    The military presents a unique opportunity to study the incidence of disease in a population with complete knowledge of person-time and occupation. Women in the Army are employed more frequently in non-traditional, industrial jobs such as auto mechanic and motor transport operators than in the general US population, increasing the probability of exposure to industrial chemicals. A cohort to investigate the risk of breast cancer among active duty Army women occupationally exposed to volatile organic chemicals (VOCs) was constructed. Age-adjusted incidence rates for breast cancer were calculated for more than 270,000 enlisted women who served between 1980-1996. Twenty-one VOCs, described in previously published literature as having a potential risk of breast cancer, were identified in an Army industrial hygiene survey database. Job title histories were linked to workplace chemical evaluations conducted by Army industrial hygienists, which included a subjective exposure potential rating (high, medium, low, and none) for each VOC. Poisson regression analysis was used to evaluate the association between the exposure rating by job title and breast cancer. The incidence of breast cancer in the cohort was significantly elevated in women younger than 35 years of age, especially among black women, when compared to the age-specific rates in the general population. Women who worked in occupations with a moderate to high exposure potential to at least one VOC had a 48% increased risk (P women with low to no exposure potential. This study provides preliminary evidence that exposure to one or more of the study VOCs is associated with an increased risk of breast cancer. Further substance-specific, quantitative analyses are warranted.

  3. Cancer mortality in an international cohort of reinforced plastics workers exposed to styrene: a reanalysis.

    Science.gov (United States)

    Loomis, Dana; Guha, Neela; Kogevinas, Manolis; Fontana, Vincenzo; Gennaro, Valerio; Kolstad, Henrik A; McElvenny, Damien Martin; Sallmén, Markku; Saracci, Rodolfo

    2018-04-17

    To investigate the carcinogenicity of styrene by reanalysing data from a previous international cohort study of workers in the reinforced plastics industry. Mortality from cancers of prior interest was analysed with more detailed consideration of exposure-response relations and an updated classification of leukaemias and lymphomas in data from a previous international cohort study of 37 021 reinforced plastics workers exposed to airborne styrene. Increased mortality from non-Hodgkin's lymphoma (NHL) was associated with the mean level of exposure to styrene in air (relative risk (RR) 2.31, 95% CI 1.29 to 4.12 per 100 ppm), but not with cumulative styrene exposure. Similar associations with mean exposure were observed for the oesophagus (RR 2.44, 95% CI 1.11 to 5.36 per 100 ppm) and pancreas (RR 1.89, 95% CI 1.17 to 3.09). Oesophageal cancer mortality was also associated with cumulative styrene exposure lagged 20 years (RR 1.16, 95% CI 1.03 to 1.31). No other cancer, including lung cancer, was associated with any indicator of styrene exposure. This reanalysis does not substantially change the conclusions of the original study with respect to NHL or lung cancer but new evidence concerning cancers of the oesophagus and pancreas merits further investigation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Cancer mortality in a Chinese population exposed to hexavalent chromium in drinking water

    Science.gov (United States)

    Beaumont, J.J.; Sedman, R.M.; Reynolds, S.D.; Sherman, C.D.; Li, L.-H.; Howd, R.A.; Sandy, M.S.; Zeise, L.; Alexeeff, G.V.

    2008-01-01

    BACKGROUND: In 1987, investigators in Liaoning Province, China, reported that mortality rates for all cancer, stomach cancer, and lung cancer in 1970-1978 were higher in villages with hexavalent chromium (Cr)-contaminated drinking water than in the general population. The investigators reported rates, but did not report statistical measures of association or precision. METHODS: Using reports and other communications from investigators at the local Jinzhou Health and Anti-Epidemic Station, we obtained data on Cr contamination of groundwater and cancer mortality in 9 study regions near a ferrochromium factory. We estimated:(1) person-years at risk in the study regions, based on census and population growth rate data, (2) mortality counts, based on estimated person-years at risk and previously reported mortality rates, and (3) rate ratios and 95% confidence intervals. RESULTS: The all-cancer mortality rate in the combined 5 study regions with Cr-contaminated water was negligibly elevated in comparison with the rate in the 4 combined study regions without contaminated water (rate ratio = 1.13; 95% confidence interval = 0.86-1.46), but was somewhat more elevated in comparison with the whole province (1.23; 0.97-1.53). Stomach cancer mortality in the regions with contaminated water was more substantially elevated in comparison with the regions without contaminated water (1.82; 1.11-2.91) and the whole province (1.69; 1.12-2.44). Lung cancer mortality was slightly elevated in comparison with the unexposed study regions (1.15; 0.62-2.07), and more strongly elevated in comparison with the whole province (1.78; 1.03-2.87). Mortality from other cancers combined was not elevated in comparison with either the unexposed study regions (0.86; 0.53-1.36) or the whole province (0.92; 0.58-1.38). CONCLUSIONS: While these data are limited, they are consistent with increased stomach cancer risk in a population exposed to Cr in drinking water. ?? 2008 Lippincott Williams & Wilkins, Inc.

  5. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    Science.gov (United States)

    Mahmood, M.; Xu, Y.; Dantuluri, V.; Mustafa, T.; Zhang, Y.; Karmakar, A.; Casciano, D.; Ali, S.; Biris, A.

    2013-02-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

  6. Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics

    International Nuclear Information System (INIS)

    Mahmood, M; Xu, Y; Dantuluri, V; Mustafa, T; Karmakar, A; Casciano, D; Biris, A; Zhang, Y; Ali, S

    2013-01-01

    Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells. (paper)

  7. Female cancer survivors exposed to alkylating-agent chemotherapy have unique reproductive hormone profiles.

    Science.gov (United States)

    Johnson, Lauren; Sammel, Mary D; Schanne, Allison; Lechtenberg, Lara; Prewitt, Maureen; Gracia, Clarisa

    2016-12-01

    To evaluate reproductive hormone patterns in women exposed to alkylating-agent chemotherapy. Prospective cohort. University hospital. Normally menstruating mid-reproductive-age women (20-35 years old) who had previously been exposed to alkylating-agent chemotherapy for cancer treatment were compared with two healthy control populations: similarly-aged women and late-reproductive-age women (43-50 years old). Subjects collected daily urine samples for one cycle. Integrated urinary pregnanediol glucuronide (PDG) and estrone conjugate (E1c) and urinary excretion of gonadotropins (FSH and LH). Thirty-eight women (13 survivors, 11 same-age control subjects, 14 late-reproductive-age control subjects) provided 1,082 urine samples. Cycle length, luteal phase length, and evidence of luteal activity were similar among the groups. As expected, ovarian reserve was impaired in cancer survivors compared with same-age control subjects but similar between survivors and late-reproductive-age control subjects. In contrast, survivors had total and peak PDG levels that were similar to same-age control subjects and higher than those observed in late-reproductive-age control subjects. Survivors had higher E1c levels than both same-age and late-reproductive-age control subjects. There was no difference in urinary gonadotropins among the groups. Women exposed to alkylating agents have a unique reproductive hormone milieu that is not solely explained by age or ovarian reserve. The urinary hormone profile observed in survivors appears more similar to same-age control subjects than to late-reproductive-age women with similar ovarian reserve, which may suggest that age plays a more important role than ovarian reserve in the follicular dynamics of survivors. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. A POX on Renal Cancer Cells | Center for Cancer Research

    Science.gov (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  9. Skin Cancer Treatment

    Science.gov (United States)

    ... Unusual Cancers of Childhood Treatment Genetics of Skin Cancer Skin color and being exposed to sunlight can increase ... is based on the type of nonmelanoma skin cancer or other skin condition diagnosed: Basal cell carcinoma Enlarge Basal cell ...

  10. Stages of Skin Cancer

    Science.gov (United States)

    ... Unusual Cancers of Childhood Treatment Genetics of Skin Cancer Skin color and being exposed to sunlight can increase ... is based on the type of nonmelanoma skin cancer or other skin condition diagnosed: Basal cell carcinoma Enlarge Basal cell ...

  11. CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

    Directory of Open Access Journals (Sweden)

    Mariam El-Ashmawy

    Full Text Available Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs. In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF = 1.3, and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

  12. Extinction models for cancer stem cell therapy

    Science.gov (United States)

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  13. Effect of radiation on microtubule structure in cancer cells

    International Nuclear Information System (INIS)

    Tripath, Shambhoo Sharan; Panda, Dulal; Jayakumar, S.; Maikho, Thoh; Sandur, Santosh Kumar

    2017-01-01

    Microtubules (MT) are dynamic structural cellular components. In proliferating cells, they are essential components in cell division through the formation of the mitotic spindle. Radiotherapy is an integral part of cancer treatment for most of the solid cancers. Scanty data exists in the literature related to how ionizing radiation affects microtubule reorganization in tumor cells. In the present study, breast cancer cell line (MCF-7 cells) was exposed to different doses of radiation (2-10Gy). Cells were cultured for 24 h, fixed and stained with antitubulin antibody and subjected to immunofluorescence microscopy. In another experiment, cells were subjected to cold treatment for 5 min or 30 min for studying the disassembly of microtubules after 24 h of irradiation. Further, these cells were incubated at 37°C for 20 min for studying the reassembly of microtubules. Acetylation of microtubule was also examined after exposure of cells to radiation. Experiments were also performed by combining radiation with low concentration of CXI-Benzo 84 (MT destabilizing agent 1 and 2.5 uM). Exposure of MCF-7 cells to radiation lead to destabilization of microtubules. Interestingly, destabilization of microtubule was faster upon cold treatment in irradiated group as compared to control group. These cells failed to re-stabilize at 37°C. Radiation also reduced the acetylation level of microtubule. Combination treatment of CXI-Benzo 84 with radiation exhibited additive effect in terms of depolymerization of MT. Our results suggest that ionizing radiation indeed modulates microtubule dynamics. (author)

  14. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    thor Straten, Eivind Per; Garrido, Federico

    2016-01-01

    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell...... infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However......, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells...

  15. Micronucleus frequency in exfoliated buccal cells from hairdresser who expose to hair products

    Directory of Open Access Journals (Sweden)

    Koh Hui Yee

    2015-06-01

    Full Text Available Background: Hairdresser is one of the fastest growing occupations in today’s society. Hairdresser help styling, cutting, colouring, perming, curling, straightening hair and various treatment to customer. Somehow, hairdresser are constantly exposed to chemical substances such as aromatic amines, hydrogen peroxide, thioglycolic acid, formaldehyde in hair products which can cause damage to human’s genome. Micronucleus is one of the effective biomarker for processes associated with the induction of DNA damage. Purpose: The aim of this study was to determine the micronucleus frequencies in buccal mucosa epithelial cells of hairdresser who were exposed to chemical of hair products. Method: This study was conducted on twenty female subjects, who were divided into 2 groups: exposed and non-exposed (control group. All subjects recruited were working in the same beauty salon. Buccal cells were obtained from each individual by using cytobrush. The cells were stained with modified Feulgen-Ronssenback method and counting of micronucleus per 1000 cell was done under light microscope. The data were analyzed using independent t-test and one-way Anova (p<0.05. Result: The result showed a significant difference in micronucleus frequency between 2 groups. There were a significantly increase of micronucleus frequency in hairdressers and increase of  micronucleus frequency with the longer duration of exposure. Conclusion: It concluded that the chemical substances of hair products had affected the micronucleus frequency ofthe epithelial cells in buccal mucosa of hairdressers.

  16. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.

    Science.gov (United States)

    Lin, Chia-Han; Lu, Wei-Cheng; Wang, Che-Wei; Chan, Ya-Chi; Chen, Mu-Kuan

    2013-02-25

    Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

  17. Lung cancer mortality among nonsmoking uranium miners exposed to radon daughters

    International Nuclear Information System (INIS)

    Roscoe, R.J.; Stenland, K.; Halperin, W.E.; Waxweiler, R.J.

    1990-01-01

    This paper reports on radon daughters, both in the workplace and in the household, that are a continuing cause of concern because of the well-documented association between exposure to radon daughters and lung cancer. To estimate the risk of lung cancer mortality among nonsmokers exposed to varying levels of radon daughters, 516 white men who never smoked cigarettes, pipes, or cigars were selected from the U.S. Public Health Service cohort of Colorado Plateau uranium miners and followed up from 1950 through 1984. Age-specific mortality rates for nonsmokers from a study of U.S. veterans were used for comparison. Fourteen deaths from lung cancer were observed among the nonsmoking miners, while 1.1 deaths were expected, yielding a standardized mortality radio of 12.7 with 95% confidence limits of 8.0 and 20.1. These results confirm that exposure to radon daughters in the absence of cigarette smoking is a potent carcinogen that should be strictly controlled

  18. Basal Cell Carcinoma on the Sole: An Easily Missed Cancer

    Directory of Open Access Journals (Sweden)

    Natalie L. Hone

    2016-10-01

    Full Text Available Basal cell carcinoma (BCC is the most common skin cancer, and solar ultraviolet ray exposure is the most significant risk factor for its development. The plantar foot is infrequently exposed to the sun, thus the presence of BCC on the sole is rare. We report a case of BCC on the sole of the foot and its treatment in the hope to facilitate its detection.

  19. Targeting Stromal Recruitment by Prostate Cancer Cells

    Science.gov (United States)

    2006-03-01

    Ensinger, C., Tumer , Z., Tommerup, N. et al.: Hedgehog signaling in small-cell lung cancer : frequent in vivo but a rare event in vitro. Lung Cancer , 52...W81XWH-04-1-0157 TITLE: Targeting Stromal Recruitment by Prostate Cancer Cells PRINCIPAL INVESTIGATOR: Jingxian Zhang, Ph.D...DATES COVERED (From - To) 15 Feb 2004 – 14 Feb 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Stromal Recruitment by Prostate Cancer

  20. Comprehensive analysis of 5-aminolevulinic acid dehydrogenase (ALAD variants and renal cell carcinoma risk among individuals exposed to lead.

    Directory of Open Access Journals (Sweden)

    Dana M van Bemmel

    Full Text Available BACKGROUND: Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD gene affects lead toxicokinetics and may modify the adverse effects of lead. METHODS: The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC. Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR and 95% confidence intervals (CI were calculated using logistic regression. RESULTS: The adjusted risk associated with the ALAD variant rs8177796(CT/TT was increased (OR = 1.35, 95%CI = 1.05-1.73, p-value = 0.02 when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles ((GGOR = 2.68, 95%CI = 1.17-6.12, p = 0.01; (GAOR = 1.79, 95%CI = 1.06-3.04 with an interaction approaching significance (p(int = 0.06. No significant modification in RCC risk was observed for the functional variant rs1800435(K68N. Haplotype analysis identified a region associated with risk supporting tagging SNP results. CONCLUSION: A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure.

  1. Chromosome aberrations of bone marrow cells in heavily exposed atomic bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Kamada, Nanao; Kuramoto, Atsushi; Ohkita, Takeshi

    1986-01-01

    Seven hundred and ten bone marrow cells from 13 A-bomb survivors, who were heavily exposed to atomic radiation, were examined using chromosome banding method. An average frequency of chromosome aberrations was 17 %. The most common structural abnormality was translocation (47 %), followed by complex aberrations involving three or more chromosomes (32 %). These abnormalities were frequently seen in A-bomb survivors exposed to estimated doses of 3.5 - 4.0 Gy. Eighty two percent of the structural aberrations were stable. Diploid cells were seen in 0.4 % and tetraploid cells were seen in 0.7 %. The frequency of breakpoint sites was high in chromosomes 1 and 17; while it was low in chromosomes 3, 6, 9, and 11. Abnormal clones were seen in one of the 13 survivors. Chromosome aberrations common to the bone marrow cells and peripheral lymphocytes were not seen in the same individual. (Namekawa, K.)

  2. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...CA130273 - Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM...hypothesis, we originally proposed to transform neural stem cells (NSCs) and neural progenitor cells (NPCs) in vivo by expressing an activated form

  3. Gene expression profile in bone marrow and hematopoietic stem cells in mice exposed to inhaled benzene

    International Nuclear Information System (INIS)

    Faiola, Brenda; Fuller, Elizabeth S.; Wong, Victoria A.; Recio, Leslie

    2004-01-01

    Acute myeloid leukemia and chronic lymphocytic leukemia are associated with benzene exposure. In mice, benzene induces chromosomal breaks as a primary mode of genotoxicity in the bone marrow (BM). Benzene-induced DNA lesions can lead to changes in hematopoietic stem cells (HSC) that give rise to leukemic clones. To gain insight into the mechanism of benzene-induced leukemia, we investigated the DNA damage repair and response pathways in total bone marrow and bone marrow fractions enriched for HSC from male 129/SvJ mice exposed to benzene by inhalation. Mice exposed to 100 ppm benzene for 6 h per day, 5 days per week for 2 week showed significant hematotoxicity and genotoxicity compared to air-exposed control mice. Benzene exposure did not alter the level of apoptosis in BM or the percentage of HSC in BM. RNA isolated from total BM cells and the enriched HSC fractions from benzene-exposed and air-exposed mice was used for microarray analysis and quantitative real-time RT-PCR. Interestingly, mRNA levels of DNA repair genes representing distinct repair pathways were largely unaffected by benzene exposure, whereas altered mRNA expression of various apoptosis, cell cycle, and growth control genes was observed in samples from benzene-exposed mice. Differences in gene expression profiles were observed between total BM and HSC. Notably, p21 mRNA was highly induced in BM but was not altered in HSC following benzene exposure. The gene expression pattern suggests that HSC isolated immediately following a 2 weeks exposure to 100 ppm benzene were not actively proliferating. Understanding the toxicogenomic profile of the specific target cell population involved in the development of benzene-associated diseases may lead to a better understanding of the mechanism of benzene-induced leukemia and may identify important interindividual and tissue susceptibility factors

  4. Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction.

    Science.gov (United States)

    Javeed, Naureen; Sagar, Gunisha; Dutta, Shamit K; Smyrk, Thomas C; Lau, Julie S; Bhattacharya, Santanu; Truty, Mark; Petersen, Gloria M; Kaufman, Randal J; Chari, Suresh T; Mukhopadhyay, Debabrata

    2015-04-01

    Pancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer-derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. We characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown. Exosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species. Pancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin(+)/CA19-9(+) exosomes into

  5. Differential cisplatin responses in human carcinoma cell lines pre-exposed to fractionated X-irradiation

    International Nuclear Information System (INIS)

    Dempke, W.C.M.; Hosking, L.K.; Shellard, S.A.; Hill, B.T.

    1991-01-01

    These results suggest that cells exposed to X-irradiation may respond differently to subsequent cisplatin (CDDP) treatment. Initial studies of possible mechanisms responsible for these differential sensitivities indicate that they may differ according to whether resistance or hypersensitivity is expressed. (author)

  6. Immune cells in Chernobyl radiation workers exposed to low-dose irradiation

    International Nuclear Information System (INIS)

    Bazyka, D.; Chumak, A.; Byelyaeva, N.; Gulaya, N.; Margytich, V.; Thevenon, C.; Guichardant, M.; Lagarde, M.

    2002-01-01

    the aim of this work was to study immune response parameters in Chernobyl emergency and recovery operation radiation workers and nuclear industry workers exposed under professional limits. The monohydroxylated fatty acid content in peripheral blood mononuclear cell of radiation workers compared to unexposed control at the 12-th year after Chernobyl NPP accident was studied too

  7. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  8. Isolation and Characterization of Cancer Stem Cells of the Non-Small-Cell Lung Cancer (A549) Cell Line.

    Science.gov (United States)

    Halim, Noor Hanis Abu; Zakaria, Norashikin; Satar, Nazilah Abdul; Yahaya, Badrul Hisham

    2016-01-01

    Cancer is a major health problem worldwide. The failure of current treatments to completely eradicate cancer cells often leads to cancer recurrence and dissemination. Studies have suggested that tumor growth and spread are driven by a minority of cancer cells that exhibit characteristics similar to those of normal stem cells, thus these cells are called cancer stem cells (CSCs). CSCs are believed to play an important role in initiating and promoting cancer. CSCs are resistant to currently available cancer therapies, and understanding the mechanisms that control the growth of CSCs might have great implications for cancer therapy. Cancer cells are consist of heterogeneous population of cells, thus methods of identification, isolation, and characterisation of CSCs are fundamental to obtain a pure CSC populations. Therefore, this chapter describes in detail a method for isolating and characterizing a pure population of CSCs from heterogeneous population of cancer cells and CSCs based on specific cell surface markers.

  9. Gigantocellular macrophagal reaction in epidermoid cancer of the lung in patients exposed to preoperative irradiation

    International Nuclear Information System (INIS)

    Galil-Ogly, G.A.; Kharchenko, V.P.; Poroshin, K.K.; Pereslegin, O.I.; Krylov, L.M.; Ivanov, E.D.

    1980-01-01

    The histologic and electron microscopic study of frequently occurring gigantocellular macrophagal reaction in the stroma of 83 irradiated epidermoid carcinomas of the lung is carried out. It is found that gigantic multinuclear macrophages take part in the resorption of necrotic and corneous masses as well as in the absorption of viable tumour cells. The presence of gigantocellular macrophagal reaction in the stroma of irradiated tumoUr evidences a more favourable prognosis in patients after the combined treatment of epidermoid lung cancer. Gigantocellular macrophagal reaction should be considered as the manifestation of cell antitumour immunity which makes stronger the tumour irradiation damage

  10. Ultrastructure of cells of Ulmus americana cultured in vitro and exposed to the culture filtrate of Ceratocystis ulmi

    Science.gov (United States)

    Paula M. Pijut; R. Daniel Lineberger; Subhash C. Domir; Jann M. Ichida; Charles R. Krause

    1990-01-01

    Calli of American elm susceptible and resistant to Dutch elm disease were exposed to a culture filtrate of a pathogenic isolate of Ceratocystis ulmi. Cells from untreated tissue exhibited typical internal composition associated with healthy, actively growing cells. All cells exposed to culture filtrate showed appreciable ultrastructural changes....

  11. Stem cells and cancer: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-05-01

    Full Text Available Stem cells are the small units of multicellular creature. Regeneration and self-renewal are the ability of the stem cells. Each tissue is having particular stem cells, specific to it. These normal stem cells are converted into cancer stem cells through mutations in it. Although the expression of oncogenes is enhanced a lot, the tumor-supressing gene is lessened. Cancer stem cells are isolated and visualized through different techniques like immunocytochemical staining, spectral karyotyping, immunohistochemistry, induction method and dissection measures, then are performed histological procedures which include fascination, immunohistochemistry, dispensation, in situ hybridization and also quantitative examination of tissue flow cytometric analysis. For the analysis of quantization, statistical tests are also performed as two-sample t-test, Chi-square test, SD and arithmetic mean. Tumor cells generate glioma spheres. These are used in cancer study. Axin 1 is the gene suppressing cancer. Its removal causes the generation of liver cancer. Curcumin is the most effective for suppressing cancer as it increases the normal stem cell function and decreases the cancer stem cell function. Brahma-related gene 1 is crucial for the safeguarding of the stem cell residents in tissue-specific comportment. Different types of cancers originate through genetic mutation, tissue disorganization and cell proliferation. Tumor configuration is produced by the alteration in original cell culture having stem cells and progenitor cell populations. The developmental facets about cancer cells and cancer stem cells as well as their personal natal functions sustain an intricate steadiness to settle on their personal donations to the efficacy or harmfulness of the biological organization.

  12. The stem cell division theory of cancer.

    Science.gov (United States)

    López-Lázaro, Miguel

    2018-03-01

    All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and lung cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations and epigenetic mistakes occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the

  13. Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

    Science.gov (United States)

    Rieger, Daniela; Assinger, Alice; Einfinger, Katrin; Sokolikova, Barbora; Geiger, Margarethe

    2014-01-01

    Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10–30% of cells). PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal. PMID:25000564

  14. Nuclear microprobe imaging of gallium nitrate in cancer cells

    Science.gov (United States)

    Ortega, Richard; Suda, Asami; Devès, Guillaume

    2003-09-01

    Gallium nitrate is used in clinical oncology as treatment for hypercalcemia and for cancer that has spread to the bone. Its mechanism of antitumor action has not been fully elucidated yet. The knowledge of the intracellular distribution of anticancer drugs is of particular interest in oncology to better understand their cellular pharmacology. In addition, most metal-based anticancer compounds interact with endogenous trace elements in cells, altering their metabolism. The purpose of this experiment was to examine, by use of nuclear microprobe analysis, the cellular distribution of gallium and endogenous trace elements within cancer cells exposed to gallium nitrate. In a majority of cellular analyses, gallium was found homogeneously distributed in cells following the distribution of carbon. In a smaller number of cells, however, gallium appeared concentrated together with P, Ca and Fe within round structures of about 2-5 μm diameter located in the perinuclear region. These intracellular structures are typical of lysosomial material.

  15. Nuclear microprobe imaging of gallium nitrate in cancer cells

    International Nuclear Information System (INIS)

    Ortega, Richard; Suda, Asami; Deves, Guillaume

    2003-01-01

    Gallium nitrate is used in clinical oncology as treatment for hypercalcemia and for cancer that has spread to the bone. Its mechanism of antitumor action has not been fully elucidated yet. The knowledge of the intracellular distribution of anticancer drugs is of particular interest in oncology to better understand their cellular pharmacology. In addition, most metal-based anticancer compounds interact with endogenous trace elements in cells, altering their metabolism. The purpose of this experiment was to examine, by use of nuclear microprobe analysis, the cellular distribution of gallium and endogenous trace elements within cancer cells exposed to gallium nitrate. In a majority of cellular analyses, gallium was found homogeneously distributed in cells following the distribution of carbon. In a smaller number of cells, however, gallium appeared concentrated together with P, Ca and Fe within round structures of about 2-5 μm diameter located in the perinuclear region. These intracellular structures are typical of lysosomial material

  16. Cytologic studies on irradiated gestric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Isono, S; Takeda, T; Amakasu, H; Asakawa, H; Yamada, S [Miyagi Prefectural Adult Disease Center, Natori (Japan)

    1981-06-01

    The smears of the biopsy and resected specimens obtained from 74 cases of irradiated gastric cancer were cytologically analyzed for effects of irradiation. Irradiation increased the amount of both necrotic materials and neutrophils in the smears. Cancer cells were decreased in number almost in inverse proportion to irradiation dose. Clusters of cancer cells shrank in size and cells were less stratified after irradiation. Irradiated cytoplasms were swollen, vacuolated and stained abnormally. Irradiation with less than 3,000 rads gave rise to swelling of cytoplasms in almost all cases. Nuclei became enlarged, multiple, pyknotic and/or stained pale after irradiation. Nuclear swelling was more remarkable in cancer cells of differentiated adenocarcinomas.

  17. Cellular and exosome mediated molecular defense mechanism in bovine granulosa cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed Saeed-Zidane

    Full Text Available Various environmental insults including diseases, heat and oxidative stress could lead to abnormal growth, functions and apoptosis in granulosa cells during ovarian follicle growth and oocyte maturation. Despite the fact that cells exposed to oxidative stress are responding transcriptionally, the potential release of transcripts associated with oxidative stress response into extracellular space through exosomes is not yet determined. Therefore, here we aimed to investigate the effect of oxidative stress in bovine granulosa cells in vitro on the cellular and exosome mediated defense mechanisms. Bovine granulosa cells were aspirated from ovarian follicles and cultured in DMEM/F-12 Ham culture medium supplemented with 10% exosome-depleted fetal bovine serum. In the first experiment sub-confluent cells were treated with 5 μM H2O2 for 40 min to induce oxidative stress. Thereafter, cells were subjected to ROS and mitochondrial staining, cell proliferation and cell cycle assays. Furthermore, gene and protein expression analysis were performed in H2O2-challenged versus control group 24 hr post-treatment using qRT-PCR and immune blotting or immunocytochemistry assay, respectively. Moreover, exosomes were isolated from spent media using ultracentrifugation procedure, and subsequently used for RNA isolation and qRT-PCR. In the second experiment, exosomes released by granulosa cells under oxidative stress (StressExo or those released by granulosa cells without oxidative stress (NormalExo were co-incubated with bovine granulosa cells in vitro to proof the potential horizontal transfer of defense molecules from exosomes to granulosa cells and investigate any phenotype changes. Exposure of bovine granulosa cells to H2O2 induced the accumulation of ROS, reduced mitochondrial activity, increased expression of Nrf2 and its downstream antioxidant genes (both mRNA and protein, altered the cell cycle transitions and induced cellular apoptosis. Granulosa cells

  18. Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals

    International Nuclear Information System (INIS)

    Ji, Xunmin; Li, Zhiliang; Chen, Hongxia; Li, Junqi; Tian, Huajian; Li, Zengli; Gao, Xuejuan; Xiang, Qi; Su, Zhijian; Huang, Yadong; Zhang, Qihao

    2015-01-01

    Heavy metals are common environmental toxicants with adverse effects on steroid biosynthesis. The importance of mitochondria has been recognized in cytotoxic mechanism of heavy metals on Leydig cells these years. But it is still poorly known. Our previous study reported that dihydrolipoamide dehydrogenase (DLD) located on the mitochondria was significantly decreased in Leydig cells exposed to cadmium, which suggested that DLD might be involved in the cytotoxic effects. Therefore, the altered expression of DLD was validated in rats and R2C cells exposed to cadmium, manganese and lead, and the role of DLD in the steroid synthesis pathway cAMP/PKA-ERK1/2 was investigated in this study. With a low expression of DLD, heavy metals dramatically reduced the levels of steroid hormone by inhibiting the activation of cAMP/PKA, PKC signaling pathway and the steroidogenic enzymes StAR, CYP11A1 and 3β-HSD. After knockdown of DLD in R2C cells, progesterone synthesis was reduced by 40%, and the intracellular concentration of cAMP, protein expression of StAR, 3β-HSD, PKA, and the phosphorylation of ERK1/2 were also decreased. These results highlight that DLD is down-regulation and related to steroid biosynthesis in Leyig cells exposed to heavy metals; cAMP/PKA act as downstream effector molecules of DLD, which activate phosphorylation of ERK1/2 to initiate the steroidogenesis

  19. 'Rogue' cells observed in children exposed to radiation from the Chernobyl accident

    International Nuclear Information System (INIS)

    Sevan'kaev, A.V.; Tsyb, A.F.; Zhloba, A.A.; Moiseenko, V.V.; Skrjabin, A.M.; Climov, V.M.

    1993-01-01

    Eight 'rogue' lymphocyte metaphases containing a large number of aberrant chromosomes were noted during a survey of chromosomal damage in 328 Belarussian children. The study population comprised children of families living in territory contaminated by radiation from the Chernobyl accident. The majority of the sample had been evacuated within 1 week from very heavily polluted territory to areas that had received much less fallout. Two hundred cells were scored per subject and one rogue cell was found in a child exposed in utero; one in a child conceived after the accident and six in the postnatally exposed group. The possibility that the damage was due to exposure to radio-iodine concentrated in the thyroid gland, or to radiation from incorporated hot particles' of an alpha or beta/gamma emitter is discussed. It is concluded that the damage to these cells is unlikely to have been caused by radiation. (Author)

  20. The problematic on the cancer development in occupationally exposed workers to ionizing radiations

    International Nuclear Information System (INIS)

    Nouailhetas, Y.; Mezrahi, A.; Heilbron Filho, P.F.L.; Oliveira, S.M.V.

    1996-01-01

    Frequently and in an increasing perspective, the Brazilian Nuclear Energy Commission is inquired on the development of cancer in occupationally exposed workers to ionizing radiation. These workers try to compensate their state of ill health juridically. Taking into account that cancer is a probabilistic effect of radiation, it could be only detected by an increase in cases that normally occur in a particular population. Whether or not the occurrence of the illness is identified as having occupational origin misses scientific consistence. Regarding the probabilistic effect of low level radiation doses, radiation protection is founded on the linear dose-effect without threshold hypothesis. Thus, it could be call into a question: is it possible that the illness, presented by an individual, derives from occupational causes. If the answer is positive, the responsibility can be imputed, at first, to the employer and the link of causality turns out to be fundamented not any more in measurable objective facts but in social, economic, ethic and moral aspects, which arise from the radiological protection quality and measures offered by the employer. (author)

  1. Increased frequency of micronucleated exfoliated cells among humans exposed in vivo to mobile telephone radiations

    International Nuclear Information System (INIS)

    Manoj Kumar Sharma; Abhay Singh Yadav

    2007-01-01

    Complete text of publication follows. The health concerns have been raised following the enormous increase in the use of wireless mobile telephones through out the world. This investigation had been taken, with the motive to find out whether mobile phone radiations cause any in vivo effects on the frequency of micronucleated exfoliated cells in the exposed subjects. A total of 109 subjects including 85 regular mobile phone users (exposed) and 24 non-users (controls) had participated in this study. Exfoliated cells were obtained by swabbing the buccal-mucosa from exposed as well as sex-age-matched controls. One thousand exfoliated cells were screened from each individual for nuclear anomalies including micronuclei (MN), karyolysis (KL), karyorrhexis (KH), broken egg (BE) and bi-nucleated (BN) cells. The average daily duration of exposure to mobile phone radiations is 61.26 minutes with an overall average duration of exposure in term of years is 2.35 years in exposed subjects along with the 9.84±0.745 MNC (micronucleated cells) and 10.72±0.889 TMN (total micronuclei) as compared to zero duration of exposure along with average 3.75±0.774 MNC and 4.00±0.808 TMN in controls. The means are significantly different in case MNC and TMN at 0.01% level of significance. For all other nuclear anomalies (KL, KH, BE and BN cells) the means are found statistically nonsignificant. A positive correlation was found in the frequency of MNC and TMN with respect to duration of exposure time.

  2. Natural Killer T Cells in Cancer Immunotherapy

    Science.gov (United States)

    Nair, Shiny; Dhodapkar, Madhav V.

    2017-01-01

    Natural killer T (NKT) cells are specialized CD1d-restricted T cells that recognize lipid antigens. Following stimulation, NKT cells lead to downstream activation of both innate and adaptive immune cells in the tumor microenvironment. This has impelled the development of NKT cell-targeted immunotherapies for treating cancer. In this review, we provide a brief overview of the stimulatory and regulatory functions of NKT cells in tumor immunity as well as highlight preclinical and clinical studies based on NKT cells. Finally, we discuss future perspectives to better harness the potential of NKT cells for cancer therapy. PMID:29018445

  3. Cancer mortality among female and male workers occupationally exposed to inorganic lead in the printing industry.

    Science.gov (United States)

    Ilychova, Svetlana A; Zaridze, David G

    2012-02-01

    Evaluation of the carcinogenicity of lead for humans has been based primarily on the results of studies on occupationally exposed men, although gender differences in lead metabolism have been reported. In addition, most of the previous studies have been limited by a failure to identify and control for co-exposures to other known occupational carcinogens. The present study follows an industrial cohort of workers, mostly women, with moderate lead exposure and no confounding by other occupational exposures. Workers, employed at least 2 years between 1950 and 1978 in manual and mechanical (linotype) typesetting and type foundries in 27 printing plants in Moscow, were included in the cohort, which comprised 1423 men and 3102 women. The cohort was followed up during 1979-2003 and contributed 93,682 person-years of observation. Follow-up was 97.7% complete. Standardised mortality ratios (SMRs) and 95% CIs, based on mortality rates of the Moscow general population and adjusted for gender, age and calendar time, were calculated for the total cohort as well as subcohorts stratified by various exposure parameters. Among women, mortality from all causes, circulatory diseases and all cancers combined was lower than that in the Moscow general population and was similar across work groups. Among men, there was excess overall mortality, mainly due to increased mortality from ischaemic heart disease. For both sexes, no significant excess risk for any cancer site was observed, although some dose-response patterns were found. In the overall cohort, mortality from cancers of the kidney and pancreas increased up to twofold in the highest tertile of cumulative lead exposure based on duration and a relative ranking of the three subcohorts (9 deaths; SMR=2.12, 95% CI 1.10 to 4.07) and (18 deaths; SMR=2.32, 95% CI 1.46 to 3.68), respectively. Similar mortality trends for these two cancers were found in analyses by gender. Consistencies by sex and exposure level make a strong case for a

  4. Doxorubicin-induced mitophagy contributes to drug resistance in cancer stem cells from HCT8 human colorectal cancer cells.

    Science.gov (United States)

    Yan, Chen; Luo, Lan; Guo, Chang-Ying; Goto, Shinji; Urata, Yoshishige; Shao, Jiang-Hua; Li, Tao-Sheng

    2017-03-01

    Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133 + /CD44 + CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs. Interestingly, the level of mitochondrial superoxide was detected to be significantly lower in CSCs than in parental cells after DXR treatment. Furthermore, the mitophagy level and expression of BNIP3L, a mitophagy regulator, were significantly higher in CSCs than in parental cells after DXR treatment. Silencing BNIP3L significantly halted mitophagy and enhanced the sensitivity to DXR in CSCs. Our data suggested that mitophagy, but not non-selective autophagy, likely contributes to drug resistance in CSCs isolated from HCT8 cells. Further studies in other cancer cell lines will be needed to confirm our findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  6. Breast cancer cell lines: friend or foe?

    International Nuclear Information System (INIS)

    Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

    2003-01-01

    The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research

  7. Low white blood cell count and cancer

    Science.gov (United States)

    ... gov/ency/patientinstructions/000675.htm Low white blood cell count and cancer To use the sharing features on this page, please enable JavaScript. White blood cells (WBCs) fight infections from bacteria, viruses, fungi, and ...

  8. Cancer stem cells of the digestive system.

    Science.gov (United States)

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

    Science.gov (United States)

    Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

    2004-01-01

    In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

  10. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  11. Low Temperature Plasma for the Treatment of Epithelial Cancer Cells

    Science.gov (United States)

    Mohades, Soheila

    Biomedical applications of low temperature plasmas (LTP) may lead to a paradigm shift in treating various diseases by conducting fundamental research on the effects of LTP on cells, tissues, organisms (plants, insects, and microorganisms). This is a rapidly growing interdisciplinary research field that involves engineering, physics, life sciences, and chemistry to find novel solutions for urgent medical needs. Effects of different LTP sources have shown the anti-tumor properties of plasma exposure; however, there are still many unknowns about the interaction of plasma with eukaryotic cells which must be elucidated in order to evaluate the practical potential of plasma in cancer treatment. Plasma, the fourth state of matter, is composed of electrons, ions, reactive molecules (radicals and non-radicals), excited species, radiation, and heat. A sufficient dose (time) of plasma exposure can induce death in cancer cells. The plasma pencil is employed to study the anti-tumor properties of this treatment on epithelial cells. The plasma pencil has been previously used for the inactivation of bacteria, destroying amyloid fibrils, and the killing of various cancer cells. Bladder cancer is the 9th leading cause of cancer. In this dissertation, human urinary bladder tissue with the squamous cell carcinoma disease (SCaBER cells) is treated with LTP utilizing two different approaches: direct plasma exposure and Plasma Activated Media (PAM) as an advancement to the treatment. PAM is produced by exposing a liquid cell culture medium to the plasma pencil. Direct LTP treatment of cancer cells indicates a dose-dependent killing effect at post-treatment times. Similarly, PAM treatment shows an anti-cancer effect by inducing substantial cell death. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have an important role in the biomedical effects of LTP treatment. This study demonstrates the capability of the plasma pencil to transport ROS/RNS into cell culture media

  12. Apoptosis and necroptosis are induced in rainbow trout cell lines exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Krumschnabel, Gerhard, E-mail: Gerhard.Krumschnabel@i-med.ac.at [Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Fritz-Preglstr. 3, Innsbruck (Austria); Ebner, Hannes L.; Hess, Michael W. [Division of Histology and Embryology, Medical University Innsbruck, Innsbruck (Austria); Villunger, Andreas [Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Fritz-Preglstr. 3, Innsbruck (Austria)

    2010-08-01

    Cadmium is an important environmental toxicant that can kill cells. A number of studies have implicated apoptosis as well as necrosis and, most recently, a form of programmed necrosis termed necroptosis in the process of cadmium-mediated toxicity, but the exact mechanism remains ill-defined and may depend on the affected cell type. This study investigated which mode of cell death may be responsible for cell death induction in cadmium-exposed trout cell lines from gill and liver and if this cell death was sensitive to inhibitors of necroptosis or apoptosis, respectively. It was observed that intermediate levels of cadmium that killed approximately 50% of the cells over 96-120 h of exposure caused cell death that morphologically resembled apoptosis and was associated with an increase of apoptotic markers such as the number of cells with diminished DNA content (sub-G1 cells), condensed or fragmented nuclei, and elevation of caspase-3 activity. At the same time, however, cells also lost plasma membrane integrity, as indicated by uptake of propidium iodide, showed a decrease of ATP levels and mitochondrial membrane potential, and displayed cell swelling, signs associated with secondary necrosis, or equally possible, necroptotic cell death. Importantly, many of these alterations were at least partly inhibited by the necroptosis inhibitor necrostatin-1 and were to a lesser extent also sensitive to the pan-caspase inhibitor zVAD-fmk, indicating that multiple modes of cell death are concurrently induced in cadmium-exposed trout cells, including necroptosis and apoptosis. Cell death appeared to lack concurrent radical formation, consistent with genetically regulated necroptotic cell death, but was characterized by the rapid induction of DNA damage markers, and the early onset of disintegration of the Golgi complex. Comparative experiments evaluating copper-toxicity indicated that in comparison to cadmium much higher concentrations of this metal were required to induce cell

  13. Apoptosis and necroptosis are induced in rainbow trout cell lines exposed to cadmium

    International Nuclear Information System (INIS)

    Krumschnabel, Gerhard; Ebner, Hannes L.; Hess, Michael W.; Villunger, Andreas

    2010-01-01

    Cadmium is an important environmental toxicant that can kill cells. A number of studies have implicated apoptosis as well as necrosis and, most recently, a form of programmed necrosis termed necroptosis in the process of cadmium-mediated toxicity, but the exact mechanism remains ill-defined and may depend on the affected cell type. This study investigated which mode of cell death may be responsible for cell death induction in cadmium-exposed trout cell lines from gill and liver and if this cell death was sensitive to inhibitors of necroptosis or apoptosis, respectively. It was observed that intermediate levels of cadmium that killed approximately 50% of the cells over 96-120 h of exposure caused cell death that morphologically resembled apoptosis and was associated with an increase of apoptotic markers such as the number of cells with diminished DNA content (sub-G1 cells), condensed or fragmented nuclei, and elevation of caspase-3 activity. At the same time, however, cells also lost plasma membrane integrity, as indicated by uptake of propidium iodide, showed a decrease of ATP levels and mitochondrial membrane potential, and displayed cell swelling, signs associated with secondary necrosis, or equally possible, necroptotic cell death. Importantly, many of these alterations were at least partly inhibited by the necroptosis inhibitor necrostatin-1 and were to a lesser extent also sensitive to the pan-caspase inhibitor zVAD-fmk, indicating that multiple modes of cell death are concurrently induced in cadmium-exposed trout cells, including necroptosis and apoptosis. Cell death appeared to lack concurrent radical formation, consistent with genetically regulated necroptotic cell death, but was characterized by the rapid induction of DNA damage markers, and the early onset of disintegration of the Golgi complex. Comparative experiments evaluating copper-toxicity indicated that in comparison to cadmium much higher concentrations of this metal were required to induce cell

  14. Extracellular Molecules Involved in Cancer Cell Invasion

    International Nuclear Information System (INIS)

    Stivarou, Theodora; Patsavoudi, Evangelia

    2015-01-01

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion

  15. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  16. Comparative analysis of the surface exposed proteome of two canine osteosarcoma cell lines and normal canine osteoblasts.

    Science.gov (United States)

    Milovancev, Milan; Hilgart-Martiszus, Ian; McNamara, Michael J; Goodall, Cheri P; Seguin, Bernard; Bracha, Shay; Wickramasekara, Samanthi I

    2013-06-13

    Osteosarcoma (OSA) is the most common primary bone tumor of dogs and carries a poor prognosis despite aggressive treatment. An improved understanding of the biology of OSA is critically needed to allow for development of novel diagnostic, prognostic, and therapeutic tools. The surface-exposed proteome (SEP) of a cancerous cell includes a multifarious array of proteins critical to cellular processes such as proliferation, migration, adhesion, and inter-cellular communication. The specific aim of this study was to define a SEP profile of two validated canine OSA cell lines and a normal canine osteoblast cell line utilizing a biotinylation/streptavidin system to selectively label, purify, and identify surface-exposed proteins by mass spectrometry (MS) analysis. Additionally, we sought to validate a subset of our MS-based observations via quantitative real-time PCR, Western blot and semi-quantitative immunocytochemistry. Our hypothesis was that MS would detect differences in the SEP composition between the OSA and the normal osteoblast cells. Shotgun MS identified 133 putative surface proteins when output from all samples were combined, with good consistency between biological replicates. Eleven of the MS-detected proteins underwent analysis of gene expression by PCR, all of which were actively transcribed, but varied in expression level. Western blot of whole cell lysates from all three cell lines was effective for Thrombospondin-1, CYR61 and CD44, and indicated that all three proteins were present in each cell line. Semi-quantitative immunofluorescence indicated that CD44 was expressed at much higher levels on the surface of the OSA than the normal osteoblast cell lines. The results of the present study identified numerous differences, and similarities, in the SEP of canine OSA cell lines and normal canine osteoblasts. The PCR, Western blot, and immunocytochemistry results, for the subset of proteins evaluated, were generally supportive of the mass spectrometry data

  17. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  18. Chemo Resistance of Breast Cancer Stem Cells

    Science.gov (United States)

    2007-05-01

    165-72. 60. Vestergaard J, Pedersen MW, Pedersen N, Ensinger C, Tumer Z, Tommerup N, et al. Hedgehog signaling in small-cell lung cancer : frequent......NUMBER Chemo Resistance of Breast Cancer Stem Cells 5b. GRANT NUMBER W81XWH-04-1-0471 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  19. Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells.

    Science.gov (United States)

    Klose, Johannes; Kattner, Sarah; Borgström, Björn; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Oredsson, Stina; Strand, Daniel; Ulrich, Alexis

    2018-01-01

    Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Mechanisms of mutagenesis in human cells exposed to 55 MeV protons

    Science.gov (United States)

    Gauny, S.; Wiese, C.; Kronenberg, A.

    2001-01-01

    Protons represent the major type of charged particle radiation in spaceflight environments. The purpose of this study was to assess mutations arising in human lymphoid cells exposed to protons. Mutations were quantitated at the thymidine kinase (TK1) locus in cell lines derived from the same donor: TK6 cells (wt TP53) and WTK1 cells (mutant TP53). WTK1 cells were much more susceptible to mutagenesis following proton exposure than TK6 cells. Intragenic deletions were observed among early-arising TK1 mutants in TK6 cells, but not in WTK1 cells where all of the mutants arose by LOH. Deletion was the predominant mode of LOH in TK6 cells, while allelic recombination was the major mode of LOH in WTK1 cells. Deletions were of variable lengths, from <1 cM to 64 cM, while mutations that arose by allelic recombination often extended to the telomere. In summary, proton exposures elicited many types of mutations at an autosomal locus in human cells. Most involved large scale loss of genetic information, either through deletion or by recombination.

  1. Engineered T cells for pancreatic cancer treatment

    Science.gov (United States)

    Katari, Usha L; Keirnan, Jacqueline M; Worth, Anna C; Hodges, Sally E; Leen, Ann M; Fisher, William E; Vera, Juan F

    2011-01-01

    Objective Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. Methods Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr51) release. Results Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. Conclusions Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer. PMID:21843265

  2. Frequency patterns of T-cell exposed motifs in immunoglobulin heavy chain peptides presented by MHCs

    Directory of Open Access Journals (Sweden)

    Robert D. Bremel

    2014-10-01

    Full Text Available Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV to assess the diversity of T-cell exposed motifs (TCEM. TCEM comprise those amino acids in a MHC-bound peptide which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM. Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of T-cell exposed motif re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by clonal expansion that develop along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs.

  3. Are cancer cells really softer than normal cells?

    Science.gov (United States)

    Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste

    2017-05-01

    Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  4. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  5. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of {sup 111}In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Reilly, Raymond M. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network Toronto, Toronto, ON, M5S 3M2 (Canada)], E-mail: raymond.reilly@utoronto.ca

    2008-08-15

    Introduction: Our objective was to define the relationships between tumor uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10{sup 4}, 1.4x10{sup 4}, 4.0x10{sup 4} and 1.0x10{sup 5} IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 {mu}g) or IGFBP-3 (2 or 25 {mu}g) was studied. The relationship between tumor uptake of [{sup 111}In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [{sup 111}In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 {mu}g/ml) in the absence/presence of IGFBP-3 (1 {mu}g/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 {mu}g/ml), was determined. Results: [{sup 111}In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9{+-}0.1 vs. 1.0{+-}0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [{sup 111}In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r{sup 2}=0.99) between the tumor uptake of {sup 111}In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4{+-}0.05 %ID/g for H2N to 2.5{+-}0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC

  6. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of 111In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    International Nuclear Information System (INIS)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle; Reilly, Raymond M.

    2008-01-01

    Introduction: Our objective was to define the relationships between tumor uptake of [ 111 In]-IGF-1 and [ 111 In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [ 111 In]-IGF-1 and [ 111 In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10 4 , 1.4x10 4 , 4.0x10 4 and 1.0x10 5 IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 μg) or IGFBP-3 (2 or 25 μg) was studied. The relationship between tumor uptake of [ 111 In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [ 111 In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 μg/ml) in the absence/presence of IGFBP-3 (1 μg/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 μg/ml), was determined. Results: [ 111 In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9±0.1 vs. 1.0±0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [ 111 In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r 2 =0.99) between the tumor uptake of 111 In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4±0.05 %ID/g for H2N to 2.5±0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC cells to trastuzumab was directly associated with IGF-1R expression, despite co

  7. PACAP and VIP inhibit the invasiveness of glioblastoma cells exposed to hypoxia through the regulation of HIFs and EGFR expression

    Directory of Open Access Journals (Sweden)

    Grazia eMaugeri

    2016-05-01

    Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP and vasoactive intestinal peptide (VIP through the binding of vasoactive intestinal peptide receptors (VIPRs, perform a wide variety of effects in human cancers, including glioblastoma multiforme (GBM. This tumor is characterized by extensive areas of hypoxia, which triggers the expression of hypoxia-inducible factors (HIFs. HIFs not only mediate angiogenesis but also tumor cell migration and invasion. Furthermore, HIFs activation is linked to epidermal growth factor receptor (EGFR overexpression. Previous studies have shown that VIP interferes with the invasive nature of gliomas by regulating cell migration. However, the role of VIP family members in GBM infiltration under low oxygen tension has not been clarified yet. Therefore, in the present study we have investigated, for the first time, the molecular mechanisms involved in the anti-invasive effect of PACAP or VIP in U87MG glioblastoma cells exposed to hypoxia induced by treatment with desferrioxamine (DFX. The results suggest that either PACAP or VIP exert an anti-infiltrative effect under low oxygen tension by modulating HIFs and EGFR expression, key elements involved in cell migration and angiogenesis. These peptides act through the inhibition of PI3K/Akt and MAPK/ERK signaling pathways, which are known to have a crucial role in HIFs regulation. In conclusion, the modulation of hypoxic event and the anti-invasive effect exerted by some VIP family members might open new insights in the therapeutic approach to GBM.

  8. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S

    2012-11-01

    Full Text Available Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs, also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal, giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division. A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on

  9. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  10. Models for comparing lung-cancer risks in radon- and plutonium-exposed experimental animals

    International Nuclear Information System (INIS)

    Gilbert, E.S.; Cross, F.T.; Sanders, C.L.; Dagle, G.E.

    1990-10-01

    Epidemiologic studies of radon-exposed underground miners have provided the primary basis for estimating human lung-cancer risks resulting from radon exposure. These studies are sometimes used to estimate lung-cancer risks resulting from exposure to other alpha- emitters as well. The latter use, often referred to as the dosimetric approach, is based on the assumption that a specified dose to the lung produces the same lung-tumor risk regardless of the substance producing the dose. At Pacific Northwest Laboratory, experiments have been conducted in which laboratory rodents have been given inhalation exposures to radon and to plutonium ( 239 PuO 2 ). These experiments offer a unique opportunity to compare risks, and thus to investigate the validity of the dosimetric approach. This comparison is made most effectively by modeling the age-specific risk as a function of dose in a way that is comparable to analyses of human data. Such modeling requires assumptions about whether tumors are the cause of death or whether they are found incidental to death from other causes. Results based on the assumption that tumors are fatal indicate that the radon and plutonium dose-response curves differ, with a linear function providing a good description of the radon data, and a pure quadratic function providing a good description of the plutonium data. However, results based on the assumption that tumors are incidental to death indicate that the dose-response curves for the two exposures are very similar, and thus support the dosimetric approach. 14 refs., 2 figs., 6 tabs

  11. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  12. Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.

    Science.gov (United States)

    Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza

    2017-01-01

    Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

  13. Metformin is synthetically lethal with glucose withdrawal in cancer cells.

    Science.gov (United States)

    Menendez, Javier A; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Corominas-Faja, Bruna; Joven, Jorge; Martin-Castillo, Begoña; Vazquez-Martin, Alejandro

    2012-08-01

    Glucose deprivation is a distinctive feature of the tumor microecosystem caused by the imbalance between poor supply and an extraordinarily high consumption rate. The metabolic reprogramming from mitochondrial respiration to aerobic glycolysis in cancer cells (the "Warburg effect") is linked to oncogenic transformation in a manner that frequently implies the inactivation of metabolic checkpoints such as the energy rheostat AMP-activated protein kinase (AMPK). Because the concept of synthetic lethality in oncology can be applied not only to genetic and epigenetic intrinsic differences between normal and cancer cells but also to extrinsic ones such as altered microenvironment, we recently hypothesized that stress-energy mimickers such as the AMPK agonist metformin should produce metabolic synthetic lethality in a glucose-starved cell culture milieu imitating the adverse tumor growth conditions in vivo. Under standard high-glucose conditions, metformin supplementation mostly caused cell cycle arrest without signs of apoptotic cell death. Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis. Significantly, representative cell models of breast cancer heterogeneity underwent massive apoptosis (by >90% in some cases) when glucose-starved cell cultures were supplemented with metformin. Our current findings may uncover crucial issues regarding the cell-autonomous metformin's anti-cancer actions: (1) The offently claimed clinically irrelevant, non-physiological concentrations needed to observe the metformin's anti-cancer effects in vitro merely underlie the artifactual interference of erroneous glucose-rich experimental conditions that poorly reflect glucose-starved in vivo conditions; (2) the preferential killing of cancer stem cells (CSC) by metformin may simply expose the best-case scenario for its synthetically lethal activity because an increased

  14. Cancer cell adaptation to chemotherapy

    International Nuclear Information System (INIS)

    Di Nicolantonio, Federica; Johnson, Penny; Somers, Shaw S; Toh, Simon; Higgins, Bernie; Lamont, Alan; Gulliford, Tim; Hurren, Jeremy; Yiangou, Constantinos; Cree, Ian A; Mercer, Stuart J; Knight, Louise A; Gabriel, Francis G; Whitehouse, Pauline A; Sharma, Sanjay; Fernando, Augusta; Glaysher, Sharon; Di Palma, Silvana

    2005-01-01

    Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation

  15. Immune cells in Chernobyl recovery operation workers exposed over 500 mSv

    International Nuclear Information System (INIS)

    Bazyka, D.; Byelyaeva, N.; Chumak, A.; Golyarnik, N.; Maznichenko, O.; Kovalenko, Ju.

    2004-01-01

    Immune response parameters were studied in Chernobyl radiation emergency workers exposed to radiation over 500 mSv during 1986. Initial response stage to the radiation exposure was characterised by immunological deficiency with T-cell subsets changes. In the reconstitution period inhibition of immune function was associated with lymphocyte subset changes such as decreased CD3 + and CD4 + cell counts and increased number of somatic mutations in TCR-locus. Late period after the acute radiation exposure in Chernobyl radiation emergency workers is characterized by decreased CD8 + suppressor cell function that could lead to poor proliferation control. Subset analysis of CD34 + cells showed in ARS survivors counts significantly higher than in control especially for the most primitive progenitors with CD34 + CD90 + CD45 -/l ow and CD34 + CD45 - CD38 - phenotypes. (author)

  16. Cancer Cell Metabolism: One Hallmark, Many Faces

    OpenAIRE

    Cantor, Jason R.; Sabatini, David M.

    2012-01-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such chang...

  17. Protective Effects of Hydroalcoholic Extract of Nasturtium officinale on Rat Blood Cells Exposed to Arsenic

    Directory of Open Access Journals (Sweden)

    Felor Zargari

    2015-06-01

    Full Text Available Background: Arsenic is one of the most toxic metalloids. Anemia and leukopenia are common results of poisoning with arsenic, which may happen due to a direct hemolytic or cytotoxic effect on blood cells. The aim of this study was to examine the effects of hydroalcoholic extract of Nasturtium officinale on blood cells and antioxidant enzymes in rats exposed to sodium (metaarsenite. Methods: 32 Male Sprague Dawley rats were randomly divided into four groups; Group I (normal healthy rats, Group II (treated with 5.5mg/kg of body weight of NaAsO2, Group III (treated with 500mg/kg of body weight of hydro-alcoholic extract of N. officinale, and Group IV (treated with group II and III supplementations. Blood samples were collected and red blood cell, white blood cell, hematocrit, hemoglobin, platelet, total protein and albumin levels and total antioxidant capacity were measured. Data was analyzed with Mann-Whitney U test. Results: WBC, RBC and Hct were decreased in the rats exposed to NaAsO2 (p<0.05. A significant increase was seen in RBC and Hct after treatment with the plant extract (p<0.05. There was no significant decrease in serum albumin and total protein in the groups exposed to NaAsO2 compared to the group I, but NaAsO2 decreased the total antioxidant capacity, significantly. Conclusion: The Nasturtium officinale extract have protective effect on arsenic-induced damage of blood cells.

  18. T cell recognition of breast cancer antigens

    DEFF Research Database (Denmark)

    Petersen, Nadia Viborg; Andersen, Sofie Ramskov; Andersen, Rikke Sick

    Recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability ofimmunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described, thus it is necessary to identify T cell targets to develop immune mediated therapies.......This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, NEK3, and PIAS3 contribute to increase growth, survival, and motility of malignant cells. Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse...... recognition utilizing DNA barcode labeled MHC multimers to screen peripheral blood lymphocytes from breast cancer patients and healthy donor samples. Signif-icantly more TAA specific T cell responses were detected in breast cancer patients than healthy donors for both HLA-A*0201 (P

  19. Cancer stem cells in colorectal cancer: a review.

    Science.gov (United States)

    Munro, Matthew J; Wickremesekera, Susrutha K; Peng, Lifeng; Tan, Swee T; Itinteang, Tinte

    2018-02-01

    Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. Adenocarcinoma accounts for 90% of CRC cases. There has been accumulating evidence in support of the cancer stem cell (CSC) concept of cancer which proposes that CSCs are central in the initiation of cancer. CSCs have been the focus of study in a range of cancers, including CRC. This has led to the identification and understanding of genes involved in the induction and maintenance of pluripotency of stem cells, and markers for CSCs, including those investigated specifically in CRC. Knowledge of the expression pattern of CSCs in CRC has been increasing in recent years, revealing a heterogeneous population of cells within CRC ranging from pluripotent to differentiated cells, with overlapping and sometimes unique combinations of markers. This review summarises current literature on the understanding of CSCs in CRC, including evidence of the presence of CSC subpopulations, and the stem cell markers currently used to identify and localise these CSC subpopulations. Future research into this field may lead to improved methods for early detection of CRC, novel therapy and monitoring of treatment for CRC and other cancer types. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells

    NARCIS (Netherlands)

    Michaelis, M.; Rothweiler, F.; Barth, S.; Cinatl, J.; van Rikxoort, M.; Loeschmann, N.; Voges, Y.; Breitling, R.; von Deimling, A.; Roedel, F.; Weber, K.; Fehse, B.; Mack, E.; Stiewe, T.; Doerr, H. W.; Speidel, D.; Cinatl, J.; Cinatl jr., J.; Stephanou, A.

    2011-01-01

    Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines

  1. The exposed breast

    International Nuclear Information System (INIS)

    Ingman, Wendy

    2014-01-01

    The skin and lungs are two tissues that are frequently bombarded with cancer-initiating factors, such as ultraviolet rays from the sun and smoke and pollutants in the air we breathe. Yet breast cancer is the most common type of cancer in Australian women, affecting one in eight before the age of 85. It is more common than skin melanoma and lung cancer. Why, then, does the breast so commonly get cancer when it is not a tissue that is particularly exposed to the environmental agents that increase cancer risk in other major organs? Is there something unique about this tissue that makes it particularly susceptible? The breast undergoes cellular changes over the course of the monthly menstrual cycle, and and these changes affect cancer susceptibility. Rising levels of the hormones oestrogen and progesterone occur immediately after the egg is released from the ovary, and these hormones cause the breast cells to divide and change to accommodate further development if pregnancy occurs. If the woman becomes pregnant, the cells in the breast continue to develop and become the milk-producing structures required to feed a newborn baby. But if pregnancy does not occur there is a drop in progesterone, which triggers the death of the newly developed breast cells. This occurs at the same time women have their period. Then the cycle starts again, and continues every month until menopause, unless the woman becomes pregnant.

  2. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  3. Live-cell imaging study of mitochondrial morphology in mammalian cells exposed to X-rays

    International Nuclear Information System (INIS)

    Noguchi, M.; Yokoya, A.; Narita, A.; Fujii, K.; Kanari, Y.

    2015-01-01

    Morphological changes in mitochondria induced by X-irradiation in normal murine mammary gland cells were studied with a live-cell microscopic imaging technique. Mitochondria were visualised by staining with a specific fluorescent probe in the cells, which express fluorescent ubiquitination-based cell-cycle indicator 2 (Fucci2) probes to visualise cell cycle. In unirradiated cells, the number of cells with fragmented mitochondria was about 20 % of the total cells through observation period (96 h). In irradiated cells, the population with fragmented mitochondria significantly increased depending on the absorbed dose. Particularly, for 8 Gy irradiation, the accumulation of fragmentation persists even in the cells whose cell cycle came to a stand (80 % in G1 (G0-like) phase). The fraction reached to a maximum at 96 h after irradiation. The kinetics of the fraction with fragmented mitochondria was similar to that for cells in S/G2/M phase (20 %) through the observation period (120 h). The evidences show that, in irradiated cells, some signals are continually released from a nucleus or cytoplasm even in the G0-like cells to operate some sort of protein machineries involved in mitochondrial fission. It is inferred that this delayed mitochondrial fragmentation is strongly related to their dysfunction, and hence might modulate radiobiological effects such as mutation or cell death. (authors)

  4. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance.

    Science.gov (United States)

    Li, Xiao-Feng; Chen, Cheng; Xiang, Dai-Min; Qu, Le; Sun, Wen; Lu, Xin-Yuan; Zhou, Teng-Fei; Chen, Shu-Zhen; Ning, Bei-Fang; Cheng, Zhuo; Xia, Ming-Yang; Shen, Wei-Feng; Yang, Wen; Wen, Wen; Lee, Terence Kin Wah; Cong, Wen-Ming; Wang, Hong-Yang; Ding, Jin

    2017-12-01

    The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6-positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted tumor necrosis factor-α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self-renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6-positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Our results not only clarify the cellular and molecular mechanisms underlying the inflammation-mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934-1951). © 2017 by the American Association for the Study of Liver Diseases.

  5. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.

    Directory of Open Access Journals (Sweden)

    Alyson C Yoder

    2017-02-01

    Full Text Available Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a

  6. Sensitivity of HTB140 cell exposed to protons and alkylating agents

    International Nuclear Information System (INIS)

    Koricanac, L.; Petrovic, I.; Privitera, G.; Cuttone, G.; Ristic-Fira, A.

    2006-01-01

    Malignant melanoma is a highly aggressive cancer with a poor prognosis due to resistance to radiotherapy and chemotherapy regimens. The mainstay of treatment remains DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), chloroethylnitrosourea agent, also has demonstrated significant antitumoral effects in malignant melanoma. However, the resistance of melanoma cells limits their clinical application. In order to enhance the inhibition of melanoma cell growth, in this study, combined treatment of FM and DTIC with proton irradiation, was investigated. We analyzed the effects of combined treatment on HTB140 melanoma cell viability and proliferation. Significant inhibition of cell growth, especially cell proliferation, was obtained after treatment with protons and FM compare to single irradiation or drug treatment. Treatment with protons and DTIC has shown improved growth inhibition compare to appropriate single drug treatment, but not compare to irradiation as a single treatment. (author)

  7. Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients.

    Science.gov (United States)

    Tong, Dongxia; Yu, Muxin; Guo, Li; Li, Tao; Li, Jihe; Novakovic, Valerie A; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Bi, Yayan; Wang, Jinghua; Zhou, Jin; Shi, Jialan

    2018-04-01

    The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.

  8. Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

    DEFF Research Database (Denmark)

    La Rocca, Rosanna; Tallerico, Rossana; Hassan, Almosawy Talib

    2014-01-01

    In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were...... treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells...... between 700–1800 cm-1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased...

  9. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  10. FGF2 mediates DNA repair in epidermoid carcinoma cells exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Marie, Melanie; Hafner, Sophie; Moratille, Sandra; Vaigot, Pierre; Rigaud, Odile; Martin, Michele T.; Mine, Solene

    2012-01-01

    Fibroblast growth factor 2 (FGF2) is a well-known survival factor. However, its role in DNA repair is poorly documented. The present study was designed to investigate in epidermoid carcinoma cells the potential role of FGF2 in DNA repair. The side population (SP) with cancer stem cell-like properties and the main population (MP) were isolated from human A431 squamous carcinoma cells. Radiation-induced DNA damage and repair were assessed using the alkaline comet assay. FGF2 expression was quantified by enzyme linked immunosorbent assay (ELISA). SP cells exhibited rapid repair of radiation induced DNA damage and a high constitutive level of nuclear FGF2. Blocking FGF2 signaling abrogated the rapid DNA repair. In contrast, in MP cells, a slower repair of damage was associated with low basal expression of FGF2. Moreover, the addition of exogenous FGF2 accelerated DNA repair in MP cells. When irradiated, SP cells secreted FGF2, whereas MP cells did not. FGF2 was found to mediate DNA repair in epidermoid carcinoma cells. We postulate that carcinoma stem cells would be intrinsically primed to rapidly repair DNA damage by a high constitutive level of nuclear FGF2. In contrast, the main population with a low FGF2 content exhibits a lower repair rate which can be increased by exogenous FGF2. (authors)

  11. Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?

    Science.gov (United States)

    Yeh, Albert C; Ramaswamy, Sridhar

    2015-12-01

    Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. ©2015 American Association for Cancer Research.

  12. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Cancer Stem-Like Cells Accumulated in Nickel-Induced Malignant Transformation

    Science.gov (United States)

    Wang, Lei; Fan, Jia; Hitron, John Andrew; Son, Young-Ok; Wise, James T.F.; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Shi, Xianglin

    2016-01-01

    Nickel compounds are known as human carcinogens. Chronic environmental exposure to nickel is a worldwide health concern. Although the mechanisms of nickel-induced carcinogenesis are not well understood, recent studies suggest that stem cells/cancer stem cells are likely important targets. This study examines the role of cancer stem cells in nickel-induced cell transformation. The nontransformed human bronchial epithelial cell line (Beas-2B) was chronically exposed to nickel chloride for 12 months to induce cell transformation. Nickel induced Beas-2B cell transformation, and cancer stem-like cells were enriched in nickel-transformed cell (BNiT) population. The BNiT cancer stem-like cells demonstrated enhanced self-renewal and distinctive differentiation properties. In vivo tumorigenesis studies show that BNiT cancer stem-like cells possess a high tumor-initiating capability. It was also demonstrated that superoxide dismutase 1 was involved in the accumulation of cancer stem-like cells; the regulation of superoxide dismutase 1 expression was different in transformed stem-like cells and nontransformed. Overall, the accumulation of stem-like cells and their enhanced stemness functions contribute to nickel-induced tumorigenesis. Our study provides additional insight into the mechanisms by which metals or other chemicals can induce carcinogenesis. PMID:26962057

  14. Are Mast Cells MASTers in Cancer?

    Science.gov (United States)

    Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Marone, Giancarlo; Iannone, Raffaella; Marone, Gianni; Granata, Francescopaolo

    2017-01-01

    Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin's lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.

  15. Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

    International Nuclear Information System (INIS)

    Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.; Contreras-Ruiz, Jose; Garcia-Vargas, Gonzalo G.; Razo, Luz M. del

    2007-01-01

    Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs III , MAs V , DMAs III , DMAs V ). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas

  16. Estimation of Future Cancer Burden Among Rescue and Recovery Workers Exposed to the World Trade Center Disaster.

    Science.gov (United States)

    Singh, Ankura; Zeig-Owens, Rachel; Moir, William; Hall, Charles B; Schwartz, Theresa; Vossbrinck, Madeline; Jaber, Nadia; Webber, Mayris P; Kelly, Kerry J; Ortiz, Viola; Koffler, Ellen; Prezant, David J

    2018-06-01

    Elevated rates of cancer have been reported in individuals exposed to the World Trade Center (WTC) disaster, including Fire Department of the City of New York (FDNY) rescue and recovery workers. To project the future burden of cancer in WTC-exposed FDNY rescue and recovery workers by estimating the 20-year cancer incidence. A total of 14 474 WTC-exposed FDNY employees who were cancer-free on January 1, 2012; subgroup analyses were conducted of the cohort's white male population (n = 12 374). In this closed-cohort study, we projected cancer incidence for the January 1, 2012, to December 31, 2031, period. Simulations were run using demographic-specific New York City (NYC) cancer and national mortality rates for each individual, summed for the whole cohort, and performed 1000 times to produce mean estimates. Additional analyses in the subgroup of white men compared case counts produced by using 2007-2011 FDNY WTC Health Program (FDNY-WTCHP) cancer rates vs NYC rates. Average and 20-year aggregate costs of first-year cancer care were estimated using claims data. World Trade Center disaster exposure defined as rescue and recovery work at the WTC site at any time from September 11, 2001, to July 25, 2002. (1) Projected number of incident cancers in the full cohort, based on NYC cancer rates; (2) cancer incidence estimates in the subgroup projected using FDNY-WTCHP vs NYC rates; and (3) estimated first-year treatment costs of incident cancers. On January 1, 2012, the cohort was 96.8% male, 87.1% white, and had a mean (SD) age of 50.2 (9.2) years. The projected number of incident cancer cases was 2960 (95% CI, 2883-3037). In our subgroup analyses using FDNY-WTCHP vs NYC cancer rates, the projected number of new cases in white men was elevated (2714 [95% CI, 2638-2786] vs 2596 [95% CI, 2524-2668]). Accordingly, we expect more prostate (1437 [95% CI, 1383-1495] vs 863 [95% CI, 816-910]), thyroid (73 [95% CI, 60-86] vs 57 [95% CI, 44-69]), and melanoma cases (201 [95

  17. Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 161

    Science.gov (United States)

    Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin

    2009-01-01

    Human papillomavirus (HPV) type 16 infects the epithelial layer of cervical mucosa and is causally associated with the generation of cervical cancer. Langerhans cells (LC) are the resident antigen-presenting cells at the site of infection and therefore are responsible for initiating an immune response against HPV16. On the contrary, LC exposed to HPV16 do not induce a specific T cell immune response, which leads to the immune evasion of HPV16. Demonstrating that Toll-like receptor 7 (TLR7) and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response. Surprisingly both phenotypic and functional hallmarks of activation are not observed when LC are exposed to HPV16 virus-like particles (VLP) and treated with imiquimod (TLR7 agonist). However, we found that LC are activated by 3M-002 (TLR8 agonist) and resiquimod (TLR8/7 agonist). LC exposed to HPV16 VLP and subsequently treated with 3M-002 or resiquimod highly up-regulate surface activation markers, secrete pro-inflammatory cytokines and chemokines, induce CCL21-directed migration, and initiate an HPV16-specific CD8+ T cell response. These data strongly indicate that 3M-002 and resiquimod are promising therapeutics for treatment of HPV-infections and HPV-induced cervical lesions. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third

  18. Colon stem cell and crypt dynamics exposed by cell lineage reconstruction.

    Directory of Open Access Journals (Sweden)

    Yitzhak Reizel

    2011-07-01

    Full Text Available Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.

  19. Molecular pathways in the bystander response of cells exposed to very low fluences of alpha particles

    International Nuclear Information System (INIS)

    Little, J.B.

    2000-01-01

    Full text: We have examined biological effects in cell populations exposed to very low mean doses of alpha radiation by which only a small fraction of the cells are actually traversed by an alpha particle. We showed earlier that an enhanced frequency of sister chromatid exchanges and HPRT mutations occur in the non-irradiated, 'bystander' cells. The frequency of mutations induced by a single alpha particle traversing the nucleus of a cell was increased nearly fivefold at the lowest fluence studied, a result of mutations occurring in bystander cells. This was associated with a similar increase in the induction of micronuclei, indicating the induction of DNA damage in bystander cells. In order to gain information concerning molecular pathways, we studied changes in gene expression in bystander cells in confluent cultures of human diploid fibroblasts or mouse embryo-derived fibroblasts (MEFs) by western analysis and in-situ immunofluorescence. The expression levels of p53, p21 Waf1 and p34 cdc2 were significantly modulated in bystander cells. The upregulation of p53 and p21 Waf1 did not occur in cultures irradiated at low density, and was markedly reduced in the presence of the gap junction inhibitor lindane. The importance of gap-junction mediated intercellular communication was confirmed in connexin-43 knockout MEFs. Western blot analyses and electrophoretic mobility shift assays indicate that the bystander response is suppressed by incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase, and is associated with the induction of NFKB, suggesting the effect is mediated by oxidative stress. The stress-activated protein kinase p38 and its downstream effector ATF2 are also induced in bystander cells independent of oxidative stress. These results will be discussed in terms of whether activation of the p53 damage response pathway is the direct result of signaling from irradiated cells, or rather is a consequence of DNA induced damage in the bystander

  20. Fate of D3 mouse embryonic stem cells exposed to X-rays or carbon ions.

    Science.gov (United States)

    Luft, S; Pignalosa, D; Nasonova, E; Arrizabalaga, O; Helm, A; Durante, M; Ritter, S

    2014-01-15

    The risk of radiation exposure during embryonic development is still a major problem in radiotoxicology. In this study we investigated the response of the murine embryonic stem cell (mESC) line D3 to two radiation qualities: sparsely ionizing X-rays and densely ionizing carbon ions. We analyzed clonogenic cell survival, proliferation, induction of chromosome aberrations as well as the capability of cells to differentiate to beating cardiomyocytes up to 3 days after exposure. Our results show that, for all endpoints investigated, carbon ions are more effective than X-rays at the same radiation dose. Additionally, in long term studies (≥8 days post-irradiation) chromosomal damage and the pluripotency state were investigated. These studies reveal that pluripotency markers are present in the progeny of cells surviving the exposure to both radiation types. However, only in the progeny of X-ray exposed cells the aberration frequency was comparable to that of the control population, while the progeny of carbon ion irradiated cells harbored significantly more aberrations than the control, generally translocations. We conclude that cells surviving the radiation exposure maintain pluripotency but may carry stable chromosomal rearrangements after densely ionizing radiation. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C

    Directory of Open Access Journals (Sweden)

    Diane M. Da Silva

    2015-12-01

    Full Text Available Human papillomaviruses (HPV establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC, the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C, and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8+ T cells in vitro. Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8+ T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection. Keywords: Papillomavirus, HPV16, Langerhans cells, Immune escape

  2. Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

    Science.gov (United States)

    Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

    2018-02-01

    The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

  3. Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

    Directory of Open Access Journals (Sweden)

    Saura C. Sahu

    Full Text Available Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver. Keywords: Nanosilver, Silver nanoparticles, Nanoparticles, Toxicogenomics, DNA microarray, Global gene expression profiles, Caco2 cells

  4. Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

    Directory of Open Access Journals (Sweden)

    Christiana Smith

    2017-04-01

    Full Text Available ObjectivesHIV-exposed uninfected (HEU infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK cell activity might occur in HEU infants and predispose them to severe infections.DesignCase–control study using cryopreserved peripheral blood mononuclear cells (PBMCs at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013.MethodsNK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells.ResultsThe proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001 and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005. At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001 and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047, but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFNγ at birth (0.77 vs. 2.64%, p = 0.008 and at 6 months (4.12 vs. 8.39%, p = 0.001, and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008. Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures.ConclusionNK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory

  5. Radiosensitization effect of CMNa on hypoxic pancreatic cancer cell in vitro

    International Nuclear Information System (INIS)

    Yin Lijie; Zhang Li; Ding Tiangui; Peng Zhaoxiang; Yu Huan; Gao Yuwei

    2006-01-01

    Objective: To investigate the effects of glycodidazolum natrium (CMNa) on pancreatic cancer cells under hypoxic condition. Methods: The human pancreatic cancer Panc-1 cells were exposed to a single fraction of high-dose γ-ray radiation either with CMNa or under hypoxic condition. The percentage of dead cells was detected with a multiwell plated reader, and fluorescence intensities of propidium iodide were measured before and after digitonin treatment. The sensitizing effect of CMNa on cell killing induced by high-dose irradiation was evaluated by time and concentration dependence. The selective radiosensitive effect of CMNa on hypoxia was evaluated by flow cytometry. Results: The death rate of pancreatic cancer Panc-1 cells paralleled with the increasing concentration of CMNa under hypoxic condition after 30 gray irradiation. The selective radiosensitive effect of CMNa on hypoxia was time-dependent. Conclusions: CMNa can enhance the radiosensitivity of pancreatic cancer Pane-1 cells under hypoxic condition with high-dose irradiation. (authors)

  6. The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida

    2016-01-01

    Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...... alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. Results: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing...... resistance relevant genomic variation appeared to arise midway towards fully resistant cells corresponding to passage 31 (5 nM docetaxel) for MDA-MB-231 and passage 16 (1.2 nM docetaxel) for MCF-7, and where the cells also exhibited a period of reduced growth rate or arrest, respectively. MCF-7 cell acquired...

  7. The ultrastructural surface morphology of oral cancer cells and keratinocytes after exposure to chitosan

    Science.gov (United States)

    Fatimah; Sarsito, A. S.; Wimardhani, Y. S.

    2017-08-01

    Low-molecular-weight chitosan (LMWC) has the same selective cytotoxic effects on oral cancer cells as cisplatin. The cell deaths caused by the anticancer characteristics of chitosan show that apoptosis is not the death pathway of the primary cells involved. The interactions between LMWC and the cells need to be explored. The objective of this study was to compare the ultrastructural morphology of oral Squamous Cell Carcinoma (SCC Ca)-922 and noncancer keratinocyte HaCaT cell lines after exposure to LMWC and cisplatin. The cells were treated with LMWC and cisplatin, and their ultrastructural morphology was analyzed using scanning electron micrographs. Features of early apoptosis, seen as the loss of microvilli, were detected in the LMWC-exposed Ca9-22 cells, and there was a material surrounding the cells. In contrast, the LMWC-exposed HaCaT cells showed no changes related to apoptosis. The results were the opposite when cisplatin was used. This study confirms that there are differences in the ultrastructural surface morphology of LMWC-exposed and cisplatin-exposed oral cancer cells and keratinocytes that could be correlated with their biological activity.

  8. Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study

    Directory of Open Access Journals (Sweden)

    Chivukula VK

    2015-01-01

    Full Text Available Venkat Keshav Chivukula,1 Benjamin L Krog,1,2 Jones T Nauseef,2 Michael D Henry,2 Sarah C Vigmostad1 1Department of Biomedical Engineering, 2Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa, Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, USA Abstract: Over 90% of cancer deaths result not from primary tumor development, but from metastatic tumors that arise after cancer cells circulate to distal sites via the circulatory system. While it is known that metastasis is an inefficient process, the effect of hemodynamic parameters such as fluid shear stress (FSS on the viability and efficacy of metastasis is not well understood. Recent work has shown that select cancer cells may be able to survive and possibly even adapt to FSS in vitro. The current research seeks to characterize the effect of FSS on the mechanical properties of suspended cancer cells in vitro. Nontransformed prostate epithelial cells (PrEC LH and transformed prostate cancer cells (PC-3 were used in this study. The Young's modulus was determined using micropipette aspiration. We examined cells in suspension but not exposed to FSS (unsheared and immediately after exposure to high (6,400 dyn/cm2 and low (510 dyn/cm2 FSS. The PrEC LH cells were ~140% stiffer than the PC-3 cells not exposed to FSS. Post-FSS exposure, there was an increase of ~77% in Young's modulus after exposure to high FSS and a ~47% increase in Young's modulus after exposure to low FSS for the PC-3 cells. There was no significant change in the Young's modulus of PrEC LH cells post-FSS exposure. Our findings indicate that cancer cells adapt to FSS, with an increased Young's modulus being one of the adaptive responses, and that this adaptation is specific only to PC-3 cells and is not seen in PrEC LH cells. Moreover, this adaptation appears to be graded in response to the magnitude of FSS experienced by the cancer cells. This is the first study

  9. Spindle Cell Metaplastic Breast Cancer: Case Report

    Directory of Open Access Journals (Sweden)

    Dursun Ozgur Karakas

    2013-08-01

    Conclusion: Spindle cell metaplastic breast cancer must be considered in differential diagnosis of breast cancers, and preoperative immunohistochemical examination, including cytokeratin and vimentin, must be added to pathological examination in intervening cases. [Arch Clin Exp Surg 2013; 2(4.000: 259-262

  10. T Cells in Gastric Cancer: Friends or Foes

    Science.gov (United States)

    Amedei, Amedeo; Della Bella, Chiara; Silvestri, Elena; Prisco, Domenico; D'Elios, Mario M.

    2012-01-01

    Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, “friend or foe”, of T-cell response in gastric cancer. PMID:22693525

  11. Chemo Resistance of Breast Cancer Stem Cells

    National Research Council Canada - National Science Library

    Wicha, Max S

    2006-01-01

    .... Development of this new tool will greatly facilitate future studies. Preliminary results both in xenograft models as well as in neoadjuvant trial are providing strong support for our hypothesis for resistance of cancer cells to chemotherapy...

  12. Proteinase activity in cell nuclei of rats exposed to γ-radiation and methyl nitrosourea

    International Nuclear Information System (INIS)

    Malakhova, L.V.; Surkenova, G.N.; Gaziev, A.I.

    1990-01-01

    Activity of nuclear proteinases in blood and liver cells of rats exposed to whole-body γ-irradiation (10 Gy) has been comparatively studied by the capacity of splitting the caseic substrate. Proteinase activity in nuclei of irradiated rat leukocytes was shown to increase by 2.5 times and to gradually decrease after 48 h reaching 150-160% as compared to the control. Two hours following a single injection of methyl nitrosourea the alteration in the activity of proteinases in nuclei of rat hepatocytes and leukocytes was different from the alteration of this index after γ-irradiation

  13. Oral epithelial stem cells – implications in normal development and cancer metastasis

    Science.gov (United States)

    Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

    2014-01-01

    Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

  14. Stem Cells and Cancer; Celulas madre y cancer

    Energy Technology Data Exchange (ETDEWEB)

    Segrelles, C.; Paraminio, J. M.; Lorz, C.

    2014-04-01

    Stem cell research has thrived over the last years due to their therapeutic and regenerative potential. Scientific breakthroughs in the field are immediately translated from the scientific journals to the mass media, which is not surprising as the characterisation of the molecular mechanisms that regulate the biology of stem cells is crucial for the treatment of degenerative and cardiovascular diseases, as well as cancer. In the Molecular Oncology Unit at Ciemat we work to unravel the role of cancer stem cells in tumour development, and to find new antitumor therapies. (Author)

  15. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

    Science.gov (United States)

    Song, Chang W.; Lee, Hyemi; Dings, Ruud P. M.; Williams, Brent; Powers, John; Santos, Troy Dos; Choi, Bo-Hwa; Park, Heon Joo

    2012-01-01

    The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Conclusion: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR. PMID:22500211

  16. Cancer stem cells: a metastasizing menace!

    Science.gov (United States)

    Bandhavkar, Saurabh

    2016-04-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan P; Jackson-Humbles, Daven N; Buglak, Nicholas; Li, Ning; White, Kaylin; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2017-08-01

    Exposure to elevated levels of ambient ozone in photochemical smog is associated with eosinophilic airway inflammation and nonatopic asthma in children. In the present study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced nonatopic asthma by using lymphoid cell-sufficient C57BL/6 mice, ILC-sufficient Rag2 -/- mice (devoid of T and B cells), and ILC-deficient Rag2 -/- Il2rg -/- mice (depleted of all lymphoid cells including ILCs). Mice were exposed to 0 or 0.8 parts per million ozone for 1 day or 9 consecutive weekdays (4 hr/day). A single exposure to ozone caused neutrophilic inflammation, airway epithelial injury, and reparative DNA synthesis in all strains of mice, irrespective of the presence or absence of ILCs. In contrast, 9-day exposures induced eosinophilic inflammation and mucous cell metaplasia only in the lungs of ILC-sufficient mice. Repeated ozone exposures also elicited increased messenger RNA expression of transcripts associated with type 2 immunity and airway mucus production in ILC-sufficient mice. ILC-deficient mice repeatedly exposed to ozone had no pulmonary pathology or increased gene expression related to type 2 immunity. These results suggest a new paradigm for the biologic mechanisms underlying the development of a phenotype of childhood nonatopic asthma that has been linked to ambient ozone exposures.

  18. Mechanisms of Cancer Cell Dormancy – Another Hallmark of Cancer?

    Science.gov (United States)

    Yeh, Albert C.; Ramaswamy, Sridhar

    2015-01-01

    Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biological level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biological insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately down-regulate the Ras/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. PMID:26354021

  19. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Rijkee, Laurie K; Skeate, Joseph G; Taylor, Julia R; Koopman, Maaike E; Brand, Heike E; Wong, Michael K; McKee, Greg M; Salazar, Andres M; Kast, W Martin

    2015-12-01

    Human papillomaviruses (HPV) establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC), the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C) is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C), and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8 + T cells in vitro . Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8 + T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection.

  20. Basic study on apoptosis induction into cancer cells U-937 and EL-4 by ultrasound exposure.

    Science.gov (United States)

    Takeuchi, Shinichi; Udagawa, Yoshiko; Oku, Yumiko; Fujii, Takuma; Nishimura, Hiroyuki; Kawashima, Norimichi

    2006-12-22

    Recently, the low invasive cancer treatments with small aftereffects have been considered. We are studying on the suppression methods of cancer cell proliferation with ultrasound. Cancer cells of mouse T lymphoma (EL-4) have been used in our study. The human histitocytic lymphoma cells (U-937) was used in this time. The cancer cells were cultured in a culture medium of RPMI1640. The standing wave acoustic field was formed in a water tank of our ultrasound exposure system by a vibrating plate driven with a Langevine type transducer. The U-937 and EL-4 were exposed to ultrasound in the acoustic field with spatial average acoustic intensity of 350 mW/cm(2) at 150 kHz. The viable rate of EL-4 decreased with the lapse of culture time after ultrasound exposure. U-937 did not show the remarkable decrease tendency. The proliferation of U-937 which exposed to ultrasound with 700 mW/cm(2) was suppressed. It can be thought that apoptosis was induced in the cancer cells in this condition. We observed the morphological change on the U-937 exposed to ultrasound with this condition. The morphological changes by apoptosis like the shrink of cells, formation of apoptotic bodies etc. can be observed with an optical microscope and a phase contrast microscope.

  1. Cell plasticity and heterogeneity in cancer.

    Science.gov (United States)

    Marjanovic, Nemanja D; Weinberg, Robert A; Chaffer, Christine L

    2013-01-01

    Heterogeneity within a given cancer arises from diverse cell types recruited to the tumor and from genetic and/or epigenetic differences amongst the cancer cells themselves. These factors conspire to create a disease with various phenotypes. There are 2 established models of cancer development and progression to metastatic disease. These are the clonal evolution and cancer stem cell models. The clonal evolution theory suggests that successive mutations accumulating in a given cell generate clonal outgrowths that thrive in response to microenvironmental selection pressures, dictating the phenotype of the tumor. The alternative cancer stem cell (CSC) model suggests that cancer cells with similar genetic backgrounds can be hierarchically organized according to their tumorigenic potential. Accordingly, CSCs reside at the apex of the hierarchy and are thought to possess the majority of a cancer's tumor-initiating and metastatic ability. A defining feature of this model is its apparent unidirectional nature, whereby CSCs undergo symmetric division to replenish the CSC pool and irreversible asymmetric division to generate daughter cells (non-CSCs) with low tumorigenic potential. However, evolving evidence supports a new model of tumorigenicity, in which considerable plasticity exists between the non-CSC and CSC compartments, such that non-CSCs can reacquire a CSC phenotype. These findings suggest that some tumors may adhere to a plastic CSC model, in which bidirectional conversions are common and essential components of tumorigenicity. Accumulating evidence surrounding the plasticity of cancer cells, in particular, suggests that aggressive CSCs can be created de novo within a tumor. Given the current focus on therapeutic targeting of CSCs, we discuss the implications of non-CSC-to-CSC conversions on the development of future therapies. © 2012 American Association for Clinical Chemistry

  2. Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances.

    Science.gov (United States)

    Sun, Yu; Liu, Jing

    2014-06-01

    Exosomes are 30- to 100-nm, membrane-bound vesicles that are released by most types of cells, including tumor cells. Exosomes contain a great variety of bioactive molecules, including signal peptides, microRNA, lipids, and DNA. In cancer, tumor cells aberrantly secrete large quantities of exosomes to transport paracrine signals or to contribute to tumor-environment interaction at a distance. The goal of this review was to discuss the recent advances on the mechanism of cancer-derived exosomes in tumor regulation. Pertinent articles and abstracts were identified through searches of PubMed for literature published from 1983 to December 2013. Search terms included exosome, tumor, cancer, diagnosis, and therapy. All of the exposed evidence points to communication between cancer cells and their surroundings, either mediated by cancer cell-derived exosomes or by stromal cell-derived exosomes. This communication probably supports tumor proliferation, motility, invasion, angiogenesis, and premetastatic niche preparation. In addition, recent research implies that cancer cell-derived exosomes play a suppressive role in cancer-directed immune response. The biomarkers detected in bodily fluid-derived exosomes imply a potential for exosomes in cancer diagnosis. Also, exosomes could be used as a vehicle to selectively deliver therapeutic nucleic-acid drugs or conventional drugs for tumor therapy. The tolerability and feasibility of cancer exosomes in diagnosis and therapy need to be further evaluated. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  3. Radiation-Induced Bystander Effects in A549 Cells Exposed to 6 MV X-rays.

    Science.gov (United States)

    Yang, Shuning; Xu, Jing; Shao, Weixian; Geng, Chong; Li, Jia; Guo, Feng; Miao, Hui; Shen, Wenbin; Ye, Tao; Liu, Yazhou; Xu, Haiting; Zhang, Xuguang

    2015-07-01

    The aim of the study is to explore the bystander effects in A549 cells that have been exposed to 6MV X-ray. Control group, irradiated group, irradiated conditioned medium (ICM)-received group, and fresh medium group were designed in this study. A549 cells in the logarithmic growth phase were irradiated with 6MV X-ray at 0, 0.5, 1, 1.5, and 2. In ICM-received group, post-irradiation A549 cells were cultured for 3 h and were transferred into non-irradiated A549 cells for further cultivation. Clone forming test was applied to detect the survival fraction of cells. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of A549 cells 24, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation, and the curves of apoptosis were drawn. The changes in the cell cycles 4, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation were detected using PI staining flow cytometry. With the increase of irradiation dose, the survival fraction of A549 cells after the application of 0.5 Gy irradiation was decreasing continuously. In comparison to the control group, the apoptosis rate of the ICM-received group was increased in a time-dependent pattern, with the highest apoptosis rate observed at 72 h (p X-ray irradiation can induce bystander effect on A549 cells, which reaches a peak at 72 h.

  4. Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium

    International Nuclear Information System (INIS)

    Dakeshita, Satoru; Kawai, Tomoko; Uemura, Hirokazu; Hiyoshi, Mineyoshi; Oguma, Etsuko; Horiguchi, Hyogo; Kayama, Fujio; Aoshima, Keiko; Shirahama, Satoshi; Rokutan, Kazuhito; Arisawa, Kokichi

    2009-01-01

    The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells, using an original oligoDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a non-Cd-polluted area individually matched for age (control group). The mRNA levels in Cd-exposed subjects were compared with those in respective controls, using a microarray containing oligoDNA probes for 1867 genes. Median Cd concentrations in blood (3.55 μg/l) and urine (8.25 μg/g creatinine) from the Cd-exposed group were 2.4- and 1.9-times higher than those of the control group, respectively. Microarray analysis revealed that the Cd-exposed group significantly up-regulated 137 genes and down-regulated 80 genes, compared with the control group. The Ingenuity Pathway Analysis Application (IPA) revealed that differentially expressed genes were likely to modify oxidative stress and mitochondria-dependent apoptosis pathways. Among differentially expressed genes, the expression of five genes was positively correlated with Cd concentrations in blood or urine. Quantitative real-time PCR (RT-PCR) analysis validated the significant up-regulation of CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4 and ITGAL, and down-regulation of BCL2A1 and COX7B. After adjustment for differences in the background characteristics of the two groups, we finally identified seven Cd-responsive genes (CASP9, TNFRSF1B, GPX3, SLC3A2, ITGAL, BCL2A1, and COX7B), all of which constituted a network that controls oxidative stress response by IPA. These seven genes may be marker genes useful for the health risk assessment of chronic low level exposure to Cd

  5. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

    Skakkebaek, N E; Rajpert-De Meyts, E; Jørgensen, N

    1998-01-01

    , including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress...... in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which...

  6. Cells exposed to nanosecond electrical pulses exhibit biomarkers of mechanical stress

    Science.gov (United States)

    Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Moen, Erick K.; Glickman, Randolph D.

    2015-03-01

    Exposure of cells to very short (stressors on a cell, including electrical, electro-chemical, and mechanical stress. Thus, nsEP exposure is not a "clean" insult, making determination of the mechanism of nanoporation quite difficult. We hypothesize that nsEP exposure creates acoustic shock waves capable of causing nanoporation. Microarray analysis of primary adult human dermal fibroblasts (HDFa) exposed to nsEP, indicated several genes associated with mechanical stress were selectively upregulated 4 h post exposure. The idea that nanoporation is caused by external mechanical force from acoustic shock waves has, to our knowledge, not been investigated. This work will critically challenge the existing paradigm that nanoporation is caused solely by an electric-field driven event and could provide the basis for a plausible explanation for electroporation.

  7. Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects

    International Nuclear Information System (INIS)

    McHale, Cliona M.; Zhang, Luoping; Hubbard, Alan E.; Zhao, Xin; Baccarelli, Andrea; Pesatori, Angela C.; Smith, Martyn T.; Landi, Maria Teresa

    2007-01-01

    Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen and exerts toxic effects on the skin (chloracne). Effects on reproductive, immunological, and endocrine systems have also been observed in animal models. TCDD acts through the aryl hydrocarbon receptor (AhR) pathway influencing largely unknown gene networks. An industrial accident in Seveso, Italy in 1976 exposed thousands of people to substantial quantities of TCDD. Twenty years after the exposure, this study examines global gene expression in the mononuclear cells of 26 Seveso female never smokers, with similar age, alcohol consumption, use of medications, and background plasma levels of 22 dioxin congeners unrelated to the Seveso accident. Plasma dioxin levels were still elevated in the exposed subjects. We performed analyses in two different comparison groups. The first included high-exposed study subjects compared with individuals with background TCDD levels (average plasma levels 99.4 and 6.7 ppt, respectively); the second compared subjects who developed chloracne after the accident, and those who did not develop this disease. Overall, we observed a modest alteration of gene expression based on dioxin levels or on chloracne status. In the comparison between high levels and background levels of TCDD, four histone genes were up-regulated and modified expression of HIST1H3H was confirmed by real-time PCR. In the comparison between chloracne case-control subjects, five hemoglobin genes were up-regulated. Pathway analysis revealed two major networks for each comparison, involving cell proliferation, apoptosis, immunological and hematological disease, and other pathways. Further examination of the role of these genes in dioxin induced-toxicity is warranted

  8. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra

    2015-01-01

    Full Text Available The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed.

  9. Cancer cell metabolism: one hallmark, many faces.

    Science.gov (United States)

    Cantor, Jason R; Sabatini, David M

    2012-10-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

  10. Genotoxic Changes to Rodent Cells Exposed in Vitro to Tungsten, Nickel, Cobalt and Iron

    Directory of Open Access Journals (Sweden)

    Stephanie Bardack

    2014-03-01

    Full Text Available Tungsten-based materials have been proposed as replacements for depleted uranium in armor-penetrating munitions and for lead in small-arms ammunition. A recent report demonstrated that a military-grade composition of tungsten, nickel, and cobalt induced a highly-aggressive, metastatic rhabdomyosarcoma when implanted into the leg muscle of laboratory rats to simulate a shrapnel wound. The early genetic changes occurring in response to embedded metal fragments are not known. In this study, we utilized two cultured rodent myoblast cell lines, exposed to soluble tungsten alloys and the individual metals comprising the alloys, to study the genotoxic effects. By profiling cell transcriptomes using microarray, we found slight, yet distinct and unique, gene expression changes in rat myoblast cells after 24 h metal exposure, and several genes were identified that correlate with impending adverse consequences of ongoing exposure to weapons-grade tungsten alloy. These changes were not as apparent in the mouse myoblast cell line. This indicates a potential species difference in the cellular response to tungsten alloy, a hypothesis supported by current findings with in vivo model systems. Studies examining genotoxic-associated gene expression changes in cells from longer exposure times are warranted.

  11. Differential induction of micronuclei in peripheral lymphocytes and exfoliated urothelial cells of workers exposed to 4,4'-methylenebis-(2-chloroaniline) (MOCA) and bitumen fumes.

    Science.gov (United States)

    Murray, E B; Edwards, J W

    2005-01-01

    Cytogenetic end-points used to estimate risk of genotoxic events in workers include the measurement of micronuclei (MN) in exfoliated cells, lymphocytes, and other tissues. Micronuclei are chromatin-containing bodies outside the cell nucleus resulting from contaminant-induced DNA damage. A review of 71 reports of human genotoxic responses to chemical or physical agents published between 1999 and 2001 revealed that 14% of such studies measured genotoxicity endpoints in specific target tissues relevant to the site of disease for the agent examined; 18% used endpoints in surrogate or non-target tissues but considered the relations between endpoints in surrogate and disease target tissues, and 68% measured genotoxicity endpoints in accessible tissues without reference to specific targets for disease. Methylenebis-(2-chloroaniline) (MOCA), used in polyurethane manufacture, is a suspected bladder carcinogen. Bitumen, used in road surfacing, contains skin and lung carcinogens. In this study, we aimed to compare genotoxicity in urothelial cells and in lymphocytes of workers exposed to these materials. Twelve men employed in polyurethane manufacture, twelve bitumen road layers, and eighteen hospital stores personnel (controls) were recruited and all provided blood and urine samples on the same day. Blood cultures were prepared using a cytochalasin B-block method. Exfoliated urothelial cells were collected from urine and stained for light microscopy. The number of MN in urothelial cells was higher in MOCA-exposed (14.27 +/- 0.56 MN/1000, 9.69 +/- 0.32 MN cells/1000) than in bitumen exposed workers (11.99 +/- 0.65 MN/1000, 8.66 +/- 0.46 MN cells/1000) or in control subjects (6.88 +/- 0.18 MN/1000, 5.17 +/- 0.11 MN cells/1000). Conversely, in lymphocytes, MN were higher in bitumen-exposed (16.24 +/- 0.63 MN/1000, 10.65 +/- 0.24 MN cells/1000) than in MOCA-exposed workers (13.25 +/- 0.48 MN/1000, 8.54 +/- 0.14 MN cells/1000) or in control subjects (9.24 +/- 0.29 MN/ 1000, 5

  12. PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide.

    Directory of Open Access Journals (Sweden)

    Akhilendra Kumar Maurya

    Full Text Available Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2 in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton's lymphoma ascite (DLA cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308, cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism.

  13. Cancer stem cells and chemoradiation resistance

    International Nuclear Information System (INIS)

    Ishii, Hideshi; Mori, Masaki; Iwatsuki, Masaaki; Ieta, Keisuke; Ohta, Daisuke; Haraguchi, Naotsugu; Mimori, Koshi

    2008-01-01

    Cancer is a disease of genetic and epigenetic alterations, which are emphasized as the central mechanisms of tumor progression in the multistepwise model. Discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. The heterogeneity of tumors can be explained with the help of CSCs supported by antiapoptotic signaling. CSCs mimic normal adult stem cells by demonstrating resistance to toxic injuries and chemoradiation therapy. Moreover, they might be responsible for tumor relapse following apparent beneficial treatments. Compared with hematopoietic malignancies, conventional therapy regimes in solid tumors have improved the overall survival marginally, illustrating the profound impact of treatment resistance. This implies that the present therapies, which follow total elimination of rapidly dividing and differentiated tumor cells, need to be modified to target CSCs that repopulate the tumor. In this review article, we report on recent findings regarding the involvement of CSCs in chemoradiation resistance and provide new insights into their therapeutic implications in cancer. (author)

  14. Proteomics in studying cancer stem cell biology.

    Science.gov (United States)

    Kranenburg, Onno; Emmink, Benjamin L; Knol, Jaco; van Houdt, Winan J; Rinkes, Inne H M Borel; Jimenez, Connie R

    2012-06-01

    Normal multipotent tissue stem cells (SCs) are the driving force behind tissue turnover and repair. The cancer stem cell theory holds that tumors also contain stem-like cells that drive tumor growth and metastasis formation. However, very little is known about the regulation of SC maintenance pathways in cancer and how these are affected by cancer-specific genetic alterations and by treatment. Proteomics is emerging as a powerful tool to identify the signaling complexes and pathways that control multi- and pluri-potency and SC differentiation. Here, the authors review the novel insights that these studies have provided and present a comprehensive strategy for the use of proteomics in studying cancer SC biology.

  15. Cancer stem cells: a metastasizing menace!

    International Nuclear Information System (INIS)

    Bandhavkar, Saurabh

    2016-01-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy

  16. Identification of Human Cutaneous Basal Cell Carcinoma Cancer Stem Cells.

    Science.gov (United States)

    Morgan, Huw; Olivero, Carlotta; Patel, Girish K

    2018-04-20

    The cancer stem cell model states that a subset of tumor cells, called "cancer stem cells," can initiate and propagate tumor growth through self-renewal, high proliferative capacity, and their ability to recreate tumor heterogeneity. In basal cell carcinoma (BCC), we have shown that tumor cells that express the cell surface protein CD200 fulfill the cancer stem cell hypothesis. CD200+ CD45- BCC cells represent 0.05-3.96% of all BCC cells and reside in small clusters at the tumor periphery. Using a novel, reproducible in vivo xenograft growth assay, we determined that tumor-initiating cell (TIC) frequencies are approximately 1 per 1.5 million unsorted BCC cells. The CD200+ CD45- BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200+ CD45- cells, representing ~1500-fold enrichment. The methods used to identify and purify CD200+ CD45- BCC cells, as well as characterize gene expression, are described herein.

  17. Induction of cancer stem cell properties in colon cancer cells by defined factors.

    Directory of Open Access Journals (Sweden)

    Nobu Oshima

    Full Text Available Cancer stem cells (CSCs are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4 into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs. Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

  18. Cancer-associated cleavage of cytokeratin 8/18 heterotypic complexes exposes a neoepitope in human adenocarcinomas

    DEFF Research Database (Denmark)

    Ditzel, Henrik; Strik, Merel C M; Larsen, Morten K

    2002-01-01

    distribution of truncated K8/K18 heterotypic complexes in viable adenocarcinomas cells was probed using COU-1 showing small fibrillar structures distinct from those of intact K8/K18 complexes. Previously we demonstrated the binding and subsequent internalization of recombinant Fab COU-1 to live cancer cells...

  19. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

    2013-01-01

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  20. Two cases of acute leukemia in heavily exposed a-bomb survivors following radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Mikami, Motoko; Kuramoto, Atsushi; Kamada, Nanao; Ohkita, Takeshi; Sawada, Hisao.

    1980-03-01

    Two cases of acute leukemia in heavily exposed atomic bomb survivors following postoperative 60 Co radiotherapy for breast cancer are presented. Case 1, a female who received an estimated dose of 364 rad from the A-bomb at the age of 22, was diagnosed as having left breast cancer 17 years later. At the age of 48, about 8 years after undergoing postoperative 60 Co radiotherapy, she developed acute monocytic leukemia. Case 2, a female who received an estimated dose of 594 rad from the A-bomb at the age of 37, was diagnosed as having right breast cancer 22 years later. At the age of 63, 4 years after postoperative 60 Co radiotherapy, she was found to have acute erythroleukemia. Both cases had been exposed to the A-bomb in Hiroshima and to therapeutic radiation after developing breast cancer presumably induced by A-bomb exposure. Thus it is proposed that acute leukemia was induced by exposure to large doses of radiation from two sources. (author)

  1. CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells.

    Science.gov (United States)

    Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

    2016-01-01

    Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, chemo-resistance property and in vivo tumor formation abilities were detected. A549 CD24- cells formed smaller colonies, slower proliferated in comparison to A549 CD24+ cells. Besides, A549 CD24- exhibited stronger resistance to chemotherapy drug. However, A549 CD24- didn't exert any stronger tumor formation ability in vivo, which is the gold standard of CSCs. These results showed that CD24- A549 cells showed some properties of CSCs but not actually CSCs. This study provides evidence that CD24 cannot be considered as lung CSCs marker.

  2. The CEA−/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells

    Science.gov (United States)

    Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

    2016-01-01

    Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA−/lo) levels of CEA. Our findings show that the abundance of CEA−/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA−/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA−/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA−/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA−/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA−/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies. PMID:27813496

  3. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  4. Cancer Stem Cells: From Identification To Eradication

    International Nuclear Information System (INIS)

    KASSEM, N.M.

    2008-01-01

    A fundamental problem in cancer research is identification of the cells within a tumor that sustain the growth of the neoplastic clone. The concept that only a subpopulation of rare cancer stem cells (CSCs) is responsible for maintenance of the neoplasm emerged nearly 50 years ago: however, conclusive proof for the existence of a CSC was obtained only relatively recently. As definition, cancer stem cells (CSCs) are a sub-population of cancer cells (found within solid tumors or hematological malignancies) that possess characteristics normally associated with stem cells as high self-renewal potential. These cells are believed to be tumorige forming) in contrast to the bulk of cancer cells, which are thought to be non-tumorigenic. The first conclusive evidence for CSCs was published in 1997 in Nature Medicine by Bonnet and Dick who isolated a subpopulation of leukemic cells in AML that express a specific surface marker CD34 but lacks the CD38 marker. The authors established that the CD34+/CD38– subpopulation is capable of initiating leukemia in NOD/SCID mice that is histologically similar to the donor [1]. This subpopulation of cells is termed SCID Leukemia-initiating cells (SLIC). A theory suggests that such cells act as a reservoir for disease recurrence, are the origin of metastasis and exert resistance towards classical antitumor regimens. This resistance was attributed to a combination of several factors [2], suggesting that conventional antitumor regimens are targeting the bulk of the tumor not the dormant stubborn CSCs. Purpose Better understanding of the leukemogenic process and the biology of CSCS to define the most applicable procedures for their identification and isolation in order to design specific targeted therapies aiming at reducing disease burden to very low levels .. up to eradication of the tumor

  5. Stem Cell Transplants in Cancer Treatment

    Science.gov (United States)

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  6. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and ... The morphology of the HepG2 cell nucleus was investigated by Hoechst 33342, ..... Gong F, Liang Y, Xie P, Chau F. Information theory.

  7. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  8. Phenotype heterogeneity in cancer cell populations

    International Nuclear Information System (INIS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-01-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  9. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  10. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  11. Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy

    DEFF Research Database (Denmark)

    Holmstrøm, Kim; Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg

    2010-01-01

    Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-polarizing differentiation signals have paved the way for the development of DC-based cancer vaccines. Critical parameters for assessment of the optimal functional state of DCs and prediction of the vaccine potency o...

  12. Common Effects on Follicular Thyroid Cancer Cells Exerted by Simulated Microgravity

    DEFF Research Database (Denmark)

    Svejgaard, Benjamin; Grimm, Daniela; Corydon, Thomas Juhl

    2015-01-01

    This study focuses on gravity-sensitive proteins of two human follicular cancer cell lines (ML-1; RO82-W-1), which were exposed to simulated microgravity (s-μg) on two different machines. Changes in protein cytoskeletal structure, growth patterns and protein expression in response to s-μg were...

  13. IL-4-mediated drug resistance in colon cancer stem cells

    NARCIS (Netherlands)

    Todaro, Matilde; Perez Alea, Mileidys; Scopelliti, Alessandro; Medema, Jan Paul; Stassi, Giorgio

    2008-01-01

    Cancer stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Cancer stem cells are thus likely to be responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The CD133 glycoprotein was recently

  14. Global gene expression profiling in human lung cells exposed to cobalt

    Energy Technology Data Exchange (ETDEWEB)

    Malard, V.; Berenguer, F.; Prat, O.; Ruat, S.; Steinmetz, G.; Quemeneur, E. [CEA VALRHO, Serv Biochim and Toxicol Nucl, DSV, iBEB, F-30207 Bagnols Sur Ceze (France)

    2007-06-06

    It has been estimated that more than 1 million workers in the United States are exposed to cobalt. Occupational exposure to {sup 59}Co occurs mainly via inhalation and leads to various lung diseases. Cobalt is classified by the IARC as a possible human carcinogen (group 2B). Although there is evidence for in vivo and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not fully known. The purpose of this work was to identify potential signatures of acute cobalt exposure using a toxico-genomic approach. Data analysis focused on some cellular processes and protein targets that are thought to be relevant for carcinogenesis, transport and bio-marker research. Results: A time course transcriptome analysis was performed on A549 human pulmonary cells, leading to the identification of 85 genes which are repressed or induced in response to soluble 59 Co. A group of 29 of these genes, representing the main biological functions, was assessed by quantitative RT-PCR. The expression profiles of six of them were then tested by quantitative RT-PCR in a time-dependent manner and three modulations were confirmed by Western blotting. The 85 modulated genes include potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress response (UBC, HSPCB, BN1P3L). We also identified nine genes coding for secreted proteins as candidates for bio-marker research. Of those, T1MP2 was found to be down-regulated and this modulation was confirmed, in a dose-dependent manner, at protein level in the supernatant of exposed cells. Conclusion: Most of these genes have never been described as related to cobalt stress and provide original hypotheses for further study of the effects of this metal ion on human lung epithelial cells. A putative bio-marker of cobalt toxicity was identified. (authors)

  15. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

    International Nuclear Information System (INIS)

    Ihlaseh-Catalano, Shadia M.; Bailey, Kathryn A.; Cardoso, Ana Paula F.; Ren, Hongzu; Fry, Rebecca C.; Camargo, João Lauro V.de; Wolf, Douglas C.

    2014-01-01

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

  16. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron.

    Science.gov (United States)

    Ihlaseh-Catalano, Shadia M; Bailey, Kathryn A; Cardoso, Ana Paula F; Ren, Hongzu; Fry, Rebecca C; de Camargo, João Lauro V; Wolf, Douglas C

    2014-11-05

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

    Science.gov (United States)

    Osorio-Yáñez, Citlalli; Chin-Chan, Miguel; Sánchez-Peña, Luz C; Atzatzi-Aguilar, Octavio G; Olivares-Reyes, Jesus A; Segovia, José; Del Razo, Luz M

    2017-08-01

    Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5μM of arsenite for 24h. We proved that arsenite at 5μM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5μM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5μM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1

    OpenAIRE

    Harrison, Luke R.E.; Micha, Dimitra; Brandenburg, Martin; Simpson, Kathryn L.; Morrow, Christopher J.; Denneny, Olive; Hodgkinson, Cassandra; Yunus, Zaira; Dempsey, Clare; Roberts, Darren; Blackhall, Fiona; Makin, Guy; Dive, Caroline

    2011-01-01

    Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic indu...

  19. Syncytin is involved in breast cancer-endothelial cell fusions

    DEFF Research Database (Denmark)

    Bjerregaard, Bolette; Holck, S.; Christensen, I.J.

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  20. Aryl hydrocarbon receptor expression is associated with a family history of upper gastrointestinal tract cancer in a high-risk population exposed to aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Roth, M.J.; Wei, W.Q.; Baer, J.; Abnet, C.C.; Wang, G.Q.; Sternberg, L.R.; Warner, A.C.; Johnson, L.L.; Lu, N.; Giffen, C.A.; Dawsey, S.M.; Qiao, Y.L.; Cherry, J. [NCI, Bethesda, MD (United States)

    2009-09-15

    Polycyclic aromatic hydrocarbon (PAH) exposure is a risk factor for esophageal squamous cell carcinoma, and PAHs are ligands of the aryl hydrocarbon receptor (AhR). This study measured the expression of AhR and related genes in frozen esophageal cell samples from patients exposed to different levels of indoor air pollution, who did or did not have high-grade squamous dysplasia and who did or did not have a family history of upper gastrointestinal tract (UGI) cancer. 147 samples were evaluated, including 23 (16%) from patients with high-grade dysplasia and 48 (33%) from patients without dysplasia who heated their homes with coal, without a chimney (a 'high' indoor air pollution group), and 27 (18%) from patients with high-grade dysplasia and 49 (33%) from patients without dysplasia who did not heat their homes at all (a 'low' indoor air pollution group). Sixty-four (44%) had a family history of UGI cancer. RNA was extracted and quantitative PCR analysis was done. AhR gene expression was detectable in 85 (58%) of the samples and was >9-fold higher in those with a family history of UGI cancer (median expression (interquartile range), -1,964 (-18,000, -610) versus -18,000 (-18,000, -1036); P = 0.02, Wilcoxon rank-sum test). Heating status, dysplasia category, age, gender, and smoking were not associated with AhR expression (linear regression; all P values {ge} 0.1). AhR expression was higher in patients with a family history of UGI cancer. Such individuals may be more susceptible to the deleterious effects of PAH exposure, including PAH-induced cancer.

  1. The Bioeffects Resulting from Prokaryotic Cells and Yeast Being Exposed to an 18 GHz Electromagnetic Field.

    Directory of Open Access Journals (Sweden)

    The Hong Phong Nguyen

    Full Text Available The mechanisms by which various biological effects are triggered by exposure to an electromagnetic field are not fully understood and have been the subject of debate. Here, the effects of exposing typical representatives of the major microbial taxa to an 18 GHz microwave electromagnetic field (EMFwere studied. It appeared that the EMF exposure induced cell permeabilisation in all of the bacteria and yeast studied, while the cells remained viable (94% throughout the exposure, independent of the differences in cell membrane fatty acid and phospholipid composition. The resulting cell permeabilisation was confirmed by detection of the uptake of propidium iodine and 23 nm fluorescent silica nanospheres using transmission electron microscopy (TEM and confocal laser scanning microscopy (CLSM. Upon EMF exposure, the bacterial cell membranes are believed to become permeable through quasi-endocytosis processes. The dosimetry analysis revealed that the EMF threshold level required to induce the uptake of the large (46 nm nanopsheres was between three and six EMF doses, with a specific absorption rate (SAR of 3 kW/kg and 5 kW/kg per exposure, respectively, depending on the bacterial taxa being studied. It is suggested that the taxonomic affiliation and lipid composition (e.g. the presence of phosphatidyl-glycerol and/or pentadecanoic fatty acid may affect the extent of uptake of the large nanospheres (46 nm. Multiple 18 GHz EMF exposures over a one-hour period induced periodic anomalous increases in the cell growth behavior of two Staphylococcus aureus strains, namely ATCC 25923 and CIP 65.8T.

  2. Mechanisms of therapeutic resistance in cancer (stem cells with emphasis on thyroid cancer cells.

    Directory of Open Access Journals (Sweden)

    Sabine eHombach-Klonisch

    2014-03-01

    Full Text Available Tissue invasion, metastasis and therapeutic resistance to anti-cancer treatments are common and main causes of death in cancer patients. Tumor cells mount complex and still poorly understood molecular defense mechanisms to counteract and evade oxygen deprivation, nutritional restrictions as well as radio- and chemotherapeutic treatment regimens aimed at destabilizing their genomes and important cellular processes. In thyroid cancer, as in other tumors, such defense strategies include the reactivation in cancer cells of early developmental programs normally active exclusively in stem cells, the stimulation of cancer stem-like cells resident within the tumor tissue and the recruitment of bone marrow-derived progenitors into the tumor (Thomas et al., 2008;Klonisch et al., 2009;Derwahl, 2011. Metastasis and therapeutic resistance in cancer (stem cells involves the epithelial-to-mesenchymal transition- (EMT- mediated enhancement in cellular plasticity, which includes coordinated dynamic biochemical and nuclear changes (Ahmed et al., 2010. The purpose of the present review is to provide an overview of the role of DNA repair mechanisms contributing to therapeutic resistance in thyroid cancer and highlight the emerging roles of autophagy and damage associated molecular pattern (DAMP responses in EMT and chemoresistance in tumor cells. Finally, we use the stem cell factor and nucleoprotein High Mobility Group A2 (HMGA2 as an example to demonstrate how factors intended to protect stem cells are wielded by cancer (stem cells to gain increased transformative cell plasticity which enhances metastasis, therapeutic resistance and cell survival. Wherever possible, we have included information on these cellular processes and associated factors as they relate to thyroid cancer cells.

  3. Measurement of Lung Cancer Tumor Markers in a Glass Wool Company Workers Exposed to Respirable Synthetic Vitreous Fiber and Dust

    Directory of Open Access Journals (Sweden)

    Shabnam Abtahi

    2018-01-01

    Full Text Available Background: Occupational exposures to respirable synthetic vitreous fiber (SVF and dust are associated with many lung diseases including lung cancer. Low-dose computed tomography is used for screening patients who are highly suspicious of having lung carcinoma. However, it seems not to be cost-effective. Serum biomarkers could be a useful tool for the surveillance of occupational exposure, by providing the possibility of diagnosing lung cancer in its early stages. Objective: To determine if serum carcinoembryonic antigen (CEA and cytokeratin fragment (CYFRA 21-1 levels in workers exposed more than normal population to respirable SVF and dust may be used as indicators of progression towards lung cancer. Methods: An analytic cross-sectional study, including 145 personnel of a glass wool company, along with 25 age-matched healthy individuals, was conducted to investigate the relationship between occupational exposure to respirable SVFs and dust and serum levels of two lung/pleura serum tumor markers, CEA and CYFRA 21-1, measured by ELISA. Results: Individuals exposed to higher than the recommended levels of respirable SVF had higher serum concentrations of CEA and CYFRA 21-1, compared to controls (p=0.008 and 0.040, respectively, as well as in comparison to those exposed to lower than recommended OSHA levels (p=0.046 and 0.033, respectively. Workers with >9 years work experience, had significantly (p=0.045 higher levels of serum CYFRA 21-1 than those with ≤9 years of experience. Conclusion: It seems that working for >9 years in sites with detectable levels of respirable SVF and dust would increase the levels of known lung cancer serum tumor markers. Transferring these workers to sites with respirable SVF concentrations lower than the limit of detection in the air is recommended.

  4. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  5. Haemostatis activity in rectal cancer patients exposed to preoperative radiotherapy: a clinical prospective cohort study

    DEFF Research Database (Denmark)

    Stender, Mogens T; Larsen, Torben B; Lundbye-Christensen, Søren

    2009-01-01

    To investigate whether markers of haemostasis activity increased during preoperative radiotherapy and whether postoperative marker levels were increased in irradiated rectal cancer patients when compared with nonirradiated rectal and colon cancer patients. In 45 rectal cancer patients, we measured...... plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex, and D-dimer during radiotherapy. Postoperative levels of F1 + 2, thrombin-antithrombin complex, and D-dimer in irradiated patients were compared with postoperative levels in 123 nonirradiated colon and rectal cancer...... for activation of the haemostatic system during preoperative radiotherapy in patients with rectal cancer. Some evidence was provided for increased postoperative haemostatic activity among rectal cancer patients who received short-term high-intensity radiotherapy, when compared with patients who received long...

  6. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators

    International Nuclear Information System (INIS)

    Orona, N.S.; Tasat, D.R.

    2012-01-01

    Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO 3 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO 3 . We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O 2 − ). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O 2 − may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O 2 − may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through all the range of doses tested.

  7. Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Ulsh, B.A.; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R.

    2004-01-01

    In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60 Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment

  8. Cellular radiosensitivity of small-cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Krarup, M; Poulsen, H S; Spang-Thomsen, M

    1997-01-01

    PURPOSE: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based...

  9. Micromagnetic Cancer Cell Immobilization and Release for Real-Time Single Cell Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jaiswal, Devina; Rad, Armin Tahmasbi [Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269 (United States); Nieh, Mu-Ping [Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269 (United States); Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269 (United States); Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT 06269 (United States); Claffey, Kevin P. [Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 (United States); Hoshino, Kazunori, E-mail: hoshino@engr.uconn.edu [Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269 (United States)

    2017-04-01

    Understanding the interaction of live cells with macromolecules is crucial for designing efficient therapies. Considering the functional heterogeneity found in cancer cells, real-time single cell analysis is necessary to characterize responses. In this study, we have designed and fabricated a microfluidic channel with patterned micromagnets which can temporarily immobilize the cells during analysis and release them after measurements. The microchannel is composed of plain coverslip top and bottom panels to facilitate easy microscopic observation and undisturbed application of analytes to the cells. Cells labeled with functionalized magnetic beads were immobilized in the device with an efficiency of 90.8±3.6%. Since the micromagnets are made of soft magnetic material (Ni), they released cells when external magnetic field was turned off from the channel. This allows the reuse of the channel for a new sample. As a model drug analysis, the immobilized breast cancer cells (MCF7) were exposed to fluorescent lipid nanoparticles and association and dissociation were measured through fluorescence analysis. Two concentrations of nanoparticles, 0.06 µg/ml and 0.08 µg/ml were tested and time lapse images were recorded and analyzed. The microfluidic device was able to provide a microenvironment for sample analysis, making it an efficient platform for real-time analysis.

  10. Gastric cancer stem cells: A novel therapeutic target

    Science.gov (United States)

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  11. Cellular processes involved in human epidermal cells exposed to extremely low frequency electric fields.

    Science.gov (United States)

    Collard, J-F; Hinsenkamp, M

    2015-05-01

    We observed on different tissues and organisms a biological response after exposure to pulsed low frequency and low amplitude electric or electromagnetic fields but the precise mechanism of cell response remains unknown. The aim of this publication is to understand, using bioinformatics, the biological relevance of processes involved in the modification of gene expression. The list of genes analyzed was obtained after microarray protocol realized on cultures of human epidermal explants growing on deepidermized human skin exposed to a pulsed low frequency electric field. The directed acyclic graph on a WebGestalt Gene Ontology module shows six categories under the biological process root: "biological regulation", "cellular process", "cell proliferation", "death", "metabolic process" and "response to stimulus". Enriched derived categories are coherent with the type of in vitro culture, the stimulation protocol or with the previous results showing a decrease of cell proliferation and an increase of differentiation. The Kegg module on WebGestalt has highlighted "cell cycle" and "p53 signaling pathway" as significantly involved. The Kegg website brings out interactions between FoxO, MAPK, JNK, p53, p38, PI3K/Akt, Wnt, mTor or NF-KappaB. Some genes expressed by the stimulation are known to have an exclusive function on these pathways. Analyses performed with Pathway Studio linked cell proliferation, cell differentiation, apoptosis, cell cycle, mitosis, cell death etc. with our microarrays results. Medline citation generated by the software and the fold change variation confirms a diminution of the proliferation, activation of the differentiation and a less well-defined role of apoptosis or wound healing. Wnt and DKK functional classes, DKK1, MACF1, ATF3, MME, TXNRD1, and BMP-2 genes proposed in previous publications after a manual analysis are also highlighted with other genes after Pathway Studio automatic procedure. Finally, an analysis conducted on a list of genes

  12. Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

    National Research Council Canada - National Science Library

    Navone, Nora

    2001-01-01

    .... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

  13. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  14. Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells.

    Science.gov (United States)

    Lo Re, Oriana; Panebianco, Concetta; Porto, Stefania; Cervi, Carlo; Rappa, Francesca; Di Biase, Stefano; Caraglia, Michele; Pazienza, Valerio; Vinciguerra, Manlio

    2018-02-01

    Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use. © 2017 Wiley Periodicals, Inc.

  15. Immunotropic potency of microwave fields: preliminary studies on immunocompetent cells exposed in vitro

    International Nuclear Information System (INIS)

    Stankiewicz, W.; Dabrowski, M.P.; Sobiczewska, E.; Kubacki, R.; Szmigielski, S.

    2006-01-01

    Exposure in radiofrequency (RF) and microwave (MW) fields can influence the function of the immune system, but the data available on the immunotropic potency of RF/MW radiation are still full of uncertainties and controversies. In the available literature there exist no reports on complex assessment of function and responsiveness of the immune system. All investigations have been aimed to evaluate selected, fragmentary reaction of the system and/or functional response of immunocompetent cells in RF/MW-exposed subjects. However, at the present state of knowledge it is not possible to conclude about the possible immunotropic potencies of RF/MW radiation. The undisturbed defensive, tolerogenic, and proregenerative activities of the immune system are commonly recognised as one of the most important homeostatic functions of the organism. Thus, basic immunoregulatory activities which can be observed and precisely quantified in microcultures of immune cells separated from the human blood, represent a unique and objective model for the investigation of possible immunotropic effects of electromagnetic fields (EMFs). To determine the potential immunomodulatory influences of EMFs, the immunotropic effects of pulse modulated microwave (1300 MHz) were investigated in the cultures of blood mononuclear cells from sixteen healthy donors

  16. Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles.

    Science.gov (United States)

    Pongrac, Igor M; Pavičić, Ivan; Milić, Mirta; Brkić Ahmed, Lada; Babič, Michal; Horák, Daniel; Vinković Vrček, Ivana; Gajović, Srećko

    2016-01-01

    Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs) are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs - uncoated, coated with d-mannose, or coated with poly-l-lysine - affects biocompatibility. We sought to investigate murine neural stem cells (NSCs) as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions presented in this work highlights the need for further safety evaluations. This investigation helps to fill the knowledge gaps on the criteria that should be considered in evaluating the biocompatibility and safety of novel nanoparticles.

  17. Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to fluoride

    International Nuclear Information System (INIS)

    Chen Jia; Shan, K.-R.; Long, Y.-G.; Wang, Y.-N.; Nordberg, Agneta; Guan, Z.-Z.

    2003-01-01

    In an attempt to elucidate the mechanism by which excessive fluoride damages the central nervous system, the effects of exposure of PC12 cells to different concentrations of fluoride for 48 h on nicotinic acetylcholine receptors (nAChRs) were characterized here. Significant reductions in the number of binding sites for both [ 3 H]epibatidine and [ 125 I]α-bungarotoxin, as well as a significant decrease in the B max value for the high-affinity of epibatidine binding site were observed in PC12 cells subjected to high levels of fluoride. On the protein level, the α3 and α7 subunits of nAChRs were also significantly decreased in the cells exposed to high concentrations of fluoride. In contrast, such exposure had no significant effect on the level of the β2 subunit. These findings suggest that selective decreases in the number of nAChRs may play an important role in the mechanism(s) by which fluoride causes dysfunction of the central nervous system

  18. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

    Science.gov (United States)

    Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing

    2015-01-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-NG-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. PMID:25431453

  19. DNA damage and the bystander response in tumor and normal cells exposed to X-rays.

    Science.gov (United States)

    Subhashree, M; Venkateswarlu, R; Karthik, K; Shangamithra, V; Venkatachalam, P

    2017-09-01

    Monolayer and suspension cultures of tumor (BMG-1, CCRF-CEM), normal (AG1522, HADF, lymphocytes) and ATM-mutant (GM4405) human cells were exposed to X-rays at doses used in radiotherapy (high dose and high dose-rate) or radiological imaging (low dose and low dose-rate). Radiation-induced DNA damage, its persistence, and possible bystander effects were evaluated, based on DNA damage markers (γ-H2AX, p53 ser15 ) and cell-cycle-specific cyclins (cyclin B1 and cyclin D1). Dose-dependent DNA damage and a dose-independent bystander response were seen after exposure to high dose and high dose-rate radiation. The level of induced damage (expression of p53 ser15 , γ-H2AX) depended on ATM status. However, low dose and dose-rate exposures neither increased expression of marker proteins nor induced a bystander response, except in the CCRF-CEM cells. Bystander effects after high-dose irradiation may contribute to stochastic and deterministic effects. Precautions to protect unexposed regions or to inhibit transmission of DNA damage signaling might reduce radiation risks. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Expression profile of cell cycle genes in the fish CATLA CATLA (Ham.) exposed to gamma radiation

    International Nuclear Information System (INIS)

    Anbumani, S.; Mohankumar Mary, N.

    2012-01-01

    The International Commission on Radiological Protection (ICRP) emphasized the need to protect non-human biota from the potential effects of ionizing radiation and proposed to include molecular effects such as DNA damage as endpoints. Molecular effects of ionizing radiation exposure in representative non-humans are largely unexplored and sufficient data is not available in fishes. Gene expression is a fast and sensitive end point in detecting the molecular cues as a result of ionizing radiation exposure in a wide variety of aquatic organisms under suspected environmental contamination. Exposure to ionizing radiation transiently alters gene expression profiles as cells regulate certain genes to protect cellular structures and repair damage. The present study focused on genes like Gadd45á, Cdk1 and Bcl-2 in DNA damage repair and cell cycle machinery and its implication as molecular markers of radiation exposure. This study is first of its kind showing the in vivo expression profile of cell cycle genes in fish exposed to gamma radiation. Although this preliminary investigation points to certain molecular markers of ionizing radiation, elaborate studies with various doses and dose-rates are required before these markers find application as prospective molecular markers in aquatic radiation biodosimetry

  1. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  2. Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms.

    Science.gov (United States)

    Kanwar, Jagat R; Samarasinghe, Rasika M; Kamalapuram, Sishir K; Kanwar, Rupinder K

    2017-01-01

    Increasing evidence suggests that stem cells, a small population of cells with unique selfrenewable and tumour regenerative capacity, are aiding tumour re-growth and multidrug resistance. Conventional therapies are highly ineffective at eliminating these cells leading to relapse of disease and formation of chemoresistance tumours. Cancer and stem cells targeted therapies that utilizes nanotherapeutics to delivery anti-cancer drugs to specific sites are continuously investigated. This review focuses on recent research using nanomedicine and targeting entities to eliminate cancer cells and cancer stem cells. Current nanotherapeutics in clinical trials along with more recent publications on targeted therapies are addressed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Circulating tumor cells in breast cancer.

    Science.gov (United States)

    Bidard, Francois-Clement; Proudhon, Charlotte; Pierga, Jean-Yves

    2016-03-01

    Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Cell membrane softening in human breast and cervical cancer cells

    Science.gov (United States)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

  5. Diet, Stem Cells, and Breast Cancer Prevention

    Science.gov (United States)

    2011-01-01

    pepper [39], flavonoids such as hesperetin and naringenin in citrus fruits and tomatoes [40], isoflavones (e.g., GEN, daidzein) from legumes and red...Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 1996;26:167–81. [41...38], capsaicin from chili pepper [39], flavonoids such as hesperetin and naringenin in citrus fruits and tomatoes [40], isoflavones (e.g., GEN

  6. Evaluation of cancer mortality in a cohort of workers exposed to low-level radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lea, C.S.

    1995-12-01

    The purpose of this dissertation was to re-analyze existing data to explore methodologic approaches that may determine whether excess cancer mortality in the ORNL cohort can be explained by time-related factors not previously considered; grouping of cancer outcomes; selection bias due to choice of method selected to incorporate an empirical induction period; or the type of statistical model chosen.

  7. Evaluation of cancer mortality in a cohort of workers exposed to low-level radiation

    International Nuclear Information System (INIS)

    Lea, C.S.

    1995-12-01

    The purpose of this dissertation was to re-analyze existing data to explore methodologic approaches that may determine whether excess cancer mortality in the ORNL cohort can be explained by time-related factors not previously considered; grouping of cancer outcomes; selection bias due to choice of method selected to incorporate an empirical induction period; or the type of statistical model chosen

  8. Genetic damage in human cells exposed to non-ionizing radiofrequency fields: a meta-analysis of the data from 88 publications (1990-2011).

    Science.gov (United States)

    Vijayalaxmi; Prihoda, Thomas J

    2012-12-12

    Based on the 'limited' evidence suggesting an association between exposure to radiofrequency fields (RF) emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as 'possibly carcinogenic to humans' in group 2B. In view of this classification and the positive correlation between increased genetic damage and carcinogenesis, a meta-analysis was conducted to determine whether a significant increase in genetic damage in human cells exposed to RF provides a potential mechanism for its carcinogenic potential. The extent of genetic damage in human cells, assessed from various end-points, viz., single-/double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges, reported in a total of 88 peer-reviewed scientific publications during 1990-2011 was considered in the meta-analysis. Among the several variables in the experimental protocols used, the influence of five specific variables related to RF exposure characteristics was investigated: (i) frequency, (ii) specific absorption rate, (iii) exposure as continuous wave, pulsed wave and occupationally exposed/mobile phone users, (iv) duration of exposure, and (v) different cell types. The data indicated the following. (1) The magnitude of difference between RF-exposed and sham-/un-exposed controls was small with some exceptions. (2) In certain RF exposure conditions there was a statistically significant increase in genotoxicity assessed from some end-points: the effect was observed in studies with small sample size and was largely influenced by publication bias. Studies conducted within the generally recommended RF exposure guidelines showed a smaller effect. (3) The multiple regression analyses and heterogeneity goodness of fit data indicated that factors other than the above five variables as well as the quality of publications have contributed to the overall results. (4) More

  9. Anti-inflammatory activity of the basolateral fraction of Caco-2 cells exposed to a rosemary supercritical extract

    NARCIS (Netherlands)

    Arranz, E.; Mes, J.J.; Wichers, H.J.; Jaime, L.; Reglero, G.; Santoyo, S.

    2015-01-01

    The anti-inflammatory activity of the basolateral fraction of Caco-2 cells exposed to a rosemary supercritical extract was examined. Uptake of rosemary extract fractions was tested on Caco-2 cell monolayers (2–12 h incubation times) and the quantification of carnosic acid and carnosol was performed

  10. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.

    Science.gov (United States)

    Sada, Masafumi; Ohuchida, Kenoki; Horioka, Kohei; Okumura, Takashi; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Oda, Yoshinao; Nakamura, Masafumi

    2016-03-28

    Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen.

    Science.gov (United States)

    Abos Gracia, Beatriz; López Relaño, Juan; Revilla, Ana; Castro, Lourdes; Villalba, Mayte; Martín Adrados, Beatriz; Regueiro, Jose Ramon; Fernández-Malavé, Edgar; Martínez Naves, Eduardo; Gómez Del Moral, Manuel

    2017-01-01

    Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses. © 2017 S. Karger AG, Basel.

  12. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

    International Nuclear Information System (INIS)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-01-01

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial-mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer. The online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users

  13. Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

    Directory of Open Access Journals (Sweden)

    Dropkin Greg

    2009-12-01

    Full Text Available Abstract Background The International Commission on Radiological Protection (ICRP recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years, liver (36.9, lung (13.6, leukaemia (23.66, and pancreas (11.86 and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of

  14. Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

    Science.gov (United States)

    2009-01-01

    Background The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model. Methods Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model. Results The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range. Conclusion Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10

  15. Cancer Mortality Among Techa Riverside Residents (Southern Urals). Chronically Exposed to Radiation During the Prenatal Period and in Childhood

    International Nuclear Information System (INIS)

    Ostroumova, E. V.; Akleyev, A. V.

    2004-01-01

    Imperfect technology and lack of management and utilization facilities for reprocessing liquid waste released by the Mayak PA resulted in a protracted combined (external and internal) environmental radiation exposure of the population resident on the banks of the Techa River. The followup of 8.640 subjects exposed during the prenatal period and in childhood covered the period of 49 years (1.1.1950-31.12.1998), the total person-years under observation amounted to 222,686. From 1950 through 1998 1,231 death cases were registered in the catchment area (5 raions in Chelyabinsk OBlast through which the Techa flows). In 70 cases death was caused by solid cancers, and in 12 cases by leukemia. Analyses of solid cancer mortality yielded higher rates for men as compared to women (p<0.001). No significant differences in death rates were observed between different ethnic groups (Slavs vs Tartars and Bashkirs). A statistically significant increase in solid cancer mortality with attained age was shown (p<0.001). The age at first exposure was demonstrated to be a factor modifying the solid cancer mortality rate (p=0.049). The highest risk of death from solid cancers was manifested by persons whose exposure started in the prenatal period or at the age under 5 years. There were 4.6 excess cases in this group of 30 observed solid cancer cases, whereas in the group including subjects aged 5 years or older at first exposure only 1 excess case was registered among the 40 observed cancer cases. The obtained leukemia mortality ERR value (CLL excluded) was 7.76, p=0.09. The excess leukemia death was found to be 7.6 out of of 10 observed cases. The analysis performed should be regarded as a preliminary one, taking into account the need to further extend the followup of the cohort and a potential verification of dose estimates in the future. (Author) 11 refs

  16. Risk of cancer in workers exposed to styrene at eight British companies making glass-reinforced plastics.

    Science.gov (United States)

    Coggon, David; Ntani, Georgia; Harris, E Clare; Palmer, Keith T

    2015-03-01

    To provide further information on the risks of lymphohaematopoietic (LH) and other cancers associated with styrene. We extended follow-up to December 2012 for 7970 workers at eight companies in England which used styrene in the manufacture of glass-reinforced plastics. Mortality was compared with that for England and Wales by the person-years method, and summarised by SMRs with 95% CIs. A supplementary nested case-control analysis compared styrene exposures, lagged by 5 years, in 122 incident or fatal cases of LH cancer and 1138 matched controls. A total of 3121 cohort members had died (2022 since the last follow-up). No elevation of mortality was observed for LH cancer, either in the full cohort (62 deaths, SMR 0.90, 95% CI 0.69 to 1.15), or in those with more than background exposure to styrene (38 deaths, SMR 0.82, 95% CI 0.58 to 1.14). Nor did the case-control analysis suggest any association with LH cancer. In comparison with background exposure, the OR for non-Hodgkin's lymphoma/chronic lymphocytic leukaemia in workers with high exposure (estimated 8-h time-weighted average of 40-100 ppm) for ≥1 year was 0.54 (95% CI 0.23 to 1.27). Mortality from lung cancer was significantly elevated, and risk increased progressively across exposure categories, with an SMR of 1.44 (95% CI 1.10 to 1.86) in workers highly exposed for ≥1 year. We found no evidence that styrene causes LH cancer. An association with lung cancer is not consistently supported by other studies. It may have been confounded by smoking, but would be worth checking further. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. Alterations in body weight and blood glucose level of female hamsters exposed to electromagnetic fields of cell phones

    Directory of Open Access Journals (Sweden)

    A.R Lotfi

    2010-02-01

    Group 2 was exposed to electromagnetic field emitted by cell phones for 10 days (short term and group 3 for 50 day (long term. In the latter groups, the exposure was 1 hour per day. At the end of the experimental period, the animals were weighed and blood glucose concentrations were determined by obtaining blood samples from 8 randomly selected hamsters in each group.  The blood glucose level was significantly higher in long-term exposed group in comparison with the control and short-term exposed groups (175, 11.6 and 107 mg/dl, respectively (p

  18. The protective effect of curcumin in Olfactory Ensheathing Cells exposed to hypoxia.

    Science.gov (United States)

    Bonfanti, Roberta; Musumeci, Teresa; Russo, Cristina; Pellitteri, Rosalia

    2017-02-05

    Curcumin, a phytochemical component derived from the rhizomes of Curcuma longa, has shown a great variety of pharmacological activities, such as anti-inflammatory, anti-tumor, anti-depression and anti-oxidant activity. Therefore, in the last years it has been used as a therapeutic agent since it confers protection in different neurodegenerative diseases, cerebral ischemia and excitotoxicity. Olfactory Ensheathing Cells (OECs) are glial cells of the olfactory system. They are able to secrete several neurotrophic growth factors, promote axonal growth and support the remyelination of damaged axons. OEC transplantation has emerged as a possible experimental therapy to induce repair of spinal cord injury, even if the functional recovery is still limited. Since hypoxia is a secondary effect in spinal cord injury, this in vitro study investigates the protective effect of curcumin in OECs exposed to hypoxia. Primary OECs were obtained from neonatal rat olfactory bulbs and placed both in normal and hypoxic conditions. Furthermore, some cells were grown with basic Fibroblast Growth Factor (bFGF) and/or curcumin at different concentration and times. The results obtained through immunocytochemical procedures and MTT test show that curcumin stimulates cell viability in OECs grown in normal and hypoxic conditions. Furthermore, the synergistic effect of curcumin and bFGF is the most effective exerting protection on OECs. Since spinal cord injury is often accompanied by secondary insults, such as ischemia or hypoxia, our results suggest that curcumin in combination with bFGF might be considered a possible approach for restoration in injuries. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Construction and identification of differential expression genes of peripheral blood cells in radon-exposed mice

    International Nuclear Information System (INIS)

    Chen Rui; Shi Minhua; Hu Huacheng; Li Jianxiang; Nie Jihua; Tong Jian

    2009-01-01

    Objective: To screen and identify the differential expression genes on peripheral blood cells of mice based on the experimental animal model of radon exposure. Methods: BALB/c mice were exposed in a type HD-3 multifunctional radon-room, with the accumulative doses of radon-exposure group at 105 WLM and control group at 1 WLM. Total RNA was extracted from peripheral blood cells and the methods of SMART for dscDNA synthesis and SSH for gene screening was applied. With the construction of the cDNA library enriched with differentially expressed genes, the pMD 18-T plasmid containing LacZ operator at the multiple cloning site was used to allow a blue-white screening. The TA clones were amplified by nested PCR and the reverse Northern blot was used to identify up and down regulation of the clones. The differently expressed cDNA was then sequenced and analyzed. Results: The subtracted cDNA libraries were successfully constructed. A total of 390 recombinant white colonies were randomly selected. Among the 312 cDNA monoclones selected from both forward- and reverse-subtracted libraries, 41 clones were chosen to sequence for their differential expressions based on reverse Northern blot. Among the 41 sequenced clones, 10 clones with known function/annotation and 3 new ESTs with the GenBank accession numbers were obtained. Most of the known function/annotation genes were revealed to be related with cell proliferation, metabolism, cellular apoptosis and carcinogenesis. Conclusions: The animal model of radon exposure was established and the cDNA library of peripheral blood cells was successfully constructed. Radon exposure could up- and down-regulate a series of genes. Differentially expressed genes could be identified by using SSH technique and the results may help exploring mechanisms of random exposure. (authors)

  20. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  1. Sphingosine 1-Phosphate and Cancer: Lessons from Thyroid Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kid Törnquist

    2013-05-01

    Full Text Available Sphingomyelin is found in the cell membrane of all eukaryotic cells, and was for a long time considered merely as a structural component. However, during the last two decades, metabolites of sphingomyelin, especially sphingosine 1-phosphate (S1P, have proven to be physiologically significant regulators of cell function. Through its five different G protein-coupled receptors, S1P regulates a wide array of cellular processes, ranging from stimulating cellular proliferation and migration, to the inhibition of apoptosis and induction of angiogenesis and modulation of cellular calcium homeostasis. Many of the processes regulated by S1P are important for normal cell physiology, but may also induce severe pathological conditions, especially in malignancies like cancer. Thus, understanding S1P signaling mechanisms has been the aim of a multitude of investigations. Great interest has also been shown in understanding the action of sphingosine kinase (SphK, i.e., the kinase phosphorylating sphingosine to S1P, and the interactions between S1P and growth factor signaling. In the present review, we will discuss recent findings regarding the possible importance of S1P and SphK in the etiology of thyroid cancer. Although clinical data is still scarce, our in vitro findings suggest that S1P may function as a “double-edged sword”, as the receptor profile of thyroid cancer cells largely determines whether S1P stimulates or blocks cellular migration. We will also discuss the interactions between S1P- and VEGF-evoked signaling, and the importance of a S1P1-VEGF receptor 2 complex in thyroid cancer cells.

  2. Foxp3 expression in human cancer cells

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2008-04-01

    Full Text Available Abstract Objective Transcription factor forkhead box protein 3 (Foxp3 specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs. Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

  3. Radiosensitization of mammalian cells by misonidazole and oxygen: DNA damage exposed by Micrococcus luteus enzymes

    International Nuclear Information System (INIS)

    Skov, K.A.; Palcic, B.; Skarsgard, L.D.

    1979-01-01

    When misonidazole is present during irradiation of hypoxic mammalian cells, an enhancement of single-strand breaks (SSB) in DNA is observed. Oxygen also enhances SSB, presumably in a manner similar to that of misonidazole. The dose-modifying factor (DMF) for 15 mM misonidazole was found to be 3.4, compared to an oxygen enhancement ratio (OER) of 3.5. Another class of DNA damage, namely, sites exposed by an extract of Micrococcus luteus, was examined. Radiation-induced M. luteus extract-sensitive sites (MLS) were also found to be enhanced by the presence of misonidazole or molecular oxygen. The DMF for this damage by 15 mM misonidazole was 1.6 while the OER was 2.5. The ratio of MLS to SSB is approximately 1.25 under hypoxia, 0.9 in the presence of oxygen, and 0.6 in the presence of 15 mM misonidazole under hypoxic conditions. Incubation with misonidazole under conditions which are toxic to mammalian cells (37 0 C, hypoxia), and which result in many SSB, produces no detectable lesions sensitive to the M. luteus extract

  4. Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells.

    Science.gov (United States)

    Bonvicini, Francesca; Bua, Gloria; Manaresi, Elisabetta; Gallinella, Giorgio

    2016-07-15

    Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500μM 1day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    International Nuclear Information System (INIS)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara

    2011-01-01

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs

  6. Radiation risk assessment of the thyroid cancer in Ukrainian children exposed due to Chernobyl

    International Nuclear Information System (INIS)

    Sobolev, B.; Likhtarev, I.; Kairo, I.; Tronko, N.; Oleynik, V.; Bogdanova, T.

    1996-01-01

    The children's thyroid exposure to radioiodine is one of the most serious consequences of the Chernobyl accident. The collective dose to children aged 0-18 in the entire Ukraine was estimated to be 400000 person-Gy. The dose estimates were calculated on the basis of measurements of thyroid content of 131 I for about 108000 people in Ukraine aged 0-18 years in May-June 1986. Up to the end of 1994, 542 thyroid cancers throughout the Ukraine have been reported in children and young adults who were aged 0-18 at the time of the accident. Rates of thyroid cancer have climbed, from about 0.7 per million children aged 0-14 in 1986 to more 7 per million in 1994. Rates increased most in region closest to Pripyat'. Between 1990 and 1994, 9 of the 14,580 people who had been children at the time of the accident in Pripyat' developed thyroid cancer. This corresponds to an annual incidence of 123 cases per million persons. The estimated average thyroid dose in Ukrainian children varies by several orders of magnitude. There is a more than 30-fold gradient in thyroid cancer incidence rates corresponding to the gradient in thyroid doses from 131 I. A preliminary investigation shows an excess in the annual incidence rate of thyroid cancer, throughout the northern territory of Ukraine, corresponding to the average doses to thyroid from 131 I. Coefficients of regression of excess cancers versus thyroid dose have been calculated

  7. Bioanalytical system for detection of cancer cells with photoluminescent ZnO nanorods

    Science.gov (United States)

    Viter, R.; Jekabsons, K.; Kalnina, Z.; Poletaev, N.; Hsu, S. H.; Riekstina, U.

    2016-11-01

    Using photoluminescent ZnO nanorods and carbohydrate marker SSEA-4, a novel cancer cell recognition system was developed. Immobilization of SSEA-4 antibodies (αSSEA-4) on ZnO nanorods was performed in buffer solution (pH = 7.1) over 2 h. The cancer cell line probes were fixed on the glass slide. One hundred microliters of ZnO-αSSEA-4 conjugates were deposited on the cell probe and exposed for 30 min. After washing photoluminescence spectra were recorded. Based on the developed methodology, ZnO-αSSEA-4 probes were tested on patient-derived breast and colorectal carcinoma cells. Our data clearly show that the carbohydrate SSEA-4 molecule is expressed on cancer cell lines and patient-derived cancer cells. Moreover, SSEA-4 targeted ZnO nanorods bind to the patient-derived cancer cells with high selectivity and the photoluminescence signal increased tremendously compared to the signal from the control samples. Furthermore, the photoluminescence intensity increase correlated with the extent of malignancy in the target cell population. A novel portable bioanalytical system, based on optical ZnO nanorods and fiber optic detection system was developed. We propose that carbohydrate SSEA-4 specific ZnO nanorods could be used for the development of cancer diagnostic biosensors and for targeted therapy.

  8. Cell-Cell Adhesion and Breast Cancer.

    Science.gov (United States)

    1998-01-01

    Lodish, H., Baltimore, D., Berk, A., Zipurski, S. L, Matsudaira, P., and J. Darnell. (1995). Molecular Cell Biology. Scientific American Books , New...Bruhn, L., Wedlich, D., Grosschedl, R., and Birchmeier, W. (1996) Nature 382, 638-642 6. Molenaar , M., van de Wetering, M., Oosterwegel, M., Peterson

  9. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    Science.gov (United States)

    ... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

  10. Proliferation assay of mouse embryonic stem (ES) cells exposed to atmospheric-pressure plasmas at room temperature

    International Nuclear Information System (INIS)

    Miura, Taichi; Hirano, Kazumi; Ogura, Chika; Ikeguchi, Masamichi; Seki, Atsushi; Nishihara, Shoko; Ando, Ayumi; Kanazawa, Tatsuya; Hamaguchi, Satoshi

    2014-01-01

    Proliferation assays of mouse embryonic stem (ES) cells have been performed with cell culture media exposed to atmospheric-pressure plasmas (APPs), which generate reactive species in the media at room temperature. It is found that serum in cell culture media functions as a scavenger of highly reactive species and tends to protect cells in the media against cellular damage. On the other hand, if serum is not present in a cell culture medium when it is exposed to APP, the medium becomes cytotoxic and cannot be detoxified by serum added afterwards. Plasma-induced cytotoxic media hinder proliferation of mouse ES cells and may even cause cell death. It is also shown by nuclear magnetic resonance spectroscopy that organic compounds in cell culture media are in general not significantly modified by plasma exposure. These results indicate that if there is no serum in media when they are exposed to APPs, highly reactive species (such as OH radicals) generated in the media by the APP exposure are immediately converted to less reactive species (such as H 2 O 2 ), which can no longer readily react with serum that is added to the medium after plasma exposure. This study has clearly shown that it is these less reactive species, rather than highly reactive species, that make the medium cytotoxic to mouse ES cells. (paper)

  11. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone

    International Nuclear Information System (INIS)

    Castleman, W.L.; Dungworth, D.L.; Schwartz, L.W.; Tyler, W.S.

    1980-01-01

    The pathogenesis of acute respiratory bronchiolitis was examined in Rhesus monkeys exposed to 0.8 ppM ozone for 4 to 50 hours. Epithelial injury and renewal were qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4 to 12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18%) was measured after 50 hours of exposure. Most (67 to 80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20 to 33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell types most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal

  12. Comet assay in gill cells of Prochilodus lineatus exposed in vivo to cypermethrin.

    Science.gov (United States)

    Poletta, G L; Gigena, F; Loteste, A; Parma, M J; Kleinsorge, E C; Simoniello, M F

    2013-11-01

    Agricultural chemicals can induce genetic alterations on aquatic organisms that have been associated with effects on growth, reproduction and population dynamics. The evaluation of DNA damage in fish using the comet assay (CA) frequently involves the utilization of erythrocytes. However, epithelial gill cells (EGC) can be more sensitive, as they are constantly dividing and in direct contact with potentially stressing compounds from the aquatic environment. The aim of the present study was to evaluate (1) the sensitivity and suitability of epithelial gill cells of Prochilodus lineatus in response to different genotoxic agents through the application of the CA, (2) the induction of DNA damage in this cell population after in vivo exposure to cypermethrin. Baseline value of the CA damage index (DI) for EGC of juvenile P. lineatus was 144.68±5.69. Damage increased in a dose-dependent manner after in vitro exposure of EGC to methyl methanesulfonate (MMS) and H2O2, two known genotoxic agents. In vivo exposure of fish to cypermethrin induced a significant increase in DNA DI of EGC at 0.150μg/l (DI: 239.62±6.21) and 0.300μg/l (270.63±2.09) compared to control (150.25±4.38) but no effect was observed at 0.075μg/l (168.50±10.77). This study shows that EGC of this species are sensitive for the application of the CA, demonstrating DNA damage in response to alkylation (MMS), oxidative damage (H2O2), and to the insecticide cypermethryn. These data, together with our previous study on DNA damage induction on erythrocytes of this species, provides useful information for future work involving biomonitoring in regions where P. lineatus is naturally exposed to pesticides and other genotoxic agents. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Exercise regulates breast cancer cell viability

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Lillelund, Christian; Midtgaard, Julie

    2016-01-01

    .003) and cytokines. Yet, these systemic adaptations had no effect on breast cancer cell viability in vitro. During 2 h of acute exercise, increases in serum lactate (6-fold, p ... no impact. Our data question the prevailing dogma that training-dependent baseline reductions in risk factors mediate the protective effect of exercise on breast cancer. Instead, we propose that the cancer protection is driven by accumulative effects of repeated acute exercise responses.......Purpose: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses...

  14. Principles of cancer cell culture.

    Science.gov (United States)

    Cree, Ian A

    2011-01-01

    The basics of cell culture are now relatively common, though it was not always so. The pioneers of cell culture would envy our simple access to manufactured plastics, media and equipment for such studies. The prerequisites for cell culture are a well lit and suitably ventilated laboratory with a laminar flow hood (Class II), CO(2) incubator, benchtop centrifuge, microscope, plasticware (flasks and plates) and a supply of media with or without serum supplements. Not only can all of this be ordered easily over the internet, but large numbers of well-characterised cell lines are available from libraries maintained to a very high standard allowing the researcher to commence experiments rapidly and economically. Attention to safety and disposal is important, and maintenance of equipment remains essential. This chapter should enable researchers with little prior knowledge to set up a suitable laboratory to do basic cell culture, but there is still no substitute for experience within an existing well-run laboratory.

  15. Self-renewal molecular mechanisms of colorectal cancer stem cells

    OpenAIRE

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2016-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...

  16. Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

    2012-01-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  17. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. Copyright © 2012 S. Karger AG, Basel.

  18. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    Hu, Brian; Rochefort, Holly; Goldkorn, Amir

    2013-01-01

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management

  19. Thyroid cancer incidence in iodine deficient areas exposed to radiation after Chernobyl accident

    International Nuclear Information System (INIS)

    Szybinski, Z.; Mazurek-Przybylik, E.

    1996-01-01

    In two districts of Southern Poland; Krakow and Nowy Sacz (2 million people), standardized thyroid cancer incidence rate IR was evaluated from 1976 to 1992. This area was classified as a moderate iodine deficiency endemic goiter region and belonged to the most contaminated areas in Poland after Chernobyl accident. Recalculated - in terms of real iodine intake-thyroid commitment equivalent dose in the youngest age groups reached 100 mSv. The aim of the study was to evaluate, 6 years after Chernobyl accident, thyroid cancer incidence rate and histotype. Age and sex specific incidence rate in Krakow for male was 0.827 and for female 3.093 and 0.93 and 2.164 for Nowy Sacz respectively. There was no increase of IR in the group of age 0-19 yrs, however in the group over 44 yrs in females in the period of time 1989-1992 significant increase of follicular cancer was observed. In the histotype, the follicular cancerpredominated over the papillary one: 42,9% against 33,6%. Predominance of the follicular cancer is typical for iodine deficient area. Significant increase of the follicular cancer may be due to the increase of iodine deficiency. (author). 14 refs, 1 fig., 5 tabs

  20. Thyroid cancer incidence in iodine deficient areas exposed to radiation after Chernobyl accident

    Energy Technology Data Exchange (ETDEWEB)

    Szybinski, Z; Mazurek-Przybylik, E [Jagiellonian Univ., Cracow (Poland). Dept. of Endocrinology; Pawlega, J [Institute of Oncology, Cracow (Poland)

    1996-08-01

    In two districts of Southern Poland; Krakow and Nowy Sacz (2 million people), standardized thyroid cancer incidence rate IR was evaluated from 1976 to 1992. This area was classified as a moderate iodine deficiency endemic goiter region and belonged to the most contaminated areas in Poland after Chernobyl accident. Recalculated - in terms of real iodine intake-thyroid commitment equivalent dose in the youngest age groups reached 100 mSv. The aim of the study was to evaluate, 6 years after Chernobyl accident, thyroid cancer incidence rate and histotype. Age and sex specific incidence rate in Krakow for male was 0.827 and for female 3.093 and 0.93 and 2.164 for Nowy Sacz respectively. There was no increase of IR in the group of age 0-19 yrs, however in the group over 44 yrs in females in the period of time 1989-1992 significant increase of follicular cancer was observed. In the histotype, the follicular cancerpredominated over the papillary one: 42,9% against 33,6%. Predominance of the follicular cancer is typical for iodine deficient area. Significant increase of the follicular cancer may be due to the increase of iodine deficiency. (author). 14 refs, 1 fig., 5 tabs.

  1. Are All Highly Malignant Cancer Cells Identical?

    Science.gov (United States)

    1979-01-01

    embryo cells or even the original fertilized ovum. If this speculation has validity, the carcinogenesis and differentiation have the same destinies but...whose activity leads to the suppression of the transcrip- tion of the genes responsible for the unique set of embryo -cancer proteins and whose mutation

  2. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

    Sorensen, M; Lassen, U; Hansen, H H

    1998-01-01

    This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...

  3. Forcing Cancer Cells to Commit Suicide

    NARCIS (Netherlands)

    Vangestel, Christel; Van de Wiele, Christophe; Mees, Gilles; Peeters, Marc

    Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro-and antiapoptotic proteins. Resistance to

  4. (Asteraceae) Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquidliquid extraction ...

  5. Radiation related basic cancer research : research for radiation induced tumor cell killing

    International Nuclear Information System (INIS)

    Lee, Seung Hoon; Hong, Seok Il; Cho, Kyung Ja; Kim, Byung Gi; Lee, Kee Ho; Nam, Myung Jin

    1999-04-01

    The radioresistant clones was established from human U251 glioblastoma cell line through intermittently exposed to 3 Gy gamma-radiation for six months. Treatment of SNU-16 cells with various doses of radiation, TNF alpha and PMA resulted in a decrease in cell viability. The results prove that cell death of SNU16 is a apoptosis mediated by caspase-3. We have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia (CIN) to determine the role of coexpression of bcl-3 and c-myc during progression into cervical cancer. The frequent alterations in FHIT expression in many cervical carcinomas and their cell lines suggest that FHIT gene alterations are pla a role in cervical tumorigenesis. According to these correlation between the viability and apoptosis of RD cells, the proper range of the dosage for the investigation of differentiation potency in RD cells was assessed as 1 to 3Gy

  6. Radiation related basic cancer research : research for radiation induced tumor cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hoon; Hong, Seok Il; Cho, Kyung Ja; Kim, Byung Gi; Lee, Kee Ho; Nam, Myung Jin

    1999-04-01

    The radioresistant clones was established from human U251 glioblastoma cell line through intermittently exposed to 3 Gy gamma-radiation for six months. Treatment of SNU-16 cells with various doses of radiation, TNF alpha and PMA resulted in a decrease in cell viability. The results prove that cell death of SNU16 is a apoptosis mediated by caspase-3. We have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia (CIN) to determine the role of coexpression of bcl-3 and c-myc during progression into cervical cancer. The frequent alterations in FHIT expression in many cervical carcinomas and their cell lines suggest that FHIT gene alterations are pla a role in cervical tumorigenesis. According to these correlation between the viability and apoptosis of RD cells, the proper range of the dosage for the investigation of differentiation potency in RD cells was assessed as 1 to 3Gy.

  7. Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Narumol Bhummaphan

    2015-01-01

    Full Text Available As cancer stem cells (CSCs contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

  8. Cancer incidence among glyphosate-exposed pesticide applicators in the Agricultural Health Study.

    Science.gov (United States)

    De Roos, Anneclaire J; Blair, Aaron; Rusiecki, Jennifer A; Hoppin, Jane A; Svec, Megan; Dosemeci, Mustafa; Sandler, Dale P; Alavanja, Michael C

    2005-01-01

    Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993-1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or "cumulative exposure days" (years of use times days/year); and c) intensity-weighted cumulative exposure days (years of use times days/year times estimated intensity level). Poisson regression was used to estimate exposure-response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers.

  9. Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

    International Nuclear Information System (INIS)

    Yamagishi, Naoko; Teshima-Kondo, Shigetada; Masuda, Kiyoshi; Nishida, Kensei; Kuwano, Yuki; Dang, Duyen T; Dang, Long H; Nikawa, Takeshi; Rokutan, Kazuhito

    2013-01-01

    Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Our findings suggest that chronic inhibition of tumor cell-derived VEGF

  10. A DRD1 Polymorphism Predisposes to Lung Cancer among those Exposed to Secondhand smoke during Childhood

    OpenAIRE

    Robles, Ana I.; Yang, Ping; Jen, Jin; McClary, Andrew C.; Calhoun, Kara; Bowman, Elise D.; Vähäkangas, Kirsi; Greathouse, K. Leigh; Wang, Yi; Olivo-Marston, Susan; Wenzlaff, Angela S.; Deng, Bo; Schwartz, Ann G.; Ryan, Bríd M.

    2014-01-01

    Lung cancer has a familial component which suggests a genetic contribution to its etiology. Given the strong evidence linking smoking with lung cancer, we studied miRNA-related loci in genes associated with smoking behavior. CHRNA, CHRNB gene families, CYP2A6 and DRD1 were mined for single nucleotide polymorphisms (SNPs) that fell within the seed region of miRNA binding sites and then tested for associations with risk in a three-stage validation approach. A 3’UTR SNP in DRD1 (Dopamine Recepto...

  11. Cell Phones and Cancer Risk

    Science.gov (United States)

    ... bias , which can occur when data about prior habits and exposures are collected from study participants using ... operates at a different frequency and a lower power level than analog phones. Digital cell phones have ...

  12. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  13. Frequency of Acentric Fragments Are Associated with Cancer Risk in Subjects Exposed to Ionizing Radiation.

    Czech Academy of Sciences Publication Activity Database

    Fucic, A.; Bonassi, S.; Gundy, S.; Šrám, Radim; Ceppi, M.; Lucas, J.N.

    2016-01-01

    Roč. 36, č. 5 (2016), s. 2451-2457 ISSN 0250-7005 Institutional support: RVO:68378041 Keywords : ionizing radiation * cancer risk * acentric fragments * chromosomal aberrations Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 1.937, year: 2016

  14. Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Pongrac IM

    2016-04-01

    Full Text Available Igor M Pongrac,1 Ivan Pavičić,2 Mirta Milić,2 Lada Brkič Ahmed,1 Michal Babič,3 Daniel Horák,3 Ivana Vinković Vrček,2 Srećko Gajović1 1School of Medicine, Croatian Institute for Brain Research, University of Zagreb, 2Institute for Medical Research and Occupational Health, Zagreb, Croatia; 3Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic Abstract: Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs – uncoated, coated with D-mannose, or coated with poly-L-lysine – affects biocompatibility. We sought to investigate murine neural stem cells (NSCs as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions

  15. DNA repair studies in mouse germ cells exposed to two carcinogens and two non-carcinogens

    International Nuclear Information System (INIS)

    Sega, G.A.; Owens, J.G.

    1987-01-01

    An in vivo test was used to measure induced unscheduled DNA synthesis (UDS) in the germ cells of male mice exposed to the carcinogens benzo(a)pyrene [B(a)P] and 2-acetylaminofluorene (2AAF), and to the noncarcinogens pyrene (PYR) and 4-acetylaminofluorene (4AAF). Early spermatids, a DNA-repair competent stage, were used to test the effects of all chemicals. After chemical treatment and testicular injection of [ 3 H]dThd, sperm were recovered 16 days later from the caudal epididymides (these sperm were in early spermatid stages at the time of treatment) and assayed for the unscheduled incorporation of [ 3 H]dThd using liquid scintillation counting (LSC). Exposures of 2AAF ranged from 125 to 1600 mg/kg, 4AAF from 125 to 2000 mg/kg, PYR from 100 to 600 mg/kg, B(a)P from 100 to 400 mg/kg. Chemicals were administered both by intraperitoneal (i.p.) injection and by gavage. Methyl methanesulfonate (MMS) was used as a positive control

  16. Cancer Stem Cells – New Approach to Cancerogenensis and Treatment

    Directory of Open Access Journals (Sweden)

    Zuzana Mačingová

    2008-01-01

    Full Text Available Recently, there is an increasing evidence supporting the theory of cancer stem cells not only in leukemia but also in solid cancer. To date, the existence of cancer stem cells has been proven in acute and chronic myeloid leukemia, in breast cancer, in brain tumors, in lung cancer and gastrointestinal tumors. This review is focusing on the recent discovery of stem cells in leukemia, human brain tumors and breast cancer. A small population of cells in the tumor (less than 1 % shows the potential to give rise to the tumor and its growth. These cells have a substantial characteristic of stem cells – ability for self-renewal without loss of proliferation capacity with each cell division. Furthermore they are immortal, rather resistant to treatment and express typical markers of stem cells. The origin of these resident cancer stem cells is not clear. Whether the cancer stem cells originate from normal stem cells in consequence of genetic and epigenetic changes and/or redifferentiation from somatic tumor cells to the stem-like cells remains to be investigated. We propose the idea of the relation between normal tissue stem cells and cancer stem cells and their populations – progenitor cells. Based on this we highlight one of the major characteristic of stem cell – plasticity, which is equally important in the physiological regeneration process as well as carcinogenesis. Furthermore, we consider the microenvironment as a limiting factor for tumor genesis in AML, breast cancer and brain tumors. Thus the biological properties of cancer stem cells are just beginning to be revealed, the continuation of these studies should lead to the development of cancer stem cells target therapies for cancer treatment.

  17. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Hao Yumei; He Xin; Song Naling

    2013-01-01

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  18. Fibrogenic response of hepatic stellate cells in ovariectomised rats exposed to ketogenic diet.

    Science.gov (United States)

    Bobowiec, R; Wojcik, M; Jaworska-Adamu, J; Tusinska, E

    2013-02-01

    The discrepancy about the role of estrogens in hepatic fibrogenesis and lack of studies addressed of ketogenic diet (KD) on hepatic stellate cells (HSC), prompted us to investigate the activity of HSC in control, KD- and thioacetamide (TAA)-administrated rats with different plasma concentration of estradiol (E2). HSC were isolated by the collagenase perfusion methods and separated by the Percoll gradient centrifugation. After the 4(th) and 8(th) day of incubation, lysates of HSC and the media were collected for further analysis. The HSC derived from KD-rats released remarkably more transforming growth factor (TGF)-β1 than cells obtained from animals fed with a standard diet. The ovariectomy of KD-rats markedly intensified the secretion of this fibrogenic cytokine on the 8(th) day of incubation (201.33 ±1 7.15 pg/ml). In HSC of rats exposed to E2, the TGF-β1 concentration did not exceed 157 ± 34.39 pg/ml. In respect to the collagen type I, the HSC obtained from ovariectomised KD-rats released an augmented amount of this ECM protein after the 8(th) day of culture (1.83 ± 0.14 U/ml). In the same time, higher quantities of ASMA appeared in the KD rats (1.41 ± 0.3 pg/mg protein). Exposition of rats to E2 did not markedly decrease the amount of ASMA. In summary, KD was able to induce morphological and functional changes in HSC, especially derived from rats deprived of ovarian estrogens. However, the preservation of E2 in ovariectomised rats didn't substantially alter the activation of HSC.

  19. Celecoxib and GABA cooperatively prevent the progression of pancreatic cancer in vitro and in xenograft models of stress-free and stress-exposed mice.

    Directory of Open Access Journals (Sweden)

    Hussein A N Al-Wadei

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis and is associated with high levels of psychological distress. We have shown that beta-adrenergic receptors (β-ARs, which are activated by stress neurotransmitters, regulate PDAC cells via cyclic AMP (cAMP-dependent signaling in vitro, that social stress promotes PDAC progression in mouse xenografts and that γ-aminobutyric acid (GABA inhibits these responses in vitro and in vivo. The targeted inhibition of stress-induced regulatory pathways may abolish the potentially negative impact of psychological stress on clinical outcomes. Our current data show that chronic exposure of PDAC cell lines Panc-1 (activating point mutations in K-ras and BXPC-3 (no mutations in K-ras in vitro to the stress neurotransmitter epinephrine at the concentration (15 nM previously measured in the serum of mice exposed to social stress significantly increased proliferation and migration. These responses were inhibited in a concentration-dependent manner by celecoxib. The effects of celecoxib alone and in combination with γ-aminobutyric acid (GABA on the progression of subcutaneous mouse xenografts from the cell line (BXPC-3 most responsive to epinephrine were then investigated in the presence and absence of social stress. Cancer-stimulating factors (VEGF & prostaglandin E(2 [PGE(2] and levels of cAMP were measured by immunoassays in blood and xenograft tissue. Phosphorylation of the signaling proteins ERK, CREB, Src, and AKT was assessed by ELISA assays and Western blotting. Expression of COX-2, 5-lipoxygenase, and p-5-LOX were determined by semi-quantitative Western blotting. Celecoxib alone significantly inhibited xenograft progression and decreased systemic and tumor VEGF, PGE2, and cAMP as well as phosphorylated signaling proteins in stress-exposed and stress-free mice. These responses were significantly enhanced by co-treatment with GABA. The celecoxib-induced downregulation of COX-2 protein and p-5-LOX

  20. Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Lam, R.K.K. [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Han, Wei [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong (Hong Kong)

    2015-12-15

    Highlights: • Rescue effect was observed in both irradiated and HeLa and NIH/3T3 cells. • Novel setup and procedures to separate the rescue signals and the bystander signals. • Confirmed activation of NF-κB pathway in rescue effect using activation inhibitor. • Confirmed activation of NF-κB pathway in rescue effect using anti-NF-κB p65 antibody. - Abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased

  1. Oncolytic viral therapy: targeting cancer stem cells

    Directory of Open Access Journals (Sweden)

    Smith TT

    2014-02-01

    Full Text Available Tyrel T Smith,1 Justin C Roth,1 Gregory K Friedman,1 G Yancey Gillespie2 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Cancer stem cells (CSCs are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. Keywords: oncolytic virotherapy, cancer stem cell niche

  2. Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

    Science.gov (United States)

    Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N

    2015-01-01

    Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315

  3. Verrucous Squamous Cell Cancer in the Esophagus

    DEFF Research Database (Denmark)

    Egeland, C; Achiam, M P; Federspiel, B

    2016-01-01

    Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic...... examinations showed a similar wart-like, white, irregular mucosa in both cases. The diagnosis was difficult to make since all biopsies taken from the affected area showed no malignancy. This cancer type has a relatively good prognosis when the diagnosis is finally obtained. Both our patients presented...

  4. Albendazole sensitizes cancer cells to ionizing radiation

    International Nuclear Information System (INIS)

    Patel, Kirtesh; Doudican, Nicole A; Schiff, Peter B; Orlow, Seth J

    2011-01-01

    Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted

  5. Albendazole sensitizes cancer cells to ionizing radiation

    Science.gov (United States)

    2011-01-01

    Background Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Methods Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. Results ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Conclusions Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted. PMID:22094106

  6. Impact of Hypoxia on the Metastatic Potential of Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Dai Yao; Bae, Kyungmi; Siemann, Dietmar W.

    2011-01-01

    Purpose: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells. Methods and Materials: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. 'Wound-healing' and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. Results: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. Conclusions: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype.

  7. Experimental investigation of the cytotoxicity of medium-borne signals in human prostate cancer cell line

    International Nuclear Information System (INIS)

    Sjostedt, Svetlana; Bezak, Eva

    2012-01-01

    Introduction. Evidence exists that exposure of non-irradiated cells to Irradiated Cell Conditioned Medium (ICCM) can cause effects similar to those resulting from direct radiation damage. This study attempts to validate the stochastic model, relating absorbed dose to the emission and processing of cell death signals by non-irradiated cells, in vitro in PC3 human prostate cancer cell line. Methods. The recipient cell survival was measured after exposure of cells to ICMM derived from donor cells: a) exposed to radiation doses from 2 Gy to 8 Gy and b) of concentrations varying from 2 x 10 2 to 6 x 10 6 irradiated with 2 Gy. Results. Exposure to ICCM, irradiated with doses between 2-8 Gy, resulted in a significant (p 2 cells was significantly higher (p < 0.5) compared to the rest of donor cell concentrations, indicating that the toxicity of ICCM depends on the cellular concentration of donor cells. Non-linear regression data fitting provided reasonable agreement with the microdosimetric model for the induction of cell killing through medium-borne signals. Conclusion. For the given cell line and given experimental conditions, significant decreases in cell survival were observed in non-irradiated cells exposed to ICCM derived from donor cells of various concentrations and irradiated with different doses

  8. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators

    Energy Technology Data Exchange (ETDEWEB)

    Orona, N.S. [School of Science and Technology, National University of General Martín, Avda Gral Paz 5445 (1650) San Martín, Buenos Aires (Argentina); Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar [School of Science and Technology, National University of General Martín, Avda Gral Paz 5445 (1650) San Martín, Buenos Aires (Argentina); School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142 (1122), Buenos Aires (Argentina)

    2012-06-15

    Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO{sub 3} 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO{sub 3}. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O{sub 2}{sup −}). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O{sub 2}{sup −} may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O{sub 2}{sup −} may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through

  9. A Quantitative Assessment of the Morphofunctional Activity of the Population of Mast Cells Exposed to Biotechnological Strains of Microorganisms

    Directory of Open Access Journals (Sweden)

    Natalia Sheina

    2018-06-01

    Full Text Available In order to assess the sensitizing properties of bacteria, micromycetes and actinomycetes, the morphofunctional activity of the population of mast cells was tested in rats exposed to biotechnological microorganisms. The result showed the high informative value of the test of peritoneal must cell degranulation. Both the result and the intensity of the response of mast cells to the exposure to the tested strains depend on the taxonomy of microorganisms, their concentration and the mode of inoculation. The test of peritoneal must cell degranulation can be recommended for assessing the biological safety of industrial microorganisms.

  10. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    Science.gov (United States)

    2013-03-25

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  11. Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study

    OpenAIRE

    De Roos, Anneclaire J.; Blair, Aaron; Rusiecki, Jennifer A.; Hoppin, Jane A.; Svec, Megan; Dosemeci, Mustafa; Sandler, Dale P.; Alavanja, Michael C.

    2004-01-01

    Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in...

  12. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  13. Effects of hydroxyapatite nanoparticles on proliferation and apoptosis of human breast cancer cells (MCF-7)

    International Nuclear Information System (INIS)

    Meena, Ramovatar; Kesari, Kavindra Kumar; Rani, Madhu; Paulraj, R.

    2012-01-01

    The study aimed to correlate cell proliferation inhibition with oxidative stress and p53 protein expression in cancerous cells. Hydroxyapatite (HAP) (Ca 10 (PO 4 ) 6 (OH) 2 ) is the essential component of inorganic composition in human bone. It has been found to have obvious inhibitory function on growth of many kinds of tumor cells and its nanoparticle has stronger anti-cancerous effect than macromolecule microparticles. Human breast cancer cells (MCF-7) were cultured and treated with HAP nanoparticles at various concentrations. Cells viability was detected with MTT colorimetric assay. The morphology of the cancerous cells was performed by transmission electron microscopy and the expression of a cell apoptosis related gene (p53) was determined by ELISA assay and flow cytometry (FCM). The intracellular reactive oxygen species (ROS) level in HAP exposed cells was measured by H 2 DCFDA staining. DNA damage was measured by single-cell gel electrophoresis assay. The statistical analysis was done by one way ANOVA. The cellular proliferation inhibition rate was significantly (p < 0.05) increasing in a dose-dependent manner of HAP nanoparticles. Cell apoptotic characters were observed after MCF-7 cells were treated by HAP nanoparticles for 48 h. Moreover, ELISA assay and FCM shows a dose-dependent activation of p53 in MCF-7 cells treated with nanoHAP. These causative factors of the above results may be justified by an overproduction of ROS. In this study, a significant (p < 0.05) increase in the level of intracellular ROS in HAP-treated cells was observed. This study shows that HAP inhibits the growth of human breast cancer MCF-7 cells as well as induces cell apoptosis. This study shows that HAP NPs Induce the production of intracellular reactive oxygen species and activate p53, which may be responsible for DNA damage and cell apoptosis.

  14. Analysis of Pseudomonas aeruginosa Cell Envelope Proteome by Capture of Surface-Exposed Proteins on Activated Magnetic Nanoparticles

    OpenAIRE

    Vecchietti, Davide; Di Silvestre, Dario; Miriani, Matteo; Bonomi, Francesco; Marengo, Mauro; Bragonzi, Alessandra; Cova, Lara; Franceschi, Eleonora; Mauri, Pierluigi; Bertoni, Giovanni

    2012-01-01

    We report on specific magneto-capturing followed by Multidimensional Protein Identification Technology (MudPIT) for the analysis of surface-exposed proteins of intact cells of the bacterial opportunistic pathogen Pseudomonas aeruginosa. The magneto-separation of cell envelope fragments from the soluble cytoplasmic fraction allowed the MudPIT identification of the captured and neighboring proteins. Remarkably, we identified 63 proteins captured directly by nanoparticles and 67 proteins embedde...

  15. Responses of well-differentiated nasal epithelial cells exposed to particles: Role of the epithelium in airway inflammation

    International Nuclear Information System (INIS)

    Auger, Floriane; Gendron, Marie-Claude; Chamot, Christophe; Marano, Francelyne; Dazy, Anne-Catherine

    2006-01-01

    Numerous epidemiological studies support the contention that ambient air pollution particles can adversely affect human health. To explain the acute inflammatory process in airways exposed to particles, a number of in vitro studies have been performed on cells grown submerged on plastic and poorly differentiated, and on cell lines, the physiology of which is somewhat different from that of well-differentiated cells. In order to obtain results using a model system in which epithelial cells are similar to those of the human airway in vivo, apical membranes of well-differentiated human nasal epithelial (HNE) cells cultured in an air-liquid interface (ALI) were exposed for 24 h to diesel exhaust particles (DEP) and Paris urban air particles (PM 2.5 ). DEP and PM 2.5 (10-80 μg/cm 2 ) stimulated both IL-8 and amphiregulin (ligand of EGFR) secretion exclusively towards the basal compartment. In contrast, there was no IL-1β secretion and only weak non-reproducible secretion of TNF-α. IL-6 and GM-CSF were consistently stimulated towards the apical compartment and only when cells were exposed to PM 2.5 . ICAM-1 protein expression on cell surfaces remained low after particle exposure, although it increased after TNF-α treatment. Internalization of particles, which is believed to initiate oxidative stress and proinflammatory cytokine expression, was restricted to small nanoparticles (≤ 40 nm). Production of reactive oxygen species (ROS) was detected, and DEP were more efficient than PM 2.5 . Collectively, our results suggest that airway epithelial cells exposed to particles augment the local inflammatory response in the lung but cannot alone initiate a systemic inflammatory response

  16. Carcinogenicity of Mustard Gas: Report of the Cancer Registry Project Among Mustard Gas Exposed Iranian Veterans

    International Nuclear Information System (INIS)

    Soroush, M. R.

    2007-01-01

    Since 2003 The Janbazan Medical and Engineering Research Center in collaboration with Tehran University has conducted a nationwide cancer registry project among all Iranian Veterans with history of exposure to mustard gas during 1980-1988 Iran Iraq war. The mixed cohort study has a retrospective phase from the exposure time to 2003 and a prospective phase from 2003 to 2013. The main goal is to find any possible relationship between exposure to mustard gas and developing cancer as a long term health effect. A total number of 7500 individual (both military and civilians) with confirmed medical records of exposure to mustard gas have been included in the study to be compared with the same number of control population as well as the statistics of the national cancer registry system. The follow up of all cases is being done as a part of the national health monitoring program of the Janbazan (veterans) organization. In this report the latest findings of this project will be presented.(author)

  17. Thyroid cancer incidence among Swedish patients exposed to diagnostic doses of iodine-131: A preliminary report

    International Nuclear Information System (INIS)

    Hall, P.E.

    1996-01-01

    The level of risk associated with I-131 is not well defined but appears lower than equivalent doses of x-rays. To provide quantitative data on the risk of thyroid cancer following I-131 exposure, 34,104 patients surviving ≅ 5 years after I-131 administration between 1950-69 for diagnostic purposes were studied. The mean thyroid dose was estimated to be 1.1 Gy (range 0-40.5). A significantly increased risk of a subsequent thyroid cancer was found, however, the excess rates were based entirely on patients referred because of a suspicion of a thyroid tumor. There was no suggestion of an increasing risk with increasing dose or time since exposure. No significant excess risk was found among those less than 20 years of age at exposure. The absence of a risk among those over age 20 is consistent with studies of A-bomb survivors and implies that any type of exposure to ionizing radiation later in life is associated with a minimal cancer risk. (author). 23 refs, 4 tabs

  18. Thyroid cancer incidence among Swedish patients exposed to diagnostic doses of iodine-131: A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Hall, P E [Karolinska Hospital, Stockhom (Sweden). Dept. of General Oncology; Holm, L E [National Inst. of Public Health, Stockholm (Sweden)

    1996-08-01

    The level of risk associated with I-131 is not well defined but appears lower than equivalent doses of x-rays. To provide quantitative data on the risk of thyroid cancer following I-131 exposure, 34,104 patients surviving {approx_equal} 5 years after I-131 administration between 1950-69 for diagnostic purposes were studied. The mean thyroid dose was estimated to be 1.1 Gy (range 0-40.5). A significantly increased risk of a subsequent thyroid cancer was found, however, the excess rates were based entirely on patients referred because of a suspicion of a thyroid tumor. There was no suggestion of an increasing risk with increasing dose or time since exposure. No significant excess risk was found among those less than 20 years of age at exposure. The absence of a risk among those over age 20 is consistent with studies of A-bomb survivors and implies that any type of exposure to ionizing radiation later in life is associated with a minimal cancer risk. (author). 23 refs, 4 tabs.

  19. Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells.

    Science.gov (United States)

    Son, Young-Ok; Jang, Yong-Suk; Heo, Jung-Sun; Chung, Wan-Tae; Choi, Ki-Choon; Lee, Jeong-Chae

    2009-06-01

    It has been proposed that continuously generated hydrogen peroxide (H(2)O(2)) inhibits typical apoptosis and instead initiates an alternate, apoptosis-inducing factor (AIF)-dependent process. Aside from the role of AIF, however, the detailed morphological characterization of H(2)O(2)-induced cell death is not complete. This study examined the cellular mechanism(s) by which the continuous presence of H(2)O(2) induces cell death. We also further analyzed the precise role of AIF by inhibiting its expression with siRNA. Exposure of cells to H(2)O(2) generated by glucose oxidase caused mitochondrion-mediated, caspase-independent cell death. In addition, H(2)O(2) exposure resulted in cell shrinkage and chromatin condensation without nuclear fragmentation, indicating that H(2)O(2) stimulates a pyknotic cell death. Further analysis of AIF-transfected cells clearly demonstrated that nuclear translocation of AIF is the most important event required for nuclear condensation, phosphatidyl serine translocation, and ultimately cell death in H(2)O(2)-exposed cells. Furthermore, ATP was rapidly and severely depleted in cells exposed to H(2)O(2) generated by glucose oxidase but not by H(2)O(2) added as a bolus. Suppression of the H(2)O(2)-mediated ATP depletion by 3-aminobenzamide led to a significant increase of nuclear fragmentation in glucose oxidase-exposed cells. Collectively, these findings suggest that an acute energy reduction by H(2)O(2) causes caspase-independent and AIF-dependent cell death.

  20. Effects of radiation from a radiofrequency identification (RFID) microchip on human cancer cells.

    Science.gov (United States)

    Lai, Henry C; Chan, Ho Wing; Singh, Narendra P

    2016-01-01

    Radiofrequency identification (RFID) microchips are used to remotely identify objects, e.g. an animal in which a chip is implanted. A passive RFID microchip absorbs energy from an external source and emits a radiofrequency identification signal which is then decoded by a detector. In the present study, we investigated the effect of the radiofrequency energy emitted by a RFID microchip on human cancer cells. Molt-4 leukemia, BT474 breast cancer, and HepG2 hepatic cancer cells were exposed in vitro to RFID microchip-emitted radiofrequency field for 1 h. Cells were counted before and after exposure. Effects of pretreatment with the spin-trap compound N-tert-butyl-alpha-phenylnitrone or the iron-chelator deferoxamine were also investigated. Results We found that the energy effectively killed/retarded the growth of the three different types of cancer cells, and the effect was blocked by the spin-trap compound or the iron-chelator, whereas an inactive microchip and energy from the external source had no significant effect on the cells. Conclusions Data of the present study suggest that radiofrequency field from the microchip affects cancer cells via the Fenton Reaction. Implantation of RFID microchips in tumors may provide a new method for cancer treatment.

  1. DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase

    Energy Technology Data Exchange (ETDEWEB)

    Cogan, Nicola [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom); Baird, Duncan M. [Department of Pathology School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, CF14 4XN (United Kingdom); Phillips, Ryan [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom); Crompton, Lucy A.; Caldwell, Maeve A. [Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, BS1 3NY (United Kingdom); Rubio, Miguel A. [Center of Regenerative Medicine in Barcelona, CMRB Dr. Aiguader, 88, 7th Floor, 08003 Barcelona (Spain); Newson, Roger [Radiation and Environmental Science Centre, Focas Institute, Dublin Institute of Technology, Dublin 2 (Ireland); Lyng, Fiona [National Heart and Lung Institute, Imperial College London, London, SW7 2AZ (United Kingdom); Case, C. Patrick, E-mail: c.p.case@bristol.ac.uk [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom)

    2010-01-05

    The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

  2. DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase

    International Nuclear Information System (INIS)

    Cogan, Nicola; Baird, Duncan M.; Phillips, Ryan; Crompton, Lucy A.; Caldwell, Maeve A.; Rubio, Miguel A.; Newson, Roger; Lyng, Fiona; Case, C. Patrick

    2010-01-01

    The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

  3. AFM indentation study of breast cancer cells

    International Nuclear Information System (INIS)

    Li, Q.S.; Lee, G.Y.H.; Ong, C.N.; Lim, C.T.

    2008-01-01

    Mechanical properties of individual living cells are known to be closely related to the health and function of the human body. Here, atomic force microscopy (AFM) indentation using a micro-sized spherical probe was carried out to characterize the elasticity of benign (MCF-10A) and cancerous (MCF-7) human breast epithelial cells. AFM imaging and confocal fluorescence imaging were also used to investigate their corresponding sub-membrane cytoskeletal structures. Malignant (MCF-7) breast cells were found to have an apparent Young's modulus significantly lower (1.4-1.8 times) than that of their non-malignant (MCF-10A) counterparts at physiological temperature (37 deg. C), and their apparent Young's modulus increase with loading rate. Both confocal and AFM images showed a significant difference in the organization of their sub-membrane actin structures which directly contribute to their difference in cell elasticity. This change may have facilitated easy migration and invasion of malignant cells during metastasis

  4. Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models

    International Nuclear Information System (INIS)

    Phelan, J. P.; Reen, F. J.; Dunphy, N.; O'Connor, R.; O'Gara, F.

    2016-01-01

    The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1α is known to be active under hypoxic conditions. HIF-1α status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. Intracellular HIF-1α was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1α in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression

  5. Selective eradication of cancer cells in vitro

    International Nuclear Information System (INIS)

    Schneiderman, M.H.; Schneiderman, G.S.

    1984-01-01

    A simple system consisting of cultured HeLa (human cancer) and WI38 (normal human fetal lung) cells and the control cultures of the individual cells were set up to test and compare the effects of the cell cycle-active agents /sup 125/I-iododeoxyuridine (/sup 125/IUdR) and hydroxyurea (HU) on cell survival. The presence of cells and growth after treatment were used as a positive indication of survival. The experimental cultures were first seeded with WI38 cells and allowed to grow to confluency before adding 1.0 x 10/sup 5/ HeLa cells. After two days of treatment-free growth, the co-cultures were continuously treated with /sup 125/IUdR (0.5-2.0 μCi/ml, carrier free) or HU (1.0 x 10/sup -9/ and 1.0 x 10/sup -3/M). At the termination of treatment the co-cultures were split 3 to 1 and incubated for seven days. As expected, there was little or no detectable effect on the growth of WI38 cells treated with HU or /sup 125/IUdR while the cells were confluent. However, HeLa cells were reduced by 1.0 x 10/sup -3/M HU and were eradicated after all concentrations of /sup 125/IUdR

  6. Clinical perspectives of cancer stem cell research in radiation oncology

    International Nuclear Information System (INIS)

    Bütof, Rebecca; Baumann, Michael; Dubrovska, Anna

    2013-01-01

    Radiotherapy has a proven potential to eradicate cancer stem cells which is reflected by its curative potential in many cancer types. Considerable progress has been made in identification and biological characterisation of cancer stem cells during the past years. Recent biological findings indicate significant inter- and intratumoural and functional heterogeneity of cancer stem cells and lead to more complex models which have potential implications for radiobiology and radiotherapy. Clinical evidence is emerging that biomarkers of cancer stem cells may be prognostic for the outcome of radiotherapy in some tumour entities. Perspectives of cancer stem cell based research for radiotherapy reviewed here include their radioresistance compared to the mass of non-cancer stem cells which form the bulk of all tumour cells, implications for image- and non-image based predictive bio-assays of the outcome of radiotherapy and a combination of novel systemic treatments with radiotherapy

  7. Stromal-cell and cancer-cell exosomes leading the metastatic exodus for the promised niche

    OpenAIRE

    Hoffman, Robert M

    2013-01-01

    Exosomes are thought to play an important role in metastasis. Luga and colleagues have described the production of exosomes by stromal cells such as cancer-associated fibroblasts that are taken up by breast cancer cells and are then loaded with Wnt 11, which is associated with stimulation of the invasiveness and metastasis of the breast cancer cells. Previous studies have shown that exosomes produced by breast cancer cells are taken up by stromal fibroblasts and other stromal cells, suggestin...

  8. Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

    Directory of Open Access Journals (Sweden)

    Lisa Y. Pang

    2016-01-01

    Full Text Available Cyclooxygenase-2 (COX-2 is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2, a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

  9. Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in Uremic Serum-Exposed Human Rhabdomyosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Hitoshi Uchiyama

    2018-01-01

    Full Text Available Patients with end-stage kidney disease (ESKD are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity of various trace elements in ESKD patients likely contribute as well. The purpose of this study is to determine the effect of trace elements on statin-induced toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells for a long time. Cell viability, apoptosis, mRNA expression, and intracellular trace elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity than cells long-time exposed with normal serum (NS cells (non-overlapping 95% confidence intervals. Intracellular levels of Mg, Mn, Cu, and Zn were significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01. Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated the distinction between both cells of simvastatin-induced cytotoxicity. These results suggest that Zn deficiencies may be involved in the increased risk for muscle complaints in ESKD patients. In conclusion, the increased severity of statin-induced rhabdomyolysis in ESKD patients may be partly due to trace elements deficiencies.

  10. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  11. Rifampicin sensitivity of residual RNA synthesis in Escherichia coli cells exposed to ultraviolet radiation and combined ultraviolet and γ radiations

    International Nuclear Information System (INIS)

    Prakash, R.K.; Netrawali, M.S.; Pradhan, D.S.

    1976-01-01

    UV-irradiation prevents rifampicin inhibition of the initiation of RNA synthesis by E.coli cells, but such rifampicin insensitivity is not exhibited by the residual RNA synthesis in γ-irradiated cells. Studies of the rate of [ 3 H]-uridine incorporation by E.coli cells at various times of incubation have been used to show that when γ-irradiation was given either before or after UV-irradiation of cells, the observed rifampicin insensitivity of residual RNA synthesis in the UV-irradiated cells was obliterated. RNA synthesis in cells subjected to combined exposures of UV- and γ-radiations was lowered to a lesser extent than that in the cells exposed to UV-irradiation alone. Possible mechanisms are discussed. (U.K.)

  12. Tetraploidy in monkey kidney epithelial cells exposed to various doses of radiation in vitro and in vivo. Comm.3

    International Nuclear Information System (INIS)

    Machavariani, M.G.

    1979-01-01

    The tetraploidy phenomenon in three and five day cultures of monkey kidney epithelial cells exposed to various doses of X-rays at Gsub(0) stage has been revealed. The data are presented on simple and complex tetraploidal enclo-reduplicated cells in monkey kidney epithelium after whole-body irradiaiton of animals by 60 Co γ-rays in dosage of 620-660 R. The frequency decrease of endoreduplicated cells at the second month coincides with the frequency increase of simple tetraploidal cells. In the investigated culture of monkey kidney epithelial cells, irradiated in vitro, a trend is observed towards the increase of the number of tetraploidal cells. An assumption is made on the possibility of using the frequency of tetraploidal cells ( including lymphocytes) for the purposes of biological dosimetry

  13. Rifampicin sensitivity of residual RNA synthesis in Escherichia coli cells exposed to ultraviolet radiation and combined ultraviolet and. gamma. radiations

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, R K; Netrawali, M S; Pradhan, D S [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1976-09-01

    UV-irradiation prevents rifampicin inhibition of the initiation of RNA synthesis by E.coli cells, but such rifampicin insensitivity is not exhibited by the residual RNA synthesis in ..gamma..-irradiated cells. Studies of the rate of (/sup 3/H)-uridine incorporation by E.coli cells at various times of incubation have been used to show that when ..gamma.. irradiation was given either before or after uv-irradiation of cells, the observed rifampicin insensitivity of residual RNA synthesis in the uv-irradiated cells was obliterated. RNA synthesis in cells subjected to combined exposures of uv- and ..gamma..-radiations was lowered to a lesser extent than that in the cells exposed to uv-irradiation alone. Possible mechanisms are discussed.

  14. Enhancement of cell death by TNF α-related apoptosis-inducing ligand (TRAIL) in human lung carcinoma A549 cells exposed to X rays under hypoxia

    International Nuclear Information System (INIS)

    Takahashi, Momoko; Inanami, Osamu; Yasui, Hironobu; Ogura, Aki; Kuwabara, Mikinori; Kubota, Nobuo; Tsujitani, Michihiko

    2007-01-01

    Our previous study showed that ionizing radiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines and that the death receptor of the TNF α-related apoptosis-inducing ligand TRAIL enhanced the apoptotic pathway (Hamasu et al., (2005) Journal of Radiation Research, 46:103-110). The present experiments were performed to examine whether treatment with TRAIL enhanced the cell killing in tumor cells exposed to ionizing radiation under hypoxia, since the presence of radioresistant cells in hypoxic regions of solid tumors is a serious problem in radiation therapy for tumors. When human lung carcinoma A549 cells were irradiated under normoxia and hypoxia, respectively, radiation-induced enhancement of expression of DR5 was observed under both conditions. Incubation in the presence of TRAIL enhanced the caspase-dependent and chymotrypsin-like-protease-dependent apoptotic cell death in A549 cells exposed to X rays. Furthermore, it was shown that treatment with TRAIL enhanced apoptotic cell death and loss of clonogenic ability in A549 cells exposed to X rays not only under normoxia but also under hypoxia, suggesting that combination treatment with TRAIL and X irradiation is effective for hypoxic tumor cells. (author)

  15. Gallic acid induced apoptotic events in HCT-15 colon cancer cells

    Science.gov (United States)

    Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

    2016-01-01

    AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2’,7’-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells. PMID:27099438

  16. Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen

    International Nuclear Information System (INIS)

    Hulette, Ben C.; Ryan, Cindy A.; Gildea, Lucy A.; Gerberick, G. Frank

    2005-01-01

    Human peripheral blood-derived dendritic cells (DC) respond to a variety of chemical allergens by up-regulating expression of the co-stimulatory molecule CD86. It has been postulated that this measure might provide the basis for an in vitro alternative approach for the identification of skin sensitizing chemicals. We recently reported that DC, exposed in culture to the highest non-cytotoxic concentrations of various chemical allergens, displayed marginal up-regulation of membrane CD86 expression; the interpretation being that such changes were insufficiently sensitive for the purposes of hazard identification. For the work presented here, immature DC were derived from human monocytes and treated with the chemical allergens 2,4-dinitrobenzenesulfonic acid (DNBS), nickel sulfate (NiSO 4 ), p-phenylenediamine (PPD), Bandrowski's base (BB), hydroquinone (HQ) and propyl gallate (PG) for 48 h at concentrations which induced both no to slight to moderate cytotoxicity. For comparison, DC were treated with the irritants sodium dodecyl sulfate (SDS), benzoic acid (BA), and benzalkonium chloride (BZC) at concentrations resulting in comparable levels of cytotoxicity. CD86 expression, as measured by flow cytometry, was consistently up-regulated (ranging from 162 to 386% control) on DC treated with concentrations of chemical allergens that induced approximately 10-15% cytotoxicity. The irritants BA and BZC did not induce up-regulation of CD86 expression when tested at concentrations that induced similar levels of cytotoxicity. SDS, however, up-regulated CD86 expression to 125-138% of control in 2/4 preparations when tested at concentrations which induced similar toxicity. Our results confirm that chemical allergens up-regulate CD86 expression on blood-derived DC and illustrate further that up-regulation of CD86 surface marker expression is more robust when DC are treated with concentrations of chemical allergen that induce slight to moderate cytotoxicity

  17. Low CD4+ T-cell levels and B-cell apoptosis in vertically HIV-exposed noninfected children and adolescents.

    Science.gov (United States)

    Miyamoto, Maristela; Pessoa, Silvana D; Ono, Erika; Machado, Daisy M; Salomão, Reinaldo; Succi, Regina C de M; Pahwa, Savita; de Moraes-Pinto, Maria Isabel

    2010-12-01

    Lymphocyte subsets, activation markers and apoptosis were assessed in 20 HIV-exposed noninfected (ENI) children born to HIV-infected women who were or not exposed to antiretroviral (ARV) drugs during pregnancy and early infancy. ENI children and adolescents were aged 6-18 years and they were compared to 25 age-matched healthy non-HIV-exposed children and adolescents (Control). ENI individuals presented lower CD4(+) T cells/mm(3) than Control group (control: 1120.3 vs. ENI: 876.3; t-test, p = 0.030). ENI individuals had higher B-cell apoptosis than Control group (Control: 36.6%, ARV exposed: 82.3%, ARV nonexposed: 68.5%; Kruskal-Wallis, p ENI and in Control children and adolescents. Subtle long-term immune alterations might persist among ENI individuals, but the clinical consequences if any are unknown, and these children require continued monitoring.

  18. Glucocorticoid receptor beta increases migration of human bladder cancer cells.

    Science.gov (United States)

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

  19. Difference in membrane repair capacity between cancer cell lines and a normal cell line

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; McNeil, Anna K.; Novak, Ivana

    2016-01-01

    repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique...... cancer cell lines (p immortalized cell line (p

  20. Numerical study of induced current perturbations in the vicinity of excitable cells exposed to extremely low frequency magnetic fields

    International Nuclear Information System (INIS)

    Hassan, Noha; Chatterjee, Indira; Publicover, Nelson G; Craviso, Gale L

    2003-01-01

    Realistic three-dimensional cell morphologies were modelled to determine the current density induced in excitable cell culture preparations exposed to 60 Hz magnetic fields and to identify important factors that can influence the responses of cells to these fields. Cell morphologies representing single spherical adrenal chromaffin cells, single elongated smooth muscle cells and chromaffin cell aggregates in a Petri dish containing culture medium were modelled using the finite element method. The computations for a spherical cell revealed alterations in the magnitude and spatial distribution of the induced current density in the immediate vicinity of the cell. Maxima occurred at the equatorial sides and minima at the poles. Proximity of cells to each other as well as cell aggregate shape, size and orientation with respect to the induced current influenced the magnitude and spatial distribution of the induced current density. For an elongated cell, effects on the induced current density were highly dependent on cell orientation with respect to the direction of the induced current. These results provide novel insights into the perturbations in induced current that occur in excitable cell culture preparations and lay a foundation for understanding the mechanisms of interaction with extremely low frequency magnetic fields at the tissue level

  1. Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

    KAUST Repository

    La Rocca, Rosanna

    2014-12-26

    In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells) was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal), depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm−1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK) cells cytotoxic recognition.

  2. Mechanical stress downregulates MHC class I expression on human cancer cell membrane.

    Directory of Open Access Journals (Sweden)

    Rosanna La Rocca

    Full Text Available In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal, depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700-1800 cm(-1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK cells cytotoxic recognition.

  3. Mechanisms of drug resistance in cancer cells

    International Nuclear Information System (INIS)

    Iqbal, M.P.

    2003-01-01

    Development of drug resist chemotherapy. For the past several years, investigators have been striving hard to unravel mechanisms of drug resistance in cancer cells. Using different experimental models of cancer, some of the major mechanisms of drug resistance identified in mammalian cells include: (a) Altered transport of the drug (decreased influx of the drug; increased efflux of the drug (role of P-glycoprotein; role of polyglutamation; role of multiple drug resistance associated protein)), (b) Increase in total amount of target enzyme/protein (gene amplification), (c) alteration in the target enzyme/protein (low affinity enzyme), (d) Elevation of cellular glutathione, (e) Inhibition of drug-induced apoptosis (mutation in p53 tumor suppressor gene; increased expression of bcl-xl gene). (author)

  4. Small cell lung cancer: chemo- and radiotherapy

    International Nuclear Information System (INIS)

    Drings, P.

    1992-01-01

    Small-Cell Lung Cancer - Chemo- and Radiotherapy: Small-cell lung cancer (SCLC) should be regarded as a systematic disease for which systematic therapy, i.e. chemotherapy, is considered as the cornerstone of treatment. Combination chemotherapy consisting of 2 or mostly 3 active drugs, given at an adequate dose, should be used. Thoracic radiation therapy promises both survival and local-regional control benefits to patients though its optimal role remains to be definitively established. The results of treatment have reached a plateau with a remission rate of up to 90% in stage 'limited disease' and 60% in stage 'extensive disease'. But considering long-term results diseasefree survival and cure only seem possible in 5-10% of patients with limited disease. (orig.) [de

  5. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

    Directory of Open Access Journals (Sweden)

    Hidehiko Takigawa

    2017-05-01

    Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

  6. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  7. Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.

    Science.gov (United States)

    Nakamura, Koji; Sawada, Kenjiro; Kinose, Yasuto; Yoshimura, Akihiko; Toda, Aska; Nakatsuka, Erika; Hashimoto, Kae; Mabuchi, Seiji; Morishige, Ken-Ichirou; Kurachi, Hirohisa; Lengyel, Ernst; Kimura, Tadashi

    2017-01-01

    Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR. ©2016 American

  8. Metastasis Targeted Therapies in Renal Cell Cancer

    OpenAIRE

    K. Fehmi Narter; Bora Özveren

    2018-01-01

    Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

  9. NK cells, pregnancy, cancer. A short review

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Pospíšil, Miloslav; Fišerová, Anna

    2005-01-01

    Roč. 8, č. 4 (2005), s. 147-152 ISSN 1506-4794 R&D Projects: GA AV ČR IAA500200509; GA AV ČR IAA5020403; GA ČR GA524/04/0102; GA AV ČR IAA500200510 Institutional research plan: CEZ:AV0Z50200510 Keywords : natural killer cells * immune tolerance * cancer Subject RIV: EE - Microbiology, Virology

  10. Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    International Nuclear Information System (INIS)

    Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

    2010-01-01

    Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

  11. Membrane Proteins : The Key Players of a Cancer Cell

    NARCIS (Netherlands)

    Kampen, Kim R.

    Membrane proteins are involved in the prognosis of the most common forms of cancer. Membrane proteins are the hallmark of a cancer cell. The overexpressed membrane receptors are becoming increasingly important in cancer cell therapy. Current renewing therapy approaches based on receptor

  12. USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS

    Science.gov (United States)

    People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic properties in experimental systems. It has been estimated that exposure to environmental chemical carcinogens in the environment may contribute significantly to t...

  13. Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: The role of glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Brechbuhl, Heather M. [Pediatrics, National Jewish Health, Denver, Colorado (United States); Kachadourian, Remy; Min, Elysia [Department of Medicine, National Jewish Health, Denver, Colorado (United States); Chan, Daniel [Medical Oncology, University of Colorado Denver Health Sciences Center (United States); Day, Brian J., E-mail: dayb@njhealth.org [Department of Medicine, University of Colorado Denver Health Sciences Center (United States); Immunology, University of Colorado Denver Health Sciences Center (United States); Pharmaceutical Sciences, University of Colorado Denver Health Sciences Center (United States); Department of Medicine, National Jewish Health, Denver, Colorado (United States)

    2012-01-01

    We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi-drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a viable mechanism to sensitize cancer cells to chemotherapies. This concept was demonstrated using chrysin (5–25 μM) induced GSH efflux in human non-small cell lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX). Treatment with chrysin resulted in significant and sustained intracellular GSH depletion and the GSH enzyme network in the four cancer cell types was predictive of the severity of chrysin induced intracellular GSH depletion. Gene expression data indicated a positive correlation between basal MRP1, MRP3 and MRP5 expression and total GSH efflux before and after chrysin exposure. Co-treating the cells for 72 h with chrysin (5–30 μM) and DOX (0.025–3.0 μM) significantly enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone treatment in all four cell lines. The maximum decrease in the IC{sub 50} values of cells treated with DOX alone compared to co-treatment with chrysin and DOX was 43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin worked synergistically with DOX to induce cancer cell death. This approach could allow for use of lower concentrations and/or sensitize cancer cells to drugs that are typically resistant to therapy. -- Graphical abstract: Possible mechanisms by which chrysin enhances doxorubicin-induced toxicity in cancer cells. Highlights: ► Chyrsin sustains a significant depletion of GSH levels in lung cancer cells. ► Chyrsin synergistically potentiates doxorubicin-induced cancer cell cytotoxicity. ► Cancer cell sensitivity correlated with GSH and MRP gene network expression. ► This approach could allow for lower side effects and targeting resistant tumors.

  14. Cell-ECM Interactions During Cancer Invasion

    Science.gov (United States)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  15. The role of dendritic cells in cancer

    DEFF Research Database (Denmark)

    Hansen, Morten; Andersen, Mads Hald

    2017-01-01

    Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8+ T-cells and Th1 helper CD4+ T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when...... infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103+ DCs, which have been shown to be experts in cross-priming and the induction...... of anti-tumor immunity. We also focus on two different mediators that impair the function of tumor-associated DCs: prostaglandin E2 and β-catenin. Both of these mediators seem to be important for the exclusion of T-cells in the tumor microenvironment and may represent key pathways to target in optimized...

  16. Generation of Breast Cancer Stem Cells by the EMT

    Science.gov (United States)

    2009-10-01

    shift in the type of human breast cancer cells. We began to use experimentally immortalized HMLE cells that were then transformed through...Generation of Breast Cancer Stem Cells by the EMT PRINCIPAL INVESTIGATOR: Robert A. Weinberg, Ph.D. CONTRACTING...Generation of Breast Cancer Stem Cells by the EMT 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0464 5c. PROGRAM ELEMENT NUMBER 6

  17. Environmental impact of heavy metals on the blood cells in professionally exposed workers

    OpenAIRE

    Velickova, Nevenka

    2017-01-01

    Aims of the study is to explain and research the effects of the heavy metals (lead, zinc and cadmium) on erythrocytes and leukocytes in miners with different work experience or exposure. The results and conclusions are made based on a three-year period of continuous testing on 120 miners, as professionally exposed workers. We confirmed that the miners long been professionally exposed to heavy metals, in the blood have an increased content of heavy metals (lead, zinc and cadmium) and they ha...

  18. Age standardized cancer mortality ratios in areas heavily exposed to methyl mercury.

    Science.gov (United States)

    Yorifuji, Takashi; Tsuda, Toshihide; Kawakami, Norito

    2007-08-01

    Methyl-mercury (MeHg) was discharged from a chemical factory in Minamata, and consequently spread throughout the Shiranui Sea in Kumamoto, Japan. Although many studies have focused on MeHg-induced neurological disorders, the association between MeHg and malignant neoplasms has not been adequately investigated. Therefore, we explored this association using the age standardized mortality ratio (ASMR) in an ecologic study over a wide area allowing for a long empirical induction period. The subjects were residents in areas around the Shiranui Sea. We divided these areas into exposure groups 1 (Minamata and Ashikita regions) and 2 (Amakusa region). Exposure group 1 was contaminated from the late 1930s, and exposure group 2 was contaminated from the late 1950s. In addition, exposure group 1 was contaminated more heavily than exposure group 2. There were 92,525 and 152,541 residents in each group in 1960, respectively. We analyzed the cancer ASMR in both exposure groups using data from two reference populations (Japan and Kumamoto prefecture) from 1961 to 1997. There were 94,301,494 and 1,856,192 people in each reference group in 1960, respectively. We abstracted population and mortality data from the censuses and the vital statistics of the prefecture and Japan. An increased leukemia ASMR and a decreased gastric cancer ASMR were observed in both exposure groups, while other ASMRs were around unity and less precise. Furthermore, the leukemia ASMRs were elevated differently between the two exposure groups: the leukemia ASMR was already elevated early in the study period in exposure group 1 and increased gradually in exposure group 2. While the negative association between MeHg and gastric cancer might be explained by salt intake, the positive association between MeHg and leukemia could not be explained by potential confounders. Despite some limitations mainly due to its ecologic design, this study indicates the necessity of an individual-level study evaluating the

  19. In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+Tumor-Initiating Cell Subset

    Czech Academy of Sciences Publication Activity Database

    Kučerová, L.; Feketeová, L.; Kozovská, Z.; Poturnajová, M.; Matusková, M.; Nencka, Radim; Babál, P.

    2014-01-01

    Roč. 24, č. 3 (2014), s. 520-532 ISSN 1050-7256 Institutional support: RVO:61388963 Keywords : cancer stem cells * thymidylate synthase * colorectal cancer Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.493, year: 2014

  20. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Kucerova, Lucia; Skolekova, Svetlana; Matuskova, Miroslava; Bohac, Martin; Kozovska, Zuzana

    2013-01-01

    Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses

  1. EMMPRIN regulates cytoskeleton reorganization and cell adhesion in prostate cancer.

    Science.gov (United States)

    Zhu, Haining; Zhao, Jun; Zhu, Beibei; Collazo, Joanne; Gal, Jozsef; Shi, Ping; Liu, Li; Ström, Anna-Lena; Lu, Xiaoning; McCann, Richard O; Toborek, Michal; Kyprianou, Natasha

    2012-01-01

    Proteins on cell surface play important roles during cancer progression and metastasis via their ability to mediate cell-to-cell interactions and navigate the communication between cells and the microenvironment. In this study a targeted proteomic analysis was conducted to identify the differential expression of cell surface proteins in human benign (BPH-1) versus malignant (LNCaP and PC-3) prostate epithelial cells. We identified EMMPRIN (extracellular matrix metalloproteinase inducer) as a key candidate and shRNA functional approaches were subsequently applied to determine the role of EMMPRIN in prostate cancer cell adhesion, migration, invasion as well as cytoskeleton organization. EMMPRIN was found to be highly expressed on the surface of prostate cancer cells compared to BPH-1 cells, consistent with a correlation between elevated EMMPRIN and metastasis found in other tumors. No significant changes in cell proliferation, cell cycle progression, or apoptosis were detected in EMMPRIN knockdown cells compared to the scramble controls. Furthermore, EMMPRIN silencing markedly decreased the ability of PC-3 cells to form filopodia, a critical feature of invasive behavior, while it increased expression of cell-cell adhesion and gap junction proteins. Our results suggest that EMMPRIN regulates cell adhesion, invasion, and cytoskeleton reorganization in prostate cancer cells. This study identifies a new function for EMMPRIN as a contributor to prostate cancer cell-cell communication and cytoskeleton changes towards metastatic spread, and suggests its potential value as a marker of prostate cancer progression to metastasis. Copyright © 2011 Wiley Periodicals, Inc.

  2. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

  3. Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia

    International Nuclear Information System (INIS)

    Sun, Hong; Shamy, Magdy; Kluz, Thomas; Muñoz, Alexandra B.; Zhong, Mianhua; Laulicht, Freda; Alghamdi, Mansour A.; Khoder, Mamdouh I.; Chen, Lung-Chi; Costa, Max

    2012-01-01

    Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. This study aims to investigate the global gene expression changes in human cells exposed to PM 10 and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM 10 collected from Saudi Arabia for 1 or 4 days, and whole transcript expression was profiled using the GeneChip human gene 1.0 ST array. A total of 140 and 230 genes were identified that significantly changed more than 1.5 fold after PM 10 exposure for 1 or 4 days, respectively. Ingenuity Pathway Analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significant changes in genes related to cholesterol and lipid synthesis pathways. These observed changes in cellular oxidative stress and lipid synthesis might contribute to PM related respiratory and cardiovascular disease. -- Highlights: ► PM exposure modulated gene expression and associated pathways in BEAS-2B cells. ► One-day exposure to PM induced genes involved in responding to oxidative stress. ► 4-day exposure to PM changed genes associated to cholesterol and lipid synthesis.

  4. Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions.

    Science.gov (United States)

    Kim, Sang Eun; Park, Hye-Jin; Jeong, Hye Kyoung; Kim, Mi-Jung; Kim, Minyeong; Bae, Ok-Nam; Baek, Seung-Hoon

    2015-07-31

    Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating type of cancer with high mortality. Given the dense stroma and poor vascularization, accessibility to nutrients is limited in the tumor microenvironment. Here, we aimed to elucidate the role of autophagy in promoting the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial depolarization. NDM also time-dependently increased LC3-II accumulation, number of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These results suggested that autophagy was progressively activated through Akt- and AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z-VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that autophagy is anti-apoptotic and sustains the survival of PANC-1 cells following extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic option for cancer cells located in the core of solid tumors with a nutrient-deficient microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Global gene expression changes in human urothelial cells exposed to low-level monomethylarsonous acid

    International Nuclear Information System (INIS)

    Medeiros, Matthew; Zheng, Xinghui; Novak, Petr; Wnek, Shawn M.; Chyan, Vivian; Escudero-Lourdes, Claudia; Gandolfi, A. Jay

    2012-01-01

    Highlights: ► Chronic exposure to 50 nM monomethylarsonous acid in UROtsa was investigated. ► At 3 months of exposure substantial changes were observed in gene expression. ► Notable changes occurred in mitogenic signaling, stress, immune and inflammatory responses. ► Gene expression changes correlate with phenotypic changes from previous studies. -- Abstract: Bladder cancer has been associated with chronic arsenic exposure. Monomethylarsonous acid [MMA(III)] is a metabolite of inorganic arsenic and has been shown to transform an immortalized urothelial cell line (UROtsa) at concentrations 20-fold less than arsenite. MMA(III) was used as a model arsenical to examine the mechanisms of arsenical-induced transformation of urothelium. A microarray analysis was performed to assess the transcriptional changes in UROtsa during the critical window of chronic 50 nM MMA(III) exposure that leads to transformation at 3 months of exposure. The analysis revealed only minor changes in gene expression at 1 and 2 months of exposure, contrasting with substantial changes observed at 3 months of exposure. The gene expression changes at 3 months were analyzed showing distinct alterations in biological processes and pathways such as a response to oxidative stress, enhanced cell proliferation, anti-apoptosis, MAPK signaling, as well as inflammation. Twelve genes selected as markers of these particular biological processes were used to validate the microarray and these genes showed a time-dependent changes at 1 and 2 months of exposure, with the most substantial changes occurring at 3 months of exposure. These results indicate that there is a strong association between the acquired phenotypic changes that occur with chronic MMA(III) exposure and the observed gene expression patterns that are indicative of a malignant transformation. Although the substantial changes that occur at 3 months of exposure may be a consequence of transformation, there are common occurrences of altered

  6. Long term imaging of living brain cancer cells

    Science.gov (United States)

    Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

    2018-02-01

    QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

  7. Antiproliferative activity of tea catechins associated with casein micelles, using HT29 colon cancer cells.

    Science.gov (United States)

    Haratifar, S; Meckling, K A; Corredig, M

    2014-02-01

    Numerous studies have shown that green tea polyphenols display anticancer activities in many organ sites by using different experimental models in rodents and in cultured cell lines in vitro. The present study tested the ability of casein micelles to deliver biologically active concentrations of polyphenols to HT-29 colon cancer cells. Epigallocatechin gallate (EGCG), the major catechin found in green tea, was used as the model molecule, as it has been shown to have antiproliferative activity on colon cancer cells. In the present work, we hypothesized that due to the binding of caseins with EGCG, casein micelles may be an ideal platform for the delivery of this bioactive molecule and that the binding would not affect the bioaccessibility of EGCG. The cytotoxicity and proliferation behavior of HT-29 colon cancer cells when exposed to free EGCG was compared with that of nanoencapsulated EGCG in casein micelles of skim milk. Epigallocatechin gallate-casein complexes were able to decrease the proliferation of HT-29 cancer cells, demonstrating that bioavailability may not be reduced by the nanoencapsulation. As casein micelles may act as protective carriers for EGCG in foods, it was concluded that nanoencapsulation of tea catechins in casein micelles may not diminish their antiproliferative activity on colon cancer cells compared with free tea catechins. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

    Science.gov (United States)

    Zhan, Han-Xiang; Zhou, Bin; Cheng, Yu-Gang; Xu, Jian-Wei; Wang, Lei; Zhang, Guang-Yong; Hu, San-Yuan

    2017-04-28

    Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

    International Nuclear Information System (INIS)

    Ogata, Hiromitsu; Magae, Junji

    2008-01-01

    Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

  10. Induction of Immunogenic Cell Death with Non-Thermal Plasma for Cancer Immunotherapy

    Science.gov (United States)

    Lin, Abraham G.

    Even with the recent advancements in cancer immunotherapy, treatments are still associated with debilitating side effects and unacceptable fail rates. Induction of immunogenic cell death (ICD) in tumors is a promising approach to cancer treatment that may overcome these deficiencies. Cells undergoing ICD pathways enhance the interactions between cancerous cells and immune cells of the patient, resulting in the generation of anti-cancer immunity. The goal of this therapy relies on the engagement and reestablishment of the patient's natural immune processes to target and eliminate cancerous cells systemically. The main objective of this research was to determine if non-thermal plasma could be used to elicit immunogenic cancer cell death for cancer immunotherapy. My hypothesis was that plasma induces immunogenic cancer cell death through oxidative stress pathways, followed by development of a specific anti-tumor immune response. This was tested by investigating the interactions between plasma and multiple cancerous cells in vitro and validating anti-tumor immune responses in vivo. Following plasma treatment, two surrogate ICD markers, secreted adenosine triphosphate (ATP) and surface exposed calreticulin (ecto-CRT), were emitted from all three cancerous cell lines tested: A549 lung carcinoma cell line, CNE-1 radiation-resistant nasopharyngeal cell line and CT26 colorectal cancer cell line. When these cells were co-cultured with macrophages, cells of the innate immune system, the tumoricidal activity of macrophages was enhanced, thus demonstrating the immunostimulatory activity of cells undergoing ICD. The underlying mechanisms of plasma-induced ICD were also evaluated. When plasma is generated, four major components are produced: electromagnetic fields, ultraviolet radiation, and charged and neutral reactive species. Of these, we determined that plasma-generated charged and short-lived reactive oxygen species (ROS) were the major effectors of ICD. Following plasma

  11. Effects on elevating cancer risk in population exposed to natural radionuclide 226Ra if parent radionuclide 238U is entered the body by inhalation or ingestion

    International Nuclear Information System (INIS)

    Zupunski, Lj.; Trobok, M.; Gordanic, V.; Spasic-Jokic, V.; Sovilj, P.

    2009-01-01

    People have always been exposed to ionizing radiation originating from natural radionuclides including 238 U, 40 K, 232 Th that exist in earths crust. Although received doses are small, due to the fact that threshold does not exist, there is a certain risk of developing cancer. Purpose of this study was to measure 238 U concentrations in soil of Bela Crkva territory. Based on these measurements, risks of developing cancers are calculated using Monte Carlo method.(author) [sr

  12. Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth

    Science.gov (United States)

    Kim, EuiJoo

    2017-01-01

    Introduction The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. Method Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. Results We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. Conclusion Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells. PMID:28708871

  13. Niche construction game cancer cells play.

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  14. Niche construction game cancer cells play

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  15. Production and excision of thymine damage in the DNA of mammalian cells exposed to high-LET radiations

    International Nuclear Information System (INIS)

    Mattern, M.R.; Welch, G.P.

    1979-01-01

    HeLa S3 and Chinese hamster ovary cells were irradiated with high doses of carbon ions having linear energy transfers (LETs) of 170 and 780 keV/μm. The DNA was analyzed for 5,6-dihydroxydihydrothymine (t'-type) radiation products both before and after postirradiation incubation at 37 0 C. In HeLa cells, 2.1 x 10 -5 ring-damaged thymines were produced per kilorad per 10 6 daltons after irradiation with high-LET carbon ions - approximately one-fifth the efficiency of t' formation in HeLa cells exposed to low-LET x rays. t' products were also formed less efficiently in Chinese hamster ovary cells exposed to carbon ions than in those exposed to x rays. In both cell lines, up to 80% of the t' formed initially was excised selectively from the DNA during 60 min of postirradiation incubation at 37 0 C. Product excision was accompanied by small amounts of DNA degradation (less than 1%). Radiation with LET of 170 keV/μm - nearly the most effective LET for cell killing and the generation of unrejoined DNA strand breaks - produced ring-damaged thymines that were removed selectively from the DNA. This result is consistent with the conclusion that t'-type products do not contribute substantially to lethality after high-LET irradiation, although the alternative possibilities remain that t' is not excised as efficiently after biological doses, or that a particular subclass of t' or defective postexcision events contribute to cell killing

  16. From gametogenesis and stem cells to cancer: common metabolic themes.

    Science.gov (United States)

    Pereira, Sandro L; Rodrigues, Ana Sofia; Sousa, Maria Inês; Correia, Marcelo; Perestrelo, Tânia; Ramalho-Santos, João

    2014-01-01

    Both pluripotent stem cells (PSCs) and cancer cells have been described as having similar metabolic pathways, most notably a penchant for favoring glycolysis even under aerobiosis, suggesting common themes that might be explored for both stem cell differentiation and anti-oncogenic purposes. A search of the scientific literature available in the PubMed/Medline was conducted for studies on metabolism and mitochondrial function related to gametogenesis, early development, stem cells and cancers in the reproductive system, notably breast, prostate, ovarian and testicular cancers. Both PSCs and some types of cancer cells, particularly reproductive cancers, were found to obtain energy mostly by glycolysis, often reducing mitochondrial activity and oxidative phosphorylation. This strategy links proliferating cells, allowing for the biosynthesis reactions necessary for cell division. Interventions that affect metabolic pathways, and force cells to change their preferences, can lead to shifts in cell status, increasing either pluripotency or differentiation of stem cells, and causing cancer cells to become more or less aggressive. Interestingly metabolic changes in many cases seemed to lead to cell transformation, not necessarily follow it, suggesting a direct role of metabolic choices in influencing the (epi)genetic program of different cell types. There are uncanny similarities between PSCs and cancer cells at the metabolic level. Furthermore, metabolism may also play a direct role in cell status and targeting metabolic pathways could therefore be a promising strategy for both the control of cancer cell proliferation and the regulation of stem cell physiology, in terms of manipulating stem cells toward relevant phenotypes that may be important for tissue engineering, or making cancer cells become less tumorigenic. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For

  17. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

  18. Are ovarian cancer stem cells the target for innovative immunotherapy?

    Directory of Open Access Journals (Sweden)

    Wang L

    2018-05-01

    Full Text Available Liang Wang, Tianmin Xu, Manhua Cui Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Abstract: Cancer stem cells (CSCs, a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy, immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR- T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. Keywords: cancer stem cells, ovarian cancer, epigenetics, tumor cell surface marker, immunotherapy, CAR

  19. Regulation of Breast Cancer Stem Cell by Tissue Rigidity

    Science.gov (United States)

    2014-06-01

    metastasis. Cancer Cell 20: 576– 590 . Ledford H. 2011. Cancer theory faces doubts. Nature 472: 273. Lee KE, Bar-Sagi D. 2010. Oncogenic KRas suppresses...blocks the cell cycle and confers resistance to cell death. Genes Dev 18: 1131–1143. Vesuna F, Lisok A, Kimble B, Raman V. 2009. Twist modulates

  20. Mutagenic adaptive response to high-LET radiation in human lymphoblastoid cells exposed to X-rays.

    Science.gov (United States)

    Varès, Guillaume; Wang, Bing; Tanaka, Kaoru; Kakimoto, Ayana; Eguchi-Kasai, Kyomi; Nenoi, Mitsuru

    2011-01-10

    The ability of cells to adapt low-dose or low-dose rate radiation is well known. High-LET radiation has unique characteristics, and the data concerning low doses effects and high-LET radiation remain fragmented. In this study, we assessed in vitro the ability of low doses of X-rays to induce an adaptive response (AR) to a subsequent challenging dose of heavy-ion radiation. Lymphoblastoid cells (TK6, AHH-1, NH32) were exposed to priming 0.02-0.1Gy X-rays, followed 6h later by challenging 1Gy heavy-ion radiation (carbon-ion: 20 and 40keV/μm, neon-ion: 150keV/μm). Pre-exposure of p53-competent cells resulted in decreased mutation frequencies at hypoxanthine-guanine phosphoribosyl transferase locus and different H2AX phosphorylation kinetics, as compared to cells exposed to challenging radiation alone. This phenomenon did not seem to be linked with cell cycle effects or radiation-induced apoptosis. Taken together, our results suggested the existence of an AR to mutagenic effects of heavy-ion radiation in lymphoblastoid cells and the involvement of double-strand break repair mechanisms. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.

    Science.gov (United States)

    Alexsandra da Silva Neto Trajano, Larissa; da Silva, Camila Luna; de Carvalho, Simone Nunes; Cortez, Erika; Mencalha, André Luiz; de Souza da Fonseca, Adenilson; Stumbo, Ana Carolina

    2016-07-01

    Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells.

  2. Proteomic Profiling Reveals That Resveratrol Inhibits HSP27 Expression and Sensitizes Breast Cancer Cells to Doxorubicin Therapy

    OpenAIRE

    D?az-Ch?vez, Jos?; Fonseca-S?nchez, Miguel A.; Arechaga-Ocampo, Elena; Flores-P?rez, Ali; Palacios-Rodr?guez, Yadira; Dom?nguez-G?mez, Guadalupe; Marchat, Laurence A.; Fuentes-Mera, Lizeth; Mendoza-Hern?ndez, Guillermo; Gariglio, Patricio; L?pez-Camarillo, C?sar

    2013-01-01

    The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found s...

  3. Kinetics of hemopoietic stem cells and survival of mice treated with hydroxyurea and exposed to prolonged γ-radiation

    International Nuclear Information System (INIS)

    Chertkov, K.S.; Rogozkin, V.D.; Dikovenko, E.A.; Mosina, Z.M.

    1979-01-01

    A study was made of radioprotective efficiency of hydroxyurea in relation to mice exposed to prolonged 137 Cs-γ-radiation. It was found that a 30-day survival rate, under optimal conditions of treatment with hydroxyurea, was more than 40 per cent higher than that of the controls. The protective effect of hydroxyurea was manifested at the level of hemopoietic stem cells due to a quicker onset and accelerated rate of the repopulation process

  4. Therapeutic Approaches to Target Cancer Stem Cells

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC

  5. Advanced Merkel cell cancer and the elderly.

    LENUS (Irish Health Repository)

    Bird, B R

    2012-02-03

    BACKGROUND: Merkel cell cancer (MCC) is an uncommon neuroendocrine skin cancer occurring predominantly in elderly Caucasians. It tends to metastasize to regional lymph nodes and viscera and is sensitive to chemotherapy but recurs rapidly. AIM: To report one such case, its response to chemotherapy and briefly review the literature. METHODS: A 73-year-old male with a fungating primary lesion on his left knee and ulcerated inguinal lymph nodes was diagnosed with MCC and treated with chemotherapy. The two largest case series and reviews of case reports were summarised. RESULTS: His ulcer healed after two cycles of carboplatin and etoposide with improvement in quality of life. Overall response rates of nearly 60% to chemotherapy are reported but median survival is only nine months with metastatic disease. CONCLUSIONS: Chemotherapy should be considered for fit elderly patients with MCC who have recurrent or advanced disease.

  6. Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

    International Nuclear Information System (INIS)

    Terasaki, Takeo; Shimosato, Yukio; Wada, Makio; Yokota, Jun; Terada, Masaaki

    1990-01-01

    Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line. (author)

  7. Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells

    International Nuclear Information System (INIS)

    Kim, Suzy; Kwon, Eun Kyung; Lee, B. S.; Lee, Seung Hee; Park, B. S.; Wu, Hong Gyun

    2007-01-01

    Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according

  8. CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

    International Nuclear Information System (INIS)

    Desai, Amar; Webb, Bryan; Gerson, Stanton L.

    2014-01-01

    Background: Radioresistance in human tumors has been linked in part to a subset of cells termed cancer stem cells (CSCs). The prominin 1 (CD133) cell surface protein is proposed to be a marker enriching for CSCs. We explore the importance of DNA repair in contributing to radioresistance in CD133+ lung cancer cells. Materials and methods: A549 and H1299 lung cancer cell lines were used. Sorted CD133+ cells were exposed to either single 4 Gy or 8 Gy doses and clonogenic survival measured. ϒ-H2AX immunofluorescence and quantitative real time PCR was performed on sorted CD133+ cells both in the absence of IR and after two single 4 Gy doses. Lentiviral shRNA was used to silence repair genes. Results: A549 but not H1299 cells expand their CD133+ population after single 4 Gy exposure, and isolated A549 CD133+ cells demonstrate IR resistance. This resistance corresponded with enhanced repair of DNA double strand breaks (DSBs) and upregulated expression of DSB repair genes in A549 cells. Prior IR exposure of two single 4 Gy doses resulted in acquired DNA repair upregulation and improved repair proficiency in both A549 and H1299. Finally Exo1 and Rad51 silencing in A549 cells abrogated the CD133+ IR expansion phenotype and induced IR sensitivity in sorted CD133+ cells. Conclusions: CD133 identifies a population of cells within specific tumor types containing altered expression of DNA repair genes that are inducible upon exposure to chemotherapy. This altered gene expression contributes to enhanced DSB resolution and the radioresistance phenotype of these cells. We also identify DNA repair genes which may serve as promising therapeutic targets to confer radiosensitivity to CSCs

  9. Antioxidant Activity of Ixora parviflora in a Cell/Cell-Free System and in UV-Exposed Human Fibroblasts

    Directory of Open Access Journals (Sweden)

    Hsiu-Mei Chiang

    2011-07-01

    Full Text Available Polyphenols and flavonoids possess a variety of biological activities including antioxidant and anti-tumor activities. Ixora parviflora is a member of the flavonoid-rich Rubiaceae family of flowering plants and used as folk medicine in India. The aim of this study was to investigate the antioxidant activity of Ixora parviflora extract (IPE in a cell-free system and erythrocytes, and the ability of IPE to inhibit reactive oxygen species (ROS generation in human fibroblasts (Hs68 after ultraviolet (UV exposure. Various in vitro antioxidant assays were employed in this study. The extraction yield of IPE was 17.4 ± 3.9%, the total phenolic content of IPE was 26.2 μg gallic acid equivalent (GAE/mg leaves dry weight and the total flavonoids content was 54.2 ± 4.4 μg quercetin equvalent (QE/mg extract. The content of chlorogenic acid was 9.7 ± 1.2 mg/g extract. IPE at 1000 μg/mL exhibited a reducing capacity of 90.5 ± 0.6%, a 1,1-diphenyl-2-picrylhydrazy (DPPH radical scavenging activity of 96.0 ± 0.4%, a ferrous chelating activity of 72.2 ± 3.5%, a hydroxyl radical scavenging activity of 96.8 ± 1.4%, and a hydrogen peroxide scavenging activity of 99.5 ± 3.3%. IPE at 500 μg/mL also possessed inhibitory activity against 2,2'-azobis (2-methylpropionamidine dihydrochloride (AAPH-induced hemolysis of erythrocytes (89.4 ± 1.8% and resulted in a 52.9% reduction in ROS generation in UV-exposed fibroblasts. According to our findings, IPE is a potent antioxidant and a potential anti-photoaging agent.

  10. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

  11. LASER CAPTURE MICRODISSECTION AND GENE ARRAY ANALYSIS OF PALATAL EPITHELIAL AND MESENCHYMAL CELLS EXPOSED TO TCDD

    Science.gov (United States)

    Palatal shelves from embryos exposed on gestation day (GD) 12 to either retinoic acid (RA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) contact but fail to fuse. It is of interest to know if diverse agents that induce clefting via the same etiology also activate the same biochem...

  12. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available Lung cancer (LC with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC, large cell carcinoma (LCC, squamous cell carcinoma (SCC and adenocarcinoma (AC. We identified a small population of cells strongly positive for CD44 (CD44(high and a main population which was either weakly positive or negative for CD44 (CD44(low/-. Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(highCD90(+ sub-population. Moreover, these CD44(highCD90(+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(highCD90(+ population a good candidate for the lung CSCs. Both CD44(highCD90(+ and CD44(highCD90(- cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/- cells were lacking this potential. These results indicate that CD44(highCD90(+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high sub-population.

  13. Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

    Science.gov (United States)

    Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

    2013-01-01

    Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

  14. Angular-dependent light scattering from cancer cells in different phases of the cell cycle.

    Science.gov (United States)

    Lin, Xiaogang; Wan, Nan; Weng, Lingdong; Zhou, Yong

    2017-10-10

    Cancer cells in different phases of the cell cycle result in significant differences in light scattering properties. In order to harvest cancer cells in particular phases of the cell cycle, we cultured cancer cells through the process of synchronization. Flow cytometric analysis was applied to check the results of cell synchronization and prepare for light scattering measurements. Angular-dependent light scattering measurements of cancer cells arrested in the G1, S, and G2 phases have been performed. Based on integral calculations for scattering intensities from 5° to 10° and from 110° to 150°, conclusions have been reached. Clearly, the sizes of the cancer cells in different phases of the cell cycle dominated the forward scatter. Accompanying the increase of cell size with the progression of the cell cycle, the forward scattering intensity also increased. Meanwhile, the DNA content of cancer cells in every phase of the cell cycle is responsible for light scattering at large scatter angles. The higher the DNA content of cancer cells was, the greater the positive effect on the high-scattering intensity. As expected, understanding the relationships between the light scattering from cancer cells and cell cycles will aid in the development of cancer diagnoses. Also, it may assist in the guidance of antineoplastic drugs clinically.

  15. Oxygen enhancement ratios in synchronous HeLa cells exposed to low-LET radiation

    International Nuclear Information System (INIS)

    Sapozink, M.D.

    1977-01-01

    HeLa cells were synchronized by the mitotic selection method and rendered hypoxic by coincubation with an excess of heavily irradiated, but metabolically active, feeder cells. An oxygen enhancement ratio (OER) of about 3 was obtained in interphase HeLa cells irradiated with x or gamma rays. A significantly lower OER was obtained with cells in, or close to, mitosis. The significance of this decrease in the oxygen effect in mitotic cells is discussed

  16. Automatic cell cloning assay for determining the clonogenic capacity of cancer and cancer stem-like cells.

    Science.gov (United States)

    Fedr, Radek; Pernicová, Zuzana; Slabáková, Eva; Straková, Nicol; Bouchal, Jan; Grepl, Michal; Kozubík, Alois; Souček, Karel

    2013-05-01

    The clonogenic assay is a well-established in vitro method for testing the survival and proliferative capability of cells. It can be used to determine the cytotoxic effects of various treatments including chemotherapeutics and ionizing radiation. However, this approach can also characterize cells with different phenotypes and biological properties, such as stem cells or cancer stem cells. In this study, we implemented a faster and more precise method for assessing the cloning efficiency of cancer stem-like cells that were characterized and separated using a high-speed cell sorter. Cell plating onto a microplate using an automatic cell deposition unit was performed in a single-cell or dilution rank mode by the fluorescence-activated cell sorting method. We tested the new automatic cell-cloning assay (ACCA) on selected cancer cell lines and compared it with the manual approach. The obtained results were also compared with the results of the limiting dilution assay for different cell lines. We applied the ACCA to analyze the cloning capacity of different subpopulations of prostate and colon cancer cells based on the expression of the characteristic markers of stem (CD44 and CD133) and cancer stem cells (TROP-2, CD49f, and CD44). Our results revealed that the novel ACCA is a straightforward approach for determining the clonogenic capacity of cancer stem-like cells identified in both cell lines and patient samples. Copyright © 2013 International Society for Advancement of Cytometry.

  17. Stem cells and cancer of the stomach and intestine.

    Science.gov (United States)

    Vries, Robert G J; Huch, Meritxell; Clevers, Hans

    2010-10-01

    Cancer in the 21st century has become the number one cause of death in developed countries. Although much progress has been made in improving patient survival, tumour relapse is one of the important causes of cancer treatment failure. An early observation in the study of cancer was the heterogeneity of tumours. Traditionally, this was explained by a combination of genomic instability of tumours and micro environmental factors leading to diverse phenotypical characteristics. It was assumed that cells in a tumour have an equal capacity to propagate the cancer. This model is currently known as the stochastic model. Recently, the Cancer stem cell model has been proposed to explain the heterogeneity of a tumour and its progression. According to this model, the heterogeneity of tumours is the result of aberrant differentiation of tumour cells into the cells of the tissue the tumour originated from. Tumours were suggested to contain stem cell-like cells, the cancer stem cells or tumour-initiating cells, which are uniquely capable of propagating a tumour much like normal stem cells fuel proliferation and differentiation in normal tissue. In this review we discuss the normal stem cell biology of the stomach and intestine followed by both the stochastic and cancer stem cell models in light of recent findings in the gastric and intestinal systems. The molecular pathways underlying normal and tumourigenic growth have been well studied, and recently the stem cells of the stomach and intestine have been identified. Furthermore, intestinal stem cells were identified as the cells-of-origin of colon cancer upon loss of the tumour suppressor APC. Lastly, several studies have proposed the positive identification of a cancer stem cell of human colon cancer. At the end we compare the cancer stem cell model and the stochastic model. We conclude that clonal evolution of tumour cells resulting from genetic mutations underlies tumour initiation and progression in both cancer models. This

  18. Novel psammaplin A derivatives sensitize human cancer cells to x-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Ho; Kim, Hak Jae; Wee, Chan Woo; Suh, Soo Youn; Kim, Il Han [Seoul National University College of Medicine, Seoul (Korea, Republic of); Ma, Eun Sook; Shin, Beom Soo [College of Pharmacy, Catholic University of Daegu. Daegu (Korea, Republic of)

    2015-04-15

    Since therapeutics such as temozolomide (TMZ) showed survival benefit in a particular subgroup of patients whose cancer cells carried methylated O6-methylguanin-DNA methyltransferase genes, the field of developing novel epigenic anticancer agents seems promising. DNA methylation and histone modifications are the two principal factors in epigenetic phenomena. These two mechanisms perform a crucial function in carcinogenesis and tumor progression. DNA methylation is controlled by DNA methyltransferase (DNMT), which have been detected to be over expressed in a variety of malignancies. As a nucleoside or a non-nucleoside, DNMT inhibitors demonstrate anticancer effects by directly trapping DNMTs or by blocking DNMTs at a proper site, respectively. Psammaplin A (PsA) is an inhibitor of both DNA methyltransferase (DNMT) and histone deacetylase inhibitor, and as previously reported from our institution, enhances radiation cell killing by increasing the sub-G1 fraction of cancer cells compared to cells exposed to radiation alone.

  19. Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Eunice Yuen-Ting Lau

    2017-01-01

    Full Text Available Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

  20. Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells.