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Sample records for chemosensitivity test-guided systemic

  1. A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Kazumichi Abe; Takeru Wakatsuki; Fumiko Katsushima; Kyoko Monoe; Yukiko Kanno; Atsushi Takahashi; Junko Yokokawa; Hiromasa Ohira

    2009-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment Ⅷ of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion.After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

  2. The Effect of Primary Cancer Cell Culture Models on the Results of Drug Chemosensitivity Assays: The Application of Perfusion Microbioreactor System as Cell Culture Vessel

    OpenAIRE

    Chia-Hsun Hsieh; Yi-Dao Chen; Shiang-Fu Huang; Hung-Ming Wang; Min-Hsien Wu

    2015-01-01

    To precisely and faithfully perform cell-based drug chemosensitivity assays, a well-defined and biologically relevant culture condition is required. For the former, a perfusion microbioreactor system capable of providing a stable culture condition was adopted. For the latter, however, little is known about the impact of culture models on the physiology and chemosensitivity assay results of primary oral cavity cancer cells. To address the issues, experiments were performed. Results showed that...

  3. Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

    Science.gov (United States)

    One mode of action of the antimycotics amphotericin B (AMB) or itraconazole (ITZ) against filamentous fungi involves cellular oxidative stress response. Aspergillus fumigatus sakA', a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidation system, was more sensitive to AMB ...

  4. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Wen-Lin; Das, Debopriya; Ziyad, Safiyyah; Bhattacharya, Sanchita; Gibb, William J.; Heiser, Laura M.; Sadanandam, Anguraj; Fontenay, Gerald V.; Hu, Zhi; Wang, Nicholas J.; Bayani, Nora; Feiler, Heidi S.; Neve, Richard M.; Wyrobek, Andrew J.; Spellman, Paul T.; Marton, Laurence J.; Gray, Joe W.

    2009-11-14

    Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signaling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.

  5. Inhibition of Bcl-2 expression by a novel tumor-specific RNA interference system increases chemosensitivity to 5-fluorouracil in Hela cells

    Institute of Scientific and Technical Information of China (English)

    Sheng-lin HUANG; Yi WU; Hai YU; Ping ZHANG; Xing-qian ZHANG; Lei YING; Han-fang ZHAO

    2006-01-01

    Aim: RNA interference (RNAi) has been proposed as a potential treatment for cancer, but the lack of cellular targets limits its use in cancer gene therapy. No current technology has achieved direct tumor-specific gene silencing using RNAi.In the present study we attempt to develop a tumor-specific RNAi system using the human telomerase reverse transcriptase (hTERT) promoter; furthermore, we analyzed its inhibitive effect on Bcl-2 expression. Methods: The vectors containing a small hairpin RNA (shRNA) to target exogenous reporters [firefly luciferase and enhanced green fluorescent protein (EGFP)] and endogenous gene (Bcl-2)were constructed. Luciferase expression was determined by dual luciferase assay.Reverse transcription-polymerase chain reaction (RT-PCR), fluorescence microscopy and fluorescence-activated cell sorting (FACS) were used to measure EGFP expression. Inhibition of Bcl-2 was evaluated by RT-PCR and Western blotting.Cell proliferation and viability were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. FACS was used to analyze the cell cycle distribution profile. Results: We showed that with the hTERT promoter directly driving shRNA transcription, expression of the exogenous reporters (LUC and EGFP) in tumor cells, but not normal cells, was specifically inhibited in vitro. The hTERT promoter-driven shRNA also depressed the expression of Bcl-2. Inhibition of Bcl-2 did not affect cell proliferation, but increased the chemosensitivity of HeLa cells to 5-fluorouracil. Conclusion: The present study describes an efficient RNAi system for gene silencing that is specific to tumor cells using the hTERT promoter. Suppression of Bcl-2 by using this system sensitized HeLa cells to 5-fluorouracil. This system may be useful for RNAi therapy.

  6. Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zeeberg, Katrine; Cardone, Rosa Angela; Greco, Maria Raffaella; Saccomano, Mara; Nøhr-Nielsen, Asbjørn; Alves, Frauke; Pedersen, Stine Falsig; Reshkin, Stephan Joel

    2016-07-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis, due to the influence of the tumor stroma, which promotes tumor growth, early invasion and chemoradiation resistance. Efforts to develop models for identifying novel anticancer therapeutic compounds have been hampered by the limited ability of in vitro models to mimic these in vivo tumor-stroma interactions. This has led to the development of various three-dimensional (3D) culture platforms recapitulating the in vivo tumor-stroma crosstalk and designed to better understand basic cancer processes and screen drug action. However, a consensus for different experimental 3D platforms is still missing in PDAC. We compared four PDAC cell lines of different malignancy grown in 2D monolayers to three of the more commonly used 3D techniques (ultralow adhesion concave microwells, Matrigel inclusion and organotypic systems) and to tumors derived from their orthotopic implantation in mice. In these 3D platforms, we observed that cells grow with very different tumor morphologies and the organotypic setting most closely resembles the tumor cytoarchitecture obtained by orthotopically implanting the four cell lines in mice. We then analyzed the molecular and cellular responses of one of these cell lines to epidermal growth factor receptor (EGFR) stimulation with EGF and inhibition with erlotinib and found that only in the 3D platforms, and especially the organotypic, cells: i) responded to EGF by changing the expression of signalling components underlying cell-stroma crosstalk and tissue architecture, growth, invasion and drug resistance (E-cadherin, EGFR, ezrin, β1 integrin, NHERF1 and HIF-1α) similar to those reported in vivo; ii) had stimulated growth and increased erlotinib sensitivity in response to EGF, more faithfully mimicking their known in vivo behaviour. Altogether, these results, indicate the organotypic as the most relevant physiological 3D system to study the

  7. CO2 chemosensitivity during immersion in humans.

    Science.gov (United States)

    Chang, L P; Lundgren, C E

    1995-01-01

    Hypercapnic ventilatory response was compared in 9 seated subjects during head-out immersion in 35 degrees C (thermoneutral) water and during non-immersion in 28 degrees C (thermoneutral) room air. Using Read's CO2-rebreathing technique, minute ventilation (VE) and end-tidal (ET) PCO2 were sampled continuously for 4-5 min with a spirometer and a mass spectrometer, while the subject rebreathed a 6 L gas mixture initially containing 7% CO2 and 93% O2 in a bag-in-box system. The slope of the hypercapnic ventilatory response curve, expressed as delta VE/delta PETCO2, ranged from 0.76 to 2.49 L/min/mmHg. Immersion affected neither the slope nor the position of the hypercapnic ventilatory response curve. The rate of rise of PETCO2 during immersed CO2-rebreathing was significantly reduced (4.47 +/- 0.19 [SE] mmHg/min), as compared to the control value (5.67 +/- 0.24). It was concluded that the CO2 chemosensitivity during immersion in humans did not change and that the capacity to store CO2 in tissue might have been increased. PMID:8549236

  8. Ethical hacking and penetration testing guide

    CERN Document Server

    Baloch, Rafay

    2014-01-01

    Requiring no prior hacking experience, Ethical Hacking and Penetration Testing Guide supplies a complete introduction to the steps required to complete a penetration test, or ethical hack, from beginning to end. You will learn how to properly utilize and interpret the results of modern-day hacking tools, which are required to complete a penetration test. The book covers a wide range of tools, including Backtrack Linux, Google reconnaissance, MetaGooFil, dig, Nmap, Nessus, Metasploit, Fast Track Autopwn, Netcat, and Hacker Defender rootkit. Supplying a simple and clean explanation of how to effectively utilize these tools, it details a four-step methodology for conducting an effective penetration test or hack.Providing an accessible introduction to penetration testing and hacking, the book supplies you with a fundamental understanding of offensive security. After completing the book you will be prepared to take on in-depth and advanced topics in hacking and penetration testing. The book walks you through each ...

  9. Heterogeneity of chemosensitivity in esophagealcancer using ATP-tumor chemosensitivity assay

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang LING; Zhi-xing YANG; Jian YIN; Wei-min MAO; Chun-jian QI; Xiao-xiao LU; Li-juan QIAN; Lin-hui GU; Zhi-guo ZHENG; Qiang ZHAO; Shi WANG; Xian-hua FANG

    2012-01-01

    Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials,which fails to take into account the known heterogeneity of chemosensitivity between patients.This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers.Methods:A total of 42 esophageal cancer specimens were collected.The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA).Results:Thirty eight specimens produced evaluable results (90.5%).The most active single agent tested was nedaplatin,to which 28.9% of samples were sensitive.Combinations of chemotherapy agents exhibited much higher sensitivity:cisplatin+paclitaxel was sensitive in 16 of 38 (42.1%) of samples,while nedaplatin+paclitaxel was more effective,which was sensitive in 20 of 38 cases (52.6%).Conclusion:There was a marked heterogeneity of chemosensitivity in esophageal cancer.Chemosensitivity testing may provide apractical method for testing new regimens before clinical trials in esophageal cancer patients.

  10. Accessing chemosensitivity and ventilatory stability from transient stimuli.

    Science.gov (United States)

    Bruce, E N

    1996-12-01

    The degree of ventilatory stability of human subjects is inferred from the presence or absence of oscillations in ventilation in response to a brief CO2 disturbance using the method of pseudorandom stimulation. Simultaneously, chemosensitivity is measured. Stability and chemosensitivity are compared in hyperoxia between wakefulness and stage 2 non-rapid eye movement (NREM) sleep and between normoxia and hyperoxia awake. Stability is unchanged between wakefulness and sleep but chemosensitivity decreases in sleep. In contrast, stability is reduced in normoxia whereas chemosensitivity is larger than in hyperoxia. It is concluded that chemosensitivity and ventilatory stability may change independently, implying that chemosensitivity alone is not an adequate indicator of the likelihood of a subject to exhibit periodic breathing. PMID:9085498

  11. In vitro chemosensitivity of head and neck cancer cell lines

    Directory of Open Access Journals (Sweden)

    Schuler PJ

    2010-08-01

    Full Text Available Abstract Background Systemic treatment of head and neck squamous cell carcinoma (HNSCC includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. Methods Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. Results All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. Conclusion Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

  12. Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Amer Khalid

    2009-08-01

    Full Text Available Abstract Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

  13. Respiratory control in the newborn : Central chemosensitivity, neuropeptides and nicotinic effects

    OpenAIRE

    Wickström, Ronny

    2002-01-01

    Breathing is regulated by a complex network of neurons located mainly in the brainstem. For the newborn, it is critical for survival that a continuous respiration is established after birth. However, the regulation of respiration also undergoes maturation in the postnatal period. This thesis focuses on some of the systems modulating respiration that may be of great importance for the newborn: central (C02) chemosensitivity and the neuropeptides substance P (SP) and galanin ...

  14. EFFECTS OF SIMULATED MICROGRAVITY ON PROLIFERATION AND CHEMOSENSITIVITY IN MALIGNANT GLIOMA CELLS

    OpenAIRE

    Kurisu, Kaoru; Takeda, Masaaki; Okazaki, Takahito; Kawahara, Yumi; Yuge, Lous

    2014-01-01

    BACKGROUND: Everything on the earth can be affected by gravity of the earth. So, microgravity, as small as 10 minus 3 times G, can make some effects to the growth or maturation of cells. Under this hypothesis we examined cell proliferation and chemosensitivity after exposure to simulated microgravity using the malignant glioma cell lines. We exposed cells to simulated microgravity using a 3D-clinostat which is a type of rotating culture system that has two independent axes of rotation to disp...

  15. N-methylformamide: cytotoxic, radiosensitizer, or chemosensitizer

    International Nuclear Information System (INIS)

    N-methylformamide (NMF), a polar solvent, is currently being evaluated by the National Cancer Institute (NCI) as an antineoplastic agent because of its activity against colon, mammary, and lung tumor xenografts. Results from preclinical studies suggest that it has radiosensitizing, chemosensitizing, and differentiating activity. Its mechanism of action remains unknown, but may involve cellular depletion of glutathione, cell membrane changes, or modulation of proto-oncogene expression. Preclinical toxicology studies conducted in mice, rats, and beagle dogs showed reversible hepatotoxicity to be dose-limiting. Clinically, NMF is administered both orally and by intravenous (IV) injection. The bioavailability with oral administration is 90% to 95%. The highest reported plasma concentration of NMF is approximately 4 mmol/L in a patient who received a dose of 2,000 mg/m2 of IV NMF. Biphasic elimination with IV NMF is seen on both the daily for five days and weekly for 3 weeks schedule. Approximately 5% to 7% of the total administered IV dose is excreted in the urine. In phase I studies, dose-limiting toxicities included reversible hepatotoxicity, a generalized malaise syndrome, and nausea and vomiting. One partial response has been reported in the 111 patients treated on phase II trials in colorectal, head and neck, and renal carcinomas. Suggestions for the future development of this drug are presented. 82 references

  16. Chemosensitization of plant pathogenic fungi to agricultural fungicides

    Science.gov (United States)

    Continual use of fungicides in agriculture often results in development of resistance in pathogens. A new strategy to aid in overcoming or minimizing this problem is enhancement of pathogen sensitivity to fungicides by chemosensitization. This involves combining fungicides with certain non-fungicida...

  17. Comparison of the ability of some radiosensitizers undergoing clinical trials to act as chemosensitizers

    International Nuclear Information System (INIS)

    The abilities of misonidazole, Ro 05-9963, Ro 03-8799 and Sr-2508 to enhance the action of the drugs cyclophosphamide (CY) and melphalan (L-PAM) have been compared in two mouse fibrosarcomas at acute and chronic sensitizer doses. SR-2508 was not effective with either CY or L-PAM in either tumor. Some enhancement of CY was obtained with Ro 05-9963 and Ro 03-8799; however, the degree of enhancement varied according to tumor and acute or chronic sensitizer dose. In all cases, the degree of enhancement was less than that obtained with an equivalent dose of misonidazole in both tumor systems. Of the four compounds tested, MISO would appear to have the most potential as a chemosensitizer

  18. MicroRNA-mediated Silencing of RhoC Inhibits Tumor Invasion and Increases Chemosensitivity to Paclitaxel in SKOV3 Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    PAN Ying; DU Zhen-wu; LENG Wei-chun; ZHOU Jia-wen; WANG Ying-jian; SHENG Min-jia; WANG Jun-rong; ZHANG Gui-zhen

    2011-01-01

    RhoC is a member of the Ras-homologous family of genes which are implicated in tumorigenesis and tumor progression. Up-regulation of RhoC is associated with tumor progression in ovarian carcinoma and RhoC is significantly correlated with the invasive capability of ovarian cancer cell lines in vitro. We developed a system that blocks RhoC in the human ovarian cancer SKOV3 cells using specific MicroRNA(miRNA) interference. By transfecting SKOV3 cells with the plasmid vector to express specific MiRNA that targets human RhoC, we were able to establish a stable clone in which RhoC expression was significantly downregnlated. This resulted in the decreased invasive potential of SKOV3 cells as well as increased chemosensitivity to paclitaxel. RhoC involves in invasion and chemosensitivity of SKOV3, indicating that RhoC may be a promising therapeutic target for ovarian cancer.

  19. Association of telomerase activity with radio- and chemosensitivity of neuroblastomas

    International Nuclear Information System (INIS)

    Telomerase activity compensates shortening of telomeres during cell division and enables cancer cells to escape senescent processes. It is also supposed, that telomerase is associated with radio- and chemoresistance. In the here described study we systematically investigated the influence of telomerase activity (TA) and telomere length on the outcome of radio- and chemotherapy in neuroblastoma. We studied the effects on dominant negative (DN) mutant, wild type (WT) of the telomerase catalytic unit (hTERT) using neuroblastoma cell lines. The cells were irradiated with 60Co and treated with doxorubicin, etoposide, cisplatin and ifosfamide, respectively. Viability was determined by MTS/MTT-test and the GI50 was calculated. Telomere length was measured by southernblot analysis and TA by Trap-Assay. Compared to the hTERT expressing cells the dominant negative cells showed increased radiosensitivity with decreased telomere length. Independent of telomere length, telomerase negative cells are significantly more sensitive to irradiation. The effect of TA knock-down or overexpression on chemosensitivity were dependent on TA, the anticancer drug, and the chemosensitivity of the maternal cell line. Our results supported the concept of telomerase inhibition as an antiproliferative treatment approach in neuroblastomas. Telomerase inhibition increases the outcome of radiotherapy while in combination with chemotherapy the outcome depends on drug- and cell line and can be additive/synergistic or antagonistic. High telomerase activity is one distinct cancer stem cell feature and the here described cellular constructs in combination with stem cell markers like CD133, Aldehyddehydrogenase-1 (ALDH-1) or Side population (SP) may help to investigate the impact of telomerase activity on cancer stem cell survival under therapy

  20. Private and Commercial Pilot: Ligher-Than-Air Airship. Flight Test Guide. (Part 61 Revised).

    Science.gov (United States)

    Federal Aviation Administration (DOT), Washington, DC. Flight Standards Service.

    The flight test guide assists the applicant and his instructor in preparing for the flight test for the Private or Commercial Pilot Certificate with a Lighter-Than-Air Category and Airship Class Rating under Part 61 (revised) of Federal Aviation Regulations. It contains information and guidance concerning pilot operations, procedures, and…

  1. Rapid in vitro chemosensitivity analysis of human colon tumor cell lines

    International Nuclear Information System (INIS)

    In oncology, diagnostic assays have the potential to individualize treatment. Due to a large number of chemotherapeutic agents available, a chemosensitivity assay would be of great value for patients receiving chemotherapy. However, no broadly accepted test exists to date. Our work aims at establishing a chemosensitivity test using a microphysiometer, a device that measures the extracellular acidification rate of cells. The test assesses chemosensitivity by comparing the acidification rate of cells treated with cytostatic agents with that of nontreated cells. We performed experiments with two human colon tumor cell lines, HCT 116 and SW620, and cytostatic agents commonly used in therapy of colon carcinoma. We showed that a chemosensitivity test can be reproducibly performed using a microphysiometer. Suitable media and conditions for the assay were found. Test results were further correlated with the crystal violet assay and a tetrazolium salt assay. In comparison, cytostatic effects were rapidly and most clearly displayed with the microphysiometer. Our results suggest that microphysiometry is a promising platform for chemosensitivity testing

  2. In Vitro Chemosensitivity Testing of Primary and Recurrent Breast Carcinomas and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    Zhi LI; Haiping SONG; Wenshan HE; Yuan TIAN; Tao HUANG

    2008-01-01

    In this study, in vitro chemosensitivity testing was conducted on primary cultured breast cancer cells from 96 patients with breast cancer, and the results showed that the cells from a few patients with primary breast cancer developed multidrug resistance (MDR) prior to the first chemotherapy exposure. All the cells from the recurrent cancer patients had MDR. The findings suggested that patients having MDR would benefit from high-dose chemotherapy (HDC) regimens. In vitro chemosensitivity screening, which was aimed at improving the therapeutic efficacy and minimizing side effects, helps in choosing individualized treatment for breast cancer.

  3. Targeting the Mitochondrial Respiratory Chain of Cryptococcus through Antifungal Chemosensitization: A Model for Control of Non-Fermentative Pathogens

    Directory of Open Access Journals (Sweden)

    Kathleen L. Chan

    2013-07-01

    Full Text Available Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain (MRC inhibition compared to species of Candida. This higher sensitivity results from the inability of Cryptococcus to generate cellular energy through fermentation. To heighten disruption of cellular MRC, octyl gallate (OG or 2,3-dihydroxybenzaldehyde (2,3-DHBA, phenolic compounds inhibiting mitochondrial functions, were selected as chemosensitizers to pyraclostrobin (PCS; an inhibitor of complex III of MRC. The cryptococci were more susceptible to the chemosensitization (i.e., PCS + OG or 2,3-DHBA than the Candida with all Cryptococcus strains tested being sensitive to this chemosensitization. Alternatively, only few of the Candida strains showed sensitivity. OG possessed higher chemosensitizing potency than 2,3-DHBA, where the concentration of OG required with the drug to achieve chemosensitizing synergism was much lower than that required of 2,3-DHBA. Bioassays with gene deletion mutants of the model yeast Saccharomyces cerevisiae showed that OG or 2,3-DHBA affect different cellular targets. These assays revealed mitochondrial superoxide dismutase or glutathione homeostasis plays a relatively greater role in fungal tolerance to 2,3-DHBA or OG, respectively. These findings show that application of chemosensitizing compounds that augment MRC debilitation is a promising strategy to antifungal control against yeast pathogens.

  4. Systematically characterizing and prioritizing chemosensitivity related gene based on Gene Ontology and protein interaction network

    Directory of Open Access Journals (Sweden)

    Chen Xin

    2012-10-01

    Full Text Available Abstract Background The identification of genes that predict in vitro cellular chemosensitivity of cancer cells is of great importance. Chemosensitivity related genes (CRGs have been widely utilized to guide clinical and cancer chemotherapy decisions. In addition, CRGs potentially share functional characteristics and network features in protein interaction networks (PPIN. Methods In this study, we proposed a method to identify CRGs based on Gene Ontology (GO and PPIN. Firstly, we documented 150 pairs of drug-CCRG (curated chemosensitivity related gene from 492 published papers. Secondly, we characterized CCRGs from the perspective of GO and PPIN. Thirdly, we prioritized CRGs based on CCRGs’ GO and network characteristics. Lastly, we evaluated the performance of the proposed method. Results We found that CCRG enriched GO terms were most often related to chemosensitivity and exhibited higher similarity scores compared to randomly selected genes. Moreover, CCRGs played key roles in maintaining the connectivity and controlling the information flow of PPINs. We then prioritized CRGs using CCRG enriched GO terms and CCRG network characteristics in order to obtain a database of predicted drug-CRGs that included 53 CRGs, 32 of which have been reported to affect susceptibility to drugs. Our proposed method identifies a greater number of drug-CCRGs, and drug-CCRGs are much more significantly enriched in predicted drug-CRGs, compared to a method based on the correlation of gene expression and drug activity. The mean area under ROC curve (AUC for our method is 65.2%, whereas that for the traditional method is 55.2%. Conclusions Our method not only identifies CRGs with expression patterns strongly correlated with drug activity, but also identifies CRGs in which expression is weakly correlated with drug activity. This study provides the framework for the identification of signatures that predict in vitro cellular chemosensitivity and offers a valuable

  5. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal

    Directory of Open Access Journals (Sweden)

    Choi Cheol-Hee

    2005-10-01

    Full Text Available Abstract One of the major problems related with anticancer chemotherapy is resistance against anticancer drugs. The ATP-binding cassette (ABC transporters are a family of transporter proteins that are responsible for drug resistance and a low bioavailability of drugs by pumping a variety of drugs out cells at the expense of ATP hydrolysis. One strategy for reversal of the resistance of tumor cells expressing ABC transporters is combined use of anticancer drugs with chemosensitizers. In this review, the physiological functions and structures of ABC transporters, and the development of chemosensitizers are described focusing on well-known proteins including P-glycoprotein, multidrug resistance associated protein, and breast cancer resistance protein.

  6. 20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

    Science.gov (United States)

    Liu, Junhua; Wang, Xu; Liu, Peng; Deng, Rongxin; Lei, Min; Chen, Wantao; Hu, Lihong

    2013-07-15

    Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. PMID:23683834

  7. CD80 antigen expression as a predictor of ex vivo chemosensitivity in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kivekäs, Ilkka; Hulkkonen, Janne; Hurme, Mikko; Vilpo, Leena; Vilpo, Juhani

    2002-05-01

    We investigated the correlation between expression of 31 surface membrane antigens and chemosensitivity of peripheral blood mononuclear cells from 36 patients with CLL. The sensitivity of CLL cells to nine drugs (2'-chlorodeoxyadenosine, cisplatin, chlorambucil, cyclosporin A, doxorubicin, fludarabine, prednisolone, verapamil and vincristine) and two types of irradiation (gamma and UV-irradiation) was determined from dose-response curves of 4-day cultures ex vivo. The results indicated that the CLL cases responding to purine analogs (2'-chlorodeoxyadenosine and fludarabine) can be identified according to CD80 expression: all resistant cases had low or negative CD80 expression. No other correlations were revealed. CD80 may be a surrogate chemosensitivity marker for purine analogs. PMID:11916516

  8. Increased leucine-rich repeats and immunoglobulin- like domains 1 expression enhances chemosensitivity in glioma

    Institute of Scientific and Technical Information of China (English)

    Baohui Liu; Shenqi Zhang; Dong Ruan; Xiaonan Zhu; Zhentao Guo; Huimin Dong; Mingmin Yan; Qianxue Chen; Daofeng Tian; Liquan Wu; Junmin Wang; Qiang Cai; Heng Shen; Baowei Ji; Long Wang

    2011-01-01

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is an anti-oncogene.LRIG1 is correlated with Bcl-2 in ependymomas.Decreased Bcl-2 and manganese superoxide dismutase expression can improve the chemosensitivity of glioma.In the present study, a tissue microarray of human brain astrocytomas was constructed.To investigate the relationship of LRIG1 with Bcl-2 and manganese superoxide dismutase, LRIG1, Bcl-2 and manganese superoxide dismutase expression in our tissue microarray was determined using immunohistochemistry.In addition, we constructed the LRIG1-U251 cell line, and its responses to doxorubicin and temozolomide were detected using the MTT assay.Results showed that LRIG1 expression was significantly negatively correlated with Bcl-2 and manganese superoxide dismutase expression in glioma.Also, proliferation of LRIG1-U251 cells exposed to doxorubicin or temozolomide was significantly inhibited, i.e.in the LRIG1-U251 cell line, the chemosensitivity to doxorubicin and temozolomide was increased.This indicates that increased LRIG1 expression produces a chemosensitivity in glioma.

  9. Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

    Directory of Open Access Journals (Sweden)

    Navid Kashaninejad

    2016-07-01

    Full Text Available With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1 Lung; (2 Bone marrow; (3 Brain; (4 Breast; (5 Urinary system (kidney, bladder and prostate; (6 Intestine; and (7 Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET of

  10. Noscapine chemosensitization enhances docetaxel anticancer activity and nanocarrier uptake in triple negative breast cancer.

    Science.gov (United States)

    Doddapaneni, Ravi; Patel, Ketan; Chowdhury, Nusrat; Singh, Mandip

    2016-08-01

    Chemosensitization and enhanced delivery to solid tumor are widely explored strategies to augment the anticancer efficacy of existing chemotherapeutics agents. The aim of current research was to investigate the role of low dose Noscapine (Nos) in potentiating docetaxel cytotoxicity and enhancing tumor penetration of nanocarriers. The objectives are; (1) To evaluate the chemo-sensitizing effect of Nos in combination with docetaxel (DTX), and to elucidate the possible mechanism (2) To investigate the effect of low dose Nos on tumor stroma and enhancing nanocarrier uptake in triple negative breast cancer (TNBC) bearing nude mice. Cytotoxicity and flow cytometry analysis of DTX in Nos (4µM) pre-treated MDA-MB-231 cells showed 3.0-fold increase in cell killing and 30% increase in number of late apoptotic cells, respectively. Stress transducer p38 phosphorylation was significantly upregulated with Nos exposure. DTX showed remarkable downregulation in expression of bcl-2, survivin and pAKT in Nos pre-treated MDA-MB-231 cells. Nos pre-sensitization significantly (p<0.02) enhanced the anti-migration effect of DTX. In vivo studies in orthotopic TNBC tumor bearing mice showed marked reduction in tumor collagen-I levels and significantly (p<0.03) higher intra-tumoral uptake of coumarin-6 loaded PEGylated liposomes (7-fold) in Nos treated group. Chemo-sensitization and anti-fibrotic effect of Nos could be a promising approach to increase anticancer efficacy of DTX which can be used for other nanomedicinal products. PMID:27177833

  11. Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas

    International Nuclear Information System (INIS)

    Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects

  12. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2011-01-14

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  13. Cerebral and muscle deoxygenation, hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness during incremental exercise.

    Science.gov (United States)

    Peltonen, Juha E; Paterson, Donald H; Shoemaker, J Kevin; Delorey, Darren S; Dumanoir, Gregory R; Petrella, Robert J; Kowalchuk, John M

    2009-10-31

    To examine if cerebral (frontal cortex) and skeletal muscle (m. vastus lateralis) deoxygenation and cerebral blood flow velocity (V(mean)) in the middle cerebral artery differentiated between normoxic and hypoxic (end-tidal P(O)(2) 71 mmHg) conditions, and if they were associated with hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness, 8 men performed incremental cycling trials (30W/min ramp) under normoxic (T1-N) and hypoxic (T1-H) conditions until volitional fatigue, or until arterial O2 saturation decreased below 80%. The tests were repeated (T2-N; T2-H) on another day with supplemental O2 (Sup-O2) at the end of exercise. The V(mean) response was similar in normoxia and hypoxia. In hypoxia compared to normoxia, cerebral deoxygenation ( upward arrow deoxyhemoglobin concentration (Delta[HHb]) and downward arrow tissue oxygenation index (TOI)) was greater at a given work rate. A strong hypoxic ventilatory chemosensitivity was associated with a rapid reduction of cerebral TOI (r=0.94, PMuscle deoxygenation was similar in normoxia and hypoxia suggesting greater muscle blood flow in hypoxia compared to normoxia and thus the existence of control features that match muscle perfusion and O2 delivery tightly with O2 demand during exercise. Sup-O2 reduced both cerebral and muscle deoxygenation, at least transiently. PMID:19729079

  14. Growth-inhibitory and chemosensitizing effects of the glutathione-S-transferase-π-activated nitric oxide donor PABA/NO in malignant gliomas.

    Science.gov (United States)

    Kogias, Evangelos; Osterberg, Nadja; Baumer, Brunhilde; Psarras, Nikolaos; Koentges, Christoph; Papazoglou, Anna; Saavedra, Joseph E; Keefer, Larry K; Weyerbrock, Astrid

    2012-03-01

    Glutathione-S-transferases (GSTs) are upregulated in malignant gliomas and contribute to their chemoresistance. The nitric oxide (NO) donor PABA/NO (O(2) -{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) generates NO upon selective enzymatic activation by GST-π-inducing selective biological effects in tumors. Tumor cell killing and chemosensitization were observed in a variety of tumors after exposure to GST-activated NO donor drugs. In our project, cytotoxic and chemosensitizing effects of PABA/NO in combination with carboplatin (CPT) and temozolomide (TMZ) were studied in human U87 glioma cells in vitro and in vivo. U87 glioma cells were exposed to PABA/NO alone or in combination with CPT or TMZ for 24 hr. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after 24-hr incubation and 48 hr after drug removal. The antiproliferative effect of PABA/NO was assessed in an intracranial U87 glioma nude rat model comparing subcutaneous administration and intratumoral delivery by convection-enhanced delivery. PABA/NO monotherapy showed a strong dose-dependent growth-inhibitory effect in U87 glioma cells in vitro, and a strong synergistic effect was observed after concomitant treatment with TMZ, but not with CPT. Systemic and intratumoral PABA/NO administration significantly reduced cell proliferation, but this did not result in prolonged survival in nude rats with intracranial U87 gliomas. PABA/NO has potent antiproliferative effects, sensitizes U87 glioma cells to TMZ in vitro and shows some in vivo efficacy. Further studies are still required to consolidate the role of NO donor therapy in glioma treatment. PMID:21455987

  15. Regression of Stage IV Pancreatic Cancer to Curative Surgery and Introduction of a Novel Ex-Vivo Chemosensitivity Assay.

    Science.gov (United States)

    Rios Perez, Mayrim V; Dai, Bingbing; Koay, Eugene J; Wolff, Robert A; Fleming, Jason B

    2015-01-01

    Although data suggests little hope for survival when patients present with metastatic pancreatic cancer, recent advances in systemic therapy offer the possibility for dramatic tumor responses like those observed in other disease sites. Here, we present the case of a 50-year-old woman who presented with adenocarcinoma of the pancreas with two liver metastases and a CA 19-9 level of 1,659 U/mL. The patient received FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) with a dramatic reduction in CA 19-9 level to 23.9 U/mL, and complete regression of both liver metastases. The patient then received capecitabine with the maintenance of a normal CA19-9 over the next 12 months. With no evidence of distant disease, concurrent systemic and local therapy with capecitabine-based chemoradiation (CapeXRT) was performed followed by observation for eight months with normal CA 19-9 readings. A mild increase in CA 19-9 (143 U/mL) prompted a restaging demonstrating an active primary tumor but no distant disease. Therefore, a pancreaticoduodenectomy (PD or Whipple) was performed rendering this patient free of detectable cancer. Our team has developed an ex-vivo chemosensitivity assay in which the tumor tissue from an individual patient can be rapidly examined for sensitivity to available systemic therapy treatment strategies. We tested this patient's tumor for its sensitivity to gemcitabine (Gem) versus a combination of 5-fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Remarkably, our assay confirmed a profound sensitivity of this patient's tumor to the agents she had received. PMID:26848412

  16. Aptamer–polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing

    Science.gov (United States)

    Shen, Qinglin; Peng, Caixia; Zhan, Yan; Fan, Liang; Wang, Mengyi; Zhou, Qing; Liu, Jue; Lv, Xiaojuan; Tang, Qiu; Li, Jun; Huang, Xiaodong; Xia, Jiahong

    2016-01-01

    Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer–poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate–tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing. PMID:27274239

  17. Aptamer-polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing.

    Science.gov (United States)

    Shen, Qinglin; Peng, Caixia; Zhan, Yan; Fan, Liang; Wang, Mengyi; Zhou, Qing; Liu, Jue; Lv, Xiaojuan; Tang, Qiu; Li, Jun; Huang, Xiaodong; Xia, Jiahong

    2016-01-01

    Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer-poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate-tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing. PMID:27274239

  18. In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Pathak K

    2007-01-01

    Full Text Available Context : Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s will achieve the maximum clinical response. Aims : To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. Settings and Design : Prospective study in a tertiary cancer care center. Methods and Material : We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA and correlated them to the clinical response to chemotherapy. Statistical Analysis Used : Chi Square test. Results : Biopsy samples were successfully histocultured in 52/57 (91% cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52% tumors were sensitive to cisplatin, 27 (52% to methotrexate, 24 (46% to 5-fluorouracil, 38 (73% to combination of cisplatin and methotrexate and 36 (69% to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03 between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. Conclusions : We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

  19. Chemosensitivity of radioresistant cells in the multicellular spheroids of A549 lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Huang Gang

    2009-06-01

    Full Text Available Abstract Background The relapse of cancer after radiotherapy is a clinical knotty problem. Previous studies have demonstrated that the elevation of several factors is likely in some way to lead to the development of treatment tolerance, so it is necessary to further explore the problem of re-proliferated radioresistant cells to chemotherapeutic agents. In the present study, we aimed to investigate the chemosensitivity of radioresistant cells originated from the multicellular spheroids of A549 lung adenocarcinoma. Methods After irradiated with 25 Gy of 6 MV X-ray to A549 multicellular spheroids, whose 10th re-proliferated generations were employed as radioresistant cells, and the control groups were A549 parental cells and MCF7/VCR resistant cells. The chemo-sensitivity test was made by six kinds of chemotherapeutic drugs which were DDP, VDS, 5-Fu, HCP, MMC and ADM respectively, while verapamil (VPL was used as the reversal agent. Then the treatment effect was evaluated by MTT assay, and the multidrug resistant gene expressions of mdr1 and MRP were measured by RT-PCR. Results Both A549 parental cells and A549 derived radioresistant cells were resistant to DDP, but sensitive to VDS, 5-Fu, HCP, MMC and ADM. The inhibitory rates of VPL to these two types of cell were 98% and 25% respectively (P Mdr1/β2-MG and MRP/β2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCF7/VCR cells were 35 and 4.36. Conclusion The chemosensitivity of A549 radioresistant cells had not changed markedly, and the decreased sensitivity to VPL could not be explained by the gene expression of mdr1 and MRP. It is possible that the changes in the cell membrane and decreased proliferate ability might be attributed to the resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to radioresistant cells. Therefore, the new biological strategy needs to be developed to treat recurring radioresistant tumor in combination

  20. Chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma. Methods: The A549 irradiated resistant cells were the 10th regrowth generations after irradiated with 2.5 Gy of 6 MV X-ray, the control groups were A549 parent cells and MCFY/VCR resistant cells. The 6 kinds of chemotherapeutic drugs were DDP, VDS, 5-FU, HCP, MMC and ADM respectively, with verapamil (VPL) as reverse agent. The treatment effect was compared with MTT assay, and the multidrug resistant gene expressions of mdrl and MRP were measured with RT-PCR method. Results: A549 cells and irradiated resistant cells were resistant to DDP, but sensitivity to VDS,5-FU, HCP, MMC and ADM. The inhibitory rates of VPL to the above two cells were 98% and 25% respectively(P2-MG and MRP/β2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCFT/VCR cells were 35 and 4.36. Conclusion: The chemosensitivity of A549 irradiated resistant cells had not changed markedly, the decreased sensitivity to VPL could not be explained by the gene expression of mdrl and MRP. It is conferred that some kinds of changes in the cell membrane and decreased regrowth ability to result in resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to irradiated resistant cells. The new kinds of biological preparation should be sought to combine chemotherapy to treat recurring tumor with irradiated resistance. (authors)

  1. Chemosensitivity assay in mice prostate tumor: Preliminary report of flow cytometry, DNA fragmentation, ion ratiometric methods of anti-neoplastic drug monitoring

    OpenAIRE

    Kline Richard; Sharma Rakesh

    2004-01-01

    Abstract Flow cytometry, DNA fragmentation, ion ratiomateric analysis and NMR peaks characterized drug chemosensitivity of antineoplastic drugs. Hypotheses were: 1. The chemosensitive effect of different cancer cell lines is characteristic; 2. DNA fragmentation, ion ratiometric analysis suggest apoptosis status of tumor cells. Methods PC-3 cell lines were compared with DU-145, LNCaP cell lines in culture for the [Na]i and [Ca]i ion sensing dyes, cell death, NMR peaks and apoptosis staining fo...

  2. Aptamer-polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing

    Directory of Open Access Journals (Sweden)

    Shen QL

    2016-05-01

    Full Text Available Qinglin Shen1,2,*, Caixia Peng2,3,*, Yan Zhan1, Liang Fan1, Mengyi Wang1, Qing Zhou4, Jue Liu2,4, Xiaojuan Lv1, Qiu Tang1, Jun Li1,2, Xiaodong Huang2, Jiahong Xia2 1Department of Oncology, 2Key Laboratory for Molecular Diagnosis of Hubei Province, 3Central Laboratory, 4Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs, which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer–poly (N-isopropylacrylamide functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush, which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate–tumor chemosensitivity

  3. Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

    DEFF Research Database (Denmark)

    Wan, P; Li, Q; Eklund, AC;

    2012-01-01

    The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333...... compounds with reliable experimental half maximum growth inhibitions (GI(50)) values for 30 cell lines from the NCI60 data set and evaluated their growth inhibitory effect (chemosensitivity) with respect to tissue of origin. This was done by identifying natural clusters in the chemosensitivity data set and...... in a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively...

  4. Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

    DEFF Research Database (Denmark)

    Wan, Peng; Li, Qiyuan; Larsen, Jens Erik Pontoppidan;

    2012-01-01

    The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333...... compounds with reliable experimental half maximum growth inhibitions (GI50) values for 30 cell lines from the NCI60 data set and evaluated their growth inhibitory effect (chemosensitivity) with respect to tissue of origin. This was done by identifying natural clusters in the chemosensitivity data set and in...... a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively...

  5. Clinical significance of chemosensitivity in chronic heart failure: influence on neurohormonal derangement, Cheyne-Stokes respiration and arrhythmias

    OpenAIRE

    Giannoni, Alberto; Emdin, Michele; Poletti, Roberta; Bramanti, Francesca; Prontera, Concetta; Piepoli, Massimo; Passino, Claudio

    2007-01-01

    Abstract Increased chemosensitivity has been observed in heart failure (HF). To investigate its pathophysiological and clinical relevance, we evaluated its impact on neurohormonal balance, breathing pattern, response to exercise, and arrhythmic profile. Sixty patients with chronic HF (age 66?1 years, left ventricular ejection fraction, EF, 31?1%, mean?SEM) underwent assessment of hypoxic-normocapnic (HVR) and hypercapnic-normoxic ventilatory response (HCVR), neurohormonal evaluat...

  6. Impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer

    OpenAIRE

    Xu, Ke; Liu, Bin; Liu, Yongyu

    2015-01-01

    The objective of the current study was to investigate the impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer (NSCLC). In 115 archived NSCLC tissue samples, the expression of Brachyury was observed to be significantly higher than that in adjacent normal lung tissues. In addition, the current study demonstrated that the expression of Brachyury is closely associated with TNM staging, lymph node metastasis and the prognosis of NSCLC, altho...

  7. STUDY ON RELATIONSHIP BETWEEN CHEMOSENSITIVITY OF BREAST CANCER AND EXPRESSION OF p73α AND p53

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xin; SUN Zhi-jun

    2005-01-01

    Objective: To investigate the relationship between the expression of p73α and p53 versus the chemosensitivity in breast cancer cells. Methods: Twelve surgical samples of breast cancer diagnosed by pathology were used. The cancer sample cells were separately cultured in the incubator at 37℃, 5% CO2 in vitro. The relative inhibition rate of cancer cells by 4 kinds of anticancer drugs, which were EPI, MMC, 5-Fu and DDP, were assayed by MTT method. Immunocytochemistry was used to detect the expression of p73α and p53 in the cancer cells. Results: The positive expression of p73α was found in 5/12 (41.67%), and p53 positive expression rate was 50.0% (6/12). The relative inhibition rate of MMC, EPI, 5-Fu and DDP were significantly higher in the p73α positive cancer cells than in the p73α negative cancer cells. A positive correlation was found between expression of p73α and chemosensitivity for all the four anticancer drugs. Conclusion: The expression of p73α is related with the chemosensitivity of the breast cancer cells, and it may become one of the markers for judging the effect of chemotherapy in clinic.

  8. Overexpression of miR-100 inhibits cell proliferation, migration, and chemosensitivity in human glioblastoma through FGFR3

    Directory of Open Access Journals (Sweden)

    Luan YX

    2015-11-01

    Full Text Available Yongxin Luan,1 Shuyan Zhang,1 Ling Zuo,2 Lixiang Zhou1 1Department of Neurosurgery, First Bethune Hospital of Jilin University, 2Department of Ophthalmology, Second Bethune Hospital of Jilin University, Changchun, People’s Republic of China Background: Glioblastoma multiforme is one of the most deadly forms of brain cancer. We investigated the regulatory effects of microRNA-100 (miR-100 on cell proliferation, migration, and chemosensitivity in human glioblastoma. Methods: miR-100 expression was assessed by quantitative real-time polymerase chain reaction in both glioblastoma cells and human tumors. Lentiviruses of miR-100 mimics and inhibitors were transfected into U251 and T98G cells. The regulatory effects of either overexpressing or downregulating miR-100 on glioblastoma were evaluated by a viability assay, growth assay, migration assay, chemosensitivity assay, and an in vivo tumor transplantation assay. Expression of fibroblast growth factor receptor 3 (FGFR3, the bioinformatically predicted target of miR-100, was examined by Western blot in glioblastoma. FGFR3 was then ectopically overexpressed in U251 and T98G cells, and its effects on miR-100-mediated cancer regulation were evaluated by growth, migration, and chemosensitivity assays. Results: MiR-100 was markedly downregulated in both glioblastoma cell lines and human tumors. Overexpressing miR-100 through lentiviral transfection in U251 and T98G cells significantly inhibited cancer growth (both in vitro and in vivo and migration and increased chemosensitivity to cisplatin and 1, 3-bis (2-chloroethyl-l-nitrosourea, whereas downregulation of miR-100 had no effects on development of cancer. FGFR3 was directly regulated by miR-100 in glioblastoma. Ectopically overexpressing FGFR3 was able to ameliorate the anticancer effects of upregulation of miR-100 on glioblastoma growth, migration, and chemosensitivity. Conclusion: MiR-100 was generally downregulated in glioblastoma. Overexpressing mi

  9. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun Ah Song

    2016-08-01

    Full Text Available The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA, shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells’ molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies.

  10. Role of EGFR mutations in lung cancers: prognosis and tumor chemosensitivity.

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2015-08-01

    Lung cancers with an epidermal growth factor receptor (EGFR) gene mutation account for ~40 % of adenocarcinomas in East Asians and ~15 % of those in Caucasians and African Americans, which makes them one of the most common molecularly defined lung cancer subsets. The discriminative clinical and pathological features of lung cancers with EGFR mutations have been intensively studied, and the predictive role of an EGFR mutation for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) is well established. However, controversial issues remain regarding the clinical and therapeutic implications of EGFR mutations in lung cancers. These include the prognostic impact of the EGFR mutation, its predictive implication for successful treatment with anticancer agents other than EGFR-TKIs, appropriate cytotoxic agents for lung cancers with this mutation, and the chemosensitivity of EGFR-mutation-positive lung cancers after acquisition of resistance to EGFR-TKIs. In this review, we discuss these unanswered but important questions, referring to in vitro studies, basic research, retrospective analyses, and the results of phase III clinical trials. PMID:25983263

  11. Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.

    Science.gov (United States)

    Gruosso, Tina; Mieulet, Virginie; Cardon, Melissa; Bourachot, Brigitte; Kieffer, Yann; Devun, Flavien; Dubois, Thierry; Dutreix, Marie; Vincent-Salomon, Anne; Miller, Kyle Malcolm; Mechta-Grigoriou, Fatima

    2016-01-01

    Anti-cancer drugs often increase reactive oxygen species (ROS) and cause DNA damage. Here, we highlight a new cross talk between chronic oxidative stress and the histone variant H2AX, a key player in DNA repair. We observe that persistent accumulation of ROS, due to a deficient JunD-/Nrf2-antioxidant response, reduces H2AX protein levels. This effect is mediated by an enhanced interaction of H2AX with the E3 ubiquitin ligase RNF168, which is associated with H2AX poly-ubiquitination and promotes its degradation by the proteasome. ROS-mediated H2AX decrease plays a crucial role in chemosensitivity. Indeed, cycles of chemotherapy that sustainably increase ROS reduce H2AX protein levels in Triple-Negative breast cancer (TNBC) patients. H2AX decrease by such treatment is associated with an impaired NRF2-antioxidant response and is indicative of the therapeutic efficiency and survival of TNBC patients. Thus, our data describe a novel ROS-mediated regulation of H2AX turnover, which provides new insights into genetic instability and treatment efficacy in TNBC patients. PMID:27006338

  12. Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Hui; Xie, Jing [Medical College, Qingdao University, Qingdao, Shandong 266071 (China); Peng, Jianjun, E-mail: jianjunpeng@126.com [College of Life Sciences, Chongqing Normal University, Chongqing 401331 (China); Han, Yantao, E-mail: hanyt19@126.com [Medical College, Qingdao University, Qingdao, Shandong 266071 (China); Jiang, Qixiao; Han, Mei; Wang, Chunbo [Medical College, Qingdao University, Qingdao, Shandong 266071 (China)

    2015-03-15

    Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment. - Highlights: • Hispidulin inhibits proliferation of gallbladder cancer cells by targeting HIF-1α. • Hispidulin regulates HIF-1α via activating AMPK signaling. • Hispidulin sensitized the GBC cells to chemotherapeutics by down-regulating P-gp.

  13. The chemosensitizing agent lubeluzole binds calmodulin and inhibits Ca(2+)/calmodulin-dependent kinase II.

    Science.gov (United States)

    Bruno, Claudio; Cavalluzzi, Maria Maddalena; Rusciano, Maria Rosaria; Lovece, Angelo; Carrieri, Antonio; Pracella, Riccardo; Giannuzzi, Giulia; Polimeno, Lorenzo; Viale, Maurizio; Illario, Maddalena; Franchini, Carlo; Lentini, Giovanni

    2016-06-30

    An affinity capillary electrophoresis (ACE) method to estimate apparent dissociation constants between bovine brain calmodulin (CaM) and non-peptidic ligands was developed. The method was validated reproducing the dissociation constants of a number of well-known CaM ligands. In particular, the potent antagonist 125-C9 was ad hoc synthesized through an improved synthetic procedure. The ACE method was successfully applied to verify CaM affinity for lubeluzole, a well-known neuroprotective agent recently proved useful to potentiate the activity of anti-cancer drugs. Lubeluzole was slightly less potent than 125-C9 (Kd = 2.9 ± 0.7 and 0.47 ± 0.06 μM, respectively) and displayed Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibition (IC50 = 40 ± 1 μM). Possible binding modes of lubeluzole to CaM were explored by docking studies based on the X-ray crystal structures of several trifluoperazine-CaM complexes. An estimated dissociation constant in good agreement with the experimental one was found and the main aminoacidic residues and interactions contributing to complex formation were highlighted. The possibility that interference with Ca(2+) pathways may contribute to the previously observed chemosensitizing effects of lubeluzole on human ovarian adenocarcinoma and lung carcinoma cells are discussed. PMID:27043269

  14. Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α

    International Nuclear Information System (INIS)

    Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment. - Highlights: • Hispidulin inhibits proliferation of gallbladder cancer cells by targeting HIF-1α. • Hispidulin regulates HIF-1α via activating AMPK signaling. • Hispidulin sensitized the GBC cells to chemotherapeutics by down-regulating P-gp

  15. Integration of photothermal therapy and synergistic chemotherapy by a porphyrin self-assembled micelle confers chemosensitivity in triple-negative breast cancer.

    Science.gov (United States)

    Su, Shishuai; Ding, Yanping; Li, Yiye; Wu, Yan; Nie, Guangjun

    2016-02-01

    Triple-negative breast cancer is a malignant cancer type with a high risk of early recurrence and distant metastasis. Unlike other breast cancers, triple-negative breast cancer is lack of targetable receptors and, therefore, patients largely receive systemic chemotherapy. However, inevitable adverse effects and acquired drug resistance severely constrain the therapeutic outcome. Here we tailor-designed a porphyrin-based micelle that was self-assembled from a hybrid amphiphilic polymer comprising polyethylene glycol, poly (d, l-lactide-co-glycolide) and porphyrin. The bilayer micelles can be simultaneously loaded with two chemotherapeutic drugs with synergistic cytotoxicity and distinct physiochemical properties, forming a uniform and spherical nanostructure. The drug-loaded micelles showed a tendency to accumulate in the tumor and can be internalized by tumor cells for drug release in acidic organelles. Under near-infrared laser irradiation, high density of self-quenched porphyrins in the hydrophobic layer absorbed light efficiently and converted into an excited state, leading to the release of sufficient heat for photothermal therapy. The integration of localized photothermal effect and synergistic chemotherapy conferred great chemosensitivity to cancer cells and achieved tumor regression using about 1/10 of traditional drug dosage. As a result, chemotherapy-associated adverse effects were successfully avoided. Our present study established a novel porphyrin-based nanoplatform with photothermal activity and expanded drug loading capacity, providing new opportunities for challenging conventional chemotherapy and fighting against stubborn triple-negative breast cancer. PMID:26708642

  16. Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhao, Ziyi; Chen, Changjin; Lin, Junzhi; Zeng, Wentong; Zhao, Juan; Liang, Yindan; Tan, Qinrui; Yang, Chao; Li, Hui

    2016-09-01

    The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC), and therefore these tumors are highly resistant to chemotherapeutic agents, including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53 (TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is frequently functional, yet the tumors remain highly insensitive to chemotherapy. This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC. The present study aimed to detect the chemosensitivity of CCRCC. The expression of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm that VHL and P53 are both required for chemosensitivity, VHL and P53 were co‑expressed in 786‑O cells. The results of the functional antagonist assay (which assessed the IC50 values, i.e. the half maximal inhibitory concentration) confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle arrest was measured by propidium iodide staining following treatment with ADM or sunitinib. Further analysis indicated that co‑expression of VHL and P53 inhibited cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase, and promoted apoptosis following treatment with ADM or sunitinib. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the regulatory role of VHL is dependant on the activation P53. PMID:27485825

  17. Effect of Recepteur d'Origine Nantais expression on chemosensitivity and tumor cell behavior in colorectal cancer.

    Science.gov (United States)

    Kim, Nuri; Cho, Sung-Bum; Park, Young-Lan; Park, Sun-Young; Myung, Eun; Kim, Seung-Hun; Yu, Hyung-Min; Son, Young-Ae; Myung, Dae-Seong; Lee, Wan-Sik; Joo, Young-Eun

    2016-06-01

    Recepteur d'Origine Nantais (RON) expression is known to induce oncogenic properties including tumor cell growth, survival, motility, angiogenesis and chemoresistance. In the present study, we evaluated whether RON affects chemosensitivity and oncogenic behavior of colorectal cancer cells and investigated its prognostic value in colorectal cancer. To evaluate the impact of RON on chemosensitivity and tumor cell behavior, we treated colorectal cancer cells with small interfering RNAs specific to RON. This was followed by flow cytometric analyses and migration, Matrigel invasion and endothelial tube formation assays. The expression of RON was investigated by immunohistochemistry in colorectal cancer tissues. TUNEL assay and immunohistochemical staining for CD34 and D2-40 were deployed to determine apoptosis, angiogenesis and lymphangiogenesis. RON knockdown enhanced 5-fluorouracil (FU)-induced apoptosis by upregulating the activities of caspases and expression of proapoptotic genes. Moreover, it enhanced 5-FU-induced cell cycle arrest by decreasing the expression of cyclins and cyclin‑dependent kinases and inducing that of p21. Furthermore, RON knockdown augmented the 5-FU-induced inhibition of invasion and migration of colorectal cancer cells. The β-catenin signaling cascade was blocked by RON knockdown upon 5-FU treatment. RON knockdown also decreased endothelial tube formation and expression of VEGF-A and HIF-1α and increased angiostatin expression. Furthermore, it inhibited lymphatic endothelial cell tube formation and the expression of VEGF-C and COX-2. RON expression was observed to be associated with age, tumor size, lymphovascular and perineural invasion, tumor stage, lymph node and distant metastasis, and poor survival rate. The mean microvessel density value of RON-positive tumors was significantly higher than that of RON-negative ones. These results indicate that RON is associated with tumor progression by inhibiting chemosensitivity and enhancing

  18. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kasamatsu, Atsushi, E-mail: kasamatsua@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Uzawa, Katsuhiro, E-mail: uzawak@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Endo-Sakamoto, Yosuke; Ogawara, Katsunori [Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Shiiba, Masashi; Takiguchi, Yuichi [Medical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Tanzawa, Hideki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan)

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  19. Chemosensitization of cancer cells by siRNA using targeted nanogel delivery

    International Nuclear Information System (INIS)

    Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics. We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated. Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05). This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs

  20. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    International Nuclear Information System (INIS)

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  1. Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular carcinoma Be17402 / 5-FU cells

    Institute of Scientific and Technical Information of China (English)

    Yu-xiuLI; Zhi-binLIN; Huan-ranTAN

    2004-01-01

    AIM: To study the effect of wild type (wt) p53 gene transfection on drug resistant human hepatocellular carcinoma(HCC) cells induced by 5-Fluorouracil (5-FU). METHODS: The cytotoxicity of anticancer drugs on Be17402 and Be17402/5-FU cells was assessed using SRB assay, p53 expression was detected at its mRNA level by RT-PCR assay and at its protein level Western blot or immunocytochemistry assay in Be17402/5-FU cells transfected with either control vector or wt p53. AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The chemosensitivity of Be17402/5-FU cells transfected with wt p53 was assessed using SRB assay. RESULTS: Be17402/5-FU cells exhibited cross-resistance to vincristine, doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the expression of p53 in Be17402/5-FU cells, wt p53 was able to greatly inhibit cell proliferation and significantly induce apoptosis in Be17402/5-FU cells. Moreover, wt p53 gene transfection increased the chemosensitivity of Be17402/5-FU cells to some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene transfection not only induced suppression of cell growth, but also increased the sensitivity of Be17402/5-FU cells to 5-FU, vincristine, and doxorubicin.

  2. Restoration of IGFBP-rP1 increases radiosensitivity and chemosensitivity in hormone-refractory human prostate cancer

    International Nuclear Information System (INIS)

    We previously reported the tumor-suppressive activity of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) through induction of apoptosis in human prostate cancer cells. The aim of this study was to investigate the effects of IGFBP-rP1 for radiosensitivity and chemosensitivity in hormone-refractory human prostate PC-3 cancer cells. Five assays were performed using PC-3 cells transfected with IGFBP-rP1 (PC-3rP1) and control cells transfected with an empty vector (PC-3N): PC-3rP1 and PC-3N were compared by clonogenic survival assay, cell cycle analysis and apoptotic assay for radiosensitivity. The number of colonies of PC-3rP1 cells significantly decreased after 4 and 8 Gy of irradiation, compared with those of PC-3N in the clonogenic survival assay. After 16 hr irradiation at 8 Gy, the percentage of apoptotic cells significantly increased in PC-3rP1 compared with PC-3N. Growth of PC-3rP1 was significantly lower than that of PC-3N after docetaxel treatment both in vitro and in vivo. These results indicate that restoration of IGFBP-rP1 to PC-3 cells increases both their radiosensitivity and chemosensitivity. (author)

  3. Chemosensitizing effect of podophyllotoxin acetate on topoisomerase inhibitors leads to synergistic enhancement of lung cancer cell apoptosis

    Science.gov (United States)

    HONG, WAN GI; CHO, JEONG HYUN; HWANG, SANG-GU; LEE, EUNAH; LEE, JAESEOK; KIM, JONG-IL; UM, HONG-DUCK; PARK, JONG KUK

    2016-01-01

    Podophyllotoxin acetate (PA) acts as a radiosensitizer against non-small cell lung cancer (NSCLC) in vitro and in vivo. In this study, we examined its potential role as a chemosensitizer in conjunction with the topoisomerase inhibitors etoposide (Eto) and camptothecin (Cpt). The effects of combinations of PA and Eto/Cpt were examined with CompuSyn software in two NSCLC cell lines, A549 and NCI-H1299. Combination index (CI) values indicated synergistic effects of PA and the topoisomerase inhibitors. The intracellular mechanism underlying synergism was further determined using propidium iodide uptake, immunoblotting and electrophoretic mobility shift assay (EMSA). Combination of PA with Eto/Cpt promoted disruption of the dynamics of actin filaments, leading to subsequent enhancement of apoptotic cell death via induction of caspase-3, -8, and -9, accompanied by increased phosphorylation of p38. Conversely, suppression of p38 phosphorylation blocked the apoptotic effect of the drug combinations. Notably, CREB-1, a transcription factor, was constitutively activated in both cell types, and synergistically inhibited upon combination treatment. Our results collectively indicate that PA functions as a chemosensitizer by enhancing apoptosis through activation of the p38/caspase axis and suppression of CREB-1. PMID:27035096

  4. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    International Nuclear Information System (INIS)

    Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC)

  5. Predictive value of MTT assay as an in vitro chemosensitivity testing for gastric cancer: One institution's experience

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Jin-Shui Zhu; Yi Zhang; Wei-Ming Shen; Qiang Zhang

    2008-01-01

    AIM: To investigate the predictive clinical value of in vitro 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay for directing chemosensitivity in patients with gastric cancer.METHODS: Results of a total of 353 consecutive patients with gastric cancer treated with MTT-directed chemotherapy or physician's empirical chemotherapy from July 1997 to April 2003 were reviewed and analyzed retrospectively.RESULTS: The overall 5-year survival rate of MTTsensitive group (MSG) and control group (CG) was 47.5% and 45.1%, respectively. The results of subgroup analysis with Cox proportional-hazards model were favorable for the MSG-sensitive group. However, no statistically significant difference in survival rate was observed between the two groups.CONCLUSION: Individualized chemotherapy based on in vitro MTT assay is beneficial, but needs to be confirmed by further randomized controlled trials.

  6. Suppression of bcl-2 Gene by RNA Interference Increases Chemosensitivity to Cisplatin in Nasopharyngeal Carcinoma Cell Line CNE1

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua YIN; Cai-Ping REN; Feng LI; Xu-Yu YANG; Hui LI; Ming ZHAO; Kai-Tai YAO

    2004-01-01

    To explore the effect of suppressing BCL-2 expression using RNA interference (RNAi) technique in nasopharyngeal carcinoma cell line CNE1. CNE1 cell lines stably expressing shRNAs targeted bcl-2 and GL3 gene were established and gene expression inhibition was assessed by Western blotting analysis. The effect of suppressing bcl-2 by RNAi on cell growth was studied, the apoptosis induction and the sensitization of CNE 1 cells to cisplatin were quantified by MTT assay and flow cytometry. The results showed that: stable transfection of CNE 1 cells with vectors expressing shRNAs against bcl-2 decreased the expression of BCL-2 protein; suppression of BCL-2 expression did not affect cell proliferation but could increase the chemosensitivity to cisplatin in CNE1 cells. This will help physicians to make some clinical trials of gene therapy on nasopharyngeal carcinoma by RNAi.

  7. RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    GUAN Hong-geng; XUE Wan-jiang; QIAN Hai-xin; ZHOU Xiao-jun; QIN Lei; LAN Jing

    2009-01-01

    Background The antitumor role of Ras association domain family 1A (RASSFIA) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSFIA in hepatoceliular carcinoma, and study the mechanisms of cell apoptosis induced by RASSFIA.Methods After stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Westem blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.Results Wild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatJn treatment.Conclusion Wild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

  8. Chemosensitizing effects of carbon-based nanomaterials in cancer cells: enhanced apoptosis and inhibition of proliferation as underlying mechanisms

    Science.gov (United States)

    Erdmann, Kati; Ringel, Jessica; Hampel, Silke; Rieger, Christiane; Huebner, Doreen; Wirth, Manfred P.; Fuessel, Susanne

    2014-10-01

    Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight (EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation, clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion, the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel

  9. Effects of hypoxia on expression of a panel of stem cell and chemosensitivity markers in glioblastoma cell line-derived spheroids

    DEFF Research Database (Denmark)

    Kolenda, Jesper; Jensen, Stine Skov; Aaberg-Jessen, Charlotte;

    entire immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67) and stem cell (CD133, nestin, podoplanin, Bmi-1, Sox-2) markers as well as markers related to chemosensitivity (MGMT, MDR-1, TIMP-1, Lamp-1). Since spheroids derived in hypoxia were smaller than in normoxia, a set...... differences were found for podoplanin, nestin and TIMP-1 as well as for Ki-67. Hif-2α, Sox-2, MGMT and MDR-1 were not detectable in normoxic and hypoxic U87 spheroids. In conclusion, the expression of tumor stem cell and chemosensitivity markers seems to depend on the oxygen tension suggesting that future...... oxygen tensions below 1-5% O2 has been attributed to play a crucial role in tumorigenesis and therapeutic resistance in glioblastoma. This is in contrast to most in vitro experiments in this field being performed in atmospheric air with 21% O2. In this study the influence of hypoxia on the expression of...

  10. Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway.

    Science.gov (United States)

    Xie, Jie; Tao, Zhong-Hua; Zhao, Jiang; Li, Ting; Wu, Zheng-Hua; Zhang, Jin-Feng; Zhang, Jian; Hu, Xi-Chun

    2016-06-01

    The underlying mechanism of gemcitabine resistance during breast cancer treatment remains unclear. Glucose regulated protein 78 (GRP78) frequently triggered by anticancer agents, was substantially elevated in gemcitabine resistant sublines. Ectopic expression of GRP78 changes gemcitabine chemosensitivity and apoptosis levels in breast cancer cells. Further experiments showed an involvement of caspase 9, not caspase 8, in gemcitabine resistance and GRP78-mediated chemosensitivity, suggesting that mitochondria apoptotic pathway was activated by GRP78. This finding was further supported by the observations of AKT activation, Bcl-2 increase, Bax and Bim decrease. Conclusively, GRP78 plays a vital role in gemcitabine resistance and clinical strategy to improve gemcitabine efficacy in breast cancer by manipulating GRP78 should be explored. PMID:27012209

  11. Chemosensitivity Predicted by BluePrint 80-Gene Functional Subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

    OpenAIRE

    Whitworth, Pat; Stork-Sloots, Lisette; de Snoo, Femke A.; Richards, Paul; Rotkis, Michael; Beatty, Jennifer; Mislowsky, Angela; Pellicane, James V.; Nguyen, Bichlien; Lee, Laura; Nash, Charles; Gittleman, Mark; Akbari, Stephanie; Beitsch, Peter D.

    2014-01-01

    Purpose The purpose of the NBRST study is to compare a multigene classifier to conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping to predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity as defined by partial response. Methods The study includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy. BluePrint in combination with Mam...

  12. RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro

    Directory of Open Access Journals (Sweden)

    Zhu Chan

    2010-06-01

    Full Text Available Abstract Background CD147 is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. CD147 has been implicated in numerous physiological and pathological activities. Enriched on the surface of many tumor cells, CD147 promotes tumor growth, invasion, metastasis and angiogenesis and confers resistance to some chemotherapeutic drugs. In this study, we investigated the possible role of CD147 in the progression of gastric cancer. Methods Short hairpin RNA (shRNA expressing vectors targeting CD147 were constructed and transfected into human gastric cancer cells SGC7901 and CD147 expression was monitored by quantitative realtime RT-PCR and Western blot. Cell proliferation, the activities of MMP-2 and MMP-9, the invasive potential and chemosensitivity to cisplatin of SGC7901 cells were determined by MTT, gelatin zymography, Transwell invasion assay and MTT, respectively. Results Down-regulation of CD147 by RNAi approach led to decreased cell proliferation, MMP-2 and MMP-9 activities and invasive potential of SGC7901 cells as well as increased chemosensitivity to cisplatin. Conclusion CD147 involves in proliferation, invasion and chemosensitivity of human gastric cancer cell line SGC7901, indicating that CD147 may be a promising therapeutic target for gastric cancer.

  13. Co-expression of ING4 and P53 enhances hypopharyngeal cancer chemosensitivity to cisplatin in vivo.

    Science.gov (United States)

    Ren, Xin; Liu, Hao; Zhang, Mingjie; Wang, Mengjun; Ma, Shiyin

    2016-09-01

    Hypopharyngeal cancer is a distinct type of malignant head and neck tumor, which exhibits low sensitivity to anti-cancer drugs. The importance of developing methods for reducing chemotherapy resistance, and improving and enhancing prognosis has previously been emphasized and is considered a challenge for effective clinical treatment of hypopharyngeal cancer. The current study investigated the effects of co‑expression of inhibitor of growth protein 4 (ING4) and P53, a tumor suppressor gene, on chemosensitivity to cisplatin in human hypopharyngeal cancer xenografts in vivo, and the potential molecular mechanisms involved. A tumor model was established by injecting athymic nude mice with FADU human hypopharyngeal cancer cells. Five days after intratumoral and peritumoral injections of an empty adenoviral vector (Ad), Ad‑ING4‑P53, cisplatin, or a combination of Ad‑ING4‑P53 and cisplatin (Ad‑ING4‑P53 + cisplatin) every other day for 5 days, the mice were euthanized and their tumors, livers, and kidneys were removed. The tumor weights were used to calculate the inhibition rate, and the expression levels of ING4 and P53 were detected by reverse transcription‑polymerase chain reaction. Additionally, apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunohistochemistry determined the levels ING4, P53, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2 associated X protein (Bax) protein expression. The results demonstrated increased expression of ING4 and P53 in the Ad‑ING4‑P53 groups compared with PBS and Ad groups, indicating successful introduction of the genes into the tumor cells. Notably, the Ad‑ING4‑P53 + cisplatin group exhibited a higher inhibition rate compared with the four other groups. The results of immunohistochemistry analysis demonstrated that Bax expression was increased and Bcl‑2 was decreased in the Ad‑ING4‑P53 + cisplatin group. This suggested that the enhanced

  14. Assessment of central chemosensitivity and cardiac sympathetic nerve activity using I-123 MIBG imaging in central sleep apnea syndrome in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Iodine-123 m-iodobenzylguanidine (MIBG) imaging has been used to study cardiac sympathetic function in various cardiac diseases. Central sleep apnea syndrome (CSAS) occurs frequently in patients with chronic heart failure (CHF) and is reported to be associated with a poor prognosis. One of the mechanisms of its poor prognosis may be related to impaired cardiac sympathetic activity. However, the relationship between chemosensitivity to carbon dioxide, which is reported to correlate with the severity of CSAS, and cardiac sympathetic activity has not been investigated. Therefore, this study was undertaken to assess cardiac sympathetic function and chemosensitivity to carbon dioxide in CHF patients. The oxygen desaturation index (ODI) was evaluated in 21 patients with dilated cardiomyopathy (male/female: 19/2, left ventricular ejection fraction (LVEF)5 times/h underwent polysomnography. Patients with an apnea hypopnea index >15/h but without evidence of obstructive apnea were defined as having CSAS. Early (15 min) and delayed (4 hr) planar MIBG images were obtained from these patients. The mean counts in the whole heart and the mediastinum were obtained. The heart-to-mediastinum count ratio of the delayed image (H/M) and the corrected myocardial washout rate (WR) were also calculated. The central chemoreflex was assessed with the rebreathing method using a hypercapnic gas mixture (7% CO2 and 93% O2). Ten of the 21 patients had CSAS. The H/M ratio was similar in patients both with and without CSAS (1.57±0.18 vs. 1.59±0.14, p=0.82). However, the WR was higher in patients with CSAS than in patients without CSAS (40±8% vs. 30±12%, p<0.05). ODI significantly correlated with central chemosensitivity to carbon dioxide. Moreover, there was a highly significant correlation between WR and central chemosensitivity (r=0.65, p<0.05). However, there was no correlation between ODI and the WR (r=0.36, p=0.11). Cardiac sympathetic nerve activity in patients with CHF and CSAS is

  15. Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel

    Directory of Open Access Journals (Sweden)

    Joana Fonseca

    2016-07-01

    Full Text Available We previously reported that prenylated chalcone 2 (PC2, the O-prenyl derivative (2 of 2′-hydroxy-3,4,4′,5,6′-pentamethoxychalcone (1, induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination.

  16. Factors associated with the preincubation effect of hypoxic cell sensitizers in vitro and their possible implications in chemosensitization

    International Nuclear Information System (INIS)

    The enhancement of melphalan toxicity was observed by preincubation of V-79-379A cells in spinner culture with multiple doses of misonidazole (miso) or SR-2508 under hypoxic conditions. Chemosensitization was shown to be a function of sensitizer concentration and duration of exposure to the alkylating agent. Cells preincubated with miso not only had lower levels of nonprotein thiols, but also were shown to have altered levels of intracellular calcium and a lower threshold to oxidative stress as measured by toxicity to cysteamine or H2O2. Preincubated cells, hypoxic cells, and cells receiving moderate hyperthermia (42.50C for 3 hr) all showed increased sensitivity to either cysteamine or H2O2. The increased killing of preincubated cells by cysteamine was shown to be similar to that of H2O2, and the dramatic reduction of cysteamine toxicity by catalase indicated H2O2 was the major reaction associated with this effect. These results indicate that preincubated cells exhibit a variety of biological effects that may significantly influence their response to further treatment with drugs or radiation, especially where peroxidative and free radical mechanisms are involved

  17. Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

    International Nuclear Information System (INIS)

    Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

  18. Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Lamont Alan

    2003-07-01

    Full Text Available Abstract Background We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. Methods From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse Results The overall response rate was 59% (33/56 per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS was 6.6 months per course of chemotherapy; median overall survival (OAS for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9–12.8 months. Conclusion The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centres.

  19. Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel.

    Science.gov (United States)

    Fonseca, Joana; Marques, Sandra; Silva, Patrícia M A; Brandão, Pedro; Cidade, Honorina; Pinto, Madalena M; Bousbaa, Hassan

    2016-01-01

    We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination. PMID:27483224

  20. Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Xie Li

    2009-02-01

    Full Text Available Abstract Background Astrocyte elevated gene-1 (AEG-1 was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of AEG-1 in promoting tumor progression and metastasis. The aim of this study was to investigate if AEG-1 serves as a potential therapeutic target of human neuroblastoma. Methods We employed RNA interference to reduce AEG-1 expression in human neuroblastoma cell lines and analyzed their phenotypic changes. Results We found that the knockdown of AEG-1 expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G0/G1 phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of AEG-1. Conclusion Our study suggests that overexpressed AEG-1 enhance the tumorogenic properties of neuroblastoma cells. The inhibition of AEG-1 expression could be a new adjuvant therapy for neuroblastoma.

  1. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    International Nuclear Information System (INIS)

    Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

  2. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA2

    Directory of Open Access Journals (Sweden)

    Jaeyoung Lim

    2014-04-01

    Full Text Available In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3 inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.

  3. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA212

    Science.gov (United States)

    Lim, Jaeyoung; Yang, Kun; Taylor-Harding, Barbie; Wiedemeyer, W. Ruprecht; Buckanovich, Ronald J.

    2014-01-01

    In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors. PMID:24862760

  4. Water extract from Pleurotus pulmonarius with antioxidant activity exerts in vivo chemoprophylaxis and chemosensitization for liver cancer.

    Science.gov (United States)

    Xu, Wen Wen; Li, Bin; Lai, Emily Tsz Ching; Chen, Lei; Huang, Jim Jun Hui; Cheung, Annie Lai Man; Cheung, Peter Chi Keung

    2014-01-01

    Chemoprophylaxis and chemosensitization are promising strategies to combat human cancers. Natural antioxidant agents show great promise in cancer therapy, and the use of edible mushrooms against cancer is receiving more interest globally. In this study, the radical scavenging activities including diphenyl-1-picrylhydrazyl, superoxide anion radical, hydroxyl radical, and hydrogen peroxide were compared among hot water extracts from 3 edible mushrooms, among which Pleurotus pulmonarius (Pp) possessed the highest antioxidant potential. Oral administration of Pp 2 wk in advance could markedly inhibit the incidence and size of tumor (Huh7 liver cancer cells) with an inhibition rate of 93.1% in nude mice. No obvious side effect was observed in the Pp-treated mice as indicated by their body weight and histological analysis of major organs. The cancer prevention by Pp treatment might be explained by the inhibition of cancer cell proliferation indicated by reduction of ki-67 staining and the inactivation of phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in the Pp-treated mice. Furthermore, a significant synergistic effect was observed when the mice were treated with a combination of low dose of cisplatin and Pp. Taken together, these results suggest the potential application of Pp as an adjuvant in the chemotherapy of liver cancer. PMID:25072857

  5. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    International Nuclear Information System (INIS)

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer

  6. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu; Du, Feiya; Chen, Wei; Yao, Minya; Lv, Kezhen; Fu, Peifen, E-mail: fupeifendoczju@163.com

    2013-12-10

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer.

  7. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells

    Directory of Open Access Journals (Sweden)

    He Fan

    2010-12-01

    Full Text Available Abstract Background Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. Methods Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death. Results Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scanvengers butylated hydroxyanisole (BHA and N-acetyl-L-cysteine (NAC dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin. Conclusions These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy.

  8. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.

    Science.gov (United States)

    Silden, Elisabeth; Hjelle, Sigrun M; Wergeland, Line; Sulen, André; Andresen, Vibeke; Bourdon, Jean-Christophe; Micklem, David R; McCormack, Emmet; Gjertsen, Bjørn Tore

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1)), Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(P)H quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level. PMID:23409163

  9. PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer.

    Science.gov (United States)

    Zhu, Haiyan; Wu, Jun; Zhang, Wenwen; Luo, Hui; Shen, Zhaojun; Cheng, Huihui; Zhu, Xueqiong

    2016-01-01

    Pyruvate kinase M2 (PKM2) is a key driver of aerobic glycolysis in cancer cells and has been shown to be up-regulated by mTOR in vitro. Our previous proteomic profiling studies showed that PKM2 was significantly upregulated in cervical cancer tissues after treatment with neoadjuvant chemotherapy (NACT). Whether PKM2 expression predicts cisplatin-based NACT sensitivity and is mTOR dependent in cervical cancer patients remains unclear. Using paired tumor samples (pre- and post-chemotherapy) from 36 cervical cancer patients, we examined mTOR, HIF-1α, c-Myc, and PKM2 expression in cervical cancer samples and investigated the response to cisplatin-based NACT. In addition, we established PKM2 suppressed cervical cancer cell lines and evaluated their sensitivity to cisplatin in vitro. We found that the mTOR/HIF-1α/c-Myc/PKM2 signaling pathway was significantly downregulated in post-chemotherapy cervical cancer tissues. High levels of mTOR, HIF-1α, c-Myc, and PKM2 were associated with a positive chemotherapy response in cervical cancer patients treated with cisplatin-based NACT. In vitro, PKM2 knockdown desensitized cervical cancer cells to cisplatin. Moreover, PKM2 had complex interactions with mTOR pathways. mTOR, HIF1α, c-Myc, and PKM2 expression in cervical cancer may serve as predictive biomarkers to cisplatin-based chemotherapy. PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer. PMID:27492148

  10. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null cell lines.

    Directory of Open Access Journals (Sweden)

    Elisabeth Silden

    Full Text Available The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1, Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(PH quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level.

  11. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses

  12. Using 99mTc-MIBI to Evaluate the Effects of Chemosensitizer on P-glycoprotein in Multidrug-resistant Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhenwei; ZHANGXuemei; WUHua; ZHAOMing; XIANYUZhiqun; ZHOUJian; LAIShiying

    2005-01-01

    Objective: To establish a method to evaluate the effects of chemosensitizer on P-glycoprotein using 99mTc-MIBI, and observe the changes of 99mTc-MIBI uptake kinetics and P-glycoprotein levels after using verapamil in MDR human breast cells MCF-7/Adr. Methods: MDR breast carcinoma cells, MCF-7/Adr, were incubated and different protocols were performed. Protocol I: a chemosensitizer, verapamil (10μmol/L), was added into cell culture medium, while in control group, the same volume of DMEM was given. Cells were harvested after 2 h incubation with 99mTc-MIBI. Protocol Ⅱ: Verapamil (10μmol/L) was added into cell culture medium and incubated for 20 min, 40 min, 60 rain, 80 min, 8 h, 24 h, 48 h and 72 h respectively. Cells were harvested after 2 h incubation with 99mTc-MIBI. The radioactivity of the cells was measured and P-glycoprotein expression levels were determined with immunohistochemical stain. Results: Protocol I: After 2h incubation with verapamil the cellular uptake of 99mTc-MIBI was remarkably higher than control group (t=2.33, P0.05). Protocol

  13. Radio- and chemosensitivity-testing of tumour tissue grown in vitro

    International Nuclear Information System (INIS)

    Chemo- and radiosensitivity-testing of tumour cells should be performed in vitro under in vivo-like conditions. One problem is to grow cells to tissue-like cell densities in vitro. A hollow fiber reactor was prepared for cell growth to high densities. In order to obtain cells during and after sensitivity testing for quantitating cell damage, a harvesting fiber system was developed which can be inserted hollow fiber system. These hollow fibers have a diameter of 300 μm and a wall thickness of 10 μm. Small holes between 10 and 100 μm can be cut into the fibers for cell heavesting by electric sparks. Up to 60 holes per mm fiber length can be produced. (orig.)

  14. Application of silicon sensor technologies to tumor tissue in vitro: detection of metabolic correlates of chemosensitivity.

    Science.gov (United States)

    Mestres-Ventura, Pedro; Morguet, Andrea; Schofer, Anette; Laue, Michael; Schmidt, Werner

    2005-01-01

    Silicon sensor technologies, developed during the 1990s, allow measurement of extracellular chemical changes related to cell metabolism. Exposition of tumor cells in vitro to anticancer drugs modifies cell metabolism, making it possible to detect on-line with sensor chips patterns of metabolic activity, which depend on drug sensitivity, or drug resistance of the cells. Sensor devices are composed of an incubation chamber with a sensor chip and a fluidic system for medium supply. Basically, two sensor types are available: (1) monosensor systems to detect extracellular acidification; and (2) multisensor arrays for many parameters such as pH, oxygen consumption, and impedance. Two companies have developed such systems: Molecular Devices (USA) and Bionas (Germany). In this chapter, in addition to operation of the sensor devices, we describe techniques for tissue (tumor and non-tumor) preparation. Basically, three procedures are described: (1) tissue dissociation and further cultivation on the sensor chip or on Transwell inserts; (2) preparation of tissue slices (300 microm thick) and attachment to the sensor chip or to inserts, and (3) cultivation of cells in dialysis tubes, a procedure necessary for nonadherent cells and cell suspensions to avoid their washing away. Evaluation of results and selection of controls are also discussed. PMID:15911976

  15. B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells

    Directory of Open Access Journals (Sweden)

    Zhang W

    2015-07-01

    function of B7-H3 and a promising therapeutic approach targeting B7-H3 in acute monocytic leukemia. Keywords: B7-H3, acute monocytic leukemia, cancer gene therapy, chemosensitivity

  16. Expression of the apoptosis-related genes BCL-2 and BAD in human breast carcinoma and their associated relationship with chemosensitivity

    Directory of Open Access Journals (Sweden)

    Fan Yuan-ming

    2010-08-01

    Full Text Available Abstract Objective To evaluate the expression of BCL-2 and BAD genes in tissues of breast carcinoma and investigate the relationship between the expression of BCL-2 and BAD in breast cancer cells with chemosensitivity. Methods Immunohistochemical technique was used to detect the expression of BCL-2, BAD in 10 normal breast tissues, 10 breast fibroadenoma tissues, 40 youth human breast carcinoma tissues, 40 menopause human breast carcinoma tissues. And to detect the expression of ER, PR in 80 human breast carcinoma tissues. 20 Surgical samples of breast cancer, diagnosed by pathology, were obtained from The First Affiliated Hospital of Chongqing Medical University. The cancer sample cells were cultured separately in the incubator at 37°C, 5% CO2 in vitro. The rate of inhibition of cancer cells in 4 kinds of anticancer drugs-- Epirubicin Adriamycin (EADM,5-Fluorouracil (5-Fu, Navelbine(NVB and Diaminedichloroplatinum (DDP, were assayed by MTT method. Results The expression of BCL-2, BAD genes in young human breast carcinoma tissues were lower than that in menopause human breast carcinoma tissues (P . There was a negative correlation between the positive expression rate of BCL-2 and histologic grade or the lymph node metastasis (P . There was a positive correlation between the expression rates of BCL-2 and of ER, PR (P . The expression of BAD had no relationship with the expression of ER, PR, histologic grade and the lymph node metastasis(P = NS. Sensitivity rates of 20 breast cancer cells in 0.1 × PPC within 48 h in vitro were 30% EADM,20% 5-Fu,45% NVB and 25% DDP. Respectively, the rate of inhibition of EADM,5- Fu, NVB and DDP were significantly higher in the BCL-2 negative cancer cells than in the BCL-2 positive cancer cells. A negative correlation was found between expression of BCL-2 and chemosensitivity for all the 4 anticancer drugs. The inhibition rates of EADM and NVB were significantly lower in the BAD negative cancer cells than in the

  17. Chemosensitization of aflatoxigenic fungi to antimycin A and strobilurin using salicylaldehyde, a volatile natural compound targeting cellular antioxidation system

    Science.gov (United States)

    Salicylaldehyde (SA), a volatile natural compound, exhibited potent antifungal and antiaflatoxigenic activities to Aspergillus flavus and A. parasiticus. Exposure to volatilized SA, inhibited growth of A. parasiticus from 10% - 75% at 9.5 - 16.0 mM, with complete inhibition at 19.0 mM. Similar trend...

  18. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

    2013-11-15

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  19. Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3

    Science.gov (United States)

    Yang, Dejun; Yan, Ronglin; Zhang, Xin; Zhu, Zhenxin; Wang, Changming; Liang, Chao; Zhang, Xin

    2016-01-01

    Background: The expression pattern and regulatory effect of microRNA-375 (miR-375) in human pancreatic cancer was explored. Methods: Gene expression of miR-375 was compared between pancreatic tumors and non-tumorous pancreatic tissues, as well as pancreatic cancer cell lines and normal epithelial cells. MiR-375 was downregulated in pancreatic cancer cell lines, Capan-1 and PANC-1 cells, to assess possible tumor suppressive effects on cancer proliferation, migration, cisplatin chemosensitivity and in vivo growth of tumor explant. The regulation of miR-375 on its target gene, homeobox B3 (HOXB3) gene, was assessed though luciferase activity assay and qRT-PCR. HOXB3 was also downregulated in Capan-1 and PANC-1 cells to assess its functional correlation with miR-375 on cancer regulation. Results: MiR-375 was upregulated in pancreatic tumors and pancreatic cancer cell lines. MiR-375 downregulation had tumor suppressive effects in Capan-1 and PANC-1 cells by reducing cancer proliferation & migration, increasing cisplatin sensitivity and inhibiting in vivo tumor explant growth. HOXB3 was directly bound by miR-375, and was negatively regulated by miR-375 in pancreatic cancer cells. Subsequent HOXB3 downregulation reversed the suppression of miR-375 downregulation on cancer proliferation, migration and cisplatin chemosensitivity in pancreatic cancer. Conclusion: MiR-375 is an oncogene in pancreatic cancer. Deregulation of miR-375 is inhibitory to the development of pancreatic cancer, and reversely regulated by HOXB3. PMID:27186281

  20. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    International Nuclear Information System (INIS)

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  1. Tumor-derived hepatocyte growth factor is associated with poor prognosis of patients with glioma and influences the chemosensitivity of glioma cell line to cisplatin in vitro

    Directory of Open Access Journals (Sweden)

    Guo You-feng

    2012-06-01

    Full Text Available Abstract Background We examined the association of tumor-derived hepatocyte growth factor (HGF with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients. Methods Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro. Results Both high HGF expression in tumor cells (59.2%, 45/76 and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P P = 0.004 and high-expression of HGF (P = 0.008 emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin. Conclusion This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.

  2. ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel

    Directory of Open Access Journals (Sweden)

    Wang Tingting

    2008-04-01

    Full Text Available Abstract Background One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1 and BRCA1 (breast cancer susceptibility gene 1. To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity. Methods Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC, gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay. Results ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001. In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002 while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032. A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45. Conclusion Our results demonstrate that ERCC1 and BRCA1 mRNA expression levels are correlated with in vitro chemosensitivity to cisplatin and/or docetaxel in malignant effusions of NSCLC and gastric cancer patients. And combination of ERCC1 and BRCA1 may have a better role on predicting the sensitivity to cisplatin than the single one is considered.

  3. ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel

    International Nuclear Information System (INIS)

    One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer susceptibility gene 1). To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity. Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC), gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay. ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001). In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002) while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032). A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45). Our results demonstrate that ERCC1 and BRCA1 mRNA expression levels are correlated with in vitro chemosensitivity to cisplatin and/or docetaxel in malignant effusions of NSCLC and gastric cancer patients. And combination of ERCC1 and BRCA1 may have a better role on predicting the sensitivity to cisplatin than the single one is considered

  4. Study of chemosensitivity testing in vitro on astrocytoma%星形细胞瘤体外化疗药物敏感程度的研究

    Institute of Scientific and Technical Information of China (English)

    滕晓华; 刘波; 周蓉; 曾年菊; 卢明

    2011-01-01

    目的 了解星形细胞瘤对常用化疗药物的敏感程度,探讨化疗药物体外敏感试验对于胶质瘤化疗的指导意义,比较不同WHO分级星形细胞瘤对化疗药物敏感度的差异,为临床治疗提供依据.方法 收集手术切除的新鲜星形细胞瘤标本共142例,其中低级别星形细胞瘤(Ⅰ、Ⅱ级)55例,高级别星形细胞瘤(Ⅲ、Ⅳ级)87例,分别进行星形细胞瘤细胞分离培养,采用MTT法检测临床常用11种化疗药物对肿瘤细胞的生长抑制情况,判定药物敏感程度.结果 142例患者中有78例(54.93%)获临床推荐使用药物,其中低级别星形细胞瘤为41.82%(23/55),而高级别星形细胞瘤为63.22%(55/87).不同WHO分级星形细胞瘤敏感化疗药物基本相似,以替尼泊苷、卡铂、长春新碱更为敏感.结论 化疗药物体外敏感试验对于胶质瘤的化疗药物筛选具有一定的指导意义,恶性程度越高,作用越突出.不同WHO分级的星形细胞瘤在化疗药物的选择上差异不明显.%Objective To observe the sensitivity ofastrocytoma to chemotherapeutic drugs, in order to explore the drug selection using chemosensitivity testing in vitro on astrocytoma. Comparing different WHO grade astrocytoma to chemotherapeutic drugs sensitivity differences,providing the basis data for clinical treatment. Methods The astrocytoma cells were seperated and cultured in vitro from 142 tumor tissues by glioma resection, including 55 cases of low-grade astrocytoma (WHO grade Ⅰ , Ⅱ) and 87 cases of high-grade astrocytoma (WHO grade Ⅲ, Ⅳ). The proliferation inhibition and chemosensitivity of tumor cells to 11 drugs were investigated by using MTT method. Results There were 54.93% (78/142) patients recommended chemotherapeutic drug in 142 cases. The percentage was 41.82%(23/55) in the low-grade astrocytoma, and 63.22% (55/87) in the high-grade astrocytoma respectively. Teniposide,carboplatin,vincristine as the sensitive drugs were similar in

  5. 胰岛素增加肿瘤细胞化疗敏感性的研究%The effect of insulin on the chemosensitivity of cancer cells

    Institute of Scientific and Technical Information of China (English)

    孙龙昊; 何向辉; 朱理玮

    2010-01-01

    Objective To investigate the effect and mechanism of insulin and hypoglycemia on the chemosensitivity of cancer cells. Methods Human colon cancer cells SW480, mouse colon cancer cells CT-26 and mouse breast cancer cells 4T1 were cultured and treated with insulin and chemotheraputic drugs, 5-fluorouracil or methotrexate. MTT assay was used to measure the cytotoxity. Fluorescence microscopy and flow cytometry were used to determine the effects of insulin on the uptake of fluorescent methotrexate by cancer cells. Mouse breast cancer cells 4T1 were inoculated into syngeneic BALB/C mice. Insulin was administrated to the mice before giving methotrexate and the therapeutic effect was monitored. Results (1) Insulin enhanced the chemocytotoxity of chemotheraputic drugs on cancer cells by 4. 1% to 11.5%;(2) Insulin increased the uptake of fluorescent methotrexate by cancer cells in vitro by 141. 9% ;(3) Insulin and hypoglycemia enhanced the chemotherapeutic effect of methotrexate on mouse breast cancer models by 20. 1%. Conclusion Insulin and hypoglycemia increase absorption of chemotherapeutic agents by cancer cells and enhance the chemosensitivity of cancer cells.%目的 探讨胰岛素对肿瘤细胞化疗敏感性的影响及机制.方法 以胰岛素和甲氨蝶呤(MTX)或5-氟尿嘧啶(5-Fu)处理人结肠癌细胞SW480,小鼠结肠癌细胞CT-26及小鼠乳腺癌细胞4T1,噻唑蓝(MTT)法分析细胞活力,荧光显微镜和流式细胞术观察肿瘤细胞对荧光标记MTX的摄取,并利用小鼠荷瘤模型,观察胰岛素及低MTX糖对MTX化疗疗效的影响.结果 (1)胰岛素增加MTX和5-Fu的细胞毒作用4.1%-11.5%.(2)胰岛素增加肿瘤细胞对MTX摄取141.9%.(3)胰岛素及低血糖状态增强MTX抑瘤作用20.1%.结论 胰岛素及低血糖状态增加肿瘤细胞对化疗药物的吸收,提高肿瘤细胞对化疗药物的敏感性.

  6. MiR-92b regulates the cell growth, cisplatin chemosensitivity of A549 non small cell lung cancer cell line and target PTEN.

    Science.gov (United States)

    Li, Yan; Li, Li; Guan, Yan; Liu, Xiuju; Meng, Qingyong; Guo, Qisen

    2013-11-01

    MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance of human cancer. Fewer studies were explored the roles of miR-92b on human lung cancer cell growth and resistance to cisplatin (CDDP). In this paper, we utilized real-time PCR to verify miR-92b was significantly up-regulated in non-small cell lung cancer (NSCLC) tissues compared to matched adjacent normal tissues. In vitro assay demonstrated that knock-down of miR-92b inhabits cell growth and sensitized the A549/CDDP cells to CDDP. Furthermore, we found miR-92b could directly target PTEN, a unique tumor suppressor gene, which was downregulated in lung cancer tissues compared to the matched adjacent normal tissues. These data indicate that the miR-92b play an oncogene roles by regulates cell growth, cisplatin chemosensitivity phenotype, and could serve as a novel potential maker for NSCLC therapy. PMID:24099768

  7. Application value of ATP based bioluminescence tumor chemosensitivity assay in the chemotherapy for hydrothorax caused by non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Kaijian Le; Yuming Jia; Jing Wang; Maoqiong Jiang

    2013-01-01

    Objective: The aim of the study was to investigate the clinical value and application of ATP based bioluminescencetumor chemosensitivity assay (ATP-TCA) in the chemotherapy for hydrothorax caused by non-small cell lung cancer(NSCLC). Methods: Hydrothorax specimens from 120 NSCLC patients were analyzed by ATP-TCA and the most sensitivechemotherapeutic drugs were used in NSCLC patients (treatment group). At the same time, 56 NSCLC patients with hydrothoraxwere admitted in our Hospital (Department of Oncology, The No. 2 People's Hospital of Yibin, China) and given chemotherapywithout guidance of the ATP-TCA (control group). Before the third chemotherapeutic cycle, clinical outcomes wereanalyzed in the two groups. Results: Effective rate of hydrothorax in treatment group was 67%, while 46% in control group(P < 0.05). In refractory hydrothorax patients, they were 69% and 40% (P < 0.05), respectively. In vitro results correlated wellwith clinical outcomes (P < 0.01). Conclusion: Effective rate of chemotherapy for hydrothorax in NSCLC is higher in treatmentgroup than that in control group. ATP-TCA is especially helpful for refractory hydrothorax.

  8. MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

    Science.gov (United States)

    Pascual-Serra, Raquel; García-Cano, Jesus; Garcia-Gil, Elena; De la Cruz-Morcillo, Miguel; Ortega-Muelas, Marta; Serrano-Oviedo, Leticia; Gutkind, J. Silvio; Sánchez-Prieto, Ricardo

    2015-01-01

    The adenoviral gene E1a is known to enhance the antitumor effect of cisplatin, one of the cornerstones of the current cancer chemotherapy. Here we study the molecular basis of E1a mediated sensitivity to cisplatin in an experimental model of Non-small cell lung cancer. Our data show how E1a blocks the induction of autophagy triggered by cisplatin and promotes the apoptotic response in resistant cells. Interestingly, at the molecular level, we present evidences showing how the phosphatase MKP1 is a major determinant of cisplatin sensitivity and its upregulation is strictly required for the induction of chemosensitivity mediated by E1a. Indeed, E1a is almost unable to promote sensitivity in H460, in which the high expression of MKP1 remains unaffected by E1a. However, in resistant cell as H1299, H23 or H661, which display low levels of MKP1, E1a expression promotes a dramatic increase in the amount of MKP1 correlating with cisplatin sensitivity. Furthermore, effective knock down of MKP1 in H1299 E1a expressing cells restores resistance to a similar extent than parental cells. In summary, the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. PMID:26689986

  9. Biostimulative effects of Nd:YAG Q-switch dye on normal human fibroblast cultures: study of a new chemosensitizing agent for the Nd:YAG laser

    Energy Technology Data Exchange (ETDEWEB)

    Castro, D.J.; Saxton, R.E.; Fetterman, H.R.; Castro, D.J.; Ward, P.H.

    1987-12-01

    Kodak Q-switch II is a new chemical with an absorption maxima at 1051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q-switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 micrograms/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of (/sup 3/H)-thymidine at 6 and 24 hours postexposure to Q-switch II dye. At concentrations up to 10 micrograms/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 micrograms/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q-switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 micrograms/ml. Further studies will be required to determine the usefulness of Q-switch II dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1060 nm) at nonthermal levels of energies.

  10. The effect of adenovirus expressing wild-type p53 on 5-fiuorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Sven Eisold; Michael Linnebacher; Eduard Ryschich; Dalibor Antolovic; Ulf Hinz; Ernst Klar; Jan Schmidt

    2004-01-01

    AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.METHODS: Human pancreatic cancer cell lines Capan-1p53mut,Capan-2p53wt, FAMPACp53mut, PANC1p53mut, and rat pancreatic cancer cell lines ASp53wt and DSL6Ap53null were used for in vitro studies. Following infection with different ratios of Adp53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies.Tumor size, apoptosis (TUNEL) and survival were determined.RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

  11. Biostimulative effects of Nd:YAG Q-switch dye on normal human fibroblast cultures: study of a new chemosensitizing agent for the Nd:YAG laser

    International Nuclear Information System (INIS)

    Kodak Q-switch II is a new chemical with an absorption maxima at 1051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q-switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 micrograms/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of [3H]-thymidine at 6 and 24 hours postexposure to Q-switch II dye. At concentrations up to 10 micrograms/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 micrograms/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q-switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 micrograms/ml. Further studies will be required to determine the usefulness of Q-switch II dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1060 nm) at nonthermal levels of energies

  12. 流式细胞术应用于抗肿瘤药物敏感性实验的可行性研究%The feasibility of antitumor drugs chemosensitivity testing by flow Cytometry

    Institute of Scientific and Technical Information of China (English)

    Jing Yao; Jianhong Wu; Daxing Xie; Xiaolan Li; Deding Tao; Junbo Hu; Jianping Gong

    2007-01-01

    Objective:To investigate the feasibility of chemosensitivity testing of antitumor drugs by flow cytometry in clinical applications so as to provide experimental and theoretical basis for the establishment of a novel antitumor drugs sensitivity testing and the screening of particular antitumor drugs.Methods:Detect the apoptosis rate of 12 cases of Molt-4 cell line.57 cases of fresh clinical gastrointestinal tumor cells by Sub-G1 and Annexin V assay of flow cytometry under the effects of antitumor drugs at different times and the outcomes were compared with the ones of the MTT(3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide)assay.Results:The lethality of drugs on Molt-4 cell clinica gastrointestinal tumor cells had a positive correlation with the acting time of antidrugs by employing Annexin V.Sub-G1 and MTT assay.Drug-incurring maximum lethality of Annexin V assay was higher than MTT colorimetric assay.that of Sub-G1 was lower than MTT assay.the virtual times of Annexin V and Sub-G1 assay were obviously earlier than that of MTT colorimetric assay.Conclusion:Annexin V and Sub-G1 assay of flow cytometry can be taken as potent protocols testing anti-tumor drug chemosensitivity.Annexin V assay is featured by more sensitive,concise,reliable compared with the classical chemosensilivity testing assay Of MTT colorimetric assay and it possesses clinical applied value.

  13. Comparative study of chemosensitivity and efficacy between pirarubicin and epirubicin in breast cancer%乳腺癌对吡柔比星和表柔比星的药物敏感性及有效性的对比观察

    Institute of Scientific and Technical Information of China (English)

    臧梦芳; 张咏梅; 智英辉; 翟震; 张敏; 谷峰; 付丽; 只向成

    2011-01-01

    Objective To compare the chemosensitivity of pirarubicin(THP)and epimbicin (EPI)in primary breast cancer(PBC)cells so as to examine tIleir difierential chemosensitivity to THP and EPI by CD-DST(collagen gel droplet embedded culture-drug sensitivity test)system;To detect the differences in the short.term clinical efficacy and side effects between TAC(docetaxel+pirarubicin+cyclophosphamide)and IEC(docetaxel + epirubicin + cyclophosphamide)as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF ( cyclophosphamide+pirarubicin+fluoroumcil)and CEF(cyclophosphamide+epirubicin+fluorouracil)as the chemotherapy regimens in breast callcer:To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer.Methods From January 2008 to January 2009,a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients in II b-Ⅲ c phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axiltary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups. Results There was no significant difference of chemosensitivity between THP and EPI in PBC cells ( P = 0. 743 ) ; The overall response rate (RR) of neoadjuvant chemotherapy was 87.8% ; there was no significant difference between TAC and TEC groups (P > 0.05 ). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0. 05 ). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that

  14. Lesion-based detection of early chemosensitivity using serial static FDG PET/CT in metastatic colorectal cancer

    OpenAIRE

    Buvat, Irène; Necib, Hatem; Garcia, Camilo; Wagner, Antoine; Vanderlinden, Bruno; Emonts, Patrick; Hendlisz, Alain; Flamen, Patrick

    2012-01-01

    Purpose Medical oncology needs early identification of patients that are not responding to systemic therapy. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) performed before and early during treatment has been proposed for this purpose. However, the best way to assess the change in FDG uptake between two scans has not been identified. We studied cutoff thresholds to identify responding tumours as a function of the method used to measure tumour uptake. Methods The study include...

  15. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kinya Okamoto

    Full Text Available BACKGROUND AND AIMS: Cholangiocarcinoma (CCA is highly resistant to chemotherapy, including gemcitabine (Gem treatment. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that can regulate multiple genes expression. Some miRNAs play important roles in the chemosensitivity of tumors. Here, we examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. METHODS: Microarray analysis was used to determine the miRNA expression profiles of two CCA cell lines, HuH28 and HuCCT1. To determine the effect of candidate miRNAs on Gem sensitivity, expression of each candidate miRNA was modified via either transfection of a miRNA mimic or transfection of an anti-oligonucleotide. Ontology-based programs were used to identify potential target genes of candidate miRNAs that were confirmed to affect the Gem sensitivity of CCA cells. RESULTS: HuCCT1 cells were more sensitive to Gem than were HuH28 cells, and 18 miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221 restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Selective siRNA-mediated downregulation of either of two software-predicted targets, PIK3R1 (target of miR-29b and miR-221 or MMP-2 (target of miR-29b, also conferred Gem sensitivity to HuH28. CONCLUSIONS: miRNA expression profiling was used to identify key miRNAs that regulate Gem sensitivity in CCA cells, and software that predicts miRNA targets was used to identify promising target genes for anti-tumor therapies.

  16. A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    WEI Hai-bo; HU Jing; SHANG Li-hua; ZHANG Yun-yan; LU Fei-fei; WEI Min; YU Yan

    2012-01-01

    Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer (NSCLC) patients.To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC,we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T/MDR1 C3435T single-nucleotide polymorphism (SNP).Methods Relevant studies were identified by searching the PubMed,Embase,Cochrane,OVID,Springer,EBSCO and CNKI databases.Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy,an evaluated polymorphism of ERCC/MDR1 and overall response rate.We excluded duplicate publications,letters and review articles.The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment.Results A total of 11 studies were included in this meta-analysis.For studies evaluating ERCC1 C118T,test for heterogeneity was done (x2=13.41,P=0.1),and the odds ratio (OR) for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 (95% CI 1.09-2.06,P=-0.01).In four studies evaluating MDR1 polymorphism,test for heterogeneity was also done (x2=3.22,P=0.36),and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 (95% CI 1.44-3.68,P=0.0005).Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP.In further perspective studies,the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.

  17. Suppression of SPIN1-mediated PI3K-Akt pathway by miR-489 increases chemosensitivity in breast cancer.

    Science.gov (United States)

    Chen, Xu; Wang, Ya-Wen; Xing, Ai-Yan; Xiang, Shuai; Shi, Duan-Bo; Liu, Lei; Li, Yan-Xiang; Gao, Peng

    2016-08-01

    Drug resistance is one of the major obstacles for improving the prognosis of breast cancer patients. Increasing evidence has linked the association of aberrantly expressed microRNAs (miRNAs) with tumour development and progression as well as chemoresistance. Despite recent advances, there is still little known about the potential role and mechanism of miRNAs in breast cancer chemoresistance. Here we describe that 16 miRNAs were found to be significantly down-regulated and 11 up-regulated in drug-resistant breast cancer tissues compared with drug-sensitive tissues, using a miRNA microarray. The results also showed miR-489 to be one of the most down-regulated miRNAs in drug-resistant tissues and cell lines, as confirmed by miRNA microarray screening and real-time quantitative PCR. A decrease in miR-489 expression was associated with chemoresistance as well as lymph node metastasis, increased tumour size, advanced pTNM stage and poor prognosis in breast cancer. Functional analysis revealed that miR-489 increased breast cancer chemosensitivity and inhibited cell proliferation, migration and invasion, both in vitro and in vivo. Furthermore, SPIN1, VAV3, BCL2 and AKT3 were found to be direct targets of miR-489. SPIN1 was significantly elevated in drug-resistant and metastatic breast cancer tissues and inversely correlated with miR-489 expression. High expression of SPIN1 was associated with higher histological grade, lymph node metastasis, advanced pTNM stage and positive progesterone receptor (PR) status. Increased SPIN1 expression enhanced cell migration and invasion, inhibited apoptosis and partially antagonized the effects of miR-489 in breast cancer. PIK3CA, AKT, CREB1 and BCL2 in the PI3K-Akt signalling pathway, demonstrated to be elevated in drug-resistant breast cancer tissues, were identified as downstream effectors of SPIN1. It was further found that either inhibition of SPIN1 or overexpression of miR-489 suppressed the PI3K-Akt signalling pathway. These data

  18. Bioimpedance microelectronics in a 24-microwell plate with metabolic-sensors for testing chemosensitivity of tumor cells and tissues

    Science.gov (United States)

    Schwarzenberger, T.; Demmel, F.; Becker, B.; Zottmann, M.; Wolf, P.; Kleinhans, R.; Brischwein, M.; Otto, A.; Wolf, B.

    2010-04-01

    Living cells react to external influences such as pharmacological agents in an intricate manner due to their complex internal signal processing. Cell reactions are an impact on vitality, cell-cell or cell-matrix interaction and morphological changes. A number of published techniques on impedance spectroscopy (IS) of adherent cells with planar electrodes address these changes. However, IS can merely serve as an indicator of cellular events rather than provide detailed information on a specific cell process. Thus our approach is a 24-microwell sensor-plate with impedance-electrodes in parallel to pH- and O2-sensors, capable of being integrated into a fully automated screening system. For the purpose of IS, high precision impedance-electronics have been developed based on integrated circuits and validated against a Solartron 1260 impedance analyzer. IS data is correlated to the metabolic-sensors and additionally compared with cell images shot by an inverse optical microscope which is also part of the screening system. Proof of principle is demonstrated by experimental growth monitoring of a MCF-7 culture and cellular response to chemotherapeutics. Furthermore, the potential to monitor living tissue probes is presented for the first time.

  19. Enhancement of chemosensitivity of quiescent cell populations in solid tumors by combined treatment with nicotinamide and low temperature hyperthermia

    International Nuclear Information System (INIS)

    C3H/He and Balb/c mice bearing SCC VII and EMT6/KU tumors, respectively, received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Nicotinamide was administered intraperitoneally before cisplatin injection and/or tumors were locally heated at 40degC for 60 minutes immediately after cisplatin injection. The tumors were then excised, minced and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumor cells was determined from tumors that were not pretreated with BrdU labeling. The sensitivity to cisplatin was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). In both tumor systems, the MN frequency in Q cells was lower than that in the total cell population. Nicotinamide treatment elevated the MN frequency in total SCC VII cells. Mild heating raised the MN frequency more markedly in Q cells than total cells. The combination of nicotinamide and mild heat treatment increased the MN frequency more markedly than either treatment alone. In total SCC VII cells, nicotinamide increased 195mPt-cisplatin uptake. Mild heating elevated 195mPt-cisplatin uptake in total EMT6/KU cells. Cisplatin-sensitivity of Q cells was lower than that of total cells in both tumor systems. Nicotinamide sensitized tumor cells including a large acutely hypoxic fraction such as those of SCC VII tumors through inhibition of the fluctuations in tumor blood flow. Tumor cells including a large chronically hypoxic fraction such as Q cells were thought to be sensitized by mild heating through an increase in tumor blood flow. (author)

  20. Chemosensitization and radiosensitization of a lung cancer cell line A549 induced by a composite polymer micelle.

    Science.gov (United States)

    Xu, Jing; Zhang, Bi-Cheng; Li, Xiang-Long; Xu, Wen-Hong; Zhou, Juan; Shen, Li; Wei, Qi-Chun

    2016-08-01

    Multidrug resistance (MDR) to Doxorubicin (DOX) remains a major obstacle to successful cancer treatment. The present study sought to overcome the MDR of lung cancer cells and achieve radiosensitization by developing a composite DOX-loaded micelle (M-DOX). M-DOX containing PEG-PCL/Pluronic P105 was prepared by the solvent evaporation method. Lung cancer cell line A549 was adopted in this study. In vitro cytotoxicity, cellular uptake behavior, subcellular distribution, and radiosensitivity were evaluated by the treatment with M-DOX, and free DOX was used as a control. A549 cells treated with M-DOX as opposed to free DOX showed greater cellular uptake as well as greater cytotoxicity. Furthermore, M-DOX reached the mitochondria and lysosome effectively after cellular uptake, and fluorescence used to track M-DOX was found to be surrounding the nucleus. Finally, colony-forming assays demonstrated that M-DOX treatment improved radiosensitization when compared to free DOX. Based on the increased cytotoxicity and radiosensitization, M-DOX could be considered as a promising drug delivery system to overcome MDR in lung cancer therapy. PMID:27585226

  1. Drugs reverting multidrug resistance (chemosensitizers)

    Energy Technology Data Exchange (ETDEWEB)

    Gualtieri, F. [Florence Univ. (Italy). Dip. di Scienze Farmaceutiche

    1996-12-01

    Drug resistance is a phenomenon that frequently impairs proper treatment of cancer. Multidrug resistance (MDR) is a particular case of acquired drug resistance, resulting from overexpression of a protein (P-170) that functions as a pump, clearing cells from the chemotherapic. The P-170 protein functions can be inhibited by a variety of lipophilic drugs containing a hydrophilic nitrogen, protonated at physiological pH. A considerable effort is underway to identify new drugs able to reverse MDR. Few of these molecules are already undergoing clinical trials.

  2. Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): Protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study

    International Nuclear Information System (INIS)

    Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available. Identifying which patients are unlikely to respond to adjuvant chemotherapy from among those who are eligible for such treatment would be a major step towards treatment personalization. It would spare such patients from unnecessary toxicities and would improve the allocation of societal healthcare resources. PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer. The study’s primary objective is to examine the ability of PET/CT-assessed tumor FDG uptake after one course of preoperative chemotherapy to predict the outcome of adjuvant therapy, as measured by 3-year disease-free survival. Secondary objectives are to examine the predictive value of changes in PET/CT-assessed tumor FDG uptake on overall survival, to define the best cut-off value of FDG uptake for predicting treatment outcome, and to analyse the cost-effectiveness of such preoperative chemo-sensitivity testing. At study planning, exploratory translational research objectives were 1) to assess the predictive value of circulating tumor cells for disease-free survival, 2) to examine the predictive value of single nucleotide polymorphisms for disease-free survival with respect to genes related either to

  3. 小径管对接焊缝超声波探伤规程、导则的应用及缺陷波的识别%Discussion on Application of Small Diameter Tube Related Ultrasonic Testing Guides or Rules and Defects Wave Identification

    Institute of Scientific and Technical Information of China (English)

    李树军; 王志永; 牛晓光; 董国振; 梁红方

    2012-01-01

    Combining with the practical experience, this article gave the comparative analysis of the small diameter tube related ultrasonic testing guides and the rules, and discussed the wave identification features of ultrasonic testing of the small diameter tubes. Through the analysis and comparison, this article gave the suggestion on application of different thicknesses of small diameter tubes ultrasonic testing guides and rules.%结合多年实践,对小径管对接焊缝超声波探伤相关规程、导则主要异同及其对缺陷判伤影响进行了分析,并对缺陷波的识别进行了论述,对不同壁厚的小径管超声波探伤如何执行规程和导则给出了建议。

  4. ATP-TCA检测乳腺癌细胞对体外化疗药物敏感性的研究%Chemosensitivity in Vitro by ATP-TPC in Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    张大庆; 崔振; 余辉; 陈凯; 余建军

    2012-01-01

    Objective To measure the appropriate chemotherapeutic agents on breast cancer cells in vitro by ATP - TCA and to evaluate the possibility of individual chemotherapy of breast cancer patients. Methods The study included 35 women with breast cancer who were subjected to modified radical mastectomy. All patients were initially treated, without adjuvant chemotherapy and radiotherapy. Tumor tissue were cultured with 9 kinds of chemotherapeutic agents at respective peak plasma concentration with three repeats for 3-5 days. The inhibition rate of the samples was measured by ATP bioluminescence assay. Results 32 of 35 assays completed successfully with ATP - TCA, with a evaluability rate of 91. 4% . The assay results suggested that 32 specimens from different breast cancer patients responded to chemotherapeutic drugs with individualized profiles. The most effective drug in the experiment was Adriamycin , and then Docetaxel, Paclitaxel, Vinorelbine, 5 - Fluorouracil, Cis - platinum and Gemcitabine, the rates of chemosensitivity of which were 81. 2% , 68.8% ,59.4% ,43.8% ,34.4%,31.2% and 25% respectively. While Methotrexate and Etoposide ( VP-16) were almost weakly active or resistive(0&12. 5% ) . Conclusion The anthracycline and taxane chemotherapeutic program has a better consistence of breast cancer in vitro chemosensitivity test. The vitro susceptibility test may provide the experimental basis for the implementation of the individual chemotherapeutic drugs.%目的 ATP-TCA检测乳腺癌患者肿瘤细胞对化疗药物的敏感性,评价本方法指导乳腺癌个体化疗的可行性.方法 35例行乳腺癌改良根治术患者纳入本研究,术中取新鲜无菌肿瘤组织,进行原代细胞培养,分别加入9种化疗药物,采用 ATP-TCA 测定药物对肿瘤细胞的抑制情况.结果 35例标本中32例完成药敏检测,标本的可评价率为91.4%.患者对化疗药物的体外敏感性存在个体差异,乳腺癌细胞对ADM

  5. Rapid in vivo Taxotere quantitative chemosensitivity response by 4.23 Tesla sodium MRI and histo-immunostaining features in N-Methyl-N-Nitrosourea induced breast tumors in rats

    Directory of Open Access Journals (Sweden)

    Wu Ed X

    2005-08-01

    Full Text Available Abstract Background Sodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere. Aim To evaluate the association of in vivo intracellular sodium magnetic resonance image intensities with immuno-biomarkers and histopathological features to monitor the early tumor response to Taxotere chemotherapy in Methyl-Nitroso-Urea induced rat xenograft breast tumors. Methods and Materials Methyl-Nitroso-Urea (MNU induced rat xenograft breast tumors were imaged for sodium MRI and compared with tumor histology, immunostaining after 24 hours chemotherapy. Results Sodium MRI signal intensities represented sodium concentrations. Excised tumor histological sections showed different in vitro histological end points i.e. single strand DNA content of cell nuclei during cell cycle (G1/S-G2/M, distinct S or M histograms (Feulgen labeling to nuclear DNA content by CAS 200, mitotic figures and apoptosis at different locations of breast tumors. Necrosis and cystic fluid appeared gray on intracellular (IC sodium images while apoptosis rich regions appeared brighter on IC sodium images. After 24 hours Taxotere-treated tumors showed lower 'IC/EC ratio' of viable cells (65–76% with higher mitotic index; apoptotic tumor cells at high risk due to cytotoxicity (>70% with high apoptotic index; reduced proliferation index (270 vs 120 per high power field associated with enhanced IC sodium in vivo MR image intensities and decreased tumor size (3%; p in vivo associated with apoptosis and different pre-malignant features within 24 hours of exposure of cancer cells to anti-neoplastic Taxotere drug. Conclusion Sodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features.

  6. Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity

    Science.gov (United States)

    Guyenet, Patrice G.; Bayliss, Douglas A.; Stornetta, Ruth L.; Fortuna, Michal G.; Abbott, Stephen B.; Depuy, Seth D.

    2009-01-01

    SUMMARY Breathing automaticity and CO2 regulation are inseparable neural processes. The retrotrapezoid nucleus (RTN), a group of glutamatergic neurons that express the transcription factor Phox2b, may be a crucial nodal point through which breathing automaticity is regulated to maintain CO2 constant. This review updates the analysis presented in prior publications. Additional evidence that RTN neurons have central respiratory chemoreceptor properties is presented but this is only one of many factors that determine their activity. The RTN is also regulated by powerful inputs from the carotid bodies and, at least in the adult, by many other synaptic inputs. We also analyze how RTN neurons may control the activity of the downstream central respiratory pattern generator. Specifically, we review the evidence which suggests that RTN neurons a) innervate the entire ventral respiratory column, and b) control both inspiration and expiration. Finally, we argue that the RTN neurons are the adult form of the parafacial respiratory group in neonate rats. PMID:19712903

  7. Uso de teste de químio-sensibilidade para escolha da quimioterapia adjuvante no câncer gástrico avançado Use of the chemosensitivity test to choose appropriate adjuvant chemotherapy for advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Wilson Shinjiro Matsuzaki

    2006-08-01

    Full Text Available OBJETIVO: Introduzir e familiarizar em nosso meio o uso do teste de químio-sensibilidade MTT avaliando a ação de agentes quimioterápicos sobre células tumorais de 30 doentes com câncer gástrico avançado. Correlacionar os resultados do teste MTT com os aspectos clínicos, anátomo-patológicos e estádio utlizando a mesma metodologia do estudo realizado em pacientes japoneses na Universidade de Keio, Japão. MÉTODO: Foi realizado o teste MTT em tumores de 30 pacientes com diagnóstico de adenocarcinoma gástrico, submetidos ao tratamento cirúrgico no Departamento de Cirurgia da Faculdade de Ciências Médicas da Santa Casa de São Paulo. Foram estudados in vitro os seguintes agentes quimioterápicos: mitomicina C, doxorrubicina, cisplatina e 5-fluorouracil. RESULTADOS: Os índices de atividade sobre células tumorais foram: 16,6% para a mitomicina C, 10,0% para a doxorrubicina, 6,6% para a cisplatina e 6,6% para o 5-fluorouracil. Os resultados do teste MTT não tiveram correlação com a idade, sexo, aspectos microscópicos e estádio (p0,05. CONCLUSÕES: A ação dos agentes quimioterápicos estudados sobre células tumorais do câncer gástrico foi baixa. Os resultados da ação dos quimioterápicos in vitro não apresentou correlação estatística com a idade, sexo, aspectos microscópicos e estádio destes doentes. Utilizando a mesma metodologia, tanto em nosso meio como em pacientes japoneses, a quimio-sensibilidade se mostrou baixa em ambos os estudos, podendo-se deduzir também que os resultados da químiosensibilidade independe da etnia. Com o surgimento de novos agentes quimioterápicos, a expectativa é grande para melhores resultados na prática clínica. Com a utilização e difusão do teste MTT em nosso meio, poder-se-á criar protocolos e estudos multicêntricos para selecionar os quimioterápicos a serem utlizados.BACKGROUND: Utilizing the MTT chemosensitivity test to evaluated the action of chemotherapeutic agents on

  8. Commercial Pilot Airplane Written Test Guide. Revised Edition.

    Science.gov (United States)

    Federal Aviation Administration (DOT), Washington, DC. Flight Standards Service.

    This guide is intended to help applicants prepare for the Commercial Airplane Pilot Written Test. The guide outlines the aeronautical knowledge requirements for a commercial pilot, informs the applicant of source material that can be used to acquire their knowledge, and includes test items and illustrations representative of those used in the…

  9. Private Pilot Airplane Written Test Guide. Revised Edition.

    Science.gov (United States)

    Federal Aviation Administration (DOT), Washington, DC. Flight Standards Service.

    This guide is intended to assist persons preparing to take the written test for the private airplane pilot rating. Guidance is offered on what to expect on the FAA-administered test. Recommendations for study material are presented. Samples of test forms are included and 119 pages of sample questions are provided. (RE)

  10. Flight Test Guide (Part 61 Revised): Instrument Pilot: Helicopter.

    Science.gov (United States)

    Federal Aviation Administration (DOT), Washington, DC. Flight Standards Service.

    The guide provides an outline of the skills required to pass the flight test for an Instrument Pilot Helicopter Rating under Part 61 (revised) of Federal Aviation Regulations. General procedures for flight tests are described and the following pilot operations outlined: maneuvering by reference to instruments, IFR navigation, instrument…

  11. Tau蛋白表达与ER阳性乳腺癌紫杉类化疗敏感性的临床分析%Clinical analysis of Tau protein expressions and taxane-based chemo-sensitivity of breast cancer with ER positive

    Institute of Scientific and Technical Information of China (English)

    李志华; 涂剑宏; 龚宇; 雷秋模; 魏文嵩; 罗永辉

    2012-01-01

    目的 探讨Tau蛋白表达与ER阳性乳腺癌紫杉类化疗敏感性的关系.方法 采用Elivison二步法免疫组化检测乳腺癌组织Tau蛋白的表达,统计分析乳腺癌组织Tau蛋白与ER的相关性,及其与含紫杉类方案新辅助化疗疗效的关系.结果 Tau蛋白在乳腺癌组织的表达率为44%(88/200),与ER表达呈正相关(r = 0.32,P < 0.0001).Tau蛋白阴性的乳腺癌患者,紫杉类新辅助化疗疗效、病理化疗反应分级和病理完全缓解率均高于Tau蛋白阳性组,差异有统计学意义(P = 0.002、P < 0.000 1、P < 0.000 1),且这种差异在ER阳性分层分析中也存在(P = 0.008、P < 0.000 1、P < 0.000 1),但在ER阴性的乳腺癌患者中不存在(P = 1.000、0.623、0.119).结论 乳腺癌组织Tau蛋白表达与ER正相关,检测Tau蛋白表达可作为ER阳性乳腺癌患者选择紫杉类化疗药物的临床依据.%Objective To investigate the relationship between tau protein expressions and taxane-based chemo-sensitivity of breast cancer with estrogen receptor (ER) positive. Methods The expression of tau protein in breast cancer was detected by elivison two-step immunohistochemical methods, and the results were analyzed with the correlation to ER expression and chemo-sensitivity of taxane. Results The expressions of tau protein in breast cancer tissues were 44% (88/200). Tau protein expression was positively correlated with ER expression (r = 0.32, P < 0.000 1). The clinical efficacy, Miller-Payne pathological reactive grade and pathologic complete response rate of taxane-containing neoadjuvant chemotherapy in tau negative patients were higher than in tau positive (P = 0.002, P < 0.000 1, P < 0.000 1). There were significant differences in ER-positive subgroups (P = 0.008, P < 0.000 1, P < 0.000 1), but no significant differences in ER-negative subgroups (P = 1.000, 0.623, 0.119). Conclusion Tau protein expression is positively correlated with ER expression in breast cancer. The

  12. Effects of Downregulation of Bcl - 2 Expression by Small Interfering RNA on Cell Growth and Chemosensitivity to Methotrexate in Human Hepatoma Cell Line Hep3B%siRNA介导的Bcl-2表达下调对肝癌细胞Hep3B的影响及对氨甲蝶呤化疗敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    黄维亮; 徐丹; 谢元林

    2012-01-01

    目的 构建靶向Bcl -2基因的siRNA表达质粒,观察其对肝癌细胞Hep3B的影响及对氨甲蝶呤(MTX)化疗敏感性的影响.方法 根据siRNA设计原则,设计并合成Bcl -2的siRNA序列,克隆到pRNAT- U6.1/Neo质粒U6启动子下游构建重组质粒;经序列分析确认质粒构建成功后,将重组质粒转染入人肝癌细胞Hep3B,通过RT- PCR、Western blot分析Bcl -2的表达,细胞生长实验分析其对肝癌细胞生长的影响及对MTX化疗敏感性的影响.结果 重组质粒pRNAT- U6.1/Neo- Bcl-2经过基因序列分析,siRNA片段成功插入,转染此质粒可使Bcl -2的翻译和蛋白表达水平一定程度的降低,并且可抑制Hep3B细胞的生长,增加其对MTX化疗的敏感性.结论 成功构建并筛选出靶向Bcl-2基因的siRNA表达载体,它能抑制肝癌细胞Hep3B的生长及增加其对MTX化疗的敏感性,为基因治疗肝癌提供了新策略和实验基础.%Objective To construct small interfering RNA (siRNA) expression plasmid to Bel -2 gene and observe its effects on cell growth and chemosensitivity to methotrexate (MTX) in human hepatoma cell line Hep3B. Methods Bel - 2 siRNA sequence was designed, synthesized and cloned into the downstream of U6 promoter of the pRNAT - U6.1/Neo plasmid to construct recombinant plasmid. After the successful construction was confirmed by sequence analysis, the recombinant plasmid was transfected into human hepatoma cell line Hep3B. The expression of Bel - 2 was analyzed by RT - PCR and Western blot. Its effects on the cell growth and chemosensitivity to MTX in Hep3B cell was detected by cell growth assay. Results Sequence analysis of the recombinant plasmid pRNAT - U6.1/Neo - Bel -2 confirmed that the siRNA fragments were successfully inserted into the plasmid. Transfection of the recombinant plasmid into Hep3B cell could reduce the translation and expression of Bel - 2 by a certain extent. It can also inhibit the growth of Hep3B and increase its sensitivity to

  13. Survivin基因在牛蒡子苷元增强人肺癌H460细胞化疗敏感性中的作用%Biological functions of Survivin in chemosensitization of arctigenin in lung cancer H460 cells

    Institute of Scientific and Technical Information of China (English)

    王焕勤; 王静

    2015-01-01

    Objective To explore the role of survivin in the chemosensitization of arctigenin in lung cancer H460 cells.Methods Human full-length Survivin cDNA was amplified by polymerase chain reaction and cloned into pcDNA3.1 (+) expression vector.The resultant survivin-expressing plasmid or empty vector was individually transfected into H460 cells using Lipofectamine 2000.Twenty-four hours after transfection,survivin expression in H460 cells was tested by Western blot.Transfected cells were exposed to arctigenin alone or combined with cisplatin and cell apoptosis was assessed using Annexin-Ⅴ/ PI staining methods.Results Compared to untransfected and empty vector-transfected H460 cells,survivin-transfected cells had a 10-fold elevation in the survivin expression.Low-dose cisplatin did not significantly affect the expression of survivin in H460 cells.In contrast,arctigenin significantly inhibited the expression of survivin protein.When cisplatin was combined with arctigenin,a greater inhibition of survivin expression was observed.Compared to transfection of empty vector,pre-transfection with pcDNA3.1-Survivin plasmid significantly reversed the pro-apoptotic activity of arctigenin alone or combined with cisplatin,leading to a significant reduction in the apoptotic index.Conclusions Arctigenin can inhibit the expression of survivin in lung cancer H460 cells.Arctigenin-mediated chemosensitization of lung cancer H460 cells to cisplatin is associated with suppression of survivin signaling pathway.%目的 研究Survivin基因在牛蒡子苷元促进肺癌细胞化疗敏感性中的作用.方法 应用RT-PCR技术从H460细胞中扩增全长人Survivin cDNA,并将其克隆至pcDNA3.1(+)表达载体,构建人Survivin基因真核表达质粒.将pcDNA3.1-Survivin重组质粒或空载体分别转染H460细胞,孵育24 h后,应用Western blot法检测Survivin过表达情况;转染细胞与牛蒡子苷元单独或联合顺铂处理,应用Annexin-Ⅴ/PI染色法检

  14. 浸润性乳腺癌中肝细胞生长因子的表达及其与化疗敏感性和预后的相关性%Expression of HGF and its influence on chemosensitivity and prognosis in invasive breast cancer

    Institute of Scientific and Technical Information of China (English)

    杨桦; 张崇建; 王子兵; 崔树德

    2012-01-01

    目的 探讨肝细胞生长因子(HGF)在浸润性乳腺癌中的表达及其对新辅助化疗敏感性和预后的影响.方法 免疫组化法检测125例浸润性乳腺癌组织中HGF的表达,分析HGF与患者术前化疗及5年生存率的关系;利用si-RNA沉默乳腺癌细胞株MCF-7检测 HGF的表达,MTT法检测加入不同浓度表阿霉素共培养后的细胞增殖能力.结果 HGF阳性组与阴性组在TNM分期、组织学分级、淋巴结转移、新辅助化疗疗效及预后方面差异有统计学意义(P<0.05),下调HGF后的MCF-7细胞对表阿霉素的耐药性减弱.结论 HGF在乳腺癌中表达与淋巴结转移、预后及化疗敏感性密切相关,有可能作为判断预后和预测化疗疗效的指标之一.%Objective To study the expression of hepatocyte growth factor( HGF ) in tissue and cells in patients with invasive breast cancer and the effects of HGF on neoadjuvant chemotherapy and prognosis of the patients. Methods Immunohistochemical method was used to detect the expression of HGF in the paraffin section of 125 cases of invasive breast cancer. The relationship of the HGF expression, preoperative chemotherapy and five years' survival rate was analyzed. The expression of HGF was detected by si-RNA MCF-7. The cell proliferation of breast cancer cells co-cultured with different concentrations of doxorubicin was determined by MTT. Results The expression of HGF between negative and positive group was significant difference in the histological grade, TNM stage, lymphonodus metastasis, chemotherapy effect and prognosis ( P <0. 05 ). The drug resistance of cells to doxorubicin was weakened after down-regulation of the level of HGF. Conclusion HGF is strongly associated with lymphonodus metastasis, prognosis and chemosensitivity in breast neoplasm, which may be used as one of the independent parameters to the prognostic and the effect of chemotherapy.

  15. systems

    Directory of Open Access Journals (Sweden)

    Alexander Leonessa

    2000-01-01

    Full Text Available A nonlinear robust control-system design framework predicated on a hierarchical switching controller architecture parameterized over a set of moving nominal system equilibria is developed. Specifically, using equilibria-dependent Lyapunov functions, a hierarchical nonlinear robust control strategy is developed that robustly stabilizes a given nonlinear system over a prescribed range of system uncertainty by robustly stabilizing a collection of nonlinear controlled uncertain subsystems. The robust switching nonlinear controller architecture is designed based on a generalized (lower semicontinuous Lyapunov function obtained by minimizing a potential function over a given switching set induced by the parameterized nominal system equilibria. The proposed framework robustly stabilizes a compact positively invariant set of a given nonlinear uncertain dynamical system with structured parametric uncertainty. Finally, the efficacy of the proposed approach is demonstrated on a jet engine propulsion control problem with uncertain pressure-flow map data.

  16. Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Jenkinson, Michael D. [Walton Centre for Neurology and Neurosurgery, Department of Neurosurgery, Liverpool (United Kingdom); University of Liverpool, Division of Neuroscience, Liverpool (United Kingdom); Smith, Trevor S. [Walton Centre for Neurology and Neurosurgery, Department of Neuroradiology, Liverpool (United Kingdom); Joyce, Kathy A.; Fildes, Diane [JK Douglas Laboratories, Clatterbridge Cancer Research Trust, Wirral (United Kingdom); Broome, John [Walton Centre for Neurology and Neurosurgery, Department of Neuropathology, Liverpool (United Kingdom); Plessis, Daniel G. du [University of Liverpool, Division of Neuroscience, Liverpool (United Kingdom); Haylock, Brian; Husband, David J. [Clatterbridge Hospital, Clatterbridge Centre for Oncology, Neuro-Oncology, Wirral (United Kingdom); Warnke, Peter C. [Leibniz Institute for Neurobiology, Magdeburg (Germany); Walker, Carol [University of Liverpool, Division of Neuroscience, Liverpool (United Kingdom); JK Douglas Laboratories, Clatterbridge Cancer Research Trust, Wirral (United Kingdom)

    2006-10-15

    The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy. Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33). 1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss. (orig.)

  17. Nasal trigeminal chemosensitivity across the adult life span

    Czech Academy of Sciences Publication Activity Database

    Wysocki, C. J.; Cowart, B. J.; Radil, Tomáš

    2003-01-01

    Roč. 65, č. 1 (2003), s. 115-122. ISSN 0031-5117 Grant ostatní: NI on Deafness (US) P50 DC00214; NI on Deafness (US) RO1 DC00298; Fogarty Center(US) F05 TW04839; Garfield Foundation(US) x Institutional research plan: CEZ:AV0Z5011922 Keywords : chemesthesis * trigeminal Subject RIV: FH - Neurology Impact factor: 1.856, year: 2003

  18. 抑制人类生殖器形成抑制基因对非小细胞肺癌H1299细胞化疗敏感性的影响%Effect of inhibiting the expression of hSMG-1 on chemosensitivity of human non-small cell lung cancer H1299 cells

    Institute of Scientific and Technical Information of China (English)

    夏启胜; 李源贞; 李红艳; 刘轩; 徐波; 向青; 喻长远; 陈志华

    2011-01-01

    Objective To investigate the effect of inhibiting the expression of human suppressor of morphogenesis in genitalia-1 (hSMG-1) on chemosensitivity in human lung cancer H1299 cells. Methods Specialized small interference RNAs (siRNAs) of hSMG-1 were transfected into H1299 cells. The knockdown effect was evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. After the administration of anti-cancer drugs, the cell viable rate was determined by cell counting kit (CCK-8) and apoptotic rate was measured by Annexin V-FITC PI double staining on flow cytometry. The apoptotic related activated caspase 3 and caspase 9 were determined by colorimetric assay. Results The expression of hSMG-1 mRNA was significantly inhibited by hSMG-1 siRNA. And the inhibition rate of (73.8 ± 10. 3) % was obtained ( P < 0. 01 ). The knockdown effect was further confirmed by immunofluorescence. The inhibition of hSMG-1 enhanced the sensitivity of H1299 cells to gemcitabine and cisplatin. The survival rates significantly decreased when the hSMG-1 siRNA transfected cells were treated with 10. 0 mg/L gemcitabine and 10. 0 mg/L cisplatin for 48 h respectively (0. 51 ±0. 02 vs 0. 69 ± 0. 01, P < 0. 01 and 0. 34 ± 0. 03 vs 0. 48 ± 0. 01, P < 0. 02; all compared with control siRNA group). Annexin V-FITC PI double staining showed that, under the treatment of anti-cancer drugs, the apoptotic rate of H1299 cells was significantly increased by hSMG-1 knockdown [gemcitabine, (20.9 ±3.4)% vs (12.0±2.7)%, P<0.05; cisplatin, (10.2 ±1.8)% vs (4.5 ±2.0)%, P<0.05; all compared with control siRNA group]. Further study showed the inhibition of hSMG-1 up-regulated the activated caspase 3 and caspase 9 in the treated H1299 cells (gemcitabine, 0. 1 mg/L, 48 h, caspase 3:14. 4 ± 3.8 vs 2. 3 ± 0. 4, P < 0. 01; caspase 9: 15.5 ± 2.4 vs 4. 2 ± 0. 9, P < 0. 01; cisplatin, 1. 0 mg/L,48 h, caspase 3:18.8±3.0 vs 6.5 ±1.5, P<0. 01

  19. Facilitation of breathing by leptin effects in the central nervous system.

    Science.gov (United States)

    Bassi, M; Furuya, W I; Zoccal, D B; Menani, J V; Colombari, D S A; Mulkey, D K; Colombari, E

    2016-03-15

    With the global epidemic of obesity, breathing disorders associated with excess body weight have markedly increased. Respiratory dysfunctions caused by obesity were originally attributed to mechanical factors; however, recent studies have suggested a pathophysiological component that involves the central nervous system (CNS) and hormones such as leptin produced by adipocytes as well as other cells. Leptin is suggested to stimulate breathing and leptin deficiency causes an impairment of the chemoreflex, which can be reverted by leptin therapy. This facilitation of the chemoreflex may depend on the action of leptin in the hindbrain areas involved in the respiratory control such as the nucleus of the solitary tract (NTS), a site that receives chemosensory afferents, and the ventral surface of the medulla that includes the retrotrapezoid nucleus (RTN), a central chemosensitive area, and the rostral ventrolateral medulla (RVLM). Although the mechanisms and pathways activated by leptin to facilitate breathing are still not completely clear, evidence suggests that the facilitatory effects of leptin on breathing require the brain melanocortin system, including the POMC-MC4R pathway, a mechanism also activated by leptin to modulate blood pressure. The results of all the studies that have investigated the effect of leptin on breathing suggest that disruption of leptin signalling as caused by obesity-induced reduction of central leptin function (leptin resistance) is a relevant mechanism that may contribute to respiratory dysfunctions associated with obesity. PMID:26095748

  20. Desogestrel enhances ventilation in ondine patients: Animal data involving serotoninergic systems.

    Science.gov (United States)

    Joubert, Fanny; Perrin-Terrin, Anne-Sophie; Verkaeren, Emilienne; Cardot, Philippe; Fiamma, Marie-Noëlle; Frugière, Alain; Rivals, Isabelle; Similowski, Thomas; Straus, Christian; Bodineau, Laurence

    2016-08-01

    Congenital central hypoventilation syndrome (CCHS) is a neurorespiratory disease characterized by life-threatening sleep-related hypoventilation involving an alteration of CO2/H(+) chemosensitivity. Incidental findings have suggested that desogestrel may allow recovery of the ventilatory response to CO2. The effects of desogestrel on resting ventilation have not been reported. This study was designed to test the hypothesis that desogestrel strengthens baseline ventilation by analyzing the ventilation of CCHS patients. Rodent models were used in order to determine the mechanisms involved. Ventilation in CCHS patients was measured with a pneumotachometer. In mice, ventilatory neural activity was recorded from ex vivo medullary-spinal cord preparations, ventilation was measured by plethysmography and c-fos expression was studied in medullary respiratory nuclei. Desogestrel increased baseline respiratory frequency of CCHS patients leading to a decrease in their PETCO2. In medullary spinal-cord preparations or in vivo mice, the metabolite of desogestrel, etonogestrel, induced an increase in respiratory frequency that necessitated the functioning of serotoninergic systems, and modulated GABAA and NMDA ventilatory regulations. c-FOS analysis showed the involvement of medullary respiratory groups of cell including serotoninergic neurons of the raphe pallidus and raphe obscurus nuclei that seem to play a key role. Thus, desogestrel may improve resting ventilation in CCHS patients by a stimulant effect on baseline respiratory frequency. Our data open up clinical perspectives based on the combination of this progestin with serotoninergic drugs to enhance ventilation in CCHS patients. PMID:27040794

  1. Low levels of graphene and graphene oxide inhibit cellular xenobiotic defense system mediated by efflux transporters.

    Science.gov (United States)

    Liu, Su; Jiang, Wei; Wu, Bing; Yu, Jing; Yu, Haiyan; Zhang, Xu-Xiang; Torres-Duarte, Cristina; Cherr, Gary N

    2016-06-01

    Low levels of graphene and graphene oxide (GO) are considered to be environmentally safe. In this study, we analyzed the potential effects of graphene and GO at relatively low concentrations on cellular xenobiotic defense system mediated by efflux transporters. The results showed that graphene (<0.5 μg/mL) and GO (<20 μg/mL) did not decrease cell viability, generate reactive oxygen species, or disrupt mitochondrial function. However, graphene and GO at the nontoxic concentrations could increase calcein-AM (CAM, an indicator of membrane ATP-binding cassette (ABC) transporter) activity) accumulation, indicating inhibition of ABC transporters' efflux capabilities. This inhibition was observed even at 0.005 μg/mL graphene and 0.05 μg/mL GO, which are 100 times and 400 times lower than their lowest toxic concentration from cytotoxicity experiments, respectively. The inhibition of ABC transporters significantly increased the toxicity of paraquat and arsenic, known substrates of ABC transporters. The inhibition of ABC transporters was found to be based on graphene and GO damaging the plasma membrane structure and fluidity, thus altering functions of transmembrane ABC transporters. This study demonstrates that low levels of graphene and GO are not environmentally safe since they can significantly make cell more susceptible to other xenobiotics, and this chemosensitizing activity should be considered in the risk assessment of graphene and GO. PMID:26554512

  2. Naloxone application to the ventrolateral medulla enhances the respiratory response to inspired carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Trouth, C.O.; Bada, F.J.; Pan, Yi; Holloway, J.A.; Millis, R.M.; Bernard, D.G. (Howard Univ., Washington, D.C. (USA))

    1991-01-01

    Previous studies have shown that systemic administration of the opiate antagonist naloxone potentiates the ventilatory response to inspired carbon dioxide. The present study was designed to localize the site of action of naloxone for increasing the respiratory chemosensitivity to inhaled carbon dioxide (CO{sub 2}) in cats. Naloxone applied topically to the caudal chemosensitive area on the ventral medullary surface (VMS) during hypercapnic breathing produced a 75% greater increase in minute ventilation than hypercapnic breathing alone. Furthermore, hypercapnic breathing produced a 200% increase in neuronal activity of VMS chemosensitive cells; this was further increased 120% by naloxone. It is concluded that naloxone increases the sensitivity of neurons in the caudal respiratory chemosensitive area of cats to hypercapnia, and that endogenous opiates may act as modulators at VMS chemosensitive sites during hypercapnic breathing.

  3. Learning to Talk Like the Test: Guiding Speakers of African American Vernacular English

    Science.gov (United States)

    Fisher, Douglas; Lapp, Diane

    2013-01-01

    In this article, we focus on instructional support for 91 students who speak African American Vernacular English and who are at high risk for not passing the required state exams. We profile the instruction that was provided and the results from that instruction, providing examples of how students' language was scaffolded such that they could…

  4. Systems biology of cisplatin resistance: past, present and future.

    Science.gov (United States)

    Galluzzi, L; Vitale, I; Michels, J; Brenner, C; Szabadkai, G; Harel-Bellan, A; Castedo, M; Kroemer, G

    2014-01-01

    The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant

  5. Systemic Leptin Produces a Long-Lasting Increase in Respiratory Motor Output in Rats

    Directory of Open Access Journals (Sweden)

    DonaldRMcCrimmon

    2013-02-01

    Full Text Available Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO2 chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO2 is maintained constant. We examined the effects of intravenous leptin to test the hypothesis that systemic leptin administration in isoflurane anesthetized, mechanically ventilated and vagotomized rats would lead to a sustained increase in respiratory motor output that was independent of changes in end-tidal PCO2, body temperature or lung inflation pressure (an indicator of overall lung and chest wall compliance. In anesthetized Sprague-Dawley rats with end-tidal PCO2, lung compliance and rectal temperature maintained constant, injection of a bolus of leptin (0.25 mg, 0.5 mg/ml, i.v., followed over the next 1 hour by the intravenous infusion of an additional 0.25 mg, elicited a progressive increase in the peak amplitude of integrated phrenic nerve discharge lasting at least 1 hr beyond the end of the infusion. The increase peaked at 90 min at 58.3 ± 5.7% above baseline. There was an associated increase in the slope of the phrenic response to increasing inspired CO2.. There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate. These data indicate that leptin elicits a sustained increase in respiratory motor output that outlasts the administration leptin via a mechanism that does not require alterations in arterial PCO2, body temperature or systemic afferent feedback via the vagus nerves. Leptin may play an important role in matching alveolar ventilation to metabolism.

  6. Unique chemosensitivity of MAC 16 tumours to flavone acetic acid (LM975, NSC 347512).

    OpenAIRE

    Bibby, M. C.; Double, J A; Loadman, P.M.

    1988-01-01

    MAC 16 is one of a series of mouse colon tumours originally induced by dimethylhydrazine. It is a relatively slow growing subcutaneous adenocarcinoma which becomes necrotic as it grows and causes severe body wasting in the host. This study has indicated that the tumour is resistant to a large number of standard anti-cancer drugs but is highly responsive to the investigational agent flavone acetic acid (FAA). The levels of FAA achieved in tumours are lower than those necessary for activity in ...

  7. Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer

    Science.gov (United States)

    Winther, Mette; Knudsen, Steen; Dahlgaard, Jesper; Jensen, Thomas; Hansen, Anker; Jensen, Peter Buhl; Tramm, Trine; Alsner, Jan; Nordsmark, Marianne

    2016-01-01

    Background miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS). Material and Methods The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS. Results A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17–0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16–0.87)) and DSS (HR: 0.32 (0.12–0.87)). Conclusion The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer. PMID:26885979

  8. Temporal Characteristics of Gustatory Responses in Rat Parabrachial Neurons Vary by Stimulus and Chemosensitive Neuron Type

    OpenAIRE

    Laura Geran; Susan Travers

    2013-01-01

    It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of "sweet" (sucrose), "salty" (NaCl), "sour" (citric acid), and "bitter" (quinine and...

  9. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    International Nuclear Information System (INIS)

    Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer

  10. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Weigel Marion T

    2010-08-01

    Full Text Available Abstract Background Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Methods Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. Results The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Conclusions Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer.

  11. Chemosensitivity, Cardiovascular Risk, and the Ventilatory Response to Exercise in COPD.

    Directory of Open Access Journals (Sweden)

    Michael K Stickland

    Full Text Available COPD is associated with elevated cardiovascular risk and a potentiated ventilatory response to exercise. Enhanced carotid chemoreceptor (CC activity/sensitivity is present in other clinical conditions, has been shown to contribute to sympathetic vasoconstrictor outflow, and is predictive of mortality. CC activity/sensitivity, and the resulting functional significance, has not been well examined in COPD. We hypothesized that CC activity/sensitivity would be elevated in COPD, and related to increased pulse wave velocity (a marker of CV risk and the ventilatory response to exercise.30 COPD patients and 10 healthy age-matched controls were examined. Participants performed baseline cardiopulmonary exercise and pulmonary function testing. CC activity was later evaluated by the drop in ventilation with breathing 100% O2, and CC sensitivity was then assessed by the ventilatory response to hypoxia (ΔVE/ΔSpO2. Peripheral arterial stiffness was subsequently evaluated by measurement of pulse wave velocity (PWV using applanation tonometry while the subjects were breathing room air, and then following chemoreceptor inhibition by breathing 100% O2 for 2 minutes.CC activity, CC sensitivity, PWV and the ventilatory response to exercise were all increased in COPD relative to controls. CC sensitivity was related to PWV; however, neither CC activity nor CC sensitivity was related to the ventilatory response to exercise in COPD. CC inhibition by breathing 100% O2 normalized PWV in COPD, while no effect was observed in controls.CC activity and sensitivity are elevated in COPD, and appear related to cardiovascular risk; however, CC activity/sensitivity does not contribute to the potentiated ventilatory response to exercise.

  12. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity.

    Directory of Open Access Journals (Sweden)

    Julia P Brandt

    Full Text Available Many animals possess neurons specialized for the detection of carbon dioxide (CO(2, which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2. The ETS-5 transcription factor is necessary for the specification of CO(2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO(2-detection and transforms neurons into CO(2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2-sensing neurons in other phyla.

  13. Assessment of the chemosensitizing activity of TAT-RasGAP317-326 in childhood cancers.

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    Nadja Chevalier

    Full Text Available Although current anti-cancer protocols are reasonably effective, treatment-associated long-term side effects, induced by lack of specificity of the anti-cancer procedures, remain a challenging problem in pediatric oncology. TAT-RasGAP317-326 is a RasGAP-derived cell-permeable peptide that acts as a sensitizer to various anti-cancer treatments in adult tumor cells. In the present study, we assessed the effect of TAT-RasGAP317-326 in several childhood cancer cell lines. The RasGAP-derived peptide-induced cell death was analyzed in several neuroblastoma, Ewing sarcoma and leukemia cell lines (as well as in normal lymphocytes. Cell death was evaluated using flow cytometry methods in the absence or in the presence of the peptide in combination with various genotoxins used in the clinics (4-hydroperoxycyclophosphamide, etoposide, vincristine and doxorubicin. All tested pediatric tumors, in response to at least one genotoxin, were sensitized by TAT-RasGAP317-326. The RasGAP-derived peptide did not increase cell death of normal lymphocytes, alone or in combination with the majority of the tested chemotherapies. Consequently, TAT-RasGAP317-326 may benefit children with tumors by increasing the efficacy of anti-cancer therapies notably by allowing reductions in anti-cancer drug dosage and the associated drug-induced side effects.

  14. Myricetin enhance chemosensitivity of 5-fluorouracil on esophageal carcinoma in vitro and in vivo

    OpenAIRE

    Wang, Lei; Feng, Jianfang; Chen, Xiaonan; Guo, Wei; Du, Yuwen; Wang, Yuanyuan; Zang, Wenqiao; Zhang, Shijie; Zhao, Guoqiang

    2014-01-01

    Background Flavonoids are structurally heterogeneous, polyphenolic compounds present in high concentrations in fruits, vegetables, and other plant-derived foods. Currently, there is growing interest in the therapeutic applications of bioflavonoids for the treatment and prevention of diseases in humans. Myricetin is a naturally occurring flavonoid that is commonly found in tea, berries, fruits, vegetables, and medicinal herbs. Previous studies have shown that myricetin has antioxidant, anti-in...

  15. Temporal characteristics of gustatory responses in rat parabrachial neurons vary by stimulus and chemosensitive neuron type.

    Directory of Open Access Journals (Sweden)

    Laura Geran

    Full Text Available It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN neurons elicited by multiple applications of "sweet" (sucrose, "salty" (NaCl, "sour" (citric acid, and "bitter" (quinine and cycloheximide stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500 ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H compared to the later response (9.5%. Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H in neurons that responded optimally to bitter stimuli (B-best. Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs.

  16. A Study on the radiosensitivity and chemosensitivity of YAC-1 Cell Line in Vitroand Maxillofacial

    International Nuclear Information System (INIS)

    The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for mouse lymphoma YAC-1 cell line using semiautomated MTT assay. 2, 4, 6, 8, 10 Gy were irradiated at a dose rate of 210 cGy/min using 60Co Irradiator ALDORADO 8. After irradiation, YAC-1 cell lines (3 X 104 cells/ml) were exposed to bleomycin or cisplatin for 1 hour. The viable cells were determined for each radiation dose and/or each concentration of drug at the 4th day. And they were compared to control values. The obtained results were as follows : 1. The surviving curve with gentle slope was obtained after irradiation of 2, 4, 6, 8, 10 Gy on YAC-1 cell line. 2. The cytotoxicity of bleomycin or cisplatin was increased significantly at all concentration of 0.2 μg/ml, 2 μg/ml and 20 μg/ml on YAC-1 cell line (P<0.01). 3. There were no significant differences of surviving fractions among 4 Gy, 6 Gy, and 8 Gy after irradiation of each radiation dose with 2 μg/ml of bleomycin compared with irradiation only on YAC-1 cell line (P<0.05). 5. There were significant differences of surviving fractions between the groups of irradiation only and the groups of irradiation with 2 μg/ml of bleomycin or cisplatin at all doses of 2, 4, 6, 8 and 10 Gy on YAC-1 cell line (P<0.05).

  17. An experimental study on the radiosensitivity and chemosensitivity of MG-63 cell line

    International Nuclear Information System (INIS)

    The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human osteosarcoma MG-63 cell line using semiautomated MTT ass ay. 2, 4, 6, 8, 10 Gy were irradiated at a dose rate of 210 cGy/min using 60Co Irradiator ALDORADO 8. After irradiation, MG- 63 cell lines (3X104 cells/ml) were exposed to bleomycin and cisplatin at concentration of 0.2, 2, 20 μg/ml for 1 hour respectively. The viable cells were determined for each radiation dose and/or each concentration of drug. And they were compared to control values. The obtained results were as follows: 1. There was significant difference of surviving fraction at 4, 6, 8, 10 Gy on MG-63 cell line (p<0.05). 2. There was significant difference of cytotoxicity of bleomycin or cisplatin at all concentration of 0.2, 2, 20 μg/ml (p<0.05) on mg-63 cell line. The cytotoxicity of cisplatin was more effective than bleomycin at concentration after irradiation of 2 Gy on MG-63 cell line. 3. there was significant difference of cytotoxicity of bleomycin or cisplatin at all concentration after irradiation of Gy on MG-63 cell line. 4. There was significant difference of cytotoxicity of bloeomycin or cisplatin at concentration of 20 μg/ml after irradiation than that of irradiation alone (p<0.01). but there was no significant difference of cytotoxicity of bleomycin at concentration of 20 μg/ml after irradiation of 10 Gy than that of irradiation alone.

  18. Experimental Study on the Radiosensitivity and Chemosensitivity of A-431 Cell Line

    International Nuclear Information System (INIS)

    The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. Human epidermoid carcinoma A-431 cell line were irradiated by 2, 4, 6, 8, 10 Gy at a dose rate of 210 cGy/min using 60Co Irradiator ALDORADO 8 and then were exposed to bleomycin or cisplatin at concentration of 2 μg/ml for 1 hour. The viable cells were determined for each radiation dose and/or each drug at the 4th day and cell surviving curves were obtained using semiautomated MTT assay. The surviving fraction after irradiation of 2 Gy was 0.99, and there was not significant difference of surviving fraction in comparison with the control group on A-431 cell line (p>0.05). But there were significant differences of surviving fractions at doses of 4, 6, 8, 10 Gy in comparison with the control group (p0.05).

  19. Increased chemosensitivity of paclitaxel by telomeric fusion-induced genomic instability

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Seon Rang; Juhn, Kyoung Mi; Park, Jeong Eun; Ju, Yeun Jin; Yun, Mi Yong; Lee, Kee Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Gil Hong; Kim, Joon [College of Medicine, Korea University, Seoul (Korea, Republic of)

    2009-05-15

    A telomere is a region of repetitive DNA at the end of chromosomes. They protect a cell's chromosomes from fusing with each other or rearranging and so cells are normally destroyed when their telomeres are consumed. Most normal somatic cells lose telomeric repeats after each cell division. Telomeric shortening in humans can induce replicative senescence which blocks cell division. This mechanism appears to prevent genomic instability by limiting the number of cell divisions. Telomerase is an attractive molecular target, since its activity has been found in more than 85% of human cancers. Combination therapy with chemotherapeutic agent is superior to single in overall response rate and progression free survival. In this study, we showed that telomerase null cells are more hypersensitive by paclitaxel treatment than at wild type cells.

  20. Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear Factor-kappaB Signaling Pathway.

    Science.gov (United States)

    Rimmon, A; Vexler, A; Berkovich, L; Earon, G; Ron, I; Lev-Ari, S

    2013-01-01

    Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut) known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23). Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s) of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF- κ B-related proteins (p65, I κ Bα, and p-I κ Bα) and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10-20 M. Escin combined with gemcitabine showed only additive effect, while its combination with cisplatin resulted in a significant synergistic cytotoxic effect in Panc-1 cells. High concentrations of Escin induced apoptosis and decreased NF- κ B-related proteins and cyclin D expression. Conclusions. Escin decreased pancreatic cancer cell survival, induced apoptosis, and downregulated NF- κ B signaling pathway. Moreover, Escin sensitized pancreatic cancer cells to chemotherapy. Further translational research is required. PMID:24282639

  1. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang Fanjie

    2009-09-01

    Full Text Available Background: Accelerated glucose uptake for anerobic glycolysis is one of the major metabolic changes found in malignant cells. This property has been exploited for imaging malignancies and as a possible anticancer therapy. The nonmetabolizable glucose analog 2-deoxyglucose (2 DG interferes with glucose metabolism leading to breast cancer cell death. Aims: To determine whether 2DG can synergize with chemotherapeutic agents commonly used in breast cancer treatment and identify cellular characteristics associated with sensitivity to 2DG. Materials and Methods: SkBr3 breast cancer cells were incubated with varying concentrations of 5-fluorouracil (5FU, doxorubicin, cisplatin, cyclophosphamide, or herceptin with or without 2DG. Cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results: Combining 2DG with doxorubicin, 5 FU, cyclophosphamide, and herceptin resulted in enhanced cell death compared with each agent alone, while in combination with cisplatin, the amount of cell death was additive. Mouse embryo fibroblasts (MEF mutated for p53 (-/- were 30% more sensitive to the cytotoxic effects of 2DG than the parental cell lines. Cells mutated for Bax/Bac, genes involved in protection from apoptosis, are slightly more sensitive than the parental cell lines. Conclusions: These results indicate that 2DG acts synergistically with specific chemotherapeutic agents in causing cell death and the class of chemicals most sensitive appear to be those which cause DNA damage.

  2. Epigenetic regulation of REG1A and chemosensitivity of cutaneous melanoma

    OpenAIRE

    Sato, Yusuke; Marzese, Diego M; OHTA, KATSUYA; Huang, Sharon K.; Sim, Myung Shin; Chong, Kelly; Hoon, Dave SB

    2013-01-01

    Regenerating gene 1A (REG1A) plays an important role in tissue regeneration and in cell proliferation in epithelium origin tumors; however, its role in melanoma has not been explored in details. The objective of this study was to identify whether REG1A is expressed in cutaneous melanoma and if REG1A expression status can predict prognosis in cutaneous melanoma patients with metastasis. We also determined whether epigenetic regulation of the promoter region regulates REG1A expression. AJCC sta...

  3. Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models.

    Science.gov (United States)

    Pchejetski, Dimitri; Doumerc, Nicolas; Golzio, Muriel; Naymark, Maria; Teissié, Justin; Kohama, Takafumi; Waxman, Jonathan; Malavaud, Bernard; Cuvillier, Olivier

    2008-07-01

    We have previously reported that, in prostate cancer, inhibition of the oncogenic sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway is a key element in chemotherapy-induced apoptosis. Here, we show that selective pharmacologic inhibition of SphK1 triggers apoptosis in LNCaP and PC-3 prostate cancer cells, an effect that is reversed by SphK1 enforced expression. More importantly, we show for the first time that the up-regulation of the SphK1/S1P pathway plays a crucial role in the resistance of prostate cancer cells to chemotherapy. Importantly, pharmacologic SphK1 inhibition with the B-5354c compound sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to S1P sphingolipid ratio. To conclude, our study highlights the notion that drugs specifically designed to inhibit SphK1 could provide a means of enhancing the effects of conventional treatment through the prosurvival antiapoptotic SphK1/S1P pathway. PMID:18644996

  4. A Serial Analysis of Gene Expression (SAGE) database analysis of chemosensitivity

    DEFF Research Database (Denmark)

    Stein, Wilfred D; Litman, Thomas; Fojo, Tito;

    2004-01-01

    Drug sensitivity and resistance has been most extensively studied in cell lines carried in tissue culture. Furthermore, cell lines have been widely used in testing new anticancer agents, despite the widely recognized observation that cell lines are more sensitive to cytotoxic drugs than are their...... corresponding solid tumors. We used the Serial Analysis of Gene Expression (SAGE) database to identify differences between solid tumors and cell lines, hoping to detect genes that could potentially explain differences in drug sensitivity. SAGE libraries were available for both solid tumors and cell lines from...

  5. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.M.; Gao, S.J.; Guo, X.F.; Sun, W.J. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Yan, Z.Q. [Department of Breast Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Wang, W.X.; Xu, Y.Q.; Lu, D. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China)

    2014-03-21

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

  6. Modulation of P-Glycoprotein Mediated Multidrug Resistance (Mdr in Cancer Using Chemosensitizers.

    Directory of Open Access Journals (Sweden)

    Velingkar V.S

    2010-03-01

    Full Text Available Multidrug resistance (MDR is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp, resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had bettertolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

  7. Chemosensitization of Trypanosoma congolense strains resistant to isometamidium chloride by tetracyclines and enrofloxacin.

    Directory of Open Access Journals (Sweden)

    Vincent Delespaux

    Full Text Available BACKGROUND: Because of the development of resistance in trypanosomes to trypanocidal drugs, the livelihood of millions of livestock keepers in sub-Saharan Africa is threatened now more than ever. The existing compounds have become virtually useless and pharmaceutical companies are not keen on investing in the development of new trypanocides. We may have found a breakthrough in the treatment of resistant trypanosomal infections, through the combination of the trypanocide isometamidium chloride (ISM with two affordable veterinary antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: In a first experiment, groups of mice were inoculated with Trypanosoma congolense strains resistant to ISM and either left untreated or treated with (i tetracycline, (ii ISM or (iii the combination of the antibiotic and the trypanocide. Survival analysis showed that there was a significant effect of treatment and resistance to treatment on the survival time. The groups treated with ISM (with or without antibiotic survived significantly longer than the groups that were not treated with ISM (P<0.01. The group treated with the combination trypanocide/antibiotic survived significantly longer than the group treated with ISM (P<0.01. In a second experiment, groups of cattle were inoculated with the same resistant trypanosome strain and treated with (i ISM, (ii ISM associated with oxytetracycline or (iii ISM associated with enrofloxacine. All animals treated with ISM became parasitaemic. In the groups treated with ISM-oxytetracycline and ISM-enrofloxacine, 50% of the animals were cured. Animals from the groups treated with a combination trypanocide/antibiotic presented a significantly longer prepatent period than animals treated with ISM (p<0.001. The impact of the disease on the haematocrit was low in all ISM treated groups. Yet, it was lower in the groups treated with the combination trypanocide/antibiotic (p<0.01. CONCLUSIONS/SIGNIFICANCE: After optimization of the administration protocol, this new therapeutic combination could constitute a promising treatment for livestock infected with drug resistant T. congolense.

  8. Critical role for BRCA1 expression as a marker of chemosensitivity response and prognosis.

    Science.gov (United States)

    De Luca, Paola; De Siervi, Adriana

    2016-01-01

    Chemotherapy is still the leader option for cancer treatment. Nevertheless some patients develop chemotherapy resistance. One major research goal is to identify the critical genes involved in chemotherapy response to predict the best therapy option for patients. Germline mutations in the BReast Cancer susceptibility gene (BRCA1) are associated to increased risk of developing breast, ovarian and other types of cancers. However, due to harmful BRCA1 gene mutations are relatively rare in the general population, nowadays most researchers focused on BRCA1 expression downregulation and/or epigenetic inactivation in sporadic tumors as a prognosis tool for chemotherapy response in patients. Chemotherapy response can be dramatically different depending on BRCA1 expression status, tumor type and drug. Hence, the chemotherapy response could be dissimilar in breast, ovarian, uterine, prostate, esophageal, gastric and lung cancers. Additionally, differential BRCA1 expression in sporadic tumors shows different response to DNA-damaging agents, mitotic inhibitors or PARP inhibitors. In this review we will examine the response to different chemotherapy agents in several cancer types depending on BRCA1 expression status. PMID:26709647

  9. P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A re

    Directory of Open Access Journals (Sweden)

    Hossam M. Abdallah

    2015-01-01

    Full Text Available Resistance of solid tumors to treatment is significantly attributed to pharmacokinetic reasons at both cellular and multi-cellular levels. Anticancer agent must be bio-available at the site of action in a cytotoxic concentration to exert its proposed activity. P-glycoprotein (P-gp is a member of the ATP-dependent membrane transport proteins; it is known to pump substrates out of cells in ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the cytotoxicity of a broad spectrum of antitumor drugs. Accordingly, P-gp inhibitors/blockers are potential enhancer for the cellular bioavailability of several clinically important anticancer drugs such as, anthracyclines, taxanes, vinca alkaloids, and podophyllotoxins. Besides several chemically synthesized P-gp inhibitors/blockers, some naturally occurring compounds and plant extracts were reported for their modulation of multidrug resistance; however, this review will focus only on major classes of naturally occurring inhibitors viz., flavonoids, coumarins, terpenoids, alkaloids and saponins.

  10. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    International Nuclear Information System (INIS)

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression

  11. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity

    DEFF Research Database (Denmark)

    Brandt, Julia P; Aziz-Zaman, Sonya; Juozaityte, Vaida;

    2012-01-01

    . We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2). The ETS-5 transcription factor is necessary for the specification of CO(2)-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient......Many animals possess neurons specialized for the detection of carbon dioxide (CO(2)), which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2) is poorly understood...... to bypass a requirement for ets-5 in CO(2)-detection and transforms neurons into CO(2)-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2)-sensing neurons in other phyla....

  12. Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear Factor-kappaB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    A. Rimmon

    2013-01-01

    Full Text Available Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23. Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF-κB-related proteins (p65, IκBα, and p-IκBα and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10–20 M. Escin combined with gemcitabine showed only additive effect, while its combination with cisplatin resulted in a significant synergistic cytotoxic effect in Panc-1 cells. High concentrations of Escin induced apoptosis and decreased NF-κB-related proteins and cyclin D expression. Conclusions. Escin decreased pancreatic cancer cell survival, induced apoptosis, and downregulated NF-κB signaling pathway. Moreover, Escin sensitized pancreatic cancer cells to chemotherapy. Further translational research is required.

  13. Spectroscopic imaging system for high-throughput viability assessment of ovarian spheroids or microdissected tumor tissues (MDTs) in a microfluidic chip

    Science.gov (United States)

    St-Georges-Robillard, A.; Masse, M.; Kendall-Dupont, J.; Strupler, M.; Patra, B.; Jermyn, M.; Mes-Masson, A.-M.; Leblond, F.; Gervais, T.

    2016-02-01

    There is a growing effort in the biomicrosystems community to develop a personalized treatment response assay for cancer patients using primary cells, patient-derived spheroids, or live tissues on-chip. Recently, our group has developed a technique to cut tumors in 350 μm diameter microtissues and keep them alive on-chip, enabling multiplexed in vitro drug assays on primary tumor tissue. Two-photon microscopy, confocal microscopy and flow cytometry are the current standard to assay tissue chemosensitivity on-chip. While these techniques provide microscopic and molecular information, they are not adapted for high-throughput analysis of microtissues. We present a spectroscopic imaging system that allows rapid quantitative measurements of multiple fluorescent viability markers simultaneously by using a liquid crystal tunable filter to record fluorescence and transmittance spectra. As a proof of concept, 24 spheroids composed of ovarian cancer cell line OV90 were formed in a microfluidic chip, stained with two live cell markers (CellTrackerTM Green and Orange), and imaged. Fluorescence images acquired were normalized to the acquisition time and gain of the camera, dark noise was removed, spectral calibration was applied, and spatial uniformity was corrected. Spectral un-mixing was applied to separate each fluorophore's contribution. We have demonstrated that rapid and simultaneous viability measurements on multiple spheroids can be achieved, which will have a significant impact on the prediction of a tumor's response to multiple treatment options. This technique may be applied as well in drug discovery to assess the potential of a drug candidate directly on human primary tissue.

  14. IEEE Std 99-1980: IEEE recommended practice for the preparation of test procedures for the thermal evaluation of insulation systems for electric equipment

    International Nuclear Information System (INIS)

    The purpose of this recommended practice is to provide a general form for the preparation of test procedures and to suggest the points to be considered by technical committees in the preparation of specific instructions for the thermal evaluation of insulation systems for equipment. The thermal evaluation of an insulation system involves the thermal (T) factor of influence as described in IEC 505 (1975), Guide for the Evaluation and Identification of Insulation Systems of Electric Equipment. These test procedures involve accelerated thermal aging of insulation systems and specify tests which the committees deem pertinent, based on conditions of use. The objective of these test procedures is to provide for the functional evaluation, by test, of insulation systems for electric equipment. The evaluation of insulating materials and simple combinations thereof is provided for by a separate material test guide, IEEE Std 98-1972, Guide for the Preparation of Test Procedures for the Thermal Evaluation and Establishment of Temperature Indexes of Solid Electrical Insulating Materials

  15. System Budgets

    DEFF Research Database (Denmark)

    Jeppesen, Palle

    1996-01-01

    The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers.......The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers....

  16. Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

    International Nuclear Information System (INIS)

    Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such

  17. System Identification

    NARCIS (Netherlands)

    Keesman, K.J.

    2011-01-01

    Summary System Identification Introduction.- Part I: Data-based Identification.- System Response Methods.- Frequency Response Methods.- Correlation Methods.- Part II: Time-invariant Systems Identification.- Static Systems Identification.- Dynamic Systems Identification.- Part III: Time-varying Syste

  18. Systems autonomy

    Science.gov (United States)

    Lum, Henry, Jr.

    1988-01-01

    Information on systems autonomy is given in viewgraph form. Information is given on space systems integration, intelligent autonomous systems, automated systems for in-flight mission operations, the Systems Autonomy Demonstration Project on the Space Station Thermal Control System, the architecture of an autonomous intelligent system, artificial intelligence research issues, machine learning, and real-time image processing.

  19. Immune System

    Science.gov (United States)

    ... Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  20. Thermal systems; Systemes thermiques

    Energy Technology Data Exchange (ETDEWEB)

    Lalot, S. [Valenciennes Univ. et du Hainaut Cambresis, LME, 59 (France); Lecoeuche, S. [Ecole des Mines de Douai, Dept. GIP, 59 - Douai (France)]|[Lille Univ. des Sciences et Technologies, 59 - Villeneuve d' Ascq (France); Ahmad, M.; Sallee, H.; Quenard, D. [CSTB, 38 - Saint Martin d' Heres (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Gascoin, N.; Gillard, P.; Bernard, S. [Laboratoire d' Energetique, Explosion, Structure, 18 - Bourges (France); Gascoin, N.; Toure, Y. [Laboratoire Vision et Robotique, 18 - Bourges (France); Daniau, E.; Bouchez, M. [MBDA, 18 - Bourges (France); Dobrovicescu, A.; Stanciu, D. [Bucarest Univ. Polytechnique, Faculte de Genie Mecanique (Romania); Stoian, M. [Reims Univ. Champagne Ardenne, Faculte des Sciences, UTAP/LTM, 51 (France); Bruch, A.; Fourmigue, J.F.; Colasson, S. [CEA Grenoble, Lab. Greth, 38 (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Voicu, I.; Mare, T.; Miriel, J. [Institut National des Sciences Appliquees (INSA), LGCGM, IUT, 35 - Rennes (France); Galanis, N. [Sherbrooke Univ., Genie Mecanique, QC (Canada); Nemer, M.; Clodic, D. [Ecole des Mines de Paris, Centre Energetique et Procedes, 75 (France); Lasbet, Y.; Auvity, B.; Castelain, C.; Peerhossaini, H. [Nantes Univ., Ecole Polytechnique, Lab. de Thermocinetiquede Nantes, UMR-CNRS 6607, 44 (France)

    2005-07-01

    This session about thermal systems gathers 26 articles dealing with: neural model of a compact heat exchanger; experimental study and numerical simulation of the thermal behaviour of test-cells with walls made of a combination of phase change materials and super-insulating materials; hydraulic and thermal modeling of a supercritical fluid with pyrolysis inside a heated channel: pre-dimensioning of an experimental study; energy analysis of the heat recovery devices of a cryogenic system; numerical simulation of the thermo-hydraulic behaviour of a supercritical CO{sub 2} flow inside a vertical tube; mixed convection inside dual-tube exchangers; development of a nodal approach with homogenization for the simulation of the brazing cycle of a heat exchanger; chaotic exchanger for the cooling of low temperature fuel cells; structural optimization of the internal fins of a cylindrical generator; a new experimental approach for the study of the local boiling inside the channels of exchangers with plates and fins; experimental study of the flow regimes of boiling hydrocarbons on a bundle of staggered tubes; energy study of heat recovery exchangers used in Claude-type refrigerating systems; general model of Carnot engine submitted to various operating constraints; the free pistons Stirling cogeneration system; natural gas supplied cogeneration system with polymer membrane fuel cell; influence of the CRN coating on the heat flux inside the tool during the wood unrolling process; transport and mixture of a passive scalar injected inside the wake of a Ahmed body; control of a laser welding-brazing process by infrared thermography; 2D self-adaptative method for contours detection: application to the images of an aniso-thermal jet; exergy and exergy-economical study of an 'Ericsson' engine-based micro-cogeneration system; simplified air-conditioning of telephone switching equipments; parametric study of the 'low-energy' individual dwelling; brief synthesis of

  1. Data Systems vs. Information Systems

    OpenAIRE

    Amatayakul, Margret K.

    1982-01-01

    This paper examines the current status of “hospital information systems” with respect to the distinction between data systems and information systems. It is proposed that the systems currently existing are incomplete data dystems resulting in ineffective information systems.

  2. Harbor systems; Kowan system

    Energy Technology Data Exchange (ETDEWEB)

    Yasumoto, K.; Mitsuhashi, M. [Fuji Electric Co. Ltd., Tokyo (Japan)

    1997-03-10

    Container terminals these days are required to be enlarged, automated in operation, and enhanced in reliability so that they can properly deal with ships growing larger in size and containers increasing in number. Stable supply of electric power and efficient monitor and control of the related equipment are very important in securing stabilized, continuous operation for such container terminals. Outlined in this report are the electrical equipment of a modern container terminal and the large-capacity voltage fluctuation compensation unit delivered by Fuji Electric Co., Ltd., to West 5 Container Terminal, Nagoya Harbor. The electrical equipment of a terminal is a special high voltage reception/transformation facility capable of loop reception at 66kV. The 66kV cubicle type gas-insulated switch is provided with a current transformer for a sectionalized protection relay, current transformer for bus protection, and VCT bypass disconnector. The main transformer is a gas-insulated transformer, and a molded transformer is adopted for the special high voltage reception/transformation facility. The equipment monitor and control system employs a UNIX-base computer as the central processing system, and the information LAN is so designed as to be connectable to the Ethernet and P-link. 6 figs.

  3. Multibody Systems

    DEFF Research Database (Denmark)

    Wagner, Falko Jens

    1999-01-01

    Multibody Systems is one area, in which methods for solving DAEs are of special interst. This chapter is about multibody systems, why they result in DAE systems and what kind of problems that can arise when dealing with multibody systems and formulating their corresponding DAE system....

  4. Digestive System

    Science.gov (United States)

    ... 5 Things to Know About Zika & Pregnancy Digestive System KidsHealth > For Parents > Digestive System Print A A ... body can absorb and use. About the Digestive System Almost all animals have a tube-type digestive ...

  5. Respiratory System

    Science.gov (United States)

    ... page from the NHLBI on Twitter. The Respiratory System The respiratory system is made up of organs ... and the muscles that enable breathing. The Respiratory System Figure A shows the location of the respiratory ...

  6. Conceiving systems

    OpenAIRE

    Hitchins, D.K.

    1990-01-01

    The thesis is concerned with the development of innovative, robust design concepts for a class of systems called Information Decision Action (IDA) Systems. IDA systems are typified by Command and Control (C2) and Command, Control, Communications and Intelligence (C3I) systems as used by police, emergency services and the military - the two titles refer respectively to the human activity and the technological systems. The class of systems is much wider, however, and includes, financial, traffi...

  7. System dynamics

    International Nuclear Information System (INIS)

    This book introduces systems thinking and conceptual tool and modeling tool of dynamics system such as tragedy of single thinking, accessible way of system dynamics, feedback structure and causal loop diagram analysis, basic of system dynamics modeling, causal loop diagram and system dynamics modeling, information delay modeling, discovery and application for policy, modeling of crisis of agricultural and stock breeding products, dynamic model and lesson in ecosystem, development and decadence of cites and innovation of education forward system thinking.

  8. An illegitimate microRNA target site within the 3' UTR of MDM4 affects ovarian cancer progression and chemosensitivity

    DEFF Research Database (Denmark)

    Wynendaele, Jessika; Böhnke, Anja; Leucci, Eleonora;

    2010-01-01

    Overexpression of MDM4 (also known as MDMX or HDMX) is thought to promote tumorigenesis by decreasing p53 tumor suppressor function. Even modest decrease in Mdm4 levels affects tumorigenesis in mice, suggesting that genetic variants of MDM4 might have similar effects in humans. We sequenced the MDM...... interval (CI) = 1.2-13.5; P = 0.02] increased risk of recurrence and 5.5-fold (95% CI = 1.5-20.5; P = 0.01) increased risk of tumor-related death. Unexpectedly, the frequency of p53 mutations was not significantly lower in A/A patients. We conclude that acquisition of an illegitimate miR-191 target site...... causes downregulation of MDM4 expression, thereby significantly delaying ovarian carcinoma progression and tumor-related death. Importantly, these effects appear to be, at least partly, independent of p53....

  9. Expression of TP53 Isoforms p53β or p53γ Enhances Chemosensitivity in TP53null Cell Lines

    OpenAIRE

    Elisabeth Silden; Hjelle, Sigrun M; Line Wergeland; André Sulen; Vibeke Andresen; Jean-Christophe Bourdon; Micklem, David R; Emmet McCormack; Bjørn Tore Gjertsen

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate wi...

  10. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J; McGranahan, A; Gao, D; Liang, X; Deryckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. PMID:23353780

  11. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J.; McGranahan, A; Gao, D.; Liang, X; DeRyckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic...

  12. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities

  13. Characterization of the DNA methylation patterns of chemosensitive and chemoresistant human cancer cells: Biological and clinical impact

    OpenAIRE

    Moutinho, Cátia

    2014-01-01

    Tesi realitzada a l'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) Although chemotherapeutic drugs are widely used in order to improve the cancer outcome, drug resistance remain the most unpredictable factor affecting chemotherapy and a major impediment to successful patient’s treatment. Understanding the cellular mechanisms leading to chemoresistance may dramatically impact on the way chemotherapeutic drugs are used. Then, it would allow selecting the most suitable personalized ...

  14. Intrinsic and chemo-sensitizing activity of SMAC-mimetics on high-risk childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Schirmer, M; Trentin, L; Queudeville, M; Seyfried, F; Demir, S; Tausch, E; Stilgenbauer, S; Eckhoff, S M; Meyer, L H; Debatin, K-M

    2016-01-01

    SMAC-mimetics represent a targeted therapy approach to overcome apoptosis resistance in many tumors. Here, we investigated the efficacy of the SMAC-mimetic BV6 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In ALL cell lines, intrinsic apoptosis sensitivity was associated with rapid cIAP degradation, NF-κB activation, TNF-α secretion and induction of an autocrine TNF-α-dependent cell death loop. This pattern of responsiveness was also observed upon ex vivo analysis of 40 primograft BCP-ALL samples. Treatment with BV6 induced cell death in the majority of ALL primografts including leukemias with high-risk and poor-prognosis features. Inhibition of cell death by the TNF receptor fusion protein etanercept demonstrated that BV6 activity is dependent on TNF-α. In a preclinical NOD/SCID/huALL model of high-risk ALL, marked anti-leukemia effectivity and significantly prolonged survival were observed upon BV6 treatment. Interestingly, also in vivo, intrinsic SMAC-mimetic activity was mediated by TNF-α. Importantly, BV6 increased the effectivity of conventional induction therapy including vincristine, dexamethasone and asparaginase leading to prolonged remission induction. These data suggest SMAC-mimetics as an important addendum to efficient therapy of pediatric BCP-ALL. PMID:26775704

  15. Pregnane × Receptor (PXR expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation

    Directory of Open Access Journals (Sweden)

    Lumbroso Serge

    2010-03-01

    Full Text Available Abstract Background Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11 is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR, we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. Results PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies. Conclusion Our results demonstrate that tumoral metabolism of SN38 is affected by PXR and point to potential therapeutic significance of PXR quantification in the prediction of irinotecan response. Furthermore, our observations are pharmacologically relevant since many patients suffering from cancer diseases are often exposed to co-medications, food additives or herbal supplements able to activate PXR. A substantial part of the variability observed among patients might be caused by such interactions

  16. Expression of TP53 Isoforms p53β or p53γ Enhances Chemosensitivity in TP53null Cell Lines

    OpenAIRE

    Silden, Elisabeth; Hjelle, Sigrun M; Wergeland, Line; Sulen, André; Andresen, Vibeke; Bourdon, Jean-Christophe; Micklem, David R.; McCormack, Emmet; Gjertsen, Bjørn Tore

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53null background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with...

  17. Enhanced chemosensitivity of p73α gene transferred into H1299 cell line of human lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Yong; FAN Shi-zhi; Kalkunte S Srivenugopal; JIANG Yao-guang; QIN Chuan

    2004-01-01

    Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome;The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents ( 1.25 μmol/L of cDDP and 0.05 μmol/L of ADM)could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38.4% ( P < 0.01 ) and that of ADM from 12.1% to 49.3 % ( P < 0.01 ). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P < 0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.

  18. Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain

    OpenAIRE

    Moparthi, Lavanya; Survery, Sabeen; Kreir, Mohamed; Simonsen, Charlotte; Kjellbom, Per; Edward D. Högestätt; Johanson, Urban; Zygmunt, Peter M.

    2014-01-01

    The ability of an organism to detect and avoid noxious temperatures is crucial for survival. It is, therefore, of great interest that several transient receptor potential (TRP) ion channels have been proposed as temperature sensors. However, to date, only the menthol receptor (TRP subtype M8) and the chili pepper receptor (TRP subtype V1) have been shown to be intrinsically temperature-sensitive proteins in mammals. In this study, we show that the purified wasabi receptor (TRP subtype A1) is ...

  19. Central Respiratory Chemosensitivity and Cerebrovascular CO[subscript 2] Reactivity: A Rebreathing Demonstration Illustrating Integrative Human Physiology

    Science.gov (United States)

    MacKay, Christina M.; Skow, Rachel J.; Tymko, Michael M.; Boulet, Lindsey M.; Davenport, Margie H.; Steinback, Craig D.; Ainslie, Philip N.; Lemieux, Chantelle C. M.; Day, Trevor A.

    2016-01-01

    One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations…

  20. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA2

    OpenAIRE

    Jaeyoung Lim; Kun Yang; Barbie Taylor-Harding; W. Ruprecht Wiedemeyer; Buckanovich, Ronald J.

    2014-01-01

    In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with gr...

  1. Arctigenin enhances chemosensitivity to cisplatin in human nonsmall lung cancer H460 cells through downregulation of survivin expression.

    Science.gov (United States)

    Wang, Huan-qin; Jin, Jian-jun; Wang, Jing

    2014-01-01

    Arctigenin, a dibenzylbutyrolactone lignan, enhances cisplatin-mediated cell apoptosis in cancer cells. Here, we sought to investigate the effects of arctigenin on cisplatin-treated non-small-cell lung cancer (NSCLC) H460 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V/propidium iodide staining were performed to analyze the proliferation and apoptosis of H460 cells. Arctigenin dose-dependently suppressed cell proliferation and potentiated cell apoptosis, coupled with increased cleavage of caspase-3 and poly(ADP-ribose) polymerase. Moreover, arctigenin sensitized H460 cells to cisplatin-induced proliferation inhibition and apoptosis. Arctigenin alone or in combination with cisplatin had a significantly lower amount of survivin. Ectopic expression of survivin decreased cell apoptosis induced by arctigenin (P arctigenin (P arctigenin has a therapeutic potential in combina-tion with chemotherapeutic agents for NSLC. PMID:24395429

  2. Selenium enrichment of broccoli sprout extract increases chemosensitivity and apoptosis of LNCaP prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Suzuki Kazuhiro

    2009-11-01

    Full Text Available Abstract Background Broccoli is a Brassica vegetable that is believed to possess chemopreventive properties. Selenium also shows promise as an anticancer agent. Thus, selenium enrichment of broccoli has the potential to enhance the anticancer properties of broccoli sprouts. Method Selenium-enriched broccoli sprouts were prepared using a sodium selenite solution. Their anticancer properties were evaluated in human prostate cancer cell lines and compared with those of a control broccoli sprout extract. Results Selenium-enriched broccoli sprouts were superior to normal broccoli sprouts in inhibiting cell proliferation, decreasing prostate-specific antigen secretion, and inducing apoptosis of prostate cancer cells. Furthermore, selenium-enriched broccoli sprouts but, not normal broccoli sprouts, induced a downregulation of the survival Akt/mTOR pathway. Conclusion Our results suggest that selenium-enriched broccoli sprouts could potentially be used as an alternative selenium source for prostate cancer prevention and therapy.

  3. Systems effectiveness

    CERN Document Server

    Habayeb, A R

    1987-01-01

    Highlights three principal applications of system effectiveness: hardware system evaluation, organizational development and evaluation, and conflict analysis. The text emphasizes the commonality of the system effectiveness discipline. The first part of the work presents a framework for system effectiveness, partitioning and hierarchy of hardware systems. The second part covers the structure, hierarchy, states, functions and activities of organizations. Contains an extended Appendix on mathematical concepts and also several project suggestions.

  4. Auxiliary systems

    International Nuclear Information System (INIS)

    Systems included under the heading ''Reactor Auxillary Systems'' are those immediately involved with the reactor operation. These include the systems for dosing and letdown of reactor coolant, as well as for the chemical dosing, purification and treatment of the reactor coolant and the cooling system in the controlled area. The ancillary systems are mainly responsible for liquid and gaseous treatment and the waste treatment for final storage. (orig.)

  5. Stem system

    Directory of Open Access Journals (Sweden)

    Shajmardanova L.R.

    2008-01-01

    Full Text Available The article shows the stem cells from the point of view of systemic anatomy, where they are united into an entire stem system. This integration shows various advantages for better understanding the stem cells role in the body. Authors, considering functions and action mechanism of stem cells, phylogeny, ontogeny, regulation of functions, explain the base for stem cells system existance. The definition and terminology, age peculiarities, relationship with other systems of organs and differences are offered. The theoretical proof of primary-integrative role of stem system is provided for all other systems in body. Of particular importance is the role of stem system as a link between neural and endocrine systems. The work helps to sistematize data on investigations of stem cells, their entire-system perception, that will ease the goals determining for further research and their clinical use.

  6. Auxiliary systems

    International Nuclear Information System (INIS)

    For a undisturbed reactor operation, the various Auxiliary and Ancillary Systems must function perfectly with the Reactor Coolant System together. While the Auxiliary Systems are directly connected to the Reactor Coolant System and therefore have contact with the Reactor Coolant, the Ancillary Systems perform tasks which do not directly influence reactor operation and in part are necessary exclusively for environment protection. The design criteria of the individual systems are a result of these tasks, especially in relation to availability, operational readiness and probability of failure. (orig.)

  7. Lymph system

    Science.gov (United States)

    The lymph system is a network of organs, lymph nodes, lymph ducts, and lymph vessels that make and move lymph from tissues to the bloodstream. The lymph system is a major part of the body's immune ...

  8. Intelligent Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — The autonomous systems (AS) project, led by NASA Ames, is developing software for system operation automation. AS technology will help astronauts make more...

  9. Retrofitting Systems

    DEFF Research Database (Denmark)

    Rose, Jørgen

    1997-01-01

    This report gives an overview of the different retrofitting possibilities that are available today. The report looks at both external and internal systems for external wall constructions, roof constructions, floor constructions and foundations. All systems are described in detail in respect to use...... and methods, and the efficiency of the different systems are discussed....

  10. Systems Engineering

    Science.gov (United States)

    Pellerano, Fernando

    2015-01-01

    This short course provides information on what systems engineering is and how the systems engineer guides requirements, interfaces with the discipline leads, and resolves technical issues. There are many system-wide issues that either impact or are impacted by the thermal subsystem. This course will introduce these issues and illustrate them with real life examples.

  11. Multifunction system

    International Nuclear Information System (INIS)

    The development, the characteristics and the applications of a multifunction system are presented. The system is used on the RBES laboratory pipes, at Marcoule. The system was developed in order to allow, without time loss, the modification of the circuit function by replacing only one component. The following elements form the multifunction system: a fixed base, which is part of the tube, a removable piece, which is inserted into the base, a cover plate and its locking system. The material, chosen among commercial trade marks, required small modifications in order to be used in the circuit

  12. Operating systems

    CERN Document Server

    Tsichritzis, Dionysios C; Rheinboldt, Werner

    1974-01-01

    Operating Systems deals with the fundamental concepts and principles that govern the behavior of operating systems. Many issues regarding the structure of operating systems, including the problems of managing processes, processors, and memory, are examined. Various aspects of operating systems are also discussed, from input-output and files to security, protection, reliability, design methods, performance evaluation, and implementation methods.Comprised of 10 chapters, this volume begins with an overview of what constitutes an operating system, followed by a discussion on the definition and pr

  13. Cryogenic Systems

    Science.gov (United States)

    Hosoyama, Kenji

    2002-02-01

    In this lecture we discuss the principle of method of cooling to a very low temperature, i.e. cryogenic. The "gas molecular model" will be introduced to explain the mechanism cooling by the expansion engine and the Joule-Thomson expansion valve. These two expansion processes are normally used in helium refrigeration systems to cool the process gas to cryogenic temperature. The reverse Carnot cycle will be discussed in detail as an ideal refrigeration cycle. First the fundamental process of liquefaction and refrigeration cycles will be discussed, and then the practical helium refrigeration system. The process flow of the system and the key components; -compressor, expander, and heat exchanger- will be discussed. As an example of an actual refrigeration system, we will use the cryogenic system for the KEKB superconducting RF cavity. We will also discuss the liquid helium distribution system, which is very important, especially for the cryogenic systems used in accelerator applications. 1 Principles of Cooling and Fundamental Cooling Cycle 2 Expansion engine, Joule-Thomson expansion, kinetic molecular theory, and enthalpy 3 Liquefaction Systems 4 Refrigeration Systems 5 Practical helium liquefier/refrigeration system 6 Cryogenic System for TRISTAN Superconducting RF Cavity

  14. A systemic risk warning system

    OpenAIRE

    Sibert, Anne

    2010-01-01

    Economists largely neglected systemic risk in the financial sector. This column discusses how governments should gather data about systemic risk and assess its implications. It says the new European Systemic Risk Board is far from the ideal – it is too big, too homogeneous, and lacks independence.

  15. Material Systems

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Mortensen, Henrik Rubæk; Mullins, Michael;

    2009-01-01

    This paper describes and reflects upon the results of an investigative project which explores the setting up of a material system - a parametric and generative assembly consisting of and taking into consideration material properties, manufacturing constraints and geometric behavior. The project...... approaches the subject through the construction of a logic-driven system aiming to explore the possibilities of a material system that fulfills spatial, structural and performative requirements concurrently and how these are negotiated in situations where they might be conflicting....

  16. Cognitive Systems

    OpenAIRE

    Larsen, Jan

    2008-01-01

    The tutorial will discuss the definition of cognitive systems as the possibilities to extend the current systems engineering paradigm in order to perceive, learn, reason and interact robustly in open-ended changing environments. I will also address cognitive systems in a historical perspective and its relation and potential over current artificial intelligence architectures. Machine learning models that learn from data and previous knowledge will play an increasingly important role in all lev...

  17. Recommender systems

    CERN Document Server

    Kembellec, Gérald; Saleh, Imad

    2014-01-01

    Acclaimed by various content platforms (books, music, movies) and auction sites online, recommendation systems are key elements of digital strategies. If development was originally intended for the performance of information systems, the issues are now massively moved on logical optimization of the customer relationship, with the main objective to maximize potential sales. On the transdisciplinary approach, engines and recommender systems brings together contributions linking information science and communications, marketing, sociology, mathematics and computing. It deals with the understan

  18. Geothermal systems

    Science.gov (United States)

    Mohl, C.

    1978-01-01

    Several tasks of JPL related to geothermal energy are discussed. The major task is the procurement and test and evaluation of a helical screw drive (wellhead unit). A general review of geothermal energy systems is given. The presentation focuses attention on geothermal reservoirs in California, with graphs and charts to support the discussion. Included are discussions on cost analysis, systems maintenance, and a comparison of geothermal and conventional heating and cooling systems.

  19. Intelligent systems

    CERN Document Server

    Irwin, J David

    2011-01-01

    Technology has now progressed to the point that intelligent systems are replacing humans in the decision making processes as well as aiding in the solution of very complex problems. In many cases intelligent systems are already outperforming human activities. Artificial neural networks are not only capable of learning how to classify patterns, such images or sequence of events, but they can also effectively model complex nonlinear systems. Their ability to classify sequences of events is probably more popular in industrial applications where there is an inherent need to model nonlinear system

  20. Energetic Systems

    Data.gov (United States)

    Federal Laboratory Consortium — The Energetic Systems Division provides full-spectrum energetic engineering services (project management, design, analysis, production support, in-service support,...

  1. Monitoring system

    International Nuclear Information System (INIS)

    The patent relates to monitoring systems for, and a method of monitoring, industrial process plants or apparatus. The system monitors a plurality of data signals representing a number of parameters of a plant or apparatus. One application of the invention is in nuclear reactors for the detection of fault conditions. (U.K.)

  2. cardiovascular system

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    6.1 Cardiac arrhythmias 2006037 Electroanatomical systems guided circumferential pulmonary veins ablation for atrial fibrillation: initial experience from comparison between the EnSite -NavX and CARTO system LIU Xu(刘旭 ), et al. Dept Cardiol, Shanghai Chest Hosp, Shanghai, 200030, China. Chin J Cardiol 2005; 33 (22): 975 -978.

  3. Creative Systems

    DEFF Research Database (Denmark)

    Manelius, Anne-Mette; Beim, Anne

    2007-01-01

    Opsamling af diskussioner på konferencen og udstillingen Creative Systems i september/oktober 2007. Konferencen og Udstillingen Creative Systems sætter fokus på systemer som en positiv drivkraft i den kreative skabelsesproces. CINARK inviterede fire internationale kapaciteter, som indenfor hver...... deres felt har beskæftiget sig med udviklingen af systemer. Kieran Timberlake, markant amerikansk tegnestue; Mark West, Professor på University of Manitoba, Canada, og pioner indenfor anvendelse af tekstilforskalling til betonstøbninger; Matilda McQuaid, Arkitekturhistoriker og kurator på udstillingen...... om Extreme Textiles på amerikanske Cooper Hewit Design Museum, samt Professor Ludger Hovestadt, ved ETH, Zürich der fokuserer på udvikling og anvendelse af logaritmiske systemtilgange. Udstillingen diskuterede ud fra deres meget forskellige arbejder, det kreative potentiale i anvendelsen af systemer...

  4. Power system

    Science.gov (United States)

    Hickam, Christopher Dale

    2008-03-18

    A power system includes a prime mover, a transmission, and a fluid coupler having a selectively engageable lockup clutch. The fluid coupler may be drivingly connected between the prime mover and the transmission. Additionally, the power system may include a motor/generator drivingly connected to at least one of the prime mover and the transmission. The power-system may also include power-system controls configured to execute a control method. The control method may include selecting one of a plurality of modes of operation of the power system. Additionally, the control method may include controlling the operating state of the lockup clutch dependent upon the mode of operation selected. The control method may also include controlling the operating state of the motor/generator dependent upon the mode of operation selected.

  5. Reactive Systems

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand;

    A reactive system comprises networks of computing components, achieving their goals through interaction among themselves and their environment. Thus even relatively small systems may exhibit unexpectedly complex behaviours. As moreover reactive systems are often used in safety critical systems......, the need for mathematically based formal methodology is increasingly important. There are many books that look at particular methodologies for such systems. This book offers a more balanced introduction for graduate students and describes the various approaches, their strengths and weaknesses, and when...... they are best used. Milner's CCS and its operational semantics are introduced, together with the notions of behavioural equivalences based on bisimulation techniques and with recursive extensions of Hennessy-Milner logic. In the second part of the book, the presented theories are extended to take timing issues...

  6. Upgraded RECOVER system - CASDAC system

    International Nuclear Information System (INIS)

    The CASDAC (Containment And Surveillance Data Authenticated Communication) system has been developed by JAERI for nuclear safeguards and physical protection of nuclear material. This system was designed and constructed as an upgraded RECOVER system, design concept of which was based on the original RECOVER system and also the TRANSEAVER system. Both of them were developed several years ago as a remote monitoring system for continual verification of security and safeguards status of nuclear material. The system consists of two subsystems, one of them is a Grand Command Center (GCC) subsystem and the other is a facility subsystem. Communication between the two subsystems is controlled through the international telephone line network. Therefore all communication data are encrypted to prevent access by an unauthorized person who may intend to make a falsification, or tapping. The facility subsystem has an appropriate measure that ensure data security and reliable operation under unattended mode of operator. The software of this system is designed so as to be easily used in other different types of computers. This report describes the outline of the CASDAC system and the results of its performance test. This work has been carried out in the framework of Japan Support Programme for Agency Safeguards (JASPAS) as a project, JA-1. (author)

  7. Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target Cell Wall Integrity.

    Science.gov (United States)

    Kim, Jong H; Chan, Kathleen L; Mahoney, Noreen

    2015-01-01

    Disruption of cell wall integrity system should be an effective strategy for control of fungal pathogens. To augment the cell wall disruption efficacy of monoterpenoid phenols (carvacrol, thymol), antimycotic potency of benzaldehyde derivatives that can serve as chemosensitizing agents were evaluated against strains of Saccharomyces cerevisiae wild type (WT), slt2Δ and bck1Δ (mutants of the mitogen-activated protein kinase (MAPK) and MAPK kinase kinase, respectively, in the cell wall integrity pathway). Among fourteen compounds investigated, slt2Δ and bck1Δ showed higher susceptibility to nine benzaldehydes, compared to WT. Differential antimycotic activity of screened compounds indicated "structure-activity relationship" for targeting the cell wall integrity, where 2-hydroxy-4-methoxybenzaldehyde (2H4M) exhibited the highest antimycotic potency. The efficacy of 2H4M as an effective chemosensitizer to monoterpenoid phenols (viz., 2H4M + carvacrol or thymol) was assessed in yeasts or filamentous fungi (Aspergillus, Penicillium) according to European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory Standards Institute M38-A protocols, respectively. Synergistic chemosensitization greatly lowers minimum inhibitory or fungicidal concentrations of the co-administered compounds. 2H4M also overcame the tolerance of two MAPK mutants (sakAΔ, mpkCΔ) of Aspergillus fumigatus to fludioxonil (phenylpyrrole fungicide). Collectively, 2H4M possesses chemosensitizing capability to magnify the efficacy of monoterpenoid phenols, which improves target-based (viz., cell wall disruption) antifungal intervention. PMID:26569223

  8. Water systems

    International Nuclear Information System (INIS)

    The present paper describes the coolant chemistry and its consequences for 1300 MWsub(e) KWU PWR plants. Some selected systems, i.e. primary heat transport system, steam water cycle and cooling water arrangements, are chosen for this description. Various aspects of coolant chemistry regarding general corrosion, selective types of corrosion and deposits on heat transfer surfaces have been discussed. The water supply systems necessary to fulfill the requirements of the coolant chemistry are discussed as well. It has been concluded that a good operating performance can only be achieved when - beside other factors - the water chemistry has been given sufficient consideration. (orig./RW)

  9. Water systems

    International Nuclear Information System (INIS)

    The present paper describes the coolant chemistry and its consequences for 1300 MWsub(e) KWU PWR plants. Some selected systems, i.e. primary heat transport system, steam water cycle and cooling water arrangements, are chosen for this description. Various aspects of coolant chemistry regarding general corrosion, selective types of corrosion and deposits on heat transfer surface have been discussed. The water supply systems necessary to fulfill the requirements of the coolant chemistry are discussed as well. It has been concluded that a good operating performance can only be achieved when - beside other factors - the water chemistry has been given sufficient consideration. (orig./RW)

  10. Dynamical systems

    CERN Document Server

    Sternberg, Shlomo

    2010-01-01

    Celebrated mathematician Shlomo Sternberg, a pioneer in the field of dynamical systems, created this modern one-semester introduction to the subject for his classes at Harvard University. Its wide-ranging treatment covers one-dimensional dynamics, differential equations, random walks, iterated function systems, symbolic dynamics, and Markov chains. Supplementary materials offer a variety of online components, including PowerPoint lecture slides for professors and MATLAB exercises.""Even though there are many dynamical systems books on the market, this book is bound to become a classic. The the

  11. Physical Systems

    CERN Document Server

    Belkind, Ori

    2012-01-01

    Based on the concept of a physical system, this book offers a new philosophical interpretation of classical mechanics and the Special Theory of Relativity. According to Belkind's view the role of physical theory is to describe the motions of the parts of a physical system in relation to the motions of the whole. This approach provides a new perspective into the foundations of physical theory, where motions of parts and wholes of physical systems are taken to be fundamental, prior to spacetime, material properties and laws of motion. He defends this claim with a constructive project, deriving b

  12. Creative systems

    DEFF Research Database (Denmark)

    Beim, Anne

    2007-01-01

    At udvikle systemer har altid været et væsentligt element i den arkitektoniske skabelsesproces. Systemer er ikke nødvendigvis begrænsninger, men kan ses som positive faktorer i skabelses og fremstillinsprocessen. Center for Industriel Arkitektur, Cinark, har afholdt en international konference, en...... workshop og en udstilling under overskriften; Creative Systems. Artiklen præsenterer de fire oplægsholdere Matilda McQuaid, Mark West, Stephen Kieran og Ludger Hovestadt og en række diskussionstemaer....

  13. The systems integration modeling system

    International Nuclear Information System (INIS)

    This paper discusses the systems integration modeling system (SIMS), an analysis tool for the detailed evaluation of the structure and related performance of the Federal Waste Management System (FWMS) and its interface with waste generators. It's use for evaluations in support of system-level decisions as to FWMS configurations, the allocation, sizing, balancing and integration of functions among elements, and the establishment of system-preferred waste selection and sequencing methods and other operating strategies is presented. SIMS includes major analysis submodels which quantify the detailed characteristics of individual waste items, loaded casks and waste packages, simulate the detailed logistics of handling and processing discrete waste items and packages, and perform detailed cost evaluations

  14. Bubble systems

    CERN Document Server

    Avdeev, Alexander A

    2016-01-01

    This monograph presents a systematic analysis of bubble system mathematics, using the mechanics of two-phase systems in non-equilibrium as the scope of analysis. The author introduces the thermodynamic foundations of bubble systems, ranging from the fundamental starting points to current research challenges. This book addresses a range of topics, including description methods of multi-phase systems, boundary and initial conditions as well as coupling requirements at the phase boundary. Moreover, it presents a detailed study of the basic problems of bubble dynamics in a liquid mass: growth (dynamically and thermally controlled), collapse, bubble pulsations, bubble rise and breakup. Special emphasis is placed on bubble dynamics in turbulent flows. The analysis results are used to write integral equations governing the rate of vapor generation (condensation) in non-equilibrium flows, thus creating a basis for solving a number of practical problems. This book is the first to present a comprehensive theory of boil...

  15. Avionics Systems

    Directory of Open Access Journals (Sweden)

    P.M. Soundar Rajan

    2013-03-01

    Full Text Available ‘Avionics’ systems, over the decades, have grown from simple communication radios and navigation equipments to complex integrated equipments primarily infiuenced by dominance of digital technology. Continuous growth in integrated circuit technology, functional integration of complete system on chip, very high speed communication channels and fault tolerant communication protocols have brought remarkable advancements in avionics systems. Further Mechanical and Pneumatic functional blocks are being replaced by digital systems progressively and decisively. New generation aircraft are being built around powerful avionics assets to provide stress free cockpit to the pilot.Defence Science Journal, 2013, 63(2, pp.129-130, DOI:http://dx.doi.org/10.14429/dsj.63.4269

  16. Cognitive Systems

    DEFF Research Database (Denmark)

    The tutorial will discuss the definition of cognitive systems as the possibilities to extend the current systems engineering paradigm in order to perceive, learn, reason and interact robustly in open-ended changing environments. I will also address cognitive systems in a historical perspective and...... its relation and potential over current artificial intelligence architectures. Machine learning models that learn from data and previous knowledge will play an increasingly important role in all levels of cognition as large real world digital environments (such as the Internet) usually are too complex...... to be modeled within a limited set of predefined specifications. There will inevitably be a need for robust decisions and behaviors in novel situations that include handling of conflicts and ambiguities based on the capability and knowledge of the artificial cognitive system. Further, there is a need...

  17. AEG System

    Data.gov (United States)

    Department of Transportation — The AEG System is used to create, revise, approve, and distribute text of the AEGS and Flight Standard Board (FSB)/Type Rating Report. The MMEL specifies under what...

  18. System zeros

    OpenAIRE

    Smagina, Ye. M.

    2006-01-01

    The present book is the first publication in English considered the modern problems of control theory and analysis connected with a concept of system zeros. The previous book by Ye.M. Smagina (1990) had been written in Russian and it is inaccessible to English speaking researchers. The purpose of the offered book is to systematize and consistently to state basic theoretical results connected with properties of multivariable system zeros. Different zeros definitions and different types of zero...

  19. Expert Systems

    OpenAIRE

    Lucas, P.J.F.

    2005-01-01

    Expert systems mimic the problem-solving activity of human experts in specialized domains by capturing and representing expert knowledge. Expert systems include a knowledge base, an inference engine that derives conclusions from the knowledge, and a user interface. Knowledge may be stored as if-then rules, orusing other formalisms such as frames and predicate logic. Uncertain knowledge may be represented using certainty factors, Bayesian networks, Dempster-Shafer belief functions, or fuzzy se...

  20. Systems Thinkers

    OpenAIRE

    Ramage, Magnus; Shipp, Karen

    2009-01-01

    Systems Thinkers presents a biographical history of the field of systems thinking, by examining the life and work of thirty of its major thinkers. It discusses each thinker's key contributions, the way this contribution was expressed in practice and the relationship between their life and ideas. This discussion is supported by an extract from the thinker's own writing, to give a flavour of their work and to give readers a sense of which thinkers are most relevant to their own interests. ...

  1. Systems studies

    International Nuclear Information System (INIS)

    The Systems Studies Activity had two objectives: (1) to investigate nontechnical barriers to the deployment of biomass production and supply systems and (2) to enhance and extend existing systems models of bioenergy supply and use. For the first objective, the Activity focused on existing bioenergy markets. Four projects were undertaken: a comparative analysis of bioenergy in Sweden and Austria; a one-day workshop on nontechnical barriers jointly supported by the Production Systems Activity, the development and testing of a framework for analyzing barriers and drivers to bioenergy markets; and surveys of wood pellet users in Sweden, Austria and the U.S.A. For the second objective, two projects were undertaken. First, the Activity worked with the Integrated Bioenergy Systems (IBS) Activity of IEA Bioenergy Task XIII to enhance the BioEnergy Assessment Model (BEAM). This model is documented in the final report of the IBS Activity. The Systems Studies Activity contributed to enhancing the feedstock portion of the model by developing a coherent set of willow, poplar, and switchgrass production modules relevant to both the U.S.A. and the U.K. The Activity also developed a pretreatment module for switchgrass. Second, the Activity sponsored a three-day workshop on modelling bioenergy systems with the objectives of providing an overview of the types of models used to evaluate bioenergy and promoting communication among bioenergy modelers. There were nine guest speakers addressing different types of models used to evaluate different aspects of bioenergy, ranging from techno-economic models based on the ASPEN software to linear programming models to develop feedstock supply curves for the U.S.A. The papers from this workshop have been submitted to Biomass and Bioenergy and are under editorial review 8 refs, 10 tabs

  2. Systems Studies

    Energy Technology Data Exchange (ETDEWEB)

    Graham, R.L.

    1998-03-17

    The Systems Studies Activity had two objectives: (1) to investigate nontechnical barriers to the deployment of biomass production and supply systems and (2) to enhance and extend existing systems models of bioenergy supply and use. For the first objective, the Activity focused on existing bioenergy markets. Four projects were undertaken: a comparative analysis of bioenergy in Sweden and Austria; a one-day workshop on nontechnical barriers jointly supported by the Production Systems Activity; the development and testing of a framework for analyzing barriers and drivers to bioenergy markets; and surveys of wood pellet users in Sweden, Austria and the US. For the second objective, two projects were undertaken. First, the Activity worked with the Integrated BioEnergy Systems (TBS) Activity of TEA Bioenergy Task XIII to enhance the BioEnergy Assessment Model (BEAM). This model is documented in the final report of the IBS Activity. The Systems Studies Activity contributed to enhancing the feedstock portion of the model by developing a coherent set of willow, poplar, and switchgrass production modules relevant to both the US and the UK. The Activity also developed a pretreatment module for switchgrass. Second, the Activity sponsored a three-day workshop on modeling bioenergy systems with the objectives of providing an overview of the types of models used to evaluate bioenergy and promoting communication among bioenergy modelers. There were nine guest speakers addressing different types of models used to evaluate different aspects of bioenergy, ranging from technoeconomic models based on the ASPEN software to linear programming models to develop feedstock supply curves for the US. The papers from this workshop have been submitted to Biomass and Bioenergy and are under editorial review.

  3. Fiscal system analysis - contractual systems

    International Nuclear Information System (INIS)

    Production sharing contracts are one of the most popular forms of contractual system used in petroleum agreements around the world, but the manner in which the fiscal terms and contract parameters impact system measures is complicated and not well understood. The purpose of this paper is to quantify the influence of private and market uncertainty in contractual fiscal systems. A meta-modelling approach is employed that couples the results of a simulation model with regression analysis to construct numerical functionals that quantify the fiscal regime. Relationships are derived that specify how the present value, rate of return, and take statistics vary as a function of the system parameters. The deepwater Girassol field development in Angola is taken as a case study. (author)

  4. Systemic trauma.

    Science.gov (United States)

    Goldsmith, Rachel E; Martin, Christina Gamache; Smith, Carly Parnitzke

    2014-01-01

    Substantial theoretical, empirical, and clinical work examines trauma as it relates to individual victims and perpetrators. As trauma professionals, it is necessary to acknowledge facets of institutions, cultures, and communities that contribute to trauma and subsequent outcomes. Systemic trauma-contextual features of environments and institutions that give rise to trauma, maintain it, and impact posttraumatic responses-provides a framework for considering the full range of traumatic phenomena. The current issue of the Journal of Trauma & Dissociation is composed of articles that incorporate systemic approaches to trauma. This perspective extends conceptualizations of trauma to consider the influence of environments such as schools and universities, churches and other religious institutions, the military, workplace settings, hospitals, jails, and prisons; agencies and systems such as police, foster care, immigration, federal assistance, disaster management, and the media; conflicts involving war, torture, terrorism, and refugees; dynamics of racism, sexism, discrimination, bullying, and homophobia; and issues pertaining to conceptualizations, measurement, methodology, teaching, and intervention. Although it may be challenging to expand psychological and psychiatric paradigms of trauma, a systemic trauma perspective is necessary on both scientific and ethical grounds. Furthermore, a systemic trauma perspective reflects current approaches in the fields of global health, nursing, social work, and human rights. Empirical investigations and intervention science informed by this paradigm have the potential to advance scientific inquiry, lower the incidence of a broader range of traumatic experiences, and help to alleviate personal and societal suffering. PMID:24617751

  5. Memory systems.

    Science.gov (United States)

    Wolk, David A; Budson, Andrew E

    2010-08-01

    Converging evidence from patient and neuroimaging studies suggests that memory is a collection of abilities that use different neuroanatomic systems. Neurologic injury may impair one or more of these memory systems. Episodic memory allows us to mentally travel back in time and relive an episode of our life. Episodic memory depends on the hippocampus, other medial temporal lobe structures, the limbic system, and the frontal lobes, as well as several other brain regions. Semantic memory provides our general knowledge about the world and is unconnected to any specific episode of our life. Although semantic memory likely involves much of the neocortex, the inferolateral temporal lobes (particularly the left) are most important. Procedural memory enables us to learn cognitive and behavioral skills and algorithms that operate at an automatic, unconscious level. Damage to the basal ganglia, cerebellum, and supplementary motor area often impair procedural memory. PMID:22810510

  6. Turbine system

    Energy Technology Data Exchange (ETDEWEB)

    McMahan, Kevin Weston; Dillard, Daniel Jackson

    2016-05-03

    A turbine system is disclosed. The turbine system includes a transition duct having an inlet, an outlet, and a passage extending between the inlet and the outlet and defining a longitudinal axis, a radial axis, and a tangential axis. The outlet of the transition duct is offset from the inlet along the longitudinal axis and the tangential axis. The turbine system further includes a turbine section connected to the transition duct. The turbine section includes a plurality of shroud blocks at least partially defining a hot gas path, a plurality of buckets at least partially disposed in the hot gas path, and a plurality of nozzles at least partially disposed in the hot gas path. At least one of a shroud block, a bucket, or a nozzle includes means for withstanding high temperatures.

  7. System Description:

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Poswolsky, Adam

    2009-01-01

    Delphin is a functional programming language [Adam Poswolsky and Carsten Schürmann. Practical programming with higher-order encodings and dependent types. In European Symposium on Programming (ESOP), 2008] utilizing dependent higher-order datatypes. Delphin's two-level type-system cleanly separates...... data from computation, allowing for decidable type checking. The data level is LF [Robert Harper, Furio Honsell, and Gordon Plotkin. A framework for defining logics. Journal of the Association for Computing Machinery, 40(1):143-184, January 1993], which allows for the specification of deductive systems...

  8. Kreative systemer

    DEFF Research Database (Denmark)

    Manelius, Anne-Mette

    2007-01-01

    Artikel med eksempler på armerede teglhvælv produceret i hængende tekstiler ud fra kædebueprincipper og inspireret af Eladio Dieste. Beskriver desuden konferencen og udstillingen Creative Systems på KA september 2007......Artikel med eksempler på armerede teglhvælv produceret i hængende tekstiler ud fra kædebueprincipper og inspireret af Eladio Dieste. Beskriver desuden konferencen og udstillingen Creative Systems på KA september 2007...

  9. Computer systems

    Science.gov (United States)

    Olsen, Lola

    1992-01-01

    In addition to the discussions, Ocean Climate Data Workshop hosts gave participants an opportunity to hear about, see, and test for themselves some of the latest computer tools now available for those studying climate change and the oceans. Six speakers described computer systems and their functions. The introductory talks were followed by demonstrations to small groups of participants and some opportunities for participants to get hands-on experience. After this familiarization period, attendees were invited to return during the course of the Workshop and have one-on-one discussions and further hands-on experience with these systems. Brief summaries or abstracts of introductory presentations are addressed.

  10. Communication systems

    International Nuclear Information System (INIS)

    This paper gives a survey of the field of data communication. The topics covered are: Types of communication, protocols, communication control systems, communication equipment and techniques, and types of data nets. Further, some of the data nets in use today, and the techniques applied in their implementation, are described. The intent of the paper is not to give an in-depth analysis of the various data communication techniques; rather, to describe the principles and problems involved in the construction of a state-of-the-art communication system. (Auth.)

  11. Lindenmayer Systems

    Science.gov (United States)

    Honkala, Juha

    The theory of Lindenmayer systems studies free monoid morphisms, free monoid substitutions and their iterations. In this chapter, we discuss similar ideas in a more general framework. Instead of a free monoid, we consider the free semi-algebra S consisting of polynomials with non-commuting variables in Σ and coefficients in a semiring S and we study the iteration of endomorphisms of S. We allow various modes of iteration and we consider various classes of morphisms. Classical L systems are obtained as special cases by taking S to be the Boolean semiring. Our approach also generalizes the theory of algebraic series in noncommuting variables.

  12. Microbiology System

    Science.gov (United States)

    1992-01-01

    Technology originating in a NASA-sponsored study of the measurement of microbial growth in zero gravity led to the development of Biomerieux Vitek, Inc.'s VITEK system. VITEK provides a physician with accurate diagnostic information and identifies the most effective medication. Test cards are employed to identify organisms and determine susceptibility to antibiotics. A photo-optical scanner scans the card and monitors changes in the growth of cells contained within the card. There are two configurations - VITEK and VITEK JR as well as VIDAS, a companion system that detects bacteria, viruses, etc. from patient specimens. The company was originally created by McDonnell Douglas, the NASA contractor.

  13. Neuromodulatory Systems

    Directory of Open Access Journals (Sweden)

    Gerhard eWerner

    2013-03-01

    Full Text Available Abstract We examine the interactions and interdependencies between Neuroglia, the Brain-Cell Microenvironment, and the processes commonly subsumed under Neuromodulation. The interactions of the component processes covering a wide spectrum of frequencies are designated as Neuromodulatory Systems (NMS. This implies NMS's scale-invariance as the capacity of linking actions across many time scales, and self-similarity at any scale. These features endow NMS with the ability to respond adaptively to neural impulse traffic of an unpredictably wide frequency spectrum. In this preliminary perspective, the components of NMS are only outlined based on concepts of Complex Systems Dynamics. However, their interactions must be formally elaborated in further investigations.

  14. Irrigation System

    Science.gov (United States)

    1984-01-01

    Under contract with Marshall Space Flight Center, Midwest Research Institute compiled a Lubrication Handbook intended as a reference source for designers and manufacturers of aerospace hardware and crews responsible for maintenance of such equipment. Engineers of Lindsay Manufacturing Company learned of this handbook through NASA Tech Briefs and used it for supplemental information in redesigning gear boxes for their center pivot agricultural irrigation system.

  15. Systemic Planning

    DEFF Research Database (Denmark)

    Leleur, Steen

    This book presents principles and methodology for planning in a complex world. It sets out a so-called systemic approach to planning, among other things, by applying “hard” and “soft” methodologies and methods in combination. The book is written for Ph.D and graduate students in engineering...

  16. Superpave System

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    The Superpave is the acronym for 'SUperior PERforming Asphalt PAVEments' system. It was developed by Strategic Highway Research Program (SHRP) to give highway engineers and contractors the tools they need to design asphalt pavements that will perform better under extremes of temperature and heavy traffic loads.

  17. Solar system

    CERN Document Server

    Homer, Charlene

    2007-01-01

    Thrill young astronomers with a journey through our Solar System. Find out all about the Inner and Outer Planets, the Moon, Stars, Constellations, Asteroids, Meteors and Comets. Using simplified language and vocabulary, concepts such as planetary orbits, the asteroid belt, the lunar cycle and phases of the moon, and shooting stars are all explored.

  18. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  19. Hierarchical systems

    NARCIS (Netherlands)

    Hamers, A.S.

    2016-01-01

    The thesis addresses the long-term dynamical evolution of hierarchical multiple systems. First, we consider the evolution of orbits of stars orbiting a supermassive black hole (SBH). We study the long-term evolution and compute tidal disruption rates of stars by the SBH. Such disruption events revea

  20. Energy systems

    International Nuclear Information System (INIS)

    Up to the present the production, transmission and distribution of energy has been considered mostly as a fragmented problem; at best only subsystems have been considered. Today the scale of energy utilization is increasing rapidly, and correspondingly, the reliance of societies on energy. Such strong quantitative increases influence the qualitative nature of energy utilization in most of its aspects. Resources, reserves, reliability and environment are among the key words that may characterize the change in the nature of the energy utilization problem. Energy can no longer be considered an isolated technical and economical problem, rather it is embedded in the ecosphere and the society-technology complex. Restraints and boundary conditions have to be taken into account with the same degree of attention as in traditional technical problems, for example a steam turbine. This results in a strong degree of interweaving. Further, the purpose of providing energy becomes more visible, that is, to make survival possible in a civilized and highly populated world on a finite globe. Because of such interweaving and finiteness it is felt that energy should be considered as a system and therefore the term 'energy systems' is used. The production of energy is only one component of such a system; the handling of energy and the embedding of energy into the global and social complex in terms of ecology, economy, risks and resources are of similar importance. he systems approach to the energy problem needs more explanation. This paper is meant to give an outline of the underlying problems and it is hoped that by so doing the wide range of sometimes confusing voices about energy can be better understood. Such confusion starts already with the term 'energy crisis'. Is there an energy crisis or not? Much future work is required to tackle the problems of energy systems. This paper can only marginally help in that respect. But it is hoped that it will help understand the scope of the

  1. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    2012-01-01

    This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational...... design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  2. TUBO system

    International Nuclear Information System (INIS)

    Proceedings recently incorporated to TUBO system like the seismic analysis and the stress verification acccording to ASME-Boiler Rule and Pressure Vessel Code-section III are presented. The seismic analysis comprehend the consideration of uniform motion of the support, its multiple excitation, and the attainment of the spectral response for both cases. The module for stress verification uses stresses resulting fromthe combination of the loads specified by the user, in the automatic verification of permissible stresses for the pipings class 1 and 2, based on criteria NB-3650 and NC-3650 of ASME. The implementation of these proceedings in the TUBO system are discussed and a numerical example that covers the different phases of a stress analysis in a piping is presented

  3. Bilateral system. The ABACC system

    International Nuclear Information System (INIS)

    After relating the antecedents of the creation of the Brazilian-Argentine Agency for the Accounting and Control of Nuclear Materials (ABACC), the paper describes the common system of accounting and control set up by Argentina and Brazil. The organization of ABACC is also outlined

  4. Navigation systems

    OpenAIRE

    Ocepek, Marjan

    2013-01-01

    In this thesis we present different navigation systems which may be used also in surveying. Map as a basis of navigation is described at the beginning. Next, we focus on navigation based on celestial bodies. We present basic terms such as navigation and orientation and describe some primitive methods, which had been used for orientation without compass. We present two important time keeping instruments that facilitated the process of position determination, the chronometer and chronograph, an...

  5. Security system

    Science.gov (United States)

    Baumann, Mark J.; Kuca, Michal; Aragon, Mona L.

    2016-02-02

    A security system includes a structure having a structural surface. The structure is sized to contain an asset therein and configured to provide a forceful breaching delay. The structure has an opening formed therein to permit predetermined access to the asset contained within the structure. The structure includes intrusion detection features within or associated with the structure that are activated in response to at least a partial breach of the structure.

  6. Systems paleobiology

    OpenAIRE

    Knoll, Andrew Herbert

    2013-01-01

    Systems paleobiology seeks to interpret the history of life within the framework of Earth’s environmental history, using physiology as the conceptual bridge between paleontological and geochemical data sets. In some cases, physiological performance can be estimated directly and quantitatively from fossils—this is commonly the case for vascular plant remains. In other instances, statistical inferences about physiology can be made on the basis of phylogenetic relationships. Examples from resear...

  7. Italgrip System

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    The ever increasing number of registered vehicles has resulted in, up until the present time, a parallel increase in the number of road accidents. One of the reasons for this is that the quality of the road surface has not adequately kept pace with the increased volume of traffic. The Italgrip System increases skid resistance, reduces hydroplaning risk, reduces noise, and reduces salt consumption and can be applied to asphalt, concrete, or steel surfaces. It has been applied to several roadwa...

  8. Neuromodulatory systems

    OpenAIRE

    Werner, Gerhard; Mitterauer, Bernhard J.

    2013-01-01

    We examine the interactions and interdependencies between Neuroglia, the Brain-Cell Microenvironment, and the processes commonly subsumed under Neuromodulation. The interactions of the component processes covering a wide spectrum of frequencies are designated as Neuromodulatory Systems (NMS). This implies NMS's scale-invariance as the capacity of linking actions across many time scales, and self-similarity at any scale. These features endow NMS with the ability to respond adaptively to neural...

  9. Neuromodulatory Systems

    OpenAIRE

    Gerhard eWerner; Mitterauer, Bernhard J.

    2013-01-01

    Abstract We examine the interactions and interdependencies between Neuroglia, the Brain-Cell Microenvironment, and the processes commonly subsumed under Neuromodulation. The interactions of the component processes covering a wide spectrum of frequencies are designated as Neuromodulatory Systems (NMS). This implies NMS's scale-invariance as the capacity of linking actions across many time scales, and self-similarity at any scale. These features endow NMS with the ability to respond adaptively ...

  10. Organizational Systems

    OpenAIRE

    2004-01-01

    Kirk A. Astroth: So...You Want to Serve on The NAE4-HA Board! Marilyn Corbin: Diversity in Action: Promising Practices of CASD. Teresa Hogue: Can Extension Programs Afford Not to Invest in Business Plans? Dallas L. Holmes: FOCIS an Extension Web-Based Accountability in Action Reporting System. Maureen Hosty: 4-H Wildlife Stewards- Unleashing the Force and Vitality of Communities. Beverly Kelbaugh: Identifying Professional Development Needs of Extension Personnel. Jane E. Keyser: Property Tax ...

  11. Modular system

    International Nuclear Information System (INIS)

    Members of the Earth and Planetary Sciences community plan to use the APS facility for a variety of applications. Each type of beam line described in the previous chapter offers a set of properties that are valuable for several applications. Therefore, each beam line will need to serve several different experiments. In addition many of the experiments will need more than one type of radiation. As a result, flexibility will be extremely important to the success of the program. In order to provide the required flexibility, we propose a system consisting of modules. Each module will be a rack on which there will be mounted all of the necessary instrumentation for a particular type of experiment. It will be designed so that it can be moved by crane from one beam line hutch to another or from staging area to beam line hutch and back. Each beam line, in turn, will be equipped to receive any of the various modules. There will be a simple arrangement for indexing each module on each beam line so that a minimum of alignment will be necessary when a module is installed. An example of a module would be an energy dispersive x-ray diffraction system consisting of adjustable fine slits, a sample mounting system with computer-driven translational and orientational alignment capabilities, telescopes for alignment, solid state detector, multichannel analyzer, computer, and the associated power supplies and electronics. Such a module would be suitable for high pressure-temperature diamond cell studies

  12. Complex Systems

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2012-01-01

    Full Text Available Quantum instanton (QI approximation is recently proposed for the evaluations of the chemical reaction rate constants with use of full dimensional potential energy surfaces. Its strategy is to use the instanton mechanism and to approximate time-dependent quantum dynamics to the imaginary time propagation of the quantities of partition function. It thus incorporates the properties of the instanton idea and the quantum effect of partition function and can be applied to chemical reactions of complex systems. In this paper, we present the QI approach and its applications to several complex systems mainly done by us. The concrete systems include, (1 the reaction of H+CH4→H2+CH3, (2 the reaction of H+SiH4→H2+SiH3, (3 H diffusion on Ni(100 surface; and (4 surface-subsurface transport and interior migration for H/Ni. Available experimental and other theoretical data are also presented for the purpose of comparison.

  13. Systemic amyloidosis.

    Science.gov (United States)

    Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N

    2016-06-25

    Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses. PMID:26719234

  14. Ration System

    OpenAIRE

    Vymazalova, Hana

    2016-01-01

    The distribution of rations can be found in documents from different period of the Egyptian history but the general features of the ration system is not easy to trace. Most of the sources are the more or less fragmentary lists of wages/payments that reflect various conditions, such as status of the recipients, period to which the payment corresponds etc, that are not always known to us. Other documents provide us with categories of allowances ascribed to the workmen and officials who particip...

  15. Nuclear systems

    CERN Document Server

    Todreas, Neil E

    2011-01-01

    Principal Characteristics of Power ReactorsIntroductionPower CyclesPrimary Coolant SystemsReactor CoresFuel AssembliesAdvanced Water- and Gas-Cooled Reactors (Generation III And III+)Advanced Thermal and Fast Neutron Spectrum Reactors (Generation IV)ReferencesProblemsThermal Design Principles and ApplicationIntroductionOverall Plant Characteristics Influenced by Thermal Hydraulic ConsiderationsEnergy Production and Transfer ParametersThermal Design LimitsThermal Design MarginFigures of Merit for Core Thermal PerformanceThe Inverted Fuel ArrayThe Equivalent Annulus ApproximationReferencesProble

  16. Balance System

    Science.gov (United States)

    1988-01-01

    TherEx Inc.'s AT-1 Computerized Ataxiameter precisely evaluates posture and balance disturbances that commonly accompany neurological and musculoskeletal disorders. Complete system includes two-strain gauged footplates, signal conditioning circuitry, a computer monitor, printer and a stand-alone tiltable balance platform. AT-1 serves as assessment tool, treatment monitor, and rehabilitation training device. It allows clinician to document quantitatively the outcome of treatment and analyze data over time to develop outcome standards for several classifications of patients. It can evaluate specifically the effects of surgery, drug treatment, physical therapy or prosthetic devices.

  17. Scanning system

    International Nuclear Information System (INIS)

    An improved transversally cutting radionuclide scanning system is described which can be used for medical diagnosis and medical treatment of men, particularly, for brain investingations. 99mTc43 is named as a radionuclide. The device described is more sensitive, and displays results in a shorter period of time than devices known until now. By means of laser emitting diodes a continuous transmission and collection of signals is obtained, due to a rotating picture framework of offset and meshing detectors surrounding completely the scanning field around a single rotation axis - coaxialy with the axis of the head. Signals are processed and displayed by a connected computer. Description in detail, 7 figures. (UWI)

  18. Sterilization System

    Science.gov (United States)

    1990-01-01

    Cox Sterile Products, Inc.'s Rapid Heat Transfer Sterilizer employs a heat exchange process that induces rapid air movement; the air becomes the heat transfer medium, maintaining a uniform temperature of 375 degrees Fahrenheit. It features pushbutton controls for three timing cycles for different instrument loads, a six-minute cycle for standard unpackaged instruments, eight minutes for certain specialized dental/medical instruments and 12 minutes for packaged instruments which can then be stored in a drawer in sterile condition. System will stay at 375 degrees all day. Continuous operation is not expensive because of the sterilizer's very low power requirements.

  19. Linear systems

    CERN Document Server

    Bourlès, Henri

    2013-01-01

    Linear systems have all the necessary elements (modeling, identification, analysis and control), from an educational point of view, to help us understand the discipline of automation and apply it efficiently. This book is progressive and organized in such a way that different levels of readership are possible. It is addressed both to beginners and those with a good understanding of automation wishing to enhance their knowledge on the subject. The theory is rigorously developed and illustrated by numerous examples which can be reproduced with the help of appropriate computation software. 60 exe

  20. Radiographic system

    International Nuclear Information System (INIS)

    This invention discloses a radiographic system comprising an X-ray source disposed to direct an X-ray beam through an adjustable shutter aperture in an aligned collimator and onto an image receptor in a holder located at a preselected distance from the source; and automatic means for preventing an X-ray exposure until prescribed operating conditions have been satisfied, the automatic means including a readily interchangeable read-only-memory module for storing the prescribed conditions therein and ascertaining whether or not the prescribed conditions have been met

  1. System update

    International Nuclear Information System (INIS)

    The Laser Experiments Analysis Facility consists of two DEC computers - PDP-11/34 and a VAX/VMS-11/780; and a Perkin-Elmer 1010GM microdensitometer - a photodigitizing system (PDS). The PDP-11/34 is a dedicated machine used to control the PDS, and the VAX is used for storage and analysis of ICF data and for general purpose computing. A one-way, fiber-optic link connects the LEAF VAX to the Nova VAX for transfer of shot data. Over the past year, major improvements were made in the hardware, system software, and applications codes. The VAX hardware was modernized by the addition of two high-speed tape drives and four Winchester disks. The disks have a combined capacity of over 4 gigabytes. A number of special peripherals were also added: an array processor, an IBM Personal Computer (PC), a Versatec Random Element Processor (REP), a high-resolution color monitor, and two 1000-line-per-minute Versatec printer/plotters. Currently on order is an upgrade to the VAX central processing unit (CPU) that will increase its computing speed by about 50%

  2. System analysis and design

    International Nuclear Information System (INIS)

    This book deals with information technology and business process, information system architecture, methods of system development, plan on system development like problem analysis and feasibility analysis, cases for system development, comprehension of analysis of users demands, analysis of users demands using traditional analysis, users demands analysis using integrated information system architecture, system design using integrated information system architecture, system implementation, and system maintenance.

  3. Nuva - System (**)

    OpenAIRE

    BAYIRLI, Gündüz

    2013-01-01

    «Nuva-fil», «Nuva-seal» ve «Nuva-lite» dan oluşan maddeler ve apareye fabrika tarafından «Nuva-system» adı verilmiştir.«Nuva-seal» bir fissür koruyucusudur; «Nuva-fil» bir kompozit dolgu maddesidir; «Nuva-lite» ultraviyole ışını sağlayan bir apareydir."Nuva-seal» ve «Nuva-fil» bu güne kadar kullanılan dolgu maddelerinden şu nokta da ayrılırlar : Her ikisi de yalnız ultraviyole ışığı etkisiyle sertleşmektedir. «Nuva-seal» asit etkisinde kalan mineye bağlanır; «Nuva-fil» «Nuva-seal» in üzerinde...

  4. Quantum systems as classical systems

    CERN Document Server

    Cassa, A

    2001-01-01

    A characteristical property of a classical physical theory is that the observables are real functions taking an exact outcome on every (pure) state; in a quantum theory, at the contrary, a given observable on a given state can take several values with only a predictable probability. However, even in the classical case, when an observer is intrinsically unable to distinguish between some distinct states he can convince himself that the measure of its ''observables'' can have several values in a random way with a statistical character. What kind of statistical theory is obtainable in this way? It is possible, for example, to obtain exactly the statistical previsions of quantum mechanics? Or, in other words, can a physical system showing a classical behaviour appear to be a quantum system to a confusing observer? We show that from a mathematical viewpoint it is not difficult to produce a theory with hidden variables having this property. We don't even try to justify in physical terms the artificial construction ...

  5. Systems engineering simplified

    CERN Document Server

    Cloutier, Robert; Bone, Mary Alice

    2015-01-01

    IntroductionOverviewDiscussion of Common TerminologyThe Case for Systems EngineeringA Brief History of Systems EngineeringSystem ExamplesSummaryThe System Life CycleManaging System Development-The Vee ModelSystem ProductionSystem Utilization and SupportSystem Retirement and DisposalOther Systems Engineering Development ModelsSpiral ModelAgile Model for Systems EngineeringSystem of InterestAbstraction and DecompositionIntegrationDeveloping and Managing RequirementsCyclone Requiremen

  6. The role of substance P in respiratory control in the newborn : Effects of morphine and nicotine

    OpenAIRE

    Berner, Jonas

    2008-01-01

    We breathe in order to maintain oxygen, carbon dioxide and pH levels within the physiological range in response to the metabolic demands of the body. To achieve this, the respiratory control system is dependent on input from peripheral and/ central chemosensitive areas and on participation of different neuromodulator systems. This thesis focuses on the role of one of the neurotransmitters, substance P, involved in the complex and finely tuned control of respiration. It also ...

  7. Chem systems

    International Nuclear Information System (INIS)

    This paper reports that world styrene demand, paced by a near doubling of combined requirements in East Asia and Oceania, could reach 19.3 million metric tons by 2000, an average growth rate of 3.7%/year. So concludes Chem Systems Inc., Tarrytown, N.Y., in a study of world styrene markets through the end of the century. Pacific Rim styrene production and consumption throughout the 1990s are predicted to make up increasingly larger shares of world markets, while demand and production lag in the U.S. and western Europe. Demand and capacity in other parts of the world will grow in real terms, increasing combined market shares only slightly. Most of the increase will be driven by demand in East Asia and Oceania, where consumption by century's end is expected to increase 4.48 million metric tons from 2.25 million tons in 1991. Meantime, Japan's styrene demand in 2000 is projected at 2.64 million tons, a 500,000 ton increase from 1991 demand but a net market loss of 1.9%

  8. [Systemic sclerosis].

    Science.gov (United States)

    Tamborrini, Giorgio; Distler, Meike; Distler, Oliver

    2008-05-01

    Systemic sclerosis (SSc) is a severe fibrotic multiorgan connective tissue disease. Vascular abnormalities such as fingertip ulcers and Raynaud's syndrome as well as involvement of organs including the lungs, heart, kidney and the gastrointestinal tract are prominent features of the disease. There are currently no disease modifying drugs available that can modify the course of the disease. In this review we will discuss medications that have been found to be effective in improving specific organ involvement due to SSc. For the treatment of gastroesophageal reflux disease (GERD), proton pump inhibitors are effective agents. In the setting of clinically significant gastrointestinal dysmotility, metoclopramide, erythromycin and octreotide may be beneficial. Small bowel bacterial overgrowth should be treated with oral antibiotics. Angiotensin converting enzyme inhibitors are the first-line agents for acute renal crisis. A variety of treatment options are available for Raynaud's phenomenon and include calcium channel blockers, iloprost (i. v.), losartan, fluoxetine and sildenafil. Fingertip ulcers can be prevented by using the endothelin receptor antagonist bosentan. The therapeutic options for treatment of pulmonary hypertension associated with SSc include bosentan, sildenafil and various prostacyclin analogs (eg, epoprostenol, treprostinil, iloprost). Sitaxentan, ambrisentan and new phosphodiesterase-5 inhibitors could be new options for therapy as well. Therapeutic options for interstitial lung fibrosis include cyclophosphamide, however, clinical effects are mild to moderate. Methotrexate has been used to treat skin fibrosis and can be beneficial when arthritis is present. PMID:18552072

  9. Endocrine System (For Teens)

    Science.gov (United States)

    ... Can I Help a Friend Who Cuts? Endocrine System KidsHealth > For Teens > Endocrine System Print A A ... called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  10. Prosthetic Knee Systems

    Science.gov (United States)

    ... of fluid control systems — pneumatic (using air) and hydraulic (using fluid). Pneumatic control. These systems: compress air ... control than friction systems are less effective than hydraulic systems. Hydraulic control. These systems: use liquid (usually ...

  11. System safety education focused on system management

    Science.gov (United States)

    Grose, V. L.

    1971-01-01

    System safety is defined and characteristics of the system are outlined. Some of the principle characteristics include role of humans in hazard analysis, clear language for input and output, system interdependence, self containment, and parallel analysis of elements.

  12. Symmetries, Groups, Groupoids and Systems of Systems

    OpenAIRE

    Alonso, E.; Karcanias, N.; Hessami, A. G.

    2013-01-01

    In this paper we propose an algebraic model of systems based on the concept of symmetry that can be instrumental in representing Systems of Systems two main characteristics, namely complexity and (hierarchical) emergence.

  13. Respiratory System

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    8.1 Respiratory failure2007204 Comparison of the effects of BiPAP ventilation combined with lung recruitment maneuvers and low tidal volume A/C ventilation in patients with acute respiratory distress syndrome. WANG Xiaozhi(王晓芝),et al. Dept Respir & Intensive Care Unit, Binzhou Med Coll, Binzhou 256603. Chin J Tuberc Respir Dis 2007;30(1):44-47. Objective To compare the effects of BiPAP ventilation combined with lung recruitment maneuvers(LRM) with low tidal volume A/C ventilation in patients with acute respiratory distress syndrome (ARDS). Methods A prospective, randomized comparison of BiPAP mechanical ventilation combined with lung recruitment maneuvers(test group) with low tidal volume A/C ventilation (control group) was conducted in 28 patients with ARDS. FiO2/PaO2 ratio, respiratory system compliance(Cs), central venous pressure (CVP), duration of ventilation support were recorded at 0 h, 48 h and 72 h separately. The ventilation associated lung injury and mortality at 28 d were also recorded. Results The FiO2/PaO2 ratio were (298±16) and (309±16) cm H2O, Cs were (38.4±2.2) and (42.0±1.3) ml/cm H2O, CVP were (13.8±0.8) and (11.6±0.7) cm H2O in the test group at 48 h and 72 h separately. In the control group, FiO2/PaO2 ratio were (212±12) and (246±17) cm H2O, Cs were (29.5±1.3) and (29.0±1.0) ml/cm H2O, CVP were 18.6±1.1 and (16.8±1.0) cm H2O. The results were better in the test group as compared with the control group (t=10.03-29. 68, all P<0.01). The duration of ventilation support in the test group was shorter than the control group [(14±3) d vs (19±3)d, t=4.80, P<0.01]. The mortality in 28 d and ventilation associated lung injury were similar in the two groups. Conclusion The results show that combination of LRM with BiPAP mode ventilation, as compared with the control group, contributes to the improved FiO2/PaO2 ratio, pulmonary compliance, stable homodynamic and shorter duration of ventilation support in patients with ARDs.

  14. Paradigms of Intelligent Systems

    OpenAIRE

    Dana Ramona ANDRISESCU

    2007-01-01

    This paper approaches the subject of paradigms for the categories of intelligent systems. First we can look at the term paradigm in its scientific meaning and then we make acquaintance with the main categories of intelligent systems (expert systems, intelligent systems based on genetic algorithms, artificial neuronal systems, fuzzy systems, hybrid intelligent systems). We will see that every system has one or more paradigms, but hybrid intelligent systems combine paradigms because they are ma...

  15. Information Systems in the Polish Payment System

    OpenAIRE

    Murowaniecki, Łukasz; Woźniacki, Konrad

    2007-01-01

    The paper focuses on computerised information systems responsible for payment information exchange in Polish payment system. Firstly some terms, connected with the topic of funds transfer system, are ordered. Then, relying on the taxonomy, the paper presents a comprehensive view of domestic payment system.

  16. Geoinformation Systems as Automated Management System

    OpenAIRE

    Andrey Pavlov

    2013-01-01

    The article analyzes geoinformation systems (GIS) development as management systems, highlights the basic principles of decision-making in GIS, describes GIS storage systems and decision-making systems, discloses the use of GIS for the territory management and briefly describes the use of GIS for transport management and monitoring.

  17. Geoinformation Systems as Automated Management System

    Directory of Open Access Journals (Sweden)

    Andrey Pavlov

    2013-01-01

    Full Text Available The article analyzes geoinformation systems (GIS development as management systems, highlights the basic principles of decision-making in GIS, describes GIS storage systems and decision-making systems, discloses the use of GIS for the territory management and briefly describes the use of GIS for transport management and monitoring.

  18. Understanding Patterns for System of Systems Integration

    DEFF Research Database (Denmark)

    Kazman, Rick; Schmid, Klaus; Nielsen, Claus Ballegård;

    2013-01-01

    Architecting systems of systems is well known to be a formidable challenge. A major aspect in this is defining the integration among the systems that constitute the system of systems. In this paper, we aim to support the SoS architect by systematically developing a way to characterize system of...... systems integration patterns. These characteristics at the same time support the architecting process by highlighting important issues a SoS architect needs to consider. We discuss the consolidated template and illustrate it with an example pattern. We also discuss the integration of this novel pattern...

  19. Networked control of microgrid system of systems

    Science.gov (United States)

    Mahmoud, Magdi S.; Rahman, Mohamed Saif Ur; AL-Sunni, Fouad M.

    2016-08-01

    The microgrid has made its mark in distributed generation and has attracted widespread research. However, microgrid is a complex system which needs to be viewed from an intelligent system of systems perspective. In this paper, a network control system of systems is designed for the islanded microgrid system consisting of three distributed generation units as three subsystems supplying a load. The controller stabilises the microgrid system in the presence of communication infractions such as packet dropouts and delays. Simulation results are included to elucidate the effectiveness of the proposed control strategy.

  20. Concept and System of Personification Control System

    Institute of Scientific and Technical Information of China (English)

    Bai,Fengshuang; Yin,Yixin; Tu,Xuyan; Zhang,Ying

    2006-01-01

    This paper provides the system and conception of the Personification Control System (PCS) on the basis of Intelligent Control System based on Artificial life (ICS/AL), Artificial Emotion, Humanoid Control, and Intelligent Control System based on Field bus. According to system science and deciding of organize of biology, the Pyramid System of PCS are created. Then Pyramid System of PCS which is made up of PCS1/H, PCS1/S, PCS1/O, PCS1/C and PCS1/G is described.

  1. D0 Cryo System Control System Autodialer

    Energy Technology Data Exchange (ETDEWEB)

    Urbin, J.; /Fermilab

    1990-04-17

    The DO cryogenic system is controlled by a TI565-PLC based control system. This allows the system to be unmanned when in steady state operation. System experts will need to be contacted when system parameters exceed normal operating points and reach alarm setpoints. The labwide FIRUS system provides one alarm monitor and communication link. An autodialer provides a second and more flexible alarm monitor and communication link. The autodialer monitors contact points in the control system and after receiving indication of an alarm accesses a list of experts which it calls until it receives an acknowledgement. There are several manufacturers and distributors of autodialer systems. This EN explains the search process the DO cryo group used to fmd an autodialer system that fit the cryo system's needs and includes information and specs for the unit we chose.

  2. Systems design of long-life systems

    Science.gov (United States)

    Miles, R. F., Jr.

    1974-01-01

    A long-life system is defined as a system which cannot be life-tested in its operational environment. Another restriction is that preventive maintenance and repair shall be either impossible or economically disadvantageous. Examples of such systems include planetary spacecraft, communication satellites, undersea telephone cables, and nuclear power plants. The questions discussed are related to the implementation of system functions, approaches to determine the required level of system reliability, and aspects of tradeoffs between requirements and reliability.

  3. Port contact systems for irreversible thermodynamical systems

    OpenAIRE

    Eberard, D.; Maschke, B. M.; Schaft, A.J. van der

    2005-01-01

    In this paper we propose a definition of control contact systems, generalizing input-output Hainiltonian systems, to cope with models arising from irreversible Thermodynamics. We exhibit a particular subclass of these systems, called conservative, that leaves invariant some Legendre submanifold (the geometric structures associated with thermodynamic properties). These systems, both energy-preserving and irreversible, are then used to analyze the loss-lessness of these systems with respect to ...

  4. Fibroblast growth factors: An epigenetic mechanism of broad spectrum resistance to anticancer drugs

    OpenAIRE

    Song, SaeHeum; Wientjes, M. Guillaume; Gan, Yuebo; Au, Jessie L. -S.

    2000-01-01

    Based on the observation that removal of tumors from metastatic organs reversed their chemoresistance, we hypothesized that chemoresistance is induced by extracellular factors in tumor-bearing organs. By comparing chemosensitivity and proteins in different tumors (primary vs. metastases) and different culture systems (tumor fragment histocultures vs. monolayer cultures derived from the same tumor), we found elevated levels of acidic (aFGF) and basic (bFGF) fibroblast growth factors in the con...

  5. The human carotid body in sensing and signaling of oxygen and inflammation

    OpenAIRE

    Kåhlin, Jessica

    2014-01-01

    Oxygen is essential for cell survival and global oxygenation is closely monitored in order to protect tissues from hypoxic damage. The carotid body is an important systemic oxygen sensor responding to hypoxia and a multitude of other blood borne stimuli, including inflammatory mediators. Activation of the carotid body by depolarization of the chemosensitive type 1 cells ultimately leads to appropriate ventilatory and cardiovascular responses. While animal carotid body oxygen sensing and signa...

  6. Your Digestive System

    Science.gov (United States)

    ... Here's Help White House Lunch Recipes Your Digestive System KidsHealth > For Kids > Your Digestive System Print A ... flush we were talking about! Dig That Digestive System You can help your digestive system by drinking ...

  7. Male Reproductive System

    Science.gov (United States)

    ... I Help a Friend Who Cuts? Male Reproductive System KidsHealth > For Teens > Male Reproductive System Print A ... reproductive systems. continue What Is the Male Reproductive System? Most species have two sexes: male and female. ...

  8. Multiple System Atrophy

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy Information Page Condensed from Multiple System Atrophy ... Trials Organizations Publicaciones en Español What is Multiple System Atrophy? Multiple system atrophy (MSA) is a progressive ...

  9. System design specification Brayton Isotope Power System (BIPS) Flight System (FS), and Ground Demonstration System (GDS)

    Energy Technology Data Exchange (ETDEWEB)

    1976-06-14

    The system design specification for ground demonstration, development, and flight qualification of a Brayton Isotope Power System (BIPS) is presented. The requirements for both a BIPS conceptual Flight System (FS) and a Ground Demonstration System (GDS) are defined.

  10. System design specification Brayton Isotope Power System (BIPS) Flight System (FS), and Ground Demonstration System (GDS)

    International Nuclear Information System (INIS)

    The system design specification for ground demonstration, development, and flight qualification of a Brayton Isotope Power System (BIPS) is presented. The requirements for both a BIPS conceptual Flight System (FS) and a Ground Demonstration System (GDS) are defined

  11. Integrated library systems.

    OpenAIRE

    Goldstein, C M

    1983-01-01

    The development of integrated library systems is discussed. The four major discussion points are (1) initial efforts; (2) network resources; (3) minicomputer-based systems; and (4) beyond library automation. Four existing systems are cited as examples of current systems.

  12. Situation awareness with systems of systems

    CERN Document Server

    Tretmans, Jan; Borth, Michael

    2013-01-01

    This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security.  Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier selection, rule-based anomaly detection, an ontology-based event model for semantic reasoning, new methods for semi-automatic generation of adapters bridging communication gaps, security policies for systems-of-systems, trust assessment, and methods to deal with the dynamics of systems-of-systems in run-time monitoring, testing, and diagnosis. Architectural considerations for designing information-centric systems-of-systems such as situation awareness systems, and an integrated demonstrator implementing many of the investigated aspects, complete the book.

  13. System of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E. (Intera, Inc., Austin, TX); Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  14. The MAST data acquisition system - system architecture

    International Nuclear Information System (INIS)

    A new data acquisition (DA) system has been developed for the MAST experiment at Culham. It has also been implemented on the COMPASS experiment as a replacement for the old PDP-11 based data acquisition system and as a test bed for MAST. The DA system is distributed across a number of computers with a DA process for each distinct diagnostic system. An object-orientated approach is taken to the control and readout of each device in the system. It is designed to be independent of the hardware interfaces used on each diagnostic. The system is flexible enough to cope with diagnostics ranging from those involving simple time evolving signals to complex spectrometers, and will incorporate a new high speed distributed timing system. This system is also being considered as the interface to the real time Plasma Control system on MAST. A distributed scheduling system is used to co-ordinate the activity of each DA process with the Central Control system for each experiment. This paper describes the architecture of this data acquisition system with particular emphasis on the core of the data acquisition system. Aspects of distributed implementation of the system on real diagnostics are discussed in a companion paper

  15. Computer System Design System-on-Chip

    CERN Document Server

    Flynn, Michael J

    2011-01-01

    The next generation of computer system designers will be less concerned about details of processors and memories, and more concerned about the elements of a system tailored to particular applications. These designers will have a fundamental knowledge of processors and other elements in the system, but the success of their design will depend on the skills in making system-level tradeoffs that optimize the cost, performance and other attributes to meet application requirements. This book provides a new treatment of computer system design, particularly for System-on-Chip (SOC), which addresses th

  16. System specifications for the NDS EXFOR System

    International Nuclear Information System (INIS)

    EXFOR is the agreed exchange format for the magnetic-tape exchange of nuclear reaction data between national and international nuclear data centers for the benefit of nuclear data users in all countries. The NDS EXFOR System is a computerized system for the storage and retrieval of EXFOR information compiled or received of the IAEA. This document is an internal manual for the system specifications of the NDS EXFOR System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. The manual is updated from time to time when system modifications are made; the first version was issued in July 1979. (author)

  17. System specifications for the NDS EXFOR System

    International Nuclear Information System (INIS)

    EXFOR is the agreed exchange format for the magnetic-tape exchange of nuclear reaction data between national and international nuclear data centres for the benefit of nuclear data users in all countries. The NDS EXFOR System is a computerized system for the storage and retrieval of EXFOR information compiled or received by the IAEA. This document is an internal manual for the system specifications of the NDS EXFOR System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. The manual is updated from time to time when system modifications are made

  18. Plumbagin, Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization

    OpenAIRE

    Sandur, Santosh K.; Pandey, Manoj K.; Sung, Bokyung; Aggarwal, Bharat B.

    2010-01-01

    The activation of STAT3 has been linked with carcinogenesis through survival, proliferation, and angiogenesis of tumor cells. Agents that can suppress STAT3 activation have potential not only for prevention but also for treatment of cancer. In the present report, we investigated whether plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), an analogue of Vitamin K and isolated from chitrak (Plumbago zeylanica), an Ayurvedic medicinal plant, can modulate the STAT3 pathway. We found that plumbagin...

  19. Overexpression of Lin28 Decreases the Chemosensitivity of Gastric Cancer Cells to Oxaliplatin, Paclitaxel, Doxorubicin, and Fluorouracil in Part via microRNA-107.

    Directory of Open Access Journals (Sweden)

    Rongyue Teng

    Full Text Available Higher Lin28 expression is associated with worse pathologic tumor responses in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. However, the characteristics of Lin28 and its mechanism of action in chemotherapy resistance is still unclear. In this study, we found that transfection of Lin28 into gastric cancer cells (MKN45 and MKN28 increased their resistance to the chemo-drugs oxaliplatin (OXA, paclitaxel (PTX, doxorubicin (ADM, and fluorouracil (5-Fu compared with gastric cancer cells transfected with a control vector. When knockdown Lin28 expression by Lin28 small interfering RNA (siRNA was evaluated in vitro, we found that the resistance to chemo-drugs was reduced. Furthermore, we found that Lin28 up-regulates C-myc and P-gp and down-regulates Cylin D1. Finally, we found that miR-107 is a target microRNA of Lin28 and that it participates in the mechanism of chemotherapy resistance. Our results suggest that the Lin28/miR-107 pathway could be one of many signaling pathways regulated by Lin28 and associated with gastric cancer chemo-resistance.

  20. The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization

    OpenAIRE

    Hoellenriegel, Julia; Zboralski, Dirk; Maasch, Christian; Rosin, Nathalie Y.; Wierda, William G.; Keating, Michael J.; Kruschinski, Anna; Burger, Jan A.

    2014-01-01

    NOX-A12, a structured mirror-image RNA oligonucleotide that neutralizes CXCL12, interferes with CLL migration and drug resistance.NOX-A12 inhibits chemotaxis and sensitizes CLL cells toward cytotoxic drugs, providing a rationale for NOX-A12 combination therapy.

  1. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation.

    Science.gov (United States)

    Calviño, Eva; Estañ, María Cristina; Sánchez-Martín, Carlos; Brea, Rocío; de Blas, Elena; Boyano-Adánez, María del Carmen; Rial, Eduardo; Aller, Patricio

    2014-02-01

    3-Bromopyruvate (3-BrP) is an alkylating, energy-depleting drug that is of interest in antitumor therapies, although the mechanisms underlying its cytotoxicity are ill-defined. We show here that 3-BrP causes concentration-dependent cell death of HL60 and other human myeloid leukemia cells, inducing both apoptosis and necrosis at 20-30 μM and a pure necrotic response at 60 μM. Low concentrations of 3-BrP (10-20 μM) brought about a rapid inhibition of glycolysis, which at higher concentrations was followed by the inhibition of mitochondrial respiration. The combination of these effects causes concentration-dependent ATP depletion, although this cannot explain the lethality at intermediate 3-BrP concentrations (20-30 μM). The oxidative stress caused by exposure to 3-BrP was evident as a moderate overproduction of reactive oxygen species and a concentration-dependent depletion of glutathione, which was an important determinant of 3-BrP toxicity. In addition, 3-BrP caused glutathione-dependent stimulation of p38 mitogen-activated protein kinase (MAPK), mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK), and protein kinase B (Akt)/mammalian target of rapamycin/p70S6K phosphorylation or activation, as well as rapid LKB-1/AMP kinase (AMPK) activation, which was later followed by Akt-mediated inactivation. Experiments with pharmacological inhibitors revealed that p38 MAPK activation enhances 3-BrP toxicity, which is conversely restrained by ERK and Akt activity. Finally, 3-BrP was seen to cooperate with antitumor agents like arsenic trioxide and curcumin in causing cell death, a response apparently mediated by both the generation of oxidative stress induced by 3-BrP and the attenuation of Akt and ERK activation by curcumin. In summary, 3-BrP cytotoxicity is the result of several combined regulatory mechanisms that might represent important targets to improve therapeutic efficacy. PMID:24307199

  2. Cytoreductive Surgery and Intraperitoneal Chemotherapy in Patients with Peritoneal Metastases from Colorectal Cancer : Aspects of loco-regional treatment outcome, patient selection, and chemo-sensitivity

    OpenAIRE

    Cashin, Peter H.

    2012-01-01

    Previously, peritoneal metastases(PM) from colorectal cancer(CRC) have been considered a terminal and generalised form of cancer. A new treatment strategy combining cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) has recently shown promising results. The aim of this thesis was to investigate different aspects of this treatment in order to optimise the treatment and to clarify its potential as a new treatment option. Treatment outcome, patient selection, method of IPC (hyperth...

  3. Piperlongumine chemosensitizes tumor cells through interaction with cysteine 179 of IκBα kinase, leading to suppression of NF-κB-regulated gene products.

    Science.gov (United States)

    Han, Jia Gang; Gupta, Subash C; Prasad, Sahdeo; Aggarwal, Bharat B

    2014-10-01

    Recently, two different reports appeared in prominent journals suggesting a mechanism by which piperlongumine, a pyridine alkaloid, mediates anticancer effects. In the current report, we describe another novel mechanism by which this alkaloid mediates its anticancer effects. We found that piperlongumine blocked NF-κB activated by TNFα and various other cancer promoters. This downregulation was accompanied by inhibition of phosphorylation and degradation of IκBα. Further investigation revealed that this pyridine alkaloid directly interacts with IκBα kinase (IKK) and inhibits its activity. Inhibition of IKK occurred through interaction with its cysteine 179 as the mutation of this residue to alanine abolished the activity of piperlongumine. Inhibition in NF-κB activity downregulated the expression of proteins involved in cell survival (Bcl-2, Bcl-xL, c-IAP-1, c-IAP-2, survivin), proliferation (c-Myc, cyclin D1), inflammation (COX-2, IL6), and invasion (ICAM-1, -9, CXCR-4, VEGF). Overall, our results reveal a novel mechanism by which piperlongumine can exhibit antitumor activity through downmodulation of proinflammatory pathway. PMID:25082961

  4. Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

    OpenAIRE

    Gelsomino, Giada; Corsetto, Paola A.; Campia, Ivana; Montorfano, Gigliola; Kopecka, Joanna; Castella, Barbara; Gazzano, Elena; Ghigo, Dario; Rizzo, Angela M; Riganti, Chiara

    2013-01-01

    Background The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the respo...

  5. TAp73-mediated the activation of C-jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells

    OpenAIRE

    Pingde Zhang; Stephanie Si Liu; Hextan Yuen Sheung Ngan

    2012-01-01

    P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. ...

  6. Terahertz split-ring metamaterials as transducers for chemical sensors based on conducting polymers: a feasibility study with sensing of acidic and basic gases using polyaniline chemosensitive layer

    International Nuclear Information System (INIS)

    We report on the first application of terahertz metamaterials acting as transducers for chemical sensors based on conducting polymers. In our feasibility study aimed at sensing of gaseous hydrochloric and ammonia, a two-dimensional sensor metamaterial consisting of an array of split-ring resonators on the surface of undoped silicon wafer was prepared. The surface of the resonator was coated with a 150-μm layer of polyaniline. Binding of hydrogen chloride to polyaniline leads to distinct changes in the resonance frequency of the metamaterial. Measurements can be performed both in the reflection and transmission mode. A numerical simulation of the response revealed an increase of both the real and the imaginary components of the dielectric function of the polyaniline film. These changes are attributed to the transition from emaraldine base to emeraldine salt. The results demonstrate a new approach for formation of highly sensitive transducers for chemical sensors. (author)

  7. Inter-experiment variation and dependence on culture conditions in assaying the chemosensitivity of human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Roed, H; Christensen, I B; Vindeløv, L L; Spang-Thomsen, M; Hansen, H H

    1987-01-01

    Sensitivity of five human small cell lung cancer cell lines to doxorubicin was assessed by a double layer agar technique using two different bottom-layers. Neither of the bottom-layers provided proportionality between numbers of cells plated and numbers of colonies, but they were correlated by a...

  8. AKT–THE MAMMALIAN TARGET OF RAPAMYCIN (MTOR PATHWAY INHIBITION INCREASES CERVICAL CANCER CELL CHEMOSENSITIVITY TO ACTIVE FORM OF IRINOTECAN (SN-38

    Directory of Open Access Journals (Sweden)

    Leri Septiani

    2015-07-01

    Full Text Available Objective: To investigate the molecular pathway of the cytotoxic effect of SN-38 in human cervical cancer cell lines. Methods: Two human cervical cancer cell lines were treated with various concentrations of irinotecan for 24–72 hours and the sensitivity was analysed using the MTT assay. Apoptosis was further observed through microscopic examinations. The protein expression was determined using Western blot analysis. Results: CaSki cells demonstrated the highest sensitivity to SN-38, whereas HeLa cells showed the lowest. In cervical cancer cells, SN-38 induced apoptosis through an intrinsic- and extrinsic-pathways. In addition, we showed that SN-38 downregulated the phosphorylation of Akt-mTOR pathways in CaSki cells, but not in HeLa cells. Interestingly, in HeLa cells, which were more suggestive of a resistant phenotype, pre-treatment with LY294002 and rapamycin inhibited activation of Akt-mTOR signaling and significantly enhanced the sensitivity of HeLa cells to SN-38. Conclusions: Irinotecan exerts its anti-neoplastic effects on cervical cancer cells by inducing apoptosis through caspase-cascade. Inhibition of Akt-mTOR, LY294002 and rapamycin, which is targeted to Akt-mTOR pathways, may sensitize irinotecan-resistant cervical cancer cells.

  9. TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Pingde Zhang

    Full Text Available P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. We found that TAp73 acted as an activator of the c-Jun N-terminal kinase (JNK signaling pathway by up-regulating the expression of its target growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45α and subsequently activating mitogen-activated protein kinase kinase-4 (MKK4. Inhibition of JNK activity by a specific inhibitor or small interfering RNA (siRNA significantly abrogated TAp73-mediated apoptosis induced by cisplatin. Furthermore, inhibition of GADD45α by siRNA inactivated MKK4/JNK activities and also blocked TAp73-mediated apoptosis induction by cisplatin. Our study has demonstrated that TAp73 activated the JNK apoptotic signaling pathway in response to cisplatin in ovarian cancer cells.

  10. PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy.

    Science.gov (United States)

    Park, Ji-Hoon; Kim, Keun Pil; Ko, Jeong-Jae; Park, Kyung-Soon

    2016-08-19

    Drug resistance in breast cancer remains a major obstacle of clinical therapy. We found that suppression of ELK3 in the triple negative breast cancer cell line MDA-MB-231 impaired autophagy and led to a hypersensitive response to doxorubicin treatment. In ELK3-knockdown MDA-MB-231 cells (ELK3 KD), autophagy was not activated under starvation conditions, which is a major stimulus of autophagy activation. We revealed that activation of the PI3K/Akt pathway was the main cause of impaired autophagy in ELK3 KD. Our results suggest that targeting ELK3 may be a potential approach to overcome doxorubicin resistance in breast cancer therapeutics. PMID:27301639

  11. Monitoring the drug-sensitivity of Plasmodium falciparum in coastal towns in Madagascar by use of in vitro chemosensitivity and mutation detection tests

    Directory of Open Access Journals (Sweden)

    Rason M.A.

    2002-09-01

    Full Text Available The dissemination of mutant and resistant strains of Plasmodium falciparum makes a considerable contribution to the spread of drug-resistant malaria. Populations around harbours and airports could be particularly exposed to Plasmodium isolates introduced with imported cases of malaria. The use of chloroquine as well as the use of and sulfadoxine/pyrimethamine is currently an effective method for treating uncomplicated cases of malaria in Madagascar. As part of a monitoring programme, in vitro methods were used to assess the sensitivity of P. falciparum isolates in two coastal towns in Madagascar: Mahajanga on the west coast and Toamasina on the east coast. All of the isolates from both sites were sensitive to amodiaquine, quinine, pyrimethamine and cycloguanil. All of the isolates from Mahajanga were sensitive to chloroquine (n = 25; mean IC50 = 22.6 nM, 95 % confidence interval: 16.8-28.7 nM, whereas three of the isolates from Toamasina were resistant to chloroquine (n = 18; mean IC50 = 66.3 nM; 95 % confidence interval : 42.6-90 nM, The frequency of the Pfcrt Thr-76 and the dhfr Asn- 108 mutations was estimated by PCR/RFLP. The 43 P. falciparum isolates examined, including the three in vitro chloroquine-resistant isolates from Toamasina were all wild-type (Lys-76. Phenotyping and genotyping studies suggested that the prevalence of chloroquine- and pyrimethamine-resistant isolates and of mutant strains of P. falciparum is very low. These results showed that in vitro test and genotyping of resistance markers approaches could be successfully used to monitor the emergence of drug-resistant malaria and to try to alleviate the lack of medical teams able to carry out in vivo test. The possible hazard/risk associated with imported cases of malaria is discussed.

  12. Structure and conformational analysis of 5,11-dibenzyldibenzo[b,f][1,5]diazocine-6,12-dione. A novel approach for new chemosensitizers

    Science.gov (United States)

    Nonnenmacher, E.; Brouant, P.; Mrozek, A.; Karolak-Wojciechowska, J.; Barbe, J.

    2000-04-01

    On the basis of structural similarities between various calcium channel antagonists (Verapamil or Diltiazem) a novel series of derivatives belonging to the dibenzodiazocinedione family were designed and synthesised to obtain drugs able to revert multidrug resistance (MDR). X-ray structure studies and conformational analysis of 5,11-dibenzyldibenzo[b,f][1,5]diazocine-6,12-dione were performed. Molecular modelling results have shown that observed reversal activity of this new derivative could refer to a thermodynamically limited concentration in a peculiar (extended) conformation.

  13. Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

    NARCIS (Netherlands)

    L.L. Kodach; R.J. Jacobs; P.W. Voorneveld; M.E. Wildenberg; H.W. Verspaget; T. van Wezel; H. Morreau; D.W. Hommes; M.P. Peppelenbosch; G.R. van den Brink; J.C.H. Hardwick

    2011-01-01

    Promoter hypermethylation is an important and potentially reversible mechanism of tumour suppressor gene silencing in cancer. Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in cance

  14. Immunohistochemical expression of stem cell, endothelial cell, and chemosensitivity markers in primary glioma spheroids cultured in serum-containing and serum-free medium

    DEFF Research Database (Denmark)

    Christensen, Karina; Aaberg-Jessen, Charlotte; Andersen, Claus;

    2010-01-01

    To investigate the influence of serum-free medium (SFM) supplemented with epidermal growth factor and basic fibroblast growth factor compared with conventional serum-containing medium (SCM) on the phenotype of organotypic primary spheroids from seven gliomas....

  15. Intelligent systems technology infrastructure for integrated systems

    Science.gov (United States)

    Lum, Henry, Jr.

    1991-01-01

    Significant advances have occurred during the last decade in intelligent systems technologies (a.k.a. knowledge-based systems, KBS) including research, feasibility demonstrations, and technology implementations in operational environments. Evaluation and simulation data obtained to date in real-time operational environments suggest that cost-effective utilization of intelligent systems technologies can be realized for Automated Rendezvous and Capture applications. The successful implementation of these technologies involve a complex system infrastructure integrating the requirements of transportation, vehicle checkout and health management, and communication systems without compromise to systems reliability and performance. The resources that must be invoked to accomplish these tasks include remote ground operations and control, built-in system fault management and control, and intelligent robotics. To ensure long-term evolution and integration of new validated technologies over the lifetime of the vehicle, system interfaces must also be addressed and integrated into the overall system interface requirements. An approach for defining and evaluating the system infrastructures including the testbed currently being used to support the on-going evaluations for the evolutionary Space Station Freedom Data Management System is presented and discussed. Intelligent system technologies discussed include artificial intelligence (real-time replanning and scheduling), high performance computational elements (parallel processors, photonic processors, and neural networks), real-time fault management and control, and system software development tools for rapid prototyping capabilities.

  16. [X-33 Systems

    Science.gov (United States)

    1999-01-01

    Lockheed Martin Skunk Works has compiled an Annual Performance Report of the X-33/RLV Program. This report consists of individual reports from all industry team members, as well as NASA team centers. This portion of the report is comprised of a status report of Allied-Signal Aerospace's contribution to the program. The following is a summary of the work reviewed under their portion of the agreement: (1) Communication Systems; (2) Environmental Control Systems- Active Thermal Control System (ATCS), Purge and Vent System, Hydrogen Detection System (HDS), Avionics Bay Inerting System (ABIS), and Flush Air Data System (FADS); (2) Landing Systems; (3) Power Management and Generation Systems; (4) Flight Control Actuation System (FCAS)- Electric Power Control & Distribution System (EPCDS), and Battery Power System (BPS); and (5) Vehicle Management Systems (VMS)- VMS Hardware, VMS Software Development Activities, and System Integration Laboratory (SIL).

  17. Linking Political Systems and War Systems

    DEFF Research Database (Denmark)

    Harste, Gorm

    2009-01-01

    Decisive parts of the Western political system have demonstrated a seemingly surprising misinterpretation of military might. As Madelaine Albright has suggested, the mighty perceived themselves as "almighty". Political power seems to have invested in instrumental coercive power relations and found...... military coercion to be the appropriate mean. Using the system theory and the theory of systemic risks displayed by the German sociologist Niklas Luhmann the article demonstrates how military systems due to their own autonomy and autopoiesis do not fit into the idea of political government. The...... Clausewitzian ideal of a political system that could continue its power games by means of war was moderated by Clausewitz' own analysis of "friction". How can a political system be so blind towards the possibilities of another system? What are the risks of systemic blind spots? The argument of the paper...

  18. Immune System as a Sensory System

    OpenAIRE

    Dozmorov, Igor M.; Dresser, D.

    2010-01-01

    As suggested by the well-known gestalt concept the immune system can be regarded as an integrated complex system, the functioning of which cannot be fully characterized by the behavior of its constituent elements. Similar approaches to the immune system in particular and sensory systems in general allows one to discern similarities and differences in the process of distinguishing informative patterns in an otherwise random background, thus initiating an appropriate and adequate response. This...

  19. Operating System Performance Analyzer for Embedded Systems

    OpenAIRE

    Shahzada Khayyam Nisar; Maqsood Ahmed; Huma Ayub; Iram Baig

    2011-01-01

    RTOS provides a number of services to an embedded system designs such as case management, memory management, and Resource Management to build a program. Choosing the best OS for an embedded system is based on the available OS for system designers and their previous knowledge and experience. This can cause an imbalance between the OS and embedded systems. RTOS performance analysis is critical in the design and integration of embedded software to ensure that limits the application meet at runti...

  20. Intrusion Detection System: Security Monitoring System

    OpenAIRE

    ShabnamNoorani,; Sharmila Gaikwad Rathod

    2015-01-01

    An intrusion detection system (IDS) is an ad hoc security solution to protect flawed computer systems. It works like a burglar alarm that goes off if someone tampers with or manages to get past other security mechanisms such as authentication mechanisms and firewalls. An Intrusion Detection System (IDS) is a device or a software application that monitors network or system activities for malicious activities or policy violations and produces reports to a management station.Intrusio...

  1. UNMANNED AIRCRAFT SYSTEMS AS COMPLEX MULTISTRUCTURAL SYSTEM

    Directory of Open Access Journals (Sweden)

    A. S. Abufanas

    2015-08-01

    Full Text Available The principles of constructing mathematical models of unmanned aircraft systems as complex systems consisting of a plurality ofsubsystems, each of which is considered as a system. In this case, the relationship between the subsystems are described by equations based on the topological graph theory, and for the preparation of component equations describing the dynamics of the subsystems is proposed to use differential equations discontinuous type based on systems theory of random structure.

  2. Game Information System

    OpenAIRE

    Spits Warnars

    2010-01-01

    In this Information system age many organizations consider information system as their weapon to compete or gain competitive advantage or give the best services for non profit organizations. Game Information System as combining Information System and game is breakthrough to achieve organizations' performance. The Game Information System will run the Information System with game and how game can be implemented to run the Information System. Game is not only for fun and entertainment, but will ...

  3. Designing information systems

    CERN Document Server

    Blethyn, Stanley G

    2014-01-01

    Designing Information Systems focuses on the processes, methodologies, and approaches involved in designing information systems. The book first describes systems, management and control, and how to design information systems. Discussions focus on documents produced from the functional construction function, users, operators, analysts, programmers and others, process management and control, levels of management, open systems, design of management information systems, and business system description, partitioning, and leveling. The text then takes a look at functional specification and functiona

  4. Instrumentation control system

    International Nuclear Information System (INIS)

    This book explains instrumentation control system, which mentions summary, basic theory, kinds, control device, and design of each instrumentation system. The contents of this book are introduction of instrumentation system, temperature detector, pressure sensor, flow detector, level detector, ingredient detector, signal convert and transmission, instructions, record and control of instrumentation system, PID controller control valve of instrumentation system, instrumentation equipment of water system, instrumentation facility of thermal power plant, examples of advance instrumentation facility and install and design of instrumentation system.

  5. Expert Systems for auditing management information systems

    Directory of Open Access Journals (Sweden)

    Gheroghe Popescu

    2007-05-01

    Full Text Available Expert systems are built with the help of: specialised programming languages or expert system generators (shell. But this structure was reached after tens of years of work and research, because expert systems are nothing but pragmatic capitalisation of the results of research carried out in artificial intelligence and theory of knowledge.

  6. System Design of the SWRL Financial System.

    Science.gov (United States)

    Ikeda, Masumi

    To produce various management and accounting reports in order to maintain control of SWRL (Southwest Regional Laboratory) operational and financial activities, a computer-based SWRL financial system was developed. The system design is outlined, and various types of system inputs described. The kinds of management and accounting reports generated…

  7. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering o

  8. Optical system defect propagation in ABCD systems

    DEFF Research Database (Denmark)

    McKinley, W.G.; Yura, H.T.; Hanson, Steen Grüner

    1988-01-01

    We describe how optical system defects (tilt/jitter, decenter, and despace) propagate through an arbitrary paraxial optical system that can be described by an ABCD ray transfer matrix. A pedagogical example is given that demonstrates the effect of alignment errors on a typical optical system...

  9. Information Systems: Towards a System of Information Systems

    OpenAIRE

    Saleh, Majd; Abel, Marie-Helene

    2015-01-01

    International audience Information Systems are viewed as a set of services creating a workflow of information directed to specific groups and members. This allows individuals to share ideas and their talents with other members. In such manner , tasks can be carried out both efficiently and effectively. Due to the nature of Information Systems that revolves around creating information useful to users , and in some higher forms of Information Systems creating knowledge , management of inform...

  10. Potentiation of mitomycin C and porfiromycin antitumor activity in solid tumor models by recombinant human interleukin 1 alpha.

    Science.gov (United States)

    Braunschweiger, P G; Jones, S A; Johnson, C S; Furmanski, P

    1991-10-15

    The time- and dose-dependent effects of recombinant human interleukin 1 alpha (IL-1 alpha) on the antitumor activity of mitomycin C (MMC) and porfiromycin (PORF) were studied in RIF-1 and Panc02 solid tumor model systems. IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo. IL-1 alpha chemosensitization was highly schedule dependent, and the most efficacious schedules produced dose-modifying factors of 3.6 and 5.1 for MMC and PORF, respectively. More than additive clonogenic cell kill after IL-1 alpha-chemotherapy combinations reflected increased cellular sensitivity to MMC and PORF. The combinations also produced marked decreases in the yield of viable tumor cells, suggesting that the bioreductive drugs may have also potentiated the microvascular injury and ischemia produced by IL-1 alpha. Dexamethasone inhibited and ketoconazole, an inhibitor of corticosterone biosynthesis, enhanced IL-1 alpha-mediated chemosensitization in these models. IL-1 alpha mediated chemosensitization to MMC, and PORF was also demonstrated by tumor growth inhibition in the RIF-1 model and increased survival of mice in the spontaneously metastasizing Panc02 system. Chemosensitization of bone marrow spleen colony-forming units was not seen. IL-1 alpha (1000 units/ml) had no effect on MMC and PORF cytotoxicity in RIF-1 and PORF cell lines in vitro. The results indicate that the tumor-specific IL-1 alpha-induced pathophysiologies can sensitize solid tumors to agents which are preferentially activated, retained, and cytotoxic to cells under hypoxic conditions. Our results suggest that strategies combining bioreductively activated hypoxic cell cytotoxins and biological agents might offer efficacious alternatives or adjuvants to conventional combination approaches. PMID:1913664

  11. Psychology of system design

    CERN Document Server

    Meister, D

    2014-01-01

    This is a book about systems, including: systems in which humans control machines; systems in which humans interact with humans and the machine component is relatively unimportant; systems which are heavily computerized and those that are not; and governmental, industrial, military and social systems. The book deals with both traditional systems like farming, fishing and the military, and with systems just now tentatively emerging, like the expert and the interactive computer system. The emphasis is on the system concept and its implications for analysis, design and evaluation of these many di

  12. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  13. Operating System Security

    CERN Document Server

    Jaeger, Trent

    2008-01-01

    Operating systems provide the fundamental mechanisms for securing computer processing. Since the 1960s, operating systems designers have explored how to build "secure" operating systems - operating systems whose mechanisms protect the system against a motivated adversary. Recently, the importance of ensuring such security has become a mainstream issue for all operating systems. In this book, we examine past research that outlines the requirements for a secure operating system and research that implements example systems that aim for such requirements. For system designs that aimed to

  14. Lighting system with thermal management system

    Science.gov (United States)

    Arik, Mehmet; Weaver, Stanton; Stecher, Thomas; Seeley, Charles; Kuenzler, Glenn; Wolfe, Jr., Charles; Utturkar, Yogen; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2013-05-07

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  15. Systems Intelligence Inventory

    Science.gov (United States)

    Törmänen, Juha; Hämäläinen, Raimo P.; Saarinen, Esa

    2016-01-01

    Purpose: Systems intelligence (SI) (Saarinen and Hämäläinen, 2004) is a construct defined as a person's ability to act intelligently within complex systems involving interaction and feedback. SI relates to our ability to act in systems and reason about systems to adaptively carry out productive actions within and with respect to systems such as…

  16. MEA vacuum system

    International Nuclear Information System (INIS)

    This report describes construction and operation of the MEA vacuum system of NIKHEF (Netherlands). First, the klystron vacuum system, beam transport system, diode pump and a triode pump are described. Next, the isolation valve and the fast valves of the vacuum system are considered. Measuring instruments, vacuum system commands and messages of failures are treated in the last chapter. (G.J.P.)

  17. Intelligent test integration system

    Science.gov (United States)

    Sztipanovits, J.; Padalkar, S.; Rodriguez-Moscoso, J.; Kawamura, K.; Purves, B.; Williams, R.; Biglari, H.

    1988-01-01

    A new test technology is described which was developed for space system integration. The ultimate purpose of the system is to support the automatic generation of test systems in real time, distributed computing environments. The Intelligent Test Integration System (ITIS) is a knowledge based layer above the traditional test system components which can generate complex test configurations from the specification of test scenarios.

  18. Collaborative Systems Testing

    Science.gov (United States)

    Pocatilu, Paul; Ciurea, Cristian

    2009-01-01

    Collaborative systems are widely used today in various activity fields. Their complexity is high and the development involves numerous resources and costs. Testing collaborative systems has a very important role for the systems' success. In this paper we present taxonomy of collaborative systems. The collaborative systems are classified in many…

  19. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  20. Manned systems technology discipline

    Science.gov (United States)

    Bretoi, Remus

    1990-01-01

    Viewgraphs on manned systems technology discipline for Space Station Freedom are presented. Topics covered include: crew-systems interfaces and interactions; crew training; on-board systems maintenance and support; habitability and environment; and computational human factors.

  1. TWRSview system requirements specification

    International Nuclear Information System (INIS)

    This document provides the system requirements specification for the TWRSview software system. The TWRSview software system is being developed to integrate electronic data supporting the development of the TWRS technical baseline

  2. for hybrid dynamical systems

    Directory of Open Access Journals (Sweden)

    Wassim M. Haddad

    2001-01-01

    Full Text Available In this paper we develop a unified dynamical systems framework for a general class of systems possessing left-continuous flows; that is, left-continuous dynamical systems. These systems are shown to generalize virtually all existing notions of dynamical systems and include hybrid, impulsive, and switching dynamical systems as special cases. Furthermore, we generalize dissipativity, passivity, and nonexpansivity theory to left-continuous dynamical systems. Specifically, the classical concepts of system storage functions and supply rates are extended to left-continuous dynamical systems providing a generalized hybrid system energy interpretation in terms of stored energy, dissipated energy over the continuous-time dynamics, and dissipated energy over the resetting events. Finally, the generalized dissipativity notions are used to develop general stability criteria for feedback interconnections of left-continuous dynamical systems. These results generalize the positivity and small gain theorems to the case of left-continuous, hybrid, and impulsive dynamical systems.

  3. Immune System Involvement

    Science.gov (United States)

    ... to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  4. Immune System Quiz

    Science.gov (United States)

    ... Here's Help White House Lunch Recipes Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A Text Size How much do you know about your immune system? Find out by taking this quiz! View Survey ...

  5. Female Reproductive System

    Science.gov (United States)

    ... Things to Know About Zika & Pregnancy Female Reproductive System KidsHealth > For Parents > Female Reproductive System Print A ... or sperm. continue Components of the Female Reproductive System Unlike the male, the human female has a ...

  6. Brain and Nervous System

    Science.gov (United States)

    ... to Know About Zika & Pregnancy Brain and Nervous System KidsHealth > For Parents > Brain and Nervous System Print ... is quite the juggler. Anatomy of the Nervous System If you think of the brain as a ...

  7. Lungs and Respiratory System

    Science.gov (United States)

    ... to Know About Zika & Pregnancy Lungs and Respiratory System KidsHealth > For Parents > Lungs and Respiratory System Print ... have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't happen ...

  8. Photovoltaic systems test facility

    Science.gov (United States)

    1979-01-01

    Facility provides broad and flexible capability for evaluating photovoltaic systems and design concepts. As 'breadboard' system, it can be used to check out complete systems, subsystems, and components before installation in actual service.

  9. Bridge Management Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper bridge management systems are discussed with special emphasis on management systems for reinforced concrete bridges. Management systems for prestressed concrete bridges, steel bridges, or composite bridges can be developed in a similar way....

  10. Autonomic Nervous System Disorders

    Science.gov (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  11. Calo trigger acquisition system

    CERN Multimedia

    Franchini, Matteo

    2016-01-01

    Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

  12. Battery systems engineering

    CERN Document Server

    Rahn, Christopher D

    2012-01-01

    A complete all-in-one reference on the important interdisciplinary topic of Battery Systems Engineering Focusing on the interdisciplinary area of battery systems engineering, this book provides the background, models, solution techniques, and systems theory that are necessary for the development of advanced battery management systems. It covers the topic from the perspective of basic electrochemistry as well as systems engineering topics and provides a basis for battery modeling for system engineering of electric and hybrid electric vehicle platforms. This original

  13. Gas transfer system

    International Nuclear Information System (INIS)

    The state of work on the Vivitron gas transfer system and the system functions are summarized. The system has to: evacuate the Vivitron reservoir; transfer gas from storage tanks to the Vivitron; recirculate gas during operation; transfer gas from the Vivitron to storage tanks; and assure air input. The system is now being installed. Leak alarms are given by SF6 detectors, which set off a system of forced ventilation. Another system continuously monitors the amount of SF6 in the tanks

  14. Small test SDHW systems

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian

    1999-01-01

    Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

  15. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  16. Cognitive Medical Multiagent Systems

    Directory of Open Access Journals (Sweden)

    Barna Iantovics

    2010-01-01

    Full Text Available The development of efficient and flexible agent-based medical diagnosis systems represents a recent research direction. Medical multiagent systems may improve the efficiency of traditionally developed medical computational systems, like the medical expert systems. In our previous researches, a novel cooperative medical diagnosis multiagent system called CMDS (Contract Net Based Medical Diagnosis System was proposed. CMDS system can solve flexibly a large variety of medical diagnosis problems. This paper analyses the increased intelligence of the CMDS system, which motivates its use for different medical problem’s solving.

  17. RECURSIVE SYSTEM IDENTIFICATION

    Institute of Scientific and Technical Information of China (English)

    Han-Fu Chen

    2009-01-01

    Most of existing methods in system identification with possible exception of those for linear systems are off-line in nature, and hence are nonrecursive.This paper demonstrates the recent progress in recursive system identification.The recursive identifi-cation algorithms are presented not only for linear systems (multivariate ARMAX systems) but also for nonlinear systems such as the Hammerstein and Wiener systems, and the non-linear ARX systems.The estimates generated by the algorithms are online updated and converge a.s.to the true values as time tends to infinity.

  18. Control system design method

    Science.gov (United States)

    Wilson, David G.; Robinett, III, Rush D.

    2012-02-21

    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  19. Aeronautical Information System

    Data.gov (United States)

    Department of Transportation — The Aeronautical Information System (AIS) is a leased weather automated system that provides a means of collecting and distributing aeronautical weather information...

  20. Credit Management System

    Data.gov (United States)

    US Agency for International Development — Credit Management System. Outsourced Internet-based application. CMS stores and processes data related to USAID credit programs. The system provides information...

  1. Airports Geographic Information System

    Data.gov (United States)

    Department of Transportation — The Airports Geographic Information System maintains the airport and aeronautical data required to meet the demands of the Next Generation National Airspace System....

  2. Epilogue: Systems Approaches and Systems Practice

    Science.gov (United States)

    Reynolds, Martin; Holwell, Sue

    Each of the five systems approaches discussed in this volume: system dynamics (SD), the viable systems model (VSM), strategic options development and analysis (SODA), soft systems methodology (SSM) and critical systems heuristics (CSH) has a pedigree. Not in the sense of the sometimes absurd spectacle of animals paraded at dog shows. Rather, their pedigree derives from their systems foundations, their capacity to evolve and their flexibility in use. None of the five approaches has developed out of use in restricted and controlled contexts of either low or high levels of complicatedness. Neither has any one of them evolved as a consequence of being applied only to situations with either presumed stakeholder agreement on purpose, or courteous disagreement amongst stakeholders, or stakeholder coercion. The compilation is not a celebration of abstract ‘methodologies', but of theoretically robust approaches that have a genuine pedigree in practice.

  3. Integrated Systems Health Management for Intelligent Systems

    Science.gov (United States)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  4. Expert system modeling of a vision system

    Science.gov (United States)

    Reihani, Kamran; Thompson, Wiley E.

    1992-05-01

    The proposed artificial intelligence-based vision model incorporates natural recognition processes depicted as a visual pyramid and hierarchical representation of objects in the database. The visual pyramid, with based and apex representing pixels and image, respectively, is used as an analogy for a vision system. This paper provides an overview of recognition activities and states in the framework of an inductive model. Also, it presents a natural vision system and a counterpart expert system model that incorporates the described operations.

  5. Test System Impact on System Availability

    DEFF Research Database (Denmark)

    Pau, L. F.

    1987-01-01

    The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance of the...... system subject to monitoring and test. A time-dependent Markov model is presented, and applied in three cases, with examples of numerical results provided for preventive maintenance decisions, design of an automatic test system, buffer testing in computers, and data communications....

  6. Risk-based systems configuration monitoring system

    International Nuclear Information System (INIS)

    The paper presents the work done in the frame of the Research Contract No. 6993/RB - ''Risk based systems configuration monitoring system'' part of the coordinated programme ''Development of safety related expert systems''. The aim of this contract was to develop the prototype of an expert system based on PSA technology to be use for controlling the plant systems configuration taking into account the risk. The software prototype implementation was done using Visual Basic language, under Windows environment. The implemented prototype has the following features: store data/knowledge about components and human factor; store data/knowledge about the plant system and systems components, providing facilities to modify/search data/knowledge, based on the general knowledge; generate the logic model of the system; provide minimal cut sets and path sets determination; provide information to be used by the user for configuration risk management; provide user friendly interface (graphical interface under windows). The prototype can be independently used as an operator support system or for other on-line or off-line applications. After the testing of the prototype, some of the conclusions are: the developed software can be one of the most useful tools to be used by designers, PSA analysts, operators and regulatory for evaluation of the safety and reliability of the plant systems; the structure of the General Knowledge Base included into the prototype offers the possibility to combine knowledge introduced by different users. This feature can be the basis for the development of a knowledge acquisition system; the developed software and methodology can offer the basis for the risk-based data collection system development. (author). 12 refs, 30 figs

  7. Engine Auxiliary System Guideline: Cooling Systems

    OpenAIRE

    Kela, Suvi

    2015-01-01

    The thesis was done for Wärtsilä Technical Services organization. The assignment was to consolidate a guideline for cooling systems as an engine auxiliary system covering the Wärtsilä 4-stroke engines currently in production. The guideline was to include information considering both marine and power plants installations. The sources of information were internal documentation from Wärtsilä, literature review and discussions with Wärtsilä cooling system experts. The guideline includes informati...

  8. Forming different planetary systems

    Institute of Scientific and Technical Information of China (English)

    Ji-Lin Zhou; Ji-Wei Xie; Hui-Gen Liu; Hui Zhang; Yi-Sui Sun

    2012-01-01

    With the increasing number of detected exoplanet samples,the statistical properties of planetary systems have become much clearer.In this review,we summarize the major statistical results that have been revealed mainly by radial velocity and transiting observations,and try to interpret them within the scope of the classical core-accretion scenario of planet formation,especially in the formation of different orbital architectures for planetary systems around main sequence stars.Based on the different possible formation routes for different planet systems,we tentatively classify them into three major catalogs:hot Jupiter systems,standard systems and distant giant planet systems.The standard systems can be further categorized into three sub-types under different circumstances:solar-like systems,hot Super-Earth systems,and subgiant planet systems.We also review the theory of planet detection and formation in binary systems as well as planets in star clusters.

  9. Precision digital control systems

    Science.gov (United States)

    Vyskub, V. G.; Rozov, B. S.; Savelev, V. I.

    This book is concerned with the characteristics of digital control systems of great accuracy. A classification of such systems is considered along with aspects of stabilization, programmable control applications, digital tracking systems and servomechanisms, and precision systems for the control of a scanning laser beam. Other topics explored are related to systems of proportional control, linear devices and methods for increasing precision, approaches for further decreasing the response time in the case of high-speed operation, possibilities for the implementation of a logical control law, and methods for the study of precision digital control systems. A description is presented of precision automatic control systems which make use of electronic computers, taking into account the existing possibilities for an employment of computers in automatic control systems, approaches and studies required for including a computer in such control systems, and an analysis of the structure of automatic control systems with computers. Attention is also given to functional blocks in the considered systems.

  10. L-system fractals

    CERN Document Server

    Mishra, Jibitesh

    2007-01-01

    The book covers all the fundamental aspects of generating fractals through L-system. Also it provides insight to various researches in this area for generating fractals through L-system approach & estimating dimensions. Also it discusses various applications of L-system fractals. Key Features: - Fractals generated from L-System including hybrid fractals - Dimension calculation for L-system fractals - Images & codes for L-system fractals - Research directions in the area of L-system fractals - Usage of various freely downloadable tools in this area - Fractals generated from L-System including hybrid fractals- Dimension calculation for L-system fractals- Images & codes for L-system fractals- Research directions in the area of L-system fractals- Usage of various freely downloadable tools in this area

  11. Hot Spot Removal System: System description

    International Nuclear Information System (INIS)

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System''s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section

  12. Power system protection 2 systems and methods

    CERN Document Server

    1995-01-01

    The worldwide growth in demand for electricity has forced the pace of developments in electrical power system design to meet consumer needs for reliable, secure and cheap supplies. Power system protection, as a technology essential to high quality supply, is widely recognised as a specialism of growing and often critical importance, in which power system needs and technological progress have combined to result in rapid developments in policy and practice in recent years. In the United Kingdom, the need for appropriate training in power system protection was recognised in the early 1960s with t

  13. Hot Spot Removal System: System description

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

  14. Recommender Systems for Social Tagging Systems

    CERN Document Server

    Balby Marinho, Leandro

    2012-01-01

    Social Tagging Systems are web applications in which users upload resources (e.g., bookmarks, videos, photos, etc.) and annotate it with a list of freely chosen keywords called tags. This is a grassroots approach to organize a site and help users to find the resources they are interested in. Social tagging systems are open and inherently social; features that have been proven to encourage participation. However, with the large popularity of these systems and the increasing amount of user-contributed content, information overload rapidly becomes an issue. Recommender Systems are well known appl

  15. Information Systems Security Audit

    OpenAIRE

    Gheorghe Popescu; Veronica Adriana Popescu; Cristina Raluca Popescu

    2007-01-01

    The article covers:Defining an information system; benefits obtained by introducing new information technologies; IT management;Defining prerequisites, analysis, design, implementation of IS; Information security management system; aspects regarding IS security policy; Conceptual model of a security system; Auditing information security systems and network infrastructure security.

  16. Design an Information System

    OpenAIRE

    Koch, Libor

    2016-01-01

    Main object of this thesis is design information system for warehouse management for Fi & Ho Trading Company, which will be accessible through web. Warehouse will be based on portal technology and connected with E-shop. In this thesis will be described elements of information system, resources used for realization, processes coverage by information system and complex evaluation of this information system.

  17. Information Systems Security Audit

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2007-12-01

    Full Text Available The article covers:Defining an information system; benefits obtained by introducing new information technologies; IT management;Defining prerequisites, analysis, design, implementation of IS; Information security management system; aspects regarding IS security policy; Conceptual model of a security system; Auditing information security systems and network infrastructure security.

  18. Microsphere insulation systems

    Science.gov (United States)

    Allen, Mark S. (Inventor); Willen, Gary S. (Inventor); Mohling, Robert A. (Inventor)

    2005-01-01

    A new insulation system is provided that contains microspheres. This insulation system can be used to provide insulated panels and clamshells, and to insulate annular spaces around objects used to transfer, store, or transport cryogens and other temperature-sensitive materials. This insulation system provides better performance with reduced maintenance than current insulation systems.

  19. CDMA systems capacity engineering

    CERN Document Server

    Kim, Kiseon

    2004-01-01

    This new hands-on resource tackles capacity planning and engineering issues that are crucial to optimizing wireless communication systems performance. Going beyond the system physical level and investigating CDMA system capacity at the service level, this volume is the single-source for engineering and analyzing systems capacity and resources.

  20. Hybrid intelligent engineering systems

    CERN Document Server

    Jain, L C; Adelaide, Australia University of

    1997-01-01

    This book on hybrid intelligent engineering systems is unique, in the sense that it presents the integration of expert systems, neural networks, fuzzy systems, genetic algorithms, and chaos engineering. It shows that these new techniques enhance the capabilities of one another. A number of hybrid systems for solving engineering problems are presented.

  1. Medical imaging systems

    Science.gov (United States)

    Frangioni, John V

    2013-06-25

    A medical imaging system provides simultaneous rendering of visible light and diagnostic or functional images. The system may be portable, and may include adapters for connecting various light sources and cameras in open surgical environments or laparascopic or endoscopic environments. A user interface provides control over the functionality of the integrated imaging system. In one embodiment, the system provides a tool for surgical pathology.

  2. Combinatorial Hybrid Systems

    DEFF Research Database (Denmark)

    Larsen, Jesper Abildgaard; Wisniewski, Rafal; Grunnet, Jacob Deleuran

    2008-01-01

    As initially suggested by E. Sontag, it is possible to approximate an arbitrary nonlinear system by a set of piecewise linear systems. In this work we concentrate on how to control a system given by a set of piecewise linear systems defined on simplices. By using the results of L. Habets and J. v...

  3. Modelling of Information Systems

    OpenAIRE

    Hausman, Halina

    1982-01-01

    The article discusses selected problems in methodology of designing comprehensive information systems. Main emphasis has been laid on modelling of information systems for companies. Presentation of bases for construction of models and description of their main types provides a basis allowing the author to draw conclusions concerning their application. Modelling of information systems is treated as one of stages in designing information systems.

  4. On generalized Volterra systems

    Science.gov (United States)

    Charalambides, S. A.; Damianou, P. A.; Evripidou, C. A.

    2015-01-01

    We construct a large family of evidently integrable Hamiltonian systems which are generalizations of the KM system. The algorithm uses the root system of a complex simple Lie algebra. The Hamiltonian vector field is homogeneous cubic but in a number of cases a simple change of variables transforms such a system to a quadratic Lotka-Volterra system. We present in detail all such systems in the cases of A3, A4 and we also give some examples from higher dimensions. We classify all possible Lotka-Volterra systems that arise via this algorithm in the An case.

  5. System Elements Heterogeneity

    Directory of Open Access Journals (Sweden)

    Stanislav A. Kuja

    2013-01-01

    Full Text Available The paper deals with the features of the systematic approach development, shows that the systematic approach lacks the definition of system elements divisibility. This fact simplifies the system description. The article shows that, depending on the selection of the criterion of divisibility, different types of elements with different properties are got. Depending on the selection of the criterion of divisibility, the system structure becomes multidimensional. The paper recommends to indicate the criterion of the system divisibility during the systems research. It increases the certainty of the description of a complex system and characterizes the system elements.

  6. The Solar System as an Exoplanetary System

    CERN Document Server

    Martin, Rebecca G

    2015-01-01

    With the availability of considerably more data, we revisit the question of how special our Solar System is, compared to observed exoplanetary systems. To this goal, we employ a mathematical transformation that allows for a meaningful, statistical comparison. We find that the masses and densities of the giant planets in our Solar System are very typical, as is the age of the Solar System. While the orbital location of Jupiter is somewhat of an outlier, this is most likely due to strong selection effects towards short-period planets. The eccentricities of the planets in our Solar System are relatively small compared to those in observed exosolar systems, but still consistent with the expectations for an 8-planet system (and could, in addition, reflect a selection bias towards high-eccentricity planets). The two characteristics of the Solar System that we find to be most special are the lack of super-Earths with orbital periods of days to months and the general lack of planets inside of the orbital radius of Me...

  7. Efficient Evaluation System for Learning Management Systems

    Science.gov (United States)

    Cavus, Nadire

    2009-01-01

    A learning management system (LMS) provides the platform for web-based learning environment by enabling the management, delivery, tracking of learning, testing, communication, registration process and scheduling. There are many LMS systems on the market that can be obtained for free or through payment. It has now become an important task to choose…

  8. Beam alignment system for laser welding system

    International Nuclear Information System (INIS)

    The patent describes a beam alignment system for laser welding work pieces, such as fuel rod grids for nuclear fuel assemblies. The apparatus for performing various laser-machining comprises a beam alignment system including alignment target means, as well as means for emitting, directing and focusing the laser beam. (U.K.)

  9. EPICS system: system structure and user interface

    International Nuclear Information System (INIS)

    This paper present the user's view of and the general organization of the EPICS control system at Fermilab. Various subsystems of the EPICS control system are discussed. These include the user command language, software protection, the device database, remote computer interfaces, and several application utilities. This paper is related to two other papers on EPICS: an overview paper and a detailed implementation paper

  10. Performance, Performance System, and High Performance System

    Science.gov (United States)

    Jang, Hwan Young

    2009-01-01

    This article proposes needed transitions in the field of human performance technology. The following three transitions are discussed: transitioning from training to performance, transitioning from performance to performance system, and transitioning from learning organization to high performance system. A proposed framework that comprises…

  11. Local hospital systems: forerunners of regional systems?

    Science.gov (United States)

    Luke, R D

    1992-01-01

    Over the past several decades, the hospital industry has been undergoing a major organizational change that has until now been little examined. Local hospital systems (LHSs) are combinations of two or more hospitals that are in the same company and located in or around the same metropolitan areas in this country. This article presents the first detailed examination of the 402 such systems that have been identified to date. LHSs offer great potential for achieving the cost, quality, and access benefits that are often attributable to regional systems. The degree to which LHSs have attained some basic structural features expected of regional systems are examined. Differences are compared within ownership categories. Issues and challenges facing leaders in the field, should they hope to achieve the potential of regional systems, are discussed. PMID:10122669

  12. Intrusion Detection System: Security Monitoring System

    Directory of Open Access Journals (Sweden)

    ShabnamNoorani,

    2015-10-01

    Full Text Available An intrusion detection system (IDS is an ad hoc security solution to protect flawed computer systems. It works like a burglar alarm that goes off if someone tampers with or manages to get past other security mechanisms such as authentication mechanisms and firewalls. An Intrusion Detection System (IDS is a device or a software application that monitors network or system activities for malicious activities or policy violations and produces reports to a management station.Intrusion Detection System (IDS has been used as a vital instrument in defending the network from this malicious or abnormal activity..In this paper we are comparing host based and network based IDS and various types of attacks possible on IDS.

  13. Systems Thinking About Purpose

    OpenAIRE

    Gaye Lewis

    2002-01-01

    This paper argues that in the context of human activity systems, the concept of purpose is critically important and that giving purpose a central role in the development and management of human activity systems can lead to more flexible, effective and autonomous systems. The systems thinking literature is reviewed in order to consolidate and assess current thinking about purpose. The importance of intrinsic purpose is highlighted. Implications for practice in terms of information systems desi...

  14. Systems interface biology

    OpenAIRE

    Francis J Doyle; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Henc...

  15. Combustion gas scrubbing system

    Energy Technology Data Exchange (ETDEWEB)

    Dahlstrom, D.A.; Ellison, W.; Wilhelm, J.H.

    1979-04-03

    In a cooperative combination of two scrubbing systems, the first scrubbing system operates upon combustion gases with an aqueous solution to remove hydrogen chloride gas and other chlorine components. The second scrubbing system subsequently operates upon the combustion gases with a sodium-base solution to absorb sulfur oxides. The products of the two scrubbing systems are treated in combination to form a material for disposal and to generate the aqueous scrubbing solution for the chloride scrubbing system.

  16. Sustainable Water Systems

    OpenAIRE

    Miklas Scholz

    2013-01-01

    Sustainable water systems often comprise complex combinations of traditional and new system components that mimic natural processes. These green systems aim to protect public health and safety, and restore natural and human landscapes. Green infrastructure elements such as most sustainable drainage systems trap storm water but may contaminate groundwater. There is a need to summarize recent trends in sustainable water systems management in a focused document. The aim of this special issue is ...

  17. The control system

    International Nuclear Information System (INIS)

    The present control system has matured both in terms of age and capacity. Thus a new system based on a local area network (LAN) is being developed. A pilot project has been started but, owing to difficulties encountered with the present operating system used with the microprocessors, it has become necessary to reconsider the choice of operating system. A recently-released multi-tasking operating system that runs on the existing hardware has been chosen. 1 fig

  18. CRM Systems Integration

    OpenAIRE

    Vidmar, David

    2011-01-01

    Company management policy, that includes CRM (Customer Relationship Management) that is implemented with CRM computer system is rapidly growing in importance in Slovenia and worldwide. But just implementing CRM system is not enough if we want system that is well accepted and used daily. Integration with other systems in company is very important when implementing CRM system. Four types of integration are defined and they are usage, replication, synhronization and business process integrati...

  19. Discourses of systems engineering

    OpenAIRE

    Akeel, U. U.; Bell, S J

    2013-01-01

    Systems engineering is unique in being characterised by its methods rather than its artefacts. Consequently, the scope of systems engineering is difficult to define. While some systems engineers contend that systems engineering is capable of addressing sociotechnical problems, including climate change and terrorism, others argue that it is strictly a technical field. The paper presents the results of a discourse analysis of systems engineering textbooks, journal articles, and a...

  20. Electronic payment systems

    OpenAIRE

    Malakjan, Stiv

    2010-01-01

    This thesis charts the evolution of Electronic payment systems and e-commerce. The goal is to create a complex picture about circumstances and causes that led to development and creation of new payment systems. The first part describes the evolution of money and payment systems that appeared during history. The second part focuses on e-money, electronic payment systems and the participants that are involved in payment processing trough this systems. It also explores the history of credit card...

  1. Multiprocessor data acquisition system

    International Nuclear Information System (INIS)

    A multiprocessor data acquisition system has been built to replace the single processor systems at the Intense Pulsed Neutron Source (IPNS) at Argonne National Laboratory. The multiprocessor system was needed to accommodate the higher data rates at IPNS brought about by improvements in the source and changes in instrument configurations. This paper describes the hardware configuration of the system and the method of task sharing and compares results to the single processor system

  2. Photovoltaic systems and applications

    Energy Technology Data Exchange (ETDEWEB)

    1982-01-01

    Abstracts are given of presentations given at a project review meeting held at Albuquerque, NM. The proceedings cover the past accomplishments and current activities of the Photovoltaic Systems Research, Balance-of-System Technology Development and System Application Experiments Projects at Sandia National Laboratories. The status of intermediate system application experiments and residential system analysis is emphasized. Some discussion of the future of the Photovoltaic Program in general, and the Sandia projects in particular is also presented.

  3. Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

    Directory of Open Access Journals (Sweden)

    Mahoney Noreen

    2011-05-01

    Full Text Available Abstract Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI. Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ and two mitogen-activated protein kinase (MAPK mutants of A. fumigatus (sakAΔ, mpkCΔ, indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC or fungicidal (MFC

  4. A distribution management system

    Energy Technology Data Exchange (ETDEWEB)

    Verho, P.; Jaerventausta, P.; Kaerenlampi, M.; Paulasaari, H. [Tampere Univ. of Technology (Finland); Partanen, J. [Lappeenranta Univ. of Technology (Finland)

    1996-12-31

    The development of new distribution automation applications is considerably wide nowadays. One of the most interesting areas is the development of a distribution management system (DMS) as an expansion of the traditional SCADA system. At the power transmission level such a system is called an energy management system (EMS). The idea of these expansions is to provide supporting tools for control center operators in system analysis and operation planning. The needed data for new applications is mainly available in some existing systems. Thus the computer systems of utilities must be integrated. The main data source for the new applications in the control center are the AM/FM/GIS (i.e. the network database system), the SCADA, and the customer information system (CIS). The new functions can be embedded in some existing computer system. This means a strong dependency on the vendor of the existing system. An alternative strategy is to develop an independent system which is integrated with other computer systems using well-defined interfaces. The latter approach makes it possible to use the new applications in various computer environments, having only a weak dependency on the vendors of the other systems. In the research project this alternative is preferred and used in developing an independent distribution management system

  5. A System of Systems Approach to the EU Energy System

    Science.gov (United States)

    Jess, Tom; Madani, Kaveh; Mahlooji, Maral; Ristic, Bora

    2016-04-01

    Around the world, measures to prevent dangerous climate change are being adopted and may change energy systems fundamentally. The European Union (EU) is committed to reducing greenhouse gas emission by 20% by 2020 and by 80-95% by 2050. In order to achieve this, EU member states aim to increase the share of renewables in the energy mix to 20% by 2020. This commitment comes as part of a series of other aims, principles, and policies to reform the EU's energy system. Cost-efficiency in the emissions reductions measures as well as strategic goals under the Resource Efficient Europe flagship initiative which would include a more prudent approach to other natural resources such as water and land. Using the "System of Systems Approach", as from Hadian and Madani (2015), energy sources' Relative Aggregate Footprints (RAF) in the EU are evaluated. RAF aggregates across four criteria: carbon footprint, water footprint, land footprint, and economic cost. The four criteria are weighted by resource availability across the EU and for each Member State. This provides an evaluation of the overall resource use efficiency of the EU's energy portfolio and gives insight into the differences in the desirability of energy sources across Member States. Broadly, nuclear, onshore wind, and geothermal are most desirable under equal criteria weights and EU average weighting introduces only small changes in the relative performance of only few technologies. The member state specific weightings show that most countries have similar energy technology preferences. However, the UK deviates most strongly from the average, with an even stronger preference for nuclear and coal. Sweden, Malta and Finland also deviate from the typical preferences indicating the complexity in play in reforming the EU energy system. Reference Hadian S, Madani K (2015) A System of Systems Approach to Energy Sustainability Assessment: Are All Renewables Really Green? Ecological Indicators, 52, 194-206.

  6. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  7. Micro Information Systems

    DEFF Research Database (Denmark)

    Ulslev Pedersen, Rasmus; Kühn Pedersen, Mogens

    2014-01-01

    such as medical and manufacturing. These new sensor applications have implications for information systems (IS) and, the authors visualize this new class of information systems as fractals growing from an established class of systems; namely that of information systems (IS). The identified applications...... and implications are used as an empirical basis for creating a model for these small new information systems. Such sensor systems are called embedded systems in the technical sciences, and the authors want to couple it with general IS. They call the merger of these two important research areas (IS and...... embedded systems) for micro information systems (micro-IS). It is intended as a new research field within IS research. An initial framework model is established, which seeks to capture both the possibilities and constraints of this new paradigm, while looking simultaneously at the fundamental IS and ICT...

  8. Rover waste assay system

    Energy Technology Data Exchange (ETDEWEB)

    Akers, D.W.; Stoots, C.M.; Kraft, N.C.; Marts, D.J. [Idaho National Engineering Lab., Idaho Falls, ID (United States)

    1997-11-01

    The Rover Waste Assay System (RWAS) is a nondestructive assay system designed for the rapid assay of highly-enriched {sup 235}U contaminated piping, tank sections, and debris from the Rover nuclear rocket fuel processing facility at the Idaho Chemical Processing Plant. A scanning system translates a NaI(Tl) detector/collimator system over the structural components where both relative and calibrated measurements for {sup 137}Cs are made. Uranium-235 concentrations are in operation and is sufficiently automated that most functions are performed by the computer system. These functions include system calibration, problem identification, collimator control, data analysis, and reporting. Calibration of the system was done through a combination of measurements on calibration standards and benchmarked modeling. A description of the system is presented along with the methods and uncertainties associated with the calibration and analysis of the system for components from the Rover facility. 4 refs., 2 figs., 4 tabs.

  9. System performance optimization

    International Nuclear Information System (INIS)

    The System Performance Optimization has become an important and difficult field for large scientific computer centres. Important because the centres must satisfy increasing user demands at the lowest possible cost. Difficult because the System Performance Optimization requires a deep understanding of hardware, software and workload. The optimization is a dynamic process depending on the changes in hardware configuration, current level of the operating system and user generated workload. With the increasing complication of the computer system and software, the field for the optimization manoeuvres broadens. The hardware of two manufacturers IBM and CDC is discussed. Four IBM and two CDC operating systems are described. The description concentrates on the organization of the operating systems, the job scheduling and I/O handling. The performance definitions, workload specification and tools for the system stimulation are given. The measurement tools for the System Performance Optimization are described. The results of the measurement and various methods used for the operating system tuning are discussed. (Auth.)

  10. Rover waste assay system

    International Nuclear Information System (INIS)

    The Rover Waste Assay System (RWAS) is a nondestructive assay system designed for the rapid assay of highly-enriched 235U contaminated piping, tank sections, and debris from the Rover nuclear rocket fuel processing facility at the Idaho Chemical Processing Plant. A scanning system translates a NaI(Tl) detector/collimator system over the structural components where both relative and calibrated measurements for 137Cs are made. Uranium-235 concentrations are in operation and is sufficiently automated that most functions are performed by the computer system. These functions include system calibration, problem identification, collimator control, data analysis, and reporting. Calibration of the system was done through a combination of measurements on calibration standards and benchmarked modeling. A description of the system is presented along with the methods and uncertainties associated with the calibration and analysis of the system for components from the Rover facility. 4 refs., 2 figs., 4 tabs

  11. Automatic remote communication system

    International Nuclear Information System (INIS)

    The Upgraded RECOVER (Remote Continual Verification) system is a communication system for remote continual verification of security and safeguards status of nuclear material in principal nuclear facilities. The system is composed of a command center and facility sub-systems. A command center is a mini-computer system to process C/S (Containment and Surveillance) status data. Facility sub-systems consists of OSM (On-site Multiplexer), MU (Monitoring Unit) and C/S sensor. The system uses public telephone network for communication between a command center and facility sub-systems, and it encrypts communication data to prevent falsification and wiretapping by unauthorized persons. This system inherits the design principle of RECOVER system that was tested by IAEA before. We upgraded and expanded its capabilities more than those of RECOVER. The development of this system began in 1983, and it finished in 1987. Performance tests of the system were carried out since 1987. It showed a farely good result with some indications which should need further improvements. The Upgraded RECOVER system provides timely information about the status of C/S systems, which could contribute to the reduction of inspection effort and the improvement of cost performance. (author)

  12. Embedded systems handbook networked embedded systems

    CERN Document Server

    Zurawski, Richard

    2009-01-01

    Considered a standard industry resource, the Embedded Systems Handbook provided researchers and technicians with the authoritative information needed to launch a wealth of diverse applications, including those in automotive electronics, industrial automated systems, and building automation and control. Now a new resource is required to report on current developments and provide a technical reference for those looking to move the field forward yet again. Divided into two volumes to accommodate this growth, the Embedded Systems Handbook, Second Edition presents a comprehensive view on this area

  13. Nonlinearity of colloid systems oxyhydrate systems

    CERN Document Server

    Sucharev, Yuri I

    2008-01-01

    The present monograph is the first systematic study of the non-linear characteristic of gel oxy-hydrate systems involving d- and f- elements. These are the oxyhydrates of rare-earth elements and oxides - hydroxides of d- elements (zirconium, niobium, titanium, etc.) The non-linearity of these gel systems introduces fundamental peculiarities into their structure and, consequently, their properties. The polymer-conformational diversity of energetically congenial gel fragments, which continu-ously transform under the effect of, for instance, system dissipation heat, is central to the au-thor's hy

  14. Expert systems and computer based industrial systems

    International Nuclear Information System (INIS)

    Framentec is the artificial intelligence subsidiary of FRAMATOME. It is involved in expert-system activities of Shells, developments, methodology and software for maintenance (Maintex) and consulting and methodology. Specific applications in the nuclear field are presented. The first is an expert system to assist in the piping support design prototype, the second is an expert system that assists an ultrasonic testing operator in determining the nature of a welding defect and the third is a welding machine diagnosis advisor. Maintex is a software tool to provide assistance in the repair of complex industrial equipment. (author)

  15. System architecture for microprocessor based protection system

    International Nuclear Information System (INIS)

    This paper discusses the architectural design features to be employed by Westinghouse in the application of distributed digital processing techniques to the protection system. While the title of the paper makes specific reference to microprocessors, this is only one (and the newest) of the building blocks which constitutes a distributed digital processing system. The actual system structure (as realized through utilization of the various building blocks) is established through considerations of reliability, licensability, and cost. It is the intent of the paper to address these considerations licenstions as they relate to the architectural design features. (orig.)

  16. Flash evaporator systems test

    Science.gov (United States)

    Dietz, J. B.

    1976-01-01

    A flash evaporator heat rejection system representative of that proposed for the space shuttle orbiter underwent extensive system testing at the NASA Johnson Space Center (JSC) to determine its operational suitability and to establish system performance/operational characteristics for use in the shuttle system. During the tests the evaporator system demonstrated its suitability to meet the shuttle requirements by: (1) efficient operation with 90 to 95% water evaporation efficiency, (2) control of outlet temperature to 40 + or - 2 F for partial heat load operation, (3) stability of control system for rapid changes in Freon inlet temperature, and (4) repeated dormant-to-active device operation without any startup procedures.

  17. Hydraulic Yaw System

    DEFF Research Database (Denmark)

    Stubkier, Søren; Pedersen, Henrik C.; Mørkholt, M.

    system and rotor shaft when utilizing the soft yaw drive concept compared to the original stiff yaw system. The physical demands of the hydraulic yaw system are furthermore examined for a life time of 20 years. Based on the extrapolated loads, the duty cycles show that it is possible to construct...... a hydraulic soft yaw system, which is able to reduce the loads on the wind turbine significantly. A full scale hydraulic yaw test rig is available for experiments and tests. The test rig is presented as well as the system schematics of the hydraulic yaw system....

  18. Concepts, states, and systems

    Science.gov (United States)

    Wolff, Karl Erich

    2000-05-01

    Mathematical System Theory is extended to Conceptual System Theory using Formal Concept Analysis (Wille 1982). States are defined as formal concepts and `points of time' are generalized to `time granules,' interpreted as `pieces' of time needed for the realization of measurements. As a generalization of classical time systems we define conceptual time systems, their state spaces and phase spaces. Time dependent relations among the parts of a conceptual time system are introduced in `relational conceptual time systems.' Applications in psychology and industry, including `conceptual films' are mentioned.

  19. DROWSY DRIVER DETECTION SYSTEM

    OpenAIRE

    Mrs. Smita Jawale; Ms. Pragati Malvadia; Ms. Ashwini Meena

    2016-01-01

    A Drowsy Driver Detection System is an Image processing based system. This system is developed using a non-intrusive machine vision based concepts. In this system, there is a camera that will be continuously monitoring the driver’s face to detect fatigue. In case the driver is detected as fatigue, the system issues an alarm. This system detects drowsiness by checking the amount of time the eyes are closed. The first five consecutive frames of the camera is checked, if the eyes are found...

  20. Microelectronic systems 1 checkbook

    CERN Document Server

    Vears, R E

    2013-01-01

    Microelectronic Systems 1 Checkbook provides coverage of the Business and Technician Education Council level 1 unit in Microelectronic Systems. However, it can be regarded as a basic textbook in microelectronic systems for a much wider range of studies. Each topic considered in the text is presented in a way that assumes the reader has little prior knowledge of electronics. The aim of the book is to provide an introduction to the concept of systems, to differentiate analogue and digital systems, and to describe the nature of microprocessor-controlled systems. An introduction to programming is

  1. Generalized L systems

    Institute of Scientific and Technical Information of China (English)

    陆汝钤; 张文妍

    2002-01-01

    This paper proposes the concept of generalized L systems, GL systems for short, which can describe asynchronized concurrent phenomena. We have proved that the GL systems are proper extensions of the traditional L systems. We have also defined a classification of GL systems and proved a sufficient and necessary condition for the equivalence of two subclasses of GL systems: two quivalent, iff k = j and there exists a common divisor g of all mr and a common divisor h of all ni such that i: mi/g = ni/h.

  2. Electronic system hardening methodology

    International Nuclear Information System (INIS)

    The notion of hardened systems can be found in several applications (nuclear power plants, alarm systems, research installations..). Their development correspond to the functional necessity to take into account a specific radiative environment. The starting point of each hardening study is the definition of the radiative environmental constraints representative of the application. In addition to these external constraints, the specific functional characteristics of each system are considered: control or interface systems in nuclear industry, in-board control systems, remote handling systems, etc. This paper summarizes the methodology followed according to the experience gained in previous studies and anticipating the future needs. (J.S.). 6 refs., 5 figs

  3. Information system development activities and inquiring systems

    DEFF Research Database (Denmark)

    Carugati, Andrea

    2008-01-01

    This article presents a framework that maps information system development (ISD) activities on systems for the creation of knowledge. This work addresses the relevant and persisting problem of improving the chances of ISD success. The article builds upon previous research on knowledge aspects of...... provides a new way to see the development of a system in terms of the knowledge created in the process. The main practical implication of the framework is that it improves the managers' ability to guide ISD activities as knowledge activities embedded in a knowledge process, a crucial element in development...... ISD, abandoning the idea of a monolithic approach to knowledge and presenting a pluralistic approach based on the idea that different inquiring systems can support micro-level ISD activities. The article is divided into two parts. The first part presents the theoretical development of the framework...

  4. Fault injection system for automatic testing system

    Institute of Scientific and Technical Information of China (English)

    王胜文; 洪炳熔

    2003-01-01

    Considering the deficiency of the means for confirming the attribution of fault redundancy in the re-search of Automatic Testing System(ATS) , a fault-injection system has been proposed to study fault redundancyof automatic testing system through compurison. By means of a fault-imbeded environmental simulation, thefaults injected at the input level of the software are under test. These faults may induce inherent failure mode,thus bringing about unexpected output, and the anticipated goal of the test is attained. The fault injection con-sists of voltage signal generator, current signal generator and rear drive circuit which are specially developed,and the ATS can work regularly by means of software simulation. The experimental results indicate that the faultinjection system can find the deficiency of the automatic testing software, and identify the preference of fault re-dundancy. On the other hand, some soft deficiency never exposed before can be identified by analyzing the tes-ting results.

  5. Business System Planning Project System Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    NELSON, R.E.

    2000-09-08

    The purpose of the Business Systems Planning Project System Requirements Specification (SRS) is to provide the outline and contents of the requirements for the CH2M HILL Hanford Group, Inc. (CHG) integrated business and technical information systems. The SRS will translate proposed objectives into the statement of the functions that are to be performed and data and information flows that they require. The requirements gathering methodology will use (1) facilitated group requirement sessions; (2) individual interviews; (3) surveys; and (4) document reviews. The requirements will be verified and validated through coordination of the technical requirement team and CHG Managers. The SRS document used the content and format specified in Lockheed Martin Services, Inc. Organization Standard Software Practices in conjunction with the Institute of Electrical and Electronics Engineers Standard 8340-1984 for Systems Requirements Documents.

  6. Knowledge management system as a sociotechnical system

    OpenAIRE

    Grundstein, Michel; Rosenthal-Sabroux, Camille

    2007-01-01

    The research effort started at the 2006 Hawaii Conference on System Sciences identifies seven key areas of KM research: KM Foundations, Knowledge Transfers, KM Systems, KM Research Methods, KM Success, Ethical Issues in KM, and KM Education (Jennex, 2006). In this paper, we refer to MGKME, our Model for Global Knowledge Management within the Enterprise (Grundstein & Rosenthal Sabroux, 2005; Grundstein, 2005; Grundstein, 2006). Thus, considering that KM is rooted on a Sociotechnical World that...

  7. User Registration Systems for Distributed Systems

    Science.gov (United States)

    Murphy, K. J.; Cechini, M.; Pilone, D.; Mitchell, A.

    2010-12-01

    As NASA’s Earth Observing System Data and Information System (EOSDIS) systems have evolved over the years, most of the EOSDIS data are now available to users via anonymous on-line access. Although the changes have improved the dissemination efficiency of earth science data, the anonymous access has made it difficult to characterize users, capture metrics on the value of EOSDIS and provide customized services that benefit users. As the number of web-based applications continues to grow, data centers and application providers have implemented their own user registration systems and provided new tools and interfaces for their registered users. This has led to the creation of independent registration systems for accessing data and interacting with online tools and services. The user profile information maintained at each of these registration systems is not consistent and the registration enforcement varies by system as well. This problem is in no way unique to EOSDIS and represents a general challenge to the distributed computing community. In a study done in 2007(http://www2007.org/papers/paper620.pd), the average user has approximately 7 passwords for about 25 accounts and enters a password 8 times a day. These numbers have only increased in the last three years. To try and address this, a number of solutions have been offered including Single Sign-On solutions using a common backend like Microsoft Active Directory or an LDAP server, trust based identity providers like OpenID, and various forms of authorization delegation like OAuth or SAML/XACML. This talk discusses the differences between authentication and authorization, the state of the more popular user registration solutions available for distributed use, and some of the technical and policy drivers that need to be considered when incorporating a user registration system into your application.

  8. Integrated Systems Health Management for Intelligent Systems

    Science.gov (United States)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. Management implies storage, distribution, sharing, maintenance, processing, reasoning, and presentation. ISHM is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this chapter, concepts, procedures, and approaches are presented as a foundation for implementing an ISHM capability relevant to intelligent systems. The capability stresses integration of DIaK from all elements of a system, emphasizing an advance toward an on-board, autonomous capability. Both ground-based and on-board ISHM capabilities are addressed. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  9. Operating System for Runtime Reconfigurable Multiprocessor Systems

    Directory of Open Access Journals (Sweden)

    Diana Göhringer

    2011-01-01

    Full Text Available Operating systems traditionally handle the task scheduling of one or more application instances on processor-like hardware architectures. RAMPSoC, a novel runtime adaptive multiprocessor System-on-Chip, exploits the dynamic reconfiguration on FPGAs to generate, start and terminate hardware and software tasks. The hardware tasks have to be transferred to the reconfigurable hardware via a configuration access port. The software tasks can be loaded into the local memory of the respective IP core either via the configuration access port or via the on-chip communication infrastructure (e.g. a Network-on-Chip. Recent-series of Xilinx FPGAs, such as Virtex-5, provide two Internal Configuration Access Ports, which cannot be accessed simultaneously. To prevent conflicts, the access to these ports as well as the hardware resource management needs to be controlled, e.g. by a special-purpose operating system running on an embedded processor. For that purpose and to handle the relations between temporally and spatially scheduled operations, the novel approach of an operating system is of high importance. This special purpose operating system, called CAP-OS (Configuration Access Port-Operating System, which will be presented in this paper, supports the clients using the configuration port with the services of priority-based access scheduling, hardware task mapping and resource management.

  10. Torque control system

    Science.gov (United States)

    Studenick, D. K.; Tyler, A. L.; Squillari, W.

    1975-01-01

    System stabilizes aximuth of gondolas which are carried by high-altitude balloons as platforms for tracking telescopes. When telescopes must be constantly aimed at specific targets, control system stabilizes gondola to within 5 arc-seconds.

  11. Saturated Switching Systems

    CERN Document Server

    Benzaouia, Abdellah

    2012-01-01

    Saturated Switching Systems treats the problem of actuator saturation, inherent in all dynamical systems by using two approaches: positive invariance in which the controller is designed to work within a region of non-saturating linear behaviour; and saturation technique which allows saturation but guarantees asymptotic stability. The results obtained are extended from the linear systems in which they were first developed to switching systems with uncertainties, 2D switching systems, switching systems with Markovian jumping and switching systems of the Takagi-Sugeno type. The text represents a thoroughly referenced distillation of results obtained in this field during the last decade. The selected tool for analysis and design of stabilizing controllers is based on multiple Lyapunov functions and linear matrix inequalities. All the results are illustrated with numerical examples and figures many of them being modelled using MATLAB®. Saturated Switching Systems will be of interest to academic researchers in con...

  12. Immune System (For Parents)

    Science.gov (United States)

    ... lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has ... can't be prevented, you can help your child's immune system stay stronger and fight illnesses by ...

  13. Visitor Registration System

    Data.gov (United States)

    US Agency for International Development — Visitor Registration System (VRS) streamlines visitor check-in and check-out process for expediting visitors into USAID. The system captures visitor information...

  14. Design of combi systems

    DEFF Research Database (Denmark)

    Andersen, Elsa; Shah, Louise Jivan; Furbo, Simon

    2001-01-01

    system based on a tank in tank heat storage are investigated experimentally in a laboratory test facility. One of the units is based on a mantle tank the other is based on a tank with a built-in heat exchanger spiral. The thermal performances of the systems in the laboratory test facility are measured...... paper addresses an experimentally and theoretically investigation of three different marketed combi systems. Two different combi systems, based on the above mentioned system design, with units where the auxiliary energy supply system is built into the same cabinet as the hot-water tank and one combi...... with constant daily hot water consumption, consumption patterns and space heating demand for all days, and the results are used to validate TrnSys models. Based on simulation models of the combi systems, the thermal behavior is simulated and the thermal performance and the solar fraction of the systems...

  15. Information retrieval system

    Science.gov (United States)

    Berg, R. F.; Holcomb, J. E.; Kelroy, E. A.; Levine, D. A.; Mee, C., III

    1970-01-01

    Generalized information storage and retrieval system capable of generating and maintaining a file, gathering statistics, sorting output, and generating final reports for output is reviewed. File generation and file maintenance programs written for the system are general purpose routines.

  16. Avian respiratory system disorders

    Science.gov (United States)

    Olsen, G.H.

    1989-01-01

    Diagnosing and treating respiratory diseases in avian species requires a basic knowledge about the anatomy and physiology of this system in birds. Differences between mammalian and avian respiratory system function, diagnosis, and treatment are highlighted.

  17. Online data processing system

    International Nuclear Information System (INIS)

    A pulse height analyzer terminal system PHATS has been developed for online data processing via JAERI-TOKAI computer network. The system is controled by using a micro-computer MICRO-8 which was developed for the JAERI-TOKAI network. The system program consists of two subprograms, online control system ONLCS and pulse height analyzer control system PHACS. ONLCS links the terminal with the conversational programming system of FACOM 230/75 through the JAERI-TOKAI network and controls data processing in TSS and remote batch modes. PHACS is used to control INPUT/OUTPUT of data between pulse height analyzer and cassette-MT or typewriter. This report describes the hardware configuration and the system program in detail. In the appendix, explained are real time monitor, type of message, PEX to PEX protocol and Host to Host protocol, required for the system programming. (author)

  18. LIGHTWEIGHT GREEN ROOF SYSTEMS

    Science.gov (United States)

    Applying a Lightweight Green Roof System to a building can achieve in managing storm water runoff, decreasing heat gain, yielding energy savings, and mitigating the heat island effect. Currently, Most green roof systems are considerably heavy and require structural reinforceme...

  19. Cardiac conduction system

    Science.gov (United States)

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  20. Adaptive shared control system

    OpenAIRE

    Sanders, David

    2009-01-01

    A control system to aid mobility is presented that is intended to assist living independently and that provides physical guidance. The system has two levels: a human machine interface and an adaptive shared controller.

  1. Health System Measurement Project

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Health System Measurement Project tracks government data on critical U.S. health system indicators. The website presents national trend data as well as detailed...

  2. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It helps ... to find and destroy them. If your immune system cannot do its job, the results can be ...

  3. Gleason grading system

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000920.htm Gleason grading system To use the sharing features on this page, ... score of between 5 and 7. Gleason Grading System Sometimes, it can be hard to predict how ...

  4. Pneumonia - weakened immune system

    Science.gov (United States)

    ... gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  5. Human Balance System

    Science.gov (United States)

    ... Rated Nonprofit! Volunteer. Donate. Review. The Human Balance System Good balance is often taken for granted. Good ... soft, slippery, or uneven). Input from the vestibular system Sensory information about motion, equilibrium, and spatial orientation ...

  6. Highly Autonomous Systems Workshop

    Science.gov (United States)

    Doyle, R.; Rasmussen, R.; Man, G.; Patel, K.

    1998-01-01

    It is our aim by launching a series of workshops on the topic of highly autonomous systems to reach out to the larger community interested in technology development for remotely deployed systems, particularly those for exploration.

  7. Voluntary Service System (VSS)

    Data.gov (United States)

    Department of Veterans Affairs — Voluntary Service System (VSS) is a national-level application which replaced the site-based Voluntary Timekeeping System (VTK). VTK was used for many years at the...

  8. Secondary systemic amyloidosis

    Science.gov (United States)

    ... systemic amyloidosis include: Endocrine failure Heart failure Kidney failure Respiratory failure When to Contact a Medical Professional Call your ... Cystic fibrosis Endocrine glands Hairy cell leukemia Heart failure - overview Hodgkin ... arthritis Sjögren syndrome Systemic lupus erythematosus Update ...

  9. Modular optical detector system

    Science.gov (United States)

    Horn, Brent A.; Renzi, Ronald F.

    2006-02-14

    A modular optical detector system. The detector system is designed to detect the presence of molecules or molecular species by inducing fluorescence with exciting radiation and detecting the emitted fluorescence. Because the system is capable of accurately detecting and measuring picomolar concentrations it is ideally suited for use with microchemical analysis systems generally and capillary chromatographic systems in particular. By employing a modular design, the detector system provides both the ability to replace various elements of the detector system without requiring extensive realignment or recalibration of the components as well as minimal user interaction with the system. In addition, the modular concept provides for the use and addition of a wide variety of components, including optical elements (lenses and filters), light sources, and detection means, to fit particular needs.

  10. Lungs and Respiratory System

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Lungs and Respiratory System KidsHealth > For Teens > Lungs and ... you didn't breathe, you couldn't live. Lungs & Respiratory System Basics Each day we breathe about ...

  11. Henry Ford Health Systems

    Science.gov (United States)

    Henry Ford Health Systems evolved from a hospital into a system delivering care to 2.5 million patients and includes the Cancer Epidemiology, Prevention and Control Program, which focuses on epidemiologic and public health aspects of cancer.

  12. BioSystems

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NCBI BioSystems Database provides integrated access to biological systems and their component genes, proteins, and small molecules, as well as literature...

  13. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  14. US ecology data system

    International Nuclear Information System (INIS)

    The US Ecology computer data system was instituted March 1, 1982. This system was designed to manage the increasing flow of paperwork and data associated with the receipt and disposal of low-level radioactive waste at Richland, Washington and Beatty, Nevada. The system was modified and upgraded in 1984 to accommodate a revised shipping manifest pursuant to the requirements of 10 CFR 20.311. The data system is used to generate various reports for both internal and external distribution. The computer system is located at US Ecology's corporate headquarters in Louisville, Kentucky. Remote access terminals are located at the disposal sites. The system is supported by a Wang VS-100 processor. In addition to supporting the radwaste data system, the system supports a chemical waste data base, word processing, and electronic mail. The management and operation of this data base are described. 19 figures

  15. Central nervous system

    Science.gov (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  16. Cross Disciplinary Biometric Systems

    CERN Document Server

    Liu, Chengjun

    2012-01-01

    Cross disciplinary biometric systems help boost the performance of the conventional systems. Not only is the recognition accuracy significantly improved, but also the robustness of the systems is greatly enhanced in the challenging environments, such as varying illumination conditions. By leveraging the cross disciplinary technologies, face recognition systems, fingerprint recognition systems, iris recognition systems, as well as image search systems all benefit in terms of recognition performance.  Take face recognition for an example, which is not only the most natural way human beings recognize the identity of each other, but also the least privacy-intrusive means because people show their face publicly every day. Face recognition systems display superb performance when they capitalize on the innovative ideas across color science, mathematics, and computer science (e.g., pattern recognition, machine learning, and image processing). The novel ideas lead to the development of new color models and effective ...

  17. National oceanographic information system

    Digital Repository Service at National Institute of Oceanography (India)

    Desai, B.N.; Kunte, P.D.; Bhargava, R.M.S.

    Ocean. At INODC, a National Information system for oceanographic studies is under development. Bibliographic information forms an integral part of oceanographic system as it is an essential component for data analysis and interpretation. Hence two major...

  18. Component maintenance system

    International Nuclear Information System (INIS)

    A component maintenance system having a network linked to a data acquisition system, a data analysis system, a historical file of component design and inspection information, and a diagnostic system having the capability to perform structural analysis of discontinuities identified by the data acquisition system. The network nodes may be located apart from each other, for example in the maintenance of a nuclear power plant steam generator, the data acquisition system may be located in a high radiation area while the data analysis system is safely located away from the radiation areas. Furthermore, the diagnostic system and the file of component design and inspection history information may be centrally located and sheared to support component evaluations being conducted in numerous geographic locations. Network communication facilitates the rapid evaluation of discontinuities, thereby permitting the inspection plan to be modified as the inspection results are obtained. (author) figs

  19. Inductive Monitoring System (IMS)

    Data.gov (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  20. Geographical information systems

    DEFF Research Database (Denmark)

    Möller, Bernd

    2004-01-01

    The chapter gives an introduction to Geographical Information Systems (GIS) with particular focus on their application within environmental management.......The chapter gives an introduction to Geographical Information Systems (GIS) with particular focus on their application within environmental management....

  1. Flight Systems Monitor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase I project will develop the Flight System Monitor which will use non-intrusive electrical monitoring (NEMO). The electronic system health of...

  2. Audit Management System

    CERN Document Server

    Alconada, Federico

    2015-01-01

    In the need of renewing their system, the Internal Audit department has given a proposal for building a new one. Taking into consideration the problems of their system they elaborated a requirement's list with the functionalities and features they were expecting from the new management system. This new system would be primarily for the use of the Internal Audit staff but it would also support the follow-up of internal audit recommendations by potentially all CERN staff members.

  3. Memory Evolutive Systems

    OpenAIRE

    Ehresmann, Andree; Vanbremeersch, Jean-Paul

    1999-01-01

    Natural autonomous systems, such as biological, neural, social or cultural systems, are open, self-organized systems with a more or less large hierarchy of interacting complexity levels; they are able to memorize their experiences and to adapt to various conditions through a change of behavior. These last fifteen years, the Authors have developed a mathematical model for these systems, based on Category Theory. The aim of the paper is to give an overview of this model, called Memory Evolutive...

  4. On open systems

    OpenAIRE

    Chick, V.

    2004-01-01

    To many, economics is seen as increasingly divorced from reality. I shall argue that one of the causes of this divorce is the attachment to closed-system theorising, and advocate instead the method of open systems with partial and temporary closures. Definitions of closed and open systems are examined. It is evident that there are many different criteria which may define open systems. Theorists differ in their emphasis on one or other criterion. There are also different dimensions of openness...

  5. Radio over fiber systems

    OpenAIRE

    Ghafoor, Salman

    2012-01-01

    The three main types of Radio Over Fiber (ROF)communication systems, namely analogue ROF, baseband ROF and digitized ROF are investigated. Optical fibers are increasingly replacing copper wires. In long-haul, high-bit-rate communication systems optical fiber has already become the dominant mode of transmission due to its enormous bandwidth and low loss. ROF facilitate the seamless integration of optical and wireless communication systems. Since the RF spectrum is limited, wireless systems rel...

  6. Logistics Management Information System

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The logistics information is the logistics manageme nt 's inevitable request. The paper introduces several kinds of logistics informat ion system and their functions in the logistics management, such as the warehous e management system (WMS) in the delivery center, the control system for transpo rtation and delivery, the supply chain management (SCM), the optimization of th e logistics system, etc. In the author's opinion, the development of logistics could been divided into four phases. And the logistic...

  7. Linear system theory

    Science.gov (United States)

    Callier, Frank M.; Desoer, Charles A.

    1991-01-01

    The aim of this book is to provide a systematic and rigorous access to the main topics of linear state-space system theory in both the continuous-time case and the discrete-time case; and the I/O description of linear systems. The main thrusts of the work are the analysis of system descriptions and derivations of their properties, LQ-optimal control, state feedback and state estimation, and MIMO unity-feedback systems.

  8. Radiant Floor Cooling Systems

    DEFF Research Database (Denmark)

    Olesen, Bjarne W.

    2008-01-01

    In many countries, hydronic radiant floor systems are widely used for heating all types of buildings such as residential, churches, gymnasiums, hospitals, hangars, storage buildings, industrial buildings, and smaller offices. However, few systems are used for cooling.This article describes a floo...... cooling system that includes such considerations as thermal comfort of the occupants, which design parameters will influence the cooling capacity and how the system should be controlled. Examples of applications are presented....

  9. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  10. Spacecraft Energy Storage Systems

    OpenAIRE

    Robinson, Wilf; Hanks, James; Spina, Len; Havenhill, Doug; Gisler, Gary; Ginter, Steve; Brault, Sharon

    1997-01-01

    Flywheel Energy Storage Systems represent an exciting alternative to traditional battery storage systems used to power satellites during periods of eclipse. The increasing demand for reliable communication and data access is driving explosive growth in the number of satellite systems being developed as well as their performance requirements. Power on orbit is the key to this performance, and batteries are becoming increasingly unattractive as an energy storage media. Flywheel systems offer ve...

  11. Information System Design

    OpenAIRE

    Sedlák, Marek

    2016-01-01

    The diploma thesis focuses on design of the information system for the department of medical transport service, which is part of the hospital. This thesis describes the theoretical knowledge necessary for analysis and custom design, is also concerned with the analysis of the current state of processes and information system. Last but not least, based on the analysis and the requirements lays down suggestions for improvement of the information system and design of optimal information system, t...

  12. Systems of innovation

    OpenAIRE

    Bas ter Weel; Soete, L.; Verspagen, B.

    2010-01-01

    We review the literature on national innovation systems. We first focus on the emergence of the concept of innovation systems, reviewing its historical origins and three main flavours (associated to three “founding fathers†of the concept). After this, we discuss how the notion of innovation systems filled a need for providing a broader basis for innovation policy. We conclude with some perspectives on the future of the innovation systems literature.

  13. East Asia's Security System

    OpenAIRE

    Hojzáková, Věra

    2012-01-01

    The aim of the master thesis is to characterize and evaluate the current security system in East Asia, to show the security strategies of the system actors and the existing friction points, and to assess the future development of the security system in place. For this purpose the author first defines the East Asia's security system using the conceptual tools of three international relations theories, namely neo-realism, neo-liberalism, and constructivism. In the following section, the securit...

  14. Operating system Google Android

    OpenAIRE

    Haris, Marek

    2011-01-01

    This Bachelor thesis deals with the Operating system Google Android. In the introductory part the author describes the very history and a progressive development of the company Google and Android. The thesis focuses on the Operating system Google Android and contains some basic information about the system. The architecture is analysed in detail. Then the Bachelor thesis deals with the development of individual version of the system Android. Next chapters explain and deal with the topics And...

  15. TMACS system description

    International Nuclear Information System (INIS)

    This document provides a description of the Tank Monitor and Control System (TMACS). It is intended as an introduction for those persons unfamiliar with the system as well as a reference document for the users, maintenance personnel, and system designers. In addition to describing the system, the document outlines the associated drawing documentation, provides maintenance and spare parts information, and discusses other TMACS documents that provide additional detail

  16. Rainfed intensive crop systems

    DEFF Research Database (Denmark)

    Olesen, Jørgen E

    2014-01-01

    This chapter focuses on the importance of intensive cropping systems in contributing to the world supply of food and feed. The impact of climate change on intensive crop production systems is also discussed.......This chapter focuses on the importance of intensive cropping systems in contributing to the world supply of food and feed. The impact of climate change on intensive crop production systems is also discussed....

  17. Pricing for system security

    OpenAIRE

    Wu, Felix F; Kaye, RJohn; Varaiya, Pravin

    1995-01-01

    Security in power systems refers to the ability of the system to withstand imminent disturbances (contingencies). Maintaining security is an issue which must be addressed at the system level. It is shown in this paper, however, that it is possible to maintain system security in an operating environment with many participants (power companies, independent power producers, co-generators, consumers) each attempting to optimize their own benefit, through pricing incentives and appropriate informa...

  18. IAEA safeguards information system

    International Nuclear Information System (INIS)

    The basic concepts, structure, and operation of the Agency Safeguards Information System is discussed with respect to its role in accomplishing the overall objectives of safeguards. The basis and purposes of the Agency's information system, the structure and flow of information within the Agency's system, the relationship of the components is the Agency system, the requirements of Member States in respect of their reporting to the Agency, and the relationship of accounting data vis-a-vis facility and inspection data are described

  19. Electronic flight instrument system

    OpenAIRE

    Hauptman, Luka

    2009-01-01

    This thesis describes basic concepts in research and development of a simple electronic flight instrument system, which displays piston engine data to the pilot. The main purpose is to build a functional prototype and acquire knowledge, which will enable us to further develop the system. The second chapter presents fundamentals of electronic flight instrument systems used in large commercial aircrafts. A detailed description of basic approaches to system implementation used by two of the b...

  20. Interactions within wastewater systems

    OpenAIRE

    Langeveld, J.G.

    2004-01-01

    Wastewater systems consist of sewer systems and wastewater treatment works. As the performance of a wastewater treatment plant is affected by the characteristics, i.e. operation and design, of the contributing sewer systems, knowledge of the interactions between sewers and wastewater treatment works is very important when trying to understand and improve wastewater systems. The thesis comprises three main topics: Firstly, the sensitivity of wastewater treatment plant performance to influent f...