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Sample records for cells beas-2b treated

  1. Oxidative damage of BEAS-2B cells induced by depleted uranium and protection by DMSO

    International Nuclear Information System (INIS)

    Objective: To observe the oxidative damage in human bronchial epithelial cells (BEAS-2B) induced by depleted uranium (DU) and protection of DMSO. Methods: The measurement of extracellular superoxide anions (O2-·) was based on the reduction of ferricytochrome C. Quantitative analysis of extracellular hydrogen peroxides (H2O2) was used by the horseradish peroxidase-dependent oxidation of phenol red. The determination of extracellular hydroxyl radicals (· OH) was based on discoloration of safranine T. Ethidium bromide and 2, 7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes-hydroethineand 2,7'-dichloroflurescin diacetate were used to monitor the intracellular production of O2- · and H2O2 by fluorometric method. The enzyme activity of SOD and GSH were measured by chemiluminescence and spectrophotometric method, respectively. Results: The ROS production, including H2O2, O2- · and · OH, increased remarkably which induced by DU in BEAs-2B cells. The enzyme activity of SOD and GSH was descended remarkedly. These changes could be effectively inhibited by 0.5% of DMSO. Conclusions: DU causes oxidative damage to BEAS-2B cells. Through removing active oxygen, DMSO can inhibit oxidative damage of DU. (authors)

  2. Comparison of gene expression profiles in chromate transformed BEAS-2B cells.

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    Hong Sun

    Full Text Available BACKGROUND: Hexavalent chromium [Cr(VI] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium's carcinogenicity remain to be elucidated. METHODS/RESULTS: We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI followed by anchorage-independent growth. These transformed cell lines not only exhibited consistent morphological changes but also acquired altered and distinct gene expression patterns compared with normal BEAS-2B cells and control cell lines (untreated that arose spontaneously in soft agar. Interestingly, the gene expression profiles of six Cr(VI transformed cell lines were remarkably similar to each other yet differed significantly from that of either control cell lines or normal BEAS-2B cells. A total of 409 differentially expressed genes were identified in Cr(VI transformed cells compared to control cells. Genes related to cell-to-cell junction were upregulated in all Cr(VI transformed cells, while genes associated with the interaction between cells and their extracellular matrices were down-regulated. Additionally, expression of genes involved in cell proliferation and apoptosis were also changed. CONCLUSION: This study is the first to report gene expression profiling of Cr(VI transformed cells. The gene expression changes across individual chromate exposed clones were remarkably similar to each other but differed significantly from the gene expression found in anchorage-independent clones that arose spontaneously. Our analysis identified many novel gene expression changes that may contribute to chromate induced cell transformation, and collectively this type of

  3. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis.

    Science.gov (United States)

    Park, Youn-Hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG→TCG) at codon 47 and the codon 72 polymorphism (CGC→CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. PMID:26091798

  4. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    International Nuclear Information System (INIS)

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  5. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  6. Poly (I:C, an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

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    Li Yong-Gang

    2012-06-01

    Full Text Available Abstract Background Double-stranded RNA (dsRNA and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C], are recognized by toll-like receptor 3 (TLR3 and induce interferon (IFN-β in many cell types. Poly (I:C is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C elicited IFN-α/β production and natural killer (NK cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance. Results The effects of Poly (I:C on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C suppressed cytopathic effects (CPE induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. Conclusions CHIKV is sensitive to innate immune response induced by Poly (I:C. The inhibition of CHIKV replication by Poly (I:C may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

  7. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells.

    Science.gov (United States)

    Guan, Longfei; Rui, Wei; Bai, Ru; Zhang, Wei; Zhang, Fang; Ding, Wenjun

    2016-01-01

    The aim of the present study was to investigate the effects of size-fractionated (i.e., cell viability in human bronchial epithelial cells (BEAS-2B). The PM samples were collected from an urban site (uPM) in Beijing and a steel factory site (sPM) in Anshan, China, from March 2013 to December 2014. Metal elements, organic and elemental carbon, and water-soluble inorganic ions in the uPM and sPM were analyzed. The cell viability and ROS generation in PM-exposed BEAS-2B cells were measured by MTS and DCFH-DA. The results showed that both uPM and sPM caused a decrease in the cell viability and an increase in ROS generation. The level of ROS measured in sPM1.0 was approximately triple that in uPM1.0. The results of correlation analysis showed that the ROS activity and cytotoxicity were related to different PM composition. Moreover, deferoxamine (DFO) significantly prevented the increase of ROS generation and the decrease of cell viability. Taken together, our results suggest that the metals absorbed on PM induced oxidant radical generation in BEAS-2B cells that could lead to impairment of pulmonary function. PMID:27171105

  8. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells

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    Longfei Guan

    2016-05-01

    Full Text Available The aim of the present study was to investigate the effects of size-fractionated (i.e., <1; 1–2.5, and 2.5–10 µm in an aerodynamic diameter ambient particulate matter (PM on reactive oxygen species (ROS activity and cell viability in human bronchial epithelial cells (BEAS-2B. The PM samples were collected from an urban site (uPM in Beijing and a steel factory site (sPM in Anshan, China, from March 2013 to December 2014. Metal elements, organic and elemental carbon, and water-soluble inorganic ions in the uPM and sPM were analyzed. The cell viability and ROS generation in PM-exposed BEAS-2B cells were measured by MTS and DCFH-DA. The results showed that both uPM and sPM caused a decrease in the cell viability and an increase in ROS generation. The level of ROS measured in sPM1.0 was approximately triple that in uPM1.0. The results of correlation analysis showed that the ROS activity and cytotoxicity were related to different PM composition. Moreover, deferoxamine (DFO significantly prevented the increase of ROS generation and the decrease of cell viability. Taken together, our results suggest that the metals absorbed on PM induced oxidant radical generation in BEAS-2B cells that could lead to impairment of pulmonary function.

  9. Proteasome inhibitor MG-132 regulates the expression of VEGF in human bronchial epithelial cell line, BEAS-2B

    Institute of Scientific and Technical Information of China (English)

    Xuefan Cui; Kaisheng Yin; Mao Huang; Linfu Zhou

    2005-01-01

    Objective: To explore the effects of MG-132 on the expression of VEGF in bronchial epithelial cell line, BEAS2B. Methods: Semi-quantitive RT-PCR for VEGF mRNA and enzyme-linked immunosorbent assay (ELISA) for VEGF protein were performed. Results: MG-132 increased the expression of VEGF mRNA and protein BEAS-2B cells in time-and concentration-dependent manners. After 24-h stimulation, 25 μmol/L MG-132 increased the maximal levels of VEGF protein in cell-conditioned medium. When the cells were stimulated with cycloheximide(CHX) before treatment with MG-132, the MG-132-induced production of VEGF protein was inhibited compared to the unstimulated cells. Supernatant of condition-medium treatment with MG-132 enhanced the growth of HUVEC.Conclusion: MG-132 induces VEGF gene expression in human bronchial epithelial cells line, BEAS-2B, and the MG-132-induced expression of VEGF may modulate lung tissue injury due to airway inflammation.

  10. In vitro transformation of immortalized human bronchial epithelial cells BEAS-2B induced by radon and cigarette smoke

    International Nuclear Information System (INIS)

    Objective: To establish a model of malignant transformation of human cells in vitro to study the lung cancer induced by radon and cigarette smoke. Methods: The immortalized human bronchial epithelial cells BEAS-2B were divided into control group (C), radon group (Rn), cigarette smoke group (Sm) and combined group (Rn-Sm). Cells were planted onto transwell membrane one day before exposure and were directly exposed to radon and cigarette smoke pumped in a gas inhalation box. After the exposure cells were trypsinized into dishes for further growth and malignancy transformation phenotype was detected in order to compare the effects due to radon and cigarette smoke exposure. Results: BEAS-2B cells showed malignantly transformed phenotype by exposure to radon and cigarette smoke. A series of sequential steps emerged among transformed cells, including altered growth kinetics, resistance to serum has changed from 0. 31 ± 0. 18 to 1.92 ± 0. 27,2. 03 ± 0. 14,2.95 ± 0. 60, and anchorage-independence growth increased from (0.01 ±0.02)% to (4.89 ±0.30)%,(8.36 ±0.50)%,(11.74 ±0.69)%.After being subculture for 20 generations, cell apoptosis of the fifth generation cells exposed to radon,cigarette smoke and both was significant decreased from ( 11.76 ± 0. 17 ) % to (4. 62 ± 0. 42 ) %, ( 8.63 ±0. 15 )%, (3.68 ± 0. 33 )%. Conclusions: BEAS-2B cells could be malignancy transformed by radon and cigarette smoke in vitro, which could be used as a cell model in lung bronchial carcinogenesis. (authors)

  11. Identification of PM10 characteristics involved in cellular responses in human bronchial epithelial cells (Beas-2B).

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    Van Den Heuvel, Rosette; Den Hond, Elly; Govarts, Eva; Colles, Ann; Koppen, Gudrun; Staelens, Jeroen; Mampaey, Maja; Janssen, Nicole; Schoeters, Greet

    2016-08-01

    Notwithstanding evidence is present that physicochemical characteristics of ambient particles attribute to adverse health effects, there is still some lack of understanding in this complex relationship. At this moment it is not clear which properties (such as particle size, chemical composition) or sources of the particles are most relevant for health effects. This study investigates the in vitro toxicity of PM10 in relation to PM chemical composition, black carbon (BC), endotoxin content and oxidative potential (OP). In 2013-2014 PM10 was sampled (24h sampling, 108 sampling days) in ambient air at three sites in Flanders (Belgium) with different pollution characteristics: an urban traffic site (Borgerhout), an industrial area (Zelzate) and a rural background location (Houtem). To characterize the toxic potential of PM10, airway epithelial cells (Beas-2B cells) have been exposed to particles in vitro. Different endpoints were studied including cell damage and death (cell viability) using the Neutral red Uptake assay, the production of pro-inflammatory molecules by interleukin 8 (IL-8) induction and DNA-damaging activity using the FPG-modified Comet assay. The endotoxin levels in the collected samples were analysed and the capacity of PM10 particles to produce reactive oxygen species (OP) was evaluated by electron paramagnetic resonance (EPR) spectroscopy. Chemical characteristics of PM10 (BC, As, Cd, Cr, Cu, Mn, Ni, Pb, Zn) and meteorological conditions were recorded on the sampling days. PM10 particles exhibited dose-dependent cytotoxicity in Beas-2B cells and were found to significantly induce the release of IL-8 in samples from the three locations. Oxidatively damaged DNA was observed in exposed Beas-2B cells. Endotoxin levels above the detection limit were detected in half of the samples. OP was measurable in all samples. Associations between PM10 characteristics and biological effects of PM10 were assessed by single and multiple regression analyses. The

  12. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells

    OpenAIRE

    Longfei Guan; Wei Rui; Ru Bai; Wei Zhang; Fang Zhang; Wenjun Ding

    2016-01-01

    The aim of the present study was to investigate the effects of size-fractionated (i.e., <1; 1–2.5, and 2.5–10 µm in an aerodynamic diameter) ambient particulate matter (PM) on reactive oxygen species (ROS) activity and cell viability in human bronchial epithelial cells (BEAS-2B). The PM samples were collected from an urban site (uPM) in Beijing and a steel factory site (sPM) in Anshan, China, from March 2013 to December 2014. Metal elements, organic and elemental carbon, and water-soluble ...

  13. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells.

    Science.gov (United States)

    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin

    2016-07-01

    Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. PMID:27155559

  14. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    International Nuclear Information System (INIS)

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H2O2) and superoxide dismutase 2 (SOD2, antioxidant against O2·−) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study

  15. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  16. Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells

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    Haniu H

    2014-04-01

    Full Text Available Hisao Haniu,1,2 Naoto Saito,2,3 Yoshikazu Matsuda,4 Tamotsu Tsukahara,5 Yuki Usui,1,6,7 Kayo Maruyama,2,3 Seiji Takanashi,1 Kaoru Aoki,1 Shinsuke Kobayashi,1 Hiroki Nomura,1 Manabu Tanaka,1 Masanori Okamoto,1 Hiroyuki Kato1 1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Nagano, Japan; 2Insutitute for Biomedical Sciences, Shinshu University, Nagano, Japan; 3Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Nagano, Japan; 4Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Saitama, Japan; 5Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan; 6Research Center for Exotic Nanocarbons, Shinshu University, Nagano, Japan; 7Aizawa Hospital, Sports Medicine Center, Nagano, Japan Abstract: This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs and cup-stacked carbon nanotubes (CSCNTs on biological responses in vitro. Three types of MWCNTs – VGCF®-X, VGCF®-S, and VGCF® (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively – and three CSCNTs of different lengths (CS-L, 20–80 µm; CS-S, 0.5–20 µm; and CS-M, of intermediate length were tested. Human bronchial epithelial (BEAS-2B and malignant pleural mesothelioma cells were exposed to the CNTs (1–50 µg/mL, and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT

  17. Comparison of Gene Expression Profiles in Chromate Transformed BEAS-2B Cells

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    Sun, Hong; Clancy, Harriet A.; Kluz, Thomas; Zavadil, Jiri; Costa, Max

    2011-01-01

    Background Hexavalent chromium [Cr(VI)] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI) induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium's carcinogenicity remain to be elucidated. Methods/Results We established chromate transformed cell lines by chroni...

  18. Effects of corexit oil dispersants and the WAF of dispersed oil on DNA damage and repair in cultured human bronchial airway cells, BEAS-2B

    Science.gov (United States)

    Major, Danielle; Derbes, Rebecca S.; Wang, He; Roy-Engel, Astrid M.

    2016-01-01

    Large quantities of dispersants were used as a method to disperse the roughly 210 million gallons of spilled crude oil that consumed the Gulf of Mexico. Little is known if the oil-dispersant and oil-dispersant mixtures on human airway BEAS-2B epithelial cells. Here we present the cytotoxic and genotoxic in vitro effects on the human lung cells BEAS-2B following exposure to and oil-dispersant mixtures on human airway BEAS-2B epithelial cells. Here we present the cytotoxic and genotoxic in vitro effects on the human lung cells BEAS-2B following exposure to Corexit dispersants EC9500 and EC9527, Water Accommodated Fraction (WAF) -crude, WAF-9500 + Oil, and WAF-9527 + Oil. Cellular cytotoxicity to WAF-dispersed oil samples was observed at concentrations greater than 1000 ppm with over 70% of observed cellular death. At low concentration exposures (100 and 300 ppm) DNA damage was evidenced by the detection of single strand breaks (SSBs) and double strand breaks (DSBs) as measured by alkaline and neutral comet assay analyses. Immunoblot analyses of the phosphorylated histone H2A.X (ɣ-H2A.X) and tumor suppressor p53 protein confirmed activation of the DNA damage response due to the exposure-induced DNA breaks. Although, many xenobiotics interfere with DNA repair pathways, in vitro evaluation of the nucleotide excision repair (NER) and DSB repair pathways appear to be unaffected by the oil-dispersant mixtures tested. Overall, this study supports that oil-dispersant mixtures induce genotoxic effects in culture.

  19. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling

    OpenAIRE

    Son, Young-Ok; Wang, Lei; Poyil, Pratheeshkumar; Budhraja, Amit; Hitron, J. Andrew; Zhang, Zhuo; Lee, Jeong-Chae; Shi, Xianglin

    2012-01-01

    Cadmium has been widely used in industry and is known to be carcinogenic to humans. Although it is widely accepted that chronic exposure to cadmium increases the incidence of cancer, the mechanisms underlying cadmium-induced carcinogenesis are unclear. The main aim of this study was to investigate the role of reactive oxygen species (ROS) in cadmium-induced carcinogenesis and the signal transduction pathways involved. Chronic exposure of human bronchial epithelial BEAS-2B cells to cadmium ind...

  20. Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

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    Bai, Wenlin; Chen, Yujiao; Sun, Pengling; Gao, Ai

    2016-01-01

    Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells.

  1. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

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    Rosseau Simone

    2006-07-01

    Full Text Available Abstract Background Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH2-terminal kinase (JNK Methods Human bronchial epithelial cells (BEAS-2B or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP. JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1. We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser63/73-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c

  2. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Son, Young-Ok; Wang, Lei; Poyil, Pratheeshkumar; Budhraja, Amit; Hitron, J. Andrew; Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States); School of Dentistry and Institute of Oral Biosciences (BK21 program), Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States)

    2012-10-15

    Cadmium has been widely used in industry and is known to be carcinogenic to humans. Although it is widely accepted that chronic exposure to cadmium increases the incidence of cancer, the mechanisms underlying cadmium-induced carcinogenesis are unclear. The main aim of this study was to investigate the role of reactive oxygen species (ROS) in cadmium-induced carcinogenesis and the signal transduction pathways involved. Chronic exposure of human bronchial epithelial BEAS-2B cells to cadmium induced cell transformation, as evidenced by anchorage-independent growth in soft agar and clonogenic assays. Chronic cadmium treatment also increased the potential of these cells to invade and migrate. Injection of cadmium-stimulated cells into nude mice resulted in the formation of tumors. In contrast, the cadmium-mediated increases in colony formation, cell invasion and migration were prevented by transfection with catalase, superoxide dismutase-1 (SOD1), or SOD2. In particular, chronic cadmium exposure led to activation of signaling cascades involving PI3K, AKT, GSK-3β, and β-catenin and transfection with each of the above antioxidant enzymes markedly inhibited cadmium-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the cadmium-mediated increase in total and active β-catenin proteins and colony formation. Moreover, there was a marked induction of AKT, GSK-3β, β-catenin, and carcinogenic markers in tumor tissues formed in mice after injection with cadmium-stimulated cells. Collectively, our findings suggest a direct involvement of ROS in cadmium-induced carcinogenesis and implicate a role of AKT/GSK-3β/β-catenin signaling in this process. -- Highlights: ► Chronic exposure to cadmium induces carcinogenic properties in BEAS-2B cells. ► ROS involved in cadmium-induced tumorigenicity of BEAS-2B cells. ► Cadmium activates ROS-dependent AKT/GSK-3β/β-catenin-mediated signaling. ► ROS

  3. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling

    International Nuclear Information System (INIS)

    Cadmium has been widely used in industry and is known to be carcinogenic to humans. Although it is widely accepted that chronic exposure to cadmium increases the incidence of cancer, the mechanisms underlying cadmium-induced carcinogenesis are unclear. The main aim of this study was to investigate the role of reactive oxygen species (ROS) in cadmium-induced carcinogenesis and the signal transduction pathways involved. Chronic exposure of human bronchial epithelial BEAS-2B cells to cadmium induced cell transformation, as evidenced by anchorage-independent growth in soft agar and clonogenic assays. Chronic cadmium treatment also increased the potential of these cells to invade and migrate. Injection of cadmium-stimulated cells into nude mice resulted in the formation of tumors. In contrast, the cadmium-mediated increases in colony formation, cell invasion and migration were prevented by transfection with catalase, superoxide dismutase-1 (SOD1), or SOD2. In particular, chronic cadmium exposure led to activation of signaling cascades involving PI3K, AKT, GSK-3β, and β-catenin and transfection with each of the above antioxidant enzymes markedly inhibited cadmium-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the cadmium-mediated increase in total and active β-catenin proteins and colony formation. Moreover, there was a marked induction of AKT, GSK-3β, β-catenin, and carcinogenic markers in tumor tissues formed in mice after injection with cadmium-stimulated cells. Collectively, our findings suggest a direct involvement of ROS in cadmium-induced carcinogenesis and implicate a role of AKT/GSK-3β/β-catenin signaling in this process. -- Highlights: ► Chronic exposure to cadmium induces carcinogenic properties in BEAS-2B cells. ► ROS involved in cadmium-induced tumorigenicity of BEAS-2B cells. ► Cadmium activates ROS-dependent AKT/GSK-3β/β-catenin-mediated signaling. ► ROS

  4. Differential effects of nitro-PAHs and amino-PAHs on cytokine and chemokine responses in human bronchial epithelial BEAS-2B cells

    International Nuclear Information System (INIS)

    Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are found in diesel exhaust and air pollution particles. Along with other PAHs, many nitro-PAHs possess mutagenic and carcinogenic properties, but their effects on pro-inflammatory processes and cell death are less known. In the present study we examined the effects of 1-nitropyrene (1-NP), 3-nitrofluoranthene (3-NF) and 3-nitrobenzanthrone (3-NBA) and their corresponding amino forms, 1-AP, 3-AF and 3-ABA, in human bronchial epithelial BEAS-2B cells. The effects of the different nitro- and amino-PAHs were compared to the well-characterized PAH benzo[a]pyrene (B[a]P). Expression of 17 cytokine and chemokine genes, measured by real-time PCR, showed that 1-NP and 3-NF induced a completely different cytokine/chemokine gene expression pattern to that of their amino analogues. 1-NP/3-NF-induced responses were dominated by maximum effects on CXCL8 (IL-8) and TNF-α expression, while 1-AP-/3-AF-induced responses were dominated by CCL5 (RANTES) and CXCL10 (IP-10) expression. 3-NBA and 3-ABA induced only marginal cytokine/chemokine responses. However, 3-NBA exposure induced considerable DNA damage resulting in accumulation of cells in S-phase and a marked increase in apoptosis. B[a]P was the only compound to induce expression of aryl hydrocarbon receptor (AhR)-regulated genes, such as CYP1A1 and CYP1B1, but did not induce cytokine/chemokine responses in BEAS-2B cells. Importantly, nitro-PAHs and amino-PAHs induced both qualitatively and quantitatively different effects on cytokine/chemokine expression, DNA damage, cell cycle alterations and cytotoxicity. The cytokine/chemokine responses appeared to be triggered, at least partly, through mechanisms separate from the other examined endpoints. These results confirm and extend previous studies indicating that certain nitro-PAHs have a considerable pro-inflammatory potential.

  5. PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kan-o, Keiko [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsumoto, Koichiro, E-mail: koichi@kokyu.med.kyushu-u.ac.jp [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoue, Hiromasa [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2013-05-31

    Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB.

  6. Surface reactivity and in vitro toxicity on human bronchial epithelial cells (BEAS-2B) of nanomaterials intermediates of the production of titania-based composites.

    Science.gov (United States)

    Vergaro, Viviana; Aldieri, Elisabetta; Fenoglio, Ivana; Marucco, Arianna; Carlucci, Claudia; Ciccarella, Giuseppe

    2016-08-01

    Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. Evaluating the hazards associated with TiO2 NPs is crucial as it enables risk assessment related to human and environmental exposure. In this study the in vitro human toxicity of a set of TiO2 NPs modified with acetic, oleic and boric acids were studied in order to assess the hazard in view of a future scale-up of the synthesis. The surface reactivity of the powders under simulated solar illumination and in the dark has been evaluated by means of EPR spectroscopy. Human bronchial epithelial cells (BEAS-2B) have been chosen as a model for lung epithelium. Cytotoxicity has been assessed by measuring the cells membrane integrity by lactate dehydrogenase (LDH) assay, and the inflammatory response evaluated as nitric oxide (NO) and TNF-α production, and oxidative stress measured as intracellular reduced glutathione (GSH) levels, and induced lipoperoxidation. Aeroxide P25 was used for comparison. The results demonstrated a low photoreactivity and toxic effects lower than Aeroxide P25 of the nano-TiO2 powders, probably as a consequence of the presence of acidic moieties at the surface. PMID:27075777

  7. Organic extracts of urban air pollution particulate matter (PM2.5)-induced genotoxicity and oxidative stress in human lung bronchial epithelial cells (BEAS-2B cells).

    Science.gov (United States)

    Oh, Seung Min; Kim, Ha Ryong; Park, Yong Joo; Lee, Soo Yeun; Chung, Kyu Hyuck

    2011-08-16

    Traffic is a major source of particulate matter (PM), and ultrafine particulates and traffic intensity probably contribute significantly to PM-related health effects. As a strong relationship between air pollution and motor vehicle-originated pollutants has been shown to exist, air pollution genotoxicity studies of urban cities are steadily increasing. In Korea, the death rate caused by lung cancer is the most rapidly increased cancer death rate in the past 10 years. In this study, genotoxicity of PM2.5 (traffic area in Suwon City, Korea, was studied using cultured human lung bronchial epithelial cells (BEAS-2B) as a model system for the potential inhalation health effects. Organic extract of PM2.5 (CE) generated significant DNA breakage and micronucleus formation in a dose-dependent manner (1μg/cm(3)-50μg/cm(3)). In the acid-base-neutral fractionation of PM2.5, neutral samples including the aliphatic (F3), aromatic (F4) and slightly polar (F5) fractions generated significant DNA breakage and micronucleus formation. These genotoxic effects were significantly blocked by scavenging agents [superoxide dismutase (SOD), sodium selenite (SS), mannitol (M), catalase (CAT)]. In addition, in the modified Comet assay using endonucleases (FPG and ENDOIII), CE and its fractions (F3, F4, and F5) increased DNA breakage compared with control groups, indicating that CE and fractions of PM2.5 induced oxidative DNA damage. These results clearly suggest that PM2.5 collected in the Suwon traffic area has genotoxic effects and that reactive oxygen species may play a distinct role in these effects. In addition, aliphatic/chlorinated hydrocarbons, PAH/alkylderivatives, and nitro-PAH/ketones/quinones may be important causative agents of the genotoxic effects. PMID:21524716

  8. African Dust Storms Reaching Puerto Rican Coast Stimulate the Secretion of IL-6 and IL-8 and Cause Cytotoxicity to Human Bronchial Epithelial Cells (BEAS-2B).

    Science.gov (United States)

    Rodríguez-Cotto, Rosa I; Ortiz-Martínez, Mario G; Rivera-Ramírez, Evasomary; Méndez, Loyda B; Dávila, Julio C; Jiménez-Vélez, Braulio D

    2013-10-01

    African dust storm events (ADE) travel across the Atlantic Ocean (ADEAO) and reach the Puerto Rican coast (ADEPRC), potentially impacting air quality and human health. To what extent seasonal variations in atmospheric particulate matter (PM) size fractions, composition and sources trigger respiratory-adverse effects to Puerto Ricans is still unclear. In the present study, we investigated the pro-inflammatory and cytotoxic effects of PM samples harvested during ADEAO (PM10), ADEPRC (PM2.5 and PM10) and Non-ADE (Preand Post-ADEAO and Non-ADEPRC), using BEAS-2B cells. Endotoxins (ENX) in PM2.5 and PM10 extracts and traces of metals (TMET) in PM2.5 extracts were also examined. IL-6 and IL-8 secretion and cytotoxicity were used as endpoints. ADEAO and ADEPRC extracts were found to be more cytotoxic than Non-ADE and ADEAO were more toxic than ADEPRC extracts. PM10 extracts from ADEAO and Post-ADEAO caused significant secretion of IL-8. IL-6 and IL-8 secretion was higher following treatment with PM10 and PM2.5 ADEPRC than with Non-ADEPRC extracts. ENX levels were found to be higher in PM10 ADEAO than in the rest of the samples tested. TMET levels were higher in PM2.5 ADEPRC than in Non-ADEPRC extracts. Deferoxamine significantly reduced cytotoxicity and IL-6 and IL-8 secretion whereas Polymyxin B did not. TMET in PM2.5 fractions is a major determinant in ADEPRC-induced toxicity and work in conjunction with ENX to cause toxicity to lung cells in vitro. ENX and TMET may be responsible, in part, for triggering PM-respiratory adverse responses in susceptible and predisposed individuals. PMID:25002916

  9. Toxicological Impact of Air Pollution Particulate Matter PM 2.5 Collected under Urban Industrial or Rural Influence Occurrence of Oxidative Stress and Inflammatory Reaction in BEAS 2B Human Bronchial Epithelial Cells Corrected Version

    International Nuclear Information System (INIS)

    Exposure to air pollution Particulate Matter (PM) is one of the risk factors involved in the high incidence of respiratory and cardio-vascular diseases. In this work, to integrate inter-seasonal and inter-site variations, fine particle (PM2.5) samples have been collected in spring-summer 2008) and autumn 2008-winter 2009, in Dunkerque (France) under urban or industrial influence, and in Rubrouck (France), under rural influence. Attention was paid to characterize their physico-chemical characteristics, and to determine their ability to induce oxidative stress and inflammatory response in a human bronchial epithelial cell model (BEAS-2B cell line). Physico-chemical characterization of the six PM samples showed their heterogeneities and complexities depending upon their respective natural and/or anthropogenic emission sources. Lung cytotoxicity of these air pollution PM2.5 samples, as shown in BEAS-2B cells, might rely on the induction of oxidative stress conditions and particularly on the excessive inflammatory response. (author)

  10. Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

    Science.gov (United States)

    ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

  11. DNA Hypermethylation of CREB3L1 and Bcl-2 Associated with the Mitochondrial-Mediated Apoptosis via PI3K/Akt Pathway in Human BEAS-2B Cells Exposure to Silica Nanoparticles

    Science.gov (United States)

    Zou, Yang; Li, Qiuling; Jiang, Lizhen; Guo, Caixia; Li, Yanbo; Yu, Yang; Li, Yang; Duan, Junchao; Sun, Zhiwei

    2016-01-01

    The toxic effects of silica nanoparticles (SiNPs) are raising concerns due to its widely applications in biomedicine. However, current information about the epigenetic toxicity of SiNPs is insufficient. In this study, the epigenetic regulation of low-dose exposure to SiNPs was evaluated in human bronchial epithelial BEAS-2B cells over 30 passages. Cell viability was decreased in a dose- and passage-dependent manner. The apoptotic rate, the expression of caspase-9 and caspase-3, were significantly increased induced by SiNPs. HumanMethylation450 BeadChip analysis identified that the PI3K/Akt as the primary apoptosis-related pathway among the 25 significant altered processes. The differentially methylated sites of PI3K/Akt pathway involved 32 differential genes promoters, in which the CREB3L1 and Bcl-2 were significant hypermethylated. The methyltransferase inhibitor, 5-aza, further verified that the DNA hypermethylation status of CREB3L1 and Bcl-2 were associated with downregulation of their mRNA levels. In addition, mitochondrial-mediated apoptosis was triggered by SiNPs via the downregulation of PI3K/Akt/CREB/Bcl-2 signaling pathway. Our findings suggest that long-term low-dose exposure to SiNPs could lead to epigenetic alterations. PMID:27362941

  12. Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

    Science.gov (United States)

    Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

  13. 125I粒子和60Co γ射线照射对A549及BEAS-2B细胞生物学效应的影响%The biological effects of 125I seeds and 60Co γ-rays on A549 and BEAS-2B cells

    Institute of Scientific and Technical Information of China (English)

    赵真真; 茅爱武; 王忠敏; 刘芬菊; 曹燕; 贾一平

    2015-01-01

    目的 探讨125I粒子和60Co γ射线对非小细胞肺癌(NSCLC) A549细胞和正常支气管上皮BEAS-2B细胞生物学效应的影响.方法 A549、BEAS-2B细胞均行125I粒子和60Coγ射线不同剂量照射;集落形成实验检测细胞存活分数;流式细胞术检测细胞周期和细胞凋亡率;Western blot检测凋亡相关蛋白的表达水平.结果 A549细胞在4、6、8 Gy照射时,125I粒子组细胞克隆存活分数较60Co组降低更明显(t=6.06、9.42、4.90,P<0.05).A549细胞在4 Gy时,G1期细胞比例125I粒子组为70.67%±1.49%,60Co组为59.59% ±0.71%(t=10.77,P<0.05);细胞凋亡率125I粒子组为18.09%±0.73%,60Co组为9.81%±0.16%(t=19.40,P<0.05).125I粒子照射明显上调Bax、cleaved Caspase-3蛋白的表达,同时下调Bcl-2蛋白的表达.但不同射线同一剂量或相同射线不同剂量下,BEAS-2B细胞的凋亡率及凋亡相关蛋白的表达无明显变化.结论 125I粒子持续低剂量率照射较60Co γ射线高剂量率照射抑制A549细胞增殖的效应更明显.Bcl-2/Bax蛋白比失衡,最终致Caspase-3蛋白的活化在125I粒子持续低剂量率照射抑制肿瘤细胞增殖的效应中可能发挥重要的作用.%Objective To investigate the biological effects of 125I seeds and 60Co γ-rays on the non-small cell lung cancer cells A549 and the normal bronchial epithelium cells BEAS-2B.Methods A549 and BEAS-2B cells were irradiated with 125I seeds and 60Co γ-rays.The survival fraction was detected by colony formation assay.The cell cycle and cell apoptotic ratio were detected by flow cytometry.The expression of cell apoptotic related proteins was examined by western blot.Results After irradiation with different doses,the survival of A549 cells irradiated with 125I seeds was lower than that irradiated with γ-rays (t =6.06,9.42,4.90,P <0.05).After irradiation with 4 Gy of 125I seeds and 60Co γ-rays,the G1 phase percentages of A549 cells were 70.67% ± 1.49% and 59.59% ± 0

  14. Glyoxalase I drives epithelial-to-mesenchymal transition via argpyrimidine-modified Hsp70, miR-21 and SMAD signalling in human bronchial cells BEAS-2B chronically exposed to crystalline silica Min-U-Sil 5: Transformation into a neoplastic-like phenotype.

    Science.gov (United States)

    Antognelli, Cinzia; Gambelunghe, Angela; Muzi, Giacomo; Talesa, Vincenzo Nicola

    2016-03-01

    Glyoxalase I (Glo1) is the main scavenging enzyme of methylglyoxal (MG), a potent precursor of advanced glycation end products (AGEs). AGEs are known to control multiple biological processes, including epithelial to mesenchymal transition (EMT), a multistep phenomenon associated with cell transformation, playing a major role in a variety of diseases, including cancer. Crystalline silica is a well-known occupational health hazard, responsible for a great number of human pulmonary diseases, such as silicosis. There is still much debate concerning the carcinogenic role of crystalline silica, mainly due to the lack of a causal demonstration between silica exposure and carcinogenesis. It has been suggested that EMT might play a role in crystalline silica-induced lung neoplastic transformation. The aim of this study was to investigate whether, and by means of which mechanism, the antiglycation defence Glo1 is involved in Min-U-Sil 5 (MS5) crystalline silica-induced EMT in BEAS-2B human bronchial epithelial cells chronically exposed, and whether this is associated with the beginning of a neoplastic-like transformation process. By using gene silencing/overexpression and scavenging/inhibitory agents, we demonstrated that MS5 induced hydrogen peroxide-mediated c-Jun-dependent Glo1 up-regulation which resulted in a decrease in the Argpyrimidine-modified Hsp70 protein level which triggered EMT in a novel mechanism involving miR-21 and SMAD signalling. The observed EMT was associated with a neoplastic-like phenotype. The results obtained provide a causal in vitro demonstration of the MS5 pro-carcinogenic transforming role and more importantly they provide new insights into the mechanisms involved in this process, thus opening new paths in research concerning the in vivo study of the carcinogenic potential of crystalline silica. PMID:26784015

  15. 煤焦沥青烟提取物致BEAS-2B恶性转化细胞中姊妹染色单体分离相关蛋白的改变%Change of structurol maintenance of chromosome(SMC )1, SMC3, separase and securin expression in BEAS-2B malignant transformation cell induced by coal tar pitch smoke extracts

    Institute of Scientific and Technical Information of China (English)

    李智涛; 王威; 赵勇; 王丽霞; 祝寒松; 吴卫东; 吴逸明

    2010-01-01

    目的 通过检测姊妹染色体凝集和分离相关蛋白染色体结构维持蛋白(SMC)1、SMC3、分离酶(Separase)和保全素(Securin)在煤焦沥青致BEAS-2B癌变细胞中的变化,探讨其在煤焦沥青接触者肺癌发生中的作用.方法 用中温煤焦沥青烟提取物作为诱导剂,建立永生化人支气管上皮细胞BEAS-2B的恶性转化模型,用实时定量反转录-聚合酶链反应(RT-PCR)检测相关基因的mRNA表达水平;细胞爬片免疫组化半定量法检测其蛋白表达改变.以二甲亚砜(DMSO)溶剂组和未染毒的正常传代的BEAS-2B细胞为对照组.结果 与正常对照组和DMSO溶剂对照组比较,煤焦沥青烟提取物诱导转化细胞中,SMC1基因和蛋白表达水平的差异无统计学意义(P>0.05);煤焦沥青烟诱导组SMC3和Separase的基因和蛋白表达水平明显升高(基因:SMC3:2.54±0.20、Separase:2.42±0.22,蛋白:SMC3:0.27±0.02、Separase:0.25±0.02),Securin的基因和蛋白表达水平明显降低(基因:0.30±0.04,蛋白:0.17±0.01),与其他两组(DMSO溶剂对照组:基因:SMC3:1.13±0.12、Separase:1.00±0.04、Securin:0.90±0.11,蛋白:SMC3:0.10±0.03、Separase:0.18±0.02、Securin:0.22±0.02;正常对照组:基因:SMC3:1.00±0.11、Separase:1.00±0.08、Securin:1.00±0.11,蛋白:SMC3:0.09±0.01、Separase:0.18±0.01、Securin:0.23±0.02)相比,差异均有统计学意义(P<0.05).结论 在煤焦沥青致支气管上皮细胞恶性转化过程中,姊妹染色单体凝集和分离相关蛋白SMC3和Separase升高,Securin表达水平降低,参与了细胞恶性转化过程.%Objective To study the role of structural maintenance of chromosome (SMC)1, SMC3,Separase and Securin in tumorgenesis that contact with coal tar pitch. Methods The BEAS-2B cells was induced by coal tar pitch smoke extracts to form malignant transformation cell model in vitro. The gene expression levels of mRNA were assessed by real-time quantitative RT-PCR, and the protein expression variation

  16. Macrophages facilitate coal tar pitch extract-induced tumorigenic transformation of human bronchial epithelial cells mediated by NF-κB.

    Directory of Open Access Journals (Sweden)

    Feifei Feng

    Full Text Available OBJECTIVE: Chronic respiratory inflammation has been associated with lung cancer. Tumor-associated macrophages (TAMs play a critical role in the formation of inflammation microenvironment. We sought to characterize the role of TAMs in coal tar pitch extract (CTPE-induced tumorigenic transformation of human bronchial epithelial cells and the underlying mechanisms. METHODS: The expression of TAMs-specific CD68 in lung cancer tissues and paired adjacent tissues from cancer patients was determined using immunostaining. Co-culture of human bronchial epithelial cells (BEAS-2B and macrophage-like THP-1 cells were conducted to evaluate the promotive effect of macrophages on CTPE-induced tumorigenic transformation of BEAS-2B cells. BEAS-2B cells were first treated with 2.4 µg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured either with or without THP-1 cells and passaged using trypsin-EDTA. Alterations of cell cycle, karyotype, colony formation in soft agar and tumor xenograft growth in nude mice of BEAS-2B cells at passages 10, 20 and 30, indicative of tumorigenecity, were determined, respectively. In addition, mRNA and protein levels of NF-κB in BEAS-2B cells were measured with RT-PCR and western blot, respectively. B(aP was used as the positive control. RESULTS: The over-expression of TAMs-specific CD68 around lung tumor tissues was detected and associated with lung cancer progression. The tumorigenic alterations of BEAS-2B cells including increase in cell growth rate, number of cells with aneuploidy, clonogenicity in soft agar, and tumor size in nude mice in vivo occurred at passage 10, becoming significant at passages 20 and 30 of the co-culture following CTPE removal in compared to BEAS-2B cells alone. In addition, the expression levels of NF-κB in BEAS-2B cells were positively correlated to the malignancy of BEAS-2B cells under different conditions of treatment. CONCLUSION: The presence of macrophages

  17. Malignant human cell transformation of Marcellus Shale gas drilling flow back water.

    Science.gov (United States)

    Yao, Yixin; Chen, Tingting; Shen, Steven S; Niu, Yingmei; DesMarais, Thomas L; Linn, Reka; Saunders, Eric; Fan, Zhihua; Lioy, Paul; Kluz, Thomas; Chen, Lung-Chi; Wu, Zhuangchun; Costa, Max

    2015-10-01

    The rapid development of high-volume horizontal hydraulic fracturing for mining natural gas from shale has posed potential impacts on human health and biodiversity. The produced flow back waters after hydraulic stimulation are known to carry high levels of saline and total dissolved solids. To understand the toxicity and potential carcinogenic effects of these wastewaters, flow back waters from five Marcellus hydraulic fracturing oil and gas wells were analyzed. The physicochemical nature of these samples was analyzed by inductively coupled plasma mass spectrometry and scanning electron microscopy/energy dispersive X-ray spectroscopy. A cytotoxicity study using colony formation as the endpoint was carried out to define the LC50 values of test samples using human bronchial epithelial cells (BEAS-2B). The BEAS-2B cell transformation assay was employed to assess the carcinogenic potential of the samples. Barium and strontium were among the most abundant metals in these samples and the same metals were found to be elevated in BEAS-2B cells after long-term treatment. BEAS-2B cells treated for 6weeks with flow back waters produced colony formation in soft agar that was concentration dependent. In addition, flow back water-transformed BEAS-2B cells show better migration capability when compared to control cells. This study provides information needed to assess the potential health impact of post-hydraulic fracturing flow back waters from Marcellus Shale natural gas mining. PMID:26210350

  18. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  19. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    International Nuclear Information System (INIS)

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  20. Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc

    International Nuclear Information System (INIS)

    Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional and posttranscriptional events that regulate COX-2 expression in a human bronchial epithelial cell line BEAS-2B exposed to Zn2+. Zn2+ exposure resulted in pronounced increases in COX-2 mRNA and protein expression, which were prevented by pretreatment with the transcription inhibitor actinomycin D, implying the involvement of transcriptional regulation. This was supported by the observation of increased COX-2 promoter activity in Zn2+-treated BEAS-2B cells. Mutation of the cAMP response element (CRE), but not the κB-binding sites in the COX-2 promoter markedly reduced COX-2 promoter activity induced by Zn2+. Inhibition of NFκB activation did not block Zn2+-induced COX-2 expression. Measurement of mRNA stability demonstrated that Zn2+ exposure impaired the degradation of COX-2 mRNA in BEAS-2B cells. This message stabilization effect of Zn2+ exposure was shown to be dependent on the integrity of the 3'-untranslated region found in the COX-2 transcript. Taken together, these data demonstrate that the CRE and mRNA stability regulates COX-2 expression induced in BEAS-2B cells exposed to extracellular Zn2+

  1. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

    Science.gov (United States)

    Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

  2. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    Science.gov (United States)

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  3. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@kanazawa-med.ac.jp [Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan); Usui, Yuki [Research Center for Exotic Nanocarbons, Shinshu University, 4-17-1 Wakasato, Nagano-shi, Nagano 380-8553 (Japan); Haniu, Hisao [Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2013-10-18

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

  4. [Grape seed proanthocyanidins inhibits the invasion and migration of A549 lung cancer cells].

    Science.gov (United States)

    Zhou, Yehan; Ye, Xiufeng; Shi, Yao; Wang, Ke; Wan, Dan

    2016-02-01

    Objective To explore the effect of grape seed proanthocyanidins (GSPs) on the invasion and migration of A549 lung cancer cells and the underlying mechanism. Methods Trypan blue dye exclusion assay was used to determine the cytotoxic effect of varying doses of GSPs on the BEAS-2B normal human pulmonary epithelial cells. After treated with 0, 10, 20, 40, 80 μg/mL GSP, the proliferation of A549 cells was detected by MTT assay; the invasion and migration of A549 cells were determined by Transwell(TM) assay and scratch wound assay, respectively. The levels of epithelial growth factor receptor (EGFR), E-cadherin, N-cadherin in A549 cells treated with GSPs were detected by Western blotting. Results (0-40) μg/mL GSPs had no significant toxic effect on BEAS-2B cells, while 80 μg/mL GSPs had significant cytotoxicity to BEAS-2B cells. The proliferation of A549 cells was significantly inhibited within limited dosage in a dose-dependent manner, and the abilities of invasion and migration of A549 cells were also inhibited. Western blotting showed that the expression of EGFR and N-cadherin decreased, while E-cadherin increased after GSPs treatment. Conclusion GSPs could inhibit the abilities of proliferation, invasion and migration of A549 cells, which might be related to the dow-regulation of EGFR and N-cadherin and the up-regulation of E-cadherin. PMID:26927375

  5. Cross-talk between human mast cells and bronchial epithelial cells in plasminogen activator inhibitor-1 production via transforming growth factor-β1.

    Science.gov (United States)

    Cho, Seong H; Lee, Sun H; Kato, Atsushi; Takabayashi, Tetsuji; Kulka, Marianna; Shin, Soon C; Schleimer, Robert P

    2015-01-01

    Previous reports suggest that plasminogen activator inhibitor-1 (PAI-1) promotes airway remodeling and that human and mouse mast cells (MCs) are an important source of PAI-1. In the present study we investigated MC-epithelial cell (EC) interactions in the production of PAI-1. We stimulated the human MC line LAD2 with IgE-receptor cross-linking and collected the supernatants. We incubated the human bronchial EC line BEAS-2B with the LAD2 supernatants and measured the level of PAI-1. When the supernatants from IgE-stimulated LAD2 were added to BEAS-2B, there was a significant enhancement of PAI-1 production by BEAS-2B. When we treated the MC supernatants with a transforming growth factor (TGF)-β1 neutralizing antibody, the MC-derived induction of PAI-1 from BEAS-2B was completely abrogated. Although TGF-β1 mRNA was constitutively expressed in resting LAD2, it was not highly induced by IgE-mediated stimulation. Nonetheless, active TGF-β1 protein was significantly increased in LAD2 after IgE-mediated stimulation. Active TGF-β1 produced by primary cultured human MCs was significantly reduced in the presence of a chymase inhibitor, suggesting a role of MC chymase as an activator of latent TGF-β1. This study indicates that stimulation of human MCs by IgE receptor cross-linking triggers activation of TGF-β1, at least in part via chymase, which in turn induces the production of PAI-1 by bronchial ECs. Our data suggest that human MCs may play an important role in airway remodeling in asthma as a direct source of PAI-1 and by activating bronchial ECs to produce further PAI-1 via a TGF-β1-mediated activation pathway. PMID:24987792

  6. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    Energy Technology Data Exchange (ETDEWEB)

    Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2014-02-28

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  7. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    International Nuclear Information System (INIS)

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl2-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  8. Interleukin-17A and Toll-Like Receptor 3 Ligand Poly(I:C Synergistically Induced Neutrophil Chemoattractant Production by Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Hirotaka Matsuzaki

    Full Text Available Chronic inflammatory airway diseases, such as bronchial asthma and chronic obstructive pulmonary disease, are common respiratory disorders worldwide. Exacerbations of these diseases are frequent and worsen patients' respiratory condition and overall health. However, the mechanisms of exacerbation have not been fully elucidated. Recently, it was reported that interleukin (IL-17A might play an important role in neutrophilic inflammation, which is characteristic of such exacerbations, through increased production of neutrophil chemoattractants. Therefore, we hypothesized that IL-17A was involved in the pathogenesis of acute exacerbation, due to viral infection in chronic inflammatory airway diseases. In this study, we assessed chemokine production by bronchial epithelial cells and investigated the underlying mechanisms. Comprehensive chemokine analysis showed that, compared with poly(I:C alone, co-stimulation of BEAS-2B cells with IL-17A and poly(I:C strongly induced production of such neutrophil chemoattractants as CXC chemokine ligand (CXCL8, growth-related oncogene (GRO, and CXCL1. Co-stimulation synergistically induced CXCL8 and CXCL1 mRNA and protein production by BEAS-2B cells and normal human bronchial epithelial cells. Poly(I:C induced chemokine expression by BEAS-2B cells mainly via Toll-like receptor 3/TIR-domain-containing adapter-inducing interferon-β-mediated signals. The co-stimulation with IL-17A and poly(I:C markedly activated the p38 and extracellular-signal-regulated kinase 1/2 pathway, compared with poly(I:C, although there was little change in nuclear factor-κB translocation into the nucleus or the transcriptional activities of nuclear factor-κB and activator protein 1. IL-17A promoted stabilization of CXCL8 mRNA in BEAS-2B cells treated with poly(I:C. In conclusion, IL-17A appears to be involved in the pathogenesis of chronic inflammatory airway disease exacerbation, due to viral infection by promoting release of neutrophil

  9. Conjugated linoleic acids suppress inflammatory response and ICAM-1 expression through inhibition of NF-κB and MAPK signaling in human bronchial epithelial cells.

    Science.gov (United States)

    Huang, Wen-Chung; Tu, Rong-Syuan; Chen, Ya-Ling; Tsai, Yun-Yun; Lin, Chwan-Fwu; Liou, Chian-Jiun

    2016-04-20

    Conjugated linoleic acids (CLAs) comprise a group of natural unsaturated fatty acids. CLA was reported to have anti-asthma, anti-adiposity, and anti-tumor effects. The present study aimed to evaluate the suppressive effects of cis-9, trans-11-CLA (c9,t11-CLA) on the expression of proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) in TNF-α-stimulated human bronchial epithelial (BEAS-2B) cells. After treating with various doses of c9,t11-CLA (12.5-100 μg ml(-1)), BEAS-2B cells were induced into an inflamed state by adding TNF-α or TNF-α/IL-4. The presence of c9,t11-CLA significantly suppressed the secretion of cytokines IL-6, IL-8, CCL5, and MCP-1. We also found that c9,t11-CLA inhibited ICAM-1 expression, and decreased monocyte adhesion to inflamed bronchial epithelial cells. Interestingly, c9,t11-CLA attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) and down-regulated the activation of nuclear factor-κB (NF-κB). These results suggested that the anti-inflammatory effects of c9,t11-CLA were mediated by inhibiting proinflammatory cytokines, chemokines, and ICAM-1 expression by blocking NF-κB transcription regulation and by attenuating MAPK signaling pathways. PMID:27007063

  10. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

    Directory of Open Access Journals (Sweden)

    Clementina Sansone

    Full Text Available Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD, 2-trans,4-trans-octadienal (OD and 2-trans,4-trans-heptadienal (HD on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1 and Fas Associated Death Domain (FADD leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP. The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

  11. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells

    International Nuclear Information System (INIS)

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-κB (NF-κB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-α and NF-κB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30 μg/ml CSC significantly activated PKC-α, while CSC doses above 20 μg/ml CSC significantly activated NF-κB. As NF-κB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30 μg/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30 μg/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-α, NF-κB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

  12. Uptake and cytotoxic effects of multi-walled carbon nanotubes in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Carbon nanotubes (CNT) are cytotoxic to several cell types. However, the mechanism of CNT toxicity has not been fully studied, and dosimetric analyses of CNT in the cell culture system are lacking. Here, we describe a novel, high throughput method to measure cellular uptake of CNT using turbimetry. BEAS-2B, a human bronchial epithelial cell line, was used to investigate cellular uptake, cytotoxicity, and inflammatory effects of multi-walled CNT (MWCNT). The cytotoxicity of MWCNT was higher than that of crocidolite asbestos in BEAS-2B cells. The IC50 of MWCNT was 12 μg/ml, whereas that of asbestos (crocidolite) was 678 μg/ml. Over the course of 5 to 8 h, BEAS-2B cells took up 17-18% of the MWCNT when they were added to the culture medium at a concentration of 10 μg/ml. BEAS-2B cells were exposed to 2, 5, or 10 μg/ml of MWCNT, and total RNA was extracted for cytokine cDNA primer array assays. The culture supernatant was collected for cytokine antibody array assays. Cytokines IL-6 and IL-8 increased in a dose dependent manner at both the mRNA and protein levels. Migration inhibitory factor (MIF) also increased in the culture supernatant in response to MWCNT. A phosphokinase array study using lysates from BEAS-2B cells exposed to MWCNT indicated that phosphorylation of p38, ERK1, and HSP27 increased significantly in response to MWCNT. Results from a reporter gene assays using the NF-κB or AP-1 promoter linked to the luciferase gene in transiently transfected CHO-KI cells revealed that NF-κB was activated following MWCNT exposure, while AP-1 was not changed. Collectively, MWCNT activated NF-κB, enhanced phosphorylation of MAP kinase pathway components, and increased production of proinflammatory cytokines in human bronchial epithelial cells.

  13. Chromium(VI) stimulates Fyn to initiate innate immune gene induction in human airway epithelial cells

    Science.gov (United States)

    Nemec, Antonia A.; Zubritsky, Lindsey M.; Barchowsky, Aaron

    2009-01-01

    Mechanisms for pathogenic metal signaling in airway injury or disease promotion are poorly understood. It is widely believed that one mechanism for pathogenic and possible carcinogenic effects of inhaled chromium (Cr(VI)) is inhibition of inducible gene transactivation. However, we recently reported that Cr(VI) inhibition of Sp1-dependent transactivation required signal transducer and activator of transcription 1 (STAT1)-dependent expression of an inhibitory protein in airway epithelium. Thus, Cr(VI) exposures can induce genes and we hypothesized this induction resulted from Cr(VI) signaling through an innate immune-like STAT1-dependent pathway initiated by Fyn. Exposure of human airway epithelial (BEAS-2B) cells to Cr(VI) selectively transactivated STAT-responsive interferon-stimulated response element (ISRE) and induced ISRE-driven transactivation of interferon regulatory factor 7 (IRF7), without affecting the gamma interferon-activated site (GAS)-driven IRF1 expression. Cr(VI)-induced IRF7 was absent or greatly reduced in cells that lacked STAT1, were treated with the Src family kinase inhibitor, PP2, or lacked Fyn. Expressing Fyn, but not Src, in mouse embryonic fibroblasts cells null for Src, Yes, and Fyn restored Cr(VI)-stimulated STAT1 tyrosine phosphorylation and IRF7 expression. Finally, shRNA knockdown of Fyn in BEAS-2B cells prevented Cr(VI)-activated STAT1 transactivation of IRF7. These data support a novel mechanism through which Cr(VI) stimulates Fyn to initiate interferon-like signaling for STAT1-dependent gene transactivation. PMID:19994902

  14. Selective killing of cancer cells by nanoparticle-assisted ultrasound

    OpenAIRE

    Kosheleva, Olga K.; Lai, Tsung-Ching; Chen, Nelson G.; Hsiao, Michael; Chen, Chung-Hsuan

    2016-01-01

    Background Intense ultrasound, such as that used for tumor ablation, does not differentiate between cancerous and normal cells. A method combining ultrasound and biocompatible gold or magnetic nanoparticles (NPs) was developed under in vitro conditions using human breast and lung epithelial cells, which causes ultrasound to preferentially destroy cancerous cells. Results Co-cultures of BEAS-2B normal lung cells and A549 cancerous lung cells labeled with green and red fluorescent proteins, res...

  15. SILAC-based quantitative proteomic analysis of human lung cell response to copper oxide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Mariola J Edelmann

    Full Text Available Copper (II oxide (CuO nanoparticles (NP are widely used in industry and medicine. In our study we evaluated the response of BEAS-2B human lung cells to CuO NP, using Stable isotope labeling by amino acids in cell culture (SILAC-based proteomics and phosphoproteomics. Pathway modeling of the protein differential expression showed that CuO NP affect proteins relevant in cellular function and maintenance, protein synthesis, cell death and survival, cell cycle and cell morphology. Some of the signaling pathways represented by BEAS-2B proteins responsive to the NP included mTOR signaling, protein ubiquitination pathway, actin cytoskeleton signaling and epithelial adherens junction signaling. Follow-up experiments showed that CuO NP altered actin cytoskeleton, protein phosphorylation and protein ubiquitination level.

  16. Cationic polystyrene nanospheres induce autophagic cell death through the induction of endoplasmic reticulum stress

    Science.gov (United States)

    Chiu, Hui-Wen; Xia, Tian; Lee, Yu-Hsuan; Chen, Chun-Wan; Tsai, Jui-Chen; Wang, Ying-Jan

    2014-12-01

    Nanoparticles (NPs) have been used to produce a wide range of products that have applications in imaging and drug delivery in medicine. Due to their chemical stability, well-controlled sizes and surface charges, polystyrene (PS) NPs have been developed as biosensors and drug delivery carriers. However, the possible adverse biological effects and underlying mechanisms are still unclear. Recently, autophagy has been implicated in the regulation of cell death. In this study, we evaluated a library of PS NPs with different surface charges. We found that NH2-labeled polystyrene (NH2-PS) nanospheres were highly toxic with enhanced uptake in macrophage (RAW 264.7) and lung epithelial (BEAS-2B) cells. Furthermore, NH2-PS could induce autophagic cell death. NH2-PS increased autophagic flux due to reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress caused by misfolded protein aggregation. The inhibition of ER stress decreased cytotoxicity and autophagy in the NH2-PS-treated cells. In addition, the Akt/mTOR and AMPK signaling pathways were involved in the regulation of NH2-PS-triggered autophagic cell death. These results suggest an important role of autophagy in cationic NP-induced cell death and provide mechanistic insights into the inhibition of the toxicity and safe material design.Nanoparticles (NPs) have been used to produce a wide range of products that have applications in imaging and drug delivery in medicine. Due to their chemical stability, well-controlled sizes and surface charges, polystyrene (PS) NPs have been developed as biosensors and drug delivery carriers. However, the possible adverse biological effects and underlying mechanisms are still unclear. Recently, autophagy has been implicated in the regulation of cell death. In this study, we evaluated a library of PS NPs with different surface charges. We found that NH2-labeled polystyrene (NH2-PS) nanospheres were highly toxic with enhanced uptake in macrophage (RAW 264.7) and lung

  17. Absence of inflammatory response from upper airway epithelial cells after X irradiation.

    Science.gov (United States)

    Reiter, R; Deutschle, T; Wiegel, T; Riechelmann, H; Bartkowiak, D

    2009-03-01

    Radiotherapy of head and neck tumors causes adverse reactions in normal tissue, especially mucositis. The dose- and time-dependent response of upper airway cells to X radiation should be analyzed in terms of the pro-inflammatory potential. Immortalized BEAS-2B lung epithelial cells were treated with 2, 5 and 8 Gy. Out of 1232 genes, those that were transcribed differentially after 2, 6 and 24 h were assigned to biological themes according to the Gene Ontology Consortium. Enrichment of differentially regulated gene clusters was determined with GOTree ( http://bioinfo.vanderbilt.edu/gotm ). Eleven cytokines were measured in culture supernatants. The cell cycle response up to 24 h and induction of apoptosis up to 4 days after exposure were determined by flow cytometry. A significant dose- and time-dependent gene activation was observed for the categories response to DNA damage, oxidative stress, cell cycle arrest and cell death/apoptosis but not for immune/inflammatory response. This correlated with functional G(2) arrest and apoptosis. Pro-inflammatory cytokines accumulated in supernatants of control cells but not of X-irradiated cells. The complex gene expression pattern of X-irradiated airway epithelial cells is accompanied by cell cycle arrest and induction of apoptosis. In vivo, this may impair the epithelial barrier. mRNA and protein expression suggest at most an indirect contribution of epithelial cells to early radiogenic mucositis. PMID:19267554

  18. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

    OpenAIRE

    Constantopoulos Andreas G; Skevaki Chrysanthi L; Gourgiotis Dimitrios; Psarras Stelios; Bossios Apostolos; Saxoni-Papageorgiou Photini; Papadopoulos Nikolaos G

    2005-01-01

    Abstract Background Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxic...

  19. House dust mite allergen Der f enhanced bronchial epithelial cell cytokine expression

    Institute of Scientific and Technical Information of China (English)

    BAO QING SUN; WEI TANG; ALBERT CHAN; ADRIAN WU; NAN SHAN ZHONG

    2006-01-01

    The house dust mites ( Dermatophagoides farinae, Der f) are the major source of aeroallergens implicated in the expression of atopic disorders, including asthma, allergic rhinitis and atopic dermatitis. In particular, strong circumstantial evidence suggests that house dust mite antigens are important precipitating factors of asthma. Many house dust mite allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines from bronchial epithelial cells. To investigate whether Derf allergen proteases induced cytokine production from the epithelial cell line BEAS-2B,BEAS-2B cells were cultured with 4 different concentrations of Derf (0.02, 0.2, 2, 20 μg/ml) for 24-96 h, after which supernatants were assayed for interleukin (IL)-6 and IL-8 with ELISA. Reverse transcription-PCR was also performed. The cell sheets were intact throughout the observation in control group without any exposure to Derf antigen. In the experimental groups cells treated with Der f allergen showed changes in the anchorage status of the monolayer. There was a significant increase in the level of cytokine production compared with the untreated sample. The release of IL-6 and IL-8 increased in a concentration-dependent manner ( P < 0.05, respectively) with the addition of increasing dosage of Der f to the cell sheets. Levels of IL-6 and IL-8 began to rise at 24 h and 48 h after allergen exposure, and they increased significantly in the supernatants at 72 h and 96 h. At the same time the concentration dependence of induction of IL-6 and IL-8 expression as well as an increase in the expression of IL-6 and IL-8 mRNA manifested evidently. HDM-induced airway inflammation may include Der f-mediated release of inflammatory mediators, and the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium. It is suggested that IL-6 and IL-8 production by bronchial epithelial cells may play a role in the

  20. Biodiesel from soybean promotes cell proliferation in vitro.

    Science.gov (United States)

    Gioda, Adriana; Rodríguez-Cotto, Rosa I; Amaral, Beatriz Silva; Encarnación-Medina, Jarline; Ortiz-Martínez, Mario G; Jiménez-Vélez, Braulio D

    2016-08-01

    Toxicological responses of exhaust emissions of biodiesel are different due to variation in methods of generation and the tested biological models. A chemical profile was generated using ICP-MS and GC-MS for the biodiesel samples obtained in Brazil. A cytotoxicity assay and cytokine secretion experiments were evaluated in human bronchial epithelial cells (BEAS-2B). Cells were exposed to polar (acetone) and nonpolar (hexane) extracts from particles obtained from fuel exhaust: fossil diesel (B5), pure soybean biodiesel (B100), soybean biodiesel with additive (B100A) and ethanol additive (EtOH). Biodiesel and its additives exhibited higher organic and inorganic constituents on particles when compared to B5. The biodiesel extracts did not exert any toxic effect at concentrations 10, 25, 50, 75, and 100μgmL(-1). In fact quite the opposite, a cell proliferation effect induced by the B100 and B100A extracts is reported. A small increase in concentrations of inflammatory mediators (Interleukin-6, IL-6; and Interleukin-8, IL-8) in the medium of biodiesel-treated cells was observed, however, no statistical difference was found. An interesting finding indicates that the presence of metals in the nonpolar (hexane) fraction of biodiesel fuel (B100) represses cytokine release in lung cells. This was revealed by the use of the metal chelator. Results suggest that metals associated with biodiesel's organic constituents might play a significant role in molecular mechanisms associated to cellular proliferation and immune responses. PMID:27179667

  1. Pro-inflammatory response and oxidative stress induced by specific components in ambient particulate matter in human bronchial epithelial cells.

    Science.gov (United States)

    Yang, Lawei; Liu, Gang; Lin, Ziying; Wang, Yahong; He, Huijuan; Liu, Tie; Kamp, David W

    2016-08-01

    Previous studies have shown that biological effect of particulate matter (PM2.5) is involved in including chemical composition and mass concentration, but the precise components and biological action on human bronchial epithelial cell line (BEAS-2B) are still unclear. The aim of this study was to evaluate the in vitro toxicity of PM2.5 collected at six urban sites in China, and to investigate how particle composition affects cytotoxicity. We used human bronchial epithelial (BEAS-2B) cell lines as model in vitro to expose to PM2.5 from different source, and then reactive oxygen species (ROS), superoxide dismutase activity and total antioxidant capacity were analyzed. Furthermore, we estimated the polycyclic aromatic hydrocarbon (PAH) and transition metal and the endotoxin contents. The mRNA expression of IL-1β and IL-10 following exposure to PM2.5 was measured by QRT-PCR. We also observed the mitochondrial membrane potential (MMP) using JC-1 staining, and apoptosis of BEAS-2B using flow cytometry. In addition, double-stranded DNA breaks (DSBs) were assessed using γ-H2AX immunofluorescence. Our results show that high concentrations of PAHs and elemental Ni were strongly associated with high apoptosis rates and high expression of IL-1β, in addition, Fe element was associated with the ROS level, furthermore, Fe and Cr element were associated with DNA damage in BEAS-2B cells. The cytotoxic effects of urban PM2.5 derived from six different cities in China appear dependent on the specific components in each. Our results indicate that air quality standards based on PM2.5 components may be more relevant than concentration-response functions (CRF). © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 923-936, 2016. PMID:25533354

  2. Effect of Tumor Necrosis Factor Family Member LIGHT (TNFSF14 on the Activation of Basophils and Eosinophils Interacting with Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Huai Na Qiu

    2014-01-01

    Full Text Available Allergic asthma can cause airway structural remodeling, involving the accumulation of extracellular matrix and thickening of smooth muscle. Tumor necrosis factor (TNF family ligand LIGHT (TNFSF14 is a cytokine that binds herpesvirus entry mediator (HVEM/TNFRSF14 and lymphotoxin β receptor (LTβR. LIGHT induces asthmatic cytokine IL-13 and fibrogenic cytokine transforming growth factor-β release from allergic asthma-related eosinophils expressing HVEM and alveolar macrophages expressing LTβR, respectively, thereby playing crucial roles in asthmatic airway remodeling. In this study, we investigated the effects of LIGHT on the coculture of human basophils/eosinophils and bronchial epithelial BEAS-2B cells. The expression of adhesion molecules, cytokines/chemokines, and matrix metalloproteinases (MMP was measured by flow cytometry, multiplex, assay or ELISA. Results showed that LIGHT could significantly promote intercellular adhesion, cell surface expression of intercellular adhesion molecule-1, release of airway remodeling-related IL-6, CXCL8, and MMP-9 from BEAS-2B cells upon interaction with basophils/eosinophils, probably via the intercellular interaction, cell surface receptors HVEM and LTβR on BEAS-2B cells, and extracellular signal-regulated kinase, p38 mitogen activated protein kinase, and NF-κB signaling pathways. The above results, therefore, enhance our understanding of the immunopathological roles of LIGHT in allergic asthma and shed light on the potential therapeutic targets for airway remodeling.

  3. Evaluation of uptake, cytotoxicity and inflammatory effects in respiratory cells exposed to pristine and -OH and -COOH functionalized multi-wall carbon nanotubes.

    Science.gov (United States)

    Ursini, Cinzia Lucia; Maiello, Raffaele; Ciervo, Aureliano; Fresegna, Anna Maria; Buresti, Giuliana; Superti, Fabiana; Marchetti, Magda; Iavicoli, Sergio; Cavallo, Delia

    2016-03-01

    Toxic effects were reported for pristine-multi-wall carbon nanotubes (p-MWCNTs) while the role of the functionalization on MWCNT-induced toxicity is not yet well defined. We evaluated on human alveolar (A549) epithelial cells and normal bronchial (BEAS-2B) cells exposed to p-MWCNTs, MWCNTs-OH and MWCNTs-COOH: uptake by TEM, cell viability by different assays, membrane damage by the LDH assay and cytokine release by ELISA. The aims of the present study were to: (i) confirm MWCNT cytotoxicity mechanisms hypothesized in our previous studies; (ii) identify the most reliable viability assay to screen MWCNT toxicity; and (iii) to test our model to clarify the role of functionalization on MWCNT-induced toxicity. In A549 cells, p-MWCNTs and MWCNTs-OH were localized free in the cytoplasm and inside vacuoles whereas MWCNTs-COOH were confined inside filled cytoplasmic vesicles. WST-1 and Trypan blue assays showed in A549 cells a similar slight viability reduction for all MWCNTs whereas in BEAS-2B cells WST1 showed a high viability reduction at the highest concentrations, particularly for MWCNTs-COOH. The MTT assay showed a false cytotoxicity as a result of MWCNTs-interference. Pristine and MWCNTs-COOH induced membrane damage, particularly in BEAS-2B cells. MWCNTs-COOH induced interleukin-6 (IL-6) and IL-8 release in A549 cells whereas p-MWCNTs induced IL-8 release in BEAS-2B cells. MWCNTs intracellular localization in A549 cells confirms the toxicity mechanisms previously hypothesized, with p-MWCNTs disrupting the membrane and vesicle-confined MWCNTs-COOH inducing inflammation. WST-1 was more reliable than MTT to test MWCNT-toxicity. BEAS-2B cells were more susceptible then A549 cells, particularly to MWCNT-COOH cytotoxicity. Our results confirm the toxicity of p-MWCNTs and demonstrate, also for the two kinds of tested functionalized MWCNTs toxic effects with a different mechanism of action. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26370214

  4. Stem cell transplantation for treating Parkinson's disease

    OpenAIRE

    Li, Runhui

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and ind...

  5. Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Perkins Timothy N

    2012-02-01

    Full Text Available Abstract Background Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis, and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 106μm2/cm2. Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE were used to comparatively assess silica particle-induced alterations in gene expression. Results Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75 and high (150 × 106μm2/cm2 amounts, respectively (p 6μm2/cm2 induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p FOS, ATF3, IL6 and IL8 early and over time (2, 4, 8, and 24 h. Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 106μm2/cm2, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 106μm2/cm2 revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells. Conclusions Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and

  6. Nanodiamond internalization in cells and the cell uptake mechanism

    International Nuclear Information System (INIS)

    Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed

  7. Gene 33/Mig6 inhibits hexavalent chromium-induced DNA damage and cell transformation in human lung epithelial cells

    Science.gov (United States)

    Park, Soyoung; Li, Cen; Zhao, Hong; Darzynkiewicz, Zbigniew; Xu, Dazhong

    2016-01-01

    Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene 33 also tends to be lower upon Cr(VI) treatments. Cr(VI)-induced DNA damage appears primarily in the S phases of the cell cycle despite the high basal DNA damage signals at the G2M phase. Knockdown of Gene 33 with siRNA significantly elevates Cr(VI)-induced DNA damage in both BEAS-2B and A549 cells. Depletion of Gene 33 also promotes Cr(VI)-induced micronucleus (MN) formation and cell transformation in BEAS-2B cells. Our results reveal a novel function of Gene 33 in Cr(VI)-induced DNA damage and lung epithelial cell transformation. We propose that in addition to its role in the canonical EGFR signaling pathway and other signaling pathways, Gene 33 may also inhibit Cr(VI)-induced lung carcinogenesis by reducing DNA damage triggered by Cr(VI). PMID:26760771

  8. SILAC-Based Quantitative Proteomic Analysis of Human Lung Cell Response to Copper Oxide Nanoparticles

    OpenAIRE

    Edelmann, Mariola J.; Shack, Leslie A; Caitlin D Naske; Walters, Keisha B.; Nanduri, Bindu

    2014-01-01

    Copper (II) oxide (CuO) nanoparticles (NP) are widely used in industry and medicine. In our study we evaluated the response of BEAS-2B human lung cells to CuO NP, using Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics and phosphoproteomics. Pathway modeling of the protein differential expression showed that CuO NP affect proteins relevant in cellular function and maintenance, protein synthesis, cell death and survival, cell cycle and cell morphology. Some of the...

  9. Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells.

    Science.gov (United States)

    Suzukawa, Maho; Koketsu, Rikiya; Baba, Shintaro; Igarashi, Sayaka; Nagase, Hiroyuki; Yamaguchi, Masao; Matsutani, Noriyuki; Kawamura, Masafumi; Shoji, Shunsuke; Hebisawa, Akira; Ohta, Ken

    2015-10-15

    There is rising interest in how obesity affects respiratory diseases, since epidemiological findings indicate a strong relationship between the two conditions. Leptin is a potent adipokine produced mainly by adipocytes. It regulates energy storage and expenditure and also induces inflammation. Previous studies have shown that leptin is able to activate inflammatory cells such as lymphocytes and granulocytes, but little is known about its effect on lung structural cells. The present study investigated the effects of leptin on human airway epithelial cells by using human primary airway epithelial cells and a human airway epithelial cell line, BEAS-2B. Flow cytometry showed enhanced ICAM-1 expression by both of those cells in response to leptin, and that effect was abrogated by dexamethasone or NF-κB inhibitor. Flow cytometry and quantitative PCR showed that airway epithelial cells expressed leptin receptor (Ob-R), whose expression level was downregulated by leptin itself. Multiplex cytokine analysis demonstrated enhanced production of CCL11, G-CSF, VEGF, and IL-6 by BEAS-2B cells stimulated with leptin. Furthermore, transfection of Ob-R small interference RNA decreased the effect of leptin on CCL11 production as assessed by quantitative PCR. Finally, leptin induced migration of primary airway epithelial cells toward leptin, suppressed BEAS-2B apoptosis induced with TNF-α and IFN-γ, and enhanced proliferation of primary airway epithelial cells. In summary, leptin was able to directly activate human airway epithelial cells by binding to Ob-R and by NF-κB activation, resulting in upregulation of ICAM-1 expression, induction of CCL11, VEGF, G-CSF, and IL-6 synthesis, induction of migration, inhibition of apoptosis, and enhancement of proliferation. PMID:26276826

  10. Microrheology of human lung epithelial cells measured by atomic force microscopy

    OpenAIRE

    Alcaraz, Jordi; Buscemi, Lara; Grabulosa, Mireia; Trepat, Xavier; Fabry, Ben; Farré, Ramon; Navajas, Daniel

    2003-01-01

    Lung epithelial cells are subjected to large cyclic forces from breathing. However, their response to dynamic stresses is poorly defined. We measured the complex shear modulus (G*(ω)) of human alveolar (A549) and bronchial (BEAS-2B) epithelial cells over three frequency decades (0.1–100 Hz) and at different loading forces (0.1–0.9 nN) with atomic force microscopy. G*(ω) was computed by correcting force-indentation oscillatory data for the tip-cell contact geometry and for the hydrodynamic vis...

  11. [Cellular distribution and behavior of metallothionein in mammalian cells following exposure to silver nanoparticles and silver ions].

    Science.gov (United States)

    Miyayama, Takamitsu; Arai, Yuta; Suzuki, Noriyuki; Hirano, Seishiro

    2014-01-01

    Silver nanoparticles (AgNPs) are commercially used mainly as antibacterial reagents in wound dressing and deodorant powders. However, the mechanisms underlying Ag toxicity in mammals are not fully understood. In the present study, we assessed cellular distribution and toxicity of AgNPs and AgNO3 in mouse macrophage cell line (J774.1) and those of AgNO3 in human bronchial epithelial cell line (BEAS-2B) focusing on behavior of metallothionein (MT). J774.1 cells were exposed to 0-100 μg Ag/mL AgNPs or AgNO3 and BEAS-2B cells were exposed to 0-100 μM AgNO3 for 24 h. The cytotoxicity was assayed by a modified MTT method. The cellular concentration and distribution of Ag were evaluated by inductively coupled plasma-mass spectorometry (ICP-MS) and laser scanning microscopy. Distribution of Ag to MT and other proteins was determined using HPLC-ICP-MS. Most AgNPs were found in lysosomes in J774.1 at 3 h after post exposure. Ag was distributed to high molecular weight proteins in AgNPs-exposed cells, while most Ag was bound to MT in AgNO3-exposed cells. In AgNO3-exposed BEAS-2B cells cellular Ag concentration and Ag-bound MT (Ag-MT) were sharply increased up to 3 h and then decreased. ROS production appeared to cause relocation of MT-bound Ag to mitochondria, which evoked inhibition of electron transport chain. AgNPs were sequestered by high-molecular weight proteins rather than MT, probably because they were taken up by lysosomes before induction of MT. PMID:24882648

  12. Genotoxicity of short single-wall and multi-wall carbon nanotubes in human bronchial epithelial and mesothelial cells in vitro

    International Nuclear Information System (INIS)

    Although some types of carbon nanotubes (CNTs) have been described to induce mesothelioma in rodents and genotoxic effects in various cell systems, there are few previous studies on the genotoxicity of CNTs in mesothelial cells. Here, we examined in vitro DNA damage induction by short multi-wall CNTs (MWCNTs; 10–30 nm × 1–2 μm) and single-wall CNTs (SWCNTs; >50% SWCNTs, ∼40% other CNTs; 1dG) DNA adducts. In BEAS 2B cells, we also studied the induction of micronuclei (MN) by the CNTs using the cytokinesis-block method. The cells were exposed to the CNTs (5–200 μg/cm2, corresponding to 19–760 μg/ml) for 24 and 48 h in the comet assay and for 48 and 72 h in the MN and M1dG assays. Transmission electron microscopy (TEM) showed more MWCNT fibres and SWCNT clusters in BEAS 2B than MeT-5A cells, but no significant differences were seen in intracellular dose expressed as area of SWCNT clusters between TEM sections of the cell lines. In MeT-5A cells, both CNTs caused a dose-dependent induction of DNA damage (% DNA in comet tail) in the 48-h treatment and SWCNTs additionally in the 24-h treatment, with a statistically significant increase at 40 μg/cm2 of SWCNTs and (after 48 h) 80 μg/cm2 of both CNTs. SWCNTs also elevated the level of M1dG DNA adducts at 1, 5, 10 and 40 μg/cm2 after the 48-h treatment, but both CNTs decreased M1dG adduct level at several doses after the 72-h treatment. In BEAS 2B cells, SWCNTs induced a statistically significant increase in DNA damage at 80 and 120 μg/cm2 after the 24-h treatment and in M1dG adduct level at 5 μg/cm2 after 48 h and 10 and 40 μg/cm2 after 72 h; MWCNTs did not affect the level of DNA damage but produced a decrease in M1dG adducts in the 72-h treatment. The CNTs did not affect the level of MN. In conclusion, MWCNTs and SWCNTs induced DNA damage in MeT-5A cells but showed a lower (SWCNTs) or no (MWCNTs) effect in BEAS 2B cells, suggesting that MeT-5A cells were more sensitive to the DNA-damaging effect of CNTs

  13. Indeterminate cell histiocytosis successfully treated with phototherapy.

    Science.gov (United States)

    Zerbini, Maria Claudia Nogueira; Sotto, Mirian Nacagami; de Campos, Fernando Peixoto Ferraz; Abdo, Andre Neder Ramires; Pereira, Juliana; Sanches, José Antônio; Martins, Jade Cury

    2016-01-01

    First described in 1985, intermediate cell histiocytosis is a rare disorder of the cutaneous dendritic cell group with a varied clinical presentation and evolution. The pathologic substrate is constituted by the proliferation of indeterminate cells (ICs) that are immunophenotypically characterized by the positivity of CD1a, CD68, and faint/focal S100, plus the negativity for CD207 (langerin). The authors present the case of a healthy elderly woman who presented generalized dome-shaped reddish cutaneous nodules over her trunk, neck, face, and extremities over a period of 18 months. A laboratory and imaging work-up ruled out internal involvement. The skin biopsy was consistent with IC histiocytosis. The patient was treated with narrowband ultraviolet B phototherapy, which resulted in an excellent short-term outcome. PMID:27547741

  14. 36. Study on p16INK4a and p15INK4b genes of human bronchial epithelial cells malignantly transformed by cyclophosphamide and thiotepa

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Transformed human bronchial epithelial cells BEAS-2B induced by CP and TEPA were used to study abnormity of the tumor suppressor genes p15INK4b and p16INK4a, through which we can provide clues for explanations of the molecular mechanism in carcinogenesis of human bronchial epithelial cells induced by CP and TEPA. Analysis of the genomic DNA from the transformed BEAS-CP, and BEAS-T cells using PCR amplification, singe strand conformation polymorphism(SSCP) and DNA sequencing

  15. Toxicological effects of polycyclic aromatic hydrocarbons and their derivatives on respiratory cells

    Science.gov (United States)

    Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa

    2014-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are found in ambient aerosols and particulate matter. Experimental studies have shown that PAHs and related chemicals can induce toxicological effects. The present study aimed to investigate the effects of PAHs and their derivatives on the respiratory and immune systems and the underlying mechanisms. The human bronchial epithelial cell line BEAS-2B was exposed to PAHs and their derivatives, and the cytotoxicity and proinflammatory protein expression were then investigated. A cytotoxic effect was observed in BEAS-2B exposed to PAH derivatives such as naphthoquinone (NQ), phenanthrenequinone (PQ), 1-nitropyrene (1-NP), and 1-aminopyrene (1-AP). In addition, 1,2-NQ and 9,10-PQ showed more effective cytotoxicity than 1,4-NQ and 1,4-PQ, respectively. Pyrene showed a weak cytotoxic effect. On the other hand, naphthalene and phenanthrene showed no significant effects. Pyrene, 1-NP, and 1-AP also increased intercellular adhesion molecule-1 expression and interleukin-6 production in BEAS-2B. The increase was partly suppressed by protein kinase inhibitors such as the epidermal growth factor receptor-selective tyrosine kinase inhibitor and nuclear receptor antagonists such as the thyroid hormone receptor antagonist. The present study suggests that the toxicological effects of chemicals may be related to the different activities resulting from their structures, such as numbers of benzene rings and functional groups. Furthermore, the chemical-induced increase in proinflammatory protein expression in bronchial epithelial cells was possibly a result of the activation of protein kinase pathways and nuclear receptors. The increase may partly contribute to the adverse health effects of atmospheric PAHs.

  16. Treating asthma means treating airway smooth muscle cells

    NARCIS (Netherlands)

    Zuyderduyn, S; Sukkar, M B; Fust, A; Dhaliwal, S; Burgess, J K

    2008-01-01

    Asthma is characterised by airway hyperresponsiveness, airway inflammation and airway remodelling. Airway smooth muscle cells are known to be the main effector cells of airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of airway smooth muscle

  17. Types of Stem Cell Transplants for Treating Cancer

    Science.gov (United States)

    ... Sources of stem cells for transplant Types of stem cell transplants for treating cancer In a typical stem ... come from your identical twin or triplet Autologous stem cell transplants These stem cells come from you alone. ...

  18. AT-RvD1 Modulates CCL-2 and CXCL-8 Production and NF-κB, STAT-6, SOCS1, and SOCS3 Expression on Bronchial Epithelial Cells Stimulated with IL-4

    OpenAIRE

    de Oliveira, Jhony Robison; Favarin, Daniely Cornélio; Tanaka, Sarah Cristina Sato Vaz; Balarin, Marly Aparecida Spadotto; Silva Teixeira, David Nascimento; Levy, Bruce David; Rogério, Alexandre de Paula

    2015-01-01

    Bronchial epithelial cells represent the first line of defense against microorganisms and allergens in the airways and play an important role in chronic inflammatory processes such as asthma. In an experimental model, both RvD1 and AT-RvD1, lipid mediators of inflammation resolution, ameliorated some of the most important phenotypes of experimental asthma. Here, we extend these results and demonstrate the effect of AT-RvD1 on bronchial epithelial cells (BEAS-2B) stimulated with IL-4. AT-RvD1 ...

  19. How Is Sickle Cell Disease Treated?

    Science.gov (United States)

    ... sickle cell disease, go to the Health Topics Sickle Cell Anemia article. Living With and Managing Sickle Cell Disease ( ... the most severe form of sickle cell disease, sickle cell anemia, Tiffany has lived with the symptoms and complications ...

  20. Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression.

    Science.gov (United States)

    Seriani, Robson; de Souza, Claudia Emanuele Carvalho; Krempel, Paloma Gava; Frias, Daniela Perroni; Matsuda, Monique; Correia, Aristides Tadeu; Ferreira, Márcia Zotti Justo; Alencar, Adriano Mesquita; Negri, Elnara Marcia; Saldiva, Paulo Hilário Nascimento; Mauad, Thais; Macchione, Mariangela

    2016-05-01

    Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity. The genes involved in apoptosis [B cell lymphoma 2 (BCL-2 and caspase-3)] presented inversely proportional expressions (p = 0.05, p = 0.01, respectively), low expression of the genes involved in antioxidant responses [SOD1 (superoxide dismutase 1); SOD2 (superoxide dismutase 2), and GPx (glutathione peroxidase) (p = 0.01)], along with an increase in cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) (p = 0.01). These results suggest that alterations in cell rheology and cytotoxicity could be associated with oxidative stress and imbalance between pro- and anti-apoptotic genes. PMID:26856867

  1. Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for ∼ 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, the authors introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis

  2. Stem cell transplantation for treating Duchenne muscular dystrophy

    OpenAIRE

    Yang, Xiaofeng

    2012-01-01

    OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy in...

  3. A Cross-Study Biomarker Signature of Human Bronchial Epithelial Cells Infected with Respiratory Syncytial Virus

    Science.gov (United States)

    Gardinassi, Luiz Gustavo

    2016-01-01

    Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly, and immunocompromised individuals. Despite of advances in diagnosis and treatment, biomarkers of RSV infection are still unclear. To understand the host response and propose signatures of RSV infection, previous studies evaluated the transcriptional profile of the human bronchial epithelial cell line—BEAS-2B—infected with different strains of this virus. However, the evolution of statistical methods and functional analysis together with the large amount of expression data provide opportunities to uncover novel biomarkers of inflammation and infections. In view of those facts publicly available microarray datasets from RSV-infected BEAS-2B cells were analyzed with linear model-based statistics and the platform for functional analysis InnateDB. The results from those analyses argue for the reevaluation of previously reported transcription patterns and biological pathways in BEAS-2B cell lines infected with RSV. Importantly, this study revealed a biosignature constituted by genes such as ABCC4, ARMC8, BCLAF1, EZH1, FAM118A, FAM208B, FUS, HSPH1, KAZN, MAP3K2, N6AMT1, PRMT2, S100PBP, SERPINA1, TLK2, ZNF322, and ZNF337 which should be considered in the development of new molecular diagnosis tools.

  4. Stem cell therapy to treat heart ischaemia

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Mathiasen, Anders Bruun; Kastrup, Jens

    2014-01-01

    (CABG), morbidity and mortality is still high in patients with CAD. Along with PCI and CABG or in patients without options for revascularization, stem cell regenerative therapy in controlled trials is a possibility. Stem cells are believed to exert their actions by angiogenesis and regeneration of...... cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared to...... other cell types and cell therapy may be more effective in patients with known diabetes mellitus. However, further investigations are warranted....

  5. Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells

    DEFF Research Database (Denmark)

    Grigg, Jonathan; Walters, Haydn; Sohal, Sukhwinder Singh;

    2012-01-01

    BACKGROUND: Exposure to cigarette smoke (CS) is associated with increased risk of pneumococcal infection. The mechanism for this association is unknown. We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion of...... active-smokers by immunostaining. RESULTS: In A549 cells, CSE 1% increased pneumococcal adhesion (p<0.05 vs control), PAFR transcript level (p<0.01), and PAFR expression (p<0.01). Pneumococcal adhesion to A549 cells was attenuated by CV-3988 (p<0.001). CSE 1% stimulated pneumococcal adhesion to BEAS2-B...... cells and HBEpC (p<0.01 vs control). CSE 1% increased PAFR expression in BEAS2-B (p<0.01), and in HBEpC (p<0.05). Lung PAFR transcript level was increased in mice exposed to CS in vivo (p<0.05 vs room air). Active smokers (n=16) had an increased percentage of bronchial epithelium with PAFR...

  6. Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

    OpenAIRE

    Ferreira Manoel; Silva Paulo; Alvarez Silva Lucas; Bonfim Danielle; Conilho Macedo Müller Lucas; Espósito Christiano; Schanaider Alberto

    2012-01-01

    Abstract Background This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells Methods Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with ...

  7. Stem Cell Therapy to Treat Diabetes Mellitus

    OpenAIRE

    Liew, Chee Gee; Andrews, Peter W.

    2008-01-01

    Transplantation of pancreatic islets offers a direct treatment for type 1 diabetes and in some cases, insulin-dependent type 2 diabetes. However, its widespread use is hampered by a shortage of donor organs. Many extant studies have focused on deriving β-cell progenitors from pancreas and pluripotent stem cells. Efforts to generate β-cells in vitro will help elucidate the mechanisms of β-cell formation and thus provide a versatile in vivo system to evaluate the therapeutic potential of these ...

  8. Steroidogenesis in amlodipine treated purified Leydig cells

    Energy Technology Data Exchange (ETDEWEB)

    Latif, Rabia, E-mail: rabialatif08@hotmail.com [Department of Physiology, Army Medical College, National University of Sciences and Technology, Islamabad (Pakistan); Lodhi, Ghulam Mustafa, E-mail: drmustafa786@gmail.com [Department of Physiology, Wah Medical College, Wah (Pakistan); Hameed, Waqas, E-mail: waqham@hotmail.com [Department of Physiology, Rehman Medical College, Peshawar (Pakistan); Aslam, Muhammad, E-mail: professormaslam@yahoo.com [Department of Physiology, Shifa College of Medicine, Islamabad (Pakistan)

    2012-01-01

    Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of amlodipine, a calcium channel blocker, are well-illustrated in in vivo experiments but lack an in vitro proof. The present study was designed to experimentally elucidate the effects of amlodipine on Leydig cell steroidogenesis and intracellular calcium in vitro. Leydig cells of Sprague–Dawley rats were isolated and purified by Percoll. Cells were incubated for 3 h with/without amlodipine in the presence/absence of LH, dbcAMP, Pregnenolone and 25-Hydroxycholesterol. Cytosolic calcium was measured in purified Leydig cells by fluorometric technique. The results showed significantly reduced (P < 0.05) steroidogenesis and intracellular calcium in amlodipine exposed rats. The site of amlodipine induced steroidogenic inhibition seems to be prior to the formation of Pregnenolone at the level of StAR protein. -- Highlights: ► Inhibition of steroidogenesis in isolated and purified Leydig cells by amlodipine. ► Site of inhibition was before Pregnenolone formation, at the level of StAR protein. ► Inhibition of LH stimulated rise in cytosolic calcium by amlodipine.

  9. Capsaicinoids cause inflammation and epithelial cell death through activation of vanilloid receptors.

    Science.gov (United States)

    Reilly, Christopher A; Taylor, Jack L; Lanza, Diane L; Carr, Brian A; Crouch, Dennis J; Yost, Garold S

    2003-05-01

    Capsaicinoids, found in less-than-lethal self-defense weapons, have been associated with respiratory failure and death in exposed animals and people. The studies described herein provide evidence for acute respiratory inflammation and damage to epithelial cells in experimental animals, and provide precise molecular mechanisms that mediate these effects using human bronchiolar and alveolar epithelial cells. Inhalation exposure of rats to pepper sprays (capsaicinoids) produced acute inflammation and damage to nasal, tracheal, bronchiolar, and alveolar cells in a dose-related manner. In vitro cytotoxicity assays demonstrated that cultured human lung cells (BEAS-2B and A549) were more susceptible to necrotic cell death than liver (HepG2) cells. Transcription of the human vanilloid receptor type-1, VR1 or TRPV1, was demonstrated by RT-PCR in all of these cells, and the relative transcript levels were correlated to cellular susceptibility. TRPV1 receptor activation was presumably responsible for cellular cytotoxicity, but prototypical functional antagonists of this receptor were cytotoxic themselves, and did not ameliorate capsaicinoid-induced damage. Conversely, the TRPV1 antagonist capsazepine, as well as calcium chelation by EGTA ablated cytokine (IL-6) production after capsaicin exposure. To address these seemingly contradictory results, recombinant human TRPV1 was cloned and overexpressed in BEAS-2B cells. These cells exhibited dramatically increased cellular susceptibility to capsaicinoids, measured using IL-6 production and cytotoxicity, and an apoptotic mechanism of cell death. Surprisingly, the cytotoxic effects of capsaicin in TRPV1 overexpressing cells were also not inhibited by TRPV1 antagonists or by treatments that modified extracellular calcium. Thus, capsaicin interacted with TRPV1 expressed by BEAS-2B and other airway epithelial cells to cause the calcium-dependent production of cytokines and, conversely, calcium-independent cell death. These results

  10. A comparison of the biological effects of 125I seeds continuous low-dose-rate radiation and 60Co high-dose-rate gamma radiation on non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhongmin Wang

    Full Text Available To compare the biological effects of 125I seeds continuous low-dose-rate (CLDR radiation and 60Co γ-ray high-dose-rate (HDR radiation on non-small cell lung cancer (NSCLC cells.A549, H1299 and BEAS-2B cells were exposed to 125I seeds CLDR radiation or 60Co γ-ray HDR radiation. The survival fraction was determined using a colony-forming assay. The cell cycle progression and apoptosis were detected by flow cytometry (FCM. The expression of the apoptosis-related proteins caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, BAX and Bcl-2 were detected by western blot assay.After irradiation with 125I seeds CLDR radiation, there was a lower survival fraction, more pronounced cell cycle arrest (G1 arrest and G2/M arrest in A549 and H1299 cells, respectively and a higher apoptotic ratio for A549 and H1299 cells than after 60Co γ-ray HDR radiation. Moreover, western blot assays revealed that 125I seeds CLDR radiation remarkably up-regulated the expression of Bax, cleaved-caspase-3 and cleaved-PARP proteins and down-regulated the expression of Bcl-2 proteins in A549 and H1299 cells compared with 60Co γ-ray HDR radiation. However, there was little change in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment.125I seeds CLDR radiation led to remarkable growth inhibition of A549 and H1299 cells compared with 60Co HDR γ-ray radiation; A549 cells were the most sensitive to radiation, followed by H1299 cells. In contrast, normal BEAS-2B cells were relatively radio-resistant. The imbalance of the Bcl-2/Bax ratio and the activation of caspase-3 and PARP proteins might play a key role in the anti-proliferative effects induced by 125I seeds CLDR radiation, although other possibilities have not been excluded and will be investigated in future studies.

  11. A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Aysun Adan Gökbulut

    2015-06-01

    Full Text Available INTRODUCTION: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey, on 232B4 chronic lymphocytic leukemia (CLL cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. METHODS: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. RESULTS: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. DISCUSSION AND CONCLUSION: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.

  12. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xuejiao [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China); Jiaojiang District Center for Disease Control and Prevention, 518 Jingdong Rd., Taizhou 318000 (China); Zhang, Zhan; Wang, Xichen; Wang, Yun; Zhang, Xiaoming; Lu, Huiyuan [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China); Wang, Shou-Lin, E-mail: wangshl@njmu.edu.cn [Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing 211166 (China)

    2013-07-15

    Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5–80 nM) dose- and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 μM nicotine (a substrate of CYP2A13) or 1 μM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: • CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. • B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. • AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells • AFB1-induced DNA adducts and damage can be inhibited by nicotine and 8

  13. Stem cell therapies for treating osteoarthritis: prescient or premature?

    Science.gov (United States)

    Whitworth, Deanne J; Banks, Tania A

    2014-12-01

    There has been unprecedented interest in recent years in the use of stem cells as therapy for an array of diseases in companion animals. Stem cells have already been deployed therapeutically in a number of clinical settings, in particular the use of mesenchymal stem cells to treat osteoarthritis in horses and dogs. However, an assessment of the scientific literature highlights a marked disparity between the purported benefits of stem cell therapies and their proven abilities as defined by rigorously controlled scientific studies. Although preliminary data generated from clinical trials in human patients are encouraging, therapies currently available to treat animals are supported by very limited clinical evidence, and the commercialisation of these treatments may be premature. This review introduces the three main types of stem cells relevant to veterinary applications, namely, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells, and draws together research findings from in vitro and in vivo studies to give an overview of current stem cell therapies for the treatment of osteoarthritis in animals. Recent advances in tissue engineering, which is proposed as the future direction of stem cell-based therapy for osteoarthritis, are also discussed. PMID:25457267

  14. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    International Nuclear Information System (INIS)

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC50 of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G0/G1-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by the ROS generation

  15. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-12-15

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

  16. Persister cells in a biofilm treated with a biocide.

    Science.gov (United States)

    Simões, Lúcia C; Lemos, Madalena; Pereira, Ana M; Abreu, Ana C; Saavedra, Maria J; Simões, Manuel

    2011-04-01

    This study investigated the physiology and behaviour following treatment with ortho-phthalaldehyde (OPA), of Pseudomonas fluorescens in both the planktonic and sessile states. Steady-state biofilms and planktonic cells were collected from a bioreactor and their extracellular polymeric substances (EPS) were extracted using a method that did not destroy the cells. Cell structure and physiology after EPS extraction were compared in terms of respiratory activity, morphology, cell protein and polysaccharide content, and expression of the outer membrane proteins (OMP). Significant differences were found between the physiological parameters analysed. Planktonic cells were more metabolically active, and contained greater amounts of proteins and polysaccharides than biofilm cells. Moreover, biofilm formation promoted the expression of distinct OMP. Additional experiments were performed with cells after EPS extraction in order to compare the susceptibility of planktonic and biofilm cells to OPA. Cells were completely inactivated after exposure to the biocide (minimum bactericidal concentration, MBC = 0.55 ± 0.20 mM for planktonic cells; MBC = 1.7 ± 0.30 mM for biofilm cells). After treatment, the potential of inactivated cells to recover from antimicrobial exposure was evaluated over time. Planktonic cells remained inactive over 48 h while cells from biofilms recovered 24 h after exposure to OPA, and the number of viable and culturable cells increased over time. The MBC of the recovered biofilm cells after a second exposure to OPA was 0.58 ± 0.40 mM, a concentration similar to the MBC of planktonic cells. This study demonstrates that persister cells may survive in biocide-treated biofilms, even in the absence of EPS. PMID:21547756

  17. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Javed Akhtar M

    2012-02-01

    Full Text Available Mohd Javed Akhtar1,2, Maqusood Ahamed3, Sudhir Kumar1, MA Majeed Khan3, Javed Ahmad4, Salman A Alrokayan31Department of Zoology, University of Lucknow, Lucknow, India; 2Fibre Toxicology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, India; 3King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia; 4Department of Zoology, College of Science, King Saud University, Riyadh, Saudi ArabiaBackground: Zinc oxide nanoparticles (ZnO NPs have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear.Methods and results: We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B and two primary rat cells (astrocytes and hepatocytes. Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells.Conclusion: Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs.Keywords: Zn

  18. Chitin-Induced Airway Epithelial Cell Innate Immune Responses Are Inhibited by Carvacrol/Thymol

    Science.gov (United States)

    Erle, David J.

    2016-01-01

    Chitin is produced in large amounts by fungi, insects, and other organisms and has been implicated in the pathogenesis of asthma. Airway epithelial cells are in direct contact with environmental particles and serve as the first line of defense against inhaled allergens and pathogens. The potential contributions of airway epithelial cells to chitin-induced asthma remain poorly understood. We hypothesized that chitin directly stimulates airway epithelial cells to release cytokines that promote type 2 immune responses and to induce expression of molecules which are important in innate immune responses. We found that chitin exposure rapidly induced the expression of three key type 2-promoting cytokines, IL-25, IL-33 and TSLP, in BEAS-2B transformed human bronchial epithelial cells and in A549 and H292 lung carcinoma cells. Chitin also induced the expression of the key pattern recognition receptors TLR2 and TLR4. Chitin induced the expression of miR-155, miR-146a and miR-21, each of which is known to up-regulate the expression of pro-inflammatory cytokines. Also the expression of SOCS1 and SHIP1 which are known targets of miR-155 was repressed by chitin treatment. The monoterpene phenol carvacrol (Car) and its isomer thymol (Thy) are found in herbal essential oils and have been shown to inhibit allergic inflammation in asthma models. We found that Car/Thy inhibited the effects of chitin on type 2-promoting cytokine release and on the expression of TLRs, SOCS1, SHIP1, and miRNAs. Car/Thy could also efficiently reduce the protein levels of TLR4, inhibit the increase in TLR2 protein levels in chitin plus Car/Thy-treated cells and increase the protein levels of SHIP1 and SOCS1, which are negative regulators of TLR-mediated inflammatory responses. We conclude that direct effects of chitin on airway epithelial cells are likely to contribute to allergic airway diseases like asthma, and that Car/Thy directly inhibits epithelial cell pro-inflammatory responses to chitin. PMID

  19. Numerical model of dog mast cell tumor treated by electrochemotherapy.

    Science.gov (United States)

    Suzuki, Daniela O H; Anselmo, Jânio; de Oliveira, Krishna D; Freytag, Jennifer O; Rangel, Marcelo M M; Marques, Jefferson L B; Ramos, Airton

    2015-02-01

    Electrochemotherapy is a combination of high electric field and anticancer drugs. The treatment basis is electroporation or electropermeabilization of the cell membrane. Electroporation is a threshold phenomenon and, for efficient treatment, an adequate local distribution of electric field within the treated tissue is important. When this local electric field is not enough, there is a regrown tumor cell; however, if it is stronger than necessary, permanent damage to the tissue occurs. In the treatment of dogs, electrochemotherapy is not yet an established treatment for mast cell tumor in veterinary medicine, although there are studies showing evidence of its effectiveness. In this study, we examined electrochemotherapy of dog mast cell tumor with numerical simulation of local electric field distribution. The experimental result was used to validate the numerical models. The effect of tumor position and tissue thickness (tumor in different parts of dog body) was investigated using plate electrodes. Our results demonstrated that the electrochemotherapy is efficient and flexible, and even when the tumor extends into the subcutis, the treatment with plate electrode eliminated the tumor cells. This result suggests that electrochemotherapy is a suitable method to treat mast cell tumors in dog. PMID:25041415

  20. Studies on sequestration of neuraminidase-treated red blood cells

    International Nuclear Information System (INIS)

    The effects of reduction in the surface charge of red blood cells (RBCs) on regional blood flow and RBC distribution were studied in rats anesthetized with pentobarbital sodium. RBCs were treated with neuraminidase to reduce their electrophoretic mobility by 56%. Normal and neuraminidase-treated RBCs labeled with 51Cr or 111In were injected into a femoral vein while an equal volume of blood was simultaneously withdrawn from a femoral artery. More than 70% of the neuraminidase-treated RBCs injected disappeared from the circulating blood in 30 min compared with less than 2% of normal RBCs. The relative distributions of neuraminidase-treated RBCs to normal RBCs, as determined from radioactivity counting, were significantly greater than 1 in the spleen (5.65 +/- 0.97, mean +/- SD), the liver (2.84 +/- 0.21), the lung (1.48 +/- 0.31), and the kidney (1.49 +/- 0.27), indicating a preferential trapping of neuraminidase-treated RBCs in these regions. This ratio was approximately 1 in all other organs. Regional blood flows in tissues were determined with 15-micron microspheres in the control period and after the infusion of neuraminidase-treated RBCs (experimental). Experimental-to-control blood flow ratios were 0.40 +/- 0.05 in the spleen, 0.66 +/- 0.06 in the liver, 0.78 +/- 0.03 in the lung, and 0.78 +/- 0.09 in the kidneys; this ratio was approximately 1 in all other organs. An experimental-to-control blood flow ratio less than 1 indicates a reduction in blood flow; this occurred in the same organs as those with trapping of neuraminidase-treated RBCs

  1. Advanced Pyoderma Gangrenosum Previously Treated as Squamous Cell Carcinoma

    OpenAIRE

    Tamara Čuk Radović; Krešimir Kostović; Jaka Radoš; Zrinjka Paštar; Gordana Pavliša; Branka Marinović

    2015-01-01

    Pyoderma gangrenosum is a rare, neutrophilic ulcerative skin disease of unknown etiology often associated with an underlying systemic disease. We present a case of a pyoderma gangrenosum that was initially misdiagnosed and treated as squamous cell carcinoma in another hospital. Multiple surgical treatments triggered postoperative exacerbations and further rapid progression of the lesions. History of pathergy, clinical findings, and histopathological features examined at our Department indicat...

  2. Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization

    International Nuclear Information System (INIS)

    Highlights: → PM2.5 induces mitotic arrest in BEAS-2B cells. → PM2.5 induces DNA damage and activates DNA damage response. → AhR regulated genes (Cyp1A1, Cyp1B1 and AhRR) are upregulated after PM exposure. → Mitotic spindle assembly is perturbed in PM exposed cells. - Abstract: Airborne particulate matter (PM) is considered to be an important contributor to lung diseases. In the present study we report that Milan winter-PM2.5 inhibited proliferation in human bronchial epithelial cells (BEAS-2B) by inducing mitotic arrest. The cell cycle arrest was followed by an increase in mitotic-apoptotic cells, mitotic slippage and finally an increase in 'classical' apoptotic cells. Exposure to winter-PM10 induced only a slight effect which may be due to the presence of PM2.5 in this fraction while pure combustion particles failed to disturb mitosis. Fewer cells expressing the mitosis marker phospho-histone H3 compared to cells with condensed chromosomes, suggest that PM2.5 induced premature mitosis. PM2.5 was internalized into the cells and often localized in laminar organelles, although particles without apparent plasma membrane covering were also seen. In PM-containing cells mitochondria and lysosomes were often damaged, and in mitotic cells fragmented chromosomes often appeared. PM2.5 induced DNA strands breaks and triggered a DNA-damage response characterized by increased phosphorylation of ATM, Chk2 and H2AX; as well as induced a marked increase in expression of the aryl hydrocarbon receptor (AhR)-regulated genes, CYP1A1, CYP1B1 and AhRR. Furthermore, some disturbance of the organization of microtubules was indicated. It is hypothesized that the induced mitotic arrest and following cell death was due to a premature chromosome condensation caused by a combination of DNA, mitochondrial and spindle damage.

  3. Therapeutic approaches for treating hemophilia A using embryonic stem cells.

    Science.gov (United States)

    Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko

    2016-06-01

    Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future. PMID:27131224

  4. Effect of JAK Inhibitors on Release of CXCL9, CXCL10 and CXCL11 from Human Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Peter S Fenwick

    Full Text Available CD8+ T-cells are located in the small airways of COPD patients and may contribute to pathophysiology. CD8+ cells express the chemokine receptor, CXCR3 that binds CXCL9, CXCL10 and CXCL11, which are elevated in the airways of COPD patients. These chemokines are released from airway epithelial cells via activation of receptor associated Janus kinases (JAK. This study compared the efficacy of two structurally dissimilar pan-JAK inhibitors, PF956980 and PF1367550, and the glucocorticosteroid dexamethasone, in BEAS-2B and human primary airway epithelial cells from COPD patients and control subjects.Cells were stimulated with either IFNγ alone or with TNFα, and release of CXCL9, CXCL10 and CXCL11 measured by ELISA and expression of CXCL9, CXCL10 and CXCL11 by qPCR. Activation of JAK signalling was assessed by STAT1 phosphorylation and DNA binding.There were no differences in the levels of release of CXCL9, CXCL10 and CXCL11 from primary airway epithelial cells from any of the subjects or following stimulation with either IFNγ alone or with TNFα. Dexamethasone did not inhibit CXCR3 chemokine release from stimulated BEAS-2B or primary airway epithelial cells. However, both JAK inhibitors suppressed this response with PF1367550 being ~50-65-fold more potent than PF956980. The response of cells from COPD patients did not differ from controls with similar responses regardless of whether inhibitors were added prophylactically or concomitant with stimuli. These effects were mediated by JAK inhibition as both compounds suppressed STAT1 phosphorylation and DNA-binding of STAT1 and gene transcription.These data suggest that the novel JAK inhibitor, PF1367550, is more potent than PF956980 and that JAK pathway inhibition in airway epithelium could provide an alternative anti-inflammatory approach for glucocorticosteroid-resistant diseases including COPD.

  5. Cobalt chloride speciation, mechanisms of cytotoxicity on human pulmonary cells, and synergistic toxicity with zinc

    International Nuclear Information System (INIS)

    Complete text of publication follows: Cobalt is used in numerous industrial sectors, leading to occupational diseases, particularly by inhalation. Cobalt-associated mechanisms of toxicity are far from being understood and information that could improve knowledge in this area is required. We investigated the impact of a soluble cobalt compound, CoCl2, on the BEAS-2B lung epithelial cell line, as well as its impact on metal homeostasis. Cobalt speciation in different culture media, in particular soluble and precipitated cobalt species, was investigated via theoretical and analytical approaches. The cytotoxic effects of cobalt on the cells were assessed. Upon exposure of BEAS-2B cells to cobalt, intracellular accumulation of cobalt and zinc was demonstrated using direct in situ microchemical analysis based on ion micro-beam techniques and analysis after cell lysis by inductively coupled plasma mass spectrometry (ICP-MS). Microchemical imaging revealed that cobalt was rather homogeneously distributed in the nucleus and in the cytoplasm whereas zinc was more abundant in the nucleus. The modulation of zinc homeostasis led to the evaluation of the effect of combined cobalt and zinc exposure. In this case, a clear synergistic increase in toxicity was observed as well as a substantial increase in zinc content within cells. Western blots performed under the same co-exposure conditions revealed a decrease in ZnT1 expression, suggesting that cobalt could inhibit zinc release through the modulation of ZnT1. Overall, this study highlights the potential hazard to lung function, of combined exposure to cobalt and zinc

  6. PDT-treated apoptotic cells induce macrophage synthesis NO

    Science.gov (United States)

    Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

    2009-11-01

    Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

  7. Marijuana smoke condensate induces p53-mediated apoptosis in human lung epithelial cells.

    Science.gov (United States)

    Kim, Ha Ryong; Jung, Mi Hyun; Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

    2013-01-01

    Since the largely abused worldwide used of marijuana, there have been many ongoing debates regarding the adverse health effects of marijuana smoking. Marijuana smoking was recently proved to cause pulmonary toxicity by inducing genotoxic effects or generating reactive oxygen species. Because p53, a tumor suppressor gene, has an important pathophysiologic role in the regulation of lung epithelial cell DNA damage responses, we hypothesized that p53 may be involved in the oxidative stress-mediated apoptosis induced by marijuana smoking. First, we confirmed that marijuana smoke condensate (MSC) induces oxidative stress in BEAS-2B cells. We observed that reactive oxygen species (ROS) generation was increased by MSC in the DCFH-DA assay. Also, antioxidant enzyme (superoxide dismutase, catalase) activity and their mRNA expressions were up-regulated by MSC. Second, we investigated p53 involvement in the MSC-induced apoptotic pathway in BEAS-2B cells. The results showed that MSC increased caspase-3 activation and DNA fragmentation as markers of apoptosis. In addition, the mRNA levels of apoptosis-related genes (p53 and Bax) were increased by MSC and phospho-p53, along with the increase of Bax protein expression by MSC. Apoptosis and apoptosis-related gene expression were partially blocked by an inhibitor of p53-dependent transcriptional activation (pifithrin-α). The results indicate that p53 plays a role in MSC-induced apoptosis. Taken together, the findings of the present study suggest that MSC partially induces p53-mediated apoptosis through ROS generation in human lung epithelial cells and this may have broader implications for our understanding of pulmonary diseases. PMID:23665932

  8. Wood dusts induce the production of reactive oxygen species and caspase-3 activity in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Wood dusts are associated with several respiratory symptoms, e.g. impaired lung function and asthma, in exposed workers. However, despite the evidence from epidemiological studies, the underlying mechanisms are not well understood. In the present study, we investigated different wood dusts for their capacity to induce cytotoxicity and production of radical oxygen species (ROS) as well as activation of the apoptotic caspase-3 enzyme in human bronchial epithelial cells (BEAS-2B). Dusts from three different tree species widely used in wood industry were studied; birch and oak represented hardwood species, and pine a common softwood species. All the experiments were carried out in three different concentrations (10, 50, and 500 μg/ml) and the analysis was performed after 0.5, 2, 6, and 24 h exposure. All wood dusts studied were cytotoxic to human bronchial epithelial cells in a dose-dependent manner after 2 and 6 h treatment. Exposure to pine, birch, or oak dust had a significant stimulating effect on the production of ROS. Also an induction in caspase-3 protease activity, one of the central components of the apoptotic cascade, was seen in BEAS-2B cells after 2 and 6 h exposure to each of the wood dusts studied. In summary, we demonstrate that dusts from pine, birch and oak are cytotoxic, able to increase the production of ROS and the apoptotic response in human broncho-epithelial cells in vitro. Thus, our current data suggest oxidative stress by ROS as an important mechanism likely to function in wood dust related pulmonary toxicity although details of the cellular targets and cell-particle interactions remain to be solved. It is though tempting to speculate that redox-regulated transcription factors such as NFκB or AP-1 may play a role in this wood dust-evoked process leading to apparently induced apoptosis of target cells.

  9. Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract.

    Science.gov (United States)

    Starrett, Warren; Blake, David J

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide. Exposure to cigarette smoke (CS) is the primary factor associated with the COPD development. CS activates epithelial cells to secrete chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) that recruit neutrophils and macrophages to the lung. These inflammatory cells then release additional chemokines and cytokines leading to chronic inflammation that initiates apoptosis in epithelial and endothelial cells and destruction of alveolar structure. Pulmonary epithelium responds to oxidative stress mediated by CS through activating NRF2-dependent pathways, leading to an increased expression of antioxidant and cytoprotective enzymes thereby providing a protective response against CS-induced lung injury. We hypothesized that activating NRF2-dependent cytoprotective gene expression with sulforaphane (SFN) affords protection against CS-induced lung damage by inhibiting chemokine production. Results indicate that in the human BEAS-2B epithelial cell line, 5 μM SFN activated NRF2-dependent gene expression by triggering the translocation of NRF2 to the nucleus and significantly increased the expression of NRF2-dependent genes such as NADPH quinone oxidoreductase-1, heme oxygenase-1, and glutamate cysteine ligase modulatory subunit. Cigarette smoke extract (CSE) exposure of BEAS-2B cells significantly increased production of both IL-8 and MCP-1. Production of both chemokines was significantly reduced with SFN given prior to CSE; SFN inhibited IL-8 and MCP-1 gene expression at the transcription level. Our results indicate that activating NRF2 pathways with SFN inhibits CSE-induced chemokine production in human epithelial cells. However, the mechanism by which the production of chemokines is inhibited through SFN still remains to be elucidated. SFN may enhance NRF2 transcriptional activity resulting in the inhibition of proinflammatory pathways such

  10. Signal Transducer and Activator of Transcription 1 (STAT1) is Essential for Chromium Silencing of Gene Induction in Human Airway Epithelial Cells

    Science.gov (United States)

    Nemec, Antonia A.; Barchowsky, Aaron

    2009-01-01

    Hexavalent chromium (Cr(VI)) promotes lung injury and pulmonary diseases through poorly defined mechanisms that may involve the silencing of inducible protective genes. The current study investigated the hypothesis that Cr(VI) actively signals through a signal transducer and activator of transcription 1 (STAT1)–dependent pathway to silence nickel (Ni)–induced expression of vascular endothelial cell growth factor A (VEGFA), an important mediator of lung injury and repair. In human bronchial airway epithelial (BEAS-2B) cells, Ni-induced VEGFA transcription by stimulating an extracellular regulated kinase (ERK) signaling cascade that involved Src kinase–activated Sp1 transactivation, as well as increased hypoxia-inducible factor-1α (HIF-1α) stabilization and DNA binding. Ni-stimulated ERK, Src, and HIF-1α activities, as well as Ni-induced VEGFA transcript levels were inhibited in Cr(VI)-exposed cells. We previously demonstrated that Cr(VI) stimulates STAT1 to suppress VEGFA expression. In BEAS-2B cells stably expressing STAT1 short hairpin RNA, Cr(VI) increased VEGFA transcript levels and Sp1 transactivation. Moreover, in the absence of STAT1, Cr(VI), and Ni coexposures positively interacted to further increase VEGFA transcripts. This study demonstrates that metal-stimulated signaling cascades interact to regulate transcription and induction of adaptive or repair responses in airway cells. In addition, the data implicate STAT1 as a rate limiting mediator of Cr(VI)-stimulated gene regulation and suggest that cells lacking STAT1, such as many tumor cell lines, have opposite responses to Cr(VI) relative to normal cells. PMID:19403854

  11. Langerhans cell histiocytosis: An uncommon presentation, successfully treated by thalidomide

    Directory of Open Access Journals (Sweden)

    Mohammad Shahidi-Dadras

    2011-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare disease and generally affects children under 15 years of age. Adult onset form and cutaneous features at presentation are uncommon. There are some options for treatment of the skin lesions of LCH such as topical and intralesional corticosteroid, nitrogen mustard, etc., which are not completely curative. Herein, we report a case of perianal LCH in a 20-year-old man with one-year history of recalcitrant well-demarcated, erythematous, and ulcerated plaque surrounding the anal orifice, with pain and difficulty in defecation that was successfully treated with thalidomide.

  12. How to treat MDS without stem cell transplantation.

    Science.gov (United States)

    Gattermann, Norbert

    2010-01-01

    Although allogeneic hematopoietic cell transplantation (HCT) is the only proven curative treatment for myelodysplastic syndromes (MDS), it is only used to treat a minority of MDS patients. The majority of patients are too old or suffer from comorbidities rendering allogeneic HCT too risky. Alternative treatment strategies for patients with higher risk MDS try to alter the natural course of disease by preventing or delaying leukemic transformation. In patients with lower risk MDS, treatment is mainly focused on maintaining or improving the quality of life. PMID:19857591

  13. Dielectrophoretic characterization of antibiotic-treated Mycobacterium tuberculosis complex cells.

    Science.gov (United States)

    Inoue, Shinnosuke; Lee, Hyun-Boo; Becker, Annie L; Weigel, Kris M; Kim, Jong-Hoon; Lee, Kyong-Hoon; Cangelosi, Gerard A; Chung, Jae-Hyun

    2015-10-01

    Multi-drug resistant tuberculosis (MDR-TB) has become a serious concern for proper treatment of patients. As a phenotypic method, dielectrophoresis can be useful but is yet to be attempted to evaluate Mycobacterium tuberculosis complex cells. This paper investigates the dielectrophoretic behavior of Mycobacterium bovis (Bacillus Calmette-Guérin, BCG) cells that are treated with heat or antibiotics rifampin (RIF) or isoniazid (INH). The experimental parameters are designed on the basis of our sensitivity analysis. The medium conductivity (σ(m)) and the frequency (f) for a crossover frequency (f(xo1)) test are decided to detect the change of σ(m)-f(xo1) in conjunction with the drug mechanism. Statistical modeling is conducted to estimate the distributions of viable and nonviable cells from the discrete measurement of f (xo1). Finally, the parameters of the electrophysiology of BCG cells, C(envelope) and σ(cyto), are extracted through a sampling algorithm. This is the first evaluation of the dielectrophoresis (DEP) approach as a means to assess the effects of antimicrobial drugs on M. tuberculosis complex cells. PMID:26231690

  14. Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling

    Energy Technology Data Exchange (ETDEWEB)

    Skuland, Tonje, E-mail: tonje.skuland@fhi.no; Øvrevik, Johan; Låg, Marit; Schwarze, Per; Refsnes, Magne

    2014-08-15

    Amorphous silica nanoparticles (SiNPs) have previously been shown to induce marked cytokine (interleukin-6; IL-6 and interleukin-8; CXCL8/IL-8) responses independently of particle uptake in human bronchial epithelial BEAS-2B cells. In this study the involvement of the mitogen-activated protein kinases (MAP-kinases), nuclear factor-kappa Β (NF-κΒ) and in particular tumour necrosis factor-α converting enzyme (TACE) and—epidermal growth factor receptor (EGFR) signalling pathways were examined in triggering of IL-6 and CXCL8 release after exposure to a 50 nm silica nanoparticle (Si50). Exposure to Si50 increased phosphorylation of NF-κΒ p65 and MAP-kinases p38 and JUN-N-terminal protein kinase pathways (JNK), but not extracellular signal regulated kinases (ERK). Inhibition of NF-κΒ and p38 reduced the cytokine responses to Si50, whereas neither JNK- nor ERK-inhibition exerted any significant effect on the responses to Si50. Increases in membrane-bound transforming growth factor-α (TGF-α) release and EGFR phosphorylation were also observed after Si50 exposure, and pre-treatment with inhibitors of these pathways reduced the release of IL-6 and CXCL8, but did not affect the Si50-induced phosphorylation of p38 and p65. In contrast, p38-inhibition partially reduced Si50-induced TGF-α release, while the p65-inhibition was without effect. Overall, our results indicate that Si50-induced IL-6 and CXCL8 responses in BEAS-2B cells were regulated through combined activation of several pathways, including NF-κΒ and p38/TACE/TGF-α/EGFR signalling. The study identifies critical, initial events in the triggering of pro-inflammatory responses by nanoparticles. - Highlights: • Silica nanoparticles induce IL-6 and CXCL8 via NFκB and MAPKinase p38 in BEAS-2B • Silica nanoparticles induce release of the EGF-receptor ligand TGF-α • TGF-α release contributes to the IL-6 and CXCL8 release • Phosphorylation of p38 is involved in release of TGF-α.

  15. Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling

    International Nuclear Information System (INIS)

    Amorphous silica nanoparticles (SiNPs) have previously been shown to induce marked cytokine (interleukin-6; IL-6 and interleukin-8; CXCL8/IL-8) responses independently of particle uptake in human bronchial epithelial BEAS-2B cells. In this study the involvement of the mitogen-activated protein kinases (MAP-kinases), nuclear factor-kappa Β (NF-κΒ) and in particular tumour necrosis factor-α converting enzyme (TACE) and—epidermal growth factor receptor (EGFR) signalling pathways were examined in triggering of IL-6 and CXCL8 release after exposure to a 50 nm silica nanoparticle (Si50). Exposure to Si50 increased phosphorylation of NF-κΒ p65 and MAP-kinases p38 and JUN-N-terminal protein kinase pathways (JNK), but not extracellular signal regulated kinases (ERK). Inhibition of NF-κΒ and p38 reduced the cytokine responses to Si50, whereas neither JNK- nor ERK-inhibition exerted any significant effect on the responses to Si50. Increases in membrane-bound transforming growth factor-α (TGF-α) release and EGFR phosphorylation were also observed after Si50 exposure, and pre-treatment with inhibitors of these pathways reduced the release of IL-6 and CXCL8, but did not affect the Si50-induced phosphorylation of p38 and p65. In contrast, p38-inhibition partially reduced Si50-induced TGF-α release, while the p65-inhibition was without effect. Overall, our results indicate that Si50-induced IL-6 and CXCL8 responses in BEAS-2B cells were regulated through combined activation of several pathways, including NF-κΒ and p38/TACE/TGF-α/EGFR signalling. The study identifies critical, initial events in the triggering of pro-inflammatory responses by nanoparticles. - Highlights: • Silica nanoparticles induce IL-6 and CXCL8 via NFκB and MAPKinase p38 in BEAS-2B • Silica nanoparticles induce release of the EGF-receptor ligand TGF-α • TGF-α release contributes to the IL-6 and CXCL8 release • Phosphorylation of p38 is involved in release of TGF-α

  16. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  17. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

    DEFF Research Database (Denmark)

    Fox, Ira J; Daley, George Q; Goldman, Steven A;

    2014-01-01

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

  18. Cell therapeutics to treat diseases of the retina

    Directory of Open Access Journals (Sweden)

    Natarajan S

    2008-11-01

    to harvest the RPEs again. Study III: Materials & methods: Bone marrow mono nuclear cells were isolated and transported in cold containers (4-8oC over a period of 6-12 Hrs and viability was evaluated.Results: The bone marrow mononuclear cells were viable up to 12 Hrs in our methodology with a viability of more than 95% making it possible for cells isolated from Chennai centre to be taken to Mumbai or any other destination within a reach of 12 Hrs for application as reported in earlier studies.Conclusion: The in-vitro expansion of RPEs without Human Amniotic Membrane is expected to open up a new possibility for treating the Retinal Degenerative Diseases. However an animal study is needed before clinical application. Intra vitreal application of Bone Marrow Mono Nuclear cells to treat RP and AMD as reported earlier are considered safe. We plan to undertake treatment and long term follow-up of more numbers of patients with RP and AMD.

  19. Treating hearing disorders with cell and gene therapy

    Science.gov (United States)

    Gillespie, Lisa N.; Richardson, Rachael T.; Nayagam, Bryony A.; Wise, Andrew K.

    2014-12-01

    Hearing loss is an increasing problem for a substantial number of people and, with an aging population, the incidence and severity of hearing loss will become more significant over time. There are very few therapies currently available to treat hearing loss, and so the development of new therapeutic strategies for hearing impaired individuals is of paramount importance to address this unmet clinical need. Most forms of hearing loss are progressive in nature and therefore an opportunity exists to develop novel therapeutic approaches to slow or halt hearing loss progression, or even repair or replace lost hearing function. Numerous emerging technologies have potential as therapeutic options. This paper details the potential of cell- and gene-based therapies to provide therapeutic agents to protect sensory and neural cells from various insults known to cause hearing loss; explores the potential of replacing lost sensory and nerve cells using gene and stem cell therapy; and describes the considerations for clinical translation and the challenges that need to be overcome.

  20. Surface Properties of Cell-treated Polyethylene Terephthalate

    Directory of Open Access Journals (Sweden)

    Bing Shi

    2006-01-01

    Full Text Available The materials used in artificial joints undergo degradation through fatigue and corrosive wear in human body. The lifetime for well-designed artificial joints like hip joints is at most 12 years and a patient will usually have two total joint replacements during his/her lifetime. Tissue engineering, an alternative to total joint implantation, is the replacement of damaged tissue with the tissue that is designed and constructed to meet the needs of the individual patient. In this study, polyethylene terephthalate (PET in the form of overhead transparency films were investigated on their cell interactions and the tribological properties as an alternative tissue-engineering matrix. The base material of the transparency films is PET. Cell culture methods as well as atomic force microscope (AFM, contact angle goniometer, confocal microscope and universal tribotester were used to study the properties of the substrate materials and the interactions between the surface and the substrate materials. Results showed that cells grew on the substrate of the base materials of the PET. The tribological properties of the slides have been changed after being cell-treated.

  1. Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.

    Directory of Open Access Journals (Sweden)

    Priti Bahety

    Full Text Available BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA in Alzheimer's disease (AD, the mechanism by which DHA affects amyloid-β precursor protein (AβPP-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS. METHODS: The lysate and supernatant samples of CHO-wt and CHO-AβPP695 cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP695 cells shed further mechanistic insights on its neuroprotective actions.

  2. Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Gong

    2013-01-01

    Full Text Available Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20 μM suppressed the LPS-induced IL-8 production through the TLR4 activation, inhibiting eotaxin-1 induction. The in vivo study explored the demoting effects of kaempferol on asthmatic inflammation in BALB/c mice sensitized with ovalbumin (OVA. Mouse macrophage inflammatory protein-2 production and CXCR2 expression were upregulated in OVA-challenged mice, which was attenuated by oral administration of ≥10 mg/kg kaempferol. Kaempferol allayed the airway tissue levels of eotaxin-1 and eotaxin receptor CCR3 enhanced by OVA challenge. This study further explored the blockade of Tyk-STAT signaling by kaempferol in both LPS-stimulated BEAS-2B cells and OVA-challenged mice. LPS activated Tyk2 responsible for eotaxin-1 induction, while kaempferol dose-dependently inhibited LPS- or IL-8-inflamed Tyk2 activation. Similar inhibition of Tyk2 activation by kaempferol was observed in OVA-induced mice. Additionally, LPS stimulated the activation of STAT1/3 signaling concomitant with downregulated expression of Tyk-inhibiting SOCS3. In contrast, kaempferol encumbered STAT1/3 signaling with restoration of SOCS3 expression. Consistently, oral administration of kaempferol blocked STAT3 transactivation elevated by OVA challenge. These results demonstrate that kaempferol alleviated airway inflammation through modulating Tyk2-STAT1/3 signaling responsive to IL-8 in endotoxin-exposed airway epithelium and in asthmatic mice. Therefore, kaempferol may be a therapeutic agent targeting asthmatic diseases.

  3. Metabolism of oxidants and anti-oxidant protective mechanisms in dust exposed human lung cells; Oxidantienmetabolismus und anti-oxidative Schutzmechanismen in staubelasteten humanen Lungenzellen

    Energy Technology Data Exchange (ETDEWEB)

    Gillissen, A. [Berufsgenossenschaftliche Krankenanstalten Bergmannsheil, Bochum (Germany). Medizinische Klinik und Poliklinik; Jaworska, M. [Berufsgenossenschaftliche Krankenanstalten Bergmannsheil, Bochum (Germany). Medizinische Klinik und Poliklinik; Wickenburg, D. [Berufsgenossenschaftliche Krankenanstalten Bergmannsheil, Bochum (Germany). Medizinische Klinik und Poliklinik; Schultze-Werninghaus, G. [Berufsgenossenschaftliche Krankenanstalten Bergmannsheil, Bochum (Germany). Medizinische Klinik und Poliklinik

    1996-04-01

    The imbalance of the oxidant-antioxidant system in the human lung after fiber and dust exposure is to play a major pathophysiologic role in the development of diseases such as asbestosis and silicosis. We compared the effect of crocidolite and silica (SiO{sub 2}) with rockwool and basaltwool, both man made mineral fibers, (1) on the antioxidant system of bronchial epithelial cells (A549 and BEAS 2 B cell lines), and (2) on the stimulation of oxidant production (e.g. O{sub 2} and H{sub 2}O{sub 2}) of alveolar macrophages ex vivo. The alveolar macrophages were obtained from patients with asbestosis (n=8), patients with silicosis (n=10) and non-exposed volunteers (n=9). In both epithelial cell lines fiber/silica induced cytotoxicity increased dependent on incubation time and fiber/dust concentration. Simultaneously intracellular glutathione content decreased with increasing cytotoxicity. Within the particle groups crocidolite was the be most toxic fiber in all tests. Additional administration of N-acetylcysteine (NAC) - a thiol capable of scavenging oxygen radicals and having cellular glutathione precursor capabilities - reduced this cytotoxic effect significantly (p<0.05). In BEAS 2B cells intracellular glutathione and superoxide dismutase (SOD) levels rose after low fiber/dust concentrations (1 {mu}g/cm{sup 2}) and short incubation time (<5 h). However, at higher concentrations and longer incubation times glutathione and SOD levels decreased. In contrast, even at high concentrations (100 {mu}g/cm{sup 2}) and the longest incubation time (24 h) used, intracellular catalase levels did not decline. The most striking effects were detected after crocidolite, the smallest changes were found after rockwood exposure. In exposed alveolar macrophages rockwool and basaltwood caused less oxidant production than crocidolite and silica. Interestingly, even at highest concentrations (50 {mu}g/cm{sup 2}) rockwool exposure caused no significant change in oxidant release. (orig

  4. Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells.

    Science.gov (United States)

    Holden, Neil S; George, Tresa; Rider, Christopher F; Chandrasekhar, Ambika; Shah, Suharsh; Kaur, Manminder; Johnson, Malcolm; Siderovski, David P; Leigh, Richard; Giembycz, Mark A; Newton, Robert

    2014-01-01

    In asthma and chronic obstructive pulmonary disease (COPD) multiple mediators act on Gαq-linked G-protein-coupled receptors (GPCRs) to cause bronchoconstriction. However, acting on the airway epithelium, such mediators may also elicit inflammatory responses. In human bronchial epithelial BEAS-2B cells (bronchial epithelium + adenovirus 12-SV40 hybrid), regulator of G-protein signaling (RGS) 2 mRNA and protein were synergistically induced in response to combinations of long-acting β2-adrenoceptor agonist (LABA) (salmeterol, formoterol) plus glucocorticoid (dexamethasone, fluticasone propionate, budesonide). Equivalent responses occurred in primary human bronchial epithelial cells. Concentrations of glucocorticoid plus LABA required to induce RGS2 expression in BEAS-2B cells were consistent with the levels achieved therapeutically in the lungs. As RGS2 is a GTPase-activating protein that switches off Gαq, intracellular free calcium ([Ca(2+)]i) flux was used as a surrogate of responses induced by histamine, methacholine, and the thromboxane receptor agonist U46619 [(Z)-7-[(1S,4R,5R,6S)-5-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxabicyclo[2.2.1]heptan-6-yl]hept-5-enoic acid]. This was significantly attenuated by salmeterol plus dexamethasone pretreatment, or RGS2 overexpression, and the protective effect of salmeterol plus dexamethasone was abolished by RGS2 RNA silencing. Although methacholine and U46619 induced interleukin-8 (IL-8) release and this was inhibited by RGS2 overexpression, the repression of U46619-induced IL-8 release by salmeterol plus dexamethasone was unaffected by RGS2 knockdown. Given a role for Gαq-mediated pathways in inducing IL-8 release, we propose that RGS2 acts redundantly with other effector processes to repress IL-8 expression. Thus, RGS2 expression is a novel effector mechanism in the airway epithelium that is induced by glucocorticoid/LABA combinations. This could contribute to the efficacy of glucocorticoid/LABA combinations in asthma and

  5. Progress of PET imaging in the study of neural stem cell transplantation treating Parkinson's disease

    International Nuclear Information System (INIS)

    PET imaging has important value in the study of neural stem cell transplantation treating Parkinson's disease, especial in the evaluation of the effect, the study of treating mechanisms and the comparation of effect in different transplantation places. PET imaging as a non-invasive method plays a more and more important role in the study of neural stem cell transplantation treating Parkinson's disease. (authors)

  6. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    Science.gov (United States)

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  7. Phosphoproteomic profiling of selenate-treated Alzheimer's disease model cells.

    Directory of Open Access Journals (Sweden)

    Ping Chen

    Full Text Available The reversible phosphorylation of proteins regulates most biological processes, while abnormal phosphorylation is a cause or consequence of many diseases including Alzheimer's disease (AD. One of the hallmarks of AD is the formation of neurofibrillary tangles (NFTs, which is composed of hyperphosphorylated tau proteins. Sodium selenate has been recently found to reduce tau hyperphosphorylation and NFTs formation, and to improve spatial learning and motor performance in AD mice. In the current study, the phosphoproteomics of N2aSW cells treated with selenate were investigated. To avoid missing low-abundance phosphoproteins, both the total proteins of cells and the phosphor-enriched proteins were extracted and subjected to the two-dimensional gel electrophoresis with Pro-Q diamond staining and then LC-MS/MS analysis. A total of 65 proteins were altered in phosphorylation level, of which 39 were up-regulated and 26 were down-regulated. All identified phosphoproteins were bioinformatically annotated according to their physiochemical features, subcellular location, and biological function. Most of these significantly changed phosphoproteins are involved in crucial neural processes such as protesome activity, oxidative stress, cysteine and methionine metabolism, and energy metabolism. Furthermore, decreases were found in homocysteine, phosphor-tau and amyloid β upon selenate treatment. Our results suggest that selenate may intervene in the pathological process of AD by altering the phosphorylation of some key proteins involved in oxidative stress, energy metabolism and protein degradation, thus play important roles in maintaining redox homeostasis, generating ATP, and clearing misfolded proteins and aggregates. The present paper provides some new clues to the mechanism of selenate in AD prevention.

  8. Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2014-06-05

    Adult Langerhans Cell Histiocytosis; Childhood Langerhans Cell Histiocytosis; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

  9. Properties of resistant cells generated from lung cancer cell lines treated with EGFR inhibitors

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor (EGFR) signaling plays an important role in non-small cell lung cancer (NSCLC) and therapeutics targeted against EGFR have been effective in treating a subset of patients bearing somatic EFGR mutations. However, the cancer eventually progresses during treatment with EGFR inhibitors, even in the patients who respond to these drugs initially. Recent studies have identified that the acquisition of resistance in approximately 50% of cases is due to generation of a secondary mutation (T790M) in the EGFR kinase domain. In about 20% of the cases, resistance is associated with the amplification of MET kinase. In the remaining 30-40% of the cases, the mechanism underpinning the therapeutic resistance is unknown. An erlotinib resistant subline (H1650-ER1) was generated upon continuous exposure of NSCLC cell line NCI-H1650 to erlotinib. Cancer stem cell like traits including expression of stem cell markers, enhanced ability to self-renew and differentiate, and increased tumorigenicity in vitro were assessed in erlotinib resistant H1650-ER1 cells. The erlotinib resistant subline contained a population of cells with properties similar to cancer stem cells. These cells were found to be less sensitive towards erlotinib treatment as measured by cell proliferation and generation of tumor spheres in the presence of erlotinib. Our findings suggest that in cases of NSCLC accompanied by mutant EGFR, treatment targeting inhibition of EGFR kinase activity in differentiated cancer cells may generate a population of cancer cells with stem cell properties

  10. Use of stem cell transplantation to treat epilepsy: A Web of Science-based literature analysis

    OpenAIRE

    Yin, Zhongmin; Dong, Yushu; Zhang, Jiyang; Wang, Li

    2012-01-01

    OBJECTIVE: To identify global research trends in the use of stem cell transplantation to treat epilepsy. DATA RETRIEVAL: We performed a bibliometric analysis of studies on the use of stem cell transplantation to treat epilepsy during 2002–2011, retrieved from Web of Science, using the key words epilepsy or epileptic or epilepticus or seizure and “stem cell”. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on the use of stem cell transplantation to treat epilepsy i...

  11. Apoptotic cell-treated dendritic cells induce immune tolerance by specifically inhibiting development of CD4(+) effector memory T cells.

    Science.gov (United States)

    Zhou, Fang; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2016-02-01

    CD4(+) memory T cells play an important role in induction of autoimmunity and chronic inflammatory responses; however, regulatory mechanisms of CD4(+) memory T cell-mediated inflammatory responses are poorly understood. Here we show that apoptotic cell-treated dendritic cells inhibit development and differentiation of CD4(+) effector memory T cells in vitro and in vivo. Simultaneously, intravenous transfer of apoptotic T cell-induced tolerogenic dendritic cells can block development of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of the central nervous system in C57 BL/6J mouse. Our results imply that it is effector memory CD4(+) T cells, not central memory CD4(+) T cells, which play a major role in chronic inflammatory responses in mice with EAE. Intravenous transfer of tolerogenic dendritic cells induced by apoptotic T cells leads to immune tolerance by specifically blocking development of CD4(+) effector memory T cells compared with results of EAE control mice. These results reveal a new mechanism of apoptotic cell-treated dendritic cell-mediated immune tolerance in vivo. PMID:26111522

  12. Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2016-07-20

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood

  13. Persister cells in a biofilm treated with a biocide

    OpenAIRE

    Simões, Lúcia C.; Lemos, Madalena; Pereira, Ana M.; Ana C. Abreu; Saavedra, Maria J.; Simões, M.

    2011-01-01

    This study investigated the physiology and behaviour following treatment with ortho-phthalaldehyde (OPA), of Pseudomonas fluorescens in both the planktonic and sessile states. Steady-state biofilms and planktonic cells were collected from a bioreactor and their extracellular polymeric substances (EPS) were extracted using a method that did not destroy the cells. Cell structure and physiology after EPS extraction were compared in terms of respiratory activity, morphology, cell protein and poly...

  14. Stem cell transplantation for treating Parkinson's disease Literature analysis based on the Web of Science

    Institute of Scientific and Technical Information of China (English)

    Runhui Li

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items; (c) year of publication: 2002–2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) we excluded documents that were not published in the public domain; (c) we excluded a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to subject areas; (5) distribution according to country; (6) distribution according to institution; (7) comparison of countries that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease; (8) comparison of institutions that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease in the Web of Science from 2002 to 2011; (9) comparison of studies on stem cell transplantation from different cell sources for treating Parkinson's diseaseRESULTS: In total, 1 062 studies on stem cell transplantation for treating Parkinson's disease appeared in the Web of Science from 2002 to 2011, almost one third of which were from American authors and institutes. The number of studies on stem cell transplantation for treating Parkinson's disease had gradually increased over the past 10 years

  15. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hyunhee Kim

    Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

  16. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  17. Stem Cell and Biological Interventions to treat Allergic Airway Disease

    OpenAIRE

    Kavanagh, Heather

    2010-01-01

    The aim of this work was to investigate immune modulation with a particular focus on airway inflammation and allergic pathogenesis. This was probed in a model of pathogen driven immunomodulation (B. pertussis), and two models of therapeutic intervention namely immunisation (attenuated B. pertussis, BPZE1) or using a candidate cell therapy approach (mesenchymal stem cells, MSC). This work demonstrated that, in contrast to virulent B. pertussis, an attenuated, candidate vaccin...

  18. Strategies for recruitment of stem cells to treat myocardial infarction.

    Science.gov (United States)

    Shafiq, Muhammad; Lee, Sang-Hoon; Jung, Youngmee; Kim, Soo Hyun

    2015-01-01

    Heart failure is one of the most prominent causes of morbidity and mortality worldwide. According to the World Health Organization, coronary artery disease and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI results in obstruction of the blood supply to the heart and scar formation, and causes substantial death of cardiomyocytes in the infarct zone followed by an inflammatory response. Current treatment methodologies of MI and heart failure include organ transplantation, coronary artery bypass grafting, ventricular remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies has associated risks and benefits. Cellular cardiomyoplasty is a viable option to decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and improve heart function. However, the low rate of cell survival, shortage of cell sources and donors, tumorigenesis, and ethical issues hamper full exploitation of cell therapy for MI treatment. Consequently, the mobilization and recruitment of endogenous stem/progenitor cells from bone marrow, peripheral circulation, and cardiac tissues has immense potential through harnessing the host's own reparative capacities that result from interplay among cytokines, chemokines, and adhesion molecules. Therapeutic treatments to enhance the mobilization and homing of stem cells are under development. In this review, we present state-of-the-art approaches that are being pursued for stem cell mobilization and recruitment to regenerate infarcted myocardium. Potential therapeutic interventions and delivery strategies are discussed in detail. PMID:25594408

  19. HF-LPLI-treated tumor cells induce NO production in macrophage

    Science.gov (United States)

    Lu, Cuixia; Zhou, Feifan; Wu, Shengnan; Xing, Da

    2013-02-01

    High fluence low-power laser irradiation (HF-LPLI) provides a new stimulator to trigger cell apoptosis, and it is well known that apoptotic cells provide antigens to effectively trigger recognition by the immune system. In order to investigate the effect of HF-LPLI on the professional antigen-presenting cell (APC) function, in our primary study, we focused our attention on the effect of HF-LPLI-treated tumor cells on macrophages phagocytosis and NO production. Both confocal microscopy and flowcytometry analysis showed that HF-LPLI (120 J/cm2) induced significantly EMT6 death. Further experiments showed that HF-LPLI-treated EMT6 cells could be phagocyted by the murine macrophage cells RAW264.7, and could induce NO production in macrophages. Taken together, our results indicate that HF-LPLI-treated tumor cells effectively regulated the immune system. The HF-LPLI effect on the APC function needs to be further studied.

  20. Fluorescence and electron microscopic study of intracellular F-actin in concanavalin A-treated and cytochalasin B-treated Ehrlich ascites tumor cells.

    Directory of Open Access Journals (Sweden)

    Watanabe,Sadahiro

    1986-12-01

    Full Text Available To investigate the involvement of actin filaments in concanavalin A (Con A-induced cap formation and cytochalasin B (CB-induced zeiotic knob migration, the distribution of F-actin was studied in Con A-treated and CB-treated Ehrlich ascites tumor cells (EATC by fluorescence microscopy using heavy meromyosin conjugated with a fluorescent dye, N-(7-dimethylamino-4-methylcoumarinyl maleimide, (DACM-HMM. In non-treated cells, the diffuse fluorescence of DACM-HMM was observed in the cytoplasm, particularly intensely under the plasma membrane and around the nucleus. In Con A- and CB-treated cells, the fluorescence was seen at Con A-induced-capped and CB-induced-knob-accumulated regions. This fluorescence was more intense in CB-treated cells. To study the actin filaments in these fluorescent regions more clearly, the soluble components of the cells were eliminated by treatment with Triton X-100 or saponin solution containing a low concentration of glutaraldehyde, and the detergent-treated and saponin-treated cells were observed under a transmission electron microscope. Concentrated actin filaments were observed directly beneath the Con A-induced capping area and CB-induced zeiotic knob-accumulation area. The area of concentrated actin filaments appeared to correspond to the electron dense area observed in the identical region in the cells fixed without detergent treatment. More actin filaments were observed in CB-treated cells than in Con A-treated ones.

  1. Study of Paclitaxel-Treated HeLa Cells by Differential Electrical Impedance Flow Cytometry

    DEFF Research Database (Denmark)

    Kirkegaard, Julie; Clausen, Casper Hyttel; Rodriguez-Trujíllo, Romén;

    2014-01-01

    This work describes the electrical investigation of paclitaxel-treated HeLa cells using a custom-made microfluidic biosensor for whole cell analysis in continuous flow. We apply the method of differential electrical impedance spectroscopy to treated HeLa cells in order to elucidate the changes in...... on investigating the changes in the electrical properties of the cell membrane caused by the effect of paclitaxel. We observe good agreement between the model and the obtained results. This establishes the proof-of-concept for the application in cell drug therapy....

  2. Ectopic Pregnancy-Derived Human Trophoblastic Stem Cells Regenerate Dopaminergic Nigrostriatal Pathway to Treat Parkinsonian Rats

    OpenAIRE

    Lee, Tony Tung-Yin; Tsai, Cheng-Fang; Hsieh, Tsung-Hsun; Chen, Jia-Jin Jason; Wang, Yu-Chih; Kao, Mi-Chun; Wu, Ruey-Meei; Singh, Sher; Tsai, Eing-Mei; Lee, Jau-Nan

    2012-01-01

    Background Stem cell therapy is a potential strategy to treat patients with Parkinson’s disease (PD); however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies. Our objectives in this study were (i) to identify the characteristics of hTS cells as a potential cell source for therapy; an...

  3. EphA2 Mutation in Lung Squamous Cell Carcinoma Promotes Increased Cell Survival, Cell Invasion, Focal Adhesions, and Mammalian Target of Rapamycin Activation*

    Science.gov (United States)

    Faoro, Leonardo; Singleton, Patrick A.; Cervantes, Gustavo M.; Lennon, Frances E.; Choong, Nicholas W.; Kanteti, Rajani; Ferguson, Benjamin D.; Husain, Aliya N.; Tretiakova, Maria S.; Ramnath, Nithya; Vokes, Everett E.; Salgia, Ravi

    2010-01-01

    Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130Cas. Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130Cas. WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted. PMID:20360610

  4. EphA2 mutation in lung squamous cell carcinoma promotes increased cell survival, cell invasion, focal adhesions, and mammalian target of rapamycin activation.

    Science.gov (United States)

    Faoro, Leonardo; Singleton, Patrick A; Cervantes, Gustavo M; Lennon, Frances E; Choong, Nicholas W; Kanteti, Rajani; Ferguson, Benjamin D; Husain, Aliya N; Tretiakova, Maria S; Ramnath, Nithya; Vokes, Everett E; Salgia, Ravi

    2010-06-11

    Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130(Cas). Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130(Cas). WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted. PMID:20360610

  5. Radiosensitization of hypoxic cells treated with some imidazole derivatives

    International Nuclear Information System (INIS)

    Extensive investigations to seek more effective and less toxic radiosensitizers to hypoxic cells than misonidazole were carried out. It has been considered that the neurotoxicity of misonidazole was mainly due to the nitro substituent which is bounded to the imidazole ring. Instead of the nitro group, many types of sulfur group were introduced to the imidazole ring. Usually the radiosensitizing ability of the compound is supposed to be related to the electron affinity. Therefore, as an indicator of the electron affinity, the lowest unoccupied molecular orbital (LUMO) level of these compounds was determined by the MO calculation using the CNDO/2 method. The LUMO level of these compounds was almost the same as that of misonidazole. Expecting good radiosensitizing effect of these compounds, the radiation enhancement ratio to the hypoxic cells was tested in vitro. To get the hypoxic cells in vitro, HeLa S3 cells were flushed by 95% N2 + 5% CO2 gas in minimum essential medium. The oxygen enhancement ratio (OER) was measured at about 3 in this system. Unfortunately, the sulfur compounds have no radiosensitization to the hypoxic cells. Since the radiosensitizing ability seemed not directly to be related to the electron affinity and the radiosensitizing effect of misonidazole must be mainly due to the nitro substituent, certain dinitroimidazole derivatives (e.g. 2.4-dinitroimidazole-1-ethanol) were further studied for the screening test. It was found that this compound had a radiosensitizing effect on the hypoxic cells about ten times greater than misonidazole. The cytotoxicity of this compound was also investigated in our hypoxic system and it was found to have twice as much as misonidazole. Further investigation of this compound is necessary to apply animal experiments and clinical use. (author)

  6. Renal cell carcinoma-associated adult dermatomyositis treated laparoscopic nephrectomy

    Directory of Open Access Journals (Sweden)

    Elizabeth Nevins

    2013-01-01

    Full Text Available A 77-year-old female, who suffered from rheumatoid arthritis and hypothyroidism, developed severe muscle weakness. Clinical features, blood results and muscle biopsy suggested a possible diagnosis of dermatomyositis. A computed tomography of the chest, abdomen and pelvis showed a solid mass in the left kidney. She underwent a left laparoscopic nephrectomy and histology confirmed conventional (clear cell renal cell carcinoma. She recovered slowly and almost back to normal life after 6 months. Early appreciation of the typical skin rash may provide a clue to the diagnosis and screening for neoplasm may improve prognosis.

  7. Observations of xenon gas-treated barley cells in solution by atomic force microscopy.

    Science.gov (United States)

    Yoshino, T; Sotome, I; Ohtani, T; Isobe, S; Oshita, S; Maekawa, T

    2000-01-01

    Barley cells cut from a sprout were exposed to either air or high-pressure xenon gas for 3 days and the surface of those cells was observed by atomic force microscopy (AFM) to examine the effect of the gas treatment. This method enabled the direct observation of the fresh surface of the barley cells in solution at high resolution. The cuticle layer was preserved on the primary cell wall of 0.48 MPa xenon gas-treated barley cells, while air-treated barley cells lost the cuticle layer from the primary cell wall. These findings indicate that the high-pressure xenon gas treatment is effective to preserve the cuticle layer attached to the primary cell wall. AFM is a powerful tool for the observation of the surface structure of living plant cells in solution. PMID:11108038

  8. Mesenchymal stem cells as a therapeutic tool to treat sepsis

    Institute of Scientific and Technical Information of China (English)

    Eleuterio Lombardo; Tom van der Poll; Olga DelaRosa; Wilfried Dalemans

    2015-01-01

    Sepsis is a clinical syndrome caused by a deregulatedhost response to an infection. Sepsis is the mostfrequent cause of death in hospitalized patients.Although knowledge of the pathogenesis of sepsishas increased substantially during the last decades,attempts to design effective and specific therapiestargeting components of the derailed host responsehave failed. Therefore, there is a dramatic need fornew and mechanistically alternative therapies to treatthis syndrome. Based on their immunomodulatoryproperties, adult mesenchymal stem or stromal cells(MSCs) can be a novel therapeutic tool to treat sepsis.Indeed, MSCs reduce mortality in experimental modelsof sepsis by modulating the deregulated inflammatoryresponse against bacteria through the regulation ofmultiple inflammatory networks, the reprogrammingof macrophages and neutrophils towards a more antiinflammatoryphenotype and the release of antimicrobialpeptides. This report will review the currentknowledge on the effects of MSC treatment in preclinicalexperimental small animal models of sepsis.

  9. Treatment of established colon carcinoma-bearing mice by dendritic cells pulsed with lysates of heat-treated tumor cells

    Institute of Scientific and Technical Information of China (English)

    YING MinGang; ZHEN QiuHong; LIU Sheng; GONG FuSheng; XIE YunQing

    2009-01-01

    To investigate the therapeutic effect of dendritic cells pulsed with lysates of heat-treated CT26 colon carcinoma cells. Bone marrow-derived DCs were pulsed with lysates of heat-treated tumor cells and were used to immunize BALB/c mice with established colon carcinoma. Cytotoxic T lymphocyte (CTL) response was detected. The therapeutic effect induced by DCs was observed by tumor weight and survival time. DCs pulsed with lysates of heat-treated tumor cells markedly induced specific cytotoxic activity of CTLs. Tumor growth in the immunized BALB/c mice was significantly inhibited and the survival time of the tumor-bearing mice was prolonged, DCs pulsed with lysates of heat-treated tumor cells have an observable therapeutic effect on established colon carcinoma-bearing mice.

  10. Treatment of established colon carcinoma-bearing mice by dendritic cells pulsed with lysates of heat-treated tumor cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To investigate the therapeutic effect of dendritic cells pulsed with lysates of heat-treated CT26 colon carcinoma cells. Bone marrow-derived DCs were pulsed with lysates of heat-treated tumor cells and were used to immunize BALB/c mice with established colon carcinoma. Cytotoxic T lymphocyte (CTL) response was detected. The therapeutic effect induced by DCs was observed by tumor weight and survival time. DCs pulsed with lysates of heat-treated tumor cells markedly induced specific cytotoxic activity of CTLs. Tumor growth in the immunized BALB/c mice was significantly inhibited and the survival time of the tumor-bearing mice was prolonged. DCs pulsed with lysates of heat-treated tumor cells have an observable therapeutic effect on established colon carcinoma-bearing mice.

  11. Arsenic exposure induces the Warburg effect in cultured human cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  12. Arsenic exposure induces the Warburg effect in cultured human cells

    International Nuclear Information System (INIS)

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

  13. Stem cell transplantation for treating spinal cord injury A literature comparison between studies of stem cells obtained from various sources

    Institute of Scientific and Technical Information of China (English)

    Liangbi Xiang; Yu Chen

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating spinal cord injury using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating spinal cord injury from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating spinal cord injury that were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) year of publication: 2002–2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) distribution according to journals; (5) distribution according to funding agencies; and (6) top cited articles over the last 10 years.RESULTS: Bone marrow mesenchymal stem cells and embryonic stem cells have been widely used for treating spinal cord injury. In total, 191 studies of bone marrow mesenchymal stem cell transplantation and 236 studies of embryonic stem cell transplantation for treating spinal cord injury appeared in the Web of Science from 2002 to 2011, and almost half of which were derived from American or Japanese authors and institutes. The number of studies of stem cell transplantation for treating spinal cord injury has gradually increased over the past 10 years. Most papers on stem cell transplantation for treating spinal cord injury appeared in journals with a particular focus on stem cell research, such as Stem Cells and Cell Transplantation. Although umbilical cord blood stem cells and adipose

  14. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    International Nuclear Information System (INIS)

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As2O3

  15. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus

    Directory of Open Access Journals (Sweden)

    Chang HB

    2015-08-01

    Full Text Available Hong-Bin Chang,1 Bing-Huei Chen1,21Department of Food Science, 2Graduate Institute of Medicine, Fu Jen Catholic University, Taipei, TaiwanAbstract: The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell was selected for comparison. A high-performance liquid chromatography (HPLC method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 µg/mL, demethoxycurcumin (1,147.4 µg/mL, and bisdemethoxycurcumin (190.2 µg/mL. A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 µg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.Keywords: curcuminoid extract, curcuminoid nanoemulsion, Curcuma longa Linnaeus, lung cancer cell, cell cycle, apoptosis mechanism

  16. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  17. Two-dimensional polyacrylamide gel electrophoresis analysis of indomethacin-treated human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yan-Li Cheng; Gui-Ying Zhang; Zhi-Qiang Xiao; Fa-Qing Tang

    2005-01-01

    AIM: To establish the two-dimensional gel electrophoresis (2-DE) profiles of indomethacin (IN)-treated human colon cancer cell line HCT116, and to provide a new way to study its anti-tumor molecular mechanism through analyzing a variety of protein maps.METHODS: Two-DE profiles of HCT116 were established in IN-treated and untreated groups. Total proteins were separated by immobilized pH gradient-based 2-DE. The gels were stained by silver, scanned by ImageScanner,and analyzed with Image Master software.RESULTS: Clear background, well-resolved and reproducible 2-DE patterns of HCT116 cells were acquired in IN-treated and untreated group. The average deviation of spot position was 0.896±0.177 mm in IEF direction and 1.106±0.289 mm in SDS-PAGE direction respectively. In IN-treated group,1 169±36 spots were detected and 1 061±32 spots were matched, the average matching rate was 90.6% in three gels. In untreated group, 1 256±50 spots were detected and 1 168±46 spots were matched, the average matching rate was 93.0% in three gels. Forty-five differential protein spots were displayed between IN-treated and untreated groups. Of which, 34 protein spots decreased and 9showed higher expression in IN-treated group, and only two protein spots showed an expression in untreated cells.CONCLUSION: Two-DE profiles of IN-treated and untreated HCT116 cells were established. Apparent 45 different protein spots were detected in IN-treated and untreated HCT116 cells. The analysis on differential protein spots may serve as a new way to study the molecule mechanism of IN-treated colon cancer.

  18. Involvement of the MAPK and PI3K pathways in chitinase 3-like 1-regulated hyperoxia-induced airway epithelial cell death

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Na; Lee, Kyung Eun; Hong, Jung Yeon; Heo, Won Il; Kim, Kyung Won; Kim, Kyu Earn [Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Sohn, Myung Hyun, E-mail: mhsohn@yuhs.ac [Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Hyperoxia induces apoptosis and chitinase 3-like 1 expression in human airway epithelial cells. Black-Right-Pointing-Pointer Presence of chitinase 3-like 1 affects airway epithelial cell death after hyperoxic exposure. Black-Right-Pointing-Pointer Silencing chitinase 3-like 1 manipulate the phosphorylation of ERK, p38 and Akt. -- Abstract: Background: Exposure to 100% oxygen causes hyperoxic acute lung injury characterized by cell death and injury of alveolar epithelial cells. Recently, the role of chitinase 3-like 1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, in oxidative stress was demonstrated in murine models. High levels of serum CHI3L1 have been associated with various diseases of the lung, such as asthma, chronic obstructive pulmonary disease, and cancer. However, the role of CHI3L1 in human airway epithelial cells undergoing oxidative stress remains unknown. In addition, the signaling pathways associated with CHI3L1 in this process are poorly understood. Purpose: In this study, we demonstrate the role of CHI3L1, along with the MAPK and PI3K signaling pathways, in hyperoxia-exposed airway epithelial cells. Method: The human airway epithelial cell line, BEAS-2B, was exposed to >95% oxygen (hyperoxia) for up to 72 h. Hyperoxia-induced cell death was determined by assessing cell viability, Annexin-V FITC staining, caspase-3 and -7 expression, and electron microscopy. CHI3L1 knockdown and overexpression studies were conducted in BEAS-2B cells to examine the role of CHI3L1 in hyperoxia-induced apoptosis. Activation of the MAPK and PI3K pathways was also investigated to determine the role of these signaling cascades in this process. Results: Hyperoxia exposure increased CHI3L1 expression and apoptosis in a time-dependent manner. CHI3L1 knockdown protected cells from hyperoxia-induced apoptosis. In contrast, CHI3L1 overexpression promoted cell death after hyperoxia exposure. Finally

  19. Suppression of IL-8 production from airway cells by tiotropium bromide in vitro

    Directory of Open Access Journals (Sweden)

    Suzaki I

    2011-09-01

    Full Text Available Isao Suzaki1, Kazuhito Asano2, Yusuke Shikama3, Taisuke Hamasaki1, Ayako Kanei1, Harumi Suzaki11Department of Otorhinolaryngology, School of Medicine, Showa University, Tokyo, Japan; 2Division of Physiology, School of Nursing and Rehabilitation Sciences, Showa University, Yokohama, Japan; 3Department of Respiratory Diseases, Showa University Northern Yokohama Hospital, Yokohama, JapanBackground: COPD is characterized by persistent and progressive airway inflammation. Although neutrophilic airway inflammation is generally accepted to be a major factor in the pathogenesis of COPD, the influence of the agents used for the treatment of COPD on neutrophil functions such as chemotaxis is not fully understood.Purpose: The present study aimed to examine the influence of tiotropium bromide on the production of interleukin (IL-8 from human airway epithelial cells and lung fibroblasts (LFs after lipopolysaccharide (LPS stimulation in vitro.Methods: BEAS-2B cells, human bronchial epithelial cell line, and LFs, at a concentration of 5 × 105 cells/mL, were stimulated with LPS in the presence of various concentrations of tiotropium bromide. IL-8 in culture supernatants was examined by enzyme-linked immunosorbent assay (ELISA. IL-8 messenger ribonucleic acid (mRNA expression was examined by real-time polymerase chain reaction. The influence of tiotropium bromide on LPS-induced signaling pathways was also analyzed by examining nuclear factor-kappa (NF-κB activation and signaling protein phosphorylation by ELISA.Results: Tiotropium bromide at >15 pg/mL inhibited IL-8 production from both BEAS-2B cells and LFs after LPS stimulation. Tiotropium bromide also suppressed IL-8 mRNA expression through the inhibition of NF-κB activation and signaling protein, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, phosphorylation.Conclusion: The present results strongly suggest that tiotropium bromide exerts the inhibitory effect on neutrophilic

  20. Granular cell myoblastoma of the common bile duct treated by biliary drainage and surgery.

    OpenAIRE

    Dewar, J; Dooley, J S; Lindsay, I.; George, P; Sherlock, S

    1981-01-01

    A young Caucasian woman is described in whom obstructive jaundice was caused by a granular cell myoblastoma of the common bile duct. She was treated by percutaneous transhepatic biliary drainage for 10 days, before radical removal. Granular cell myoblastomas are benign lesions of disputed histogenesis, rare among biliary neoplasms, the excision of which is curative.

  1. Transcriptomic and proteomic analysis of human hepatic stellate cells treated with natural taurine.

    Science.gov (United States)

    Liang, Jian; Deng, Xin; Wu, Fa-Sheng; Tang, Yan-Fang

    2013-05-01

    The aim of this study was to investigate the differential expression of genes and proteins between natural taurine (NTau)‑treated hepatic stellate cells (HSCs) and control cells as well as the underlying mechanism of NTau in inhibiting hepatic fibrosis. A microculture tetrazolium (MTT) assay was used to analyze the proliferation of NTau‑treated HSCs. Flow cytometry was performed to compare the apoptosis rate between NTau-treated and non‑treated HSCs. Proteomic analysis using a combination of 2-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) was conducted to identify the differentially expressed proteins. Microarray analysis was performed to investigate the differential expression of genes and real-time polymerase chain reaction (PCR) was used to validate the results. The experimental findings obtained demonstrated that NTau decreased HSC proliferation, resulting in an increased number of cells in the G0/G1 phase and a reduced number of cells in the S phase. Flow cytometric analysis showed that NTau-treated HSCs had a significantly increased rate of apoptosis when compared with the non‑treated control group. A total of 15 differentially expressed proteins and 658 differentially expressed genes were identified by 2DE and MS, and microarray analysis, respectively. Gene ontology (GO) functional analysis indicated that these genes and proteins were enriched in the function clusters and pathways related to cell proliferation, cellular apoptosis and oxidation. The transcriptome and proteome analyses of NTau-treated HSCs demonstrated that NTau is able to significantly inhibit cell proliferation and promote cell apoptosis, highlighting its potential therapeutic benefits in the treatment of hepatic fibrosis. PMID:23525364

  2. Complete in vitro replication of SV40 DNA and chromatin in saponin-treated permeable cells.

    OpenAIRE

    Hosogi,Nobuo; Hanakawa,Shiro; Watanabe,Sekiko; Oda,Takuzo

    1981-01-01

    A permeable cell system has been developed by treatment with saponin for studying in vitro replication of DNA and chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in saponin-treated permeable cells was found to be more efficient than that in digitonin-treated permeable cells. Autoradiography of the agarose-gel revealed that [alpha-32P]dCTP was incorporated into SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated co...

  3. Effect of hyperthermic CO2-treated dendritic cell-derived exosomes on the human gastric cancer AGS cell line

    OpenAIRE

    Wang, Jinlin; Wang, Zhiyong; MO, YANXIA; Zeng, Zhaohui; Wei, Pei; Li, Tao

    2015-01-01

    The aim of the present study was to determine the antitumor effects of hyperthermic CO2 (HT-CO2)-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO2 at 43°C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity....

  4. Effect of surface treatments of titanium on amphotericin B-treated Candida albicans persister cells

    OpenAIRE

    Tsang, CSP; Tang, DYK

    2010-01-01

    Although persister cells in Candida albicans biofilm may contribute to its increased resistance to antifungal drugs, little information is available on the formation of Candida persister cells on titanium surfaces. The effect of different surface treatments of Ti on persister cells was determined in the present study. Titanium discs were surface-treated by three different methods (Group A - polishing, Group B - sandblasting followed by acid-etching, and Group C - sandblasting alone). Persiste...

  5. Mycoplasma contamination in cell cultures treated with ciprofloxacin and enrofloxacin: brief report

    OpenAIRE

    Bita Soltanian; Shiva Irani; Sarvenaz Hashemi; Seyed Hamid Reza Mozhgani; Mehdi Ajorloo; Yoosef Cheraghi; Alireza Gholami

    2015-01-01

    Background: Mycoplasma contamination in cell cultures is considered as a major economic, research and production problem. In this study, mycoplasma-infected Vero cell lines were treated by various dilutions of ciprofloxacin and enrofloxacin in a timely manner. Removal of mycoplasma contamination from infected cell cultures was evaluated and demonstrated by polymerase chain reaction (PCR) method. Methods: This study was done from October 2013 to May 2014, in Human Rabies Vaccine Laboratory,...

  6. NiO nanoparticles induce apoptosis through repressing SIRT1 in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Wei-Xia; He, Min-Di; Mao, Lin [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China); Qian, Feng-Hua [Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Li, Yu-Ming [Institute of Hepatobiliary Surgery, XinQiao Hospital, Third Military Medical University, Chongqing 400038 (China); Pi, Hui-Feng; Liu, Chuan; Chen, Chun-Hai; Lu, Yong-Hui; Cao, Zheng-Wang; Zhang, Lei; Yu, Zheng-Ping [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China); Zhou, Zhou, E-mail: lunazhou00@163.com [Department of Occupational Health, Third Military Medical University, Chongqing 400038 (China)

    2015-07-15

    With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni{sup 2+} inside the cells. NiONPs at doses of 5, 10, and 20 μg/cm{sup 2} inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity. - Highlights: • NiONPs were taken up by BEAS-2B cells and released Ni{sup 2+}. • NiONPs produced cytotoxicity was demonstrated through an apoptotic process. • NiONPs repressed SIRT1 expression and activated p53 and Bax. • Overexpression of SIRT1 attenuated NiONPs-induced apoptosis via deacetylation p53.

  7. Development to term of cloned cattle derived from donor cells treated with valproic acid.

    Directory of Open Access Journals (Sweden)

    Juliano Rodrigues Sangalli

    Full Text Available Cloning of mammals by somatic cell nuclear transfer (SCNT is still plagued by low efficiency. The epigenetic modifications established during cellular differentiation are a major factor determining this low efficiency as they act as epigenetic barriers restricting reprogramming of somatic nuclei. In this regard, most factors that promote chromatin decondensation, including histone deacetylase inhibitors (HDACis, have been found to increase nuclear reprogramming efficiency, making their use common to improve SCNT rates. Herein we used valproic acid (VPA in SCNT to test whether the treatment of nuclear donor cells with this HDACi improves pre- and post-implantation development of cloned cattle. We found that the treatment of fibroblasts with VPA increased histone acetylation without affecting DNA methylation. Moreover, the treatment with VPA resulted in increased expression of IGF2R and PPARGC1A, but not of POU5F1. However, when treated cells were used as nuclear donors no difference of histone acetylation was found after oocyte reconstruction compared to the use of untreated cells. Moreover, shortly after artificial activation the histone acetylation levels were decreased in the embryos produced with VPA-treated cells. With respect to developmental rates, the use of treated cells as donors resulted in no difference during pre- and post-implantation development. In total, five clones developed to term; three produced with untreated cells and two with VPA-treated cells. Among the calves from treated group, one stillborn calf was delivered at day 270 of gestation whereas the other one was delivered at term but died shortly after birth. Among the calves from the control group, one died seven days after birth whereas the other two are still alive and healthy. Altogether, these results show that in spite of the alterations in fibroblasts resulting from the treatment with VPA, their use as donor cells in SCNT did not improve pre- and post

  8. Natural and Treated FeS2 in Li/FeS2 Coin Cell

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Treated FeS2 samples were prepared by natural FeS2 samples which were ground first,heated in nitrogen and then washed in acid. The levels of impurity elements, primarily present as metallic oxides and sulfides, are higher in the natural FeS2 than those in the treated sample. Scanning electron microscopy shows that the grain sizes of treated FeS2 particles are smaller than those of natural FeS2 particles. The electrochemical performance of Li/treated FeS2 cells is attributed to the smaller grain sizes and higher purity of treated FeS2 particles in comparison to the natural FeS2sample.

  9. Nuclear Factor κB1/RelA Mediates Inflammation in Human Lung Epithelial Cells at Atmospheric Oxygen Levels.

    Science.gov (United States)

    Jagannathan, Lakshmanan; Jose, Cynthia C; Arita, Adriana; Kluz, Thomas; Sun, Hong; Zhang, Xiaoru; Yao, Yixin; Kartashov, Andrey V; Barski, Artem; Costa, Max; Cuddapah, Suresh

    2016-07-01

    Oxygen levels range from 2% to 9% in vivo. Atmospheric O2 levels (21%) are known to induce cell proliferation defects and cellular senescence in primary cell cultures. However, the mechanistic basis of the deleterious effects of higher O2 levels is not fully understood. On the other hand, immortalized cells including cancer cell lines, which evade cellular senescence are normally cultured at 21% O2 and the effects of higher O2 on these cells are understudied. Here, we addressed this problem by culturing immortalized human bronchial epithelial (BEAS-2B) cells at ambient atmospheric, 21% O2 and lower, 10% O2. Our results show increased inflammatory response at 21% O2 but not at 10% O2. We found higher RelA binding at the NF-κB1/RelA target gene promoters as well as upregulation of several pro-inflammatory cytokines in cells cultured at 21% O2. RelA knockdown prevented the upregulation of the pro-inflammatory cytokines at 21% O2, suggesting NF-κB1/RelA as a major mediator of inflammatory response in cells cultured at 21% O2. Interestingly, unlike the 21% O2 cultured cells, exposure of 10% O2 cultured cells to H2O2 did not elicit inflammatory response, suggesting increased ability to tolerate oxidative stress in cells cultured at lower O2 levels. PMID:26588041

  10. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    International Nuclear Information System (INIS)

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

  11. Gene expression profiles in BCL11B-siRNA treated malignant T cells

    Directory of Open Access Journals (Sweden)

    Grabarczyk Piotr

    2011-05-01

    Full Text Available Abstract Background Downregulation of the B-cell chronic lymphocytic leukemia (CLL/lymphoma11B (BCL11B gene by small interfering RNA (siRNA leads to growth inhibition and apoptosis of the human T-cell acute lymphoblastic leukemia (T-ALL cell line Molt-4. To further characterize the molecular mechanism, a global gene expression profile of BCL11B-siRNA -treated Molt-4 cells was established. The expression profiles of several genes were further validated in the BCL11B-siRNA -treated Molt-4 cells and primary T-ALL cells. Results 142 genes were found to be upregulated and 109 genes downregulated in the BCL11B-siRNA -treated Molt-4 cells by microarray analysis. Among apoptosis-related genes, three pro-apoptotic genes, TNFSF10, BIK, BNIP3, were upregulated and one anti-apoptotic gene, BCL2L1 was downregulated. Moreover, the expression of SPP1 and CREBBP genes involved in the transforming growth factor (TGF-β pathway was down 16-fold. Expression levels of TNFSF10, BCL2L1, SPP1, and CREBBP were also examined by real-time PCR. A similar expression pattern of TNFSF10, BCL2L1, and SPP1 was identified. However, CREBBP was not downregulated in the BLC11B-siRNA -treated Molt-4 cells. Conclusion BCL11B-siRNA treatment altered expression profiles of TNFSF10, BCL2L1, and SPP1 in both Molt-4 T cell line and primary T-ALL cells.

  12. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Hu C

    2015-03-01

    Full Text Available Chenxia Hu,1 Martin Niestroj,2,3 Daniel Yuan,4 Steven Chang,5 Jie Chen5,6 1Faculty of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Canadian Light Source, Saskatoon, SK, Canada; 3Physics Department, Bonn University, Bonn, Germany; 4Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; 5Faculty of Engineering, University of Alberta, Edmonton, AB, Canada; 6Canadian National Research Council/National Institute for Nanotechnology, Edmonton, AB, Canada Abstract: Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain. Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs with thio-PEG (polyethylene glycol and thio-glucose, the resulting functionalized GNPs (Glu-GNPs were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption

  13. Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant

    Science.gov (United States)

    2016-02-23

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Juvenile Myelomonocytic Leukemia; Previously Treated Childhood Rhabdomyosarcoma; Previously Treated Myelodysplastic Syndromes; Pulmonary Complications; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  14. Raman confocal microscopy and AFM combined studies of cancerous cells treated with Paclitaxel

    Science.gov (United States)

    Derely, L.; Collart Dutilleul, P.-Y.; Michotte de Welle, Sylvain; Szabo, V.; Gergely, C.; Cuisinier, F. J. G.

    2011-03-01

    Paclitaxel interferes with the normal function of microtubule breakdown, induces apoptosis in cancer cells and sequesters free tubulin. As this drug acts also on other cell mechanisms it is important to monitor its accumulation in the cell compartments. The intracellular spreading of the drug was followed using a WITEC 300R confocal Raman microscope equipped with a CCD camera. Hence Atomic force microscopy (an MFP3D- Asylum Research AFM) in imaging and force mode was used to determine the morphological and mechanical modifications induced on living cells. These studies were performed on living epithelial MCF-7 breast cancer cells. Paclitaxel was added to cell culture media for 3, 6 and 9 hours. Among the specific paclitaxel Raman bands we selected the one at 1670 cm-1 because it is not superposed by the spectrum of the cells. Confocal Raman images are formed by monitoring this band, the NH2 and the PO4 band. Paclitaxel slightly accumulates in the nucleus forming patches. The drug is also concentrated in the vicinity of the cell membrane and in an area close to the nucleus where proteins accumulate. Our AFM images reveal that the treated cancerous MCF-7 cells keep the same size as the non treated ones, but their shape becomes more oval. Cell's elasticity is also modified: a difference of 2 kPa in the Young Modulus characterizes the treated MCF-7 mammary cancerous cell. Our observations demonstrate that paclitaxel acts not only on microtubules but accumulates also in other cell compartments (nucleus) where microtubules are absent.

  15. Rapid characterization of the biomechanical properties of drug-treated cells in a microfluidic device

    International Nuclear Information System (INIS)

    Cell mechanics is closely related to many cell functions. Recent studies have suggested that the deformability of cells can be an effective biomarker to indicate the onset and progression of diseases. In this paper, a microfluidic chip is designed for rapid characterization of the mechanics of drug-treated cells through stretching with dielectrophoresis (DEP) force. This chip was fabricated using PDMS and micro-electrodes were integrated and patterned on the ITO layer of the chip. Leukemia NB4 cells were considered and the effect of all-trans retinoic acid (ATRA) drug on NB4 cells were examined via the microfluidic chip. To induce a DEP force onto the cell, a relatively weak ac voltage was utilized to immobilize a cell at one side of the electrodes. The applied voltage was then increased to 3.5 V pp and the cell started to be stretched along the applied electric field lines. The elongation of the cell was observed using an optical microscope and the results showed that both types of cells were deformed by the induced DEP force. The strain of the NB4 cell without the drug treatment was recorded to be about 0.08 (time t = 180 s) and the drug-treated NB4 cell was about 0.21 (time t = 180 s), indicating a decrease in the stiffness after drug treatment. The elastic modulus of the cell was also evaluated and the modulus changed from 140 Pa to 41 Pa after drug treatment. This microfluidic chip can provide a simple and rapid platform for measuring the change in the biomechanical properties of cells and can potentially be used as the tool to determine the biomechanical effects of different drug treatments for drug discovery and development applications. (paper)

  16. Promoted cell and material interaction on atmospheric pressure plasma treated titanium

    Energy Technology Data Exchange (ETDEWEB)

    Han, Inho [Convergence Technology Exam. Div. II, Korean Intellectual Patent Office, Daejeon (Korea, Republic of); Vagaska, Barbora [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Seo, Hyok Jin [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Jae Kyeong [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kwon, Byeong-Ju [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Mi Hee [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Park, Jong-Chul, E-mail: parkjc@yuhs.ac [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2012-03-01

    Surface carbon contamination is a natural phenomenon. However, it interferes with cell-biomaterial interaction. In order to eliminate the interference, atmospheric pressure plasma treatment was employed. Dielectric barrier discharge treatment of titanium surface for less than 10 min turned titanium super-hydrophilic. Adsorption of fibronectin which is the major cell adhesive protein increased after plasma treatment. Cell attachment parameters of osteoblast cells such as population, cell area, perimeter, Feret's diameter and cytoskeleton development were also enhanced. Cell proliferation increased on the plasma treated titanium. In conclusion, dielectric barrier discharge type atmospheric pressure plasma system is effective to modify titanium surface and the modified titanium promotes cell and material interactions.

  17. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation

    OpenAIRE

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H.; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H. Joachim

    2014-01-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patien...

  18. Complete in vitro DNA replication of SV40 chromatin in digitonin-treated permeable cells.

    OpenAIRE

    Oda,Takuzo; Watanabe,Sekiko; Hanakawa,Shiro; Nakamura, Takashi

    1980-01-01

    A permeable cell system has been developed by treatment with digitonin for studying in vitro DNA replication of chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in digitonin-treated permeable cells was analyzed by electrophoresis in agarose-gel. Autoradiography of the agarose-gel revealed that [32P]dCTP was incorporated in SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated the complete replication of SV40 DNA and ...

  19. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Constantopoulos Andreas G

    2005-10-01

    Full Text Available Abstract Background Human rhinoviruses (RV, the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA by flow cytometry. Results RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

  20. Polyelectrolyte Multilayer-Treated Electrodes for Real-Time Electronic Sensing of Cell Proliferation.

    Science.gov (United States)

    Mijares, Geraldine I; Reyes, Darwin R; Geist, Jon; Gaitan, Michael; Polk, Brian J; DeVoe, Don L

    2010-01-01

    We report on the use of polyelectrolyte multilayer (PEM) coatings as a non-biological surface preparation to facilitate uniform cell attachment and growth on patterned thin-film gold (Au) electrodes on glass for impedance-based measurements. Extracellular matrix (ECM) proteins are commonly utilized as cell adhesion promoters for electrodes; however, they exhibit degradation over time, thereby imposing limitations on the duration of conductance-based biosensor experiments. The motivation for the use of PEM coatings arises from their long-term surface stability as promoters for cell attachment, patterning, and culture. In this work, a cell proliferation monitoring device was fabricated. It consisted of thin-film Au electrodes deposited with a titanium-tungsten (TiW) adhesion layer that were patterned on a glass substrate and passivated to create active electrode areas. The electrode surfaces were then treated with a poly(ethyleneimine) (PEI) anchoring layer and subsequent bilayers of sodium poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH). NIH-3T3 mouse embryonic fibroblast cells were cultured on the device, observed by optical microscopy, and showed uniform growth characteristics similar to those observed on a traditional polystyrene cell culture dish. The optical observations were correlated to electrical measurements on the PEM-treated electrodes, which exhibited a rise in impedance with cell proliferation and stabilized to an approximate 15 % increase as the culture approached confluency. In conclusion, cells proliferate uniformly over gold and glass PEM-treated surfaces, making them useful for continuous impedance-based, real-time monitoring of cell proliferation and for the determination of cell growth rate in cellular assays. PMID:27134780

  1. Natural killer (NK) activity of pit cells perfused from livers of rats treated with ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Albornoz, L.; Jones, J.M.; Crutchfield, C.; Veech, R.L. (National Inst. of Alcohol Abuse and Alcoholism, Rockville, MD (United States) Univ. of Arkansas Medical Sciences, Little Rock (United States))

    1991-03-11

    The liver is the major site of ethanol (ETOH) metabolism. Liver sinusoids contain lymphocytes with NK activity. The authors treated LEW rats for 2 weeks with i.p. injection of 1.25 ml 25% ETOH/kg 3 times/week and 5% ETOH in drinking water. Livers were perfused at 5-fold physiological pressure and cells obtained were banded on 1.077 density Ficoll. Their cytotoxicity was tested against {sup 51}Cr-labeled YAC-1 or U937 and compared to spleen and blood lymphocytes. In untreated rats, pit cell NK activity was 2-fold that of splenic lymphocytes and 4-fold that of blood lymphocytes. Compared to controls, ETOH-treated rats exhibited a 30 to 90% rise in pit cell NK activity detected with YAC-1 or U937 targets. The pit cell enhanced NK activity in ETOH-treated rats was further increased if polyinosinicpolycytidilic acid was injection i.p. 18 hours before the assay. Blood and spleen lymphocyte NK activity of ETOH-treated rats was also greater than in controls. There was no evidence that ETOH merely redistributed lymphocytes among the tissues. Although ETOH acutely inhibits NK activity in vitro, chronic ETOH increases in vivo.

  2. Proteome analysis of butyrate-treated chronic myelogenous leukemia K562 cells

    Czech Academy of Sciences Publication Activity Database

    Halada, Petr; Grebeňová, D.; Pešlová, G.; Havlíček, Vladimír; Hrkal, Z.

    Edinburgh, 2003, s. -. [International Mass Spectrometry Conference /16./. Edingurgh (GB), 31.08.2003-05.09.2003] R&D Projects: GA ČR GA303/01/1445; GA MZd NL7681 Institutional research plan: CEZ:AV0Z5020903 Keywords : butyrate-treated * leukemie k562 * cells Subject RIV: EE - Microbiology, Virology

  3. Post-transfusion purpura treated with plasma exchange by haemonetics cell separator. A case report

    DEFF Research Database (Denmark)

    Laursen, B; Morling, N; Rosenkvist, J; Sørensen, H; Thyme, S

    1978-01-01

    A case of post-transfusion purpura in a 61-year-old, multiparous female with a platelet alloantibody (anti-Zwa) in her serum is reported. The patient was successfully treated with plasma exchange by means of a Haemonetics 30 cell separator and corticosteroids. Compared with other therapeutic meas...

  4. Reduced Amount of Japanese Encephalitis Viral RNA in the Infected Cells Treated with Human Interferon Beta

    OpenAIRE

    Daji, Hu; TANAKA Mariko; Morita, Kouichi; Igarashi, Akira

    1992-01-01

    Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the amount of Japanese encephalitis (JE) virus-specific positive sense RNA was found to be reduced in the infected Hep-2 cells treated with human interferon beta at 1,000 IU/ml in the medium compared with untreated specimens.

  5. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-04-01

    Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  6. Improving the development of early bovine somatic-cell nuclear transfer embryos by treating adult donor cells with vitamin C.

    Science.gov (United States)

    Chen, Huanhuan; Zhang, Lei; Guo, Zekun; Wang, Yongsheng; He, Rongjun; Qin, Yumin; Quan, Fusheng; Zhang, Yong

    2015-11-01

    Vitamin C (Vc) has been widely studied in cell and embryo culture, and has recently been demonstrated to promote cellular reprogramming. The objective of this study was to identify a suitable Vc concentration that, when used to treat adult bovine fibroblasts serving as donor cells for nuclear transfer, improved donor-cell physiology and the developmental potential of the cloned embryos that the donor nuclei were used to create. A Vc concentration of 0.15 mM promoted cell proliferation and increased donor-cell 5-hydroxy methyl cytosine levels 2.73-fold (P DNA methylation levels in donor cells, and improves the developmental competence of bovine somatic-cell nuclear transfer embryos. PMID:26212732

  7. Stem cell therapy emerging as the key player in treating type 1 diabetes mellitus.

    Science.gov (United States)

    Vanikar, Aruna V; Trivedi, Hargovind L; Thakkar, Umang G

    2016-09-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin secretion producing hyperglycemia usually affecting children. Replacement of damaged β cells by cell therapy can treat it. Currently available strategies are insulin replacement and islet/pancreas transplantation. Unfortunately these offer rescue for variable duration due to development of autoantibodies. For pancreas/islet transplantation a deceased donor is required and various shortfalls of treatment include quantum, cumbersome technique, immune rejection and limited availability of donors. Stem cell therapy with assistance of cellular reprogramming and β-cell regeneration can open up new therapeutic modalities. The present review describes the history and current knowledge of T1DM, evolution of cell therapies and different cellular therapies to cure this condition. PMID:27424148

  8. Characterization of the Stem-Cell Population of Phenylhydrazine-Treated Rodents

    International Nuclear Information System (INIS)

    A study was made of the content of stem cells in the spleen, blood and bone marrow of mice treated with phenylhydrazine; the experimental method used was transplantation in lethally-irradiated mice. There was a marked increase in the content of stem cells in liver and blood and a small increase in bone marrow in the case of animals treated with phenylhydrazine. Judging by the effects of vinblastine, about 80% of the stem cells of spleen pass through mitosis within 24 hours, while only 20% of the marrow cells and none of the blood stem cells pass through mitosis within this period. To obtain information on the average residence time of stem cells in blood, bone marrow was injected intravenously into normal rats and the blood content was determined at intervals, A disappearance half-life of 6 minutes was found. To estimate the increase in the number of stem cells in the spleen of animals treated with phenylhydrazine, rats with and without spleen were irradiated with 500 rad (137Cs gamma) after being given five phenylhydrazine injections. The rats without spleen developed severe anaemia with high mortality (70%), compared with the rats with spleen. Among the survivors, erythropoiesis started to recover later and proceeded more slowly in rats that had undergone splenectomy than in those with spleen. Transfusion corrected the anaemia in the rats without spleen and reduced the high mortality, but did not alter the rate of erythropoiesis recovery. The spleen plays an important part in erythropoiesis and the bone-marrow function recovers sooner in rats with spleen than in those without. Although the spleen is important for erythropoiesis recovery after irradiation preceded by treatment with phenylhydrazine, it has no effect on recovery after irradiation alone. It seems as though the spleen is required when proliferation of stem cells at the maximum rate is essential for survival. It is possible that the spleen constitutes a favourable local environment for the

  9. Retinoic acid-treated pluripotent stem cells undergoing neurogenesis present increased aneuploidy and micronuclei formation.

    Directory of Open Access Journals (Sweden)

    Rafaela C Sartore

    Full Text Available The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC cells, embryonic stem (ES cells and induced pluripotent stem (iPS cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naïve cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal

  10. Transplantation of primary cultured embryonic mesencephalic neural precursor cells for treating Parkinsonian rats

    Institute of Scientific and Technical Information of China (English)

    Li Fei; Chengchuan Jiang; Linyin Feng; Yaodong Ji; Zhongliang Ding

    2006-01-01

    BACKGROUND: Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy (CRT) for treating Parkinson disease (PD). Embryonic mesencephalic precursor cells (MPCs) can stably differentiate into dopaminergic neuron after in vitro proliferated culture. As compared with embryonic stem cell and neural stem cell strains, cell composition of embryonic MPCs after primary culture is also the most close to that of embryonic mesencephalic ventral cell suspension without proliferated culture. Successful experience accumulated in the latter suggests that primary cultured embryonic MPCs might be the most potential donor cells in clinical application with CRT for treating PD so far.OBJECTIVE: To investigate the feasibility of primary cultured embryonic precursor cells cultured primarily as donor cells in CRT for treating PD in rats.DESIGN: A randomized and controlled trial taking SD rats as experimental animals.SETTING: Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University.MATERIALS: This experiment was carried out at the Institute of Neuroscience, Shanghai Institute for Biological Science, Chinese Academy of Sciences from July 2003 to June 2004. Totally 26 female SD rats,with body mass of 200 to 220 g, were provided by Shanghai Experimental Animal Center of Chinese Academy of Sciences.METHODS: Stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle were perfored to develop PD model rat. Among 26 SD rats, 20 rats achieved a more than 5 turns/min in apomorphine induced rotation test, reaching the standard of PD model rats. Immunohistochemical detection was performed on 1out of 20 model rats after execution, and the other 19 rats were randomly divided into control group (n=5),sham transplantation group (n=5)and cell grafted group (n=9). Primary cultured E12 MPC cell suspension (1.2×1011 L-1)were used as donor cells. 4 μL primary cultured E12 MPC cell suspension prepared freshly was injected

  11. CD26 + CD4 + T cell counts and attack risk in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Ross, C; Koch-Henriksen, Nils;

    2005-01-01

    patients with CD26 + CD4 + T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-beta antibodies. CD26 + CD4 + T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-beta....... CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-beta-treated patients, we found that the hazard ratio for developing an attack was 28 in...

  12. Direct stimulation of immediate-early genes by intranuclear insulin in trypsin-treated H35 hepatoma cells.

    OpenAIRE

    Lin, Y J; Harada, S.; Loten, E G; Smith, R. M.; Jarett, L

    1992-01-01

    H35 hepatoma cells were treated with trypsin to abolish insulin binding and insulin-stimulated receptor kinase activity. Insulin was, however, internalized by fluid-phase endocytosis in trypsin-treated cells. Furthermore, nuclear accumulation of insulin was similar in control and trypsin-treated hepatoma cells. Northern blot analysis revealed insulin increased g33 and c-fos mRNA concentrations identically in control and trypsin-treated cells but had no effect on beta 2-microglobulin mRNA. Act...

  13. 980nm laser for difficult-to-treat basal cell carcinoma

    Science.gov (United States)

    Derjabo, A. D.; Cema, I.; Lihacova, I.; Derjabo, L.

    2013-06-01

    Begin basal cell carcinoma (BCC) is most common skin cancer over the world. There are around 20 modalities for BCC treatment. Laser surgery is uncommon option. We demonstrate our long term follow up results. Aim: To evaluate long term efficacy of a 980nm diode laser for the difficult-to-treat basal cell carcinoma. Materials and Methods: 167 patients with 173 basal cell carcinoma on the nose were treated with a 980 nm diode laser from May 1999 till May 2005 at Latvian Oncology center. All tumors were morphologically confirmed. 156 patients were followed for more than 5 years. Results: The lowest recurrence rate was observed in cases of superficial BCC, diameterConclusions: 980 nm diode laser is useful tool in dermatology with high long term efficacy, good acceptance by the patients and good cosmetics results.

  14. Quantitative and qualitative analyses of the cell death process in Candida albicans treated by antifungal agents.

    Science.gov (United States)

    Kim, Kyung Sook; Kim, Young-Sun; Han, Ihn; Kim, Mi-Hyun; Jung, Min Hyung; Park, Hun-Kuk

    2011-01-01

    The death process of Candida albicans was investigated after treatment with the antifungal agents flucytosine and amphotericin B by assessing morphological and biophysical properties associated with cell death. C. albicans was treated varying time periods (from 6 to 48 hours) and examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM). SEM and AFM images clearly showed changes in morphology and biophysical properties. After drug treatment, the membrane of C. albicans was perforated, deformed, and shrunken. Compared to the control, C. albicans treated with flucytosine was softer and initially showed a greater adhesive force. Conversely, C. albicans treated with amphotericin B was harder and had a lower adhesive force. In both cases, the surface roughness increased as the treatment time increased. The relationships between morphological changes and the drugs were observed by AFM clearly; the surface of C. albicans treated with flucytosine underwent membrane collapse, expansion of holes, and shrinkage, while the membranes of cells treated with amphotericin B peeled off. According to these observations, the death process of C. albicans was divided into 4 phases, CDP(0), CDP(1), CDP(2), and CDP(4), which were determined based on morphological changes. Our results could be employed to further investigate the antifungal activity of compounds derived from natural sources. PMID:22174777

  15. Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone

    International Nuclear Information System (INIS)

    Purpose: To identify prognostic factors for local and distant relapse and perform risk stratification for patients with advanced cervical cancer treated with radiotherapy (RT) alone. Methods and Materials: A total of 1031 patients with Stage IB-IVA squamous cell carcinoma of the cervix treated with full-course RT but without any chemotherapy were included for analysis. Of these, 311 patients with nonbulky Stage IB-IIA disease were designated the reference group and the other 720 patients were the study group. The associations of stage, squamous cell carcinoma antigen (SCC-ag) level, hemoglobin level, age, cell differentiation, and pelvic lymph node status with treatment failure were evaluated. The independent prognostic factors were identified by multivariate analysis. The study group was further stratified into subgroups using combinations of these risk factors. Results: In the study group, independent risk factors for local relapse were advanced stage and age 2, and positive pelvic lymph nodes. The 5-year distant relapse-free survival rate was 83% for patients with bulky Stage IB-IIA and IIB disease, SCC-ag level 2, and positive lymph nodes. Conclusion: The risk of treatment failure in advanced-stage cervical cancer patients treated by RT alone can be more precisely predicted by risk stratification. A certain subgroup of patients had better control than the others. The benefit of treating these relatively low-risk patients with additional treatment such as concurrent chemotherapy should be further evaluated in prospective studies or meta-analyses

  16. Exosomes from high glucose-treated glomerular endothelial cells activate mesangial cells to promote renal fibrosis

    OpenAIRE

    Xiao-ming Wu; Yan-bin Gao; Fang-qiang Cui; Na Zhang

    2016-01-01

    The interaction between glomerular endothelial cells (GECs) and glomerular mesangial cells (GMCs) is an essential aspect of diabetic nephropathy (DN). Therefore, understanding how GECs communicate with GMCs in the diabetic environment is crucial for the development of new targets for the prevention and treatment of DN. Exosomes, nanometer-sized extracellular membrane vesicles secreted by various cell types, play important roles in cell-to-cell communication via the transfer of mRNA, microRNA ...

  17. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells

    Science.gov (United States)

    Kluz, Thomas; Cohen, Lisa; Shen, Steven S.; Costa, Max

    2016-01-01

    Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress. PMID:27186882

  18. Contact Lenses: A Delivery Device for Stem Cells to Treat Corneal Blindness.

    Science.gov (United States)

    Bobba, Samantha; Di Girolamo, Nick

    2016-04-01

    : Worldwide, 45 million people are blind. Corneal blindness is a major cause of visual loss, estimated to affect 10 million. For the most difficult to treat patients, including those with a disease called limbal stem cell deficiency, a donor corneal graft is not a viable option; thus, patients are treated with specialized stem cell grafts, which fail in a significant proportion (30 to 50%) of subjects. This unacceptable failure rate means there is a pressing need to develop minimally invasive, long-lasting, cost-effective therapies to improve patient quality of life and lessen the economic burden. Restoring vision in patients with severe corneal disease is the main focus of our research program; however, to achieve our goals and deliver the best quality stem cell therapy, we must first understand the basic biology of these cells, including their residence, the factors that support their long-term existence, markers to identify and isolate them, and carriers that facilitate expansion, delivery, and protection during engraftment. We recently achieved some of these goals through the discovery of stem cell markers and the development of a novel and innovative contact lens-based cell transfer technique that has been successfully trialed on patients with corneal blindness. Although several popular methodologies are currently available to nurture and transfer stem cells to the patients' ocular surface, contact lenses provide many advantages that will be discussed in this review article. The job for clinician-researchers will be to map precisely how these cells contribute to restoring ocular health and whether improvements in the quality of cells and the cell delivery system can be developed to reduce disease burden. PMID:26390346

  19. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Shukla SD

    2016-07-01

    Full Text Available Shakti D Shukla,1,* Rory L Fairbairn,1,* David A Gell,1 Roger D Latham,1 Sukhwinder S Sohal,1,2 Eugene H Walters,1 Ronan F O’Toole11Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia; 2School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia*These authors contributed equally to this workBackground: COPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.Objective: To investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.Methods: Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE. PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.Results: PAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial

  20. Anaerobic microbial fuel cell treating combined industrial wastewater: Correlation of electricity generation with pollutants.

    Science.gov (United States)

    Abbasi, Umara; Jin, Wang; Pervez, Arshid; Bhatti, Zulfiqar Ahmad; Tariq, Madiha; Shaheen, Shahida; Iqbal, Akhtar; Mahmood, Qaisar

    2016-01-01

    Microbial fuel cell (MFC) is a new technology that not only generates energy but treats wastewater as well. A dual chamber MFC was operated under laboratory conditions. Wastewater samples from vegetable oil industries, metal works, glass and marble industries, chemical industries and combined industrial effluents were collected and each was treated for 98h in MFC. The treatment efficiency for COD in MFC was in range of 85-90% at hydraulic retention time (HRT) of 96h and had significant impact on wastewater treatment as well. The maximum voltage of 890mV was generated when vegetable oil industries discharge was treated with columbic efficiency of 5184.7C. The minimum voltage was produced by Glass House wastewater which was 520mV. There was positive significant co-relation between COD concentration and generated voltage. Further research should be focused on the organic contents of wastewater and various ionic species affecting voltage generation in MFC. PMID:26476157

  1. Fetal progenitor cell transplantation treats methylmalonic aciduria in a mouse model

    International Nuclear Information System (INIS)

    Highlights: ► Fetal cells were transplanted into a methylmalonic acid mouse model. ► Cell engraftment was detected in liver, spleen and bone marrow. ► Biochemical disease correction was measured in blood samples. ► A double dose of 5 million cells (1 week apart) proved more effective. ► Higher levels of engraftment may be required for greater disease correction. -- Abstract: Methylmalonic aciduria is a rare disorder caused by an inborn error of organic acid metabolism. Current treatment options are limited and generally focus on disease management. We aimed to investigate the use of fetal progenitor cells to treat this disorder using a mouse model with an intermediate form of methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at embryonic day 15–17 and intravenously transplanted into sub-lethally irradiated mice. Liver donor cell engraftment was determined by PCR. Disease correction was monitored by urine and blood methylmalonic acid concentration and weight change. Initial studies indicated that pre-transplantation sub-lethal irradiation followed by transplantation with 5 million cells were suitable. We found that a double dose of 5 million cells (1 week apart) provided a more effective treatment. Donor cell liver engraftment of up to 5% was measured. Disease correction, as defined by a decrease in blood methylmalonic acid concentration, was effected in methylmalonic acid mice transplanted with a double dose of cells and who showed donor cell liver engraftment. Mean plasma methylmalonic acid concentration decreased from 810 ± 156 (sham transplanted) to 338 ± 157 μmol/L (double dose of 5 million cells) while mean blood C3 carnitine concentration decreased from 20.5 ± 4 (sham transplanted) to 5.3 ± 1.9 μmol/L (double dose of 5 million cells). In conclusion, higher levels of engraftment may be required for greater disease correction; however these studies show promising results for cell transplantation biochemical

  2. Stem cell transplantation with S-59 photochemically treated T-cell add-backs to establish allochimerism in murine thalassemia.

    Science.gov (United States)

    Kuypers, Frans A; Watson, Gordon; Sage, Ezra; Walters, Mark C; Hamrick, James; Hearst, John E

    2005-01-01

    Hematopoietic cell transplantation (HCT) from HLA-identical sibling donors has curative potential for beta-thalassemia. The probability of surviving free of thalassemia under these conditions is approximately 85%. The application of this therapy is limited because many patients lack an HLA-identical sibling donor. HLA-mismatched stem cell transplantation for thalassemia is severely restricted by graft rejection and the risks for graft-versus-host disease (GVHD). Thus, the development of a novel method that facilitates immunological tolerance and improves the safety of HLA-mismatched HCT would greatly expand the opportunity of HCT for thalassemia patients. We hypothesized that removal of T cells from the donor hematopoietic stem cell preparation and subsequent add-back after photochemical treatment with S-59, a psoralen, would promote and stabilize the engraftment and significantly reduce the risk of GVHD. This was tested in a MHC-mismatched HCT model of murine thalassemia. S-59-treated T cells were infused simultaneously with bone marrow-derived stem cells into mice with a heterozygous deletion of one beta-globin alleles that had been conditioned with a sublethal dose of total body irradiation. Mice that received treated T cells showed increased engraftment compared to those that did not receive T cells. T-cell treatment improved survival without GVHD compared to recipients that received untreated T cells. We conclude that photochemical treatment of T cells facilitates engraftment and minimizes GVHD in allo-HCT for murine thalassemia, and sets the stage for further development of such protocols for the treatment of patients with thalassemia. PMID:16339668

  3. Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2015-12-18

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult

  4. Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan.

    Directory of Open Access Journals (Sweden)

    Lucia Cuppini

    Full Text Available BACKGROUND: Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF. Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA and classical antiblastic chemotherapy (n=14, independent dataset B: IDB. METHODS: rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. RESULTS: A baseline count of CD109+ CEC higher than 41.1/ml (1(st quartile was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008 and overall survival (OS; 32 versus 23 weeks, P=0.03. Longer PFS (25 versus 8 weeks, P=0.02 and OS (27 versus 17 weeks, P=0.03 were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease at baseline was an independent predictor of shorter PFS and OS (P<0.001. CONCLUSIONS: Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab.

  5. Nuclear proteome analysis of benzo(a)pyrene-treated HeLa cells

    International Nuclear Information System (INIS)

    Previously, we employed a proteomics-based 2-D gel electrophoresis assay to show that exposure to 10 μM benzo(a)pyrene (BaP) during a 24 h frame can lead to changes in nuclear protein expression and alternative splicing. To further expand our knowledge about the DNA damage response (DDR) induced by BaP, we investigated the nuclear protein expression profiles in HeLa cells treated with different concentrations of BaP (0.1, 1, and 10 μM) using this proteomics-based 2-D gel electrophoresis assay. We found 125 differentially expressed proteins in BaP-treated cells compared to control cells. Among them, 79 (63.2%) were down-regulated, 46 (36.8%) were up-regulated; 8 showed changes in the 1 μM and 10 μM BaP-treated groups, 2 in the 0.1 μM and 10 μM BaP-treated groups, 4 in the 0.1 μM and 1 μM BaP-treated groups, and only one showed changes in all three groups. Fifty protein spots were chosen for liquid chromatography–tandem mass spectrometry (LC–MS/MS) identification, and of these, 39 were identified, including subunits of the 26S proteasome and Annexin A1. The functions of some identified proteins were further examined and the results showed that they might be involved in BaP-induced DDR. Taken together, these data indicate that proteomics is a valuable approach in the study of environmental chemical–host interactions, and the identified proteins could provide new leads for better understanding BaP-induced mutagenesis and carcinogenesis.

  6. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria Gry Gundgaard; Bandak, Mikkel; Mortensen, Mette Saksø; Thomsen, Frederik Birkebæk; Mortensen, Jann; Daugaard, Gedske

    2016-01-01

    significantly influenced baseline PFT results. Pulmonary surgery, pulmonary embolism, IGCCCG poor prognosis, and smoking influenced PFT during follow-up. Mediastinal primary, pulmonary metastases, age, or doses of cisplatin and etoposide had no influence on follow-up PFT, and renal function did not influence...... PFT. CONCLUSION: After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group.......PURPOSE: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring...

  7. Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Hrvoje Holik

    2015-09-01

    Full Text Available We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.

  8. Induced pluripotent stem cells:Landscape for studying and treating hereditary hearing loss

    Institute of Scientific and Technical Information of China (English)

    Tao Peng; Yunpeng Dong; Ganghua Zhu; Dinghua Xie

    2014-01-01

    Hearing loss (HL) is one of the most widespread sensory disorders, affecting approximately 1 in 500 newborns. Heritable diseases of the inner ear are the leading causes of prelingual HL. Treating of hereditary HL and understanding its underlying mechanisms remain difficult challenges to otolaryngologists. As stem cells are capable of self-renewal and differentiation, they are ideally suited both for disease modeling and regenerative medicine. Recently, description of induced pluripotent stem cells (iPSCs) has allowed the field of disease modeling and personalized therapy to become far more accessible and physiologically relevant, as iPSCs can be generated from patients of any genetic background. This review briefly describes the advantages of iPSCs technology and discusses potential applications of this powerful biological tool in studying and treating hereditary HL.

  9. Effect of 211At treating pollen and stigma on generative cells and seed setting of rice

    Institute of Scientific and Technical Information of China (English)

    JinJian-Nan; ChenFang; 等

    1998-01-01

    Low specific radioactivity (7.4kBq/ml) 211At treating pollen and stigma can obviously affect morphological structures and physiological functions of pollen,stigma and ovule or embryo sac cells,and cause injury.Results showed that because of the radiation effects the seed setting rate of rice was decreased,and the development of some embryos were affected and others became abnormal.

  10. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Roberto Madeddu

    2013-08-01

    Full Text Available Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd, which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

  11. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A.; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A.; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  12. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  13. Identification of differentially expressed proteins in SH-SY5Y cells treated with resveratrol

    Institute of Scientific and Technical Information of China (English)

    Ying Wang; Zhong Dong; Hongyan Fan; Ming Chang; Guoyi Li; Linsen Hu

    2011-01-01

    To gain insight into the molecular mechanisms of resveratrol-mediated neuroprotection, two-dimensional difference gel electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to identify proteins differentially-expressed in SH-SY5Y cells treated with resveratrol. Compared with the control group, resveratrol treatment significantly affected the expression of four proteins: endoplasmic reticulum oxidoreductin 1-like protein alpha, p21-activated kinase 1, Archain 1, and T cell receptor beta chain. The former three were downregulated and the latter was upregulated. These proteins are primarily associated with endoplasmic reticulum stress, intracellular trafficking, and immune function.

  14. Ectopic pregnancy-derived human trophoblastic stem cells regenerate dopaminergic nigrostriatal pathway to treat parkinsonian rats.

    Directory of Open Access Journals (Sweden)

    Tony Tung-Yin Lee

    Full Text Available BACKGROUND: Stem cell therapy is a potential strategy to treat patients with Parkinson's disease (PD; however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies. Our objectives in this study were (i to identify the characteristics of hTS cells as a potential cell source for therapy; and (ii to test if hTS cells can be used as a potential therapeutic strategy for PD. METHODS AND FINDINGS: hTS cells expressed gene markers of both the trophectoderm (TE and the inner cell mass (ICM. hTS cells exhibited genetic and biological characteristics similar to that of hES cells, yet genetically distinct from placenta-derived mesenchymal stem cells. All-trans retinoic acid (RA efficiently induced hTS cells into trophoblast neural stem cells (tNSCs in 1-day. Overexpression of transcription factor Nanog was possibly achieved through a RA-induced non-genomic c-Src/Stat3/Nanog signaling pathway mediated by the subcellular c-Src mRNA localization for the maintenance of pluripotency in tNSCs. tNSC transplantation into the lesioned striatum of acute and chronic PD rats not only improved behavioral deficits but also regenerated dopaminergic neurons in the nigrostriatal pathway, evidenced by immunofluorescent and immunohistological analyses at 18-weeks. Furthermore, tNSCs showed immunological advantages for the application in regenerative medicine. CONCLUSIONS: We successfully isolated and characterized the unique ectopic pregnancy-derived hTS cells. hTS cells are pluripotent stem cells that can be efficiently induced to tNSCs with positive results in PD rat models. Our data suggest that the hTS cell is a dynamic stem cell platform that is potentially suitable for use in disease models, drug discovery, and cell therapy such as PD.

  15. Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus.

    Science.gov (United States)

    Xia, Mao; Meng, Gang; Jiang, Aiqin; Chen, Aiping; Dahlhaus, Meike; Gonzalez, Patrick; Beltinger, Christian; Wei, Jiwu

    2014-06-15

    Although apoptotic phenomena have been observed in malignant cells infected by measles virus vaccine strain Edmonston B (MV-Edm), the precise oncolytic mechanisms are poorly defined. In this study we found that MV-Edm induced autophagy and sequestosome 1-mediated mitophagy leading to decreased cytochrome c release, which blocked the pro-apoptotic cascade in non-small cell lung cancer cells (NSCLCs). The decrease of apoptosis by mitophagy favored viral replication. Persistent viral replication sustained by autophagy ultimately resulted in necrotic cell death due to ATP depletion. Importantly, when autophagy was impaired in NSCLCs MV-Edm-induced cell death was significantly abrogated despite of increased apoptosis. Taken together, our results define a novel oncolytic mechanism by which mitophagy switches cell death from apoptosis to more efficient necrosis in NSCLCs following MV-Edm infection. This provides a foundation for future improvement of oncolytic virotherapy or antiviral therapy. PMID:25004098

  16. Donor Stem Cell Transplant or Donor White Blood Cell Infusions in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2012-07-02

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unusual Cancers of Childhood

  17. Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis

    International Nuclear Information System (INIS)

    In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis

  18. Antigen-presenting cells transfected with Hsp65 messenger RNA fail to treat experimental tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, C.D.; Trombone, A.P.F.; Lorenzi, J.C.C.; Almeida, L.P.; Gembre, A.F.; Padilha, E. [Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Ramos, S.G. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, C.L.; Coelho-Castelo, A.A.M. [Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-09-21

    In the last several years, the use of dendritic cells has been studied as a therapeutic strategy against tumors. Dendritic cells can be pulsed with peptides or full-length protein, or they can be transfected with DNA or RNA. However, comparative studies suggest that transfecting dendritic cells with messenger RNA (mRNA) is superior to other antigen-loading techniques in generating immunocompetent dendritic cells. In the present study, we evaluated a new therapeutic strategy to fight tuberculosis using dendritic cells and macrophages transfected with Hsp65 mRNA. First, we demonstrated that antigen-presenting cells transfected with Hsp65 mRNA exhibit a higher level of expression of co-stimulatory molecules, suggesting that Hsp65 mRNA has immunostimulatory properties. We also demonstrated that spleen cells obtained from animals immunized with mock and Hsp65 mRNA-transfected dendritic cells were able to generate a mixed Th1/Th2 response with production not only of IFN-γ but also of IL-5 and IL-10. In contrast, cells recovered from mice immunized with Hsp65 mRNA-transfected macrophages were able to produce only IL-5. When mice were infected with Mycobacterium tuberculosis and treated with antigen-presenting cells transfected with Hsp65 mRNA (therapeutic immunization), we did not detect any decrease in the lung bacterial load or any preservation of the lung parenchyma, indicating the inability of transfected cells to confer curative effects against tuberculosis. In spite of the lack of therapeutic efficacy, this study reports for the first time the use of antigen-presenting cells transfected with mRNA in experimental tuberculosis.

  19. Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

    Science.gov (United States)

    Pizzolato, Nicola; Valenti, Davide; Adorno, Dominique; Spagnolo, Bernardo

    2009-09-01

    The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.

  20. In Vitro Toxicity of Naturally Occurring Silica Nanoparticles in C1 Coal 
in Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Guangjian LI

    2012-10-01

    Full Text Available Background and objective China’s Xuan Wei County in Yunnan Province have the world’s highest incidence of lung cancer in nonsmoking women-20 times higher than the rest of China. Previous studies showed, this high lung cancer incidence may be associated with the silica particles embedded in the production combustion from the C1 coal. The aim of this study is to separate the silica particles from production combustion from the C1 bituminous coal in Xuan Wei County of Yunnan Province, and study in vitro toxicity of naturally occurring silica particles on BEAS-2B. Methods ①Separating the silica particles from combustion products of C1 bituminous coal by physical method, observing the morphology by Scanning Electron Microscope, analysis elements by SEM-EDX, observed the single particle morphology by Transmission Electron Microscope, analyed its particle size distribution by Laser particle size analyzer, the surface area of silica particles were determined by BET nitrogen adsorption analysis; ②Cell viability of the experimental group (silica; naturally occurring, control group (silica; industrial produced and crystalline silica was detected by assay used the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT method, and the reactive oxygen species (ROS, lactate dehydrogenase (LDH were determined after 24 h-72 h exposed to these particles. Results ①The physical method can separate silica particles from production combustion from the C1 bituminous coal, which have different size, and from 30 nm to 120 nm particles accounted for 86.8%, different morphology, irregular surface area and containing trace of aluminum, calcium and iron and other elements; ②Under the same concentration, the experiment group have higher toxicity on BEAS-2B than control groups. Conclusion ①Physical method can separate silica particles from production combustion from the C1 bituminous coal and not change the original morphology and containing trace;

  1. In situ electrochemical study of the interaction of cells with thermally treated titanium.

    Science.gov (United States)

    Burgos-Asperilla, Laura; Fierro, Jose Luis Garcia; Gamero, Miriam; Escudero, Maria Lorenza; Alonso, Concepción; García-Alonso, Maria Cristina

    2015-01-01

    Micromotion and fretting wear between bone and Ti-based alloys in stem and dental implants breaks the passive film and exposes the metal to the action of the complex surrounding medium, generating substantial amounts of debris and continuous Ti ion release. In this work, oxidation treatments at low temperatures (277 °C, 5 h) have been used to promote the formation of wear-corrosion resistant titanium oxide on the Ti surface. The objective of this paper has been the study of the influence of live cells on the protectiveness of the oxide formed at these low temperatures. The interaction of cells with the modified surface has been studied by scanning electron microscopy, electrochemical impedance spectroscopy, polarization curves, and x-ray photoelectron spectroscopy (XPS). The chemical composition of the thermally treated Ti surface is mainly TiO2 as anatase-rich titanium dioxide with a low concentration of hydroxyl groups and a low mean nanoroughness that could promote good cell adhesion. The electrochemical results indicate that the cells alter the overall resistance of the thermally treated Ti surfaces by decreasing the oxide resistance with time. At the same time, the anodic current increases, which is associated with cathodic control, and is probably due to the difficulty of access of oxygen to the Ti substrate. XPS reveals the presence of proteins on the surface of the treated specimens in contact with the cells and a decrease in the Ti signal associated with the extracellular matrix on the surface and the reduction of the oxide thickness. PMID:25947388

  2. Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells.

    Science.gov (United States)

    Seriani, Robson; Junqueira, Mara S; Carvalho-Sousa, Claudia E; Arruda, Alessandra C T; Martinez, Diana; Alencar, Adriano M; Garippo, Ana L; Brito, Jôse Mara; Martins, Milton A; Saldiva, Paulo H N; Negri, Elnara M; Mauad, Thais; Macchione, Mariangela

    2015-04-01

    This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERK were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MTT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP. PMID:25769681

  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)

    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 PM10 and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM10 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 PM10 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. Suppression of epithelial signal transducer and activator of transcription 1 activation by extracts of Aspergillus fumigatus.

    Science.gov (United States)

    Bhushan, Bharat; Homma, Tetsuya; Norton, James E; Sha, Quan; Siebert, Jason; Gupta, Dave S; Schroeder, James W; Schleimer, Robert P

    2015-07-01

    Aspergillus fumigatus (AF) is often pathogenic in immune-deficient individuals and can cause life-threatening infections such as invasive aspergillosis. The pulmonary epithelial response to AF infection and the signaling pathways associated with it have not been completely studied. BEAS-2B cells or primary human bronchial epithelial cells were exposed to extracts of AF and challenged with IFN-β or the Toll-like receptor 3 agonist double-stranded RNA (dsRNA). Cytokine release (B-cell activating factor of the TNF family [BAFF], IFN-γ-induced protein-10 [IP-10], etc.) was assessed. AF extract was separated into low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions using ultra 4 centrifugal force filters to characterize the activity. Real-time PCR was performed with a TaqMan method, and protein estimation was performed using ELISA techniques. Western blot was performed to assess phosphorylation of signal transducer and activator of transcription 1 (STAT1). IFN-β and dsRNA induced messenger RNA (mRNA) expression of BAFF (350- and 452-fold, respectively [n = 3]) and IP-10 (1,081- and 3,044-fold, respectively [n = 3]) in BEAS-2B cells. When cells were pretreated with AF extract for 1 hour and then stimulated with IFN-β or dsRNA for 6 hours, induction of BAFF and IP-10 mRNA was strongly suppressed relative to levels produced by IFN-β and dsRNA alone. When compared with control, soluble BAFF and IP-10 protein levels were maximally suppressed in dsRNA-stimulated wells treated with 1:320 wt/vol AF extract (P < 0.005). Upon molecular size fractionation, a LMW fraction of AF extract had no measurable suppressive effect on IP-10 mRNA expression. However, a HMW fraction of the AF extract significantly suppressed IP-10 expression in BEAS-2B cells that were stimulated with dsRNA or IFN-β. When BEAS-2B cells were pretreated with AF extract and then stimulated with IFN-β, reduced levels of pSTAT1 were observed, with maximum suppression at 4 and 6

  5. Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload

    Science.gov (United States)

    2012-07-16

    Iron Overload; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult

  6. Use of stem cell transplantation to treat epilepsy A Web of Science-based literature analysis

    Institute of Scientific and Technical Information of China (English)

    Zhongmin Yin; Yushu Dong; Jiyang Zhang; Li Wang

    2012-01-01

    OBJECTIVE:To identify global research trends in the use of stem cell transplantation to treat epilepsy.DATA RETRIEVAL:We performed a bibliometric analysis of studies on the use of stem cell transplantation to treat epilepsy during 2002-2011,retrieved from Web of Science,using the key words epilepsy or epileptic or epilepticus or seizure and "stem cell".SELECTION CRITERIA:Inclusion criteria:(a)peer-reviewed published articles on the use of stem cell transplantation to treat epilepsy indexed in Web of Science;(b)original research articles,reviews,meeting abstracts,proceedings papers,book chapters,editorial material,and news items.MAIN OUTCOME MEASURES:(a)Annual publication output;(b)type of publication;(c)publication by research field;(d)publication by journal;(e)publication by author;(f)publication by country and institution;(g)publications by institution in China;(h)most-cited papers;and(i)papers published by Chinese authors or institutions.RESULTS:A total of 460 publications on the use of stem cell transplantation to treat epilepsy were retrieved from Web of Science,2002-2011.The number of publications gradually increased over the 10-year study period.Articles and reviews constituted the major types of publications.More than half of the studies were in the field of neuroscience/neurology.The most prolific journals for this topic were Epilepsia,Bone Marrow Transplantation,and Journal of Neuroscience.Of the 460 publications,almost half came from American authors and institutions;relatively few papers were published by Chinese authors or institutions.CONCLUSION:Literature on stem cell transplantation for epilepsy includes many reports of basic research,but few of clinical trials or treatments.Exact effects are not yet evaluated.Epilepsy rehabilitation is a long-term,complex,and comprehensive system engineering.With advances in medical development,some effective medical,social and educational measures are needed to facilitate patient's treatment and training and

  7. Effect of vitamin E on protein bound carbhohydrate complexes in radiation treated oral squamous cell carcinoma patients

    OpenAIRE

    S. Chitra; Shyamala Devi, C. S.

    2008-01-01

    Serum glycoproteins were evaluated in oral squamous cell carcinoma patients treated with radiotherapy and also the effect of vitamin E was studied. Cell surface glycoconjugates are important parameters in the detection of malignancy. Thus, the objective of the present study is to evaluate the efficacy of vitamin E on glycoproteins in oral cavity cancer patients treated with radiotherapy. The study includes 26 age and sex matched normal healthy individuals and 26 patients with squamous cell ca...

  8. [Cell-based therapies - an innovative therapeutic option in ophthalmology: Treating corneal diseases with stem cells].

    Science.gov (United States)

    Bakker, Ann-Christin; Langer, Barbara

    2015-11-01

    Pathological changes and disorders of the cornea are a major cause of severe visual impairment and blindness. Replacement of a pathologically altered cornea with healthy corneal tissue from the eye of a suitable donor is among the most common and successful transplantation procedures in medicine. In Germany, approximately 5000-6000 corneal transplantations are performed each year, but the total demand per year is estimated to be twice as high. With a success rate of 90%, the outcome of cornea transplantation is very favourable. However, long-term maintenance and regeneration of a healthy new cornea requires tissue-specific corneal stem cells residing at the basal layer of the limbus, which is the annular transition zone between the cornea and sclera. When this important limbal stem cell population is destroyed or dysfunctional, a pathological condition known as limbal stem cell deficiency (LSCD) manifests. Limbal stem cell deficiency describes conditions associated with impaired corneal wound healing and regeneration. In this situation, transplantation of healthy limbal stem cells is the only curative treatment approach for restoration of an intact and functional ocular surface. To date, treatment of LSCD presents a great challenge for ophthalmologists. However, innovative, cell-therapeutic approaches may open new, promising treatment perspectives. In February 2015, the European Commission granted marketing authorization to the first stem cell-based treatment in the European Union. The product named Holoclar® is an advanced therapy medicinal product (ATMP) for the treatment of moderate to severe LSCD due to physical and chemical burns in adults. Further cell-based treatment approaches are in clinical development. PMID:26459569

  9. Test results for a heat-treated 4-cell 805 MHz superconducting cavity

    International Nuclear Information System (INIS)

    Assessing superconducting technology for potential upgrades to existing proton accelerators as well as applications to future high-current machines necessitates developing expertise in the processing and handling of multicell cavities at useful frequencies. In order to address some of these technological issues, Los Alamos has purchased a 4-cell 805-MHz superconducting cavity from Siemens AG. The individual cavity cells were double-sided titanium heat-treated after equatorial welding, then the irises were welded to complete the cavity assembly. The resulting high RRR (residual resistance ratio) in the cells enables stable operation at higher cavity field levels than are possible with lower RRR material. Additionally, the high thermal conductivity of the material is conducive to rf and high peak power processing. The cavity was also cleaned at Los Alamos with high-pressure water rinsing. Results from the initial cavity tests, utilizing various processing techniques, are presented

  10. Coexistence of squamous cell tracheal papilloma and carcinoma treated with chemotherapy and radiotherapy: a case report

    Science.gov (United States)

    Paliouras, Dimitrios; Gogakos, Apostolos; Rallis, Thomas; Chatzinikolaou, Fotios; Asteriou, Christos; Tagarakis, Georgios; Organtzis, John; Tsakiridis, Kosmas; Tsavlis, Drosos; Zissimopoulos, Athanasios; Kioumis, Ioannis; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Konstantinos; Zarogoulidis, Paul; Barbetakis, Nikolaos

    2016-01-01

    Background Papillomatosis presents, most frequently, as multiple lesions of the respiratory tract, which are usually considered benign. Malignant degeneration into squamous cell carcinoma is quite common, although curative approaches vary a lot in modern literature. Case report We report a case of a 66-year-old male patient with the coexistence of multiple squamous cell papilloma and carcinoma in the upper trachea with severe airway obstruction that was diagnosed through bronchoscopy and treated by performing an urgent tracheostomy, followed by concurrent chemotherapy and radiotherapy. There was no evidence of recurrence after a 12-month follow-up period. Conclusion This study underlines the diagnostic and therapeutic value of bronchoscopy as well as multimodality palliative treatment in such cases. To the best of our knowledge, this is the first study to describe an immediate treatment protocol with tracheostomy and concurrent chemotherapy/radiotherapy in a patient with squamous cell tracheal papilloma and carcinoma. PMID:26730195

  11. Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells.

    Directory of Open Access Journals (Sweden)

    Shan He

    Full Text Available BACKGROUND: Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized. DESIGN AND METHODS: Using lymphocytic choriomeningitis virus (LCMV peptide gp33-specific CD8(+ T cells derived from T cell receptor transgenic mice, we characterized the metabolic phenotype of proliferating T cells that were activated and expanded in vitro in the presence or absence of rapamycin, and determined the capability of these rapamycin-treated T cells to generate long-lived memory cells in vivo. RESULTS: Antigen-activated CD8(+ T cells treated with rapamycin gave rise to 5-fold more long-lived memory T cells in vivo than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS. These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells. CONCLUSIONS: Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy.

  12. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies

    OpenAIRE

    Mahmoud Aljurf; Hala Abalkhail; Amal Alseraihy; Said Y. Mohamed; Mouhab Ayas; Fahad Alsharif; Hazza Alzahrani; Abdullah Al-Jefri; Ghuzayel Aldawsari; Ali Al-Ahmari; Belgaumi, Asim F.; Claudia Ulrike Walter; Hassan El-Solh; Walid Rasheed; Maher Albitar

    2016-01-01

    Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leuke...

  13. Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream.

    Science.gov (United States)

    Yang, Jian-Qiang; Chen, Xian-Yu; Engle, Michelle Yixiao; Wang, Jian-You

    2015-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30-year-old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP. PMID:25754701

  14. 17 cases of advanced non-small cell lung cancer treated with paclitaxel liposome plus nedaplatin

    Institute of Scientific and Technical Information of China (English)

    Tao Suo; Wei Ge; Jinzhong Zhang; Yongfa Zheng; Shunxiang Luo

    2012-01-01

    Objective: The aim of this study was to evaluate the recent efficacy and adverse reactions of paclitaxel liposome plus nedaplatin in the treatment of advanced non-small cell lung cancer (NSCLC).Methods: Seventeen cases of NSCLC treated with paclitaxel liposome and nedaplatin for 2 to 6 cycles, by infusing paclitaxel liposome 135 mg/m2 for 3 h on d1 and nedaplatin 80 mg/m2 as infusion on d2.Results: Among 17 patients being evaluated for response to treatment, 1 achieved complete response (CR), 4 achieved partial response (PR), 3 achieved stable disease (SD), 9 achieved progress disease (PD).The main adverse reaction was haematological toxicities, especially leukopenia and thrombocytopenia.The non-haematological toxicities included nausea, vomiting, mild hepatic dysfunction, alopecia and so on.Conclusion: Paclitaxel liposome plus nedaplatin was effective and well tolerated for treating patients with advanced NSCLC.

  15. Radiobiologic response of CHO-KI cells treated with vitamin A

    International Nuclear Information System (INIS)

    Treatment of CHO-KI cells with vitamin A altered their response to subsequent gamma irradiation. In general longterm preincubation with low doses of the vitamin caused a relative increase in the number of cells surviving a given radiation dose. The effect resulted in an increase in the D0 of the survival curve. Long or short term exposure to high concentrations of the vitamin caused a decrease in the number of surviving cells leading to a decrease in the extrapolation number of the survival curve. Recovery of cells from radiation damage, assessed using the split dose technique, was also impaired by vitamin A pretreatment. A mechanism involving repair of potentially lethal damage may explain the protective effect of vitamin A since this was highly dependent on the cell density of cultures at the time of irradiation. However, in view of the data showing that the vitamin A concentrations necessary to alter the radiation survival curve shoulder caused a significant release of sialic acid into the medium, a mechanism involving membrane stability may account for both the reduction in repair/recovery capacity of the treated cells and the radioprotective effect. (orig.)

  16. DNA synthesis and cell survival after X-irradiation of mammalian cells treated with caffeine or adenine

    International Nuclear Information System (INIS)

    The expression of the transient depression in the rate of DNA synthesis normally observed after exposure of randomly-dividing Chinese hamster V-79 or Chinese hamster CHO cells to ionizing radiation could be postponed by a post-irradiation treatment with 1.0 to 2.0 mM adenine or 1.5 mM caffeine. Caffeine may exert its effect by creating additional sites for replication in irradiated cells. Cells treated with caffeine or adenine for 2 or 4 hours after exposure to 3000 rad of 300 kVp X-rays exhibited depressed synthesis only after the removal of caffeine or adenine. These alterations in the timing of the X-ray-induced depression of the rate of DNA synthesis had no effect on X-ray-induced cell killing. Although a 4 hour post-irradiation treatment of randomly-dividing Chinese hamster V-79 cells with 1.0 or 2.0 mM caffeine potentiated X-ray-induced cell killing, this reduction in survival was due primarily to effects on cells not in S-phase. (author)

  17. Fetal progenitor cell transplantation treats methylmalonic aciduria in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Buck, Nicole E., E-mail: nicole.buck@mcri.edu.au [Metabolic Research, Murdoch Childrens Research Institute, The University of Melbourne, Department of Paediatrics, Royal Children' s Hospital, Flemington Road, Parkville, VIC 3052 (Australia); Pennell, Samuel D.; Wood, Leonie R. [Metabolic Research, Murdoch Childrens Research Institute, The University of Melbourne, Department of Paediatrics, Royal Children' s Hospital, Flemington Road, Parkville, VIC 3052 (Australia); Pitt, James J. [Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Royal Children' s Hospital, Parkville (Australia); Allen, Katrina J. [Gastro and Food Allergy, Murdoch Childrens Research Institute, Parkville (Australia); Peters, Heidi L. [Metabolic Research, Murdoch Childrens Research Institute, The University of Melbourne, Department of Paediatrics, Royal Children' s Hospital, Flemington Road, Parkville, VIC 3052 (Australia)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Fetal cells were transplanted into a methylmalonic acid mouse model. Black-Right-Pointing-Pointer Cell engraftment was detected in liver, spleen and bone marrow. Black-Right-Pointing-Pointer Biochemical disease correction was measured in blood samples. Black-Right-Pointing-Pointer A double dose of 5 million cells (1 week apart) proved more effective. Black-Right-Pointing-Pointer Higher levels of engraftment may be required for greater disease correction. -- Abstract: Methylmalonic aciduria is a rare disorder caused by an inborn error of organic acid metabolism. Current treatment options are limited and generally focus on disease management. We aimed to investigate the use of fetal progenitor cells to treat this disorder using a mouse model with an intermediate form of methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at embryonic day 15-17 and intravenously transplanted into sub-lethally irradiated mice. Liver donor cell engraftment was determined by PCR. Disease correction was monitored by urine and blood methylmalonic acid concentration and weight change. Initial studies indicated that pre-transplantation sub-lethal irradiation followed by transplantation with 5 million cells were suitable. We found that a double dose of 5 million cells (1 week apart) provided a more effective treatment. Donor cell liver engraftment of up to 5% was measured. Disease correction, as defined by a decrease in blood methylmalonic acid concentration, was effected in methylmalonic acid mice transplanted with a double dose of cells and who showed donor cell liver engraftment. Mean plasma methylmalonic acid concentration decreased from 810 {+-} 156 (sham transplanted) to 338 {+-} 157 {mu}mol/L (double dose of 5 million cells) while mean blood C3 carnitine concentration decreased from 20.5 {+-} 4 (sham transplanted) to 5.3 {+-} 1.9 {mu}mol/L (double dose of 5 million cells). In conclusion, higher levels of engraftment may

  18. Global analysis of protein expression and phosphorylation levels in nicotine-treated pancreatic stellate cells

    Science.gov (United States)

    Paulo, Joao A.; Gaun, Aleksandr; Gygi, Steven P.

    2016-01-01

    Smoking is a risk factor in pancreatic disease, however, the biochemical mechanisms correlating smoking with pancreatic dysfunction remain poorly understood. Strategies using multiplexed isobaric tag-based mass spectrometry facilitate the study of drug-induced perturbations on biological systems. Here, we present the first large scale analysis of the proteomic and phosphoproteomic alterations in pancreatic stellate cells following treatment with two nicotinic acetylcholine receptor (nAChR) ligands: nicotine and α-bungarotoxin. We treated cells with nicotine or α-bungarotoxin for 12hr in triplicate and compared alterations in protein expression and phosphorylation levels to mock treated cells using a tandem mass tag (TMT9plex)-based approach. Over 8,100 proteins were quantified across all nine samples of which 46 were altered in abundance upon treatment with nicotine. Proteins with increased abundance included those associated with neurons, defense mechanisms, indicators of pancreatic disease and lysosomal proteins. In addition, we measured differences for ∼16,000 phosphorylation sites across all nine samples using a titanium dioxide-based strategy, of which 132 sites were altered with nicotine and 451 with α-bungarotoxin treatment. Many altered phosphorylation sites were involved in nuclear function and transcriptional events. This study supports the development of future targeted investigations to establish a better understanding for the role of nicotine and associated receptors in pancreatic disease. PMID:26265067

  19. EMR2 Receptor Ligation Modulates Cytokine Secretion Profiles and Cell Survival of Lipopolysaccharide-treated Neutrophils

    Directory of Open Access Journals (Sweden)

    Tzu-Ying Chenee

    2011-10-01

    Full Text Available Background: Epidermal growth factor (EGF-like module-containing mucin-like hormonereceptor-like 2 (EMR2 is an adhesion G protein-coupled receptor previouslyshown to potentiate neutrophil responses to a number of inflammatory stimuli. EMR2 activation promotes neutrophil adhesion and migration, and augments production of reactive oxygen species and degranulation. In this study,we examined the effect of EMR2 ligation by its specific antibody on thecytokine expression profile and cell survival of lipopolysaccharide (LPS-treated neutrophils.Methods: Neutrophils were treated with LPS in the absence or presence of the antiEMR2 mAb, 2A1. Cell apoptosis was determined by flow cytometry analysisusing annexin-V and propidium iodide staining. Cell supernatants were collected for the detection of cytokine secretion by enzyme-linked immunosorbent assay.Results: We confirmed the specific priming effect of EMR2 on the response of neutrophils to formyl-Met-Leu-Phe by measuring the production of reactiveoxygen species. Furthermore, we showed that EMR2 ligation suppressesLPS-induced neutrophil survival. In addition, we demonstrated that ligationof EMR2 changes the secretion profiles of multiple cytokines, includinginterleukin (IL-6, IL-8, and monocyte chemotactic protein-1. Finally, higherlevels of EMR2 were detected on neutrophils of liver cirrhosis patients andwere correlated to a pro-apoptotic phenotype.Conclusion: Collectively, the present data indicate a functional role for EMR2 in themodulation of neutrophil activation during inflammation.

  20. Spatiotemporal Mapping Of Fluorescence Parameters In Cells Treated With Toxic Chemicals: The Cell's Detoxification Apparatus

    Science.gov (United States)

    Kohen, Elli; Kohen, Cahide; Hirschberg, Joseph G.; Fried, Marek; Prince, Jeffrey

    1989-03-01

    We have used a grating microspectrofluorometer equipped with phase and fluorescence microscopy to study the intracellular localization and processing of fluorescent compounds that are not part of the natural cell chemistry (xenobiotics) and of fluorescent carcinogens. Our topographic and spectral observations, in conjunction with ultrastructural analysis, lead to the hypothesis of a dynamically organized multiorganelle complex involved in the cell's detoxification processes and possible protection of the cell's genetic apparatus. Our studies with quinacrine derivatives and benzo(a)pyrene suggest that the organelle complex involves the endoplasmic reticulum, the Golgi apparatus, the lysosomes, and the nuclear membrane, with a fine microchannel network interconnecting the different organelles. We have indications that there is not only a trapping of fluorescent carcinogens in the cytoplasmic components of the complex but also a possible "nuclear pump" (powered by the substrates of the hexose monophosphate shunt pathway) involved in ejection of xenobiotics from the nucleus. The instrumental performance allows the in situ pixel-by-pixel study of extranuclear and nuclear energy metabolism related to these processes in parallel to the blue and red spectral shifts associated with metabolites of fluorescent carcinogens. Recording of fluorescence emission spectra at different excitation wavelengths in human fibroblasts and rat liver cells allows the application of multivariate statistical methods to analyze multicomponent spectra. Elucidation of mechanisms involved in the organization and activity of the organelle complex is relevant to the interpretation of drug sensitivity or resistance and should result in better targeting of cancer chemotherapeutics and gene modifiers toward their expected sites of action.

  1. Dexamethasone/1alpha-25-dihydroxyvitamin D3-treated dendritic cells suppress colitis in the SCID T-cell transfer model

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Schmidt, Esben Gjerløff Wedebye; Gad, Monika;

    2008-01-01

    Autoantigen-presenting immunomodulatory dendritic cells (DCs) that are used for adoptive transfer have been shown to be a promising therapy for a number of autoimmune diseases. We have previously demonstrated that enteroantigen-pulsed DCs treated with interleukin-10 (IL-10) can partly protect...... severe combined immunodeficient (SCID) mice adoptively transferred with CD4(+) CD25(-) T cells from the development of wasting disease and colitis. We therefore established an in vitro test that could predict the in vivo function of DCs and improve strategies for the preparation of immunomodulatory DCs...... in this model. Based on these in vitro findings, we here evaluate three methods for DC generation including short-term and long-term IL-10 exposure or DC exposure to dexamethasone in combination with vitamin D3 (Dex/D3). All DCs resulted in lower CD4(+) CD25(-) T-cell enteroantigen-specific responses...

  2. Facial basal cell carcinoma treated with topical 5% imiquimod cream with dermoscopic evaluation

    Directory of Open Access Journals (Sweden)

    Archana Singal

    2016-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common skin cancer worldwide. Surgical excision is considered to be the primary therapeutic modality wherever possible. For inoperable cases, 5% imiquimod seems to be a good alternative. We present two cases of nodular pigmented BCCs on the face in elderly women successfully treated with 5% imiquimod cream application resulting in complete clinical clearance of lesion as well as on histology and dermatoscopy. There was no recurrence of the lesion on 2 years follow-up for the first and 1.5 years for the second patient.

  3. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M; Svanvik, J; Sun, X-F

    2010-01-01

    the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1......Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...

  4. Role of oil vehicle on hepatic cell proliferation in PCB-treated rats

    OpenAIRE

    Bunaciu, Rodica Petruta; Tharappel, Job C.; Lehmler, Hans-Joachim; Lee, Eun Y.; Robertson, Larry W.; Bruckner, Geza G.; Spear, Brett T.; Glauert, Howard P.

    2011-01-01

    Here we report the role of dietary glycine and the type of oil used as a vehicle on hepatotoxicity in 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153)-treated or control rats. In the first study, glycine or valine (as control) was fed in an unrefined diet at 5% for the entire study (5 days) to inhibit Kupffer cell activity. PCB-153 (100 or 300 µmol/kg) dissolved in medium chain triglyceride (MCT) oil, was injected i.p. two days before euthanasia; the peroxisome proliferator Wy-14,643 was included ...

  5. Donor Kidney With Renal Cell Carcinoma Successfully Treated With Radiofrequency Ablation

    DEFF Research Database (Denmark)

    Christensen, S F; Hansen, J M

    2015-01-01

    BACKGROUND: The risk of donor-transmitted cancer is evident. CASE REPORT: We report the case of a 69-year-old woman who was transplanted with a kidney from a deceased donor. Four days after transplantation a routine ultrasound scan revealed a 3-cm tumor in the middle-upper pole of the allograft. A...... biopsy showed the tumor to be papillary renal cell carcinoma. The patient was treated with radiofrequency ablation. This procedure was complicated by the development of a cutaneous fistula and open surgery was done with resection of an area of necrosis in the kidney and of the fistula. The maintenance...

  6. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M;

    2010-01-01

    Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...... the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1...

  7. Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

    Science.gov (United States)

    2013-03-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Myelodysplastic Syndromes; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Disseminated Neuroblastoma; Malignant Neoplasm; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Mixed Germ Cell Tumor; Ovarian Monodermal and Highly Specialized Teratoma; Ovarian Polyembryoma; Ovarian Yolk Sac Tumor; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Seminoma; Testicular Choriocarcinoma and Teratoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular

  8. Cytotoxicity Investigation on Cultured Human Blood Cells Treated with Single-Wall Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Maria Rosaria Scarfì

    2008-01-01

    Full Text Available The single-wall carbon nanotubes (SWCNTs are one of the new materials ofemerging technologies. They are becoming increasingly studied for the possibleapplications in electronics, optics and biology. In particular, very promising fields ofapplication are the development of optical biosensors and the intracellular drug delivery.Nevertheless, there is a paucity of information on their toxicological properties and onpotential human health risk. In the present study the SWCNTs were investigated for thepossible induction of toxicity in human blood cells. Cell growth, viability, apoptosis andmetabolic activity were evaluated in proliferating human peripheral blood lymphocytes. Inun-stimulated human leukocytes primary DNA damage was also evaluated. SWCNTsconcentrations ranging from 1 to 50 μg/ml were tested, and treatment duration varied from6 to 72 h, in accordance with the biological target investigated. A statistically significantdecrease in cell growth was found in cells treated with the highest concentrations (25 and50 μg/ml. Such decrease was not associated to cell death or apoptosis, but it wasdemonstrated to be related to a decrease in metabolic activity, as assessed by resazurinassay. Moreover, treatments of 6 h with SWCNTs concentrations of 1, 5 and 10 μg/mlfailed to induce primary DNA damage on the entire human leukocytes population.

  9. Activation of Wnt/β-catenin signaling increases apoptosis in melanoma cells treated with trail.

    Directory of Open Access Journals (Sweden)

    Zachary F Zimmerman

    Full Text Available While the TRAIL pathway represents a promising therapeutic target in melanoma, resistance to TRAIL-mediated apoptosis remains a barrier to its successful adoption. Since the Wnt/β-catenin pathway has been implicated in facilitating melanoma cell apoptosis, we investigated the effect of Wnt/β-catenin signaling on regulating the responses of melanoma cells to TRAIL. Co-treatment of melanoma cell lines with WNT3A-conditioned media and recombinant TRAIL significantly enhanced apoptosis compared to treatment with TRAIL alone. This apoptosis correlates with increased abundance of the pro-apoptotic proteins BCL2L11 and BBC3, and with decreased abundance of the anti-apoptotic regulator Mcl1. We then confirmed the involvement of the Wnt/β-catenin signaling pathway by demonstrating that siRNA-mediated knockdown of an intracellular β-catenin antagonist, AXIN1, or treating cells with an inhibitor of GSK-3 also enhanced melanoma cell sensitivity to TRAIL. These studies describe a novel regulation of TRAIL sensitivity in melanoma by Wnt/β-catenin signaling, and suggest that strategies to enhance Wnt/β-catenin signaling in combination with TRAIL agonists warrant further investigation.

  10. Prognosis of esophageal squamous cell carcinoma treated by endoscopic submucosal dissection

    International Nuclear Information System (INIS)

    One hundred and fifty eight patients who had esophageal squamous cell carcinoma (SCC) were treated by endoscopic submucosal dissection (ESD) from Jan. 2,000 to Dec. 2006. The invasion depth was divided as epithelium (EP), Lamina propria mucosa (LPM), muscularis mucosa (MM) and submuosal layer. When the depth of submucosal invasion was 200 micrometers or less, the invasion depth was defined as SM1. In this study, out of 158 patients 28 patients had MM SCC, and 12 patients had SM1 SCC. The additional therapies such as Esophagectomy or Chemo Radio Therapy (CRT) were recommended to the patients, when lymphatic permeation was found. Among the patients who had MM SCC, 5 patients had lymphatic permeation. Among the patients who had SM1 SCC, 4 patients had lymphatic permeation. 2 MM and 2 SM1 patients were treated by CRT and the other 5 patients who had lymphatic permeation refused the additional therapy because of other diseases. All 4 patients who were treated by CRT are alive, but lymph node metastasis was found in 2 of the patients who refused CRT. One died of esophageal SCC, and one died of another disease. No lymph node metastasis was found in 23 patients who had MM without lymphatic permeation, and 8 patients who had SM1 without lymphatic permeation. According to our data, the indication of esophageal ESD could be expanded for MM or SM1 SCC without lymphatic permeation. (author)

  11. A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wu Xiaoyan; Chen Peili [Department of Medicine, University of Chicago, Chicago, Illinois (United States); Sonis, Stephen T. [Division of Oral Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Biomodels, Watertown, Massachusetts (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Berger, Ann [NephRx Corporation, Kalamazoo, Michigan (United States); Toback, F. Gary, E-mail: gtoback@medicine.bsd.uchicago.edu [Department of Medicine, University of Chicago, Chicago, Illinois (United States)

    2012-07-01

    Purpose: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21-amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. Methods and Materials: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. Results: Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-{alpha}-induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-{alpha}, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. Conclusions: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.

  12. A Novel Peptide to Treat Oral Mucositis Blocks Endothelial and Epithelial Cell Apoptosis

    International Nuclear Information System (INIS)

    Purpose: No effective agents currently exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head-and-neck cancer. We identified a novel 21–amino acid peptide derived from antrum mucosal protein-18 that is cytoprotective, mitogenic, and motogenic in tissue culture and animal models of gastrointestinal epithelial cell injury. We examined whether administration of antrum mucosal protein peptide (AMP-p) could protect against and/or speed recovery from OM. Methods and Materials: OM was induced in established hamster models by a single dose of radiation, fractionated radiation, or fractionated radiation together with cisplatin to simulate conventional treatments of head-and-neck cancer. Results: Daily subcutaneous administration of AMP-p reduced the occurrence of ulceration and accelerated mucosal recovery in all three models. A delay in the onset of erythema after irradiation was observed, suggesting that a protective effect exists even before injury to mucosal epithelial cells occurs. To test this hypothesis, the effects of AMP-p on tumor necrosis factor-α–induced apoptosis were studied in an endothelial cell line (human dermal microvascular endothelial cells) as well as an epithelial cell line (human adult low-calcium, high-temperature keratinocytes; HaCaT) used to model the oral mucosa. AMP-p treatment, either before or after cell monolayers were exposed to tumor necrosis factor-α, protected against development of apoptosis in both cell types when assessed by annexin V and propidium iodide staining followed by flow cytometry or ligase-mediated polymerase chain reaction. Conclusions: These observations suggest that the ability of AMP-p to attenuate radiation-induced OM could be attributable, at least in part, to its antiapoptotic activity.

  13. Biocompatibility evaluation of surface-treated AISI 316L austenitic stainless steel in human cell cultures.

    Science.gov (United States)

    Martinesi, M; Bruni, S; Stio, M; Treves, C; Bacci, T; Borgioli, F

    2007-01-01

    The effects of AISI 316L austenitic stainless steel, tested in untreated state or subjected to glow-discharge nitriding (at 10 or 20 hPa) and nitriding + post-oxidizing treatments, on human umbilical vein endothelial cells (HUVEC) and on peripheral blood mononuclear cells (PBMC) were evaluated. All the treated samples showed a better corrosion resistance in PBS and higher surface hardness in comparison with the untreated alloy. In HUVEC put in contact for 72 h with the sample types, proliferation and apoptosis decreased and increased, respectively, in the presence of the nitrided + post-oxidized samples, while only slight differences in cytokine (TNF-alpha, IL-6, and TGF-beta1) release were registered. Intercellular adhesion molecule-1 (ICAM-1) increased in HUVEC incubated with all the treated samples, while vascular cell adhesion molecule-1 (VCAM-1) and E-selectin increased in the presence of all the sample types. PBMC incubated for 48 h with the samples showed a decrease in proliferation and an increase in apoptosis in the presence of the untreated samples and the nitrided + post-oxidized ones. All the sample types induced a remarkable increase in TNF-alpha and IL-6 release in PBMC culture medium, while only the untreated sample and the nitrided at 10 hPa induced an increase in ICAM-1 expression. In HUVEC cocultured with PBMC, previously put in contact with the treated AISI 316L samples, increased levels of ICAM-1 were detected. In HUVEC coincubated with the culture medium of PBMC, previously put in contact with the samples under study, a noteworthy increase in ICAM-1, VCAM-1, and E-selectin levels was always registered, with the exception of VCAM-1, which was not affected by the untreated sample. In conclusion, even if the treated samples do not show a marked increase in biocompatibility in comparison with the untreated alloy, their higher corrosion resistance may suggest a better performance as the contact with physiological environment becomes longer. PMID

  14. Insights into plant cell wall structure, architecture, and integrity using glycome profiling of native and AFEXTM-pre-treated biomass

    OpenAIRE

    Pattathil, Sivakumar; Hahn, Michael G.; Dale, Bruce E; Chundawat, Shishir P. S.

    2015-01-01

    Cell walls, which constitute the bulk of plant biomass, vary considerably in their structure, composition, and architecture. Studies on plant cell walls can be conducted on both native and pre-treated plant biomass samples, allowing an enhanced understanding of these structural and compositional variations. Here glycome profiling was employed to determine the relative abundance of matrix polysaccharides in several phylogenetically distinct native and pre-treated plant biomasses. Eight distinc...

  15. The Effect of Therapeutic Blockades of Dust Particles-Induced Ca2+ Signaling and Proinflammatory Cytokine IL-8 in Human Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ju Hee Yoon

    2015-01-01

    Full Text Available Bronchial epithelial cells are the first barrier of defense against respiratory pathogens. Dust particles as extracellular stimuli are associated with inflammatory reactions after inhalation. It has been reported that dust particles induce intracellular Ca2+ signal, which subsequently increases cytokines production such as interleukin- (IL- 8. However, the study of therapeutic blockades of Ca2+ signaling induced by dust particles in human bronchial epithelial cells is poorly understood. We investigated how to modulate dust particles-induced Ca2+ signaling and proinflammatory cytokine IL-8 expression. Bronchial epithelial BEAS-2B cells were exposed to PM10 dust particles and subsequent mediated intracellular Ca2+ signaling and reactive oxygen species signal. Our results show that exposure to several inhibitors of Ca2+ pathway attenuated the PM10-induced Ca2+ response and subsequent IL-8 mRNA expression. PM10-mediated Ca2+ signal and IL-8 expression were attenuated by several pharmacological blockades such as antioxidants, IP3-PLC blockers, and TRPM2 inhibitors. Our results show that blockades of PLC or TRPM2 reduced both of PM10-mediated Ca2+ signal and IL-8 expression, suggesting that treatment with these blockades should be considered for potential therapeutic trials in pulmonary epithelium for inflammation caused by environmental events such as seasonal dust storm.

  16. [Secondary TFE3-associated renal cell carcinoma in a child treated for Ewing sarcoma].

    Science.gov (United States)

    Fedhila Ben Ayed, F; Rhayem, S; Doghri, R; Ben Hassine, L; Khemiri, M; Mrad, K; Bellagha, I; Barsaoui, S

    2016-02-01

    Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents. PMID:26702489

  17. A proteomic analysis of mushroom polysaccharide-treated HepG2 cells.

    Science.gov (United States)

    Chai, Yangyang; Wang, Guibin; Fan, Lili; Zhao, Min

    2016-01-01

    The anti-tumor properties of fungal polysaccharides have gained significant recognition in Asia and tropical America. In this study, the differential expression of proteins in normal HepG2 cells and those treated with polysaccharides that had been isolated from Phellinus linteus (PL), Ganoderma lucidum (GL) and Auricularia auricula (AA) was investigated. Using two-dimensional electrophoresis (2DE), a total of 104 protein spots were determined to be overexpressed in these cells compared with noncancerous regions. A total of 59 differentially expressed proteins were identified through MALDI-TOF-MS. In addition, 400 biological processes (BP), 133 cell components (CC) and 146 molecular functions (MF) were enriched by Gene Ontology (GO) analysis, and 78 KEGG pathways were enriched by pathway enrichment. Protein-Protein Interaction (PPI) analysis demonstrated the interaction networks affected by polysaccharides in HepG2 cells. Then, DJ-1 and 14-3-3 were identified as the key proteins in the networks, and the expression of the mRNA and proteins were evaluated using Real-time quantitative PCR (qRT-PCR) and Western blotting (WB), respectively. The results were in agreement with the 2DE. These results provided information on significant proteins of hepatocellular carcinoma (HCC) and form an important basis for the future development of valuable medicinal mushroom resources. PMID:27020667

  18. Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis.

    Science.gov (United States)

    Schukur, Lina; Geering, Barbara; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

    2015-12-16

    Psoriasis is a chronic inflammatory skin disease characterized by a relapsing-remitting disease course and correlated with increased expression of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 22 (IL22). Psoriasis is hard to treat because of the unpredictable and asymptomatic flare-up, which limits handling of skin lesions to symptomatic treatment. Synthetic biology-based gene circuits are uniquely suited for the treatment of diseases with complex dynamics, such as psoriasis, because they can autonomously couple the detection of disease biomarkers with the production of therapeutic proteins. We designed a mammalian cell synthetic cytokine converter that quantifies psoriasis-associated TNF and IL22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL4 and IL10, which have been shown to be immunomodulatory in patients. Implants of microencapsulated cytokine converter transgenic designer cells were insensitive to simulated bacterial and viral infections as well as psoriatic-unrelated inflammation. The designer cells specifically prevented the onset of psoriatic flares, stopped acute psoriasis, improved psoriatic skin lesions and restored normal skin-tissue morphology in mice. The antipsoriatic designer cells were equally responsive to blood samples from psoriasis patients, suggesting that the synthetic cytokine converter captures the clinically relevant cytokine range. Implanted designer cells that dynamically interface with the patient's metabolism by detecting specific disease metabolites or biomarkers, processing their blood levels with synthetic circuits in real time, and coordinating immediate production and systemic delivery of protein therapeutics may advance personalized gene- and cell-based therapies. PMID:26676608

  19. Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

    Science.gov (United States)

    2015-06-03

    ; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult

  20. Dual mechanisms of NF-κB inhibition in carnosol-treated endothelial cells

    International Nuclear Information System (INIS)

    The increased adhesion of monocytes to injured endothelial layers is a critical early event in atherogenesis. Under inflammatory conditions, there is increased expression of specific cell adhesion molecules on activated vascular endothelial cells, which increases monocyte adhesion. In our current study, we demonstrate a putative mechanism for the anti-inflammatory effects of carnosol, a diterpene derived from the herb rosemary. Our results show that both carnosol and rosemary essential oils inhibit the adhesion of TNFα-induced monocytes to endothelial cells and suppress the expression of ICAM-1 at the transcriptional level. Moreover, carnosol was found to exert its inhibitory effects by blocking the degradation of the inhibitory protein IκBα in short term pretreatments but not in 12 h pretreatments. Our data show that carnosol reduces IKK-β phosphorylation in pretreatments of less than 3 h. In TNFα-treated ECs, NF-κB nuclear translocation and transcriptional activity was abolished by up to 12 h of carnosol pretreatment and this was blocked by Nrf-2 siRNA. The long-term inhibitory effects of carnosol thus appear to be mediated through its induction of Nrf-2-related genes. The inhibition of ICAM-1 expression and p65 translocation is reversed by HO-1 siRNA. Carnosol also upregulates the Nrf-2-related glutathione synthase gene and thereby increases the GSH levels after 9 h of exposure. Treating ECs with a GSH synthesis inhibitor, BSO, blocks the inhibitory effects of carnosol. In addition, carnosol increases p65 glutathionylation. Hence, our present findings indicate that carnosol suppresses TNFα-induced singling pathways through the inhibition of IKK-β activity or the upregulation of HO-1 expression. The resulting GSH levels are dependent, however, on the length of the carnosol pretreatment period.

  1. S180 cell growth on low ion energy plasma treated TiO2 thin films

    International Nuclear Information System (INIS)

    X-ray photoelectron spectroscopy (XPS) was used to characterise the effects of low energy (2 thin films deposited by radio frequency (RF) magnetron sputter system. The low energy argon ion plasma surface modification of TiO2 in a two-stage hybrid system had increased the proportion of surface states of TiO2 as Ti3+. The proportion of carbon atoms as alcohol/ether (C-OX) was decreased with increase the RF power and carbon atoms as carbonyl (C=O) functionality had increased for low RF power treatment. The proportion of C(=O)OX functionality at the surface was decreased at low power and further increase in power has showed an increase in its relive proportion at the surface. The growth of S180 cells was observed and it seems that cells are uniformly spreads on tissue culture polystyrene surface and untreated TiO2 surfaces whereas small-localised cell free area can be seen on plasma treated TiO2 surfaces which may be due to decrease in C(=O)OX, increase in C=O and active sites at the surface. A relatively large variation in the surface functionalities with no change in the surface roughness was achieved by different RF plasma treatments of TiO2 surface whereas no significant change in S180 cell growth with different plasma treatments. This may be because cell growth on TiO2 was mainly influenced by nano-surface characteristics of oxide films rather than surface chemistry

  2. Increased accumulation of the lipophilic cation tetraphenylphosphonium+ by cyclopiazonic acid-treated renal epithelial cells

    International Nuclear Information System (INIS)

    Pig kidney renal epithelial cells (LLC-PK1) in culture were used to determine the effects of cyclopiazonic acid (CPA) on the uptake of the transmembrane potential probe, [3H]tetraphenylphosphonium bromide (TPP+). CPA had a significant stimulatory effect on TPP+ accumulation, which occurred in a dose-related manner. TPP+ accumulation in the presence of CPA was significantly reduced by high-potassium media (HK) and carbonylcyanide m-chlorophenylhydrazone (CCCP), but neither HK nor the protonophore CCCP, could completely abolish the stimulatory effect of CPA. The apparent transmembrane potential difference, calculated based on the difference in accumulation of TPP+ in low-potassium and HK media, ranged from -55.9 to -85.7 mV for control cells and -89.4 to -109.0 mV for CPA-treated cells (20 mg CPA/I). The mechanism of CPA stimulation of TPP+ accumulation was not known. However, it was hypothesized that the effect could be a result of alterations in ion pumps or altered membrane permeability

  3. Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Engell-Noerregaard, Lotte; Iversen, Trine Zeeberg;

    2012-01-01

    Dendritic cells (DC) are the most potent antigen presenting cells and have proven effective in stimulation of specific immune responses in vivo. Competing immune inhibition could limit the clinical efficacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibitor...... were treated with IL-2, Cyclophosphamide, and Celecoxib. The treatment was safe and tolerable. Sixteen patients (57 %) achieved stable disease (SD) at 1st evaluation and 8 patients had prolonged SD (7-13.7 months). The median OS was 9.4 months. Patients with SD had an OS of 10.5 months while patients...... with progressive disease (PD) had an OS of 6.0 months (p = 0.048) even though there were no differences in prognostic factors between the two groups. Despite the use of metronomic Cyclophosphamide, regulatory T cells did not decrease during treatment. Indirect IFN-γ ELISPOT assays showed a general...

  4. What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Yeung Trevor M

    2011-09-01

    Full Text Available Abstract Background Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway. Discussion The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process. Summary This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.

  5. Systemic mast cell disease (SMCD) and bone pain. A case treated with radiotherapy

    International Nuclear Information System (INIS)

    Background: Systemic mast cell disease (SMCD) is a rare disease characterized by a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells. SMCD preferentially involves the skin, spleen, liver, lymph nodes and the bone marrow. The cause of SMCD is unknown. Bony pain, caused by mast cell infiltration of the marrow cavity, is present in up to 28% of cases and is frequently chronic and difficult to palliate with medical therapy. Case Report: We report one case of refractory bone pain in a 54-year-old female Caucasian patient with advanced SMCD and associated bony involvement, which was treated with radiotherapy for pain palliation. Between 1995 and 1998, the patient was irradiated at four different locations: 1) right shoulder and proximal right humerus, 2) both hands, 3) both knees, 4) left humerus with a total dose of 40 Gy in 2.0 or 2.5 Gy daily fractions. Results: Different results of pain palliation were achieved. In one location the pain was reduced for 55 months until her death due to disease progression, whereas in two other locations a pain control was maintained for 3 and 6 months after radiotherapy. In one location, no pain reduction was achieved. Severe side effects were not observed. Conclusion: Palliative radiotherapy has a role in the control of severe intractable bone pain in patients with advanced SMCD, though in some cases the effect may be short or incomplete. The observed palliation of pain can even differ in the same patient. (orig.)

  6. Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sercarz Joel

    2006-12-01

    Full Text Available Abstract Background Conventional cancer therapy including surgery, radiation, and chemotherapy often are physically debilitating and largely ineffective in previously treated patients with recurrent head and neck squamous cell carcinoma (SCC. A natural photochemical, hypericin, could be a less invasive method for laser photodynamic therapy (PDT of these recurrent head and neck malignancies. Hypericin has powerful photo-oxidizing ability, tumor localization properties, and fluorescent imaging capabilities as well as minimal dark toxicity. The current study defined hypericin PDT in vitro with human SCC cells before the cells were grown as tumor transplants in nude mice and tested as a model for hypericin induced tumor fluorescence and PDT via laser fiberoptics. Methods SNU squamous carcinoma cells were grown in tissue culture, detached from monolayers with trypsin, and incubated with 0.1 μg to 10 μg/ml of hypericin before exposure to laser light at 514, 550, or 593 nm to define optimal dose, time, and wavelength for PDT of tumor cells. The SCC cells also were injected subcutaneously in nude mice and grown for 6–8 weeks to form tumors before hypericin injection and insertion of fiberoptics from a KTP532 surgical laser to assess the feasibility of this operating room instrument in stimulating fluorescence and PDT of tumors. Results In vitro testing revealed a hypericin dose of 0.2–0.5 μg/ml was needed for PDT of the SCC cells with an optimal tumoricidal response seen at the 593 nm light absorption maximum. In vivo tumor retention of injected hypericin was seen for 7 to10 days using KTP532 laser induced fluorescence and biweekly PDT via laser fiberoptics led to regression of SCC tumor transplants under 0.4 cm2 diameter, but resulted in progression of larger size tumors in the nude mice. Conclusion In this preclinical study, hypericin was tested for 514–593 nm dye laser PDT of human SCC cells in vitro and for KTP532 surgical laser targeting

  7. Cell toxicity and oxidative potential of engine exhaust particles: impact of using particulate filter or biodiesel fuel blend.

    Science.gov (United States)

    Gerlofs-Nijland, Miriam E; Totlandsdal, Annike I; Tzamkiozis, Theodoros; Leseman, Daan L A C; Samaras, Zissis; Låg, Marit; Schwarze, Per; Ntziachristos, Leonidas; Cassee, Flemming R

    2013-06-01

    The link between emissions of vehicular particulate matter (PM) and adverse health effects is well established. However, the influence of new emission control technologies and fuel types on both PM emissions and health effects has been less well investigated. We examined the health impact of PM emissions from two vehicles equipped with or without a diesel particulate filter (DPF). Both vehicles were powered either with diesel (B0) or a 50% v/v biodiesel blend (B50). The DPF effectively decreased PM mass emissions (∼85%), whereas the fuel B50 without DPF lead to less reduction (∼50%). The hazard of PM per unit distance driven was decreased for the DPF-equipped vehicle as indicated by a reduced cytotoxicity, oxidative, and pro-inflammatory potential. This was not evident and even led to an increase when the hazard was expressed on a per unit of mass basis. In general, the PM oxidative potential was similar or reduced for the B50 compared to the B0 powered vehicle. However, the use of B50 resulted in increased cytotoxicity and IL-6 release in BEAS-2B cells irrespective of the expression metric. This study shows that PM mass reduction achieved by the use of B50 will not necessarily decrease the hazard of engine emissions, while the application of a DPF has a beneficial effect on both PM mass emission and PM hazard. PMID:23597117

  8. Brominated flame retardants, hexabromocyclododecane and tetrabromobisphenol A, affect proinflammatory protein expression in human bronchial epithelial cells via disruption of intracellular signaling.

    Science.gov (United States)

    Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa

    2016-04-01

    Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are widely used as brominated flame retardants (BFRs) in consumer products. Because humans can be exposed to BFRs mainly through air or dust, the effects of the BFRs on the respiratory system and the underlying mechanisms were investigated. HBCD exposure significantly increased the expression of intercellular adhesion molecule (ICAM)-1 and the production of interleukin (IL)-6 and -8 in human bronchial epithelial cells (BEAS-2B). TBBPA exposure significantly increased the expression of ICAM-1 and IL-6, but not IL-8. HBCD and TBBPA stimulated epidermal growth factor (EGF) production and EGF receptor (EGFR) phosphorylation. Inhibitors of EGFR-selective tyrosine kinase and the subsequent mitogen-activated protein kinase effectively blocked the increase in the expression of proinflammatory proteins. The activation of nuclear factor-kappa B (p50, p65) and activator protein 1 (c-Jun) was also observed following HBCD exposure. Furthermore, the modulation for nuclear receptors was investigated. TBBPA but not HBCD showed ligand activity for thyroid hormone receptor (TR) and TR antagonist significantly suppressed the TBBPA-induced increase of the expression of ICAM-1 and IL-6. In conclusion, HBCD and TBBPA can disrupt the expression of proinflammatory proteins in bronchial epithelial cells, possibly via the modulation of EGFR-related pathways and/or nuclear receptors. PMID:26718265

  9. Comparison between ultrafine and fine particulate matter collected in Lebanon: Chemical characterization, in vitro cytotoxic effects and metabolizing enzymes gene expression in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    During the last few years, the induction of toxicological mechanisms by atmospheric ultrafine particles (UFP) has become one of the most studied topics in toxicology and a subject of huge debates. Fine particles (FP) and UFP collected at urban and rural sites in Lebanon were studied for their chemical composition and toxicological effects. UFP were found more enriched in trace elements, secondary inorganic ions, total carbon and organic compounds than FP. For toxicological analysis, BEAS-2B cells were exposed for 24, 48 and 72 h to increasing concentrations of FP, water-UFP suspension (UFPw) and UFP organic extract (UFPorg). Our findings showed that UFP caused earlier alterations of mitochondrial metabolism and membrane integrity from the lowest concentrations. Moreover, a significant induction of CYP1A1, CYP1B1 and AhRR genes expression was showed after cells exposure to UFPorg and to a lesser extent to UFPw and FP samples. - Highlights: • The main source of air pollution in Beirut is road traffic and generator sets. • More trace elements, secondary inorganic ions and organic compounds are found in UFP. • UFP cause early alterations of mitochondrial metabolism and membrane integrity. • PM induce XME gene expression leading to the formation of PAHs-reactive metabolites. • All the results evidenced a higher toxicity of UFP compared to FP. - Ultrafine particles collected in Lebanon: higher organic compounds contents than in fine particles and therefore higher induction of xenobiotic-metabolizing enzymes genes expression leading to more DNA damages

  10. Human bronchial epithelial cell injuries induced by fine particulate matter from sandstorm and non-sandstorm periods: Association with particle constituents.

    Science.gov (United States)

    Wang, Bin; Li, Ning; Deng, Furong; Buglak, Nicholas; Park, George; Su, Shu; Ren, Aiguo; Shen, Guofeng; Tao, Shu; Guo, Xinbiao

    2016-09-01

    Epidemiological studies have demonstrated the exacerbation of respiratory diseases following sandstorm-derived particulate matter (PM) exposure. The presence of anthropogenic and biological agents on the sandstorm PM and the escalation of PMsandstorms. We investigated how changes in PM2.5 composition, as the weather transitioned towards a sandstorm, affected human airway epithelial cells. Six PM2.5 samples covering two sandstorm events and their respective background and transition periods were collected in Baotou, an industrial city near the Gobi Desert in China. PM samples from all three periods had mild cytotoxicity in human bronchial epithelial cell line BEAS-2B, which was positively correlated with the contents of polycyclic aromatic hydrocarbons and several metals. All PM samples potently increased the release of interleukin-6 (IL-6) and interleukin-8 (IL-8). Endotoxin in all samples contributed significantly to the IL-6 response, with only a minor effect on IL-8. Cr was positively correlated with both IL-6 and IL-8 release, while Si was only associated with the increase of IL-6. Our study suggests that local agricultural and industrial surroundings in addition to the sandstorm play important roles in the respiratory effects of sandstorm-derived PM. PMID:27593287

  11. Persistent effectivity of gas plasma-treated, long time-stored liquid on epithelial cell adhesion capacity and membrane morphology.

    Directory of Open Access Journals (Sweden)

    Maxi Hoentsch

    Full Text Available Research in plasma medicine includes a major interest in understanding gas plasma-cell interactions. The immediate application of gas plasma in vitro inhibits cell attachment, vitality and cell-cell contacts via the liquid. Interestingly, in our novel experiments described here we found that the liquid-mediated plasma effect is long-lasting after storage up to seven days; i. e. the liquid preserves the characteristics once induced by the argon plasma. Therefore, the complete Dulbecco's Modified Eagle cell culture medium was argon plasma-treated (atmospheric pressure, kINPen09 for 60 s, stored for several days (1, 4 and 7 d at 37°C and added to a confluent mouse hepatocyte epithelial cell (mHepR1 monolayer. Impaired tight junction architecture as well as shortened microvilli on the cell membrane could be observed, which was accompanied by the loss of cell adhesion capacity. Online-monitoring of vital cells revealed a reduced cell respiration. Our first time-dependent analysis of plasma-treated medium revealed that temperature, hydrogen peroxide production, pH and oxygen content can be excluded as initiators of cell physiological and morphological changes. The here observed persisting biological effects in plasma-treated liquids could open new medical applications in dentistry and orthopaedics.

  12. Persistent effectivity of gas plasma-treated, long time-stored liquid on epithelial cell adhesion capacity and membrane morphology.

    Science.gov (United States)

    Hoentsch, Maxi; Bussiahn, René; Rebl, Henrike; Bergemann, Claudia; Eggert, Martin; Frank, Marcus; von Woedtke, Thomas; Nebe, Barbara

    2014-01-01

    Research in plasma medicine includes a major interest in understanding gas plasma-cell interactions. The immediate application of gas plasma in vitro inhibits cell attachment, vitality and cell-cell contacts via the liquid. Interestingly, in our novel experiments described here we found that the liquid-mediated plasma effect is long-lasting after storage up to seven days; i. e. the liquid preserves the characteristics once induced by the argon plasma. Therefore, the complete Dulbecco's Modified Eagle cell culture medium was argon plasma-treated (atmospheric pressure, kINPen09) for 60 s, stored for several days (1, 4 and 7 d) at 37°C and added to a confluent mouse hepatocyte epithelial cell (mHepR1) monolayer. Impaired tight junction architecture as well as shortened microvilli on the cell membrane could be observed, which was accompanied by the loss of cell adhesion capacity. Online-monitoring of vital cells revealed a reduced cell respiration. Our first time-dependent analysis of plasma-treated medium revealed that temperature, hydrogen peroxide production, pH and oxygen content can be excluded as initiators of cell physiological and morphological changes. The here observed persisting biological effects in plasma-treated liquids could open new medical applications in dentistry and orthopaedics. PMID:25170906

  13. Organellar proteome analyses of ricin toxin-treated HeLa cells.

    Science.gov (United States)

    Liao, Peng; Li, Yunhu; Li, Hongyang; Liu, Wensen

    2016-07-01

    Apoptosis triggered by ricin toxin (RT) has previously been associated with certain cellular organellar compartments, but the diversity in the composition of the organellar proteins remains unclear. Here, we applied a shotgun proteomics strategy to examine the differential expression of proteins in the mitochondria, nuclei, and cytoplasm of HeLa cells treated and not treated with RT. Data were combined with a global bioinformatics analysis and experimental confirmations. A total of 3107 proteins were identified. Bioinformatics predictors (Proteome Analyst, WoLF PSORT, TargetP, MitoPred, Nucleo, MultiLoc, and k-nearest neighbor) and a Bayesian model that integrated these predictors were used to predict the locations of 1349 distinct organellar proteins. Our data indicate that the Bayesian model was more efficient than the individual implementation of these predictors. Additionally, a Biomolecular Interaction Network (BIN) analysis was used to identify 149 BIN subnetworks. Our experimental confirmations indicate that certain apoptosis-related proteins (e.g. cytochrome c, enolase, lamin B, Bax, and Drp1) were found to be translocated and had variable expression levels. These results provide new insights for the systematic understanding of RT-induced apoptosis responses. PMID:25227225

  14. CT findings in non-small-cell lung cancer patients treated with gefitinib or erlotinib

    Directory of Open Access Journals (Sweden)

    Im Il Na

    2012-01-01

    Full Text Available Purpose: We performed this study to explore the association of computed tomography (CT findings with outcomes of patients with non-small-cell lung cancer (NSCLC treated with tyrosin kinase inhibitor (TKI such as gefitinib or erlotinib. Materials and Methods: We analyzed outcomes for 240 patients according to primary tumor (T, regional nodal (N staging and diffuse small pulmonary metastases (DSPM at the initial presentation. Tests for epidermal growth factor receptor (EGFR mutation were performed in 92 patients. Results: On multivariate analysis for tumor response, the N3 stage was predictive of a poor response (P < 0.001, whereas DSPM was a favorable factor (P = 0.007. Multivariate analysis for progression-free survival showed that the T3-4 stage (hazard ratio [HR]: 2.5, P < 0.001, in addition to the N3 stage (HR: 2.1, P < 0.001, was predictive of a poor outcome, whereas DSPM (HR: 0.6, P = 0.006 was a favorable factor. Notably, the multivariate model that included the EGFR mutational status revealed that the T3-4 stage predicted poor progression-free survival (HR: 2.2, P = 0.017 and poor overall survival (HR: 4.1, P < 0.001. Conclusion: Our data suggest that, in addition to EGFR mutational status, T-stage based on CT is predictive of outcomes of TKI-treated NSCLC patients.

  15. Changes of NF-KB activity in colon carcinoma cells treated with different crude extracts of abrotani herba

    Institute of Scientific and Technical Information of China (English)

    Feng Pan; Yuying Chen; Li Yang; Zhiheng Bian; Houjie Liang

    2008-01-01

    Objective: To study changes of NF-KB activity in colon carcinoma cell lines treated with different crude extracts of abrotani herba obtained through solvent extraction methods.Methods: Crude extracts of abrotani herba were extracted with ligarine, chloroform, acetoacetate and n-butanol in separating funnel.Exposure concentration of crude extracts were obtained through detecting viability of HT-29 cells by MTT.Then HT-29 cells and Lovo cells were treated with different crude extracts respectively.Changes of NF-KB activity in HT-29 cells and Lovo cells using different crude extracts were observed by EMSA.Results: Successfully extracted different crude extracts of abrotani herba and called them ligarine extract, chloroform extract,acetoacetate extract, n-butanol extract and remaining extract for short.NF-KB activity was significantly inhibited in HT-29 cells treated with chloroform extract, there were no significant differences in other groups compared with the control.The same change of NF-KB activity was observed in Lovo calls using different crude extracts of abrotani herba.Conclusion: NF-KB activity can be inhibited in colon carcinoma HT-29 calls and Lovo cells treated with chloroform extract obtained from abrotani herba through the method of solvent extraction.

  16. Squamous cell carcinoma of the anal canal treated with chemoradiotherapy in a patient with HIV.

    Science.gov (United States)

    Sugimoto, Aya; Nakazuru, Shoichi; Sakakibara, Yuko; Nishio, Kumiko; Yamada, Takuya; Ishida, Hisashi; Yajima, Keishiro; Uehira, Tomoko; Mori, Kiyoshi; Mita, Eiji

    2016-01-01

    Since the introduction of combination antiretroviral therapy (ART), the life expectancy has increased for patients infected with human immunodeficiency virus (HIV). This has been associated with reductions in the incidences of some AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma, but has coincided with an increased incidence of non-AIDS-defining malignancies, such as anal cancer. However, anal cancers are rare in patients with HIV in Japan. We report the case of an HIV-infected patient with anal cancer treated with chemoradiotherapy. A 37-year-old man receiving ART for HIV infection presented with a 1-month history of left inguinal lymphadenopathy and anal pain. Magnetic resonance imaging and computed tomography revealed a 56-mm mass, left inguinal lymphadenopathy, and left external iliac lymphadenopathy. The mass had infiltrated from the anal canal to the right levator ani and corpus spongiosum. Colonoscopy revealed a tumor with an ulcer in the anal canal. Histological examination of the tumor biopsy specimens confirmed the diagnosis of squamous cell carcinoma. The patient was diagnosed with anal cancer (T4N2M1 stage IV), and he received 5-fluorouracil (1000mg/m(2) on days 1-4 and 29-32) plus mitomycin C (10mg/m(2) on days 1 and 29) and concurrent radiotherapy (total dose, 59.4Gy in 33 fractions) along with ART. The treatment-related adverse events were grade 4 leukopenia and neutropenia, grade 3 thrombocytopenia, and grade 2 radiation dermatitis. Moreover, CD4 suppression was observed:the CD4 count decreased from 190 cells/μl before chemoradiotherapy to 138 cells/μl after 3 months, but increased to 210 cells/μl after 1 year. Because of the grade 4 leukopenia and neutropenia, the dose of 5-fluorouracil was reduced to 800mg/m(2) on days 29-32. A complete response was confirmed on magnetic resonance imaging, and colonoscopy confirmed the disappearance of the anal cancer. The patient is living with no signs of recurrence at 2 years

  17. Biocompatible, smooth, plasma-treated nickel-titanium surface--an adequate platform for cell growth.

    Science.gov (United States)

    Chrzanowski, W; Szade, J; Hart, A D; Knowles, J C; Dalby, M J

    2012-02-01

    High nickel content is believed to reduce the number of biomedical applications of nickel-titanium alloy due to the reported toxicity of nickel. The reduction in nickel release and minimized exposure of the cell to nickel can optimize the biocompatibility of the alloy and increase its use in the application where its shape memory effects and pseudoelasticity are particularly useful, e.g., spinal implants. Many treatments have been tried to improve the biocompatibility of Ni-Ti, and results suggest that a native, smooth surface could provide sufficient tolerance, biologically. We hypothesized that the native surface of nickel-titanium supports cell differentiation and insures good biocompatibility. Three types of surface modifications were investigated: thermal oxidation, alkali treatment, and plasma sputtering, and compared with smooth, ground surface. Thermal oxidation caused a drop in surface nickel content, while negligible chemistry changes were observed for plasma-modified samples when compared with control ground samples. In contrast, alkali treatment caused significant increase in surface nickel concentration and accelerated nickel release. Nickel release was also accelerated in thermally oxidized samples at 600 °C, while in other samples it remained at low level. Both thermal oxidation and alkali treatment increased the roughness of the surface, but mean roughness R(a) was significantly greater for the alkali-treated ones. Ground and plasma-modified samples had 'smooth' surfaces with R(a)=4 nm. Deformability tests showed that the adhesion of the surface layers on samples oxidized at 600 °C and alkali treatment samples was not sufficient; the layer delaminated upon deformation. It was observed that the cell cytoskeletons on the samples with a high nickel content or release were less developed, suggesting some negative effects of nickel on cell growth. These effects were observed primarily during initial cell contact with the surface. The most favorable

  18. AT-RvD1 Modulates CCL-2 and CXCL-8 Production and NF-κB, STAT-6, SOCS1, and SOCS3 Expression on Bronchial Epithelial Cells Stimulated with IL-4

    Science.gov (United States)

    de Oliveira, Jhony Robison; Favarin, Daniely Cornélio; Tanaka, Sarah Cristina Sato Vaz; Balarin, Marly Aparecida Spadotto; Silva Teixeira, David Nascimento; Rogério, Alexandre de Paula

    2015-01-01

    Bronchial epithelial cells represent the first line of defense against microorganisms and allergens in the airways and play an important role in chronic inflammatory processes such as asthma. In an experimental model, both RvD1 and AT-RvD1, lipid mediators of inflammation resolution, ameliorated some of the most important phenotypes of experimental asthma. Here, we extend these results and demonstrate the effect of AT-RvD1 on bronchial epithelial cells (BEAS-2B) stimulated with IL-4. AT-RvD1 (100 nM) decreased both CCL2 and CXCL-8 production, in part by decreasing STAT6 and NF-κB pathways. Furthermore, the effects of AT-RvD1 were ALX/FRP2 receptor dependent, as the antagonist of this receptor (BOC1) reversed the inhibition of these chemokines by AT-RvD1. In addition, AT-RvD1 decreased SOCS1 and increased SOCS3 expression, which play important roles in Th1 and Th17 modulation, respectively. In conclusion, AT-RvD1 demonstrated significant effects on the IL-4-induced activation of bronchial epithelial cells and consequently the potential to modulate neutrophilic and eosinophilic airway inflammation in asthma. Taken together, these findings identify AT-RvD1 as a potential proresolving therapeutic agent for allergic responses in the airways. PMID:26075216

  19. AT-RvD1 Modulates CCL-2 and CXCL-8 Production and NF-κB, STAT-6, SOCS1, and SOCS3 Expression on Bronchial Epithelial Cells Stimulated with IL-4

    Directory of Open Access Journals (Sweden)

    Jhony Robison de Oliveira

    2015-01-01

    Full Text Available Bronchial epithelial cells represent the first line of defense against microorganisms and allergens in the airways and play an important role in chronic inflammatory processes such as asthma. In an experimental model, both RvD1 and AT-RvD1, lipid mediators of inflammation resolution, ameliorated some of the most important phenotypes of experimental asthma. Here, we extend these results and demonstrate the effect of AT-RvD1 on bronchial epithelial cells (BEAS-2B stimulated with IL-4. AT-RvD1 (100 nM decreased both CCL2 and CXCL-8 production, in part by decreasing STAT6 and NF-κB pathways. Furthermore, the effects of AT-RvD1 were ALX/FRP2 receptor dependent, as the antagonist of this receptor (BOC1 reversed the inhibition of these chemokines by AT-RvD1. In addition, AT-RvD1 decreased SOCS1 and increased SOCS3 expression, which play important roles in Th1 and Th17 modulation, respectively. In conclusion, AT-RvD1 demonstrated significant effects on the IL-4-induced activation of bronchial epithelial cells and consequently the potential to modulate neutrophilic and eosinophilic airway inflammation in asthma. Taken together, these findings identify AT-RvD1 as a potential proresolving therapeutic agent for allergic responses in the airways.

  20. Suppression of cell-mediated immunity to challenge with P 815 mastocytoma in concanavalin A-treated mice.

    Science.gov (United States)

    Ekstedt, R D; Merdian, D J

    1983-01-01

    C57Bl/6 (B6) mice allogeneic to the P 815 mastocytoma tumor cell line when treated with concanavalin A prior to and at frequent intervals following challenge intraperitoneally with 10(7) tumor cells showed a significant suppression of their cell-mediated immune response at 9-10 days when compared with untreated animals. Suppression of the immune response of mice syngeneic (DBA/2) or hybrid (BDF1) to the tumor was also evidenced by increased mortality rates in concanavalin A-treated animals. The suppression of cell-mediated cytotoxicity observed in B6 mice treated with concanavalin A could be reversed by pretreatment with 20 mg silica injected intraperitoneally 7 days prior to challenge. These results suggest that macrophages play a significant role in the concanavalin A-induced immune suppression observed in this in vivo tumor-host system. PMID:6297806

  1. Coexistence of squamous cell tracheal papilloma and carcinoma treated with chemotherapy and radiotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Paliouras D

    2015-12-01

    Full Text Available Dimitrios Paliouras,1 Apostolos Gogakos,1 Thomas Rallis,1 Fotios Chatzinikolaou,2 Christos Asteriou,1 Georgios Tagarakis,3 John Organtzis,4 Kosmas Tsakiridis,5 Drosos Tsavlis,4 Athanasios Zissimopoulos,6 Ioannis Kioumis,4 Wolfgang Hohenforst-Schmidt,7 Konstantinos Zarogoulidis,4 Paul Zarogoulidis,4 Nikolaos Barbetakis1 1Thoracic Surgery Department, Theagenio Cancer Hospital, 2Department of Forensic Medicine and Toxicology, Faculty of Medicine, 3Department of Cardiothoracic Surgery, AHEPA University Hospital, 4Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, 5Cardiothoracic Surgery Department, “Saint Luke” Private Hospital, Panorama, Thessaloniki, 6Nuclear Medicine Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece; 7Medical Clinic I, “Fuerth” Hospital, University of Erlangen, Fuerth, Germany Background: Papillomatosis presents, most frequently, as multiple lesions of the respiratory tract, which are usually considered benign. Malignant degeneration into squamous cell carcinoma is quite common, although curative approaches vary a lot in modern literature.Case report: We report a case of a 66-year-old male patient with the coexistence of multiple squamous cell papilloma and carcinoma in the upper trachea with severe airway obstruction that was diagnosed through bronchoscopy and treated by performing an urgent tracheostomy, followed by concurrent chemotherapy and radiotherapy. There was no evidence of recurrence after a 12-month follow-up period.Conclusion: This study underlines the diagnostic and therapeutic value of bronchoscopy as well as multimodality palliative treatment in such cases. To the best of our knowledge, this is the first study to describe an immediate treatment protocol with tracheostomy and concurrent chemotherapy/radiotherapy in a patient with squamous cell tracheal papilloma and carcinoma

  2. Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

    Directory of Open Access Journals (Sweden)

    Camila Marx

    2014-01-01

    Full Text Available Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n=4 or allogeneic cultured adipose-derived stem cells (ASCs, n=5 injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases.

  3. Acupoint injection of autologous stromal vascular fraction and allogeneic adipose-derived stem cells to treat hip dysplasia in dogs.

    Science.gov (United States)

    Marx, Camila; Silveira, Maiele Dornelles; Selbach, Isabel; da Silva, Ariel Silveira; Braga, Luisa Maria Gomes de Macedo; Camassola, Melissa; Nardi, Nance Beyer

    2014-01-01

    Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n = 4) or allogeneic cultured adipose-derived stem cells (ASCs, n = 5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases. PMID:25180040

  4. Cellular Localization of the Molecular Forms of Acetylcholinesterase in rat Pheochromocytoma Pc12 Cells Treated with Nerve Growth Factor1

    OpenAIRE

    Inestrosa, Nibaldo C; Reiness, C. Gary; Reichardt, Louis F.; Hall, Zach W

    1981-01-01

    In rat pheochromocytoma (PC12) cells treated with nerve growth factor (NGF), there are several molecular forms of the enzyme acetylcholinesterase (AChE) which sediment on sucrose density gradients at 4 to 6, 10, and 16 S, respectively. We have investigated the cellular localization of these forms in PC12 cells. In order to determine which forms are soluble and which are membrane bound, we extracted PC12 cells in buffers of various ionic strengths and detergent compositions. To distinguish int...

  5. Fourier transform infrared spectroscopy for the distinction of MCF-7 cells treated with different concentrations of 5-fluorouracil

    OpenAIRE

    WU, BI-BO; Gong, Yi-Ping; Wu, Xin-Hong; Chen, Yuan-Yuan; Chen, Fang-Fang; Jin, Li-Ting; Cheng, Bo-Ran; Hu, Fen; Xiong, Bin

    2015-01-01

    Background In order to provide personalized treatment to patients with breast cancer, an accurate, reliable and cost-efficient analytical technique is needed for drug screening and evaluation of tumor response to chemotherapy. Methods Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used as a tool to assess cancer cell response to chemotherapy. MCF-7 cells (human breast adenocarcinoma cell line) were treated with different concentrations of 5-fluorouracil (5...

  6. A disease module in the interactome explains disease heterogeneity, drug response and captures novel pathways and genes in asthma.

    Science.gov (United States)

    Sharma, Amitabh; Menche, Jörg; Huang, C Chris; Ort, Tatiana; Zhou, Xiaobo; Kitsak, Maksim; Sahni, Nidhi; Thibault, Derek; Voung, Linh; Guo, Feng; Ghiassian, Susan Dina; Gulbahce, Natali; Baribaud, Frédéric; Tocker, Joel; Dobrin, Radu; Barnathan, Elliot; Liu, Hao; Panettieri, Reynold A; Tantisira, Kelan G; Qiu, Weiliang; Raby, Benjamin A; Silverman, Edwin K; Vidal, Marc; Weiss, Scott T; Barabási, Albert-László

    2015-06-01

    Recent advances in genetics have spurred rapid progress towards the systematic identification of genes involved in complex diseases. Still, the detailed understanding of the molecular and physiological mechanisms through which these genes affect disease phenotypes remains a major challenge. Here, we identify the asthma disease module, i.e. the local neighborhood of the interactome whose perturbation is associated with asthma, and validate it for functional and pathophysiological relevance, using both computational and experimental approaches. We find that the asthma disease module is enriched with modest GWAS P-values against the background of random variation, and with differentially expressed genes from normal and asthmatic fibroblast cells treated with an asthma-specific drug. The asthma module also contains immune response mechanisms that are shared with other immune-related disease modules. Further, using diverse omics (genomics, gene-expression, drug response) data, we identify the GAB1 signaling pathway as an important novel modulator in asthma. The wiring diagram of the uncovered asthma module suggests a relatively close link between GAB1 and glucocorticoids (GCs), which we experimentally validate, observing an increase in the level of GAB1 after GC treatment in BEAS-2B bronchial epithelial cells. The siRNA knockdown of GAB1 in the BEAS-2B cell line resulted in a decrease in the NFkB level, suggesting a novel regulatory path of the pro-inflammatory factor NFkB by GAB1 in asthma. PMID:25586491

  7. Gonadal cell kinetics in male mice treated with sulphur-35 during prenatal development

    International Nuclear Information System (INIS)

    Investigations on the possible hazards of the use of internally administered radioisotopes in human medicine either as therapeutic or diagnostic agents before or during child bearing age are of late gaining importance. The present investigation has been taken up to screen the effects of sulphur-35 on spermatogonia. CBA pregnant mice were injected (ip) with a dose of 20 μ Ci of sulphur-35 on 3.5, 10.5 or 15.5 days of gestation. At the similar intervals pregnant mice injected with physiological saline were kept for control data. All the animals were allowed to litter and F1 male progeny were killed at maturity at the age of 10 weeks and the testes collected. Sections of both the testes were prepared and stained by PAS-haematoxylin technique and the survival of spermatogonia types A, Int and B and preleptotene spermatocytes was evaluated. There was a significant reduction in all the cell types in the sulphur-35 treated animals. Thus the results indicate the cell-killing effect of radionuclide. (auth.)

  8. PECAM-1 is involved in neutrophil transmigration across Histophilus somni treated bovine brain endothelial cells.

    Science.gov (United States)

    Tiwari, Raksha; Sullivan, J; Czuprynski, C J

    2009-09-01

    Histophilus somni (H. somni) is a gram-negative bacterial pathogen that causes respiratory, reproductive, and central nervous system disease in cattle. The hallmark of systemic H. somni infection is diffused vasculitis that can lead to an acute central nervous system disease known as thrombotic meningoencephalitis (TME). Because platelet endothelial cell adhesion molecule-1 (PECAM-1) and endothelial nitric oxide synthase (eNOS) play fundamental roles in maintaining homeostasis in blood vessels, we sought to determine if PECAM-1 and eNOS expression play a role in events related to the pathogenesis of TME. Our findings demonstrate that neutrophil transmigration across H. somni-treated TBBEC (SV-40 transformed bovine brain endothelial cell line) was reduced by treatment with anti-PECAM-1 antibodies. Confocal microscopy indicated that H. somni treatment leads to redistribution of PECAM-1 and eNOS on the surface of TBBEC. These findings suggest that PECAM-1 and eNOS may play a role in the early pathogenesis of TME. PMID:19524660

  9. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    Science.gov (United States)

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA. PMID:26603475

  10. Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors.

    Science.gov (United States)

    Zhang, Pinghu; Liu, Fei; Guo, Fang; Zhao, Qiong; Chang, Jinhong; Guo, Ju-Tao

    2016-07-01

    Inhibitors of hepadnaviral DNA polymerases are predicted to inhibit both minus and plus strand of viral DNA synthesis and arrest viral DNA replication at the stage of pregenomic (pg) RNA-containing nucleocapsids. However, analyses of the RNA species of human and duck hepatitis B viruses (HBV and DHBV, respectively) in hepatoma cells treated with viral DNA polymerase inhibitors revealed the genesis of novel RNA species migrating slightly faster than the full-length pgRNA. The DNA polymerase inhibitor-induced accumulation of these RNA species were abolished in the presence of alpha-interferon or HBV nucleocapsid assembly inhibitors. Moreover, they were protected from microccocal nuclease digestion and devoid of a poly-A tail. These characteristics suggest that the novel RNA species are most likely generated from RNase H cleavage of encapsidated pgRNA, after primer translocation and synthesis of the 5' terminal portion of minus strand DNA. In support of this hypothesis, DNA polymerase inhibitor treatment of chicken hepatoma cells transfected with a DHBV genome encoding an RNase H inactive DNA polymerase (E696H) failed to produce such RNA species. Our results thus suggest that the currently available DNA polymerase inhibitors do not efficiently arrest minus strand DNA synthesis at the early stage in hepatocytes. Hence, development of novel antiviral agents that more potently suppress viral DNA synthesis or viral nucleocapsid assembly inhibitors that are mechanistically complementary to the currently available DNA polymerase inhibitors are warranted. PMID:27083116

  11. Effect of vitamin E on protein bound carbohydrate complexes in radiation treated oral squamous cell carcinoma patients

    International Nuclear Information System (INIS)

    Serum glycoproteins were evaluated in oral squamous cell carcinoma patients treated with radiotherapy and also the effect of vitamin E was studied. Cell surface glycoconjugates are important parameters in the detection of malignancy. Thus, the objective of the present study is to evaluate the efficacy of vitamin E on glycoproteins in oral cavity cancer patients treated with radiotherapy. The study includes 26 age and sex matched normal healthy individuals and 26 patients with squamous cell carcinoma of oral cavity. These patients were divided into two groups, one for radiotherapy alone (at a dosage of 6000 cGy in five fractions per week for a period of six weeks) and the other for radiotherapy plus vitamin E supplementation (at a dosage of 400 IU/day of vitamin E) for the entire period of radiotherapy. Levels of hexose, hexosamine, fucose and sialic acid were increased in oral squamous cell carcinoma patients and a significant decrease was observed in radiation treated patients when compared to control. The levels of glycoconjugates were significantly decreased in radiation treated patients supplemented with vitamin E. This measurement may be useful in assessing disease progression and identifying patients resistant to therapy and a possible role of vitamin E on reduction in glycoconjugate levels of radiation treated oral squamous cell carcinoma patients. (author)

  12. Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

  13. An electronic brachytherapy technique for treating squamous cell carcinoma in situ of the digit: a case report

    OpenAIRE

    Arterbery, V Elayne; Watson, Alice C.

    2013-01-01

    Background Squamous cell carcinoma in situ of the digit presents a complex management problem, which is usually treated with surgery or radiation or topical agents. The outcome of the surgical treatment can be an undesirable cosmetic result and loss of function. We report a unique Electronic Brachytherapy technique to treat the digit, which uses a 50 Kv miniaturized X-ray source with specialized applicators. Case presentation A 62-year-old African-American male was presented with a 12-month h...

  14. Protective Effect of Quercetin on the Morphology of Pancreatic β-Cells of Streptozotocin-Treated Diabetic Rats

    OpenAIRE

    Adewole, Stephen O; Caxton-Martins, Ezekiel A; Ojewole, John A O

    2006-01-01

    This study was undertaken to investigate the protective effects of quercetin (QCT) on the morphology of pancreatic β-cells against diabetes mellitus and oxidative stress experimentally-induced by streptozotocin (STZ) treatment in Wistar rats. Fifty male and female Wistar rats (200–250 g) were randomly divided into three experimental groups (i. e., control, STZ-treated, and STZ + Quercetin-treated groups). Diabetes was induced in the diabetic groups (B and C) of animals, by a single intraperit...

  15. Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation

    Science.gov (United States)

    2016-06-09

    Contiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Stage I Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma

  16. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells

    Science.gov (United States)

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-01-01

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  17. UV-treated graphene oxide as anode interfacial layers for P3HT : PCBM solar cells

    Science.gov (United States)

    Cheng, Cheng-En; Tsai, Cheng-Wei; Pei, Zingway; Lin, Tsung-Wu; Chang, Chen-Shiung; Shih-Sen Chien, Forest

    2015-06-01

    Solution-processable graphene oxide (GO) ultrathin films were introduced as anode interfacial layers (AILs) for polymer solar cells (PSCs). The photovoltaic performance of PSCs containing thermal- and UV-treated GO was comparable to that of PSCs with conventional poly(3,4-ethyledioxythiphene):poly(styrenesulfonate) AILs. UV treatment induced the surface activation of GO; an increase in the work function of UV-treated GO improved the energy band alignment at the GO/poly(3-hexylthiophene) interface, which accounted for the efficient hole collection and photovoltaic performance of PSCs with treated GO.

  18. UV-treated graphene oxide as anode interfacial layers for P3HT : PCBM solar cells

    International Nuclear Information System (INIS)

    Solution-processable graphene oxide (GO) ultrathin films were introduced as anode interfacial layers (AILs) for polymer solar cells (PSCs). The photovoltaic performance of PSCs containing thermal- and UV-treated GO was comparable to that of PSCs with conventional poly(3,4-ethyledioxythiphene):poly(styrenesulfonate) AILs. UV treatment induced the surface activation of GO; an increase in the work function of UV-treated GO improved the energy band alignment at the GO/poly(3-hexylthiophene) interface, which accounted for the efficient hole collection and photovoltaic performance of PSCs with treated GO. (paper)

  19. Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2016-05-10

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  20. Autologous bone marrow stromal cells are promising candidates for cell therapy approaches to treat bone degeneration in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Angélique Lebouvier

    2015-11-01

    SCD-ON patients have a higher frequency of BMSCs that retain their bone regeneration potential. Our findings suggest that BMSCs isolated from SCD-ON patients can be used clinically in cell therapy approaches. This work provides important preclinical data that is necessary for the clinical application of expanded BMSCs in advanced therapies and medical products.

  1. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    Science.gov (United States)

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  2. Data on cell viability of human lung fibroblasts treated with polyphenols-rich extract from Plinia trunciflora (O. Berg Kausel

    Directory of Open Access Journals (Sweden)

    Caroline Calloni

    2016-03-01

    Full Text Available Jaboticaba (Plinia trunciflora (O. Berg Kausel is a Brazilian native berry, which presents high levels of polyphenols. Here we provide data related to the effects of the polyphenols-rich extract from jaboticaba on the cell viability, mitochondrial complex I (nicotinamide adenine dinucleotide/CoQ oxidoreductase activity and ATP biosynthesis of human lung fibroblast cells (MRC-5 treated with amiodarone. The data presented in this article demonstrate that the polyphenols-rich extract from jaboticaba was able to reduce cell death as well as the decrease in complex I activity and ATP biosynthesis caused by amiodarone in MRC-5 cells.

  3. Improvement in direct methanol fuel cell performance by treating the anode at high anodic potential

    Science.gov (United States)

    Joghee, Prabhuram; Pylypenko, Svitlana; Wood, Kevin; Corpuz, April; Bender, Guido; Dinh, Huyen N.; O'Hayre, Ryan

    2014-01-01

    This work investigates the effect of a high anodic potential treatment protocol on the performance of a direct methanol fuel cell (DMFC). DMFC membrane electrode assemblies (MEAs) with PtRu/C (Hi-spec 5000) anode catalyst are subjected to anodic treatment (AT) at 0.8 V vs. DHE using potentiostatic method. Despite causing a slight decrease in the electrochemical surface area (ECSA) of the anode, associated with ruthenium dissolution, AT results in significant improvement in DMFC performance in the ohmic and mass transfer regions and increases the maximum power density by ∼15%. Furthermore, AT improves the long-term DMFC stability by reducing the degradation of the anode catalyst. From XPS investigation, it is hypothesized that the improved performance of AT-treated MEAs is related to an improved interface between the catalyst and Nafion ionomer. Among potential explanations, this improvement may be caused by incorporation of the ionomer within the secondary pores of PtRu/C agglomerates, which generates a percolating network of ionomer between PtRu/C agglomerates in the catalyst layer. Furthermore, the decreased concentration of hydrophobic CF2 groups may help to enhance the hydrophilicity of the catalyst layer, thereby increasing the accessibility of methanol and resulting in better performance in the high current density region.

  4. Application of microbial electrolysis cells to treat spent yeast from an alcoholic fermentation.

    Science.gov (United States)

    Sosa-Hernández, Ornella; Popat, Sudeep C; Parameswaran, Prathap; Alemán-Nava, Gibrán Sidney; Torres, César I; Buitrón, Germán; Parra-Saldívar, Roberto

    2016-01-01

    Spent yeast (SY), a major challenge for the brewing industry, was treated using a microbial electrolysis cell to recover energy. Concentrations of SY from bench alcoholic fermentation and ethanol were tested, ranging from 750 to 1500mgCOD/L and 0 to 2400mgCOD/L respectively. COD removal efficiency (RE), coulombic efficiency (CE), coulombic recovery (CR), hydrogen production and current density were evaluated. The best treatment condition was 750mgCOD/LSY+1200mgCOD/L ethanol giving higher COD RE, CE, CR (90±1%, 90±2% and 81±1% respectively), as compared with 1500mgCOD/LSY (76±2%, 63±7% and 48±4% respectively); ethanol addition was significantly favorable (p value=0.011), possibly due to electron availability and SY autolysis. 1500mgCOD/LSY+1200mgCOD/L ethanol achieved higher current density (222.0±31.3A/m(3)) and hydrogen production (2.18±0.66 [Formula: see text] ) but with lower efficiencies (87±2% COD RE, 71.0±.4% CE). Future work should focus on electron sinks, acclimation and optimizing SY breakdown. PMID:26512857

  5. Enhanced bioelectricity harvesting in microbial fuel cells treating food waste leachate produced from biohydrogen fermentation.

    Science.gov (United States)

    Choi, Jeongdong; Ahn, Youngho

    2015-05-01

    Microbial fuel cells (MFCs) treating the food waste leachate produced from biohydrogen fermentation were examined to enhance power generation and energy recovery. In batch mode, the maximum voltage production was 0.56 V and the power density reached 1540 mW/m(2). The maximum Coulombic efficiency (CEmax) and energy efficiency (EE) in the batch mode were calculated to be 88.8% and 18.8%, respectively. When the organic loading rate in sequencing batch mode varied from 0.75 to 6.2 g COD/L-d (under CEmax), the maximum power density reached 769.2 mW/m(2) in OLR of 3.1 g COD/L-d, whereas higher energy recovery (CE=52.6%, 0.346 Wh/g CODrem) was achieved at 1.51 g COD/L-d. The results demonstrate that readily biodegradable substrates in biohydrogen fermentation can be effectively used for the enhanced bioelectricity harvesting of MFCs and a MFC coupled with biohydrogen fermentation is of great benefit on higher electricity generation and energy efficiency. PMID:25723127

  6. Performance of anaerobic fluidized membrane bioreactors using effluents of microbial fuel cells treating domestic wastewater.

    Science.gov (United States)

    Kim, Kyoung-Yeol; Yang, Wulin; Ye, Yaoli; LaBarge, Nicole; Logan, Bruce E

    2016-05-01

    Anaerobic fluidized membrane bioreactors (AFMBRs) have been mainly developed as a post-treatment process to produce high quality effluent with very low energy consumption. The performance of an AFMBR was examined using the effluent from a microbial fuel cell (MFC) treating domestic wastewater, as a function of AFMBR hydraulic retention times (HRTs) and organic matter loading rates. The MFC-AFMBR achieved 89±3% removal of the chemical oxygen demand (COD), with an effluent of 36±6mg-COD/L over 112days operation. The AFMBR had very stable operation, with no significant changes in COD removal efficiencies, for HRTs ranging from 1.2 to 3.8h, although the effluent COD concentration increased with organic loading. Transmembrane pressure (TMP) was low, and could be maintained below 0.12bar through solids removal. This study proved that the AFMBR could be operated with a short HRT but a low COD loading rate was required to achieve low effluent COD. PMID:26921870

  7. Unattached kinetochores rather than intrakinetochore tension arrest mitosis in taxol-treated cells.

    Science.gov (United States)

    Magidson, Valentin; He, Jie; Ault, Jeffrey G; O'Connell, Christopher B; Yang, Nachen; Tikhonenko, Irina; McEwen, Bruce F; Sui, Haixin; Khodjakov, Alexey

    2016-02-01

    Kinetochores attach chromosomes to the spindle microtubules and signal the spindle assembly checkpoint to delay mitotic exit until all chromosomes are attached. Light microscopy approaches aimed to indirectly determine distances between various proteins within the kinetochore (termed Delta) suggest that kinetochores become stretched by spindle forces and compact elastically when the force is suppressed. Low Delta is believed to arrest mitotic progression in taxol-treated cells. However, the structural basis of Delta remains unknown. By integrating same-kinetochore light microscopy and electron microscopy, we demonstrate that the value of Delta is affected by the variability in the shape and size of outer kinetochore domains. The outer kinetochore compacts when spindle forces are maximal during metaphase. When the forces are weakened by taxol treatment, the outer kinetochore expands radially and some kinetochores completely lose microtubule attachment, a condition known to arrest mitotic progression. These observations offer an alternative interpretation of intrakinetochore tension and question whether Delta plays a direct role in the control of mitotic progression. PMID:26833787

  8. Unattached kinetochores rather than intrakinetochore tension arrest mitosis in taxol-treated cells

    Science.gov (United States)

    Magidson, Valentin; He, Jie; Ault, Jeffrey G.; O’Connell, Christopher B.; Yang, Nachen; Tikhonenko, Irina; McEwen, Bruce F.

    2016-01-01

    Kinetochores attach chromosomes to the spindle microtubules and signal the spindle assembly checkpoint to delay mitotic exit until all chromosomes are attached. Light microscopy approaches aimed to indirectly determine distances between various proteins within the kinetochore (termed Delta) suggest that kinetochores become stretched by spindle forces and compact elastically when the force is suppressed. Low Delta is believed to arrest mitotic progression in taxol-treated cells. However, the structural basis of Delta remains unknown. By integrating same-kinetochore light microscopy and electron microscopy, we demonstrate that the value of Delta is affected by the variability in the shape and size of outer kinetochore domains. The outer kinetochore compacts when spindle forces are maximal during metaphase. When the forces are weakened by taxol treatment, the outer kinetochore expands radially and some kinetochores completely lose microtubule attachment, a condition known to arrest mitotic progression. These observations offer an alternative interpretation of intrakinetochore tension and question whether Delta plays a direct role in the control of mitotic progression. PMID:26833787

  9. Prognostic factors in invasive squamous cell carcinoma of the vulva treated with surgery and irradiation

    International Nuclear Information System (INIS)

    From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Postoperative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2-4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (G1/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery. (orig.)

  10. Prognostic factors in invasive squamous cell carcinoma of the vulva treated with surgery and irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Malmstroem, H.; Janson, H.; Simonsen, E.; Stenson, S.; Stendahl, U. (Linkoeping Univ. Hospital (Sweden). Dept. of Gynaecological Oncology Uppsala Univ. Hospital (Sweden). Dept. of Gynaecological Oncology Umeaa Univ. Hospital (Sweden). Dept. of Gynaecological Oncology Uppsala Univ. Hospital (Sweden). Dept. of Radiophysics)

    1990-01-01

    From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Postoperative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2-4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (G1/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery. (orig.).

  11. Gene expression analysis in MCF-7 breast cancer cells treated with recombinant bromelain.

    Science.gov (United States)

    Fouz, Nour; Amid, Azura; Hashim, Yumi Zuhanis Has-Yun

    2014-08-01

    The contributing molecular pathways underlying the pathogenesis of breast cancer need to be better characterized. The principle of our study was to better understand the genetic mechanism of oncogenesis for human breast cancer and to discover new possible tumor markers for use in clinical practice. We used complimentary DNA (cDNA) microarrays to compare gene expression profiles of treated Michigan Cancer Foundation-7 (MCF-7) with recombinant bromelain and untreated MCF-7. SpringGene analysis was carried out of differential expression followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We identified 1,102 known genes differentially expressed to a significant degree (pbromelain produces a unique signature affecting different pathways, specific for each congener. The microarray results give a molecular mechanistic insight and functional effects, following recombinant bromelain treatment. The extent of changes in genes is related to and involved significantly in gap junction signaling, amyloid processing, cell cycle regulation by BTG family proteins, and breast cancer regulation by stathmin1 that play major roles. PMID:24928548

  12. Exploring cell apoptosis and senescence to understand and treat cancer: an interview with Scott Lowe

    Directory of Open Access Journals (Sweden)

    2015-11-01

    Full Text Available Scott W. Lowe is currently principal investigator at the Memorial Sloan-Kettering Cancer Center. After beginning his studies in chemical engineering, he decided to take another path and became fascinated by biochemistry, genetics and molecular biology, which ultimately led to an interest in human disease, particularly cancer. During his PhD at the Massachusetts Institute of Technology (MIT, Scott had the opportunity to benefit from the exceptional mentorship of Earl Ruley, David Housman and Tyler Jacks, and contributed to elucidating how the p53 (TP53 tumor suppressor gene limits oncogenic transformation and modulates the cytotoxic response to conventional chemotherapy. This important work earned him a fellowship from the Cold Spring Harbor Laboratory, which helped to launch his independent career. Scott is now a leading scientist in the cancer field and his work has helped to shed light on mechanisms of cell apoptosis and senescence to better understand and treat cancer. In this interview, he talks about this incredible scientific journey.

  13. Blastic plasmacytoid dendritic cell neoplasm: the first report of two cases treated by 5-azacytidine.

    Science.gov (United States)

    Laribi, Kamel; Denizon, Nathalie; Ghnaya, Habib; Atlassi, Mustapha; Besançon, Anne; Pineau-Vincent, Fabienne; Gaulard, Philippe; Petrella, Tony

    2014-07-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy which was first included as an independent cutaneous lymphoma in the 2008 World Health Organisation (WHO) classification (1). BPDCN usually has an extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and who were treated for the first time with 5-azacytidine (5-Aza); a drug approved by the Food and Drug Administration (FDA) and mainly used in the treatment of myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604-8). The first case was an 81-year-old man who presented with unusual CD10+, CD56- immunohistochemistry and 45X, -Y abnormality using fluorescent in situ hybridization (FISH) analysis. The second case was a 78-year-old woman who manifested monosomy 13 and chromosome instability due to D13S319 locus deletion in 13q14 as determined by FISH. Both patients showed excellent responses of their skin lesions after one cycle of chemotherapy, and their hematological disease was stabilized; however, pulmonary sepsis set in, followed by neutropenia after the fourth and the fifth cycle of treatment, that is, eight and 9 months postdiagnosis, respectively, leading to patient death. PMID:24571716

  14. Local failure in patients treated with radiotherapy and multidrug chemotherapy for small cell lung cancer

    International Nuclear Information System (INIS)

    Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumor. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than ±5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases. (orig.)

  15. Single-Center Study of 83 Horses with Suspensory Injuries Treated with Adipose-Derived Stem and Regenerative Cells

    OpenAIRE

    F. Ross Rich

    2014-01-01

    Adipose-derived stem and regenerative cells (ADRCs), concentrated from autologous fat tissue, have the ability to differentiate into various specific cell types including tenocytes. In this retrospective study, clinical data are presented from 83 horses with 176 suspensory ligament injuries, treated with ADRCs, given a strictly enforced standardized rehabilitation program, and followed up for at least one year after returning to work. Assessment for a successful outcome...

  16. The VZV/IE63-specific T cell response prevents herpes zoster in fingolimod-treated patients

    Science.gov (United States)

    Mathias, Amandine; Perriard, Guillaume; Canales, Mathieu; Vuilleumier, Fanny; Perrotta, Gaetano; Schluep, Myriam

    2016-01-01

    Objective: To assess longitudinally the antiviral immune response of T cells from patients with multiple sclerosis (MS) treated with fingolimod (FTY) vs other disease-modifying treatments (DMTs). Methods: We assessed cellular immune responses specific to influenza virus (FLU), JC virus (JCV), and varicella-zoster virus (VZV) using quantification of interferon-γ secretion by enzyme-linked immunospot in patients with MS on FTY (n = 31), including 2 with herpes zoster (HZ), natalizumab (n = 11), and other DMTs (n = 11). We used viral lysates for FLU and VZV and a pool of peptides for FLU, JCV (VP-1), and VZV (IE63). Results: Besides an expected drop of T cells, we found that, proportionally to the number of CD3+ T cells, only FTY-treated patients with MS exhibited an increased VZV/IE63-specific T cell response peaking 6 months into treatment, a response that returned to baseline after 12 and 24 months. Two FTY-treated patients developed an HZ 6 months into treatment, coinciding with an absent VZV/IE63-specific T cell response. However, cellular immune responses specific to VZV lysate, JCV, and FLU (lysate and pool of peptide epitopes) were similar between all 3 categories (FTY, natalizumab, and other DMTs) of study patients. Conclusions: FTY-treated patients with MS exhibit an increased VZV/IE63-specific cellular immune response after 6 months of treatment. FTY-treated patients who develop an HZ are not able to mount such a response, suggesting that a T cell response directed against this viral protein may be key in preventing the occurrence of HZ. PMID:26913291

  17. Pre dye treated titanium dioxide nanoparticles synthesized by modified sol-gel method for efficient dye-sensitized solar cells

    Science.gov (United States)

    Ananth, S.; Vivek, P.; Arumanayagam, T.; Murugakoothan, P.

    2015-06-01

    Pure and pre dye treated titanium dioxide nanoparticles were prepared by sol-gel and modified sol-gel methods, respectively. The pre dye treatment has improved the properties of TiO2, such as uniform dye adsorption, reduced agglomeration, improved morphology and less dye aggregation. The brazilein pigment-rich Caesalpinia sappan heartwood extract was used as natural dye sensitizer for pure and pre dye treated TiO2 nanoparticles. Low cost and environment friendly dye-sensitized solar cells (DSSC) fabricated using pure and pre dye treated TiO2 nanoparticles sensitized by natural dye showed solar light to electron conversion efficiencies of 1.09 and 1.65 %, respectively. The pre dye treated TiO2-based DSSC showed 51 % improvement in efficiency when compared to that of conventionally prepared DSSC.

  18. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  19. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    International Nuclear Information System (INIS)

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H2O2, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H2O2. Furthermore, both arsenic and H2O2 were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As3+) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As3+-induced EZH2 phosphorylation. • As3+ induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm

  20. Electrochemical characterisation of aluminium AA7075-T6 and solution heat treated AA7075 using a micro-capillary cell

    International Nuclear Information System (INIS)

    Localised corrosion of 7xxx aluminium alloys initiates at cathodic intermetallics containing Cu and Fe due to a strong galvanic coupling with the matrix. In order to study this galvanic coupling, the electrochemical behaviour of AA7075-T6 and solution heat treated AA7075 has been investigated by means of complementary techniques: micro-capillary cell, scanning Kelvin probe force microscopy (SKPFM) and scanning electron microscopy (SEM). Characterisation with the micro-capillary cell showed that the intermetallics cause a more cathodic breakdown potential in the solution heat treated AA7075 compared with the AA7075-T6. This is associated with a higher Volta potential difference between the intermetallics and the matrix in the solution heat treated AA7075, indicating a stronger galvanic coupling for this temper. From these results, it is concluded that the breakdown potential of areas containing the intermetallics is related to the Volta potential difference between the intermetallics and the matrix

  1. GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells.

    Science.gov (United States)

    Vaziri-Gohar, Ali; Houston, Kevin D

    2016-02-15

    Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie. IGFBPs). A significant increase in IGFBP-1 mRNA and extracellular IGFBP-1 protein was observed in 4-OHT-treated MCF-7 cells. Knockdown experiments demonstrated that both GPER1 and CREB mediate IGFBP-1 induction. Furthermore, experiments showed that 4-OHT-dependent IGFBP-1 transcription is downstream of GPER1-activation in breast cancer cells. Additionally, neutralization and knockdown experiments demonstrated a role for IGFBP-1 in the observed inhibition of IGF-1 signaling. These results suggested that 4-OHT inhibits IGF-1 signaling via GPER1 and CREB mediated extracellular IGFBP-1 accumulation in breast cancer cells. PMID:26690777

  2. Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

    Science.gov (United States)

    2016-06-15

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  3. Transcriptome and proteome analysis of tyrosine kinase inhibitor treated canine mast cell tumour cells identifies potentially kit signaling-dependent genes

    Directory of Open Access Journals (Sweden)

    Klopfleisch Robert

    2012-06-01

    Full Text Available Abstract Background Canine mast cell tumour proliferation depends to a large extent on the activity of KIT, a tyrosine kinase receptor. Inhibitors of the KIT tyrosine kinase have recently been introduced and successfully applied as a therapeutic agent for this tumour type. However, little is known on the downstream target genes of this signaling pathway and molecular changes after inhibition. Results Transcriptome analysis of the canine mast cell tumour cell line C2 treated for up to 72 hours with the tyrosine kinase inhibitor masitinib identified significant changes in the expression levels of approximately 3500 genes or 16% of the canine genome. Approximately 40% of these genes had increased mRNA expression levels including genes associated with the pro-proliferative pathways of B- and T-cell receptors, chemokine receptors, steroid hormone receptors and EPO-, RAS and MAP kinase signaling. Proteome analysis of C2 cells treated for 72 hours identified 24 proteins with changed expression levels, most of which being involved in gene transcription, e.g. EIA3, EIA4, TARDBP, protein folding, e.g. HSP90, UCHL3, PDIA3 and protection from oxidative stress, GSTT3, SELENBP1. Conclusions Transcriptome and proteome analysis of neoplastic canine mast cells treated with masitinib confirmed the strong important and complex role of KIT in these cells. Approximately 16% of the total canine genome and thus the majority of the active genes were significantly transcriptionally regulated. Most of these changes were associated with reduced proliferation and metabolism of treated cells. Interestingly, several pro-proliferative pathways were up-regulated, which may represent attempts of masitinib treated cells to activate alternative pro-proliferative pathways. These pathways may contain hypothetical targets for a combination therapy with masitinib to further improve its therapeutic effect.

  4. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    Science.gov (United States)

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  5. [Studies on changes in nucleolar organizer region of human promyelocytic leukemia cells (HL-60) treated with retinoic acid].

    Science.gov (United States)

    Xie, R L; Wang, Y Q

    1989-12-01

    Changes of nucleolar organizer region in HL-60 cells after treated with retinoic acid (RA) were studied with techniques of silver-staining nucleolar organizer region (Ag-NOR) in metaphase karyotypes, Brachet's reaction and with our improved TEM techniques for studying silver-stained active nucleolar organizer region (Ag-aNOR) in interphase nucleoli. Number of Ag-NOR in HL-60 cells is 4.5/cell on average. The Ag-NOR number of cells treated with RA showed no remarkable difference from that of control group. Ag-aNOR number treated with RA was reduced obviously as compared with that of control group. Meanwhile, the changes of nucleolus number showed by Brachet's reaction were in accordance with those of Ag-aNOR. Therefore, it may be concluded: (1). Though the number of active rRNA genes did not changed after the differentiation of HL-60 cells induced by RA, their expression was clearly inhibited: (2). The relationship between the changes of Brachet-No and Ag-aNOR is in positive correlation (r = 0.98, p less than 0.01). EM examination of Ag-aNOR of HL-60 cells reveals that Ag-protein (RNA polymerase I) only presented in fibrillar centers (FC) and the dense fibrillar components (DFC) of nucleolus. In addition, in control group, large amount of Ag-protein, FC, DFC and granular components (GC) were observed, and there were many large nucleoli in a nucleus, meanwhile, the cells of the treated group tended to be mature, with a decrease in the amount of Ag-protein, FC, DFC and GC accordingly, and the nucleoli reduced both in size and number significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2626898

  6. Novel method to reduce fishy aftertaste in wine and seafood pairing using alcohol-treated yeast cells.

    Science.gov (United States)

    Tsuji, Toshikazu; Kanai, Keiko; Yokoyama, Aki; Tamura, Takayuki; Hanamure, Kenichi; Sasaki, Kanako; Takata, Ryoji; Yoshida, Satoshi

    2012-06-20

    "Fishy aftertaste" is sometimes perceived in wine consumed with seafood. Iron in wine has been reported to be a key compound that produces fishy aftertaste. However, cost-effective methods to remove iron from wine have not been developed. Here, we describe a cost-effective and safe iron adsorbent consisting of alcohol-treated yeast (ATY) cells based on the observation that nonviable cells adsorbed iron after completion of fermentation. Treatment of cells with more than 40% (v/v) ethanol killed them without compromising their ability to adsorb iron. Drying the ATY cells did not reduce iron adsorption. Use of ATY cells together with phytic acid had a synergistic effect on iron removal. We term this means of removing iron the "ATY-PA" method. Sensory analysis indicated that fishy aftertaste in wine-seafood pairings was not perceived if the wine had been pretreated with both ATY cells and phytic acid. PMID:22630330

  7. Improved performance of microbial fuel cells enriched with natural microbial inocula and treated by electrical current

    International Nuclear Information System (INIS)

    Microbial fuel cells (MFCs) are increasingly attracting attention as a sustainable technology as they convert chemical energy in organic wastes to electricity. In this study, the effects of different inoculum sources (river sediment, activated sludge and anaerobic sludge) and electrical current stimulation were evaluated using single-chamber air-cathode MFCs as model reactors based on performance in enrichment process and electrochemical characteristics of the reactors. The result revealed the rapid anodic biofilm development and substrate utilization of the anaerobic sludge-inoculated MFC. It was also found that the river sediment-inoculated MFC achieved the highest power output of 195 μW, or 98 mW m−2, due to better developed anodic biofilm confirmed by scanning electron microscopy. The current stimulation enhanced the anodic biofilm attachment over time, and therefore reduced the MFC internal resistance by 27%, increased the electrical capacitance by four folds, and improved the anodic biofilm resilience against substrate deprivation. For mature MFCs, a transient application of a negative voltage (−3 V) improved the cathode activity and maximum power output by 37%. This improvement was due to the bactericidal effect of the electrode potential higher than +1.5 V vs. SHE, demonstrating a substantial benefit of treating MFC cathode after long-term operation using suitable direct electrical current. -- Highlights: •Voltage stimulation (+2 V) during inoculation reduced MFC internal resistance and improved biofilm resilience. •Voltage stimulation increased biofilm electrical capacitance by 5-fold. •Negative voltage stimulation (−3 V) enhanced the maximum power output by 37%. •River sediment MFC obtained higher power due to better anodic biofilm coverage. •Anaerobic sludge quickly developed anodic biofilm for MFC and quickly utilized volatile fatty acids

  8. Preliminary evaluation of a microbial fuel cell treating artificial dialysis wastewater using graphene oxide

    Science.gov (United States)

    Goto, Yuko; Yoshida, Naoko

    2016-02-01

    Artificial dialysis wastewater (ADWW) generally contains 800-2,200 mg L-1 of organic matter. Prior to its discharge to the sewage system, ADWW must be treated in order to reduce organic matter to less than 600 mg L-1. This study assesses the applicability of a microbial fuel cell (MFC) to the reduction of organic matter in ADWW as an alternative pre-treatment system to aeration. In the MFC, conductive floccular aggregates microbially produced from graphene oxide (GO-flocs) were applied as an anode material in the MFC. The GO-flocs were obtained by anaerobic incubation of graphene oxide (GO) with microorganisms in ADWW at 28 °C for a minimum of 10 days. During incubation, GO in the mixture was transformed into black conductive floccular aggregates having 0.12 mS cm-1, suggesting the microbial reduction of GO to the reduced form. The produced GO-flocs were then used as the anode material in a cylindrical MFC, which was filled with ADWW and covered with a floating, platinum (Pt)-coated carbon cathode. The MFC was polarized via an external resistance of 10 Ω and applied for 120 days by replacing half of the supernatant of the MFC with fresh ADWW, every 6-9 days. As a result, the MFC achieved a 128 mg L-1 d-1 chemical oxygen demand (CODCr) removal rate. For example, the MFC contained 1,500 mg-CODCr L-1 just after replacement, with this concentration being reduced to 1,000 mg-CODCr L-1 after 6-9 days of incubation. At the same time, the MFC showed an average power density of 28 mW m-2 and a maximum power density of 291 mW m-2. These results suggest that a MFC packed with GO-flocs can be used as an alternative biotreatment system, replacing the energy-intensive aeration process.

  9. Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    Science.gov (United States)

    2016-09-01

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  10. FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-small Cell Lung Cancer

    Science.gov (United States)

    2013-08-14

    Extensive Stage Small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

  11. Synthesis and Characterization of Inhalable Flavonoid Nanoparticle for Lung Cancer Cell Targeting.

    Science.gov (United States)

    Lee, Wing-Hin; Loo, Ching-Yee; Ong, Hui-Xin; Traini, Daniela; Young, Paul M; Rohanizadeh, Ramin

    2016-02-01

    Current cancer treatments are not adequate to cure cancer disease, as most chemotherapeutic drugs do not differentiate between cancerous and non-cancerous cells; which lead to systemic toxicity and adverse effects. We have developed a promising approach to deliver a potential anti-cancer compound (curcumin) for lung cancer treatment through pulmonary delivery. Three different sizes of curcumin micellar nanoparticles (Cur-NPs) were fabricated and their cytotoxicity effects (proliferation, apoptosis, cell cycle progression) were evaluated against non-small-cell lung cancer, human lung carcinoma (A549) and human lung adenocarcinoma (Calu-3). The in vitro cytotoxicity assay showed that Cur-NPs were more effective to kill lung cancer cells compared to DMSO-solubilised raw curcumin. The potency of the anti-cancer killing activities was size-dependent. Both raw curcumin and Cur-NPs were not toxic to healthy lung cells (BEAS-2B). Smaller Cur-NPs accumulated within nucleus, membrane and cytoplasm. Cur-NPs also induced apoptosis and caused G2/M arrest in both A549 and Calu-3 cell lines. Compared to raw curcumin, Cur-NPs were more effective in suppressing the expression of the inflammatory marker, Interleukin-8 (IL8). The aerosol performance of Cur-NPs was characterized using the next generation impactor (NGI). All Cur-NPs showed promising aerosolization property with mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranging between 4.8-5.2 and 2.0-2.1, respectively. This study suggests that inhaled curcumin nanoparticles could potentially be used for lung cancer treatment with minimal side effects. PMID:27305771

  12. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    International Nuclear Information System (INIS)

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in ≥50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1α). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  13. Mild hypothermia combined with a scaffold of NgR-silenced neural stem cells/Schwann cells to treat spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Jinhua Liang; Jianjun Zhang; Shuhong Liu; Wenwen Sun

    2014-01-01

    Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differenti-ation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previ-ous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells+PLGA group, hindlimb motor function and nerve electrophysiological function were clearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve ifbers were increased in the group treated with the NgR-silenced cell scaffold+mild hypothermia at 34°C for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviv-ing cells and nerve ifbers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.

  14. Increased blastocyst formation of cloned porcine embryos produced with donor cells pre-treated with digitonin and Xenopus egg extract

    DEFF Research Database (Denmark)

    Liu, Ying; Østrup, Olga; Li, Juan;

    2011-01-01

    Pre-treating donor cells before somatic cell nuclear transfer (SCNT, ‘cloning’) may improve the efficiency of the technology. The aim of this study was to evaluate the early development of cloned embryos produced with porcine fibroblasts pre-treated with a permeabilizing agent and extract from...... Xenopus laevis eggs. In Experiment 1, fetal fibroblasts were permeabilized by digitonin, incubated in egg extract and, after re-sealing of cell membranes, cultured for 3 or 5 days before use as donor cells in handmade cloning (HMC). Controls were produced by HMC with non-treated donor cells. The...... blastocyst rate for reconstructed embryos increased significantly when digitonin-permeabilized, extract-treated cells were used after 5 days of culture after re-sealing. In Experiment 2, fetal and adult fibroblasts were treated with digitonin alone before re-sealing the cell membranes, then cultured for 3 or...

  15. Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck

    Science.gov (United States)

    2015-12-14

    Head and Neck Cancer; Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  16. High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

    Science.gov (United States)

    2013-03-06

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Retinoblastoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  17. 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

  18. Electrical determination of viability in saline-treated mouse myeloma cells.

    OpenAIRE

    Matsushita, T.; Brendzel, A M; Shotola, M A; Groh, K R

    1982-01-01

    Suspension of mouse myeloma cells in phosphate buffered saline (PBS) induced a significant amount of cell death. The lethal effects of PBS include an increase in cell lysis, a decreased ability of cells to exclude trypan blue, and a decrease in the colony-forming ability of these cells. Dead cells were also detected on a Coulter counter by the increase in the fraction of cells with a smaller electrical size distribution (ESD). Comparing mixtures of live and dead cells by ESD and trypan-blue e...

  19. Lymphocyte Infusion in Treating Patients With Relapsed Cancer After Bone Marrow or Peripheral Stem Cell Transplantation

    Science.gov (United States)

    2011-11-28

    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

  20. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    Science.gov (United States)

    Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.

    2013-05-01

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.

  1. Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid

    International Nuclear Information System (INIS)

    Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm−2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal–Wallis and Mann–Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions. (paper)

  2. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2014-05-09

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  3. Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture.

    Directory of Open Access Journals (Sweden)

    Ramazan Kurt

    Full Text Available Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α-based combination therapy in chronic hepatitis C virus (HCV infection. Previously, we reported that free fatty acid (FFA-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1, which is why the antiviral activity of IFN-α against HCV is impaired.To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment.HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α and Type III IFN (IFN-λ was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA in the FFA-treated HCV cell culture model was investigated.FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ, which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture

  4. Culture conditions affecting the survival response of Chinese hamster ovary cells treated by hyperthermia

    International Nuclear Information System (INIS)

    Using lethally irradiated feeder cells to control cell population densities, researchers investigated the survival of Chinese hamster ovary cells heated between 42.2 and 45.5 degrees C. Test cells were plated into T25 flasks with or without feeder cells, incubated 2 hours at 37 degrees C, and then given various heat treatments. Under all heating conditions, survival increased in those flasks containing feeder cells. Increased survival (by as much as a factor of 100 for cells heated at 42.4 degrees C for 6-10 hr) was most apparent when cells were heated to thermotolerance. By adjustment of test and feeder cell numbers, survival increased as density increased; however, maximum survival followed a transition period that occurred between the plating of 1 X 10(4) and 6 X 10(4) cells. Experimental artifacts due to improper control of cell density was demonstrated

  5. Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy

    OpenAIRE

    Liao, Bin-Chi; Lin, Chia-Chi; Shih, Jin-Yuan; Yang, James Chih-Hsin

    2015-01-01

    Rearrangements in anaplastic lymphoma kinase (ALK) gene and echinoderm microtubule-associated protein-like 4 (EML4) gene were first described in a small portion of patients with non-small cell lung cancer (NSCLC) in 2007. Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4–ALK rearrangement. Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC ...

  6. Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Yi; Brink, Carsten; Knap, Marianne;

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...... radiotherapy (IMRT) and concomitant chemotherapy (CCT). METHODS: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common...

  7. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    Science.gov (United States)

    2015-12-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  8. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    Science.gov (United States)

    2016-05-02

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  9. Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    Science.gov (United States)

    2016-04-11

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non

  10. Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

    Science.gov (United States)

    2016-06-08

    HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  11. Mesenchymal stromal cells from bone marrow treated with bovine tendon extract acquire the phenotype of mature tenocytes☆

    Science.gov (United States)

    Augusto, Lívia Maria Mendonça; Aguiar, Diego Pinheiro; Bonfim, Danielle Cabral; dos Santos Cavalcanti, Amanda; Casado, Priscila Ladeira; Duarte, Maria Eugênia Leite

    2016-01-01

    Objective This study evaluated in vitro differentiation of mesenchymal stromal cells isolated from bone marrow, in tenocytes after treatment with bovine tendon extract. Methods Bovine tendons were used for preparation of the extract and were stored at −80 °C. Mesenchymal stromal cells from the bone marrow of three donors were used for cytotoxicity tests by means of MTT and cell differentiation by means of qPCR. Results The data showed that mesenchymal stromal cells from bone marrow treated for up to 21 days in the presence of bovine tendon extract diluted at diminishing concentrations (1:10, 1:50 and 1:250) promoted activation of biglycan, collagen type I and fibromodulin expression. Conclusion Our results show that bovine tendon extract is capable of promoting differentiation of bone marrow stromal cells in tenocytes. PMID:26962503

  12. Stem cells derived from testis show promise for treating a wide variety of medical conditions

    Institute of Scientific and Technical Information of China (English)

    Karim Nayernia

    2007-01-01

    @@ The continuation of the spermatogenic process throughout life relies on a proper regulation of self-renewal and differentiation of germline testis stem cells,the spermatogonial stem cells.These are single cells situated on the basal membrane of the seminiferous epithelium.Only 0.03%of all germ cells are spermatogonial stem cells(SSCs)[1-3].To maintain spermatogenesis,the processes of self-renewal and differentiation of SSCS must be precisely regulated by intrinsic gene expression in the stem cells and extrinsic signals,including soluble factors or adhesion molecules from the surrounding microenvironment,the stem cell niche.

  13. Therapeutic Potential of Adipose-Derived SSEA-3-Positive Muse Cells for Treating Diabetic Skin Ulcers

    OpenAIRE

    Kinoshita, Kahori; Kuno, Shinichiro; Ishimine, Hisako; Aoi, Noriyuki; Mineda, Kazuhide; Kato, Harunosuke; Doi, Kentaro; Kanayama, Koji; Feng, Jingwei; Mashiko, Takanobu; Kurisaki, Akira; Yoshimura, Kotaro

    2015-01-01

    Refractory skin ulcers were generated in severe combined immunodeficiency (SCID) mice with type 1 diabetes and delayed wound healing compared with nondiabetic SCID mice. Treatment with a multilineage differentiating stress-enduring (Muse)-rich cell population significantly accelerated wound healing compared with the Muse-poor cell population, and these cells be achieved in large amounts with minimal morbidity. Adipose-derived Muse cells could be a practical tool for a variety of stem cell-dep...

  14. Vanilloid receptor activation by 2- and 10-μm particles induces responses leading to apoptosis in human airway epithelial cells

    International Nuclear Information System (INIS)

    Exposure to airborne particulate matter (PM) is associated with increased mortality and morbidity. It has been previously shown that PMs and synthetic particles (PC10 and PC2) that have similar characteristics to PMs induced depolarizing currents and increases in intracellular calcium ([Ca2+]i) in capsaicin- and acid-sensitive sensory neurons and in TRPV1-expressing HEK 293 cells. To determine whether such mechanisms also underlie PM-induced toxicity in epithelial cells lining the human airways, we tested the responses of PCs on BEAS-2B (immortalized human bronchial epithelial cells), NHBE (normal human bronchial/tracheal epithelial cells), and SAEC (normal human small airway epithelial cells from the distal airways). RT-PCR revealed that all these cell types expressed TRPV1 (VR1), ASIC1a, and ASIC3 subunits of proton-gated ion channels. Calcium imaging studies revealed that in all three cell types ∼30% were activated by both capsaicin and acid. In these cells, PCs induced an increase in [Ca2+]i that was inhibited by capsazepine, a TRPV1 antagonist, and/or by amiloride, an ASIC antagonist. The capsazepine-sensitive contribution to PC-induced increases in [Ca2+]i was ∼70%. Measurements of apoptosis revealed that exposure to PCs induced a time-dependent increase in the number of apoptotic cells. After incubation for 24 (PC10) or 48 h (PC2) ∼60% of these cells were apoptotic. Pretreatment with capsazepine as well as removal of external calcium completely (∼100%) prevented PC-induced apoptosis. These data suggest that pharmacological inhibition of calcium-permeable vanilloid receptors could be used to prevent some of the pathological actions of PMs

  15. Physical, Thermal, and Spectroscopic Characterization of Biofield Energy Treated Murashige and Skoog Plant Cell Culture Media

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    The Murashige and Skoog medium (MS media) is a chemically defined and widely used as a growth medium for plant tissue culture techniques. The present study was attempted to evaluate the impact of biofield energy treatment on the physical, thermal, and spectral properties of MS media. The study was performed in two groups; one was kept as control while another was subjected to Mr. Trivedi’s biofield energy treatment and coded as treated group. Afterward, both the control and treated samp...

  16. Increased cell viability and proliferation in post-hypoxic hippocampal tissue culture treated with Acalypha indica root extract

    Directory of Open Access Journals (Sweden)

    Sophie Yolanda

    2011-05-01

    Full Text Available Background: This research was done to study the influence of Acalypha indica Linn root extract towards relative cell viability and proliferation as parameters of neurogenesis in post-hypoxic hippocampal tissue culture.Methods: Experimental in vitro study using 24 primary neuronal cell cultures obtained from adult Sprague Dawley rat exposed to hypoxia with 5% O2/5% CO2/N2 balance gas for 24 hours. Post-hypoxia, Acalypha indica Linn root extract was added at doses of 10, 15, and 20 mg/mL to 3 treatment groups. No treatment was given to the control group. Each group consists of 6 samples. After 90 hours of incubation, relative cell viability was measured by using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT examination, and cell proliferation was measured by using 5-bromo2’-deoxy-uridine (BrdU for cell proliferation. Data was analyzed using one way ANOVA parametric tests, then further analyzed with post-hoc analysis.Results: The relative cell viability of rat hippocampal tissue culture treated with Acalypha indica Linn root extract with dose of 10, 15, and 20 mg/mL was significantly higher than control (176.95%, 220.62%, and 386.02% vs. 100%. Cell proliferation of rat hippocampal tissue culture treated with Acalypha indica Linn root extract with dose of 10, 15, and 20 mg/mL was significantly higher than control (0.132, 0.117, 0.114 vs 0.096.Conclusion: Acalypha indica Linn root extract with doses of 10, 15, and 20 mg/mL can increase relative cell viability and proliferation in post-hypoxic hippocampal tissue culture. (Med J Indones 2011; 20:94-9Keywords: Acalypha indica Linn (akar kucing, cell proliferation, hypoxia, neurogenesis, relative cell viability

  17. [Modified Mechanism of Cell Walls from Chinese Fir Treated with Low-Molecular-Weight Phenol Formaldehyde Resin].

    Science.gov (United States)

    Huang, Yan-hui; Fei, Ben-hua; Zhao, Rong-jun

    2015-12-01

    Study on the modified mechanism of wood cell walls, it is very important for improving treatment reagents, optimizing treatment technology, and enhancing wood density, mechanical properties, dimensional stability, and so on. Samples of plantation Chinese fir were treated gradually with synthesized water-soluble low-molecular-weight phenol formaldehyde (PF) resins under vacuum and pressure. The correlated physical and chemical properties of the treated and untreated reference samples were determined by X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FTIR), and nuclear magnetic resonance spectrometer(NMR) (Using method of Cross Polarization/Magic Angle Spinning for continuous testing) with high precision and resolution. The results showed that, after treated with water-soluble low-molecular-weight PF resin, the average values of crystallinity from the treated samples were decreased obviously, and the average reduction rate was 12.67%, 11.91% and 6.26%, respectively. Comparing water-soluble, low-molecular-weight PF resin modified Chinese fir with untreated reference samples, no new chemical shifts and characteristic peaks of functional groups from esters, ethers, etc. were present by using FTIR and ¹³C NMR spectrum. It was considered that there was no distinct chemical reaction between the water-soluble low-molecular-weight PF resin and Chinese Fir cell walls. But water-soluble low-molecular-weight PF resin could enter into the structure relatively loose, large size spaces, relatively area large amorphous regions in cell walls of Chinese fir tracheids, and form physical filling, which resulting in the decreasing of relative crystallinity. This study has important reference value for the development of new wood modification reagents and the optimization of wood modification process. The findings also provide important theoretical foundation for further proving the modification mechanisms of wood cell walls and enriching the modified theories of

  18. Squamous cell carcinoma of the floor of the mouth treated by radiotherapy

    International Nuclear Information System (INIS)

    Retrospective analysis was made of 110 cases of squamous cell carcinoma of the floor of the mouth. Age of the cases ranged from 34 to 86, with the mean value of 59.9 years. There was high sex preponderance to male(male: 93, female:17). Habitual heavy intake of alcohol and tobacco was also detected. Five- and 10-year survival rates according to Stages were; Stage I: 69%, 38%, Stage II: 40%, 20%, Stages III-IV: 33%, 15%, respectively. Local control rates by radiotherapy were; T1:80%, T2:56%, T3:17%. Small lesion tends to be localized to the floor of the mouth and was successfully controlled by implant without complication. As the size of the tumor increases, lesion tends to infiltrate into the ventral side of the mobile tongue, alveolar ridge of mandible as well as muscle of the floor and mandibular body. External radiotherapy of 3,000 cGy/3 weeks with concomitant i.v. injection of 90 mg of Bleomycin yielded remarkable reduction of mass size in most cases with T2, and complete disappearance of the tumor after sufficient period of follow-up in 21% of the cases treated. Among the complications attributable to radiotherapy, osteoradionecrosis was most common and serious and appeared in 13 out of 29 cases withou local recurrence after radiotherapy. Incidence of complications was higher in cases with linear-arrayed sources than with seed sources, higher in combined external and interstitial radiotherapy than in interstitial alone, and was higher in the dentulous cases than in the edentulous. Cases with positive nodes on first referral were 44(40%), of which 12 cases were later proved to be false during the clinical course. Fifteen N0 cases developed neck nodes during or after the treatment to the primary site which necessitated surgery. Prognosis was related to the surgical results of the neck. Homo- and contralateral submandibular, homolateral upper jugular, homolateral middle jugular nodes were the common sites involved. (author)

  19. Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    2016-04-19

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

  20. Outcome of Patients Treated With a Single-Fraction Dose of Palliative Radiation for Cutaneous T-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Tarita O.; Agrawal, Priya [Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Guitart, Joan [Department of Dermatology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Rosen, Steven T. [Division of Hematology/Oncology, Department of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Rademaker, Alfred W. [Department of Preventive Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Querfeld, Christiane [Department of Medicine/Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hayes, John P. [Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Kuzel, Timothy M. [Division of Hematology/Oncology, Department of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Mittal, Bharat B., E-mail: bmittal@nmh.org [Department of Radiation Oncology, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States)

    2013-03-01

    Purpose: Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. Methods and Materials: This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October 1991 and January 2011. Patient and tumor characteristics were reviewed. Response rates were compared using Fisher's exact test and multiple logistic regressions. Survival rates were determined using the Kaplan-Meier method. Cost-effectiveness analysis was performed to assess the cost of a single vs a multifractionated treatment regimen. Results: Two hundred seventy individual lesions were treated, with the majority (97%) treated with ≥700 cGy; mean follow-up was 41.3 months (range, 3-180 months). Response rate by lesion was assessed, with a complete response (CR) in 255 (94.4%) lesions, a partial response in 10 (3.7%) lesions, a partial response converted to a CR after a second treatment in 4 (1.5%) lesions, and no response in 1 (0.4%) lesion. The CR in lower extremity lesions was lower than in other sites (P=.0016). Lesions treated with photons had lower CR than those treated with electrons (P=.017). Patients with lesions exhibiting large cell transformation and tumor morphology had lower CR (P=.04 and P=.035, respectively). Immunophenotype did not impact response rate (P=.23). Overall survival was significantly lower for patients with Sézary syndrome (P=.0003) and erythroderma (P<.0001). The cost of multifractionated radiation was >200% higher than that for single-fraction radiation. Conclusions: A single fraction of 700 cGy-800 cGy provides excellent palliation for CTCL lesions and is cost effective and convenient for the patient.

  1. High grade neuroendocrine carcinoma of the urinary bladder treated by radical cystectomy: a series of small cell, mixed neuroendocrine and large cell neuroendocrine carcinoma.

    Science.gov (United States)

    Gupta, Sounak; Thompson, R Houston; Boorjian, Stephen A; Thapa, Prabin; Hernandez, Loren P Herrera; Jimenez, Rafael E; Costello, Brian A; Frank, Igor; Cheville, John C

    2015-10-01

    High grade neuroendocrine carcinomas (HGNEC) treated by cystectomy often carry an original diagnosis of typical urothelial carcinoma (UC). The correct diagnosis of HGNEC is critical in influencing the decision for early chemotherapy, potentially followed by cystectomy. The objective of this study was to characterise the features of HGNEC treated by radical cystectomy. The study consisted of 79 patients with HGNEC including small cell (68 patients), large cell neuroendocrine (LCNEC) (5 patients) and mixed neuroendocrine (mixed-NEC) carcinoma (6 patients) matched with 122 patients with UC, treated at our institution between 1987 and 2014. Morphometric analysis for cell and nuclear size as well as immunophenotyping for neuroendocrine markers and cell-cycle regulators were applied to tissue microarrays. Small cell, LCNEC and mixed-NEC are a morphological spectrum of high grade neuroendocrine carcinoma with overlapping histological features, identical immunophenotype, Ki-67 proliferative rate and patient outcomes. Finally, the nuclear size criteria is misleading as HGNEC, particularly cases of LCNEC and mixed-NEC, may have enlarged nuclei compared to small cell carcinomas and are more prone to be misdiagnosed as UC, thereby preventing appropriate management. PMID:26308137

  2. Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lei; Kuang, Lisha; Hitron, John Andrew; Son, Young-Ok; Wang, Xin; Budhraja, Amit [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Institute of Oral Biosciences and BK21 Program, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Pratheeshkumar, Poyil [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Chen, Gang [Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

    2013-10-01

    Environmental exposure to arsenic is known to cause various cancers. There are some potential relationships between cell malignant transformation and C-X-C chemokine receptor type 4 (CXCR4) expressions. Metastasis, one of the major characteristics of malignantly transformed cells, contributes to the high mortality of cells. CXCR4 and its natural chemokine ligand C-X-C motif ligand 12 (CXCL12) play a critical role in metastasis. Therefore, identification of nutritional factors which are able to inhibit CXCR4 is important for protection from environmental arsenic-induced carcinogenesis and for abolishing metastasis of malignantly transformed cells. The present study demonstrates that apigenin (4′,5,7-trihydroxyflavone), a natural dietary flavonoid, suppressed CXCR4 expression in arsenic-transformed Beas-2B cells (B-AsT) and several other types of transformed/cancer cells in a dose- and time-dependent manner. Neither proteasome nor lysosome inhibitor had any effect in reducing the apigenin-induced down-regulation of CXCR4, indicating that apigenin-induced down-regulation of CXCR4 is not due to proteolytic degradation. The down-regulation of CXCR4 is mainly due to the inhibition of nuclear factor κB (NF-κB) transcriptional activity. Apigenin also abolished migration and invasion of transformed cells induced by CXCL12. In a xenograft mouse model, apigenin down-regulated CXCR4 expression and suppressed tumor growth. Taken together, our results show that apigenin is a novel inhibitor of CXCR4 expression. This dietary flavonoid has the potential to suppress migration and invasion of transformed cells and prevent environmental arsenic-induced carcinogenesis. - Highlights: • Apigenin has a potential in preventing environmental arsenic induced carcinogenesis. • Apigenin suppresses CXCR4 in malignant transformed cells in vitro and in vivo. • The down-regulation of CXCR4 is mainly due to inhibition of NF-κB activity.

  3. Study of the expression for apoptosis factors of thyroid cells after arterial embolization to treat hyperthyroidism caused by Graved' disease

    International Nuclear Information System (INIS)

    Objective: To study the expressions of Fas, FasL, Bax,Bcl-2 and P53 in thyroid tissue and to analyzis (Semi-quantitative analysis)the relation between change of apoptosis in thyroid tissues and clinical therapeutic effect after thyroid arterial embolization in treating hyperthyroidism caused by Graves' disease with observation of apoptosis for 3 years. Methods: 15 patients undergone core needle biopsy of the thyroid gland were divided into three groups according to the amount of time elapsed after thyroid arterial embolization: A group, before thyroid arterial embolization, B group, 1 year group (including 7-day subgroup, 3-month subgroup, 6-month subgroup) and C group, 1 year subgroup and mom than 1 year subgroup after arterial embolization. Results: (1) After embolisation, 15 patients' symptoms and signs of hyperthyroidism disappeared or improved greatly with 9 long term released and 6 improved with small amount of ATD maintenance. (2) The positive staining of Fas and FasL located in endochylema and cell-membrane of thyroid tissue from patients treated with transcathter arterial embolization were higher than those not treated with transcathter arterial embolization (P0.05). (4) The positive cell and the staining of P53 in thyroid tissue had significant difference before and after thyroid arterial embolization (P<0.05). Conclusions: The extra-expression and the increased expression of Fas, FasL, Bax, P53 in thyroid tissue of patient with GD treated by thyroid arterial embolization are correlated with the effects of interventional therapy. (authors)

  4. Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

    Science.gov (United States)

    2015-11-23

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  5. MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

    Science.gov (United States)

    2016-02-18

    Malignant Ovarian Brenner Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  6. Renal cell carcinoma treated with stereotactic radiotherapy with histological change confirmed on autopsy: a case report

    OpenAIRE

    Onishi, Hiroshi; Kawasaki, Tomonori; Zakoji, Hidenori; Yoshida, Takashi; Komiyama, Takafumi; Kuriyama, Kengo; Araya, Masayuki; Saito, Ryo; Aoki, Shinichi; Maehata, Yoshiyasu; Tominaga, Licht; Marino, Kan; Watanabe, Iori; Oguri, Mitsuhiko; Araki, Tsutomu

    2014-01-01

    Background Treatment of primary renal cell carcinoma using radiotherapy with curative intent is rare, because renal cell carcinoma is generally regarded as a radiation-resistant tumor. Recently, stereotactic body radiation therapy has been radically applied for cancers in various organs including renal cell carcinoma. However, there were few reports describing pathological changes of renal cell carcinoma post stereotactic body radiation therapy. This is the first report we are aware of docume...

  7. When is The Best Time of Stem Cell Transplantation for Treating Acute Myocardial Infarction——A Brief Meta-analysis of Current Clinic Trials

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The best time of stem cells transplantation for treating acute myocardial infarction (AMI) is still to be followed with interest and a focus issue for clinical cardiologist. A brief meta-analysis of clinical trials about timing-window and therapeutic effects of stem cell transplantation for treating AMI will be made out in this article.

  8. Comparative Metabolomic Profiling of Hepatocellular Carcinoma Cells Treated with Sorafenib Monotherapy vs. Sorafenib-Everolimus Combination Therapy

    OpenAIRE

    Zheng, Jian-feng; Lu, Juan; Wang, Xiao-Zhong; Guo, Wu-hua; Zhang, Ji-Xiang

    2015-01-01

    Background Sorafenib-everolimus combination therapy may be more effective than sorafenib monotherapy for hepatocellular carcinoma (HCC). To better understand this effect, we comparatively profiled the metabolite composition of HepG2 cells treated with sorafenib, everolimus, and sorafenib-everolimus combination therapy. Material/Methods A 2D HRMAS 1H-NMR metabolomic approach was applied to identify the key differential metabolites in 3 experimental groups: sorafenib (5 μM), everolimus (5 μM), ...

  9. A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine Therapy Alone

    OpenAIRE

    Lee, Dong-Hyun; Seong, Shin; Kim, Sung-Su; Han, Jae-Bok

    2013-01-01

    This report presents a case that shows a significant anticancer effect of Korean medicine therapy (KMT). A 79-year-old man, who was diagnosed as stage IV non-small cell lung cancer (NSCLC) in December 2012, was treated with KMT including intravenous pharmacopunctures and oral herbal medicine from February 22, 2013, until September 2013 without any surgical intervention, chemotherapy or radiotherapy. The intravenous pharmacopunctures were the wild ginseng pharmacopuncture, Cordyceps sinensis p...

  10. Small cell gall bladder carcinoma complicated by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) treated with mozavaptan

    OpenAIRE

    TAMURA, Tetsuo; Takeuchi, Kazuo

    2013-01-01

    Small cell gall bladder carcinoma (Scc-GB) is a very rare entity. Although some cases present with endocrine manifestations, paraneoplastic hyponatraemia has been reported in only one previous case. Recently, the antidiuretic hormone (ADH) receptor antagonist mozavaptan has become available. Herein we report a case with Scc-GB complicated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) treated with mozavaptan. A 47-year-old woman was referred to our hospital for hypon...

  11. Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens.

    OpenAIRE

    Ingram, L; Mott, M G; Mann, J R; Raafat, F; Darbyshire, P J; Morris Jones, P. H.

    1987-01-01

    Eight children treated between 1977 and 1983 with the UK Children's Cancer Study Group's non-Hodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma. These eight children were included among 261 children studied in...

  12. Alvocidib, Fludarabine Phosphate, and Rituximab in Treating Patients With Lymphoproliferative Disorders or Mantle Cell Lymphoma

    Science.gov (United States)

    2013-06-03

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

  13. Neuroprotective role of sphingosine-1-phosphate in L-BMAA treated neuroblastoma cells (SH-SY5Y).

    Science.gov (United States)

    Muñoz-Sáez, Emma; de Munck García, Estefanía; Arahuetes Portero, Rosa María; Vicente, Francisca; Ortiz-López, Francisco Javier; Cantizani, Juan; Gómez Miguel, Begoña

    2015-04-23

    Sphingosine-1-phosphate (S1P) is a bioactive lipid which regulates proliferation, cell migration, survival and differentiation by specific receptors activation. We studied its effects on L-BMAA treated neuroblastoma cells (SH-SY5Y), an amino acid that can trigger neurodegenerative diseases such as amyotrophic lateral sclerosis/Parkinson dementia complex (ALS/PDC). We found that S1P protects from necrosis and prevents the GSK3 increasing as long as the PI3K/AKT pathway is active. Moreover, GSK3 inhibition protects against neuronal death caused by L-BMAA. PMID:25769802

  14. Effects of Caloric Intake on Intestinal Mucosal Morphology and Immune Cells in Rats Treated with 5-Fluorouracil

    OpenAIRE

    Murakami, Mariko; Sato, Norifumi; Tashiro, Katsufumi; Nakamura, Tsuyoshi; Masunaga, Hiroaki

    2009-01-01

    Anticancer drugs have been reported to damage the intestinal mucosa. We evaluated the effects of caloric intake on the mucosal morphology and immune cells in rats treated with 5-fluorouracil (5-FU). Rats were received a liquid diet plus 5-FU treatment for 8 days as follows: Low calorie group (25 kcal/day with 5-FU), Normal calorie group (50 kcal/day with 5-FU), and Control group (50 kcal/day with saline). The mucosal morphology, cell numbers and phenotypes of spleen and intraepithelial lympho...

  15. Observations of microtubules and microtubule-microfilament associations in osmotically treated cells of Micrasterias denticulata Bréb.

    Science.gov (United States)

    Neuhaus-Url, G; Kiermayer, O

    1982-06-01

    As an extension of the observation and interpretation regarding the different microtubule systems of Micrasterias denticulata [12, 19], the existence of intertubular structures, such as microfilaments, which are strongly marked in osmotically treated cells, is especially interesting. The complex of microtubules and microfilaments occurs during post-telophase nuclear migration, probably engaged in the mechanism of movement. The arrangement of microtubules either parallel or perpendicular to the nuclear membrane is characteristic for the stage of nuclear migration. Another microtubule system, the microtubule band in the cortical protoplasm of the isthmus region [12], is described during morphogenesis of the new half cell. Osmotically treated cells in the stage of septum formation demonstrate the presence of cross-linked microtubules near the plasmalemma and microtubule bundles, situated in the protoplasm between the secondary wall and the chloroplast, probably representing the microtubule system in the cortical protoplasm of the old half cell described by Kiermayer [12, 16]. The frequent appearance of microtubules and intertubular structures in differentiating cells of Micrasterias denticulata after osmotic treatment is discussed along with implication for stabilization of microtubules, cross bridges, and microfilaments. PMID:6889505

  16. UPLC-MS/MS-Based Profiling of Eicosanoids in RAW264.7 Cells Treated with Lipopolysaccharide

    Science.gov (United States)

    Lee, Jae Won; Mok, Hyuck Jun; Lee, Dae-Young; Park, Seung Cheol; Ban, Myeong Soon; Choi, Jehun; Park, Chun Geon; Ahn, Young-Sup; Kim, Kwang Pyo; Kim, Hyung Don

    2016-01-01

    While both the pro- and anti-inflammatory effects of several eicosanoids have been widely studied, the degree of inflammation in cells that results from various eicosanoids has yet to be comprehensively studied. The objective of this study was to assess the effect of lipopolysaccharide (LPS) treatment on eicosanoid content in RAW264.7 cells. An Ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)-based profiling method was used to analyze the eicosanoid contents of RAW264.7 cells treated with different LPS concentrations. The profiling data were subjected to statistical analyses, such as principal component analysis (PCA) and hierarchical clustering analysis. LPS treatment increased nitric oxide production and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in a concentration-dependent manner. In total, 79 eicosanoids were identified in the cells. RAW264.7 cells treated with different LPS concentrations were well differentiated in the PCA score plot. A heatmap was used to identify the eicosanoids that were up- or down-regulated according to the degree of inflammation and LPS concentration. Thirty-nine eicosanoids were upregulated and seven were down-regulated by LPS treatment in a concentration-dependent manner. Our novel UPLC-MS/MS technique can profile eicosanoids, and can evaluate the correlations between inflammation and eicosanoid metabolism. PMID:27058537

  17. A Phenolic Extract Obtained from Methyl Jasmonate-Treated Strawberries Enhances Apoptosis in a Human Cervical Cancer Cell Line.

    Science.gov (United States)

    Spagnuolo, Carmela; Flores, Gema; Russo, Gian Luigi; Ruiz Del Castillo, Maria Luisa

    2016-10-01

    In the present study, we evaluated the effect of methyl jasmonate (MeJA) treatment on strawberry phenolic composition. Strawberry extracts contain a mixture of phenolic compounds possessing several biological properties. We demonstrated that these extracts were more effective in inducing apoptosis in HeLa cells compared to phenolic preparations derived from untreated strawberries. Treatment of strawberries with 0.5% MeJA resulted in increased polyphenols content (from 7.4 to 8.6 mM quercetin equivalents) and antioxidant properties (from 3.9 to 4.6 mM quercetin equivalents). The identification and quantification of phenolic compounds by liquid chromatography-mass spectrometry in the strawberry extracts showed that cyanidin glucoside, pelargonidin glucoside, and ellagic glucoside acid were significantly higher in strawberries treated with MeJA. Phenolic extracts from MeJA-treated strawberries significantly decreased the cell viability in HeLa cells, compared to extracts derived from untreated fruits. We hypothesized that the enhanced apoptotic activity of MeJA-treated strawberries was due to a synergistic or additive effect of different phenolic compounds present in the extract, rather than the activity of a single molecule. PMID:27618150

  18. Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Petersen, Jørgen; Nielsen, Søren Jensby; Morsczeck, Christian; Morszeck, Christian; Jensen, Peter B; Sehested, Maxwell; Grauslund, Morten

    2010-01-01

    the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images...... HSP90B that all were related to the proto-oncogene proteins p53, Myc, activator protein 1, and c-fos protein. The modulation of these proteins is consistent with the observations that belinostat is able to inhibit clonogenic cell growth of HCT116 cells and the biological role of these proteins will be...

  19. Let-7a modulates particulate matter (≤ 2.5 μm)-induced oxidative stress and injury in human airway epithelial cells by targeting arginase 2.

    Science.gov (United States)

    Song, Lei; Li, Dan; Gu, Yue; Li, Xiaoping; Peng, Liping

    2016-10-01

    Epidemiological studies show that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5-mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let-7 family might play a role in PM-mediated pathological processes. In this study, we investigated the role of let-7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let-7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let-7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let-7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3'-untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let-7a against PM2.5-induced injury. In conclusion, let-7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let-7a/ARG2 axis is a likely therapeutic target for PM2.5-induced airway epithelial injury. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26989813

  20. Elemental analysis in cultured cells, tobacco and grape, treated with aluminum

    International Nuclear Information System (INIS)

    Relationship between Al toxicity and the Al, Fe and B amount of element in tobacco and grape cells are discussed. Al and Fe were analyzed by neutron activation analysis and B was analyzed by prompt gamma-ray analysis. Callose content was also measured as an indicator of cell damage induced Al toxicity. When tobacco cells were incubated in 1 mM and 300 μM Al solution, the pattern of callose formation was much similar to that of Fe accumulation than that of Al accumulation in tobacco cells, suggesting that the increase of Fe content induced toxic effect along with Al incorporated into the cells. However, this tendency was not observed in grape cells. Boron content did not show any relation to those of Al or Fe throughout the Al treatment in both tobacco and grape cells. (author)

  1. Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells.

    Science.gov (United States)

    Perkins, Timothy N; Dentener, Mieke A; Stassen, Frank R; Rohde, Gernot G; Mossman, Brooke T; Wouters, Emiel F M; Reynaert, Niki L

    2016-06-15

    Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. PMID:27095093

  2. T-cell Subsets in Peripheral Blood and Tumors of Patients Treated With Oncolytic Adenoviruses

    Science.gov (United States)

    Kristian, Taipale; Ilkka, Liikanen; Juuso, Juhila; Aila, Karioja-Kallio; Minna, Oksanen; Riku, Turkki; Nina, Linder; Johan, Lundin; Ari, Ristimäki; Anna, Kanerva; Anniina, Koski; Timo, Joensuu; Markus, Vähä-Koskela; Akseli, Hemminki

    2015-01-01

    The quality of the antitumor immune response is decisive when developing new immunotherapies for cancer. Oncolytic adenoviruses cause a potent immunogenic stimulus and arming them with costimulatory molecules reshapes the immune response further. We evaluated peripheral blood T-cell subsets of 50 patients with refractory solid tumors undergoing treatment with oncolytic adenovirus. These data were compared to changes in antiviral and antitumor T cells, treatment efficacy, overall survival, and T-cell subsets in pre- and post-treatment tumor biopsies. Treatment caused a significant (P < 0.0001) shift in T-cell subsets in blood, characterized by a proportional increase of CD8+ cells, and decrease of CD4+ cells. Concomitant treatment with cyclophosphamide and temozolomide resulted in less CD4+ decrease (P = 0.041) than cyclophosphamide only. Interestingly, we saw a correlation between T-cell changes in peripheral blood and the tumor site. This correlation was positive for CD8+ and inverse for CD4+ cells. These findings give insight to the interconnections between peripheral blood and tumor-infiltrating lymphocyte (TIL) populations regarding oncolytic virotherapy. In particular, our data suggest that induction of T-cell response is not sufficient for clinical response in the context of immunosuppressive tumors, and that peripheral blood T cells have a complicated and potentially misleading relationship with TILs. PMID:25655312

  3. Damage in Escherichia coli cells treated with a combination of high hydrostatic pressure and subzero temperature.

    Science.gov (United States)

    Moussa, Marwen; Perrier-Cornet, Jean-Marie; Gervais, Patrick

    2007-10-01

    The relationship between membrane permeability, changes in ultrastructure, and inactivation in Escherichia coli strain K-12TG1 cells subjected to high hydrostatic pressure treatment at room and subzero temperatures was studied. Propidium iodide staining performed before and after pressure treatment made it possible to distinguish between reversible and irreversible pressure-mediated cell membrane permeabilization. Changes in cell ultrastructure were studied using transmission electron microscopy (TEM), which showed noticeable condensation of nucleoids and aggregation of cytosolic proteins in cells fixed after decompression. A novel technique used to mix fixation reagents with the cell suspension in situ under high hydrostatic pressure (HHP) and subzero-temperature conditions made it possible to show the partial reversibility of pressure-induced nucleoid condensation. However, based on visual examination of TEM micrographs, protein aggregation did not seem to be reversible. Reversible cell membrane permeabilization was noticeable, particularly for HHP treatments at subzero temperature. A correlation between membrane permeabilization and cell inactivation was established, suggesting different mechanisms at room and subzero temperatures. We propose that the inactivation of E. coli cells under combined HHP and subzero temperature occurs mainly during their transiently permeabilized state, whereas HHP inactivation at room temperature is related to a balance of transient and permanent permeabilization. The correlation between TEM results and cell inactivation was not absolute. Further work is required to elucidate the effects of pressure-induced damage on nucleoids and proteins during cell inactivation. PMID:17766454

  4. Damage in Escherichia coli Cells Treated with a Combination of High Hydrostatic Pressure and Subzero Temperature▿

    Science.gov (United States)

    Moussa, Marwen; Perrier-Cornet, Jean-Marie; Gervais, Patrick

    2007-01-01

    The relationship between membrane permeability, changes in ultrastructure, and inactivation in Escherichia coli strain K-12TG1 cells subjected to high hydrostatic pressure treatment at room and subzero temperatures was studied. Propidium iodide staining performed before and after pressure treatment made it possible to distinguish between reversible and irreversible pressure-mediated cell membrane permeabilization. Changes in cell ultrastructure were studied using transmission electron microscopy (TEM), which showed noticeable condensation of nucleoids and aggregation of cytosolic proteins in cells fixed after decompression. A novel technique used to mix fixation reagents with the cell suspension in situ under high hydrostatic pressure (HHP) and subzero-temperature conditions made it possible to show the partial reversibility of pressure-induced nucleoid condensation. However, based on visual examination of TEM micrographs, protein aggregation did not seem to be reversible. Reversible cell membrane permeabilization was noticeable, particularly for HHP treatments at subzero temperature. A correlation between membrane permeabilization and cell inactivation was established, suggesting different mechanisms at room and subzero temperatures. We propose that the inactivation of E. coli cells under combined HHP and subzero temperature occurs mainly during their transiently permeabilized state, whereas HHP inactivation at room temperature is related to a balance of transient and permanent permeabilization. The correlation between TEM results and cell inactivation was not absolute. Further work is required to elucidate the effects of pressure-induced damage on nucleoids and proteins during cell inactivation. PMID:17766454

  5. Nickel Mobilizes Intracellular Zinc to Induce Metallothionein in Human Airway Epithelial Cells

    Science.gov (United States)

    Nemec, Antonia A.; Leikauf, George D.; Pitt, Bruce R.; Wasserloos, Karla J.; Barchowsky, Aaron

    2009-01-01

    We recently reported that induction of metallothionein (MT) was critical in limiting nickel (Ni)-induced lung injury in intact mice. Nonetheless, the mechanism by which Ni induces MT expression is unclear. We hypothesized that the ability of Ni to mobilize zinc (Zn) may contribute to such regulation and therefore, we examined the mechanism for Ni-induced MT2A expression in human airway epithelial (BEAS-2B) cells. Ni induced MT2A transcript levels and protein expression by 4 hours. Ni also increased the activity of a metal response element (MRE) promoter luciferase reporter construct, suggesting that Ni induces MRE binding of the metal transcription factor (MTF-1). Exposure to Ni resulted in the nuclear translocation of MTF-1, and Ni failed to induce MT in mouse embryonic fibroblasts lacking MTF-1. As Zn is the only metal known to directly bind MTF-1, we then showed that Ni increased a labile pool of intracellular Zn in cells as revealed by fluorescence-activated cell sorter using the Zn-sensitive fluorophore, FluoZin-3. Ni-induced increases in MT2A mRNA and MRE-luciferase activity were sensitive to the Zn chelator, TPEN, supporting an important role for Zn in mediating the effect of Ni. Although neither the source of labile Zn nor the mechanism by which Ni liberates labile Zn was apparent, it was noteworthy that Ni increased intracellular reactive oxygen species (ROS). Although both N-acetyl cysteine (NAC) and ascorbic acid (AA) decreased Ni-induced increases in ROS, only NAC prevented Ni-induced increases in MT2A mRNA, suggesting a special role for interactions of Ni, thiols, and Zn release. PMID:19097988

  6. Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease After Donor Stem Cell Transplant

    Science.gov (United States)

    2011-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; De Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Gastrointestinal Complications; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Childhood Rhabdomyosarcoma; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent

  7. Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

    Science.gov (United States)

    Valor, Lara; Martínez-Estupiñán, Lina; Janta, Iustina; Nieto, Juan Carlos; Ovalles-Bonilla, Juan Gabriel; González-Fernández, Carlos; Del Rio, Tamara; Hernández-Flórez, Diana; Monteagudo, Indalecio; López-Longo, Francisco Javier; Naredo, Esperanza

    2016-06-01

    This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28  2.6 = 49.45, p = 0.52) and PDI score (PDI  1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count. PMID:27072348

  8. An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.

    Science.gov (United States)

    Filareto, Antonio; Parker, Sarah; Darabi, Radbod; Borges, Luciene; Iacovino, Michelina; Schaaf, Tory; Mayerhofer, Timothy; Chamberlain, Jeffrey S; Ervasti, James M; McIvor, R Scott; Kyba, Michael; Perlingeiro, Rita C R

    2013-01-01

    Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiate these cells into skeletal muscle progenitors and transplant them back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin-glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells. PMID:23462992

  9. Ultrastructural alterations in human lymphoblastoid B cell lines treated with tunicamycin.

    OpenAIRE

    Glassy, M C; Ferrone, S

    1981-01-01

    The ultrastructure of three human lymphoblastoid B cell lines, Raji, RPMI 4098, and WIL-2, was analyzed after the cells were incubated with tunicamycin, and antibiotic that selectively inhibits N-linked glycosylation of macromolecules. After a 24-hour exposure to 1.0 microgram/ml of tunicamycin, the lymphocytes lose their microvilli and become smooth spheres or develop a few blebs. Also, the cells show a dilation of the endoplasmic reticulum and an increase in myelin figures resulting from in...

  10. Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection

    OpenAIRE

    Kumaresan, Pappanaicken R.; Manuri, Pallavi R.; Albert, Nathaniel D.; Maiti, Sourindra; Singh, Harjeet; Mi, Tiejuan; Roszik, Jason; Rabinovich, Brian; Olivares, Simon; Krishnamurthy, Janani; Zhang, Ling; Najjar, Amer M.; Huls, M. Helen; Lee, Dean A.; Champlin, Richard E.

    2014-01-01

    Patients with compromised T-cell function are at risk for opportunistic fungal infections. We have developed a novel approach to restore immunity by using a fungal pattern-recognition receptor Dectin-1 to redirect T-cell specificity to carbohydrate antigen in the fungal cell wall. We did so by genetically modifying T cells using the nonviral Sleeping Beauty gene-transfer system to enforce expression of a chimeric antigen receptor (CAR) that recapitulates the specificity of Dectin-1 (D-CAR). T...

  11. Rearrangement of S-100 immunoreactive Langerhans' cells in human psoriatic skin treated with peptide T.

    Science.gov (United States)

    Wang, L; Hilliges, M; Talme, T; Marcusson, J A; Wetterberg, L; Johansson, O

    1995-01-01

    Dendritic cells marked by protein S-100 (S-100) antiserum in the suprabasal layers of the epidermis have previously been identified to be Langerhans' cells. In this study, S-100 immunoreactive cells have been investigated in psoriatic lesioned skin during and after peptide T treatment. Peptide T is an octapeptide with affinity for the CD4 receptor. Nine patients were intravenously infused with peptide T, 2 mg in 500 ml saline per day for 28 days. Sections from involved skin before, every week during, and after the treatment were processed by indirect immunofluorescence using S-100 antiserum. Before the treatment the epidermal Langerhans' cells were numerically decreased or even completely gone in the involved skin of psoriasis as compared to skin from normal healthy controls, while the dermal dendritic cells instead were increased and gathered in cell clusters around vascular structures. Four of the nine patients had histopathological improvements after the peptide T treatment, and, in those cases, the dendritic cells in the dermis were reduced in number, and the Langerhans' cells in the epidermis were numerically increased as well as even reversed to normal position and morphology. These changes in the distribution and density of Langerhans' cells represent their rearrangement during the course of psoriasis and/or the remission after peptide T treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7727353

  12. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    Science.gov (United States)

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  13. The Potential of Wharton's Jelly Derived Mesenchymal Stem Cells in Treating Patients with Cystic Fibrosis.

    Science.gov (United States)

    Boruczkowski, D; Gładysz, D; Demkow, U; Pawelec, K

    2015-01-01

    Cystic fibrosis (CF) is a life-threatening autosomal recessive multi-organ disorder with the mean incidence of 0.737 per 10,000 people worldwide. Despite many advances in therapy, patients fail to have a satisfactory quality of life. The end-stage lung disease still accounts for significant mortality and puts patients in the need of lung transplantation. Even though the disease is monogenic, the trials of topical gene transfer into airway epithelial cells have so far been disappointing. It is proven that stem cells can be differentiated into type II alveolar epithelial cells. Wharton's jelly-derived mesenchymal stem cells (MSC) from non-CF carrier third-party donors could be an effective alternative to bone marrow or embryonic stem cells. The harvesting process is an easy and ethically uncontroversial procedure. The MSC cell should be applied through repetitive infusions due to rapid lung epithelial cell turnover. However, the low stem cell incorporation remains a problem. Pre-clinical studies imply that even 6-10% of the wild-type cystic fibrosis transmembrane conductance regulator (CFTR) expression could be enough to restore chloride secretion. The route of administration, the optimal dose, as well as the intervals between infusions have yet to be determined. This review discusses the clinical potential of mesenchymal stem cell in CF patients. PMID:25248343

  14. Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles

    Directory of Open Access Journals (Sweden)

    S.Y. Yan

    2014-11-01

    Full Text Available This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR. It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721, induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.

  15. Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe₂O₃ nanoparticles.

    Science.gov (United States)

    Yan, S Y; Chen, M M; Fan, J G; Wang, Y Q; Du, Y Q; Hu, Y; Xu, L M

    2014-11-01

    This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe₂O₃ nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe₂O₃ nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe₂O₃ MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe₂O₃ MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe₂O₃nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe₂O₃MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G₂/M phase. Fe₂O₃ MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells. PMID:25296356

  16. Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles.

    Science.gov (United States)

    Yan, S Y; Chen, M M; Fan, J G; Wang, Y Q; Du, Y Q; Hu, Y; Xu, L M

    2014-08-29

    This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells. PMID:25184378

  17. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction.

    Science.gov (United States)

    Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko

    2016-01-01

    The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373

  18. Generation and Feasibility Assessment of a New Vehicle for Cell-Based Therapy for Treating Corneal Endothelial Dysfunction.

    Directory of Open Access Journals (Sweden)

    Naoki Okumura

    Full Text Available The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs in combination with a Rho kinase (ROCK inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use.

  19. Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles

    International Nuclear Information System (INIS)

    This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (,24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells. (author)

  20. Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LI Cai-juan; GUO Su-fen; SHI Tie-mei

    2012-01-01

    Background Parthenolide has been tested for anti-tumor activities,such as anti-proliferation and pro-apoptosis in recent studies.However,little is known about its role in the process of tumor angiogenesis.This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation,migration and lumen formation capacity of human umbilical vein endothelial cells.Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells.After 24-hour incubation,the culture supematants were harvested and used to treat human umbilical vein endothelial cells for 24 hours.Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells.The secretion of vascular endothelial growth factor (VEGF),interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.Results Suppression of proliferation,migration,and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide.Parthenolide decreased the levels of the angiogenic factors MMP-9,VEGF,and IL-8secreted by the MDA-MB-231 cells.Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation,migration and lumen-like structure formation of endothelial cells,thereby inhibiting tumor growth.It is a promising potential anti-angiogenic drug.

  1. Surface characteristics and cell-adhesion performance of titanium treated with direct-current gas plasma comprising nitrogen and oxygen

    Science.gov (United States)

    Hirano, Mitsuhiro; Yamane, Misao; Ohtsu, Naofumi

    2015-11-01

    In this study, we attempted to form titanium oxynitride (TiOxNy) layers on titanium (Ti) surfaces using direct-current (DC) plasmas generated from gas mixture comprising hydrogen, nitrogen, and oxygen. Additionally, the effect of gas mixture ratio on the surface characteristics and cell-adhesion performance was investigated. Scanning probe microscopy (SPM) images showed that the plasma-treated surfaces were slightly rougher than untreated Ti surfaces, owing to the formation of new layers. Chemical state analysis using X-ray photoelectron spectroscopy (XPS) revealed that the layers were comprised TiOxNy, titanium nitride (TiN), and titanium dioxide (TiO2); the concentrations of TiOxNy and TiN decreased and that of TiO2 increased with an increase in the amount of oxygen in the gas. An increase in the amount of oxygen gas did not affect the layer thickness, which was approximately 25 nm. Furthermore, no differences in cell morphology and cell-adhesion performance were found between the specimens treated with various plasma gases. This is probably because the treatment insufficiently improved the hydrophilicity. Layers composed of TiOxNy, TiN, and TiO2 were formed using the DC plasma treatment; however, the layers did not improve the cell-adhesion at an initial stage after the seeding.

  2. GST-π EXPRESSION IN TRANSFORMED CELLS BY TRANSFECTING OF DNA ISOLATED FROM HUMAN FETAL LUNG TISSUES TREATED WITH CARCINOGENS

    Institute of Scientific and Technical Information of China (English)

    Yao Denggao; Hu Guogang; Luo Xianmao; Zhu Ming

    1998-01-01

    Objective: To investigate the relationship between the GSTs, GST-π expression and initiation of lung carcinogenesis. Methods: The Rat-1 cells were transformed by carcinogens (DEN, MNU and CSC) treated fetal lung DNA for 24 h. Results: The GSTs activities toward 1-chloro-2, 4-dinitro-benzene (CDNB) in transformed cells were significantly higher than in the solvent control cells (P<0.05). GST-π content and GST-π mRNA expression level of transformed cells were also higher than those of control cells which were performed by ELISA and Northern blotting method respectively. The results indicated that the higher GSTS activities of transformed cells were due to the increase of GST-π content and the GST-π mRNA overexpressing may be responsible for the increase of GST-π protein level of the transformed cells. Conclusion: The changes of GSTs and GST-π may be considered as the one of the biomarkers of the initiation of human lung carcinogenesis.

  3. Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

    Directory of Open Access Journals (Sweden)

    Cao Hongcui

    2012-06-01

    Full Text Available Abstract Background Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF. Methods hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis. Results hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig

  4. Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant

    International Nuclear Information System (INIS)

    Purpose: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. Methods and Materials: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. Results: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation (p 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation (p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. Conclusions: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy

  5. VITALITY AND MORPHOLOGY OF TUMOR CELLS TREATED WITH 4-TIAZOLIDINONE DERIVATIVES IMMOBILIZED ON NANOSCALE POLYMER CARRIER

    Directory of Open Access Journals (Sweden)

    N. M. Boiko

    2015-02-01

    Full Text Available A nanoscale polymeric carrier was used for delivery of novel anticancer compounds – 4-tiazolidinone derivatives – to tumor cells of different lines. It was found that such way of delivery of the above mentioned compounds to target cells significantly (approximately 10 times decreased acting cytotoxic dose of some of these compounds with preservation of similar level of their antineoplastic effect in vitro towards various mammalian tumor cells. The microscopic investigation of these cells demonstrated that under the action of some immobilized 4-tiazolidonone derivatives, there was an increase (up to 40% of the part of apoptotic cells, as well as an appearance of 10% of cells with morphologically changed nucleus, and up to 35% of cells with an increased intensity of red fluorescence of acridine orange in the lysosomes, compared with such indicators observed under the action of free form of those compounds. Thus, the applied nanoscale carrier is a perspective polymer system for delivery of anticancer drugs to target cells.

  6. Re-programming tumour cell metabolism to treat cancer: no lone target for lonidamine.

    Science.gov (United States)

    Bhutia, Yangzom D; Babu, Ellappan; Ganapathy, Vadivel

    2016-06-01

    Tumour cell metabolism is very different from normal cell metabolism; cancer cells re-programme the metabolic pathways that occur in normal cells in such a manner that it optimizes their proliferation, growth and survival. Although this metabolic re-programming obviously operates to the advantage of the tumour, it also offers unique opportunities for effective cancer therapy. Molecules that target the tumour cell-specific metabolic pathways have potential as novel anti-cancer drugs. Lonidamine belongs to this group of molecules and is already in use in some countries for cancer treatment. It has been known for a long time that lonidamine interferes with energy production in tumour cells by inhibiting hexokinase II (HKII), a glycolytic enzyme. However, subsequent studies have uncovered additional pharmacological targets for the drug, which include the electron transport chain and the mitochondrial permeability transition pore, thus expanding the pharmacological effects of the drug on tumour cell metabolism. A study by Nancolas et al. in a recent issue of the Biochemical Journal identifies two additional new targets for lonidamine: the pyruvate transporter in the mitochondria and the H(+)-coupled monocarboxylate transporters in the plasma membrane (PM). It is thus becoming increasingly apparent that the anti-cancer effects of lonidamine do not occur through a single target; the drug works at multiple sites. Irrespective of the molecular targets, what lonidamine does in the end is to undo what the tumour cells have done in terms of re-programming cellular metabolism and mitochondrial function. PMID:27234586

  7. Can mammalian cloning combined with embryonic stem cell technologies be used to treat human diseases?

    OpenAIRE

    Hadjantonakis, Anna-Katerina; Papaioannou, Virginia E.

    2002-01-01

    Cloning is commonly perceived as a means of generating genetically identical individuals, but it can also be used to obtain genetically matched embryo-derived stem cells, which could potentially be used in the treatment of patients. A recent report offers the first 'proof of principle' of such cloning for therapeutic purposes, referred to as nuclear transplantation to produce stem cells for autologous transplantation.

  8. Plasma-treated polystyrene surfaces : model surfaces for studying cell-biomaterial interactions

    NARCIS (Netherlands)

    van Kooten, TG; Spijker, HT; Busscher, HJ

    2004-01-01

    Biocompatibility of biomaterials relates, amongst others, to the absence of adverse cellular reactions and modulation of cell adhesion and subsequent responses. With respect to tissue-engineering applications, most materials need to evoke cell adhesion and spreading, while potentially displaying dif

  9. Circulating activated T cell subsets in autoimmune thyroid diseases: differences between untreated and treated patients.

    Science.gov (United States)

    Ohashi, H; Okugawa, T; Itoh, M

    1991-11-01

    To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy. PMID:1684685

  10. Hyperexcitability and cell loss in kainate-treated hippocampal slice cultures

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Casaccia-Bonnefil, P; Stelzer, A;

    1993-01-01

    Loss of hippocampal interneurons has been reported in patients with severe temporal lobe epilepsy and in animals treated with kainate. We investigated the relationship between KA induced epileptiform discharge and loss of interneurons in hippocampal slice cultures. Application of KA (1 microM) pr......-like immunoreactive (PV-I) interneurons preceded loss of somatostatin-like immunoreactive (SS-I) interneurons suggesting a different time course of KA neurotoxicity in these subpopulations of interneurons....

  11. In Vitro and In Vivo Hepatic Differentiation of Adult Somatic Stem Cells and Extraembryonic Stem Cells for Treating End Stage Liver Diseases

    Directory of Open Access Journals (Sweden)

    Chenxia Hu

    2015-01-01

    Full Text Available The shortage of liver donors is a major handicap that prevents most patients from receiving liver transplantation and places them on a waiting list for donated liver tissue. Then, primary hepatocyte transplantation and bioartificial livers have emerged as two alternative treatments for these often fatal diseases. However, another problem has emerged. Functional hepatocytes for liver regeneration are in short supply, and they will dedifferentiate immediately in vitro after they are isolated from liver tissue. Alternative stem-cell-based therapeutic strategies, including hepatic stem cells (HSCs, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and mesenchymal stem cells (MSCs, are more promising, and more attention has been devoted to these approaches because of the high potency and proliferation ability of the cells. This review will focus on the general characteristics and the progress in hepatic differentiation of adult somatic stem cells and extraembryonic stem cells in vitro and in vivo for the treatment of end stage liver diseases. The hepatic differentiation of stem cells would offer an ideal and promising source for cell therapy and tissue engineering for treating liver diseases.

  12. Mitochondrial electron transport is inhibited by disappearance of metallothionein in human bronchial epithelial cells following exposure to silver nitrate

    International Nuclear Information System (INIS)

    Highlights: ► Ag is immediately sequestered by metallothionein (MT). ► Ag bound MT was destabilized by ROS. ► The mechanism explains inhibition of mitochondrial electron transport. - Abstract: Silver (Ag) possesses antibacterial activity and has been used in wound dressings and deodorant powders worldwide. However, the metabolic behavior and biological roles of Ag in mammals have not been well characterized. In the present study, we exposed human bronchial epithelial cells (BEAS-2B) to AgNO3 and investigated uptake and intracellular distribution of Ag, expression of metallothionein (MT), generation of reactive oxygen species (ROS), and changes in mitochondrial respiration. The culture medium concentration of Ag decreased with time and stabilized at 12 h. The concentration of both Ag and MT in the soluble cellular fraction increased up to 3 h and then decreased, indicating that cytosolic Ag relocated to the insoluble fraction of the cells. The levels of mRNAs for the major human MT isoforms MT-I and MT-II paralleled with the protein levels of Ag-MT. The intensity of fluorescence derived from ROS was elevated in the mitochondrial region at 24 h. Ag decreased mitochondrial oxygen consumption in a dose-dependent manner and the activity of mitochondrial complex I-IV enzymes was significantly inhibited following exposure to Ag. In a separate experiment, we found that hydrogen peroxide (H2O2) at concentrations as low as 0.001% (equivalent to the concentration of H2O2 in Ag-exposed cells) removed Ag from MT. These results suggest MT was decomposed by cytosolic H2O2, and then Ag released from MT relocated to insoluble cellular fractions and inhibited electron chain transfer of mitochondrial complexes, which eventually led to cell damage

  13. Mg ion implantation on SLA-treated titanium surface and its effects on the behavior of mesenchymal stem cell

    International Nuclear Information System (INIS)

    Magnesium (Mg) is one of the most important ions associated with bone osseointegration. The aim of this study was to evaluate the cellular effects of Mg implantation in titanium (Ti) surfaces treated with sand blast using large grit and acid etching (SLA). Mg ions were implanted into the surface via vacuum arc source ion implantation. The surface morphology, chemical properties, and the amount of Mg ion release were evaluated by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), Rutherford backscattering spectroscopy (RBS), and inductively coupled plasma-optical emission spectrometer (ICP-OES). Human mesenchymal stem cells (hMSCs) were used to evaluate cellular parameters such as proliferation, cytotoxicity, and adhesion morphology by MTS assay, live/dead assay, and SEM. Furthermore, osteoblast differentiation was determined on the basis of alkaline phosphatase (ALP) activity and the degree of calcium accumulation. In the Mg ion-implanted disk, 2.3 × 1016 ions/cm2 was retained. However, after Mg ion implantation, the surface morphology did not change. Implanted Mg ions were rapidly released during the first 7 days in vitro. The MTS assay, live/dead assay, and SEM demonstrated increased cell attachment and growth on the Mg ion-implanted surface. In particular, Mg ion implantation increased the initial cell adhesion, and in an osteoblast differentiation assay, ALP activity and calcium accumulation. These findings suggest that Mg ion implantation using the plasma source ion implantation (PSII) technique may be useful for SLA-treated Ti dental implants to improve their osseointegration capacity. - Highlights: ► Mg ion was coated onto surface of SLA treated titanium via vacuum arc source ion implantation method. ► The morphological characteristics did not change after Mg ion implantation. ► Mg ion implanted SLA Ti is highly cytocompatible. ► Initial cell adhesion of MSCs is improved by Mg ion implantation. ► Mg ion implantation improved

  14. Mg ion implantation on SLA-treated titanium surface and its effects on the behavior of mesenchymal stem cell

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beom-Su; Kim, Jin Seong [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan 570-749 (Korea, Republic of); Bonecell Biotech Inc., 77, Dunsan-ro, Seo-gu, Daejeon 302-830 (Korea, Republic of); Park, Young Min [DIO Corporation, 66, Centum seo-ro, Haeundae-gu, Busan (Korea, Republic of); Choi, Bo-Young [Department of Oral and maxillofacial Surgery, Wonkwang University Daejeon Dental Hospital, Daejeon 302-830 (Korea, Republic of); Lee, Jun, E-mail: omslee@wku.ac.kr [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan 570-749 (Korea, Republic of); Bonecell Biotech Inc., 77, Dunsan-ro, Seo-gu, Daejeon 302-830 (Korea, Republic of)

    2013-04-01

    Magnesium (Mg) is one of the most important ions associated with bone osseointegration. The aim of this study was to evaluate the cellular effects of Mg implantation in titanium (Ti) surfaces treated with sand blast using large grit and acid etching (SLA). Mg ions were implanted into the surface via vacuum arc source ion implantation. The surface morphology, chemical properties, and the amount of Mg ion release were evaluated by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), Rutherford backscattering spectroscopy (RBS), and inductively coupled plasma-optical emission spectrometer (ICP-OES). Human mesenchymal stem cells (hMSCs) were used to evaluate cellular parameters such as proliferation, cytotoxicity, and adhesion morphology by MTS assay, live/dead assay, and SEM. Furthermore, osteoblast differentiation was determined on the basis of alkaline phosphatase (ALP) activity and the degree of calcium accumulation. In the Mg ion-implanted disk, 2.3 × 10{sup 16} ions/cm{sup 2} was retained. However, after Mg ion implantation, the surface morphology did not change. Implanted Mg ions were rapidly released during the first 7 days in vitro. The MTS assay, live/dead assay, and SEM demonstrated increased cell attachment and growth on the Mg ion-implanted surface. In particular, Mg ion implantation increased the initial cell adhesion, and in an osteoblast differentiation assay, ALP activity and calcium accumulation. These findings suggest that Mg ion implantation using the plasma source ion implantation (PSII) technique may be useful for SLA-treated Ti dental implants to improve their osseointegration capacity. - Highlights: ► Mg ion was coated onto surface of SLA treated titanium via vacuum arc source ion implantation method. ► The morphological characteristics did not change after Mg ion implantation. ► Mg ion implanted SLA Ti is highly cytocompatible. ► Initial cell adhesion of MSCs is improved by Mg ion implantation. ► Mg ion implantation

  15. Data from SILAC-based quantitative analysis of lysates from mouse microglial cells treated with Withaferin A (WA

    Directory of Open Access Journals (Sweden)

    Malathi Narayan

    2016-06-01

    Full Text Available Mass spectrometry data collected in a study analyzing the effect of withaferin A (WA on a mouse microglial (N9 cell line is presented in this article. Data was collected from SILAC-based quantitative analysis of lysates from mouse microglial cells treated with either WA or DMSO vehicle control. This article reports all the proteins that were identified in this analysis. The data presented here is related to the published research article on the effect of WA on the differential regulation of proteins in mouse microglial cells [1]. Mass spectrometry data has also been deposited in the ProteomeXchange with the identifier http://www.ebi.ac.uk/pride/archive/projects/PXD003032.

  16. Zinc-air cell with KOH-treated agar layer between electrode and electrolyte containing hydroponics gel

    Energy Technology Data Exchange (ETDEWEB)

    Otham, R. [International Islamic University, Kuala Lumpur (Malaysia); Yahaya, A. H. [University of Malaya, Dept. of Chemistry, Kuala Lumpur (Malaysia); Arof, A. K. [University of Malaya, Dept. of Physics, Kuala Lumpur (Malaysia)

    2002-07-01

    Zinc-air electrochemical power sources possess the highest density compared to other zinc anode batteries, due their free and unlimited supply from the ambient air. In this experiment zinc-air cells have been fabricated employing hydroponics gel as an alternative alkaline electrolyte gelling agent. Thin KOH-treated agar layer was applied between the electrode-electrolyte interfaces which produced significant enhancement of the cells' capacities, indicating that the application of thin agar layer will improve the electrode-gelled electrolyte interfaces. Promising results have been achieved with porous zinc anode prepared from dried zinc-graphite-gelatinized agar paste; e g. a zinc-air cell employing a porous zinc anode has demonstrated a capacity of 1470 mAh rated at 0.1 A continuous discharge. 32 refs., 9 figs.

  17. Comparison of the behavior of fibroblast and bone marrow-derived mesenchymal stem cell on nitrogen plasma-treated gelatin films

    International Nuclear Information System (INIS)

    The attachment and growth behavior of mouse fibroblast (L929) and rat bone marrow-derived mesenchymal stem cell (MSC) on nitrogen plasma-treated and untreated gelatin films was investigated and compared. The gelatin films were prepared by solution casting (0.05% w/v) and crosslinked using dehydrothermal treatment. The crosslinked gelatin films were treated with nitrogen alternating current (AC) 50 Hz plasma systems at various treatment time. The results on the attachment and growth of two cells; L929 and MSC, on plasma-treated gelatin film showed that the number of attached and proliferated cells on plasma-treated gelatin films was significantly increased compared to untreated samples. However, no significant difference between the number of attached L929 and MSC on plasma-treated gelatin was observed. The shorter population doubling time and higher growth rate of cells cultured on plasma-treated film indicated the greater growth of cells, compared to ones on untreated films. The greatest enhancement of cell attachment and growth were noticed when the film was treated with nitrogen plasma for 9 to 15 s. This suggested that the greater attachment and growth of both cells on gelatin films resulted from the change of surface properties, i.e. hydrophilicity, surface energy, and chemistry. The suitable water contact angle and oxygen/nitrogen ratio (O/N) of gelatin film for best L929 and MSC attachment were observed at 27–32° and 1.4, respectively. These conditions also provided the best proliferation of cells on plasma-treated gelatin films. - Highlights: • We compared the attachment and growth behavior of L929 and MSC. • The attachment of two cells on plasma-treated gelatin was significantly increased. • The shorter population doubling time and higher growth rate of cells were observed. • L929 fibroblast exhibited the greater proliferation, compared to MSC

  18. Comparison of the behavior of fibroblast and bone marrow-derived mesenchymal stem cell on nitrogen plasma-treated gelatin films

    Energy Technology Data Exchange (ETDEWEB)

    Prasertsung, I. [Chemical Engineering Program, Department of Industrial Engineering, Faculty of Engineering, Naresuan University, Phitsanulok 65000 (Thailand); Research Unit on Functionalized Material for Chemical, Biochemical and Biomedical Technology, Faculty of Engineering, Naresuan University, Phitsanulok 65000 (Thailand); Kanokpanont, S. [Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok 10330 (Thailand); Mongkolnavin, R. [Department of Physics, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand); Plasma Technology and Nuclear Fusion Research Unit, Chulalongkorn University, Bangkok 10330 (Thailand); Wong, C.S. [Plasma Technology Research Centre, Department of Physics, Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Panpranot, J. [Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok 10330 (Thailand); Damrongsakkul, S., E-mail: siriporn.d@chula.ac.th [Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok 10330 (Thailand); Plasma Technology and Nuclear Fusion Research Unit, Chulalongkorn University, Bangkok 10330 (Thailand)

    2013-10-01

    The attachment and growth behavior of mouse fibroblast (L929) and rat bone marrow-derived mesenchymal stem cell (MSC) on nitrogen plasma-treated and untreated gelatin films was investigated and compared. The gelatin films were prepared by solution casting (0.05% w/v) and crosslinked using dehydrothermal treatment. The crosslinked gelatin films were treated with nitrogen alternating current (AC) 50 Hz plasma systems at various treatment time. The results on the attachment and growth of two cells; L929 and MSC, on plasma-treated gelatin film showed that the number of attached and proliferated cells on plasma-treated gelatin films was significantly increased compared to untreated samples. However, no significant difference between the number of attached L929 and MSC on plasma-treated gelatin was observed. The shorter population doubling time and higher growth rate of cells cultured on plasma-treated film indicated the greater growth of cells, compared to ones on untreated films. The greatest enhancement of cell attachment and growth were noticed when the film was treated with nitrogen plasma for 9 to 15 s. This suggested that the greater attachment and growth of both cells on gelatin films resulted from the change of surface properties, i.e. hydrophilicity, surface energy, and chemistry. The suitable water contact angle and oxygen/nitrogen ratio (O/N) of gelatin film for best L929 and MSC attachment were observed at 27–32° and 1.4, respectively. These conditions also provided the best proliferation of cells on plasma-treated gelatin films. - Highlights: • We compared the attachment and growth behavior of L929 and MSC. • The attachment of two cells on plasma-treated gelatin was significantly increased. • The shorter population doubling time and higher growth rate of cells were observed. • L929 fibroblast exhibited the greater proliferation, compared to MSC.

  19. Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2016-07-15

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Inv(3)(q21q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma

  20. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

    Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

  1. Annealing of wet treated Cu(In,Ga)(S,Se)2 solar cells with an indium sulfide buffer

    International Nuclear Information System (INIS)

    Compound evaporated indium sulfide is one commonly utilized cadmium free buffer layer for Cu(In,Ga)(S,Se)2 solar cells. However, cells with such a buffer layer usually need a post-deposition annealing step to reach the maximum short circuit current, fill factor and open circuit voltage. In this work wet chemical treatments, partly containing cadmium ions, are applied to commercially available absorber material prior to indium sulfide evaporation in order to enhance the initial solar cell parameters. Cells built on treated absorbers show maximum open circuit voltage directly after window layer deposition and a drop in open circuit voltage is observed upon annealing. All samples, however, show an increased collection length and higher fill factor after annealing. A one diode model fit to the current-voltage curves gives ideality factors of 1.7 before annealing which are reduced to values around 1.5 after annealing. Supporting calculations show that the changes upon annealing can be explained within a model including a highly p-doped absorber surface layer. During annealing the acceptor density at the absorber surface might be reduced thus leading to a larger space charge region and thereby increasing the collection length and fill factor while reducing the open circuit voltage. - Highlights: • Wet treatments raise initial voltage of In2S3 buffered Cu(In,Ga)(S,Se)2 solar cells. • Collection length increase after annealing of treated cells is observed. • Voltage decay is explained within a model including a highly p-doped surface layer. • Supporting simulations are in good agreement with the experiments

  2. The assessment of inflammatory activity and toxicity of treated sewage using RAW264.7 cells

    OpenAIRE

    Makene, Vedastus W.; Pool, Edmund J.

    2015-01-01

    Abstract Toxicity and inflammatory activity of wastewater samples were evaluated using RAW264.7 cells as a bioassay model. The RAW264.7 cell cultures were exposed to sterile filtered wastewater samples collected from a sewage treatment plant. Cell viability was evaluated using WST‐1 and XTT assays. Inflammatory effects of samples were assessed by determination of nitric oxide (NO) and interleukin 6 (IL‐6). The NO was estimated using the Griess reaction and IL‐6 was measured by enzyme‐linked i...

  3. Sustained First Remission in an Adolescent With Hepatosplenic T-Cell Lymphoma Treated With T-Cell Leukemia Induction, Nucleoside Analog-Based Consolidation, and Early Hematopoietic Stem Cell Transplant

    OpenAIRE

    Schafer, Eric; Chen, Allen; Arceci, Robert J.

    2009-01-01

    Hepatosplenic T-cell lymphoma (HTCL) is a rare malignancy. Prognosis is poor with only a few case reports of long-term survivors. While HTCL universally involves the bone marrow, the condition has been most often treated with multimodal lymphoma specific chemotherapy. We report a durable, sustained first remission in an adolescent treated for HTCL who received induction therapy according to a high risk T-cell leukemia regimen, a nucleoside analog-based consolidation, and allogeneic transplant...

  4. Mesenchymal stem cells derived in vitro transdifferentiated insulin-producing cells: A new approach to treat type 1 diabetes

    OpenAIRE

    Shruti Dave

    2014-01-01

    The pathophysiology of type 1 diabetes mellitus (T1DM) is largely related to an innate defect in the immune system culminating in a loss of self-tolerance and destruction of the insulin-producing β-cells. Currently, there is no definitive cure for T1DM. Insulin injection does not mimic the precise regulation of β-cells on glucose homeostasis, leading long term to the development of complications. Stem cell therapy is a promising approach and specifically mesenchymal stem cells (MSCs) offer a ...

  5. Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

    Directory of Open Access Journals (Sweden)

    Zeng Zhen

    2012-12-01

    Full Text Available Abstract Background Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs, has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence. Methods Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE. Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen. Results TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040. None of the other markers predicted recurrence. Conclusion High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of

  6. Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation

    International Nuclear Information System (INIS)

    Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC) but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to “downstage” patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs), has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE) treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence. Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE). Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0–3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen. TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040). None of the other markers predicted recurrence. High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of tumor cells with a CSC phenotype may be a critical factor in the

  7. A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine Therapy Alone

    Directory of Open Access Journals (Sweden)

    Dong-hyun Lee

    2013-11-01

    Full Text Available This report presents a case that shows a significant anticancer effect of Korean medicine therapy (KMT. A 79-year-old man, who was diagnosed as stage Ⅳ non-small cell lung cancer (NSCLC in December 2012, was treated with KMT including intravenous pharmacopunctures and oral herbal medicine from February 22, 2013, until September 2013 without any surgical intervention, chemotherapy or radiotherapy. The intravenous pharmacopunctures were the wild ginseng pharmacopuncture, Cordyceps sinensis pharmacopuncture and Trichosanthes kirilowii pharmacopuncture. The oral herbal medicine used was soramdan, made of cultivated wild ginseng. The effectiveness of this therapy was evaluated with computed tomography and the Eastern Cooperative Oncology Group (ECOG performance scale. The size of the tumor mass was markedly decreased and the ECOG performance scale was also improved. These results suggest that KMT alone can be an effective method to treat NSCLC.

  8. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

    Directory of Open Access Journals (Sweden)

    Vibhor Sharma

    2016-01-01

    Full Text Available Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient’s case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term.

  9. Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways.

    Science.gov (United States)

    Dhillon, Harsharan; Mamidi, Sujan; McClean, Phillip; Reindl, Katie M

    2016-06-01

    Piperlongumine (PL), an alkaloid obtained from long peppers, displays antitumorigenic properties for a variety of human cell- and animal-based models. The aim of this study was to identify the underlying molecular mechanisms for PL anticancer effects on human pancreatic cancer cells. RNA sequencing (RNA-seq) was used to identify the effects of PL on the transcriptome of MIA PaCa-2 human pancreatic cancer cells. PL treatment of pancreatic cancer cells resulted in differential expression of 683 mRNA transcripts with known protein functions, 351 of which were upregulated and 332 of which were downregulated compared to control-treated cells. Transcripts associated with oxidative stress, endoplasmic reticulum (ER) stress, and unfolded protein response pathways were significantly overexpressed with PL treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to validate the RNA-seq results, which included upregulation of HO-1, IRE1α, cytochrome c, and ASNS. The results provide key insight into the mechanisms by which PL alters cancer cell physiology and identify that activation of oxidative stress and ER stress pathways is a critical avenue for PL anticancer effects. PMID:27119744

  10. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells

    OpenAIRE

    Choi, S; Sainz, B.; Corcoran, P.; Uprichard, S.; Jeong, H

    2009-01-01

    1. The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO).

  11. Role of Epigenetics in Stem Cell Proliferation and Differentiation: Implications for Treating Neurodegenerative Diseases

    OpenAIRE

    Bhairavi Srinageshwar; Panchanan Maiti; Gary L. Dunbar; Julien Rossignol

    2016-01-01

    The main objectives of this review are to survey the current literature on the role of epigenetics in determining the fate of stem cells and to assess how this information can be used to enhance the treatment strategies for some neurodegenerative disorders, like Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. Some of these epigenetic mechanisms include DNA methylation and histone modifications, which have a direct impact on the way that genes are expressed in stem cells and...

  12. Regulation of interferon pathway in 2-methoxyestradiol-treated osteosarcoma cells

    International Nuclear Information System (INIS)

    Osteosarcoma is a bone tumor that often affects children and young adults. Although a combination of surgery and chemotherapy has improved the survival rate in the past decades, local recurrence and metastases still develop in 40% of patients. A definite therapy is yet to be determined for osteosarcoma. Anti- tumor compound and a metabolite of estrogen, 2-methoxyestradiol (2-ME) induces cell death in osteosarcoma cells. In this report, we have investigated whether interferon (IFN) pathway is involved in 2-ME-induced anti-tumor effects in osteosarcoma cells. 2-ME effects on IFN mRNA levels were determined by Real time PCR analysis. Transient transfections followed by reporter assays were used for investigating 2-ME effects on IFN-pathway. Western blot analyses were used to measure protein and phosphorylation levels of IFN-regulated eukaryotic initiation factor-2 alpha (eIF-2α). 2-ME regulates IFN and IFN-mediated effects in osteosarcoma cells. 2 -ME induces IFN gene activity and expression in osteosarcoma cells. 2-ME treatment induced IFN-stimulated response element (ISRE) sequence-dependent transcription and gamma-activated sequence (GAS)-dependent transcription in several osteosarcoma cells. Whereas, 2-ME did not affect IFN gene and IFN pathways in normal primary human osteoblasts (HOB). 2-ME treatment increased the phosphorylation of eIF-2α in osteosarcoma cells. Furthermore, analysis of osteosarcoma tissues shows that the levels of phosphorylated form of eIF-2α are decreased in tumor compared to normal controls. 2-ME treatment triggers the induction and activity of IFN and IFN pathway genes in 2-ME-sensitive osteosarcoma tumor cells but not in 2-ME-resistant normal osteoblasts. In addition, IFN-signaling is inhibited in osteosarcoma patients. Thus, IFN pathways play a role in osteosarcoma and in 2-ME-mediated anti-proliferative effects, and therefore targeted induction of IFN signaling could lead to effective treatment strategies in the control of

  13. An ex vivo Gene Therapy Approach to Treat Muscular Dystrophy Using inducible Pluripotent Stem Cells

    OpenAIRE

    Filareto, Antonio; Parker, Sarah; Darabi, Radbod; Borges, Luciene; Iacovino, Michelina; Schaaf, Tory; Mayerhofer, Timothy; Jeffrey S. Chamberlain; Ervasti, James M.; McIvor, R. Scott; Kyba, Michael; Perlingeiro, Rita C. R.

    2013-01-01

    Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem (iPS) cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic iPS cells using a Sleeping Beauty transposon carrying the micro-utrophin (μUTRN) gene, ...

  14. Heat response of mouse tumor cells treated with 5-thio-D-glucose and Rhodamine-123

    International Nuclear Information System (INIS)

    Cellular heat-sensitivity has been known to depend on intracellular energy. The authors studied the thermal response of cultured SCK mammary carcinoma cells in vitro, following glycolytic inhibition with 5-thio-D-glucose (TG) and mitochondrial inactivation with Rhodamine-123 (Rh). The cells in exponential growth phase in RPMI 1640 medium supplemented with serum and antibiotics were exposed to medium containing Rh and/or TG, heated in a prewarmed water bath, and the clonogenic survivals of the heated cells were determined. Thermal cell killing by the 30 min. heating was increased, when 10 and 20 μg/ml Rh were present in the medium at temperatures above 420 and 400C, respectively. The slope of the heat survival curve for 430C heating became steeper in the presence of 10 and 20 μg/ml Rh, and the initial shoulder of the survival curve was unaltered at the dose of 10 μg/ml Rh, but disappeared at 20 μg/ml. A TG dose of 3 mg/ml, which is about 10 times that necessary to kill 90% of cells in 5 hrs. under hypoxic condition, was ineffective in altering any parameters of the heat survival curve of aerobic cells. The combined effect of TG and Rh on the thermal cell killing in aerobic condition did not exceed the effect of Rh alone. The above results indicate that the energy supply derived by mitochondria is an important determinant for the shape of heat survival curve of the proliferating and aerobic SCK tumor cells

  15. Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats

    OpenAIRE

    Li, Ge; Huang, Li-song; Jiang, Ming-hong; Wu, Hui-Ling; Chen, Jing; Huang, Yin; Shen, Yan; He-Xi-Ge, SaiYin; Fan, Wei-wei; Lu, Zhi-qiang; Da-ru LU

    2010-01-01

    Aim: To examine whether implantation of islet preparation-derived proliferating islet cells (PIC) could ameliorate diabetes in rats. Methods: PIC were expanded from rat islet preparation by supplementation of basic fibroblast growth factor (bFGF) and implanted into rats with streptozotocin (STZ)-induced diabetes through the portal vein. Body weight and blood glucose levels were measured. Serum insulin levels were measured by radioimmunoassay. The presence of insulin-positive cells was determi...

  16. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

    OpenAIRE

    J. P. Barras; Baer, H.; Stenzl, A.; Czerniak, A

    1996-01-01

    A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indicatio...

  17. Underestimation of the Maximal Capacity of the Mitochondrial Electron Transport System in Oligomycin-Treated Cells.

    Directory of Open Access Journals (Sweden)

    Juliana S Ruas

    Full Text Available The maximal capacity of the mitochondrial electron transport system (ETS in intact cells is frequently estimated by promoting protonophore-induced maximal oxygen consumption preceded by inhibition of oxidative phosphorylation by oligomycin. In the present study, human glioma (T98G and U-87MG and prostate cancer (PC-3 cells were titrated with different concentrations of the protonophore CCCP to induce maximal oxygen consumption rate (OCR within respirometers in a conventional growth medium. The results demonstrate that the presence of oligomycin or its A-isomer leads to underestimation of maximal ETS capacity. In the presence of oligomycin, the spare respiratory capacity (SRC, i.e., the difference between the maximal and basal cellular OCR, was underestimated by 25 to 45%. The inhibitory effect of oligomycin on SRC was more pronounced in T98G cells and was observed in both suspended and attached cells. Underestimation of SRC also occurred when oxidative phosphorylation was fully inhibited by the ATP synthase inhibitor citreoviridin. Further experiments indicated that oligomycin cannot be replaced by the adenine nucleotide translocase inhibitors bongkrekic acid or carboxyatractyloside because, although these compounds have effects in permeabilized cells, they do not inhibit oxidative phosphorylation in intact cells. We replaced CCCP by FCCP, another potent protonophore and similar results were observed. Lower maximal OCR and SRC values were obtained with the weaker protonophore 2,4-dinitrophenol, and these parameters were not affected by the presence of oligomycin. In permeabilized cells or isolated brain mitochondria incubated with respiratory substrates, only a minor inhibitory effect of oligomycin on CCCP-induced maximal OCR was observed. We conclude that unless a previously validated protocol is employed, maximal ETS capacity in intact cells should be estimated without oligomycin. The inhibitory effect of an ATP synthase blocker on potent

  18. Underestimation of the Maximal Capacity of the Mitochondrial Electron Transport System in Oligomycin-Treated Cells.

    Science.gov (United States)

    Ruas, Juliana S; Siqueira-Santos, Edilene S; Amigo, Ignacio; Rodrigues-Silva, Erika; Kowaltowski, Alicia J; Castilho, Roger F

    2016-01-01

    The maximal capacity of the mitochondrial electron transport system (ETS) in intact cells is frequently estimated by promoting protonophore-induced maximal oxygen consumption preceded by inhibition of oxidative phosphorylation by oligomycin. In the present study, human glioma (T98G and U-87MG) and prostate cancer (PC-3) cells were titrated with different concentrations of the protonophore CCCP to induce maximal oxygen consumption rate (OCR) within respirometers in a conventional growth medium. The results demonstrate that the presence of oligomycin or its A-isomer leads to underestimation of maximal ETS capacity. In the presence of oligomycin, the spare respiratory capacity (SRC), i.e., the difference between the maximal and basal cellular OCR, was underestimated by 25 to 45%. The inhibitory effect of oligomycin on SRC was more pronounced in T98G cells and was observed in both suspended and attached cells. Underestimation of SRC also occurred when oxidative phosphorylation was fully inhibited by the ATP synthase inhibitor citreoviridin. Further experiments indicated that oligomycin cannot be replaced by the adenine nucleotide translocase inhibitors bongkrekic acid or carboxyatractyloside because, although these compounds have effects in permeabilized cells, they do not inhibit oxidative phosphorylation in intact cells. We replaced CCCP by FCCP, another potent protonophore and similar results were observed. Lower maximal OCR and SRC values were obtained with the weaker protonophore 2,4-dinitrophenol, and these parameters were not affected by the presence of oligomycin. In permeabilized cells or isolated brain mitochondria incubated with respiratory substrates, only a minor inhibitory effect of oligomycin on CCCP-induced maximal OCR was observed. We conclude that unless a previously validated protocol is employed, maximal ETS capacity in intact cells should be estimated without oligomycin. The inhibitory effect of an ATP synthase blocker on potent protonophore

  19. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  20. Renal cell carcinoma in patients with a solitary kidney after nephrectomy treated with radiofrequency ablation: Mid term results

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Ralf-Thorsten [Institute of Clinical Radiology, Ludwig Maximilians-University, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich (Germany)], E-mail: ralf-thorsten.hoffmann@med.uni-muenchen.de; Jakobs, Tobias F. [Institute of Clinical Radiology, Ludwig Maximilians-University, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich (Germany); Kubisch, Constanze H. [Med II Department of Internal Medicine/Gastroenterology, Ludwig Maximilians-University, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich (Germany); Trumm, Christoph [Institute of Clinical Radiology, Ludwig Maximilians-University, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich (Germany); Weber, Christof [Institute of Diagnostic and Interventional Radiology, Klinikum - Deggendorf, Deggendorf (Germany); Siebels, Michael [Urologische Gemeinschaftspraxis, Josef - Retzerstrasse, Munich (Germany); Helmberger, Thomas K. [Institute of Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Reiser, Maximilian F. [Institute of Clinical Radiology, Ludwig Maximilians-University, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich (Germany)

    2010-03-15

    This retrospective study aimed to evaluate the feasibility and effectiveness of radiofrequency ablation (RFA) in patients with solitary kidney for the treatment of renal cell carcinoma (RCC). Within 2 years 10 patients (seven males, three females; age 65 {+-} 8 years) were treated. All patients had a history of nephrectomy of the contralateral kidney. The indications for RFA were inoperability or high probability of complete renal failure after surgical enucleation of the tumor. 13 tumors with a size between 1.9 and 4.2 cm (average 2.7 cm) were treated. In patients with a tumor diameter larger than 2.5 cm a transarterial embolization was performed prior to RFA to reduce heat sink effect and risk of bleeding. Therapeutical success was defined as a lack of contrast enhancement in follow up examinations and shrinking of the treated area. Furthermore all patients' renal function was monitored. RFA of renal tumors under CT-fluoroscopy was feasible in all patients. Within the follow up (3 and 24 months) no tumor recurrence or major complication was detected. One patient developed another RCC and was successfully treated with a second RF-ablation. None of the patients developed renal failure with the need of hemodialysis. In one of the patients a hemorrhage into the surrounding tissue was noticed, which stopped spontaneously. RFA is a valuable and effective therapeutical option in patients with solitary kidney suffering from inoperable renal cell carcinoma. The complication rate is small and an excellent tumor control can be achieved without deterioration of the renal function.

  1. Risk factors associated with fatal pulmonary hemorrhage in locally advanced non-small cell lung cancer treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    The purpose of this study was to identify the risk factors associated with fatal pulmonary hemorrhage (PH) in patients with locally advanced non-small cell lung cancer (NSCLC), treated with chemoradiotherapy. The medical records of 583 patients with locally advanced NSCLC, who were treated with chemoradiotherapy between July 1992 and December 2009 were reviewed. Fatal PH was defined as PH leading to death within 24 h of its onset. Tumor cavitation size was defined by the cavitation diameter/tumor diameter ratio and was classified as minimum (< 0.25), minor (≥ 0.25, but < 0.5), and major (≥ 0.5). Of the 583 patients, 2.1% suffered a fatal PH. The numbers of patients with minimum, minor, and major cavitations were 13, 11, and 14, respectively. Among the 38 patients with tumor cavitation, all 3 patients who developed fatal PH had major cavitations. On multivariate analysis, the presence of baseline major cavitation (odds ratio, 17.878), and a squamous cell histology (odds ratio, 5.491) proved to be independent significant risk factors for fatal PH. Interestingly, all patients with fatal PH and baseline major cavitation were found to have tumors with squamous cell histology, and the occurrence of fatal PH in patients having both risk factors was 33.3%. Patients at high risk of fatal PH could be identified using a combination of independent risk factors

  2. In vitro cytokine profiles and viability of different human cells treated with whole cell lysate of Mycobacterium avium subsp. paratuberculosis

    Directory of Open Access Journals (Sweden)

    Rani Pittu

    2012-09-01

    Full Text Available Abstract Mycobacterium avium subsp. paratuberculosis (MAP is a zoonotic pathogen, a very slow growing bacterium which is difficult to isolate and passage in conventional laboratory culture. Although its association with Johne’s disease or paratuberculosis of cattle is well established, it has been only putatively linked to Crohn’s disease in humans. Further, MAP has been recently suggested to be a trigger for other autoimmune diseases such as type-1 diabetes mellitus (T1DM. Recently, some studies have indicated that exposure to MAP is associated with elevated levels of antibodies against MAP lysate although the exact mechanism and significance of the same remains unclear. Further, the cytokine profiles relevant in MAP associated diseases of humans and their exact role in the pathophysiology are not clearly known. We performed in vitro cytokine analyses after exposing different cultured human cells to the whole cell lysate of MAP and found that MAP lysate induces secretion of cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by human peripheral blood mononuclear cells (PBMCs. Also, it induces secretion of IL-8 by cultured human stomach adenocarcinoma cells (AGS and PANC-1(human pancreatic carcinoma cell line cells. We also found that MAP lysate induced cytotoxicity in PANC-1cells. Collectively, these results provide a much needed base-line data set of cytokines broadly signifying a MAP induced cellular response by human cells.

  3. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    Science.gov (United States)

    2016-02-23

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  4. Cell-Cycle-Dependent Variations in the FTIR Spectroscopy of HeLa Cells Treated with Trichostatin A

    Institute of Scientific and Technical Information of China (English)

    ZHANG Feng-qiu; QI Jian; YANG Zhan-guo

    2011-01-01

    It is quite complex to evaluate the mechanism of action for antitumor drugs on cancer cells.Studies have pointed out that there is an unique advantage of Fourier transform infrared spectrum to obtain a fingerprint of all molecules present in the cells when cancer cells were exposed to anti-cancer drugs.Trichostatin A (TSA) is a most potent reversible inhibitor of mammalian histone deacetylases.It can inhibit cancer cell growth in vitro and in vivo.In the present study,HeLa cells were exposed to 0,50,100,200,300 and 400 nmol · L-1 TSA,and FTIR spectra were applied to evaluate the effect of TSA on cancer cells.Results show that there is some significant relationship between the changes in FTIR absorption and cell cycle arresting.On the other hand,this investigation shows that the concentration of TSA had to be more than 200 nmol · L-1 in order to ensure A1080 cm-1/A1540cm-1 ≥1 for inhibiting cell proliferation.

  5. Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate

    DEFF Research Database (Denmark)

    Soleimani, A; Berntsen, A; Svane, I M; Pedersen, Anders Elm

    2009-01-01

    Patients with metastatic renal cell carcinoma (mRCC) have a limited life expectancy but still a subset of these patients develop immune and clinical responses after immunotherapy including dendritic cell (DC) vaccination. In a recently published phase I/II trials, fourteen HLA-A2 negative patients...

  6. Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

  7. Mortality in asymptomatic vs. symptomatic patients surgically treated for non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Madsen, Kirsten Riis; Bødtger, Uffe

    Introduction: Compared to incidentally found lung cancer, the presence of symptoms (eg. cough, haemoptysis, pain, weight loss) at diagnosis is associated with a 50% reduction in median survival. In surgically treated patients, it is unknown whether presence of symptoms has prognostic significance...... higher in asymptomatic than symptomatic subjects (23% vs. 12%), and in patients with former malignancy compared to patients with no former cancer (17% vs. 16%). Discussion: Symptoms at diagnosis per se appear unrelated to mortality in patients with NSCLC referred for surgery. Asymptomatic patients were...

  8. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil

    OpenAIRE

    Roberto Madeddu; Cristiano Farace; Andrea Montella; Pasquale Bandiera; Garcia, Maria A.; Houria Boulaiz; Giuliana Solinas; Yolande Asara; Juan A. Marchal; Esther Carrasco

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of th...

  9. Spag16, an axonemal central apparatus gene, encodes a male germ cell nuclear speckle protein that regulates SPAG16 mRNA expression.

    Directory of Open Access Journals (Sweden)

    David R Nagarkatti-Gude

    Full Text Available Spag16 is the murine orthologue of Chlamydomonas reinhardtii PF20, a protein known to be essential to the structure and function of the "9+2" axoneme. In Chlamydomonas, the PF20 gene encodes a single protein present in the central pair of the axoneme. Loss of PF20 prevents central pair assembly/integrity and results in flagellar paralysis. Here we demonstrate that the murine Spag16 gene encodes two proteins: 71 kDa SPAG16L, which is found in all murine cells with motile cilia or flagella, and 35 kDa SPAG16S, representing the C terminus of SPAG16L, which is expressed only in male germ cells, and is predominantly found in specific regions within the nucleus that also contain SC35, a known marker of nuclear speckles enriched in pre-mRNA splicing factors. SPAG16S expression precedes expression of SPAG16L. Mice homozygous for a knockout of SPAG16L alone are infertile, but show no abnormalities in spermatogenesis. Mice chimeric for a mutation deleting the transcripts for both SPAG16L and SPAG16S have a profound defect in spermatogenesis. We show here that transduction of SPAG16S into cultured dispersed mouse male germ cells and BEAS-2B human bronchial epithelial cells increases SPAG16L expression, but has no effect on the expression of several other axoneme components. We also demonstrate that the Spag16L promoter shows increased activity in the presence of SPAG16S. The distinct nuclear localization of SPAG16S and its ability to modulate Spag16L mRNA expression suggest that SPAG16S plays an important role in the gene expression machinery of male germ cells. This is a unique example of a highly conserved axonemal protein gene that encodes two protein products with different functions.

  10. PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Steffen Filskov Sorensen

    2016-02-01

    Full Text Available BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1 expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1 therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck. PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months. No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.

  11. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Mahmoud Aljurf

    2016-01-01

    Full Text Available Background. We studied DNA chimerism in cell-free DNA (cfDNA in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126 showed that, of 84 patients with 100% donor DNA in PMN, 16 (19% had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19% showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41% showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.

  12. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies

    Science.gov (United States)

    Aljurf, Mahmoud; Abalkhail, Hala; Alseraihy, Amal; Mohamed, Said Y.; Ayas, Mouhab; Alsharif, Fahad; Alzahrani, Hazza; Al-Jefri, Abdullah; Aldawsari, Ghuzayel; Al-Ahmari, Ali; Belgaumi, Asim F.; Walter, Claudia Ulrike; El-Solh, Hassan; Rasheed, Walid; Albitar, Maher

    2016-01-01

    Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126) showed that, of 84 patients with 100% donor DNA in PMN, 16 (19%) had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19%) showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41%) showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse. PMID:27006832

  13. Assessment of contrast flow modification in aneurysms treated with closed-cell self-deploying asymmetric vascular stents (SAVS)

    OpenAIRE

    Ionita, Ciprian N; Wang, Weiyuan; Bednarek, Daniel R.; Rudin, Stephen

    2010-01-01

    The Asymmetric Vascular Stent (AVS) for intracranial aneurysm (IA) treatment is an experimental device, specially designed for intra-aneurysmal blood flow diversion and thrombosis promotion. The stent has a low-porous patch to cover only the aneurysm neck while the rest of the stent is very porous to avoid blockage of adjacent branches. The latest AVS design is similar to state-of-art, closed-cell, self-expanding, neurovascular stent. The stents were used to treat sixteen rabbit-elastase aneu...

  14. Neuropsychological evaluation of patients with inoperable non-small cell lung cancer treated with combination chemotherapy or radiotherapy

    International Nuclear Information System (INIS)

    Neuropsychological tests were used to evaluate possible central nervous system dysfunction in patients treated with chemotherapy. Ninety-five patients with non-small cell lung cancer limited disease were randomized to either radiotherapy (2.8 Gyx15) or combination chemotherapy with cisplatin and etoposide. In order to evaluate cognitive functions three neuropsychological tests were applied: Trail Making, Benton Visual Retention Test and Verbal Learning. Changes in the patients' test scores before and after treatment were compared. The chemotherapy patients showed reduced performance on some of the neuropsychological tests compared to the radiotherapy group. This indicates a treatment related effect on the central nervous system, possibly caused by the combination chemotherapy. (orig.)

  15. Primary non-small cell lung cancer in a transplanted lung treated with stereotactic body radiation therapy. A case study

    International Nuclear Information System (INIS)

    The first case of primary lung cancer in a transplanted lung was described in 2001. Since then, only 5 cases of lung cancer in donated lung have been reported. We present one more patient with non-small cell cancer in the transplanted lung treated with stereotactic body radiation therapy. In most cases of primary lung cancer in transplanted lung, rapid progression of the cancer was reported. Occurrence of the locoregional failure in our case could be explained by factors related to the treatment protocol and also to underlying immunosuppression.

  16. Two SCID cases with Cernunnos-XLF deficiency successfully treated by hematopoietic stem cell transplantation.

    Science.gov (United States)

    Çağdaş, Deniz; Özgür, Tuba Turul; Asal, Gülten Türkkanı; Revy, Patrick; De Villartay, Jean-Pierre; van der Burg, Mirjam; Sanal, Özden; Tezcan, Ilhan

    2012-08-01

    SCID affects T and B cell differentiation and functions, presenting with severe opportunistic infections in the early postnatal period. It is fatal unless stem cell transplantation is performed. RS SCID forms are caused by defects in the NHEJ pathway, the enzymatic process required for the repair of DNA double-strand breaks. Cernunnos-XLF defect is one of the defects in this pathway. Here, we present two patients with Cernunnos-XLF defect, both having microcephaly, prominent growth retardation, and T-B-NK+SCID, one of whom had AHA. These patients received hematopoietic stem cells from HLA identical related donor without conditioning regimen and recovered without any complication. Now, both of the patients are well and alive seven and one yr after transplantation, respectively. A remarkable observation was the severe diarrhea that occurred in both patients soon after transplantation. PMID:21535335

  17. Improved recovery of bisulphite-treated cell-free DNA in plasma

    DEFF Research Database (Denmark)

    Pedersen, Inge Søkilde; Krarup, H.B.; Thorlacius-Ussing, O.;

    Detection of cell-free methylated DNA in plasma is a promising tool for tumour diagnosis and monitoring. Due to the very low amount of cell-free DNA in plasma, sensitivity of the detection methods are of utmost importance. The vast majority of currently available methods for analysing DNA...... of PCR amplifying methylated and umethylated MEST. This procedure allows low levels of DNA to be easily and reliably analysed, a prerequisite for the clinical usefulness of cell-free methylated DNA detection in plasma....... methylation are based on bisulphite-mediated deamination of cytosine. However, the recovery of bisulphite-converted DNA is very poor. Here we introduce an alternative method for the crucial steps of bisulp