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Sample records for ebp50 exerts tumor

  1. Identification of EBP50 as a Specific Biomarker for Carcinogens Via the Analysis of Mouse Lymphoma Cellular Proteome

    Science.gov (United States)

    Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

    2012-01-01

    To identify specific biomarkers generated upon exposure of L5178Y mouse lymphoma cells to carcinogens, 2-DE and MALDI-TOF MS analysis were conducted using the cellular proteome of L5178Y cells that had been treated with the known carcinogens, 1,2-dibromoethane and O-nitrotoluene and the noncarcinogens, emodin and D-mannitol. Eight protein spots that showed a greater than 1.5-fold increase or decrease in intensity following carcinogen treatment compared with treatment with noncarcinogens were selected. Of the identified proteins, we focused on the candidate biomarker ERM-binding phosphoprotein 50 (EBP50), the expression of which was specifically increased in response to treatment with the carcinogens. The expression level of EBP50 was determined by western analysis using polyclonal rabbit anti-EBP50 antibody. Further, the expression level of EBP50 was increased in cells treated with seven additional carcinogens, verifying that EBP50 could serve as a specific biomarker for carcinogens. PMID:22434383

  2. EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression.

    Science.gov (United States)

    Liu, Hongyan; Li, Zhenjie; Li, Liujuan; Peng, Haiying; Zhang, Zhijun

    2015-11-01

    Ebp1, a protein identified by its interactions with the ErbB3 receptor, has been characterized as a negative regulator of cancers. RAS GTPase-activating protein (RasGAP), RASAL1, was recently identified as a major tumor suppressor in thyroid cancer. In this study, we examined EBP1 expression in papillary and follicular thyroid cancer cells. We found that compared with normal thyroid cells, TPC1, WRO, and FTC133 thyroid tumor cells exhibited lower EBP1 expression at messenger RNA (mRNA) and protein levels. We then investigated the effects of forced EBP1 expression on growth, migration, and invasiveness of thyroid tumor cells. By using MTT and Boyden chamber assays, we showed that EBP1 overexpression dramatically reduced growth rate, migration, and invasiveness of K1 and FTC133 thyroid tumor cells. Furthermore, we explored the molecular mechanism underlying the effects of EBP1 on the cells by disclosing the correlation of EBP1 and RASAL1 expression. RASAL expression was elevated in thyroid tumor cells overexpressing EBP1. Knockdown RASAL by transduction of RASAL1 shRNA lentiviral particles markedly reduced RASAL levels with restoration of EBP1, and RASAL1 knockdown abrogated the effects of forced EBP1 expression on cell growth, migration, and invasiveness of thyroid tumor cells. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.

  3. NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

    Science.gov (United States)

    Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

    2016-01-01

    Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

  4. TonEBP modulates the protective effect of taurine in ischemia-induced cytotoxicity in cardiomyocytes

    Science.gov (United States)

    Yang, Y J; Han, Y Y; Chen, K; Zhang, Y; Liu, X; Li, S; Wang, K Q; Ge, J B; Liu, W; Zuo, J

    2015-01-01

    Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of taurine in heart is maintained by a taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although taurine supplementation upregulates TauT expression, elevates the intracellular taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of taurine governing TauT expression under ischemia. In this study, we describe the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway involved in the taurine-regulated TauT expression in ischemic CMs. Taurine inhibited the ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under ischemia. Moreover, the protective effects of taurine on myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of taurine in CMs under ischemic insult. PMID:26673669

  5. A PDZ-Like Motif in the Biliary Transporter ABCB4 Interacts with the Scaffold Protein EBP50 and Regulates ABCB4 Cell Surface Expression.

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    Quitterie Venot

    Full Text Available ABCB4/MDR3, a member of the ABC superfamily, is an ATP-dependent phosphatidylcholine translocator expressed at the canalicular membrane of hepatocytes. Defects in the ABCB4 gene are associated with rare biliary diseases. It is essential to understand the mechanisms of its canalicular membrane expression in particular for the development of new therapies. The stability of several ABC transporters is regulated through their binding to PDZ (PSD95/DglA/ZO-1 domain-containing proteins. ABCB4 protein ends by the sequence glutamine-asparagine-leucine (QNL, which shows some similarity to PDZ-binding motifs. The aim of our study was to assess the potential role of the QNL motif on the surface expression of ABCB4 and to determine if PDZ domain-containing proteins are involved. We found that truncation of the QNL motif decreased the stability of ABCB4 in HepG2-transfected cells. The deleted mutant ABCB4-ΔQNL also displayed accelerated endocytosis. EBP50, a PDZ protein highly expressed in the liver, strongly colocalized and coimmunoprecipitated with ABCB4, and this interaction required the QNL motif. Down-regulation of EBP50 by siRNA or by expression of an EBP50 dominant-negative mutant caused a significant decrease in the level of ABCB4 protein expression, and in the amount of ABCB4 localized at the canalicular membrane. Interaction of ABCB4 with EBP50 through its PDZ-like motif plays a critical role in the regulation of ABCB4 expression and stability at the canalicular plasma membrane.

  6. Teaching evidence-based practice (EBP) to speech-language therapy students: are students competent and confident EBP users?

    Science.gov (United States)

    Spek, B; Wieringa-de Waard, M; Lucas, C; van Dijk, N

    2013-01-01

    The importance and value of the principles of evidence-based practice (EBP) in the decision-making process is recognized by speech-language therapists (SLTs) worldwide and as a result curricula for speech-language therapy students incorporated EBP principles. However, the willingness actually to use EBP principles in their future profession not only depends on EBP knowledge and skills, but also on self-efficacy and task value students perceive towards EBP. To investigate the relation between EBP knowledge and skills, and EBP self-efficacy and task value in different year groups of Dutch SLT students. Students from three year groups filled in a tool that measured EBP knowledge and skills: the Dutch Modified Fresno (DMF). EBP self-efficacy and task value were assessed by using a 20-item questionnaire. Both tools were validated for this population. Mean scores for the three year groups were calculated and tested for group differences using a one-way analysis of variance (ANOVA) with a post-hoc Games-Howell procedure. With a multiple linear regression technique it was assessed whether EBP self-efficacy and task value predict learning achievement scores on the DMF. Other possible predictors included in the model were: level of prior education, standard of English, having had mathematics in prior education and the SLT study year. A total of 149 students filled in both measurement tools. Mean scores on EBP knowledge and skills were significantly different for the three year groups, with students who were further along their studies scoring higher on the DMF. Mean scores on the EBP self-efficacy and task value questionnaire were the same for the three year groups: all students valued EBP positive but self-efficacy was low in all groups. Of the possible predictors, only the year in which students study and EBP self-efficacy were significant predictors for learning achievements in EBP. Despite a significant increase in EBP knowledge and skills over the years as assessed by

  7. Marked differences in immunocytological localization of [3H]estradiol-binding protein in rat pancreatic acinar tumor cells compared to normal acinar cells

    International Nuclear Information System (INIS)

    Beaudoin, A.R.; Grondin, G.; St Jean, P.; Pettengill, O.; Longnecker, D.S.; Grossman, A.

    1991-01-01

    [ 3 H]Estradiol can bind to a specific protein in normal rat pancreatic acinar cells. Electron microscopic immunocytochemical analysis has shown this protein to be localized primarily in the rough endoplasmic reticulum and mitochondria. Rat exocrine pancreatic tumor cell lines, whether grown in tissue culture (AR42J) or as a tumor mass after sc injection into rats (DSL-2), lacked detectable amounts of this [ 3 H]estradiol-binding protein (EBP), as determined by the dextran-coated charcoal assay. Furthermore, primary exocrine pancreatic neoplasms induced with the carcinogen azaserine contained little or no detectable [ 3 H]estradiol-binding activity. However, electron immunocytochemical studies of transformed cells indicated the presence of material that cross-reacted with antibodies prepared against the [ 3 H]EBP. The immunopositive reaction in transformed cells was localized almost exclusively in lipid granules. Such lipid organelles in normal acinar cells, although present less frequently than in transformed cells, have never been observed to contain EBP-like immunopositive material. Presumably, the aberrant localization of EBP in these acinar tumor cells results in loss of function of this protein, which in normal pancreatic acinar cells appears to exert a modulating influence on zymogen granule formation and the process of secretion

  8. Effectiveness of an evidence-based practice (EBP) course on the EBP competence of undergraduate nursing students: A quasi-experimental study.

    Science.gov (United States)

    Ruzafa-Martínez, María; López-Iborra, Lidón; Armero Barranco, David; Ramos-Morcillo, Antonio Jesús

    2016-03-01

    International nursing institutions and experts recommend evidence-based practice (EBP) as a core component of the curriculum for nurses. However, the impact of EBP training on the competence of undergraduate nursing students remains unclear. To evaluate the effectiveness of an EBP course on the EBP competence undergraduate nursing students'. Quasi-experimental study carried out in non-randomized intervention and control groups. The study was conducted in a Spanish public university in 2010. Out of 420 second- and third-year nursing students, 75 were enrolled in the EBP course, forming the intervention group, and 73 were not enrolled in this course were recruited as controls. The educational intervention was a 15-week course designed to teach EBP competence. The EBP Competence Questionnaire (EBP-COQ) was administered before and after the intervention. Repeated-measure ANOVA was used to compare intervention and control group scores before and at two months after the 15-week intervention period. At 2months after the EBP course, mean EBP-COQ scores of the intervention group were significantly improved versus baseline in attitude (4.28 vs. 3.33), knowledge (3.92 vs. 2.82) and skills (4.01 vs. 2.75) dimensions, whereas little change was observed in control group scores over the same time period. Repeated-measures ANOVA revealed a significant effect of Time ×Group interaction on global competence and all three EBP-COQ dimensions. Undergraduate nursing students experience positive changes in EBP competence, knowledge, skills, and attitude as the result of a 15-week educational intervention on EBP. This EBP course may provide nursing school educators and policymakers with a useful model for integrating EBP teaching within the nursing curriculum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Three-Year Pre-Post Analysis of EBP Integration in a Magnet-Designated Community Hospital.

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    Warren, Joan Insalaco; Montgomery, Kathryn Lothschuetz; Friedmann, Erika

    2016-02-01

    Adoption of evidence-based practices (EBP) by registered nurses (RNs) and nurse leaders continues to be a challenge. Although multiple strategies and substantial resources are being invested to advance nursing practice based on evidence, little is known about the long-term impact of these interventions. This study was undertaken to assess nurse leaders' and clinical RNs' beliefs to use EBP, perceptions about organizational readiness for EBP, and frequency of implementing EBP following implementation of multifaceted interventions to achieve and maintain Magnet designation. This retrospective descriptive study compared data from two previously administered online surveys (2008 and 2012) at a mid-Atlantic Magnet-designated community hospital. Clinical RNs' self-reported attitudes toward EBP were more positive (2008: M = 53.85, standard error of the mean [SEM] = 0.65; 2012: M = 57.07,SEM = 0.58), as well as their perceptions of organizational readiness (2008: M = 50.72, SEM = 1.20; 2012: M = 81.09, SEM = 0.98), between the two survey years. Contrarily, although nurse leader scores were significantly higher for beliefs (2008: M = 61.15, SEM = 1.23; 2012: M = 60.60., SEM = 0.96), readiness (2008: M = 61.28, SEM = 2.16; 2012: M = 85.18, SEM = 1.64), and implementation (2008: M = 21.35, SEM = 1.72; 2012: M = 19.08, SEM = 1.43) little change was observed in the nurse leader scores between the two survey years compared with clinical RNs. Results from this study suggest that the multifaceted interventions have had a positive impact on clinical RNs' beliefs and readiness for EBP, but not for nurse leaders. Albeit low, self-reported implementation of EBP by RNs and nurse leaders has been sustained, but has not improved. Leaders must see their role as not only facilitators of EBP but also as active participants practicing EBP. Actively engaging leaders in EBP by serving on interprofessional EBP teams and role modeling these behaviors to staff is critical to EBP implementation

  10. Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2.

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    Le Bacquer, Olivier; Petroulakis, Emmanuel; Paglialunga, Sabina; Poulin, Francis; Richard, Denis; Cianflone, Katherine; Sonenberg, Nahum

    2007-02-01

    The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin (mTOR) signaling pathway in obesity. Eukaryotic translation initiation factor 4E-binding (eIF4E-binding) proteins (4E-BPs), which repress translation by binding to eIF4E, are downstream effectors of mTOR. We report that the combined disruption of 4E-BP1 and 4E-BP2 in mice increased their sensitivity to diet-induced obesity. Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice. Increased insulin resistance in 4E-BP1 and 4E-BP2 double KO mice was associated with increased ribosomal protein S6 kinase (S6K) activity and impairment of Akt signaling in muscle, liver, and adipose tissue. These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome.

  11. Teaching evidence-based practice (EBP) to speech-language therapy students : are students competent and confident EBP users?

    NARCIS (Netherlands)

    N. van Dijk; B. Spek; M Wieringa-de Waard; C. Lucas

    2013-01-01

    BACKGROUND: The importance and value of the principles of evidence-based practice (EBP) in the decision-making process is recognized by speech-language therapists (SLTs) worldwide and as a result curricula for speech-language therapy students incorporated EBP principles. However, the willingness

  12. Teaching evidence-based practice (EBP) to speech-language therapy students: are students competent and confident EBP users?

    NARCIS (Netherlands)

    Spek, B.; Wieringa-de Waard, M.; Lucas, C.; van Dijk, N.

    2013-01-01

    The importance and value of the principles of evidence-based practice (EBP) in the decision-making process is recognized by speech-language therapists (SLTs) worldwide and as a result curricula for speech-language therapy students incorporated EBP principles. However, the willingness actually to use

  13. Phosphorylation prevents C/EBP{beta} from the calpain-dependent degradation

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    Zhang, Yuan-yuan; Li, Shu-fen; Qian, Shu-wen; Zhang, You-you; Liu, Yuan; Tang, Qi-Qun; Li, Xi, E-mail: lixi@shmu.edu.cn

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer Phosphorylation protected C/EBP{beta} from {mu}-calpain-mediated proteolysis in vitro. Black-Right-Pointing-Pointer Phosphorylation mimic C/EBP{beta} was insensitive to calpain accelerator and inhibitor. Black-Right-Pointing-Pointer Phosphorylation on Thr{sub 188} contributed more to the stabilization of C/EBP{beta}. -- Abstract: CCAAT/enhancer-binding protein (C/EBP) {beta} plays an important role in proliferation and differentiation of 3T3-L1 preadipocytes. C/EBP{beta} is sequentially phosphorylated during the 3T3-L1 adipocyte differentiation program, first by MAPK/Cyclin A/cdk2 on Thr{sub 188} and subsequently by GSK3{beta} on Ser{sub 184} or Thr{sub 179}. Dual phosphorylation is critical for the gain of DNA binding activity of C/EBP{beta}. In this manuscript, we found that phosphorylation also contributed to the stability of C/EBP{beta}. Both ex vivo and in vitro experiments showed that phosphorylation by MAPK/Cyclin A/cdk2 and GSK3{beta} protected C/EBP{beta} from {mu}-calpain-mediated proteolysis, while phosphorylation on Thr{sub 188} by MAPK/Cyclin A/cdk2 contributed more to the stabilization of C/EBP{beta}, Further studies indicated that phosphorylation mimic C/EBP{beta} was insensitive to both calpain accelerator and calpain inhibitor. Thus, phosphorylation might contribute to the stability as well as the gain of DNA binding activity of C/EBP{beta}.

  14. Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta

    DEFF Research Database (Denmark)

    Karlsen, Joachim R; Borregaard, Niels; Cowland, Jack B

    2010-01-01

    -alpha in the presence of IL-17, a pro-inflammatory cytokine produced by the newly discovered subset of CD4(+) T helper cells, T(H)-17. In contrast to the murine NGAL orthologue, 24p3/lipocalin 2, we found no requirement for C/EBP-beta or C/EBP-delta for NGAL induction by IL-17 and TNF-alpha as neither small interfering...

  15. S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Roman Nawroth

    Full Text Available Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K/Akt/mammalian target of rapamycin (mTOR and the mitogen activated protein kinase (MAPK signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC. However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK.

  16. Development and Testing of the Nurse Manager EBP Competency Scale.

    Science.gov (United States)

    Shuman, Clayton J; Ploutz-Snyder, Robert J; Titler, Marita G

    2018-02-01

    The purpose of this study was to develop and evaluate the validity and reliability of an instrument to measure nurse manager competencies regarding evidence-based practice (EBP). The Nurse Manager EBP Competency Scale consists of 16 items for respondents to indicate their perceived level of competency on a 0 to 3 Likert-type scale. Content validity was demonstrated through expert panel review and pilot testing. Principal axis factoring and Cronbach's alpha evaluated construct validity and internal consistency reliability, respectively. Eighty-three nurse managers completed the scale. Exploratory factor analysis resulted in a 16-item scale with two subscales, EBP Knowledge ( n = 6 items, α = .90) and EBP Activity ( n = 10 items, α = .94). Cronbach's alpha for the entire scale was .95. The Nurse Manager EBP Competency Scale is a brief measure of nurse manager EBP competency with evidence of validity and reliability. The scale can enhance our understanding in future studies regarding how nurse manager EBP competency affects implementation.

  17. Competent in evidence-based practice (EBP): validation of a measurement tool that measures EBP self-efficacy and task value in speech-language therapy students

    NARCIS (Netherlands)

    Spek, B.; Wieringa-de Waard, M.; Lucas, C.; van Dijk, N.

    2013-01-01

    Worldwide speech-language therapy (SLT) students are educated in evidence-based practice (EBP). For students to use EBP in their future day-to-day clinical practice, they must value EBP as positive and must feel confident in using it. For curricula developers it is therefore important to know the

  18. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

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    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  19. 4E-BP1 regulates the differentiation of white adipose tissue.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

    2013-07-01

    4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  20. Macrophage content of murine tumors: Associations with TD50 and tumor radiocurability

    International Nuclear Information System (INIS)

    Wike, J.; Hunter, N.; Volpe, J.; Milas, L.

    1987-01-01

    The experiments were designed to investigate whether the tumor-associated macrophage (TAM) content of murine solid tumors correlates with tumor response to ionizing radiation and with the clonogenic ability of tumor cells to establish s.c. tumors. Of 13 tumors studied, 6 were sarcomas and 7 were carcinomas; all tumors were of spontaneous origin in C/sub 3/Hf/Kam mice, with the exception of one sarcoma that was induced by 3-methylcholanthrene. Tumors were growing in the hind thighs of syngeneic mice, and their TAM content was determined when they were 8 mm in diameter. Their macrophage content varied greatly, ranging from 9 to 83%. Radiocurability of 8 mm tumors, determined by TCD50, ranged from 42 Gy (fibrosarcoma FSA) to > 80 Gy (hepatocarcinoma HCA-I). There was an obvious trend toward positive correlation (r = 0.43) between TAM content and reduced local tumor radiocurability. However, there was a significant negative correlation between TAM content and TD50 values, implying that cells from tumors with higher macrophage content were more clonogenic. TAM from the NFSA sarcoma, a tumor with a low TD50 value and poorly responsive to radiation, stimulated the in vitro growth of NFSA tumor cells. These observations suggest that high TAM content could be conducive to tumor cell proliferation and could be a factor in poor tumor radioresponse

  1. Mechanism of enhanced responses after combination photodynamic therapy (cPDT) in carcinoma cells involves C/EBP-mediated transcriptional upregulation of the coproporphyrinogen oxidase (CPO) gene

    Science.gov (United States)

    Anand, Sanjay; Hasan, Tayyaba; Maytin, Edward V.

    2013-03-01

    Photodynamic therapy (PDT) with aminolevulinate (ALA) is widely accepted as an effective treatment for superficial carcinomas and pre-cancers. However, PDT is still suboptimal for deeper tumors, mainly due to inadequate ALA penetration and subsequent conversion to PpIX. We are interested in improving the effectiveness of photodynamic therapy (PDT) for deep tumors, using a combination approach (cPDT) in which target protoporphyrin (PpIX) levels are significantly enhanced by differentiation caused by giving Vitamin D or methotrexate (MTX) for 3 days prior to ALAPDT. In LNCaP and MEL cells, a strong correlation between inducible differentiation and expression of C/EBP transcription factors, as well as between differentiation and mRNA levels of CPO (a key heme-synthetic enzyme), indicates the possibility of CPO transcriptional regulation by the C/EBPs. Sequence analysis of the first 1300 base pairs of the murine CPO upstream region revealed 15 consensus C/EBP binding sites. Electrophoretic Mobility Shift Assays (EMSA) proved that these sites form specific complexes that have strong, moderate or weak affinities for C/EBPs. However, in the context of the full-length CPO promoter, inactivation of any type of site (strong or weak) reduced CPO promoter activity (luciferase assay) to nearly the same extent, suggesting cooperative interactions. A comparative analysis of murine and human CPO promoters revealed possible protein-protein interactions between C/EBPs and several neighboring transcription factors such as NFkB, Sp1, AP-1, CBP/p300 and CREB (an enhanceosome complex). Overall, these results confirm that C/EBP's are important for CPO expression via complex mechanisms which upregulate PpIX and enhance the outcome of cPDT.

  2. Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA

    Directory of Open Access Journals (Sweden)

    Taek-In Oh

    2017-09-01

    Full Text Available Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4; however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB, indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2 and tropomyosin-related kinase A (TRKA via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

  3. Endeavoring to Contextualize Curricula Within an EBP Framework: A Grounded Theory Study.

    Science.gov (United States)

    Malik, Gulzar; McKenna, Lisa; Griffiths, Debra

    2018-01-01

    Adopting evidence-based practice (EBP) principles in undergraduate education can facilitate nursing students' appreciation of EBP. Using grounded theory method, this study aimed to explore processes used by nurse academics while integrating EBP concepts in undergraduate nursing curricula across Australian universities. Twenty-three nurse academics were interviewed and nine were observed during teaching of undergraduate students. In addition, 20 unit/subject guides were analyzed using grounded theory approach of data analysis. The theory " On a path to success: Endeavoring to contextualize curricula within an EBP framework" reflects academics' endeavors toward linking EBP concepts to practice, aiming to contextualize curricula in a manner that engages students within an EBP framework. However, academics' journeys were influenced by several contextual factors which require strategies to accomplish their endeavors. In conclusion, initiatives to minimize barriers, faculty development, and provision of resources across educational and clinical settings are fundamental to achieving undergraduate curricula underpinned by EBP concepts.

  4. Leadership for evidence-based practice: strategic and functional behaviors for institutionalizing EBP.

    Science.gov (United States)

    Stetler, Cheryl B; Ritchie, Judith A; Rycroft-Malone, Jo; Charns, Martin P

    2014-08-01

    Making evidence-based practice (EBP) a reality throughout an organization is a challenging goal in healthcare services. Leadership has been recognized as a critical element in that process. However, little is known about the exact role and function of various levels of leadership in the successful institutionalization of EBP within an organization. To uncover what leaders at different levels and in different roles actually do, and what actions they take to develop, enhance, and sustain EBP as the norm. Qualitative data from a case study regarding institutionalization of EBP in two contrasting cases (Role Model and Beginner hospitals) were systematically analyzed. Data were obtained from multiple interviews of leaders, both formal and informal, and from staff nurse focus groups. A deductive coding schema, based on concepts of functional leadership, was developed for this in-depth analysis. Participants' descriptions reflected a hierarchical array of strategic, functional, and cross-cutting behaviors. Within these macrolevel "themes," 10 behavioral midlevel themes were identified; for example, Intervening and Role modeling. Each theme is distinctive, yet various themes and their subthemes were interrelated and synergistic. These behaviors and their interrelationships were conceptualized in the framework "Leadership Behaviors Supportive of EBP Institutionalization" (L-EBP). Leaders at multiple levels in the Role Model case, both formal and informal, engaged in most of these behaviors. Supportive leadership behaviors required for organizational institutionalization of EBP reflect a complex set of interactive, multifaceted EBP-focused actions carried out by leaders from the chief nursing officer to staff nurses. A related framework such as L-EBP may provide concrete guidance needed to underpin the often-noted but abstract finding that leaders should "support" EBP. © 2014 The Authors. Worldviews on Evidence-Based Nursing published by Wiley Periodicals, Inc. on behalf of

  5. Leadership for Evidence-Based Practice: Strategic and Functional Behaviors for Institutionalizing EBP

    Science.gov (United States)

    Stetler, Cheryl B; Ritchie, Judith A; Rycroft-Malone, Jo; Charns, Martin P

    2014-01-01

    Background Making evidence-based practice (EBP) a reality throughout an organization is a challenging goal in healthcare services. Leadership has been recognized as a critical element in that process. However, little is known about the exact role and function of various levels of leadership in the successful institutionalization of EBP within an organization. Aims To uncover what leaders at different levels and in different roles actually do, and what actions they take to develop, enhance, and sustain EBP as the norm. Methods Qualitative data from a case study regarding institutionalization of EBP in two contrasting cases (Role Model and Beginner hospitals) were systematically analyzed. Data were obtained from multiple interviews of leaders, both formal and informal, and from staff nurse focus groups. A deductive coding schema, based on concepts of functional leadership, was developed for this in-depth analysis. Results Participants’ descriptions reflected a hierarchical array of strategic, functional, and cross-cutting behaviors. Within these macrolevel “themes,” 10 behavioral midlevel themes were identified; for example, Intervening and Role modeling. Each theme is distinctive, yet various themes and their subthemes were interrelated and synergistic. These behaviors and their interrelationships were conceptualized in the framework “Leadership Behaviors Supportive of EBP Institutionalization” (L-EBP). Leaders at multiple levels in the Role Model case, both formal and informal, engaged in most of these behaviors. Linking Evidence to Action Supportive leadership behaviors required for organizational institutionalization of EBP reflect a complex set of interactive, multifaceted EBP-focused actions carried out by leaders from the chief nursing officer to staff nurses. A related framework such as L-EBP may provide concrete guidance needed to underpin the often-noted but abstract finding that leaders should “support” EBP. PMID:24986669

  6. Provider Agency Practices as a Source of Social Work EBP.

    Science.gov (United States)

    Blakely, Thomas J; Dziadosz, Gregory M

    2016-01-01

    Through this article the authors propose that agency service provider systems may be a source of evidence-based practices (EBP). One agency's design and implementation of a program entitled Community Treatment and Rehabilitation is presented as an example. The elements of this program conform to the creation of EBPs. It was formulated with consideration of clients' values and judgments through their participation at every step in the assessment and treatment process. Staff clinicians were trained in established EBP interventions, such as cognitive therapy, embedded in a system of ordered assessment, treatment, and outcome evaluation. A controlled research design was used to gather outcome data to inform clinicians' decisions about interventions that were then systematically applied with clients. The delivery system was organized for clinical supervisors to guide staff clinical practices so that all were operating on the same set of guidelines allowing for similar outcomes to occur with similar interventions. This method of developing EBPs makes them available for application immediately and successfully eliminates the delay between development and implementation that usually occurs with other sources of EBPs.

  7. miRNA-130a regulates C/EBP-ε expression during granulopoiesis

    DEFF Research Database (Denmark)

    Larsen, Maria T; Häger, Mattias; Glenthøj, Andreas

    2014-01-01

    cells. In contrast, C/EBP-ε protein is virtually detectable only in the MC/MM population, indicating that expression in more immature cells could be inhibited by microRNAs (miRNAs). We found that miRNA-130a (miR-130a) regulates C/EBP-ε protein expression in both murine and human granulocytic precursors...... target site for miR-130a restored both C/EBP-ε production, expression of Camp and Lcn2, and resulted in the cells having a more mature phenotype. We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-ε during granulopoiesis.......CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of secondary granule proteins, but it also regulates proliferation, cell cycle, and maturation during granulopoiesis. Cebpe(-/-) mice have...

  8. Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: Case Report and Review of Literature.

    Science.gov (United States)

    Yoneoka, Yuichiro; Akiyama, Katsuhiko; Seki, Yasuhiro; Hasegawa, Go; Kakita, Akiyoshi

    2018-03-01

    Frontoethmoidal schwannomas are rare. No case manifesting exertional cerebrospinal fluid (CSF) rhinorrhea has ever been reported to the best of our knowledge. In this report, we describe an extremely rare case of frontoethmoidal schwannoma extending through the olfactory groove with exertional CSF rhinorrhea as the initial symptom. A 50-year-old woman was presented to our clinic for frequent nasal discharge on exertion. A postcontrast computed tomographic scan demonstrated heterogeneously enhanced tumor from the anterior cranial fossa to the anterior ethmoid sinus. A gadolinium-enhanced T1-weighted magnetic resonance image revealed a well-defined heterogeneously enhanced tumor situated in the midline anterior cranial fossa and anterior ethmoid sinus. After the resection, the defect of the right anterior skull base was reconstructed with a fascia graft and adipose tissue taken from the abdomen, as well as a pedicle periosteum flap. A histologic examination revealed the tumor as schwannoma. Her rhinorrhea completely resolved. She regained her sense of smell and taste 1 month after the operation. According to previous reports, olfactory groove, and paraolfactory groove/periolfactory groove schwannomas can be divided into 4 types: subfrontal, nasoethmoidal, frontoethmoidal, and ethmofrontal. Among them, a frontoethmoidal schwannoma can manifest exertional CSF rhinorrhea as an initial symptom. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Effectiveness of the tailored EBP training program for Filipino physiotherapists: a randomised controlled trial.

    Science.gov (United States)

    Dizon, Janine Margarita; Grimmer-Somers, Karen; Kumar, Saravana

    2011-04-13

    Evidence implementation continues to challenge health professionals most especially those from developing countries. Filipino physiotherapists represent a group of health professionals in a developing country who by tradition and historical practice, take direction from a doctor, on treatment options. Lack of autonomy in decision-making challenges their capacity to deliver evidence-based care. However, this scenario should not limit them from updating and up-skilling themselves on evidence- based practice (EBP). EBP training tailored to their needs and practice was developed to address this gap. This study will be conducted to assess the effectiveness of a tailored EBP-training program for Filipino physiotherapists, in improving knowledge, skills, attitudes and behaviour to EBP. Participation in this program aims to improve capacity to EBP and engage with referring doctors to determine the most effective treatments for their patients. A double blind randomised controlled trial, assessing the effectiveness of the EBP training intervention, compared with a waitlist control, will be conducted. An adequately powered sample of 54 physiotherapists from the Philippines will be recruited and randomly allocated to EBP intervention or waitlist control. The EBP program for Filipino physiotherapists is a one-day program on EBP principles and techniques, delivered using effective adult education strategies. It consists of lectures and practical workshops. A novel component in this program is the specially-developed recommendation form, which participants can use after completing their training, to assist them to negotiate with referring doctors regarding evidence-based treatment choices for their patients.Pre and post measures of EBP knowledge, skills and attitudes will be assessed in both groups using the Adapted Fresno Test and the Questions to EBP attitudes. Behaviour to EBP will be measured using activity diaries for a period of three months. Should the EBP-training program

  10. Hepatitis C virus core protein targets 4E-BP1 expression and phosphorylation and potentiates Myc-induced liver carcinogenesis in transgenic mice.

    Science.gov (United States)

    Abdallah, Cosette; Lejamtel, Charlène; Benzoubir, Nassima; Battaglia, Serena; Sidahmed-Adrar, Nazha; Desterke, Christophe; Lemasson, Matthieu; Rosenberg, Arielle R; Samuel, Didier; Bréchot, Christian; Pflieger, Delphine; Le Naour, François; Bourgeade, Marie-Françoise

    2017-08-22

    Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation. Among the eukaryotic initiation factors that govern the translational machinery, 4E-BP1 represents a master regulator of protein synthesis that is associated with the development and progression of cancers due to its ability to increase protein expression of oncogenic pathways. Enhanced levels of 4E-BP1 in non-modified and phosphorylated forms were validated in human hepatoma cells and in mouse primary hepatocytes expressing HCV core, in the livers of HCV core transgenic mice as well as in HCV-infected human primary hepatocytes. The contribution of HCV core in carcinogenesis and the status of 4E-BP1 expression and phosphorylation were studied in HCV core/Myc double transgenic mice. HCV core increased the levels of 4E-BP1 expression and phosphorylation and significantly accelerated the onset of Myc-induced tumorigenesis in these double transgenic mice. These results reveal a novel function of HCV core in liver carcinogenesis potentiation. They position 4E-BP1 as a tumor-specific target of HCV core and support the involvement of the 4E-BP1/eIF4E axis in hepatocarcinogenesis.

  11. Evaluating Evidence-Based Practice Knowledge and Beliefs Through the e-Learning EBP Academy.

    Science.gov (United States)

    Green, Angela; Jeffs, Debra A; Boateng, Beatrice A; Lowe, Gary R; Walden, Marlene

    2017-07-01

    This research examined evidence-based practice (EBP) knowledge and beliefs before and after a 3-month e-learning program was implemented to build EBP capacity at a large children's hospital. Ten clinicians completed the development, implementation, and evaluation of the e-learning education, comprising phase one. Revision and participation by 41 clinicians followed in phase two. Participants in both phases completed the EBP Beliefs and Implementation Scales preintervention, postintervention, and 6 months after postintervention. EBP beliefs and implementation increased immediately and 6 months after postintervention, with statistically significant increases in both phases. Participants in both phases applied knowledge by completing mentor-supported EBP projects. Although EBP beliefs and implementation scores increased and e-learning provided flexibility for clinician participation, challenges arose, resulting in lower-than-expected completion. Subsequent revisions resulted in hybrid education, integrating classroom and e-learning with project mentoring. This funded e-learning research contributes knowledge to the growing specialty of professional development. J Contin Educ Nurs. 2017;48(7):304-311. Copyright 2017, SLACK Incorporated.

  12. A novel role for the Bombyx Slbo homologue, BmC/EBP, in insect choriogenesis.

    Science.gov (United States)

    Sourmeli, S; Papantonis, A; Lecanidou, R

    2005-11-18

    One previously unidentified cDNA clone coding for a C/EBP factor, BmC/EBP, was isolated from Bombyx mori follicular cells. This is the first time that a C/EBP factor has been isolated and characterized in Lepidoptera. We provide information concerning structural features and developmental specificity, as well as in vitro interaction properties with chorion gene promoter modules. BmC/EBP was capable of effectively recognizing homologous binding sites from chorion gene promoters derived from flies and other moths, despite significant diversity of chorion structure, gene organization, and gene expression profiles. We propose that the relative concentration of BmC/EBP, in relation to its differential binding affinity for promoter cis-elements, results in activation or repression of silkmoth chorion gene expression.

  13. Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

    Directory of Open Access Journals (Sweden)

    Hua Bai

    Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

  14. Evidence-based practice in physical therapy in Austria: current state and factors associated with EBP engagement.

    Science.gov (United States)

    Diermayr, Gudrun; Schachner, Herbert; Eidenberger, Margit; Lohkamp, Monika; Salbach, Nancy M

    2015-12-01

    Research examining the use of evidence-based practice (EBP) in physical therapy in many countries has revealed positive attitudes, varying degrees of EBP use and barriers at practitioner, patient and organizational levels. In contrast to these countries, Austria does not have an academic or research tradition in physical therapy. Engagement in EBP in countries such as Austria is unknown. The objectives of the study were to describe the current state of EBP engagement and identify factors associated with EBP engagement among Austrian physical therapists (PTs). A cross-sectional online survey was conducted. Existing questionnaires and the theory of planned behaviour guided questionnaire development. Face and content validity and ease of use of the questionnaire were evaluated in pilot tests. Item-level response frequencies and percentages were determined. Simple and multiple regressions were used to identify factors associated with EBP engagement. The final sample size was 588 (response rate: 17.5%). Ten percent of participants fully agreed that they regularly use guidelines and standardized assessment tools in clinical practice. While 49.9% reported not using electronic databases for literature searching, 41.9% reported reading research articles 2-5 times per month. Most frequently cited barriers to EBP engagement were lack of scientific skills, lack of time and insufficient organizational support. Research awareness, attitude, behavioural control, involvement in research and degree level were final correlates of EBP engagement. Austrian PTs show a low level of engagement in EBP. Initiatives to advance EBP in Austria and other countries with no academic or research tradition should primarily target practitioner-level factors. © 2015 John Wiley & Sons, Ltd.

  15. Mechanisms of Change in the ARC Organizational Strategy: Increasing Mental Health Clinicians' EBP Adoption Through Improved Organizational Culture and Capacity.

    Science.gov (United States)

    Williams, Nathaniel J; Glisson, Charles; Hemmelgarn, Anthony; Green, Philip

    2017-03-01

    The development of efficient and scalable implementation strategies in mental health is restricted by poor understanding of the change mechanisms that increase clinicians' evidence-based practice (EBP) adoption. This study tests the cross-level change mechanisms that link an empirically-supported organizational strategy for supporting implementation (labeled ARC for Availability, Responsiveness, and Continuity) to mental health clinicians' EBP adoption and use. Four hundred seventy-five mental health clinicians in 14 children's mental health agencies were randomly assigned to the ARC intervention or a control condition. Measures of organizational culture, clinicians' intentions to adopt EBPs, and job-related EBP barriers were collected before, during, and upon completion of the three-year ARC intervention. EBP adoption and use were assessed at 12-month follow-up. Multilevel mediation analyses tested changes in organizational culture, clinicians' intentions to adopt EBPs, and job-related EBP barriers as linking mechanisms explaining the effects of ARC on clinicians' EBP adoption and use. ARC increased clinicians' EBP adoption (OR = 3.19, p = .003) and use (81 vs. 56 %, d = .79, p = .003) at 12-month follow-up. These effects were mediated by improvement in organizational proficiency culture leading to increased clinician intentions to adopt EBPs and by reduced job-related EBP barriers. A combined mediation analysis indicated the organizational culture-EBP intentions mechanism was the primary carrier of ARC's effects on clinicians' EBP adoption and use. ARC increases clinicians' EBP adoption and use by creating proficient organizational cultures that increase clinicians' intentions to adopt EBPs.

  16. Mechanisms of change in the ARC organizational strategy: Increasing mental health clinicians’ EBP adoption through improved organizational culture and capacity

    Science.gov (United States)

    Williams, Nathaniel J.; Glisson, Charles; Hemmelgarn, Anthony; Green, Philip

    2016-01-01

    Background The development of efficient and scalable implementation strategies in mental health is restricted by poor understanding of the change mechanisms that increase clinicians’ evidence-based practice (EBP) adoption. This study tests the cross-level change mechanisms that link an empirically-supported organizational strategy for supporting implementation (labeled ARC for Availability, Responsiveness, and Continuity) to mental health clinicians’ EBP adoption and use. Method Four hundred seventy five mental health clinicians in 14 children’s mental health agencies were randomly assigned to the ARC intervention or a control condition. Measures of organizational culture, clinicians’ intentions to adopt EBPs, and job-related EBP barriers were collected before, during, and upon completion of the three-year ARC intervention. EBP adoption and use were assessed at 12-month follow-up. Multilevel mediation analyses tested changes in organizational culture, clinicians’ intentions to adopt EBPs, and job-related EBP barriers as linking mechanisms explaining the effects of ARC on clinicians’ EBP adoption and use. Results ARC increased clinicians’ EBP adoption (OR = 3.19, p = .003) and use (81% vs. 56%, d = .79, p = .003) at 12-month follow-up. These effects were mediated by improvement in organizational proficiency culture leading to increased clinician intentions to adopt EBPs and by reduced job-related EBP barriers. A combined mediation analysis indicated the organizational culture-EBP intentions mechanism was the primary carrier of ARC’s effects on clinicians’ EBP adoption and use. Conclusions ARC increases clinicians’ EBP adoption and use by creating proficient organizational cultures that increase clinicians’ intentions to adopt EBPs. PMID:27236457

  17. Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1 deficient mice

    Directory of Open Access Journals (Sweden)

    Lee Myounghee

    2008-12-01

    Full Text Available Abstract Background The ErbB3 binding protein-1 (Ebp1 belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4 gene. Results Ebp1-/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, was altered in adult tissues. Conclusion These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.

  18. Assessing the organizational context for EBP implementation: the development and validity testing of the Implementation Climate Scale (ICS).

    Science.gov (United States)

    Ehrhart, Mark G; Aarons, Gregory A; Farahnak, Lauren R

    2014-10-23

    Although the importance of the organizational environment for implementing evidence-based practices (EBP) has been widely recognized, there are limited options for measuring implementation climate in public sector health settings. The goal of this research was to develop and test a measure of EBP implementation climate that would both capture a broad range of issues important for effective EBP implementation and be of practical use to researchers and managers seeking to understand and improve the implementation of EBPs. Participants were 630 clinicians working in 128 work groups in 32 US-based mental health agencies. Items to measure climate for EBP implementation were developed based on past literature on implementation climate and other strategic climates and in consultation with experts on the implementation of EBPs in mental health settings. The sample was randomly split at the work group level of analysis; half of the sample was used for exploratory factor analysis (EFA), and the other half was used for confirmatory factor analysis (CFA). The entire sample was utilized for additional analyses assessing the reliability, support for level of aggregation, and construct-based evidence of validity. The EFA resulted in a final factor structure of six dimensions for the Implementation Climate Scale (ICS): 1) focus on EBP, 2) educational support for EBP, 3) recognition for EBP, 4) rewards for EBP, 5) selection for EBP, and 6) selection for openness. This structure was supported in the other half of the sample using CFA. Additional analyses supported the reliability and construct-based evidence of validity for the ICS, as well as the aggregation of the measure to the work group level. The ICS is a very brief (18 item) and pragmatic measure of a strategic climate for EBP implementation. It captures six dimensions of the organizational context that indicate to employees the extent to which their organization prioritizes and values the successful implementation of EBPs

  19. Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP-α and PPAR-γ Expression in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Thi Tuyet Nhung Nguyen

    2017-01-01

    Full Text Available Many studies have comprehensively examined the venom of Ophiophagus hannah snake. Its venom comprises different compounds exhibiting a wide range of pharmacological activities. In this investigation, four peptide fractions (PFs, ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O. hannah were separated by HPLC and investigated for their inhibitory activity on adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two peptides on 3T3-L1 adipocytes, it was revealed that, at 10 μg/mL, pOh2 was able to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without affecting cell viability. Furthermore, the pOh2 downregulated the gene expression of important transcription factors C/EBP-α and PPAR-γ. In addition, aP2 and GPDH adipocyte-specific markers were also significantly reduced compared to untreated differentiated cells. Taken together, pOh2 inhibited the expression of key transcription factors C/EBP-α and PPAR-γ and their target genes, aP2 and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this novel class of peptide might have potential for in vivo antiobesity effects.

  20. PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

    OpenAIRE

    Anderson, Grace R.; Wardell, Suzanne E.; Cakir, Merve; Crawford, Lorin; Leeds, Jim C.; Nussbaum, Daniel P.; Shankar, Pallavi S.; Soderquist, Ryan S.; Stein, Elizabeth M.; Tingley, Jennifer P.; Winter, Peter S.; Zieser-Misenheimer, Elizabeth K.; Alley, Holly M.; Yllanes, Alexander; Haney, Victoria

    2016-01-01

    Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that the combined inhibition of BCL-XL and the mTOR/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses MCL-1 protein translation only in ...

  1. GSK-3 directly regulates phospho-4EBP1 in renal cell carcinoma cell-line: an intrinsic subcellular mechanism for resistance to mTORC1 inhibition

    International Nuclear Information System (INIS)

    Ito, Hiromi; Ichiyanagi, Osamu; Naito, Sei; Bilim, Vladimir N.; Tomita, Yoshihiko; Kato, Tomoyuki; Nagaoka, Akira; Tsuchiya, Norihiko

    2016-01-01

    The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin 1 (mTORC1) signaling pathway is aberrantly activated in renal cell carcinoma (RCC). We previously demonstrated glycogen synthase kinase-3β (GSK-3β) positively regulated RCC proliferation. The aim of this study was to evaluate the role of GSK-3 in the PI3K/Akt/mTORC1 pathway and regulation of the downstream substrates, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), ribosomal protein S6 kinase (S6K), and ribosomal protein S6 (S6RP). We used human RCC cell lines (ACHN, Caki1, and A498) and, as normal controls, human renal proximal tubular epithelial cell (HRPTEpC) and non-tumorous kidney tissues that were obtained surgically for treatment of RCC patients. Rapamycin-resistant ACHN (ACHN/RR) cells were generated with chronic exposure of ACHN to rapamycin ranging from 1nM finally to 1 μM. Cell viability, cell cycling and direct interaction between GSK-3β and 4EBP1 were evaluated with MTS assay, flowcytometry and in vitro kinase assay with recombinant GSK-3β and 4EBP1products, respectively. Protein expression and phosphorylation of molecules associated with the PI3K/Akt/mTORC1 pathway were examined by immunoblotting. Effects of drug combination were determined as the combination index with CompuSyn software. Overexpression and phosphorylation of 4EBP1 and S6RP together with GSK-3 activation were observed in RCC cell lines, but not in human normal kidney cells and tissues. Cell proliferation, p4EBP1 and pS6RP were strongly suppressed by GSK-3 inhibition. Rapamycin and LY294002 sufficiently decreased pS6RP, but only moderately p4EBP1. In vitro kinase assays showed that recombinant GSK-3β phosphorylated recombinant 4EBP1, and the effect was blocked by GSK-3 inhibitors. Different from rapamycin, AR- A014418 remarkably inhibited cell proliferation, and rapidly suppressed p4EBP1 and pS6RP in ACHN and ACHN/RR (in 30 min to 1 h). AR- A014418 and rapamycin combination showed

  2. Expression, purification, crystallization and preliminary crystallographic analysis of the proliferation-associated protein Ebp1

    International Nuclear Information System (INIS)

    Kowalinski, Eva; Bange, Gert; Wild, Klemens; Sinning, Irmgard

    2007-01-01

    Preliminary X-ray analysis of the proliferation-associated protein Ebp1 from Homo sapiens is provided. ErbB-3-binding protein 1 (Ebp1) is a member of the family of proliferation-associated 2G4 proteins (PA2G4s) and plays a role in cellular growth and differentiation. Ligand-induced activation of the transmembrane receptor ErbB3 leads to dissociation of Ebp1 from the receptor in a phosphorylation-dependent manner. The non-associated protein is involved in transcriptional and translational regulation in the cell. Here, the overexpression, purification, crystallization and preliminary crystallographic studies of Ebp1 from Homo sapiens are reported. Initially observed crystals were improved by serial seeding to single crystals suitable for data collection. The optimized crystals belong to the tetragonal space group P4 1 2 1 2 or P4 3 2 1 2 and diffracted to a resolution of 1.6 Å

  3. Expression, purification, crystallization and preliminary crystallographic analysis of the proliferation-associated protein Ebp1

    Energy Technology Data Exchange (ETDEWEB)

    Kowalinski, Eva; Bange, Gert; Wild, Klemens; Sinning, Irmgard, E-mail: irmi.sinning@bzh.uni-heidelberg.de [Heidelberg University Biochemistry Center, INF 328, D-69120 Heidelberg (Germany)

    2007-09-01

    Preliminary X-ray analysis of the proliferation-associated protein Ebp1 from Homo sapiens is provided. ErbB-3-binding protein 1 (Ebp1) is a member of the family of proliferation-associated 2G4 proteins (PA2G4s) and plays a role in cellular growth and differentiation. Ligand-induced activation of the transmembrane receptor ErbB3 leads to dissociation of Ebp1 from the receptor in a phosphorylation-dependent manner. The non-associated protein is involved in transcriptional and translational regulation in the cell. Here, the overexpression, purification, crystallization and preliminary crystallographic studies of Ebp1 from Homo sapiens are reported. Initially observed crystals were improved by serial seeding to single crystals suitable for data collection. The optimized crystals belong to the tetragonal space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2 and diffracted to a resolution of 1.6 Å.

  4. N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors.

    Science.gov (United States)

    Vargas-Ramírez, Alba L; Medina-Enríquez, Miriam M; Cordero-Rodríguez, Neira I; Ruiz-Cuello, Tatiana; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José G; Alcántara-Farfán, Verónica; Rodríguez-Páez, Lorena

    2016-07-01

    N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

  5. Top 50 most cited articles on primary tumors of the spine.

    Science.gov (United States)

    Alan, Nima; Cohen, Jonathan; Ozpinar, Alp; Agarwal, Nitin; Kanter, Adam S; Okonkwo, David O; Hamilton, D Kojo

    2017-08-01

    Citation analysis was performed in order to identify the top 50 most cited articles pertaining to the field of primary spinal tumors. This collection of articles highlights important trends in the neurosurgical literature. We searched the Thomson Reuters Web of Knowledge in order to identify articles pertaining to primary tumors of the spine. Impertinent articles were removed. The top 50 most cited articles were identified. Thereafter, article characteristics were determined including article type, article topic, level of evidence, and citation rate. The selected articles were published between 1951 and 2008. The most productive year was 1997 with 6 publications. The top 50 articles were published in twenty-two different journals, most commonly in Neurosurgery (12), Journal of Neurosurgery (8), and Spine (6). The most frequently cited article was by Tomita et al. written in 1997 which described total en bloc spondylectomy as a novel surgical technique in management of primary tumors of the vertebral column. We identified the 50 most-cited articles in the field of primary spinal tumors. This collection of articles serves as a reference for recognizing impactful studies in the field. Copyright © 2017. Published by Elsevier Ltd.

  6. Health professions faculty beliefs, confidence, use, and perceptions of organizational culture and readiness for EBP: A cross-sectional, descriptive survey.

    Science.gov (United States)

    Milner, Kerry A; Bradley, Holly B; Lampley, Tammy

    2018-05-01

    Evidence-based practice (EBP) is an essential skill and ethical obligation for all practicing health professions clinicians because of its strong association with improved health outcomes. Emerging evidence suggests that faculty who prepare these clinicians lack proficiency to teach EBP. The purpose of this study was to describe; 1) health profession faculty beliefs about and confidence in their ability to teach and implement EBP, 2) use of EBP for education, 3) organizational culture and readiness for EBP; and to determine whether relationships exist among these variables. This study used a cross-sectional, descriptive survey design. College of Nursing (CON) and College of Health Professions (CHP) faculty from a university located in the Northeast, United States. Faculty were defined as anyone teaching a course for the CON or CHP during the fall of 2016. Faculty were invited to complete an electronic survey measuring EBP beliefs, EBP use, and EBP organizational culture and readiness. The survey was comprised of three tools developed specifically for health professions educators in 2010 by Fineout-Overholt & Melnyk. Sixty-nine faculty returned usable surveys (25.5% response rate). Mean EBP beliefs score was 89.49 (SD = 10.94) indicating respondents had a firm belief in and confidence in their ability to implement and teach EBP. Mean EBP use was 32.02 (SD = 20.59) indicating that respondents taught and implemented EBP between 1 and 3 times in the last 8-weeks. Mean EBP culture and readiness score was 90.20 (SD = 15.23) indicating essential movement toward a sustainable culture of college-wide integration of EBP. Mean scores for beliefs/confidence were higher for full-time clinical faculty compared to other groups [F (2, 55)  = 0.075, p = 0.928; ηp 2  = 0.003)]. Adjunct faculty reported higher EBP behaviors expected by health profession educators in the last 8-weeks compared to other groups [F (2, 55)  = 0.251, p = 0.779; ηp 2 . =0

  7. Exploring multi-level system factors facilitating educator training and implementation of evidence-based practices (EBP): a study protocol.

    Science.gov (United States)

    Stahmer, Aubyn C; Suhrheinrich, Jessica; Schetter, Patricia L; McGee Hassrick, Elizabeth

    2018-01-08

    This study examines how system-wide (i.e., region, district, and school) mechanisms such as leadership support, training requirements, structure, collaboration, and education affect the use of evidence-based practices (EBPs) in schools and how this affects the outcomes for students with autism spectrum disorder (ASD). Despite growing evidence for the positive effects of EBPs for ASD, these practices are not consistently or effectively used in schools. Although special education programs are mandated to use EBPs, there are very few evidence-based methods for selecting, implementing, and sustaining EBPs. Research focuses primarily on teacher training, without attention to contextual factors (e.g., implementation climate, attitudes toward EBPs, resource allocation, and social networks) that may impact outcomes. Using an implementation science framework, this project will prospectively examine relations between system-wide factors and teachers' use of EBPs and student education outcomes. Survey data will be collected from approximately 85 regional special education directors, 170 regional program specialists, 265 district special education directors, 265 behavior specialists, 925 school principals, 3538 special education teachers, and 2700 paraprofessionals. Administrative data for the students with ASD served by participating teachers will be examined. A total of 79 regional-, district-, and school-level personnel will also participate in social network interviews. Mixed methods, including surveys, administrative data, and observational checklists, will be used to gather in-depth information about system-wide malleable factors that relate to positive teacher implementation of EBPs and student outcomes. Multi-level modeling will be used to assess system-wide malleable factors related to EBP implementation which will be linked to the trainer, teacher, and student outcomes and examined based on moderators (e.g., district size, Special Education Local Plan Area structure

  8. The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is Essential for Survival in the Environment

    Science.gov (United States)

    Hu, Wei-Lin; Pappas, Christopher J.; Zhang, Jun-Jie; Yang, You-Yun; Yan, Jie

    2016-01-01

    ABSTRACT Leptospira interrogans is the agent of leptospirosis, a reemerging zoonotic disease. It is transmitted to humans through environmental surface waters contaminated by the urine of mammals chronically infected by pathogenic strains able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of L. interrogans during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway in L. interrogans. In this pathway, EbpA, a σ54 activator and putative prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN (σ54) control expression of at least three genes, encoding AmtB (an ammonium transport protein) and two proteins of unknown function. Electrophoresis mobility shift assay demonstrated that recombinant RpoN and EbpA bind to the promoter region and upstream of these three identified genes, respectively. Genetic disruption of ebpA in L. interrogans serovar Manilae virtually abolished expression of the three genes, including amtB in two independent ebpA mutants. Complementation of the ebpA mutant restored expression of these genes. Intraperitoneal inoculation of gerbils with the ebpA mutant did not affect mortality. However, the ebpA mutant had decreased cell length in vitro and had a significantly lowered cell density at stationary phase when grown with l-alanine as the sole nitrogen source. Furthermore, the ebpA mutant has dramatically reduced long-term survival ability in water. Together, these studies identify a regulatory pathway, the EbpA-RpoN pathway, that plays an important role in the zoonotic cycle of L. interrogans. IMPORTANCE Leptospirosis is a reemerging disease with global importance. However, our understanding of gene regulation of the spirochetal pathogen Leptospira interrogans is still in its infancy, largely due to the lack of robust tools for genetic manipulation of this spirochete. Little is known about how the pathogen

  9. The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is Essential for Survival in the Environment.

    Science.gov (United States)

    Hu, Wei-Lin; Pappas, Christopher J; Zhang, Jun-Jie; Yang, You-Yun; Yan, Jie; Picardeau, Mathieu; Yang, X Frank

    2017-02-01

    Leptospira interrogans is the agent of leptospirosis, a reemerging zoonotic disease. It is transmitted to humans through environmental surface waters contaminated by the urine of mammals chronically infected by pathogenic strains able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of L. interrogans during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway in L. interrogans In this pathway, EbpA, a σ 54 activator and putative prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN (σ 54 ) control expression of at least three genes, encoding AmtB (an ammonium transport protein) and two proteins of unknown function. Electrophoresis mobility shift assay demonstrated that recombinant RpoN and EbpA bind to the promoter region and upstream of these three identified genes, respectively. Genetic disruption of ebpA in L. interrogans serovar Manilae virtually abolished expression of the three genes, including amtB in two independent ebpA mutants. Complementation of the ebpA mutant restored expression of these genes. Intraperitoneal inoculation of gerbils with the ebpA mutant did not affect mortality. However, the ebpA mutant had decreased cell length in vitro and had a significantly lowered cell density at stationary phase when grown with l-alanine as the sole nitrogen source. Furthermore, the ebpA mutant has dramatically reduced long-term survival ability in water. Together, these studies identify a regulatory pathway, the EbpA-RpoN pathway, that plays an important role in the zoonotic cycle of L. interrogans IMPORTANCE: Leptospirosis is a reemerging disease with global importance. However, our understanding of gene regulation of the spirochetal pathogen Leptospira interrogans is still in its infancy, largely due to the lack of robust tools for genetic manipulation of this spirochete. Little is known about how the pathogen achieves its

  10. Chorion gene activation and repression is dependent on BmC/EBP expression and binding to cognate cis-elements.

    Science.gov (United States)

    Papantonis, Argyris; Sourmeli, Sissy; Lecanidou, Rena

    2008-05-09

    From the different cis-elements clustered on silkmoth chorion gene promoters, C/EBP binding sites predominate. Their sequence composition and dispersal vary amongst promoters of diverse developmental specificity. Occupancy of these sites by BmC/EBP was examined through Southwestern and ChIP assays modified to suit ovarian follicular cells. For the genes studied, binding of BmC/EBP coincided with the respective stages of transcriptional activation. However, the factor was reloaded on promoter sequences long after individual gene repression. Furthermore, suppression of BmC/EBP transcription in developing follicles resulted in de-regulation of chorion gene expression. A biphasic function of BmC/EBP, according to which it may act as both an activator and a repressor during silkmoth choriogenesis, is considered under the light of the presented data.

  11. Evolving with Evidence: Leveraging New Tools for EBP

    Science.gov (United States)

    Valenza, Joyce Kasman

    2015-01-01

    Focusing on evidence-based practice (EBP) aligns with the school librarian's leadership role acknowledged by the American Association of School Librarians (AASL) in "Empowering Learners: Guidelines for School Library Programs" (2009) and in AASL's newly adopted mission statement. "The American Association of School Librarians…

  12. Teaching EBP Using Game-Based Learning: Improving the Student Experience.

    Science.gov (United States)

    Davidson, Sandra J; Candy, Laurie

    2016-08-01

    Evidence-based practice (EBP) is considered a key entry to practice competency for nurses. However, many baccalaureate nursing programs continue to teach "traditional" nursing research courses that fail to address many of the critical knowledge, skills, and attitudes that foster EBP. Traditional classroom teaching strategies do little to promote the development of competencies critical for engaging in EBP in clinical contexts. The purpose of this work was to develop, implement, and evaluate an innovative teaching strategy aimed at improving student learning, engagement and satisfaction in an online EBP course. The goals of this paper are to: (1) describe the process of course development, (2) describe the innovative teaching strategy, and (3) discuss the outcomes of the pilot course offered using game-based learning. A midterm course-specific survey and standard institutional end of course evaluations were used to evaluate student satisfaction. Game platform analytics and thematic analysis of narrative comments in the midterm and end of course surveys were used to evaluate students' level of engagement. Student learning was evaluated using the end of course letter grade. Students indicated a high satisfaction with the course. Student engagement was also maintained throughout the course. The majority of students (87%, 26/30) continued to complete learning quests in the game after achieving the minimum amount of points to earn an A. Seven students completed every learning quest available in the game platform. Of the 30 students enrolled in the course, 17 students earned a final course grade of A+ and 13 earned an A. Provide students with timely, individualized feedback to enable mastery learning. Create student choice and customization of learning. Integrate the use of badges (game mechanics) to increase engagement and motivation. Level learning activities to build on each other and create flow. © 2016 Sigma Theta Tau International.

  13. The TCD50 and regrowth delay assay in human tumor xenografts: Differences and implications

    International Nuclear Information System (INIS)

    Budach, W.; Budach, V.; Stuschke, M.; Dinges, S.; Sack, H.

    1993-01-01

    The response to irradiation of five human xenograft cell lines - a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma - were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120 mm 3 under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD 50 ) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD 50 was used in order to compare the data to previously published data from spheroids. The lowest TCD 50 was found in the lymphoma with 24.9 Gy, whereas the TCD 50 of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD 50 was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD 50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD 50 and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size

  14. Exploring perceptions of a learning organization by RNs and relationship to EBP beliefs and implementation in the acute care setting.

    Science.gov (United States)

    Estrada, Nicolette

    2009-01-01

    Health care professionals are expected to provide patient care based on best evidence. The context of the acute care setting presents a challenging environment for registered nurses (RNs) to utilize research and implement best evidence in practice. No organizational infrastructure has been identified that offers acute care RNs the support needed for evidence-based practice (EBP). The value of "learning organizations" has long been understood by corporate leaders. Potentially, the dimensions of a "learning organization" may offer a supportive EBP infrastructure for acute care RNs. (1) What is the relationship of the characteristics of the learning organization to registered nurses' beliefs regarding EBP? (2) Is there an impact of EBP beliefs on RNs' implementation of EBP? A descriptive, survey design study was conducted. Three established questionnaires were distributed to 1,750 RNs employed within six acute care hospitals. There were 594 questionnaires returned for a response rate of 34%. RNs rated their organizations in the mid-range on the dimensions of learning organization. Perceptions of the learning organization were found to be significant, although relatively small, predictors explaining 6% of knowledge beliefs, 11% of value beliefs, and 14% of resource beliefs. EBP beliefs explained 23% of EBP implementation reported by RNs. The study results indicate relationships between RNs' reported perception of a learning organization and EBP beliefs, and between EBP beliefs and implementation. However, findings were mixed. Overall, nurses rated their organizations the lowest in the dimensions of "promote inquiry and dialogue" and "empower people toward a collective vision." Leaders have an opportunity to offer a more supportive infrastructure through improving their organization in these two areas. RN beliefs explained 23% of EBP implementation in this study with a residual 77% yet to be identified. Acute care hospitals were perceived mid-range on learning

  15. Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice

    Directory of Open Access Journals (Sweden)

    Shih-Yin Tsai

    2016-08-01

    Full Text Available Obesity is a major risk factor driving the global type II diabetes pandemic. However, the molecular factors linking obesity to disease remain to be elucidated. Gender differences are apparent in humans and are also observed in murine models. Here, we link these differences to expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, which, upon HFD feeding, becomes significantly reduced in the skeletal muscle and adipose tissue of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1 transgenic mice also exhibit reduced white adipose tissue accumulation accompanied by decreased circulating levels of leptin and triglycerides. Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced obesity and metabolic decline on a normal diet. These results demonstrate that 4E-BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity and energy metabolism.

  16. Expression of ErbB3-binding protein-1 (EBP1 during primordial follicle formation: role of estradiol-17ß.

    Directory of Open Access Journals (Sweden)

    Anindit Mukherjee

    Full Text Available The formation of primordial follicles involves the interaction between the oocytes and surrounding somatic cells, which differentiate into granulosa cells. Estradiol-17ß (E promotes primordial follicle formation in vivo and in vitro; however, the underlying mechanisms are poorly understood. The expression of an ERBB3-binding protein 1 (EBP1 is downregulated in 8-day old hamster ovaries concurrent with the increase in serum estradiol levels and the formation of primordial follicles. The objectives of the present study were to determine the spatio-temporal expression and putative E regulation of EBP1 in ovarian cells during perinatal development with respect to primordial follicle formation. Hamster EBP1 nucleic acid and amino acid sequences were more than 93% and 98% similar, respectively, to those of mouse and human, and contained nucleolar localization signal, RNA-binding domain and several phosphorylation sites. EBP1 protein was present in somatic cells and oocytes from E15, and declined in oocytes by P1 and in somatic cells by P5. Thereafter, EBP1 expression increased through P7 with a transient decline on P8 primarily in interstitial cells. EBP1 mRNA levels mirrored protein expression pattern. E treatment on P1 and P4 upregulated EBP1 expression by P8 whereas E treatment on P4 downregulated it by 72 h suggesting a compensatory upregulation due to E pretreatment. Treatment with an FSH-antiserum, which suppressed primordial follicle formation, prevented the decline in EBP1 levels, and the effect was reversed by E treatment. Therefore, the results provide the first evidence that EBP1 may play an important role in mediating the effect of E in the differentiation of somatic cells into granulosa cells during primordial follicle formation.

  17. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.

    Science.gov (United States)

    Zhao, Sufen; Ye, Gang; Fu, Guodong; Cheng, Jian-Xin; Yang, Burton B; Peng, Chun

    2011-05-01

    Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.

  18. Hypertonic-induced lamin A/C synthesis and distribution to nucleoplasmic speckles is mediated by TonEBP/NFAT5 transcriptional activator

    International Nuclear Information System (INIS)

    Favale, Nicolas O.; Sterin Speziale, Norma B.; Fernandez Tome, Maria C.

    2007-01-01

    Lamin A/C is the most studied nucleoskeletal constituent. Lamin A/C expression indicates cell differentiation and is also a structural component of nuclear speckles, which are involved in gene expression regulation. Hypertonicity has been reported to induce renal epithelial cell differentiation and expression of TonEBP (NFAT5), a transcriptional activator of hypertonicity-induced gene transcription. In this paper, we investigate the effect of hypertonicity on lamin A/C expression in MDCK cells and the involvement of TonEBP. Hypertonicity increased lamin A/C expression and its distribution to nucleoplasm with speckled pattern. Microscopy showed codistribution of TonEBP and lamin A/C in nucleoplasmic speckles, and immunoprecipitation demonstrated their interaction. TonEBP silencing caused lamin A/C redistribution from nucleoplasmic speckles to the nuclear rim, followed by lamin decrease, thus showing that hypertonicity induces lamin A/C speckles through a TonEBP-dependent mechanism. We suggest that lamin A/C speckles could serve TonEBP as scaffold thus favoring its role in hypertonicity

  19. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    Directory of Open Access Journals (Sweden)

    David Judah

    2010-11-01

    Full Text Available Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1 promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  20. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    Science.gov (United States)

    Judah, David; Chang, Wing Y; Dagnino, Lina

    2010-11-10

    Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  1. DMPD: The role of C/EBP isoforms in the control of inflammatory and native immunityfunctions. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9792624 The role of C/EBP isoforms in the control of inflammatory and native immunityfunction...f C/EBP isoforms in the control of inflammatory and native immunityfunctions. PubmedID 9792624 Title The rol...e of C/EBP isoforms in the control of inflammatory and native immunityfunctions.

  2. Changes in physiotherapy students' knowledge and perceptions of EBP from first year to graduation: a mixed methods study.

    Science.gov (United States)

    McEvoy, Maureen P; Lewis, Lucy K; Luker, Julie

    2018-05-11

    Dedicated Evidence-Based Practice (EBP) courses are often included in health professional education programs. It is important to understand the effectiveness of this training. This study investigated EBP outcomes in entry-level physiotherapy students from baseline to completion of all EBP training (graduation). Mixed methods with an explanatory sequential design. Physiotherapy students completed two psychometrically-tested health professional EBP instruments at baseline and graduation. The Evidence-Based Practice Profile questionnaire collected self-reported data (Terminology, Confidence, Practice, Relevance, Sympathy), and the Knowledge of Research Evidence Competencies instrument collected objective data (Actual Knowledge). Focus groups with students were conducted at graduation to gain a deeper understanding of the factors impacting changes in students' EBP knowledge, attitudes, behaviour and competency. Descriptive statistics, paired t-tests, 95% CI and effect sizes (ES) were used to examine changes in outcome scores from baseline to graduation. Transcribed focus group data were analysed following a qualitative descriptive approach with thematic analysis. A second stage of merged data analysis for mixed methods studies was undertaken using side-by-side comparisons to explore quantitatively assessed EBP measures with participants' personal perceptions. Data were analysed from 56 participants who completed both instruments at baseline and graduation, and from 21 focus group participants. Large ES were reported across most outcomes: Relevance (ES 2.29, p ≤ 0.001), Practice (1.8, p ≤ 0.001), Confidence (1.67, p ≤ 0.001), Terminology (3.13, p ≤ 0.001) and Actual Knowledge (4.3, p ≤ 0.001). A medium ES was found for Sympathy (0.49, p = 0.008). Qualitative and quantitative findings mostly aligned but for statistical terminology, participants' self-reported understanding was disparate with focus group reported experiences. Qualitative

  3. The Elastin Receptor Complex: a unique matricellular receptor with high anti-tumoral potential

    Directory of Open Access Journals (Sweden)

    Amandine eScandolera

    2016-03-01

    Full Text Available Elastin, one of the longest-lived proteins, confers elasticity to tissues with high mechanical constraints. During aging or pathophysiological conditions such as cancer progression, this insoluble polymer of tropoelastin undergoes an important degradation leading to the release of bioactive elastin-derived peptides (EDP, named elastokines. EDP exhibit several biological functions able to drive tumor development by regulating cell proliferation, invasion, survival, angiogenesis, and matrix metalloproteinase expression in various tumor and stromal cells. Although several receptors have been suggested to bind elastokines (αvβ3 and αvβ5 integrins, galectin-3, their main receptor remains the Elastin Receptor Complex (ERC. This heterotrimer comprises a peripheral subunit, named Elastin Binding Protein (EBP, associated to the Protective Protein/Cathepsin A (PPCA. The latter is bound to a membrane-associated protein called Neuraminidase-1 (Neu-1. The pro-tumoral effects of elastokines have been linked to their binding onto EBP. Additionally, Neu-1 sialidase activity is essential for their signal transduction. Consistently, EDP-EBP interaction and Neu-1 activity emerge as original anti-tumoral targets. Interestingly, besides its direct involvement in cancer progression, the ERC also regulates diabetes outcome and thrombosis, an important risk factor for cancer development and a vascular process highly increased in patients suffering from cancer. In this review, we will describe ERC and elastokines involvement in cancer development suggesting that this unique receptor would be a promising therapeutic target. We will also discuss the pharmacological concepts aiming at blocking its pro-tumoral activities. Finally, its emerging role in cancer-associated complications and pathologies such as diabetes and thrombotic events will be also considered.

  4. Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Velasquez, Celestino; Cheng, Erdong; Shuda, Masahiro; Lee-Oesterreich, Paula J.; Pogge von Strandmann, Lisa; Gritsenko, Marina A.; Jacobs, Jon M.; Moore, Patrick S.; Chang, Yuan

    2016-07-11

    mTOR-directed 4E-BP1 phosphorylation promotes cap-dependent translation and tumorigen-esis. During mitosis, CDK1 substitutes for mTOR and fully phosphorylates 4E-BP1 at canoni-cal as well a non-canonical S83 site resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. While S83 phosphorylation of 4E-BP1 does not affect in vitro cap-dependent translation, nor eIF4G/4E-BP1 cap-binding, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus (MCV) small T (sT) antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain-of-function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function.

  5. Molecular cloning, characterization and expression analysis of C/EBP α, β and δ in adipose-related tissues and adipocyte of duck (Anas platyrhynchos).

    Science.gov (United States)

    Qiu, Jiamin; Wang, Wanxia; Hu, Shenqiang; Wang, Yushi; Sun, Wenqiang; Hu, Jiwei; Gan, Xiang; Wang, Jiwen

    2018-07-01

    CCAAT/enhancer binding protein α, β, δ (C/EBP α, β, δ) are essential transcriptional factors in regulating adipose development. However, information about their sequence characteristics and functions during adipocyte development still remains scarce in birds. In present study, we found that duck C/EBP α, β, δ differed in their phosphorylation sites and low complexity regions (LCRs) among their orthologs and paralogs. Phylogenetic analysis showed that C/EBP α, β, δ had different evolutionary patterns, and each of duck C/EBP α, β, δ was strikingly diverged from orthologs of other Aves. Results of quantitative real-time PCR exhibited that C/EBP α, β, δ were all highly expressed in duck adipose tissues. Indeed, investigations of changes in both their mRNA levels and lipid droplet content during duck adipocytes differentiation showed that their expression profiles were closely related to cellular lipid accumulation. Furthermore, hierarchical clustering analysis of the C/EBPs and lipid metabolism-related genes expression profiles showed that C/EBP α was clustered with genes related to lipolysis, lipogenesis and fatty acid desaturation, whereas C/EBP β, δ were clustered with genes related to de novo lipogenesis and fatty acid elongation, which were different from mammals. In summary, C/EBP α, β, δ of duck differ from other species in their structures and have different effects on lipid metabolism during adipocytes differentiation. This research serve as a foundation for further investigations about avian C/EBP α, β, δ in adipocytes differentiation and adipose development. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1).

    Science.gov (United States)

    Liu, Jianyu; Stevens, Payton D; Eshleman, Nichole E; Gao, Tianyan

    2013-08-09

    Protein translation initiation is a tightly controlled process responding to nutrient availability and mitogen stimulation. Serving as one of the most important negative regulators of protein translation, 4E binding protein 1 (4E-BP1) binds to translation initiation factor 4E and inhibits cap-dependent translation in a phosphorylation-dependent manner. Although it has been demonstrated previously that the phosphorylation of 4E-BP1 is controlled by mammalian target of rapamycin in the mammalian target of rapamycin complex 1, the mechanism underlying the dephosphorylation of 4E-BP1 remains elusive. Here, we report the identification of PPM1G as the phosphatase of 4E-BP1. A coimmunoprecipitation experiment reveals that PPM1G binds to 4E-BP1 in cells and that purified PPM1G dephosphorylates 4E-BP1 in vitro. Knockdown of PPM1G in 293E and colon cancer HCT116 cells results in an increase in the phosphorylation of 4E-BP1 at both the Thr-37/46 and Ser-65 sites. Furthermore, the time course of 4E-BP1 dephosphorylation induced by amino acid starvation or mammalian target of rapamycin inhibition is slowed down significantly in PPM1G knockdown cells. Functionally, the amount of 4E-BP1 bound to the cap-dependent translation initiation complex is decreased when the expression of PPM1G is depleted. As a result, the rate of cap-dependent translation, cell size, and protein content are increased in PPM1G knockdown cells. Taken together, our study has identified protein phosphatase PPM1G as a novel regulator of cap-dependent protein translation by negatively controlling the phosphorylation of 4E-BP1.

  7. Conservation of Ebp-type pilus genes among Enterococci and demonstration of their role in adherence of Enterococcus faecalis to human platelets.

    Science.gov (United States)

    Nallapareddy, Sreedhar R; Sillanpää, Jouko; Mitchell, Jennifer; Singh, Kavindra V; Chowdhury, Shahreen A; Weinstock, George M; Sullam, Paul M; Murray, Barbara E

    2011-07-01

    Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the ΔsrtA, Δbps, and ΔbpsΔsrtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species.

  8. TNF-α promotes nuclear enrichment of the transcription factor TonEBP/NFAT5 to selectively control inflammatory but not osmoregulatory responses in nucleus pulposus cells.

    Science.gov (United States)

    Johnson, Zariel I; Doolittle, Alexandra C; Snuggs, Joseph W; Shapiro, Irving M; Le Maitre, Christine L; Risbud, Makarand V

    2017-10-20

    Intervertebral disc degeneration (IDD) causes chronic back pain and is linked to production of proinflammatory molecules by nucleus pulposus (NP) and other disc cells. Activation of tonicity-responsive enhancer-binding protein (TonEBP)/NFAT5 by non-osmotic stimuli, including proinflammatory molecules, occurs in cells involved in immune response. However, whether inflammatory stimuli activate TonEBP in NP cells and whether TonEBP controls inflammation during IDD is unknown. We show that TNF-α, but not IL-1β or LPS, promoted nuclear enrichment of TonEBP protein. However, TNF-α-mediated activation of TonEBP did not cause induction of osmoregulatory genes. RNA sequencing showed that 8.5% of TNF-α transcriptional responses were TonEBP-dependent and identified genes regulated by both TNF-α and TonEBP. These genes were over-enriched in pathways and diseases related to inflammatory response and inhibition of matrix metalloproteases. Based on RNA-sequencing results, we further investigated regulation of novel TonEBP targets CXCL1 , CXCL2 , and CXCL3 TonEBP acted synergistically with TNF-α and LPS to induce CXCL1 -proximal promoter activity. Interestingly, this regulation required a highly conserved NF-κB-binding site but not a predicted TonE, suggesting cross-talk between these two members of the Rel family. Finally, analysis of human NP tissue showed that TonEBP expression correlated with canonical osmoregulatory targets TauT/SLC6A6 , SMIT/SLC5A3 , and AR/AKR1B1 , supporting in vitro findings that the inflammatory milieu during IDD does not interfere with TonEBP osmoregulation. In summary, whereas TonEBP participates in the proinflammatory response to TNF-α, therapeutic strategies targeting this transcription factor for treatment of disc disease must spare osmoprotective, prosurvival, and matrix homeostatic activities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Web-Based Evidence Based Practice Educational Intervention to Improve EBP Competence among BSN-Prepared Pediatric Bedside Nurses: A Mixed Methods Pilot Study

    Science.gov (United States)

    Laibhen-Parkes, Natasha

    2014-01-01

    For pediatric nurses, their competence in EBP is critical for providing high-quality care and maximizing patient outcomes. The purpose of this pilot study was to assess and refine a Web-based EBP educational intervention focused on improving EBP beliefs and competence in BSN-prepared pediatric bedside nurses, and to examine the feasibility,…

  10. Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets ▿ †

    OpenAIRE

    Nallapareddy, Sreedhar R.; Sillanpää, Jouko; Mitchell, Jennifer; Singh, Kavindra V.; Chowdhury, Shahreen A.; Weinstock, George M.; Sullam, Paul M.; Murray, Barbara E.

    2011-01-01

    Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority ...

  11. Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.

    Science.gov (United States)

    Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D; Pelletier, Jerry; Ferraiuolo, Maria A; Sonenberg, Nahum

    2008-07-01

    Eukaryotic initiation factor (eIF) 4E, the mRNA 5'-cap-binding protein, mediates the association of eIF4F with the mRNA 5'-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (approximately 30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.

  12. Conservation of Ebp-Type Pilus Genes among Enterococci and Demonstration of Their Role in Adherence of Enterococcus faecalis to Human Platelets ▿ †

    Science.gov (United States)

    Nallapareddy, Sreedhar R.; Sillanpää, Jouko; Mitchell, Jennifer; Singh, Kavindra V.; Chowdhury, Shahreen A.; Weinstock, George M.; Sullam, Paul M.; Murray, Barbara E.

    2011-01-01

    Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the ΔsrtA, Δbps, and ΔbpsΔsrtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species. PMID:21502588

  13. Effects of Qi-Fang-Xi-Bi-Granules on Cartilage Morphology and C/ebpα Promoter Methylation in Rats with Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Xinxin Wang

    2018-01-01

    Full Text Available Objective. To investigate the effects of Qi-Fang-Xi-Bi-Granules (QFXBGs on cartilage morphology and methylation of C/ebpα (CCAAT/enhancer binding proteinα at the promoter region. Methods. Knee osteoarthritis (KOA modeling was performed in rats in accordance with Hulth’s method, and control group received sham operation. Eight weeks after KOA modeling, the rats in the KOA modeling group were further divided into 6 groups. Each group was given the appropriate drug. After 8 weeks, half of the rats were used for Micro-CT scan, HE staining, ABH/OG staining, immunohistochemistry, and TUNNEL staining of the knee joint tissue, and the other half were used to examine C/ebpα promoter methylation. Results. The three dose groups of QFXBGs all showed lower degrees of surface fissures and flaking, thicker cartilage layer, and restored chondrocyte and subchondral bone morphology, compared with the KOA model group. C/ebpα-22 promoter methylation levels in the high- and low-dose groups were significantly higher than that in the KOA modeling group (p<0.05, while C/ebpα-2 promoter methylation level in the medium-dose group was significantly higher than that in the KOA modeling group (p<0.05. Conclusions. QFXBGs may alleviate articular cartilage degeneration through promoting C/ebpα-2 or C/ebpα-22 methylation at specific promoter sites.

  14. Dissociation of eIF4E-binding protein 2 (4E-BP2 from eIF4E independent of Thr37/Thr46 phosphorylation in the ischemic stress response.

    Directory of Open Access Journals (Sweden)

    María I Ayuso

    Full Text Available Eukaryotic initiation factor (eIF 4E-binding proteins (4E-BPs are translational repressors that bind specifically to eIF4E and are critical in the control of protein translation. 4E-BP2 is the predominant 4E-BP expressed in the brain, but their role is not well known. Here, we characterized four forms of 4E-BP2 detected by two-dimensional gel electrophoresis (2-DGE in brain. The form with highest electrophoretic mobility was the main form susceptible to phosphorylation at Thr37/Thr46 sites, phosphorylation that was detected in acidic spots. Cerebral ischemia and subsequent reperfusion induced dephosphorylation and phosphorylation of 4E-BP2 at Thr37/Thr46, respectively. The induced phosphorylation was in parallel with the release of 4E-BP2 from eIF4E, although two of the phosphorylated 4E-BP2 forms were bound to eIF4E. Upon long-term reperfusion, there was a decrease in the binding of 4E-BP2 to eIF4E in cerebral cortex, demonstrated by cap binding assays and 4E-BP2-immunoprecipitation experiments. The release of 4E-BP2 from eIF4E was without changes in 4E-BP2 phosphorylation or other post-translational modification recognized by 2-DGE. These findings demonstrated specific changes in 4E-BP2/eIF4E association dependent and independent of 4E-BP2 phosphorylation. The last result supports the notion that phosphorylation may not be the uniquely regulation for the binding of 4E-BP2 to eIF4E under ischemic stress.

  15. Targeting the Epidermal Growth Factor Receptor Can Counteract the Inhibition of Natural Killer Cell Function Exerted by Colorectal Tumor-Associated Fibroblasts

    Directory of Open Access Journals (Sweden)

    Delfina Costa

    2018-05-01

    Full Text Available Mesenchymal stromal cells (MSC present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF] can exert immunosuppressive effects on T and natural killer (NK lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16. In situ, TAF express detectable levels of epidermal growth factor receptor (EGFR; thus, the therapeutic anti-EGFR humanized antibody cetuximab can trigger the antibody-dependent cellular cytotoxicity of TAF, through the engagement of FcγRIIIA on NK cells. Importantly, in the tumor, we found a lymphoid infiltrate containing NKp46+CD3− NK cells, enriched in CD16+ cells. This population, sorted and cultured with IL-2, could be triggered via CD16 and via NKG2D. Of note, ex vivo NKp46+CD3− cells were able to kill autologous TAF; in vivo, this might represent a control mechanism to reduce TAF-mediated regulatory effect on NK cell function. Altogether, these findings suggest that MSC from the neoplastic mucosa (TAF of CRC patients can downregulate the immune cell recognition of CRC tumor cells. This immunosuppression can be relieved by the anti-EGFR antibody used in CRC immunotherapy.

  16. Targeting the Epidermal Growth Factor Receptor Can Counteract the Inhibition of Natural Killer Cell Function Exerted by Colorectal Tumor-Associated Fibroblasts

    Science.gov (United States)

    Costa, Delfina; Venè, Roberta; Benelli, Roberto; Romairone, Emanuele; Scabini, Stefano; Catellani, Silvia; Rebesco, Barbara; Mastracci, Luca; Grillo, Federica; Minghelli, Simona; Loiacono, Fabrizio; Zocchi, Maria Raffaella; Poggi, Alessandro

    2018-01-01

    Mesenchymal stromal cells (MSC) present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF)] can exert immunosuppressive effects on T and natural killer (NK) lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC) and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16). In situ, TAF express detectable levels of epidermal growth factor receptor (EGFR); thus, the therapeutic anti-EGFR humanized antibody cetuximab can trigger the antibody-dependent cellular cytotoxicity of TAF, through the engagement of FcγRIIIA on NK cells. Importantly, in the tumor, we found a lymphoid infiltrate containing NKp46+CD3− NK cells, enriched in CD16+ cells. This population, sorted and cultured with IL-2, could be triggered via CD16 and via NKG2D. Of note, ex vivo NKp46+CD3− cells were able to kill autologous TAF; in vivo, this might represent a control mechanism to reduce TAF-mediated regulatory effect on NK cell function. Altogether, these findings suggest that MSC from the neoplastic mucosa (TAF) of CRC patients can downregulate the immune cell recognition of CRC tumor cells. This immunosuppression can be relieved by the anti-EGFR antibody used in CRC immunotherapy. PMID:29910806

  17. Control structure design for resource recovery using the enhanced biological phosphorus removal and recovery (EBP2R) activated sludge process

    DEFF Research Database (Denmark)

    Valverde Perez, Borja; Fuentes-Martínez, José Manuel; Flores Alsina, Xavier

    2016-01-01

    , it is concluded that the SBR is the most effective reactor configuration for the EBP2R process. Importantly, the designed control structures rely on control loops that do not require chemical dosing for nutrient management, thereby reducing the environmental footprint of the EBP2R process. The proposed control...

  18. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  19. Pulmonary antioxidants exert differential protective effects against ...

    Indian Academy of Sciences (India)

    Unknown

    PM collections from both urban and industrial sites caused 50% oxidative degradation of DNA in vitro at concentrations as low ... chemical analysis in order that progress can be made in ... One popular hypothesis is that PM exerts toxic effects.

  20. 4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression.

    Science.gov (United States)

    Shives, Katherine D; Massey, Aaron R; May, Nicholas A; Morrison, Thomas E; Beckham, J David

    2016-10-18

    West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7 GpppN m 5' cap with 2'- O -methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.

  1. 4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression

    Directory of Open Access Journals (Sweden)

    Katherine D. Shives

    2016-10-01

    Full Text Available West Nile virus (WNV is a (+ sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1 for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K and eukaryotic translation initiation factor 4E-binding protein (4EBP pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E interaction and eukaryotic initiation factor 4F (eIF4F complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6 and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome.

  2. XBP1-Independent UPR Pathways Suppress C/EBP-β Mediated Chondrocyte Differentiation in ER-Stress Related Skeletal Disease.

    Directory of Open Access Journals (Sweden)

    Trevor L Cameron

    2015-09-01

    Full Text Available Schmid metaphyseal chondrodysplasia (MCDS involves dwarfism and growth plate cartilage hypertrophic zone expansion resulting from dominant mutations in the hypertrophic zone collagen, Col10a1. Mouse models phenocopying MCDS through the expression of an exogenous misfolding protein in the endoplasmic reticulum (ER in hypertrophic chondrocytes have demonstrated the central importance of ER stress in the pathology of MCDS. The resultant unfolded protein response (UPR in affected chondrocytes involved activation of canonical ER stress sensors, IRE1, ATF6, and PERK with the downstream effect of disrupted chondrocyte differentiation. Here, we investigated the role of the highly conserved IRE1/XBP1 pathway in the pathology of MCDS. Mice with a MCDS collagen X p.N617K knock-in mutation (ColXN617K were crossed with mice in which Xbp1 was inactivated specifically in cartilage (Xbp1CartΔEx2, generating the compound mutant, C/X. The severity of dwarfism and hypertrophic zone expansion in C/X did not differ significantly from ColXN617K, revealing surprising redundancy for the IRE1/XBP1 UPR pathway in the pathology of MCDS. Transcriptomic analyses of hypertrophic zone cartilage identified differentially expressed gene cohorts in MCDS that are pathologically relevant (XBP1-independent or pathologically redundant (XBP1-dependent. XBP1-independent gene expression changes included large-scale transcriptional attenuation of genes encoding secreted proteins and disrupted differentiation from proliferative to hypertrophic chondrocytes. Moreover, these changes were consistent with disruption of C/EBP-β, a master regulator of chondrocyte differentiation, by CHOP, a transcription factor downstream of PERK that inhibits C/EBP proteins, and down-regulation of C/EBP-β transcriptional co-factors, GADD45-β and RUNX2. Thus we propose that the pathology of MCDS is underpinned by XBP1 independent UPR-induced dysregulation of C/EBP-β-mediated chondrocyte differentiation

  3. Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats.

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    Full Text Available The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP. Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.

  4. Regulation of 4E-BP1 activity in the mammalian oocyte

    Czech Academy of Sciences Publication Activity Database

    Jansová, Denisa; Končická, Markéta; Tětková, Anna; Černá, Renata; Malík, Radek; del Llano, Edgar; Kubelka, Michal; Šušor, Andrej

    2017-01-01

    Roč. 16, č. 10 (2017), s. 927-939 ISSN 1538-4101 R&D Projects: GA ČR GA13-12291S; GA ČR GA15-22765S; GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 ; RVO:68378050 Keywords : 4E-BP1 * CDK1 * cumulus cells Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.530, year: 2016

  5. Interference with PSMB4 Expression Exerts an Anti-Tumor Effect by Decreasing the Invasion and Proliferation of Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chen Cheng

    2018-01-01

    matrix metallopeptidase 9 in vivo. Conclusion: PSMB4 inhibition in combination with TMZ may exert an anti-tumor effect by decreasing cell proliferation and invasion as well as by promoting apoptosis in human glioblastoma cells. This research may improve the therapeutic efficacy of glioblastoma treatment.

  6. Betulinic Acid Exerts Cytotoxic Activity Against Multidrug-Resistant Tumor Cells via Targeting Autocrine Motility Factor Receptor (AMFR

    Directory of Open Access Journals (Sweden)

    Mohamed E. M. Saeed

    2018-05-01

    Full Text Available Betulinic acid (BetA is a naturally occurring pentacyclic triterpene isolated from the outer bark of white-barked birch trees and many other medicinal plants. Here, we studied betulinic acid's cytotoxic activity against drug-resistant tumor cell lines. P-glycoprotein (MDR1/ABCB1 and BCRP (ABCG2 are known ATP-binding cassette (ABC drug transporters that mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. Constitutive activation of the EGF receptor is tightly linked to the development of chemotherapeutic resistance. BetA inhibited P-gp, BCRP, ABCB5 and mutation activated EGFR overexpressing cells with similar efficacy as their drug-sensitive parental counterparts. Furthermore, the mRNA expressions of ABCB1, BCRP, ABCB5 and EGFR were not related to the 50% inhibition concentrations (IC50 for BetA in a panel of 60 cell lines of the National Cancer Institute (NCI, USA. In addition to well-established MDR mechanisms, we attempted to identify other molecular mechanisms that play a role in mediating BetA's cytotoxic activity. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell lines panel. Various genes significantly correlating to BetA's activity were involved in different biological processes, e.g., cell cycle regulation, microtubule formation, signal transduction, transcriptional regulation, chromatin remodeling, cell adhesion, tumor suppression, ubiquitination and proteasome degradation. Immunoblotting and in silico analyses revealed that the inhibition of AMFR activity might be one of the mechanisms for BetA to overcome MDR phenotypes. In conclusion, BetA may have therapeutic potential for the treatment of refractory tumors.

  7. Cell Cycle-Dependent Recruitment of Polycomb Proteins to the ASNS Promoter Counteracts C/ebp-Mediated Transcriptional Activation in Bombyx mori

    Science.gov (United States)

    Li, Zhiqing; Cheng, Daojun; Mon, Hiroaki; Zhu, Li; Xu, Jian; Tatsuke, Tsuneyuki; Lee, Jae Man; Xia, Qingyou; Kusakabe, Takahiro

    2013-01-01

    Epigenetic modifiers and transcription factors contribute to developmentally programmed gene expression. Here, we establish a functional link between epigenetic regulation by Polycomb group (PcG) proteins and transcriptional regulation by C/ebp that orchestrates the correct expression of Bombyx mori asparagine synthetase (BmASNS), a gene involved in the biosynthesis of asparagine. We show that the cis-regulatory elements of YY1-binding motifs and the CpG island present on the BmASNS promoter are required for the recruitment of PcG proteins and the subsequent deposition of the epigenetic repression mark H3K27me3. RNAi-mediated knockdown of PcG genes leads to derepression of the BmASNS gene via the recruitment of activators, including BmC/ebp, to the promoter. Intriguingly, we find that PcG proteins and BmC/ebp can dynamically modulate the transcriptional output of the BmASNS target in a cell cycle-dependent manner. It will be essential to suppress BmASNS expression by PcG proteins at the G2/M phase of the cell cycle in the presence of BmC/ebp activator. Thus, our results provide a novel insight into the molecular mechanism underlying the recruitment and regulation of the PcG system at a discrete gene locus in Bombyx mori. PMID:23382816

  8. NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory effects by inducing a G1 cell cycle arrest

    International Nuclear Information System (INIS)

    Andries, Vanessa; Vandepoele, Karl; Staes, Katrien; Berx, Geert; Bogaert, Pieter; Van Isterdael, Gert; Ginneberge, Daisy; Parthoens, Eef; Vandenbussche, Jonathan; Gevaert, Kris; Roy, Frans van

    2015-01-01

    NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally identified in a neuroblastoma patient on the basis of its disruption by a chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect and the frequent genomic alterations of the NBPF1 locus in several cancer types, we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. However, little is known about the mechanisms involved. Expression of NBPF was analyzed in human skin and human cervix by immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by flow cytometry. We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. Protein levels of CDKN1A-encoded p21 CIP1/WAF1 were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. Possible biological interactions between the differentially regulated proteins were investigated with the Ingenuity Pathway Analysis tool. We show that NBPF is expressed in the non-proliferative suprabasal layers of squamous stratified epithelia of human skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell

  9. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  10. Exertion Testing in Youth with Mild Traumatic Brain Injury/Concussion.

    Science.gov (United States)

    Dematteo, Carol; Volterman, Kimberly A; Breithaupt, Peter G; Claridge, Everett A; Adamich, John; Timmons, Brian W

    2015-11-01

    The decision regarding return to activity (RTA) after mild traumatic brain injuries/concussion is one of the most difficult and controversial areas in concussion management, particularly for youth. This study investigated how youth with postconcussion syndrome (PCS) are affected by exertion and whether standardized exertion testing using the McMaster All-Out Progressive Continuous Cycling Test can contribute to clinical decision making for safe RTA. Fifty-four youth (8.5-18.3 yr) with a previously confirmed concussion participated in the study. Each participant performed exertion testing on a cycle ergometer and completed a Postconcussion Symptom scale at the following time points: before exertion (baseline), 5 and 30 min, and 24 h after exertion. A modified Postconcussion Symptom scale was administered at 2-min intervals during exertion. Participants had a mean ± SD symptom duration of 6.3 ± 6.9 months after the most recent concussive injury, with a median of 4.1 months (range, 0.7-35 months). Sixty-three percent of participants had symptoms during exertion testing. Symptom profile (number and severity) significantly affected perception of exertion at 50% peak mechanical power. During acute assessment of symptoms (30-min after exertion), headache (P = 0.39), nausea (P = 0.63), and dizziness (P = 0.35) did not change. However, both the number and severity of symptoms significantly improved over 24 h, with 56.8% of youth showing improvements. The time from the most recent injury had a significant effect on the symptom score at baseline, 30 min after exertion, and 24 h after exertion. Exertion testing has an important role in the evaluation of symptoms and readiness to RTA, particularly in youth who are slow to recover. Overall, controlled exertion seemed to lesson symptoms for most youth.

  11. Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice

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    Ramon eGarcia-Areas

    2014-02-01

    Full Text Available Semaphorins, a large family of molecules involved in the axonal guidance and development of the nervous system, have been recently shown to have both angiogenic and anti-angiogenic properties. Specifically, semaphorin 7A (SEMA7A has been reported to have a chemotactic activity in neurogenesis, and to be an immune modulator via it binding to α1β1integrins. Additionally, SEMA7A has been shown to promote chemotaxis of monocytes, inducing them to produce proinflammatory mediators. In this study we explored the role of SEMA7A in the tumoral context. We show that SEMA7A is highly expressed by DA-3 murine mammary tumor cells in comparison to normal mammary cells (EpH4, and that peritoneal macrophages from mammary tumor-bearing mice also express SEMA7A at higher levels compared to peritoneal macrophages derived from normal control mice. We also show that murine macrophages treated with recombinant murine SEMA7A significantly increased their expression of proangiogenic molecules, such as CXCL2/MIP-2. Gene silencing of SEMA7A in peritoneal elicited macrophages from DA-3 tumor-bearing mice resulted in decreased CXCL2 expression. Mice implanted with SEMA7A silenced tumor cells showed decreased angiogenesis in the tumors compared to the wild type tumors. Furthermore, peritoneal elicited macrophages from mice bearing SEMA7A-silenced tumors produce significantly (p< 0.01 lower levels of angiogenic proteins, such as MIP-2, CXCL1 and MMP-9, compared to macrophages from control DA-3 mammary tumors. We postulate that SEMA7A derived from mammary carcinomas may serve as a monocyte chemoattractant and skew monocytes into a pro-tumorigenic phenotype. A putative relationship between tumor-derived SEMA7A and monocytes could prove valuable in establishing new research avenues towards unraveling important tumor-host immune interactions in breast cancer patients.

  12. Disruption of the C/EBP alpha-miR-182 balance impairs granulocytic differentiation

    Czech Academy of Sciences Publication Activity Database

    Wurm, A.A.; Zjablovskaja, Polina; Kardošová, Miroslava; Gerloff, D.; Braeuer-Hartmann, D.; Katzerke, C.; Hartmann, J.U.; Benoukraf, T.; Fricke, S.; Hilger, N.; Mueller, A.M.; Bill, M.; Schwind, S.; Tenen, D.G.; Niederwieser, D.; Alberich-Jorda, Meritxell; Behre, G.

    2017-01-01

    Roč. 8, červen (2017), č. článku 46. ISSN 2041-1723 Institutional support: RVO:68378050 Keywords : acute myeloid- leukemia * colony-stimulating factor * acute promyelocytic leukemia * hematopoietic stem-cells * c/ebp-alpha function * gene-expression * cebpa mutations * cycle control * up-regulation * in-vivo Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 12.124, year: 2016

  13. Sox4 is a key oncogenic target in C/EBP alpha mutant acute myeloid leukemia

    Czech Academy of Sciences Publication Activity Database

    Zhang, H.; Alberich-Jorda, Meritxell; Amabile, G.; Yang, H.; Staber, P.B.; DiRuscio, A.; Welner, R.S.; Ebralidze, A.; Zhang, J.; Levantini, E.; Lefebvre, V.; Valk, P.J.; Delwel, R.; Hoogenkamp, M.; Nerlov, C.; Cammenga, J.; Saez, B.; Scadden, D.T.; Bonifer, C.; Ye, M.; Tenen, D.G.

    2013-01-01

    Roč. 24, č. 5 (2013), s. 575-588 ISSN 1535-6108 R&D Projects: GA MŠk LK21307 Institutional support: RVO:68378050 Keywords : Sox4 * C/EBP alpha * acute myeloid leukemia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 23.893, year: 2013

  14. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Directory of Open Access Journals (Sweden)

    Y. V. Gavrilov

    2015-12-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  15. Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

    Science.gov (United States)

    Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

    2015-09-15

    Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1. Copyright © 2015 the American Physiological Society.

  16. Phyllodes tumor: clinical, radiological and pathological correlation in 50 cases; Tumor filodes: correlacion clinica, radiologica y anatomopatologica en 50 casos

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    Higueras, A.; Alvarez, M.; Jimenez, A.; Garcia Revillo, J.; Cano, A. [Hospital Universitario Reina Sofia. Cordoba (Spain)

    2000-07-01

    To review the radiological features of the phyllodes tumor, correlating them with the clinical presentation, histological type and response to treatment. Fifty phyllodes tumors in 29 patients aged 16 to 59 years (mean: 41 years) were analyzed retrospectively. The series included 12 cases of recurrence, 1 of bilateral tumor and 6 of multiple tumor. Forty-five lesions were studied by mammography and 36 by ultrasound. Clinically guided fine-needle aspiration cytology was performed in 8 cases. The pathological diagnosis was obtained by means of surgical biopsy in every case (31 benign and 19 malignant). Twenty-four patients underwent postoperative clinical and radiological follow-up for a mean period of 32 months. Mammography revealed the presence of a nodule or mass in 42 cases, asymmetrical density in two and a generalized increase in density in one: Multifocal lesions were detected in six cases. The size varied widely, with masses measuring >5 cm showing a greater probability of malignancy (p<0.01). Calcifications were observed in 13% of the cases. Ultrasound revealed the presence of heterogeneous, hypoechoic nodules, with cystic areas in five tumors, all of which were malignant (p<0.01). Local recurrence was detected in 31% of the cases and bone metastases in one. The phyllodes tumor is an uncommon fibroepithelial tumor that has a potential for recurrence and distant metastasis. Mammographic and ultrasound features are similar to those of the fibroadenoma, a lesion with which it is occasionally associated. Multiple lesions are not infrequent and it can present with calcifications. The presence of cystic areas and a tumor size of >5 cm are the only radiological findings that are statistically associated with malignancy. The recurrence rate is greater in malignant tumors than in benign lesions, especially in patients treated by tumor resection. (Author) 28 refs.

  17. Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

    International Nuclear Information System (INIS)

    Mitsuishi, Tsuyoshi; Kawana, Seiji; Ozaki, Kohji; Nakatake, Mayuka; Yamada, Osamu; Iwabu, Yukie; Tokunaga, Kenzo; Sata, Tetsutaro; Kaneko, Takehiko; Ohara, Kuniaki; Ohsawa, Ikuroh; Oda, Fumino; Yamada, Yuko

    2010-01-01

    The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors. We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity. Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression. Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors

  18. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells

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    Juan Li

    2014-03-01

    Full Text Available Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.

  19. Diagnostic significance of tumor markers CEA, CA50 and CA19-9 for colorectal cancer

    International Nuclear Information System (INIS)

    Chen Yumei; Huang Gang

    2005-01-01

    Objective: To investigate the expression and diagnostic significance of three serum tumor markers (CEA, CA50, CA19-9) in patients with colorectal cancer, with special emphasis on their combined assay. Methods: Serum CEA, CA19-9 levels (with chemiluminescence immunoassay) and CA50 levels (with immunoradiometric assay) were determined in 94 patients with colorectal cancer, 20 patients with benign colorectal disorders and 37 controls. Results: The expressions of the serum tumor markers were significantly higher in patients with colorectal cancer than those in patients with benign colorectal disorders and controls (P<0.05). There was no significant difference between the levels in the latter two groups. CEA assay had the highest sensitivity (57.4%) and specificity (85.9%). Combined assay of the three could enhance both the sensitivity (62.7%) and specificity (96.5%). The serum levels of the markers were significantly higher in patients with colonic cancer than those in patients with rectal cancer (P<0.05). The levels were positively correlated with the size of the growth and stage of the disease. Serum tumor marker levels were also significantly higher in patients with metastasis (regional/distant) than those in patients without metastasis (P<0.05). Conclusion: Determination of serum CEA, CA50 and CA19-9 levels had definite value for the diagnosis and assessment of the pathology as well as biologic behavior colorectal cancer. Combined assay of the three could enhance the diagnostic sensitivity and specificity. (authors)

  20. The threonine protease activity of testes-specific protease 50 (TSP50 is essential for its function in cell proliferation.

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    Yu-Yin Li

    Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50, a newly discovered threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood. METHODOLOGY/PRINCIPAL FINDINGS: To delineate whether the threonine protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-κBIκBα complex, which is necessary for TSP50 to perform its function in cell proliferation. CONCLUSION: Our data highlight the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50-induced cell proliferation and tumor formation.

  1. The novel fusion proteins, GnRH-p53 and GnRHIII-p53, expression and their anti-tumor effect.

    Directory of Open Access Journals (Sweden)

    Peiyuan Jia

    Full Text Available p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH, as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R, was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.

  2. Physical properties of LDPE/ethylene-1-butene copolymer film irradiated by electron beam

    International Nuclear Information System (INIS)

    Kim, Jeong Il; Nho, Young Chang

    2004-01-01

    In this study, ethylene-1-butene copolymer (EBP) was blended with LDPE to improve the mechanical properties as the packaging materials. After they were irradiated by electron beam, their physical properties such as tensile strength, elongation, modulus, peel strength, DSC, DMA were examined. The results showed that the addition of EBP to LDPE exerted significant effects on the mechanical properties such as the tensile strength and peel strength. The addition of EBP led to a maximum increase in peel strength of ∼430%. The addition of 10 - 25 w% EBP in LDPE was sufficient to enhance the peel strength significantly. (author)

  3. Peel strength of LDPE/ethylene-1-butene copolymer film crosslinked by radiation

    International Nuclear Information System (INIS)

    Nho, Young Chang; Kim, Jeong Il; Kang, Phil Hyun

    2003-01-01

    In this study, ethylene-1-butene copolymer(EBP) was blended with LDPE to improve the mechanical properties as the packaging materials. After they were irradiated by an electron beam, their physical properties such as tensile strength, elongation, modulus, peel strength, DSC, and DMA were examined. The results showed that the addition of EBP to LDPE exerted significant effects on the mechanical properties such as the tensile strength and peel strength. The addition of EBP led to a maximum increase in peel strength of ∼ 430%. The addition of 10-25w% EBP in LDPE was sufficient to enhance the peel strength significantly

  4. Tumor control probability after a radiation of animal tumors

    International Nuclear Information System (INIS)

    Urano, Muneyasu; Ando, Koichi; Koike, Sachiko; Nesumi, Naofumi

    1975-01-01

    Tumor control and regrowth probability of animal tumors irradiated with a single x-ray dose were determined, using a spontaneous C3H mouse mammary carcinoma. Cellular radiation sensitivity of tumor cells and tumor control probability of the tumor were examined by the TD 50 and TCD 50 assays respectively. Tumor growth kinetics were measured by counting the percentage of labelled mitosis and by measuring the growth curve. A mathematical analysis of tumor control probability was made from these results. A formula proposed, accounted for cell population kinetics or division probability model, cell sensitivity to radiation and number of tumor cells. (auth.)

  5. Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells.

    Science.gov (United States)

    Ogawa, Mutsumi; Nakai, Seiji; Deguchi, Akihiro; Nonomura, Takako; Masaki, Tsutomu; Uchida, Naohito; Yoshiji, Hitoshi; Kuriyama, Shigeki

    2007-08-01

    Although a number of studies have shown that vitamin K possesses antitumor activities on various neoplastic cell lines, there are few reports demonstrating in vivo antitumor effects of vitamin K, and the antitumor effect on colorectal cancer (CRC) remains to be examined. Therefore, antitumor effects of vitamin K on CRC were examined both in vitro and in vivo. Vitamins K2, K3 and K5 suppressed the proliferation of colon 26 cells in a dose-dependent manner, while vitamin K1 did not. On flow cytometry, induction of apoptosis by vitamins K2, K3 and K5 was suggested by population in sub-G1 phase of the cell cycle. Hoechst 33342 staining and a two-color flow cytometric assay using fluorescein isothiocyanate-conjugated annexin V and propidium iodide confirmed that vitamins K2, K3 and K5 induced apoptotic death of colon 26 cells. Enzymatic activity of caspase-3 in colon 26 cells was significantly up-regulated by vitamins K2, K3 and K5. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, substantially prevented vitamin K-mediated apoptosis. In vivo study using syngeneic mice with subcutaneously established colon 26 tumors demonstrated that intravenous administration of vitamins K2, K3 and K5 significantly suppressed the tumor growth. The number of apoptotic tumor cells was significantly larger in the vitamin K-treated groups than in the control group. These results suggest that vitamins K2, K3 and K5 exerted effective antitumor effects on CRC in vitro and in vivo by inducing caspase-dependent apoptotic death of tumor cells, suggesting that these K vitamins may be promising agents for the treatment of patients with CRC.

  6. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.

    Science.gov (United States)

    Shikata, Yuki; Kiga, Masaki; Futamura, Yushi; Aono, Harumi; Inoue, Hiroyuki; Kawada, Manabu; Osada, Hiroyuki; Imoto, Masaya

    2017-04-01

    The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Exertional heat stroke management strategies in United States high school football.

    Science.gov (United States)

    Kerr, Zachary Y; Marshall, Stephen W; Comstock, R Dawn; Casa, Douglas J

    2014-01-01

    The 5-year period of 2005-2009 saw more exertional heat stroke-related deaths in organized sports than any other 5-year period in the past 35 years. The risk of exertional heat stroke appears highest in football, particularly during the preseason. To estimate the incidence of exertional heat stroke events and assess the utilization of exertional heat stroke management strategies during the 2011 preseason in United States high school football programs. Cross-sectional study; Level of evidence, 3. A self-administered online questionnaire addressing the incidence of exertional heat stroke events and utilization of exertional heat stroke management strategies (eg, removing athlete's football equipment, calling Emergency Medical Services [EMS]) was completed in May to June 2012 by 1142 (18.0%) athletic trainers providing care to high school football athletes during the 2011 preseason. Among all respondents, 20.3% reported treating at least 1 exertional heat stroke event. An average of 0.50 ± 1.37 preseason exertional heat stroke events were treated per program. Athletic trainers responding to exertional heat stroke reported using an average of 6.6 ± 1.8 management strategies. The most common management strategies were low-level therapeutic interventions such as removing the athlete's football equipment (98.2%) and clothing (77.8%) and moving the athlete to a shaded area (91.6%). Few athletic trainers reported active management strategies such as calling EMS (29.3%) or using a rectal thermometer to check core body temperature (0.9%). Athletic trainers in states with mandated preseason heat acclimatization guidelines reported a higher utilization of management strategies such as cooling the athlete through air conditioning (90.1% vs 65.0%, respectively; P football programs. The standard of care is (and should be) to treat proactively; therefore, treatment is not a perfect proxy for incidence. Nevertheless, there is an urgent need for improved education and awareness of

  8. Capability beliefs regarding evidence-based practice are associated with application of EBP and research use: validation of a new measure.

    Science.gov (United States)

    Wallin, Lars; Boström, Anne-Marie; Gustavsson, J Petter

    2012-08-01

    Beliefs about capabilities, or self-efficacy, is a construct originating in social cognitive psychology. Capability beliefs have been found to be positively associated with intention and healthcare practice behaviour. A measure of an individual's beliefs about his/her capability to apply the components of evidence-based practice (EBP) has potential to be useful in implementation research. To evaluate the concurrent validity and internal structure of a new scale measuring nurses' capability beliefs regarding EBP. Data were taken from a prospective longitudinal study in Sweden (the Longitudinal Analyses of Nursing Education and Entry in Worklife [LANE]). A cohort of nursing students who graduated in the autumn of 2004 that was followed up 2 years after their graduation was used (n= 1,256). Concurrent validity was tested relating different levels of capability beliefs to extent of research use and application of EBP. An item-response approach was applied in the evaluation of internal structure of the proposed scale (six items). The psychometric analyses indicated that the six items could be summed to reflect a one-dimensional scale. Nurses with the highest level of capability beliefs reported that they used research findings in clinical practice more than twice as often as those with lower levels of capability beliefs. They also participated in the implementation of evidence seven times more often. There is a need for further studies of the construct and predictive validity of the scale. It should also be validated in other groups of health professionals. Learning including mastery experiences, role modelling, social persuasion, and manageable stress could be used in undergraduate education as well as practice development to increase beliefs about capabilities which might open the way to increased application of EBP in healthcare practice. This new measure is well grounded in social cognitive theory, functions as a one-dimensional scale and possesses promising

  9. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse

    Directory of Open Access Journals (Sweden)

    Kimura Shioko

    2012-12-01

    Full Text Available Abstract Background The CCAAT/enhancer binding proteins (C/EBPs play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. Methods A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined. Results A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse. Conclusions The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.

  11. Perspectives on Exertional Rhabdomyolysis.

    Science.gov (United States)

    Rawson, Eric S; Clarkson, Priscilla M; Tarnopolsky, Mark A

    2017-03-01

    Exertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and exertional rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for exertional rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of exertional rhabdomyolysis so prompt treatment can be administered. For the risk of rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.

  12. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    OpenAIRE

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and ...

  13. The definition of exertion-related cardiac events.

    Science.gov (United States)

    Rai, M; Thompson, P D

    2011-02-01

    Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

  14. Relative Biologic Effectiveness (RBE) of 50 kV X-rays Measured in a Phantom for Intraoperative Tumor-Bed Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi; Schneider, Frank; Ma, Lin; Wenz, Frederik [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany); Herskind, Carsten, E-mail: carsten.herskind@medma.uni-heidelberg.de [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany)

    2013-03-15

    Purpose: Intraoperative radiation therapy (IORT) with low-energy x-rays is used to treat the tumor bed during breast-conserving surgery. The purpose was to determine the relative biologic effectiveness (RBE) of 50-kV x-rays for inactivation of cells irradiated in a tumor-bed phantom. Methods and Materials: The RBE was determined for clonogenic inactivation of human tumor and normal cells (MCF7, human umbilical vein endothelial cells, normal skin fibroblasts), and hamster V79 cells. The 50-kV x-rays from the Intrabeam machine (Carl Zeiss Surgical) with a spherical 4-cm applicator were used. Cells were irradiated in a water-equivalent phantom at defined distances (8.1-22.9 mm) from the applicator surface. The 50-kV x-rays from a surface therapy machine (Dermopan, Siemens) were included for comparison; 6-MV x-rays were used as reference radiation. Results: At 8.1-mm depth in the phantom (dose rate 15.1 Gy/h), mean RBE values of 50-kV x-rays from Intrabeam were 1.26 to 1.42 for the 4 cell types at doses yielding surviving fractions in the range of 0.01 to 0.5. Confidence intervals were in the range of 1.2 and 1.5. Similar RBE values were found for 50-kV x-rays from Dermopan for V79 (1.30, CI 1.25-1.36, P=.74) and GS4 (1.42, CI 1.30-1.54, P=.67). No significant dependence of RBE on dose was found for Intrabeam, but RBE decreased at a larger distance (12.7 mm; 9.8 Gy/h). Conclusions: An increased clinically relevant RBE was found for cell irradiation with Intrabeam at depths in the tumor bed targeted by IORT. The reduced RBE values at larger distances may be related to increased repair of sublethal damage during protracted irradiation or to hardening of the photon beam energy.

  15. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    International Nuclear Information System (INIS)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O.; Mihaila, M.A.; Kaya, D.A.; Stan, R.; Meghea, A.

    2015-01-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL −1 has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL −1 lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor cells. • 50

  16. Lipid nanocarriers based on natural oils with high activity against oxygen free radicals and tumor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lacatusu, I.; Badea, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Mihaila, M.A. [Institute of Virusology “Stefan S. Nicolau”, Center of Immunology, Bravu Road, No. 285, 030304 Bucharest (Romania); Kaya, D.A. [Department of Field Crops, Faculty of Agriculture, Mustafa Kemal University, 31030 Antakya, Hatay (Turkey); Stan, R., E-mail: rl_stan2000@yahoo.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No 1, 011061 Bucharest (Romania)

    2015-11-01

    The development of nano-dosage forms of phytochemicals represents a significant progress of the scientific approach in the biomedical research. The aim of this study was to assess the effectiveness of lipid nanocarriers based on natural oils (grape seed oil, fish oil and laurel leaf oil) in counteracting free radicals and combating certain tumor cells. No drug was encapsulated in the nanocarriers. The cytotoxic effect exerted by bioactive nanocarriers against two tumor cells, MDA-MB 231 and HeLa cell lines, and two normal cells, L929 and B16 cell lines, was measured using the MTT assay, while oxidative damage was assessed by measuring the total antioxidant activity using chemiluminescence analysis. The best performance was obtained for nanocarriers based on an association of grape seed and laurel leaf oils, with a capacity to scavenge about 98% oxygen free radicals. A dose of nanocarriers of 5 mg·mL{sup −1} has led to a drastic decrease in tumor cell proliferation even in the absence of an antitumor drug (e.g. about 50% viability for MDA-MB 231 cell line and 60% viability for HeLa cell line). A comparative survival profile of normal and tumor cells, which were exposed to an effective dose of 2.5 mg·mL{sup −1} lipid nanocarriers, has revealed a death rate of 20% for normal B16 cells and of 40% death rate for MDA-MB 231 and HeLa tumor cells. The results in this study imply that lipid nanocarriers based on grape seed oil in association with laurel leaf oil could be a candidate to reduce the delivery system toxicity and may significantly improve the therapeutic efficacy of antitumor drugs in clinical applications. - Highlights: • Functional lipid nanocarriers with unique features and broad spectrum effectiveness • Lipid nanocarriers based on laureal leaf oil (LLO) and grape seed oil (GSO) • Antioxidant activity has reached 98% for nanocarriers containing 25% GSO and 2% LLO. • LLO exerts a significant cytotoxic effect against HeLa and MDA-MB 231 tumor

  17. Expanding the domains of attitudes towards evidence-based practice: the evidence based practice attitude scale-50.

    Science.gov (United States)

    Aarons, Gregory A; Cafri, Guy; Lugo, Lindsay; Sawitzky, Angelina

    2012-09-01

    Mental health and social service provider attitudes toward evidence-based practice have been measured through the development and validation of the Evidence-Based Practice Attitude Scale (EBPAS; Aarons, Ment Health Serv Res 6(2):61-74, 2004). Scores on the EBPAS scales are related to provider demographic characteristics, organizational characteristics, and leadership. However, the EBPAS assesses only four domains of attitudes toward EBP. The current study expands and further identifies additional domains of attitudes towards evidence-based practice. A qualitative and quantitative mixed-methods approach was used to: (1) generate items from multiples sources (researcher, mental health program manager, clinician/therapist), (2) identify potential content domains, and (3) examine the preliminary domains and factor structure through exploratory factor analysis. Participants for item generation included the investigative team, a group of mental health program managers (n = 6), and a group of clinicians/therapists (n = 8). For quantitative analyses a sample of 422 mental health service providers from 65 outpatient programs in San Diego County completed a survey that included the new items. Eight new EBPAS factors comprised of 35 items were identified. Factor loadings were moderate to large and internal consistency reliabilities were fair to excellent. We found that the convergence of these factors with the four previously identified evidence-based practice attitude factors (15 items) was small to moderate suggesting that the newly identified factors represent distinct dimensions of mental health and social service provider attitudes toward adopting EBP. Combining the original 15 items with the 35 new items comprises the EBPAS 50-item version (EBPAS-50) that adds to our understanding of provider attitudes toward adopting EBPs. Directions for future research are discussed.

  18. Neonatal Persistent Exposure to 6-Propyl-2-thiouracil, a Thyroid-Disrupting Chemical, Differentially Modulates Expression of Hepatic Catalase and C/EBP-β in Adult Rats.

    Science.gov (United States)

    Bunker, Suresh Kumar; Dandapat, Jagneshwar; Sahoo, Sunil Kumar; Roy, Anita; Chainy, Gagan B N

    2016-02-01

    Persistent exposure of rats to 6-propyl-2-thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP-β). Catalase promoter region (-185 to +52) that contains binding sites for C/EBP-β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP-β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid-disrupting properties of PTU. It is possible that besides thyroid-disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter. © 2015 Wiley Periodicals, Inc.

  19. Identification of the promoter region required for human adiponectin gene transcription: Association with CCAAT/enhancer binding protein-β and tumor necrosis factor-α

    International Nuclear Information System (INIS)

    Kita, Atsushi; Yamasaki, Hironori; Kuwahara, Hironaga; Moriuchi, Akie; Fukushima, Keiko; Kobayashi, Masakazu; Fukushima, Tetsuya; Takahashi, Ryoko; Abiru, Norio; Uotani, Shigeo; Kawasaki, Eiji; Eguchi, Katsumi

    2005-01-01

    Adiponectin, an adipose tissue-specific plasma protein, is involved in insulin sensitizing and has anti-atherosclerotic properties. Plasma levels of adiponectin are decreased in obese individuals and patients with type 2 diabetes with insulin resistance. Tumor necrosis factor-α (TNF-α) decreases the expression of adiponectin in adipocytes. The aims of the present study were: (1) to identify the promoter region responsible for basal transcription of the human adiponectin gene, and (2) to investigate the mechanism by which adiponectin was regulated by TNF-α. The human adiponectin promoter (2.1 kb) was isolated and used for luciferase reporter analysis by transient transfection into 3T3-L1 adipocytes. Deletion analysis demonstrated that the promoter region from -676 to +41 was sufficient for basal transcriptional activity. Mutation analysis of putative response elements for sterol regulatory element binding protein (SREBP) (-431 to -423) and CCAAT/enhancer binding protein (C/EBP) (-230 to -224) showed that both elements were required for basal promoter activity. Adiponectin transcription was increased 3-fold in cells that over-expressed constitutively active C/EBP-β. Electrophoretic mobility shift assay, using nuclear extract from 3T3-L1 cells and the -258 to -199 region as a probe, demonstrated specific DNA-protein binding, which was abolished by TNF-α treatment. The present data indicate that the putative response elements for SREBP and C/EBP are required for human adiponectin promoter activity, and that suppression by TNF-α may, at least in part, be associated with inactivation of C/EBP

  20. Does mental exertion alter maximal muscle activation?

    Directory of Open Access Journals (Sweden)

    Vianney eRozand

    2014-09-01

    Full Text Available Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 minutes each: i high mental exertion (incongruent Stroop task, ii moderate mental exertion (congruent Stroop task, iii low mental exertion (watching a movie. In each condition, mental exertion was combined with ten intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 minutes. Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors.

  1. Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics.

    Science.gov (United States)

    Sweeney, Carol; Bernard, Philip S; Factor, Rachel E; Kwan, Marilyn L; Habel, Laurel A; Quesenberry, Charles P; Shakespear, Kaylynn; Weltzien, Erin K; Stijleman, Inge J; Davis, Carole A; Ebbert, Mark T W; Castillo, Adrienne; Kushi, Lawrence H; Caan, Bette J

    2014-05-01

    Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9). Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Subtyping in a population-based cohort revealed distinct profiles by age and race. ©2014 AACR.

  2. Exertional dyspnoea in obesity

    Directory of Open Access Journals (Sweden)

    Vipa Bernhardt

    2016-12-01

    Full Text Available The purpose of cardiopulmonary exercise testing (CPET in the obese person, as in any cardiopulmonary exercise test, is to determine the patient's exercise tolerance, and to help identify and/or distinguish between the various physiological factors that could contribute to exercise intolerance. Unexplained dyspnoea on exertion is a common reason for CPET, but it is an extremely complex symptom to explain. Sometimes obesity is the simple answer by elimination of other possibilities. Thus, distinguishing among multiple clinical causes for exertional dyspnoea depends on the ability to eliminate possibilities while recognising response patterns that are unique to the obese patient. This includes the otherwise healthy obese patient, as well as the obese patient with potentially multiple cardiopulmonary limitations. Despite obvious limitations in lung function, metabolic disease and/or cardiovascular dysfunction, obesity may be the most likely reason for exertional dyspnoea. In this article, we will review the more common cardiopulmonary responses to exercise in the otherwise healthy obese adult with special emphasis on dyspnoea on exertion.

  3. Effects of Androgen Ablation on Anti-Tumor Immunity

    National Research Council Canada - National Science Library

    Kast, Martin

    2004-01-01

    .... This AA induced autoimmune-like response exerts limited anti-tumor activity in a murine prostate cancer model, but could be synergistic with CTLA-4 blockade that promotes the development of autoreactive T cell...

  4. Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative py235 erythrocyte binding protein

    KAUST Repository

    Ogun, Solabomi A.

    2011-02-17

    Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional

  5. Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative py235 erythrocyte binding protein

    KAUST Repository

    Ogun, Solabomi A.; Tewari, Rita; Otto, Thomas D.; Howell, Steven A.; Knuepfer, Ellen; Cunningham, Deirdre A.; Xu, Zhengyao; Pain, Arnab; Holder, Anthony A.

    2011-01-01

    Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional

  6. Targeted disruption of py235ebp-1: invasion of erythrocytes by Plasmodium yoelii using an alternative Py235 erythrocyte binding protein.

    Directory of Open Access Journals (Sweden)

    Solabomi A Ogun

    2011-02-01

    Full Text Available Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2 is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this

  7. Exerting Capacity.

    Science.gov (United States)

    Leger, J Michael; Phillips, Carolyn A

    2017-05-01

    Patient safety has been at the forefront of nursing research since the release of the Institute of Medicine's report estimating the number of preventable adverse events in hospital settings; yet no research to date has incorporated the perspectives of bedside nurses using classical grounded theory (CGT) methodology. This CGT study explored the perceptions of bedside registered nurses regarding patient safety in adult acute care hospitals. Data analysis used three techniques unique to CGT-the constant comparative method, coding, and memoing-to explore the values, realities, and beliefs of bedside nurses about patient safety. The analysis resulted in a substantive theory, Exerting Capacity, which explained how bedside nurses balance the demands of keeping their patients safe. Exerting Capacity has implications for health care organization leaders, nursing leaders, and bedside nurses; it also has indications for future research into the concept of patient safety.

  8. Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma.

    Science.gov (United States)

    Liu, Tongxin; Sun, Quanquan; Li, Qi; Yang, Hua; Zhang, Yuqin; Wang, Rong; Lin, Xiaoshan; Xiao, Dong; Yuan, Yawei; Chen, Longhua; Wang, Wei

    2015-02-01

    Although combined chemoradiotherapy has provided considerable improvements for nasopharyngeal carcinoma (NPC), recurrence and metastasis are still frequent. The PI3K/Akt/mTOR pathway plays a critical role in tumor formation and tumor cell survival after radiation-induced DNA damage. In the present study, we evaluated whether inhibition of PI3K/mTOR by two novel dual inhibitors, GSK2126458 and PKI-587, could suppress tumor progression and sensitize NPC cells to radiation. Four NPC cell lines (CNE-1, CNE-2, 5-8F, and 6-10B) were used to analyze the effects of GSK216458 and PKI-587 on cell proliferation, migration, invasion, clonogenic survival, amount of residual γ-H2AX foci, cell cycle, and apoptosis after radiation. A 5-8F xenograft model was used to evaluate the in vivo effects of the two compounds in combination with ionizing radiation (IR). Both GSK216458 and PKI-587 effectively inhibited cell proliferation and motility in NPC cells and suppressed phosphorylation of Akt, mTOR, S6, and 4EBP1 proteins in a concentration- and time-dependent manner. Moreover, both compounds sensitized NPC cells to IR by increasing DNA damage, enhancing G2-M cell-cycle delay, and inducing apoptosis. In vivo, the combination of IR with GSK2126458 or PKI-587 significantly inhibited tumor growth. Antitumor effect was correlated with induction of apoptosis and suppression of the phosphorylation of mTOR, Akt, and 4EBP1. These new findings suggest the usefulness of PI3K/mTOR dual inhibition for antitumor and radiosensitizing. The combination of IR with a dual PI3K/mTOR inhibitor, GSK2126458 or PKI-587, might be a promising therapeutic strategy for NPC. ©2014 American Association for Cancer Research.

  9. Signal Transduction Pathways (MAPKs, NF-κB, and C/EBP) Regulating COX-2 Expression in Nasal Fibroblasts from Asthma Patients with Aspirin Intolerance

    Science.gov (United States)

    Garcia-Garcia, Francesc Josep; Mullol, Joaquim; Perez-Gonzalez, Maria; Pujols, Laura; Alobid, Isam

    2012-01-01

    Background Recent studies have revealed that cyclooxygenase-2 (COX-2) expression is down-regulated in aspirin-induced asthma (AIA). Various signal pathways (MAPKs, NF-κB and C/EBP) are involved in COX-2 regulation. Objective To investigate the regulation of COX-2 expression through MAP-kinase pathway activation and nuclear factor translocation in aspirin-induced asthma (AIA). Methods Fibroblasts were isolated from specimens of nasal mucosa (NM, N = 5) and nasal polyps (NP, N = 5). After IL-1β (1 ng/ml) incubation, COX-2 and phosphorylated forms of ERK, JNK and p38 MAPK were measured by Western blot. MAPK’s role in IL-1β-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1–10 µM) prior to IL-1β exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAM® after IL-1β (10 ng/ml) exposure. Results No differences were observed in the MAPK phosphorylation time-course between NM and NP-AIA fibroblasts. The p38 MAPK inhibitor at 10 µM significantly reduced IL-1β-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 µM was not statistically significant compared to non-treated cells. ERK and JNK inhibitors had no significant effect in either the NM or NP-AIA cultures. The effect of IL-1β on NF-κB and C/EBP subunits’ nuclear translocation was similar between NM and NP-AIA fibroblasts. Conclusions These results suggest that p38 MAPK is the only MAPK involved in IL-1β-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-κB and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation. PMID:23240010

  10. [Poor tolerance of exertion during sports and bronchial hyperreactivity].

    Science.gov (United States)

    Potiron-Josse, M; Boutet, S; Ginet, J

    1992-11-01

    135 sportsmen and women, 55 girls, 80 boys, aged from 7 to 30 years, from various sports, who complained of bad tolerance of exertion were examined with an exercise test and isocapnic spontaneous hyperventilation. 61, about 45%, during a hyperventilation test had a fall of V.E.M.S. greater than or equal to 20%, showing bronchial hyperreactivity. After three tests, this fall index was greater than or equal to 50%. 68% of the positive responses were seen in boys and 2/3 of the subjects with a positive response were atopics. No other argument could be maintained from the questioning or clinical history to predict the positive or negative character of the hyperventilation (age, sporting level, symptoms, previous asthma or asthmatic, allergy). H.S.V.I. of the chests of a sporting population that complains of exertion intolerance, therefore allows verification of an H.R.B. assessment of its severity and to follow evolution after treatment.

  11. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Directory of Open Access Journals (Sweden)

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  12. Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type

    DEFF Research Database (Denmark)

    Rose, Adam John; Bisiani, Bruno; Vistisen, Bodil

    2009-01-01

    that the increase in skeletal muscle eEF2 Thr(56) phosphorylation was restricted to type I myofibers. Taken together, these data suggest that the depression of skeletal muscle protein synthesis with endurance-type exercise may be regulated at both initiation (i.e. 4EBP1) and elongation (i.e. eEF2) steps, with eEF2......Protein synthesis in skeletal muscle is known to decrease during exercise and it has been suggested that this may depend on the magnitude of the relative metabolic stress within the contracting muscle. To examine the mechanisms behind this, the effect of exercise intensity on skeletal muscle......) increased during exercise but was not influenced by exercise intensity, and was lower than rest 30min after exercise. On the other hand, 4EBP1 phosphorylation at Thr(37/46) decreased during exercise and this decrease was greater at higher exercise intensities, and was similar to rest 30min after exercise...

  13. T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

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    A. E. Albers

    2010-01-01

    Full Text Available The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

  14. Intelligence Deficits in Chinese Patients with Brain Tumor: The Impact of Tumor Resection

    Directory of Open Access Journals (Sweden)

    Chao Shen

    2013-01-01

    Full Text Available Background. Intelligence is much important for brain tumor patients after their operation, while the reports about surgical related intelligence deficits are not frequent. It is not only theoretically important but also meaningful for clinical practice. Methods. Wechsler Adult Intelligence Scale was employed to evaluate the intelligence of 103 patients with intracranial tumor and to compare the intelligence quotient (IQ, verbal IQ (VIQ, and performance IQ (PIQ between the intracerebral and extracerebral subgroups. Results. Although preoperative intelligence deficits appeared in all subgroups, IQ, VIQ, and PIQ were not found to have any significant difference between the intracerebral and extracerebral subgroups, but with VIQ lower than PIQ in all the subgroups. An immediate postoperative follow-up demonstrated a decline of IQ and PIQ in the extracerebral subgroup, but an improvement of VIQ in the right intracerebral subgroup. Pituitary adenoma resection exerted no effect on intelligence. In addition, age, years of education, and tumor size were found to play important roles. Conclusions. Brain tumors will impair IQ, VIQ, and PIQ. The extracerebral tumor resection can deteriorate IQ and PIQ. However, right intracerebral tumor resection is beneficial to VIQ, and transsphenoidal pituitary adenoma resection performs no effect on intelligence.

  15. Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer.

    Science.gov (United States)

    Castellvi, Josep; Garcia, Angel; Rojo, Federico; Ruiz-Marcellan, Carmen; Gil, Antonio; Baselga, Jose; Ramon y Cajal, Santiago

    2006-10-15

    Growth factor receptors and cell signaling factors play a crucial role in human carcinomas and have been studied in ovarian tumors with varying results. Cell signaling involves multiple pathways and a myriad of factors that can be mutated or amplified. Cell signaling is driven through the mammalian target of rapamycin (mTOR) and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K). The objectives of this study were to analyze the real role that these pathways play in ovarian cancer, to correlate them with clinicopathologic characteristics, and to identify the factors that transmit individual proliferation signals and are associated with pathologic grade and prognosis, regardless specific oncogenic alterations upstream. One hundred twenty-nine ovarian epithelial tumors were studied, including 20 serous cystadenomas, 7 mucinous cystadenomas, 11 serous borderline tumors, 16 mucinous borderline tumors, 29 serous carcinomas, 16 endometrioid carcinomas, 15 clear cell carcinomas, and 15 mucinous carcinomas. Tissue microarrays were constructed, and immunohistochemistry for the receptors epidermal growth factor receptor (EGFR) and c-erb-B2 was performed and with phosphorylated antibodies for protein kinase B (AKT), 4EBP1, p70S6K, S6, and ERK. Among 129 ovarian neoplasms, 17.8% were positive for c-erb-B2, 9.3% were positive for EGFR, 47.3% were positive for phosphorylated AKT (p-AKT), 58.9% were positive for p-ERK, 41.1% were positive for p-4EBP1, 26.4% were positive for p70S6K, and 15.5% were positive for p-S6. Although EGFR, p-AKT, and p-ERK expression did not differ between benign, borderline, or malignant tumors, c-erb-B2, p-4EBP1, p-p70S6K, and p-S6 were expressed significantly more often in malignant tumors. Only p-4EBP1 expression demonstrated prognostic significance (P = .005), and only surgical stage and p-4EBP1 expression

  16. Inhibition of tumor cell growth by Sigma1 ligand mediated translational repression

    International Nuclear Information System (INIS)

    Kim, Felix J.; Schrock, Joel M.; Spino, Christina M.; Marino, Jacqueline C.; Pasternak, Gavril W.

    2012-01-01

    Highlights: ► Sigma1 ligand treatment mediates decrease in tumor cell mass. ► Identification of a Sigma1 ligand with reversible translational repressor actions. ► Demonstration of a role for Sigma1 in cellular protein synthesis. -- Abstract: Treatment with sigma1 receptor (Sigma1) ligands can inhibit cell proliferation in vitro and tumor growth in vivo. However, the cellular pathways engaged in response to Sigma1 ligand treatment that contribute to these outcomes remain largely undefined. Here, we show that treatment with putative antagonists of Sigma1 decreases cell mass. This effect corresponds with repressed cap-dependent translation initiation in multiple breast and prostate cancer cell lines. Sigma1 antagonist treatment suppresses phosphorylation of translational regulator proteins p70S6K, S6, and 4E-BP1. RNAi-mediated knockdown of Sigma1 also results in translational repression, consistent with the effects of antagonist treatment. Sigma1 antagonist mediated translational repression and decreased cell size are both reversible. Together, these data reveal a role for Sigma1 in tumor cell protein synthesis, and demonstrate that small molecule Sigma1 ligands can be used as modulators of protein translation.

  17. Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy

    International Nuclear Information System (INIS)

    Nesto, R.W.; Phillips, R.T.; Kett, K.G.; Hill, T.; Perper, E.; Young, E.; Leland, O.S. Jr.

    1988-01-01

    Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 7 patients with diabetes compared with 17 patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted

  18. Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

    International Nuclear Information System (INIS)

    Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

    1995-01-01

    Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

  19. mTORC1 Targets the Translational Repressor 4E-BP2, but Not S6 Kinase 1/2, to Regulate Neural Stem Cell Self-Renewal In Vivo

    Directory of Open Access Journals (Sweden)

    Nathaniel W. Hartman

    2013-10-01

    Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 integrates signals important for cell growth, and its dysregulation in neural stem cells (NSCs is implicated in several neurological disorders associated with abnormal neurogenesis and brain size. However, the function of mTORC1 on NSC self-renewal and the downstream regulatory mechanisms are ill defined. Here, we found that genetically decreasing mTORC1 activity in neonatal NSCs prevented their differentiation, resulting in reduced lineage expansion and aborted neuron production. Constitutive activation of the translational repressor 4E-BP1, which blocked cap-dependent translation, had similar effects and prevented hyperactive mTORC1 induction of NSC differentiation and promoted self-renewal. Although 4E-BP2 knockdown promoted NSC differentiation, p70 S6 kinase 1 and 2 (S6K1/S6K2 knockdown did not affect NSC differentiation but reduced NSC soma size and prevented hyperactive mTORC1-induced increase in soma size. These data demonstrate a crucial role of mTORC1 and 4E-BP for switching on and off cap-dependent translation in NSC differentiation.

  20. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

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    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  1. Design Strategies for Balancing Exertion Games

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj

    2016-01-01

    In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however, it is un......In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however......, it is unclear how balancing mechanisms should be applied in exertion games, where physical and digital elements are fused. In this paper, we present an exertion game and three approaches for balancing it; a physical, an explicit-digital and an implicit-digital balancing approach. A user study that compares...... these three approaches is used to investigate the qualities and challenges within each approach and explore how the player experience is affected by them. Based on these findings, we suggest four design strategies for balancing exertion games, so that players will stay engaged in the game and contain...

  2. Does the intracellular ionic concentration or the cell water content (cell volume) determine the activity of TonEBP in NIH3T3 cells?

    DEFF Research Database (Denmark)

    Rødgaard, Tina; Schou, Kenneth; Friis, Martin Barfred

    2008-01-01

    of the present investigation was to investigate whether cell shrinkage or high intracellular ionic concentration induced the activation of TonEBP. We designed a model system for isotonically shrinking cells over a prolonged period of time. Cells swelled in hypotonic medium and performed a regulatory volume...... decrease (RVD). Upon return to the original isotonic medium, cells shrank initially followed by a regulatory volume increase (RVI). To maintain cell shrinkage, the RVI process was inhibited as follows: Ethyl-isopropyl-amiloride (EIPA) inhibited the Na(+)/H(+) antiport, Bumetanide inhibited the Na(+)/K(+)/2......Cl(-) co-transporter, and Gadolinium inhibited shrinkage-activated Na(+) channels. Cells remained shrunken for at least 4 hours (isotonically shrunken cells). The activity of TonEBP was investigated with a Luciferase assay after isotonic shrinkage and after shrinkage in a high NaCl hypertonic medium...

  3. Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

    1979-01-01

    C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

  4. Tumores de los anexos oculares Ocular adnexa tumors

    Directory of Open Access Journals (Sweden)

    Clara G. Gómez Cabrera

    2001-12-01

    Full Text Available Se realizó un estudio retrospectivo de 211 pacientes, operados por presentar alguna tumoración de los anexos, con confirmación histológica en el período comprendido entre enero de 1993 hasta diciembre de 1997. El 53,5 % de los pacientes fueron del sexo femenino. El 48,4 % eran mestizos. El 13,3 % de los pacientes eran menores de 20 años, el 36 % entre 20 y 49 y el 50,7 % más de 50 años. El 61,1 % de los tumores se localizaron en los párpados. Los signos clínicos que prevalecieron fueron el aumento de volumen (56,9 %, aumento de la pigmentación (23,71 %, vascularización (21,8 % y ulceración (7,1 %. El 61,6 % de los casos fueron asintomáticos. Encontramos 14 tipos histológicos de tumores en los párpados y 15 en la conjuntiva. No encontramos diferencia significativa en cuanto a sexo y tipo de tumor. La raza mestiza presentó el mayor número de casos y el grupo de mayor incidencia fue el de pacientes mayores e iguales a 50 años de edad. Los párpados constituyeron la localización anatómica principal. El signo clínico más importante fue el aumento de volumen y la mayoría de los pacientes estaban asintomáticos. Los tumores palpebrales de mayor incidencia fueron los quistes de inclusión seguido por el carcinoma basocelular y el granuloma. En la conjuntiva se destacaron los nevus, el carcinoma espinocelular y el granuloma.A retrospective study of 211 patients that were operated on for presenting some adnexa tumors with histologic confirmation from January, 1993, to December, 1997, was made. 53.5 % of the patients were females. 48.4 % were black. 13.3 % were under 20, 36 % were between 20 and 49 and 50.7 % were over 50. 61.1 % of the tumors were localized in the eyelids. The prevailing clinical signs were volume increase (56.9 %, pigmentation increase (23.71 %, vascularization (21.8 % and ulceration (7.1 %. 61.6 % of the patients were asymptomatic. We found 14 histologic types of tumors in the eyelids and 15 in the conjunctiva

  5. The CCAAT/enhancer binding protein (C/EBP δ is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-β peptide

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    Nilsson Lars NG

    2011-04-01

    Full Text Available Abstract Background The transcription factors CCAAT/enhancer binding proteins (C/EBP α, β and δ have been shown to be expressed in brain and to be involved in regulation of inflammatory genes in concert with nuclear factor κB (NF-κB. In general, C/EBPα is down-regulated, whereas both C/EBPβ and δ are up-regulated in response to inflammatory stimuli. In Alzheimer's disease (AD one of the hallmarks is chronic neuroinflammation mediated by astrocytes and microglial cells, most likely induced by the formation of amyloid-β (Aβ deposits. The inflammatory response in AD has been ascribed both beneficial and detrimental roles. It is therefore important to delineate the inflammatory mediators and signaling pathways affected by Aβ deposits with the aim of defining new therapeutic targets. Methods Here we have investigated the effects of Aβ on expression of C/EBP family members with a focus on C/EBPδ in rat primary astro-microglial cultures and in a transgenic mouse model with high levels of fibrillar Aβ deposits (tg-ArcSwe by western blot analysis. Effects on DNA binding activity were analyzed by electrophoretic mobility shift assay. Cross-talk between C/EBPδ and NF-κB was investigated by analyzing binding to a κB site using a biotin streptavidin-agarose pull-down assay. Results We show that exposure to fibril-enriched, but not oligomer-enriched, preparations of Aβ inhibit up-regulation of C/EBPδ expression in interleukin-1β-activated glial cultures. Furthermore, we observed that, in aged transgenic mice, C/EBPα was significantly down-regulated and C/EBPβ was significantly up-regulated. C/EBPδ, on the other hand, was selectively down-regulated in the forebrain, a part of the brain showing high levels of fibrillar Aβ deposits. In contrast, no difference in expression levels of C/EBPδ between wild type and transgenic mice was detected in the relatively spared hindbrain. Finally, we show that interleukin-1β-induced C/EBPδ DNA

  6. [Expression of erythroblastic leukemia viral oncogene homolog 3 (ErbB-3) binding protein-1, matrix metalloproteinases, eplthelial cadherin in adenoid cystic carcinoma and correlation analysis].

    Science.gov (United States)

    Sun, Jian; Yu, You-cheng; Luo, Yi-xi; Tian, Zhen

    2012-12-01

    To investigate the expression of ErbB-3 binding protein-1 (EBP-1), matrix metalloproteinase 9 (MMP-9) and E-cadherin (E-cad) in adenoid cystic carcinoma and their correlation. Immunohistochemistry(PV6000 method) was used to detect EBP-1, MMP-9 and E-cad expression in 66 cases of adenoid cystic carcinoma tissues and matched para-cancerous normal tissues. In this study all cases were successfully followed up. The positive expression rate of EBP-1 in adenoid cystic carcinoma tissues was 85%. EBP-1 expression was significantly correlated to pathological pattern and clinical stage (P correlation between EBP-1 and E-cad expression, and positive correlation between EBP-1 and MMP-9. EBP-1 and its correlation with MMP-9 and E-cad may be used as useful indicators for clinical assessment of tumor biological behavior and prognosis in patients with adenoid cystic carcinoma.

  7. Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.

    Science.gov (United States)

    Iwasaki, Takeshi; Matsushita, Michiko; Nonaka, Daisuke; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Nagata, Keiko; Nakajima, Hideki; Sano, Shigetoshi; Hayashi, Kazuhiko

    2015-02-01

    Merkel cell polyomavirus (MCPyV) integrates monoclonally into the genomes of approximately 80% of Merkel cell carcinomas (MCCs), affecting their clinicopathological features. The molecular mechanisms underlying MCC development after MCPyV infection remain unclear. We investigated the association of MCPyV infection with activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4E-BP1) signaling pathway in MCCs to elucidate the role of these signal transductions and to identify molecular targets for treatment. We analyzed the molecular and pathological characteristics of 41 MCPyV-positive and 27 MCPyV-negative MCCs. Expression of mTOR, TSC1, and TSC2 messenger RNA was significantly higher in MCPyV-negative MCCs, and Akt (T308) phosphorylation also was significantly higher (92% vs 66%; P = .019), whereas 4E-BP1 (S65 and T70) phosphorylation was common in both MCC types (92%-100%). The expression rates of most other tested signals were high (60%-100%) and not significantly correlated with MCPyV large T antigen expression. PIK3CA mutations were observed more frequently in MCPyV-positive MCCs (6/36 [17%] vs 2/20 [10%]). These results suggest that protein expression (activation) of most Akt/mTOR/4E-BP1 pathway signals was not significantly different in MCPyV-positive and MCPyV-negative MCCs, although these 2 types may differ in tumorigenesis, and MCPyV-negative MCCs showed significantly more frequent p-Akt (T308) activation. Therefore, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for MCC regardless of MCPyV infection status. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Anti-tumor effects of (1→3)-β-d-glucan from Saccharomyces cerevisiae in S180 tumor-bearing mice.

    Science.gov (United States)

    Mo, Li; Chen, Yafei; Li, Wenjian; Guo, Shuai; Wang, Xuzhao; An, Hailong; Zhan, Yong

    2017-02-01

    (1→3)-β-d-Glucan from Saccharomyces cerevisiae is a typical polysaccharide with various biological effects and is considered a candidate for the prevention and treatment of cancer in vitro. Research into the function of (1→3)-β-d-glucan in tumor-bearing animals in vivo, however, is limited. Here, we investigated the effects of (1→3)-β-d-glucan from S. cerevisiae on S180 tumor-bearing mice and on the immunity of the tumor-bearing host. The molecular mechanisms underlying the observed effects were investigated. (1→3)-β-d-Glucan was shown to exert anti-tumor effects without toxicity in normal mouse cells. The volume and weight of S180 tumors decreased dramatically following treatment with (1→3)-β-d-glucan, and treatment with the polysaccharide was furthermore shown to increase the tumor inhibition rate in a dose-dependent manner. Spleen index, T lymphocyte subsets (CD 4 and CD 8 ), as well as interleukins (IL)-2, (IL-2, IL-6), and tumor necrosis factor-α were assayed to detect the immunoregulatory and anti-tumor effects after (1→3)-β-d-glucan intragastrical administration. (1→3)-β-d-Glucan was shown to significantly potentiate the mouse immune responses by, among other effects, decreasing the ratio of CD 4 to CD 8 . The expression levels of IL-2, IL-6, and TNF-α were also significantly increased by (1→3)-β-d-glucan. These results suggest that (1→3)-β-d-glucan enhances the host's immune function during the tumor inhibition process. S180 tumor cells treated with (1→3)-β-d-glucan also exhibited significant apoptotic characteristics. (1→3)-β-d-glucan increased the ratio of Bax to Bcl-2 at the translation level by up-regulating Bax expression and down-regulating Bcl-2 expression, resulting in the initiation of cell apoptosis in S180 tumor-bearing mice. Taken together, these results indicate that the anti-tumor effects exerted by (1→3)-β-d-glucan may be attributed to the polysaccharide's immunostimulating properties and apoptosis

  9. Instructional methods used by health sciences librarians to teach evidence-based practice (EBP: a systematic review

    Directory of Open Access Journals (Sweden)

    Stephanie M. Swanberg, MSI, AHIP

    2016-09-01

    Full Text Available Background: Librarians often teach evidence-based practice (EBP within health sciences curricula. It is not known what teaching methods are most effective. Methods: A systematic review of the literature was conducted searching CINAHL, EMBASE, ERIC, LISTA, PubMed, Scopus, and others. Searches were completed through December 2014. No limits were applied. Hand searching of Medical Library Association annual meeting abstracts from 2009–2014 was also completed. Studies must be about EBP instruction by a librarian within undergraduate or graduate health sciences curricula and include skills assessment. Studies with no assessment, letters and comments, and veterinary education studies were excluded. Data extraction and critical appraisal were performed to determine the risk of bias of each study. Results: Twenty-seven studies were included for analysis. Studies occurred in the United States (20, Canada (3, the United Kingdom (1, and Italy (1, with 22 in medicine and 5 in allied health. Teaching methods included lecture (20, small group or one-on-one instruction (16, computer lab practice (15, and online learning (6. Assessments were quizzes or tests, pretests and posttests, peer review, search strategy evaluations, clinical scenario assignments, or a hybrid. Due to large variability across studies, meta-analysis was not conducted. Discussion: Findings were weakly significant for positive change in search performance for most studies. Only one study compared teaching methods, and no one teaching method proved more effective. Future studies could conduct multisite interventions using randomized or quasi-randomized controlled trial study design and standardized assessment tools to measure outcomes.

  10. Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

    Science.gov (United States)

    Lavazza, Cristiana; Carlo-Stella, Carmelo; Giacomini, Arianna; Cleris, Loredana; Righi, Marco; Sia, Daniela; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Francolini, Maura; Gloghini, Annunziata; Carbone, Antonino; Formelli, Franca; Gianni, Alessandro M

    2010-03-18

    Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.

  11. Antitumor action of 3-bromopyruvate implicates reorganized tumor growth regulatory components of tumor milieu, cell cycle arrest and induction of mitochondria-dependent tumor cell death.

    Science.gov (United States)

    Yadav, Saveg; Kujur, Praveen Kumar; Pandey, Shrish Kumar; Goel, Yugal; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

    2018-01-15

    Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Anti-tumor effect of bisphosphonate (YM529 on non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Date Hiroshi

    2007-01-01

    Full Text Available Abstract Background YM529 is a newly developed nitrogen-containing bisphosphonate (BP classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC. Methods Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157 were measured by MTS assay and calculated inhibition concentration 50 % (IC50 values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method. We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. Results We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819. Conclusion Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.

  13. Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

    International Nuclear Information System (INIS)

    Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

    2008-01-01

    Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

  14. When exercise causes exertional rhabdomyolysis.

    Science.gov (United States)

    Furman, Janet

    2015-04-01

    Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

  15. The humanized anti-human AMHRII mAb 3C23K exerts an anti-tumor activity against human ovarian cancer through tumor-associated macrophages.

    Science.gov (United States)

    Bougherara, Houcine; Némati, Fariba; Nicolas, André; Massonnet, Gérald; Pugnière, Martine; Ngô, Charlotte; Le Frère-Belda, Marie-Aude; Leary, Alexandra; Alexandre, Jérôme; Meseure, Didier; Barret, Jean-Marc; Navarro-Teulon, Isabelle; Pèlegrin, André; Roman-Roman, Sergio; Prost, Jean-François; Donnadieu, Emmanuel; Decaudin, Didier

    2017-11-21

    Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker. We then provided evidence that the tumor stroma of OC is enriched in tumor-associated macrophages and that these cells are responsible for 3C23K-induced killing of tumor cells through ADCP and ADCC mechanisms. In addition, we showed that 3C23K reduced macrophages induced-T cells immunosuppression. Finally, we evaluated the therapeutic efficacy of 3C23K alone and in combination with a carboplatin-paclitaxel chemotherapy in a panel of OC Patient-Derived Xenografts. In those experiments, we showed that 3C23K significantly increased the proportion and the quality of chemotherapy-based in vivo responses. Altogether, our data support the potential interest of AMHRII targeting in human ovarian cancers and the evaluation of 3C23K in further clinical trials.

  16. Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

    Science.gov (United States)

    Mantovani, Alberto; Locati, Massimo

    2013-07-01

    Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

  17. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  18. Hydroxyframoside B, a secoiridoid of Fraxinus rhynchophylla, inhibits adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Choi, Kyeong-Mi; Shin, Eunjin; Liu, Qing; Yoo, Hwan-Soo; Kim, Young Choong; Sung, Sang Hyun; Hwang, Bang Yeon; Lee, Mi Kyeong

    2011-07-01

    Fraxinus rhynchophylla showed significant inhibitory activity on adipocyte differentiation in the 3T3-L1 preadipocyte cell line as assessed by measuring fat accumulation using Oil Red O staining. Further fractionation led to the isolation of two secoiridoids, oleuropein and hydroxyframoside B. Hydroxyframoside B significantly reduced fat accumulation and triglyceride content in differentiated 3T3-L1 cells without affecting cell viability, whereas oleuropein showed little effect. Further studies with interval treatment demonstrated that hydroxyframoside B exerted inhibitory activity on adipocyte differentiation when treated within 2 days (days 0-2) after differentiation induction. In addition, hydroxyframoside B significantly blocked the induction of adipogenic transcription factors such as C/EBP α, C/EBP β, and PPAR γ. Taken together, these results suggest that hydroxyframoside B inhibited early/middle stage of adipogenic differentiation, in part, via inhibition of C/EBP α, C/EBP β, and PPAR γ-dependent pathways. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage

    DEFF Research Database (Denmark)

    Porse, Bo T; Bryder, David; Theilgaard-Mönch, Kim

    2005-01-01

    dissociate the ability of C/EBP alpha to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow (BM) myeloid...... progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation...

  20. Exertional Rhabdomyolysis after Spinning.

    Science.gov (United States)

    Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-11-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24-48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered.

  1. 20 CFR 404.1567 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

    ... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirements of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

  2. 20 CFR 416.967 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

    ... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirments of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

  3. Anti-tumor effects of Ganoderma lucidum (reishi in inflammatory breast cancer in in vivo and in vitro models.

    Directory of Open Access Journals (Sweden)

    Ivette J Suarez-Arroyo

    Full Text Available The medicinal mushroom Ganoderma lucidum (Reishi was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC tissue biopsies overexpress E-cadherin and the eukaryotic initiation factor 4GI (eIF4GI, two proteins that are partially responsible for the unique pathological properties of this disease. IBC is treated with a multimodal approach that includes non-targeted systemic chemotherapy, surgery, and radiation. Because of its non-toxic and selective anti-cancer activity, medicinal mushroom extracts have received attention for their use in cancer therapy. Our previous studies demonstrate these selective anti-cancer effects of Reishi, where IBC cell viability and invasion, as well as the expression of key IBC molecules, including eIF4G is compromised. Thus, herein we define the mechanistic effects of Reishi focusing on the phosphoinositide-3-kinase (PI3K/AKT/mammalian target of rapamycin (mTOR pathway, a regulator of cell survival and growth. The present study demonstrates that Reishi treated IBC SUM-149 cells have reduced expression of mTOR downstream effectors at early treatment times, as we observe reduced eIF4G levels coupled with increased levels of eIF4E bound to 4E-BP, with consequential protein synthesis reduction. Severe combined immunodeficient mice injected with IBC cells treated with Reishi for 13 weeks show reduced tumor growth and weight by ∼50%, and Reishi treated tumors showed reduced expression of E-cadherin, mTOR, eIF4G, and p70S6K, and activity of extracellular regulated kinase (ERK1/2. Our results provide evidence that Reishi suppresses protein synthesis and tumor growth by affecting survival and proliferative signaling pathways that act on translation, suggesting that Reishi is a potential natural therapeutic for breast and other cancers.

  4. Tumor thrombus of inferior vena cava in patients with renal cell carcinoma – clinical and oncological outcome of 50 patients after surgery

    Directory of Open Access Journals (Sweden)

    Kocot Arkadius

    2012-06-01

    Full Text Available Abstract Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC and tumor thrombus involving inferior vena cava (IVC treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42% distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%, thoracoabdominal (14 patients/28% or midline abdominal approach (21 patients/42%, depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB was performed in 10 patients (20% with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10 even had a better outcome (overall survival at 5 years of 58.33% than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal

  5. Acidosis-Induced Changes in Proteome Patterns of the Prostate Cancer-Derived Tumor Cell Line AT-1.

    Science.gov (United States)

    Ihling, Angelika; Ihling, Christian H; Sinz, Andrea; Gekle, Michael

    2015-09-04

    Under various pathological conditions, such as inflammation, ischemia and in solid tumors, physiological parameters (local oxygen tension or extracellular pH) show distinct tissue abnormalities (hypoxia and acidosis). For tumors, the prevailing microenvironment exerts a strong influence on the phenotype with respect to proliferation, invasion, and metastasis formation and therefore influences prognosis. In this study, we investigate the impact of extracellular metabolic acidosis (pH 7.4 versus 6.6) on the proteome patterns of a prostate cancer-derived tumor cell type (AT-1) using isobaric labeling and LC-MS/MS analysis. In total, 2710 proteins were identified and quantified across four biological replicates, of which seven were significantly affected with changes >50% and used for validation. Glucose transporter 1 and farnesyl pyrophosphatase were found to be down-regulated after 48 h of acidic treatment, and metallothionein 2A was reduced after 24 h and returned to control values after 48 h. After 24 and 48 h at pH 6.6, glutathione S transferase A3 and NAD(P)H dehydrogenase 1, cellular retinoic acid-binding protein 2, and Na-bicarbonate transporter 3 levels were found to be increased. The changes in protein levels were confirmed by transcriptome and functional analyses. In addition to the experimental in-depth investigation of proteins with changes >50%, functional profiling (statistical enrichment analysis) including proteins with changes >20% revealed that acidosis upregulates GSH metabolic processes, citric acid cycle, and respiratory electron transport. Metabolism of lipids and cholesterol biosynthesis were downregulated. Our data comprise the first comprehensive report on acidosis-induced changes in proteome patterns of a tumor cell line.

  6. Tumores malignos de pálpebra Malignant eyelid tumors

    Directory of Open Access Journals (Sweden)

    Luis Henrique Schneider Soares

    2001-08-01

    Full Text Available Objetivos: Estudar a incidência de tumores malignos de pálpebra no Hospital Banco de Olhos de Porto Alegre. Métodos: Estudo retrospectivo dos casos de tumores malignos de pálpebra no período de 1985 a 1997, que tiveram diagnóstico confirmado por exame anátomopatológico. Resultados: Foram encontradas 54 neoplasias malignas, sendo 75,92% carcinoma basocelular, 12,96% carcinoma espinocelular, 7,40% melanoma e 1,85% lentigo maligna. A maioria dos pacientes apresentava mais de 40 anos e não houve prevalência de sexo. Conclusões: O tumor de pálpebra mais freqüente em nosso meio foi o carcinoma basocelular, seguido do carcinoma espinocelular. O melanoma foi o terceiro em freqüência mais encontrado em nossa pesquisa.Purposes: To study the incidence of eyelid malignant tumors in the Banco de Olhos Hospital of Porto Alegre from 1985 to 1997. Methods: We retrospectivelly analyzed clinical archives and in this study all cases of malignant eyelid tumors with histopathologic examination were included. Results: We found 54 eyelid tumors: 75.92% basal cell, 12.96% squamous cell, 7.40% melanoma, 1.85% undifferentiated carcinoma and 1.85% lentigo maligna. The majority of the patients was over 40 years old, 50% were male and 50% female. The diagnosis was confirmed in all cases through histopathologic examination. Conclusions: Basal cell carcinoma was the most frequent eyelid malignancy followed by squamous cell carcinoma. Melanoma was the third most frequently found tumor in our study.

  7. Non-cell autonomous or secretory tumor suppression.

    Science.gov (United States)

    Chua, Christelle En Lin; Chan, Shu Ning; Tang, Bor Luen

    2014-10-01

    Many malignancies result from deletions or loss-of-function mutations in one or more tumor suppressor genes, the products of which curb unrestrained growth or induce cell death in those with dysregulated proliferative capacities. Most tumor suppressors act in a cell autonomous manner, and only very few proteins are shown to exert a non-cell autonomous tumor suppressor function on other cells. Examples of these include members of the secreted frizzled-related protein (SFRP) family and the secreted protein acidic and rich in cysteine (SPARC)-related proteins. Very recent findings have, however, considerably expanded our appreciation of non-cell autonomous tumor suppressor functions. Broadly, this may occur in two ways. Intracellular tumor suppressor proteins within cells could in principle inhibit aberrant growth of neighboring cells by conditioning an antitumor microenvironment through secreted factors. This is demonstrated by an apparent non-cell autonomous tumor suppressing property of p53. On the other hand, a tumor suppressor produced by a cell may be secreted extracellularly, and taken up by another cell with its activity intact. Intriguingly, this has been recently shown to occur for the phosphatase and tensin homolog (PTEN) by both conventional and unconventional modes of secretion. These recent findings would aid the development of therapeutic strategies that seek to reinstate tumor suppression activity in therapeutically recalcitrant tumor cells, which have lost it in the first place. © 2014 Wiley Periodicals, Inc.

  8. [Granular cell tumor of the larynx in the child. Case report].

    Science.gov (United States)

    Cuestas, Giselle; Rodríguez, Verónica; Doormann, Flavia; Bellia Munzón, Patricio; Bellia Munzón, Gastón

    2018-02-01

    Laryngeal tumors are uncommon in children, accounting only for 2% of the laryngeal anomalies. Ninety-eight percent are benign; the most frequent ones are recurrent respiratory papillomatosis and haemangioma. Granular cell tumor, also called Abrikossoff tumor, is an unusual benign neoplasm, especially in the larynx. Clinical manifestations depend on the size and location of the tumor. Dysphonia is the main presenting symptom. The diagnosis is confirmed by the biopsy. The treatment of choice is surgery. We present a 9-year-old girl with dysphonia and exertion dyspnea due to a granular cell tumor of the larynx, and we emphasize the importance of considering the endoscopic evaluation of the airway in every child with progressive or persistent dysphonia in order to determine the etiology. Sociedad Argentina de Pediatría.

  9. Musical agency reduces perceived exertion during strenuous physical performance.

    Science.gov (United States)

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-10-29

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

  10. Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

    Science.gov (United States)

    Reinhart-King, Cynthia

    2010-03-01

    Cells exert traction stresses against their substrate that mediate their ability to sense the mechanical properties of their microenvironment. These same forces mediate cell adhesion, migration and the formation of stable cell-cell contacts during tissue formation. In this talk, I will present our data on the traction stresses generated by endothelial cells and metastatic breast cancer cells focused on understanding the processes of angiogenesis and metastasis, respectively. In the context of capillary formation, our data indicate that the mechanics of the substrate play a critical role in establishing endothelial cell-cell contacts. On more compliant substrates, endothelial cell shape and traction stresses polarize and promote the formation of stable cell-cell contacts. On stiffer substrates, traction stresses are less polarized and cell connectivity is disrupted. These data indicate that the mechanical properties of the microenvironment may drive cell connectivity and the formation of stable cell-cell contacts through the reorientation of traction stresses. In our studies of metastatic cell migration, we have found that traction stresses increase with increasing metastatic potential. We investigated three lines of varying metastatic potential (MCF10A, MCF7 and MDAMB231). MDAMB231, which are the most invasive, exert the most significant forces as measured by Traction Force Microscopy. These data present the possibility that cellular traction stress generation aids in the ability of metastatic cells to migrate through the matrix-dense tumor microenvironment. Such measurements are integral to link the mechanical and chemical microenvironment with the resulting response of the cell in health and disease.

  11. Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

    OpenAIRE

    Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D.; Pelletier, Jerry; Ferraiuolo, Maria A.; Sonenberg, Nahum

    2008-01-01

    Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported...

  12. Determination of gamma radiation lethal dose (LD50) and resveratrol cytotoxicity level in tumor cells line

    International Nuclear Information System (INIS)

    Magalhaes, Vanessa D.; Rogero, Sizue O.; Rogero, Jose R.; Cruz, Aurea S.

    2011-01-01

    Cancer is a disease with high incidence and it is considered a worldwide public health problem. Resveratrol is a polyphenol occurring naturally in a wide variety of plants according to response of ultraviolet radiation (UV) exposition or according to mechanical stress resulting of pathogens or chemical and physical agents. This polyphenol possesses a pharmacological activity of carcinogenesis inhibition in multiple levels. It also protects cells by scavenging the free radicals which are considered toxic products. These free radicals are formed of natural process of cell aging and also by incidence of ionizing radiation in the organism. Thus, resveratrol is considered as a cell radioprotector. On the other hand, in some elevated concentrations resveratrol may be considered as a radiosensitizing. The aim of this work was the determination of radiation lethal dose (LD 50 ) and also verifies the cytotoxicity level of resveratrol in tumor cells line: muco epidermoid pulmonary carcinoma cells (NCI-H292) and rhabdomyosarcoma cells (RD). The cytotoxicity test was performed by neutral red uptake assay. The results of resveratrol IC 50% in NCI-H292 cells was 192μM and in RD cells was 128μM; and RD cells gamma radiation LD 50 was 435Gy. (author)

  13. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

    2014-01-01

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  14. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells

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    Shiming Ye

    2017-01-01

    Full Text Available Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies. The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models. The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor. The involvement of effector cells was further confirmed by immunohistochemistry, which revealed strong infiltration of CD45+ effector cells into tumor xenografts in responding models, but minimal infiltration in nonresponders. Consistent with the xenograft studies, human effector cells preferentially migrated toward in vivo-responsive tumor cells treated by enavatuzumab in vitro, with the majority of migratory cells being monocytes. Conditioned media from enavatuzumab-treated tumor cells contained elevated levels of chemokines, which might be responsible for enavatuzumab-triggered effector cell migration. These preclinical studies demonstrate that enavatuzumab can exert its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells. Enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity.

  15. Mutations in LRRC50 predispose zebrafish and humans to seminomas.

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    Sander G Basten

    2013-04-01

    Full Text Available Seminoma is a subclass of human testicular germ cell tumors (TGCT, the most frequently observed cancer in young men with a rising incidence. Here we describe the identification of a novel gene predisposing specifically to seminoma formation in a vertebrate model organism. Zebrafish carrying a heterozygous nonsense mutation in Leucine-Rich Repeat Containing protein 50 (lrrc50 also called dnaaf1, associated previously with ciliary function, are found to be highly susceptible to the formation of seminomas. Genotyping of these zebrafish tumors shows loss of heterozygosity (LOH of the wild-type lrrc50 allele in 44.4% of tumor samples, correlating with tumor progression. In humans we identified heterozygous germline LRRC50 mutations in two different pedigrees with a family history of seminomas, resulting in a nonsense Arg488* change and a missense Thr590Met change, which show reduced expression of the wild-type allele in seminomas. Zebrafish in vivo complementation studies indicate the Thr590Met to be a loss-of-function mutation. Moreover, we show that a pathogenic Gln307Glu change is significantly enriched in individuals with seminoma tumors (13% of our cohort. Together, our study introduces an animal model for seminoma and suggests LRRC50 to be a novel tumor suppressor implicated in human seminoma pathogenesis.

  16. NK cell-released exosomes: Natural nanobullets against tumors.

    Science.gov (United States)

    Fais, Stefano

    2013-01-01

    We have recently reported that human natural killer (NK) cells release exosomes that express both NK-cell markers and cytotoxic molecules. Similar results were obtained with circulating exosomes from human healthy donors. Both NK-cell derived and circulating exosomes exerted a full functional activity and killed both tumor and activated immune cells. These findings indicate that NK-cell derived exosomes might constitute a new promising therapeutic tool.

  17. Overview of Methods Able to Overcome Impediments to tumor Drug Delivery with Special Attention to Tumor Interstitial Fluid.

    Directory of Open Access Journals (Sweden)

    Gianfranco eBaronzio

    2015-07-01

    Full Text Available Every drug used to treat cancer (chemotherapeutics, immunologic, monoclonal antibodies, nanoparticles, radionuclides must reach the targeted cells through the tumor environment at adequate concentrations, in order to exert their cell-killing effects. For any of these agents to reach the goal cells they must overcome a number of impediments created by the tumor microenvironment, beginning with tumor interstitial fluid pressure (TIFP and a multifactorial increase in composition of the extracellular matrix (ECM. A primary modifier of tumor microenvironment is hypoxia, which increases the production of growth factors such as vascular endothelial growth factor (VEGF and platelet-derived growth factor (PDGF. These growth factors released by both tumor cells and bone marrow recruited myeloid cells (MDS, form abnormal vasculature characterized by vessels that are tortuous and more permeable. Increased leakiness combined with increased inflammatory byproducts accumulates fluid within the tumor mass [tumor interstitial fluid (TIF], ultimately creating an increased pressure (TIFP. Fibroblasts are also up-regulated by the tumor microenvironment, and deposit fibers that further augment the density of the extracellular matrix (ECM, thus, further worsening the TIFP. Increased TIFP with the ECM are the major obstacles to adequate drug delivery. By decreasing TIFP and decreasing ECM density, we can expect an associated rise in drug concentration within the tumor itself. In this overview we will describe all the methods (drugs, nutraceuticals, physical methods of treatment able to lower TIFP and to modify ECM that can be used for increasing drug concentration within the tumor tissue.

  18. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

    International Nuclear Information System (INIS)

    Wang, J.; Lu, M.L.; Dai, H.L.; Zhang, S.P.; Wang, H.X.; Wei, N.

    2014-01-01

    This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg -1 ·day -1 ), or 5-Fu (200 mg·kg -1 ·day -1 ) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC 50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway

  19. Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C

    International Nuclear Information System (INIS)

    Hatano, Yu; Nakahama, Ken-ichi; Isobe, Mitsuaki; Morita, Ikuo

    2014-01-01

    Highlights: • M-CSF and RANKL expressing HeLa cells induced osteoclastogenesis in vitro. • We established OGC-containing tumor model in vivo. • OGC-containing tumor became larger independent of M-CSF or RANKL effect. • VEGF-C secreted from OGCs was a one of candidates for OGC-containing tumor growth. - Abstract: Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These

  20. Regulation of Tumor Progression by Programmed Necrosis

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    Su Yeon Lee

    2018-01-01

    Full Text Available Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1, which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.

  1. Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity.

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    Jeong-Kook Kim

    Full Text Available Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3 contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2 or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.

  2. C/EBP{delta} targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression.

    Science.gov (United States)

    Pawar, Snehalata A; Sarkar, Tapasree Roy; Balamurugan, Kuppusamy; Sharan, Shikha; Wang, Jun; Zhang, Youhong; Dowdy, Steven F; Huang, A-Mei; Sterneck, Esta

    2010-05-18

    The transcription factor CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD, NFIL-6beta) has tumor suppressor function; however, the molecular mechanism(s) by which C/EBPdelta exerts its effect are largely unknown. Here, we report that C/EBPdelta induces expression of the Cdc27 (APC3) subunit of the anaphase promoting complex/cyclosome (APC/C), which results in the polyubiquitination and degradation of the prooncogenic cell cycle regulator cyclin D1, and also down-regulates cyclin B1, Skp2, and Plk-1. In C/EBPdelta knockout mouse embryo fibroblasts (MEF) Cdc27 levels were reduced, whereas cyclin D1 levels were increased even in the presence of activated GSK-3beta. Silencing of C/EBPdelta, Cdc27, or the APC/C coactivator Cdh1 (FZR1) in MCF-10A breast epithelial cells increased cyclin D1 protein expression. Like C/EBPdelta, and in contrast to cyclin D1, Cdc27 was down-regulated in several breast cancer cell lines, suggesting that Cdc27 itself may be a tumor suppressor. Cyclin D1 is a known substrate of polyubiquitination complex SKP1/CUL1/F-box (SCF), and our studies show that Cdc27 directs cyclin D1 to alternative degradation by APC/C. These findings shed light on the role and regulation of APC/C, which is critical for most cellular processes.

  3. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.

  4. Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

    Science.gov (United States)

    Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

    2016-10-04

    Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

  5. Determination of gamma radiation lethal dose (LD{sub 50}) and resveratrol cytotoxicity level in tumor cells line

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, Vanessa D.; Rogero, Sizue O.; Rogero, Jose R. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Cruz, Aurea S. [Instituto Adolfo Lutz (IAL-SP) Secao de Culturas Celulares, SP (Brazil)

    2011-07-01

    Cancer is a disease with high incidence and it is considered a worldwide public health problem. Resveratrol is a polyphenol occurring naturally in a wide variety of plants according to response of ultraviolet radiation (UV) exposition or according to mechanical stress resulting of pathogens or chemical and physical agents. This polyphenol possesses a pharmacological activity of carcinogenesis inhibition in multiple levels. It also protects cells by scavenging the free radicals which are considered toxic products. These free radicals are formed of natural process of cell aging and also by incidence of ionizing radiation in the organism. Thus, resveratrol is considered as a cell radioprotector. On the other hand, in some elevated concentrations resveratrol may be considered as a radiosensitizing. The aim of this work was the determination of radiation lethal dose (LD{sub 50}) and also verifies the cytotoxicity level of resveratrol in tumor cells line: muco epidermoid pulmonary carcinoma cells (NCI-H292) and rhabdomyosarcoma cells (RD). The cytotoxicity test was performed by neutral red uptake assay. The results of resveratrol IC{sub 50%} in NCI-H292 cells was 192{mu}M and in RD cells was 128{mu}M; and RD cells gamma radiation LD{sub 50} was 435Gy. (author)

  6. Do placebo expectations influence perceived exertion during physical exercise?

    Directory of Open Access Journals (Sweden)

    Hendrik Mothes

    Full Text Available This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a the effects of exercise and b the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

  7. Design of radiation dose tumor response assays

    International Nuclear Information System (INIS)

    Suit, H.D.; Hwang, T.; Hsieh, C.; Thames, H.

    1985-01-01

    The efficient utilization of animals in a radiation dose response assay for tumor control requires a definition of the goal, e.g., TCD50 or slope. A series of computer modelled ''experiments'' have been performed for each of a number of allocations of dose levels (DL) and number of animals/DL. The authors stipulated that the assumed TCD50 was .85 of true value; assumed slope was correct. They stipulated a binominal distribution of observed tumor control results at each dose level. A pilot assay used 6 tumors at 7 DL (from TCD1-TCD97). The second assay used 30 tumors assigned to 2,3,5 or 9 DL and to selected tumor control probabilities (TCP derived from the pilot run. Results from 100 test runs were combined with the pilot run for each of the combination of DL and TCP values. Logit regression lines were fitted through these ''data'' and the 95% CL around the TCD50 and the TCD37 values and the variances of the slopes were computed. These experiments were repeated using the method suggested by Porter (1980). Results show that a different strategy is needed depending upon the goal, viz. TCD50 or TCD37 vs slope. The differences between the two approaches are discussed

  8. Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

    International Nuclear Information System (INIS)

    Helbig, Linda; Koi, Lydia; Brüchner, Kerstin; Gurtner, Kristin; Hess-Stumpp, Holger; Unterschemmann, Kerstin; Pruschy, Martin

    2014-01-01

    Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD 50 ) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P 50 , with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD 50 . Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of radiation response. Whether this mechanism contributes to the improved outcome of fractionated chemoradiation therapy warrants further investigation

  9. Artesunate inhibits adipogeneis in 3T3-L1 preadipocytes by reducing the expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr

    2016-05-20

    Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. However, excessive adipogenesis is closely linked to the development of obesity. Artesunate, one of artemisinin-type sesquiterpene lactones from Artemisia annua L., is known for anti-malarial and anti-cancerous activities. In this study, we investigated the effect of artesunate on adipogenesis in 3T3-L1 preadipocytes. Artesunate strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes at 5 μM concentration. Artesunate at 5 μM also reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during adipocyte differentiation. Moreover, artesunate at 5 μM reduced leptin, but not adiponectin, mRNA expression during adipocyte differentiation. Taken together, these findings demonstrate that artesunate inhibits adipogenesis in 3T3-L1 preadipoytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. -- Highlights: •Artesunate, an artemisinin derivative, inhibits adipogenesis. •Artesunate inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. •Artesunate reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. •Artesunate thus may have therapeutic potential against obesity.

  10. Biological markers as predictors of radiosensitivity in syngeneic murine tumors

    International Nuclear Information System (INIS)

    Chang, Sei Kyung; Shin, Hyun Soo; Seong, Jin Sil; Kim, Sung Hee

    2006-01-01

    We investigated whether a relationship exists between tumor control dose 50 (TCD 50 ) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD 50 , TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 ∼ 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD 50 , TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21 WAF1/CIP1 , BAX, Bcl-2, Bcl-x L , Bcl-x S , and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD 50 or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD 50 , TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, ρ = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD 50 (ρ = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21 WAF1/CIP1 and p34 showed a significant correlation either with TCD 50 (R = 0.893, ρ = 0.041 and R = 0.904, ρ = 0.035) or with TGD (R = -0.922, ρ 0.026 and R = -0.890, ρ = 0.043). The tumors with high constitutive expression levels of p21 WAF1/CIP1 or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of p21 WAF1/CIP1 or p34 can be used as biological

  11. Biological markers as predictors of radiosensitivity in syngeneic murine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sei Kyung; Shin, Hyun Soo [Bundang CHA General Hospital, Seongnam (Korea, Republic of); Seong, Jin Sil; Kim, Sung Hee [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2006-06-15

    We investigated whether a relationship exists between tumor control dose 50 (TCD{sub 50}) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD{sub 50}, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 {approx} 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD{sub 50}, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21{sup WAF1/CIP1}, BAX, Bcl-2, Bcl-x{sub L}, Bcl-x{sub S}, and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD{sub 50} or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD{sub 50}, TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, {rho} = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD{sub 50} ({rho} = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21{sup WAF1/CIP1} and p34 showed a significant correlation either with TCD{sub 50} (R = 0.893, {rho} = 0.041 and R = 0.904, {rho} = 0.035) or with TGD (R = -0.922, {rho} 0.026 and R = -0.890, {rho} = 0.043). The tumors with high constitutive expression levels of p21{sup WAF1/CIP1} or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The

  12. Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    International Nuclear Information System (INIS)

    Jang, Byeong-Churl

    2016-01-01

    Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra S. Moore and has been shown to possess anti-inflammatory and anti-cancerous activities. In this study, the effect of tetrandrine on adipogenesis in 3T3-L1 preadipocytes was investigated. Tetrandrine at 10 μM concentration strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, tetrandrine reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 adipocyte differentiation. Tetrandrine also reduced the mRNA expression of leptin, but not adiponectin, during 3T3-L1 adipocyte differentiation. Collectively, these findings show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. - Highlights: • Tetrandrine, a bisbenzylisoquinoline alkaloid, inhibits adipogenesis. • Tetrandrine inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. • Tetrandrine reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Tetrandrine may thus have therapeutic potential against obesity.

  13. Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr

    2016-08-05

    Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra S. Moore and has been shown to possess anti-inflammatory and anti-cancerous activities. In this study, the effect of tetrandrine on adipogenesis in 3T3-L1 preadipocytes was investigated. Tetrandrine at 10 μM concentration strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, tetrandrine reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 adipocyte differentiation. Tetrandrine also reduced the mRNA expression of leptin, but not adiponectin, during 3T3-L1 adipocyte differentiation. Collectively, these findings show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. - Highlights: • Tetrandrine, a bisbenzylisoquinoline alkaloid, inhibits adipogenesis. • Tetrandrine inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. • Tetrandrine reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Tetrandrine may thus have therapeutic potential against obesity.

  14. Increase in tumor oxygen tension and radiosensitivity after administration of pentoxifylline

    International Nuclear Information System (INIS)

    Hasegawa, Takeo; Gu, Yeun Hwa; Nagao, Takashi; Miyata, Katsuyuki; Song, Chang W.; Tanake, Yoshimasa; Hasegawa, Takashi

    1999-01-01

    The effects of pentoxifylline (PTX) on the pO2 and radioresponse in SCK tumors of A/J mice were investigated. When the mice were injected intraperitoneally with 5 mg/kg of PTX, the tumor pO2 increased slowly, peaked 20-50 min postinjection, and returned to its original level in 70-90 min. The magnitude of the changes in tumor pO2 after on ip injection of 25 or 50 mg/kg PTX was similar to that caused by 5 mg/kg PTX. When the A/J mice bearing SCK tumors in the legs were injected ip with 50 mg/kg PTX and the tumors were X ray irradiated 20 min later, the tumor growth delay was greater than that of radiation alone

  15. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

    Directory of Open Access Journals (Sweden)

    J. Wang

    2015-03-01

    Full Text Available This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each given daily intraperitoneal injections of vehicle (physiological saline, esculetin (200, 400, or 700 mg·kg-1·day-1, or 5-Fu (200 mg·kg-1·day-1 for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

  16. In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2012-05-01

    Full Text Available Withania somnifera (L. Dunal (Indian ginseng, winter cherry, Solanaceae is widely used in traditional medicine. Roots are either chewed or used to prepare beverages (aqueous decocts. The major secondary metabolites of Withania somnifera are the withanolides, which are C-28-steroidal lactone triterpenoids. Withania somnifera extracts exert chemopreventive and anticancer activities in vitro and in vivo. The aims of the present in silico study were, firstly, to investigate whether tumor cells develop cross-resistance between standard anticancer drugs and withanolides and, secondly, to elucidate the molecular determinants of sensitivity and resistance of tumor cells towards withanolides. Using IC50 concentrations of eight different withanolides (withaferin A, withaferin A diacetate, 3-azerininylwithaferin A, withafastuosin D diacetate, 4-B-hydroxy-withanolide E, isowithanololide E, withafastuosin E, and withaperuvin and 19 established anticancer drugs, we analyzed the cross-resistance profile of 60 tumor cell lines. The cell lines revealed cross-resistance between the eight withanolides. Consistent cross-resistance between withanolides and nitrosoureas (carmustin, lomustin, and semimustin was also observed. Then, we performed transcriptomic microarray-based COMPARE and hierarchical cluster analyses of mRNA expression to identify mRNA expression profiles predicting sensitivity or resistance towards withanolides. Genes from diverse functional groups were significantly associated with response of tumor cells to withaferin A diacetate, e.g. genes functioning in DNA damage and repair, stress response, cell growth regulation, extracellular matrix components, cell adhesion and cell migration, constituents of the ribosome, cytoskeletal organization and regulation, signal transduction, transcription factors, and others.

  17. Physical Exertion and Immediate Classroom Mental Performance Among Elementary School Children.

    Science.gov (United States)

    Gabbard, Carl

    This study was designed (1) to investigate the relationship between physical exertion and mental performance in elementary school children and (2) to determine if male or female mental performances are more affected by physical exertion. A total of 95 second graders participated in six treatments of induced physical exertion during their regularly…

  18. Tumores del timo y cirugía Tumors of thymus and surgery

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Martín González

    2011-09-01

    Full Text Available Introducción: los tumores del timo constituyen menos del 1 % de todas las neoplasias, y es la cirugía el tratamiento de elección. Objetivos: conocer el tipo de tratamiento quirúrgico y la magnitud de la resección, así como la relación con el tamaño del tumor, el sangrado, el tiempo quirúrgico, la morbilidad y la mortalidad. Métodos: se realizó un estudio prospectivo en 22 pacientes con tumor mediastinal, que tuvieron criterios de cirugía durante el ingreso en los servicios de neurología o cirugía general del hospital "Hermanos Ameijeiras", desde enero de 2007 hasta febrero de 2009. Los resultados se presentan en por cientos y se empleó el chi cuadrado en la relación de variables. Resultados: 12 fueron del sexo femenino (54,5 %. El tratamiento más empleado fue la esternotomía total en 9 pacientes (40,9 %, el tiempo quirúrgico varió de 50 a 260 min con mediana de 127,5, mientras el sangrado por encima de 100 mL estuvo asociado a un tiempo quirúrgico de 61 a 180 min (p= 0,036. Se complicaron 11 pacientes (50 % y hubo 1 fallecido (4,5 %. El tamaño del tumor varió de 3,5 a 20 cm. El paciente con tumor neuroendocrino recidivó a los 10 meses, mientras los pacientes con timomas no muestran hasta la fecha recidiva local ni se ha comprobado actividad metastásica. Conclusión: la cirugía constituye el paso más importante en el tratamiento de los tumores mediastinales, y se logra, en la gran mayoría, la resección completa, a pesar del tamaño y la relación con estructuras vecinas.Introduction: the tumors of thymus account for less than 1 % of all neoplasms and the choice treatment is the surgery. Objectives: to know the type of surgical treatment and the magnitude of resection, as well as the relationship with the tumor size, bleeding, surgical time and morbidity and mortality. Methods: a prospective study was conducted in 20 patients presenting with mediastinum tumor with surgery criteria over the admission in the services of

  19. Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies.

    Science.gov (United States)

    Le Plénier, Servane; Goron, Arthur; Sotiropoulos, Athanassia; Archambault, Eliane; Guihenneuc, Chantal; Walrand, Stéphane; Salles, Jérome; Jourdan, Marion; Neveux, Nathalie; Cynober, Luc; Moinard, Christophe

    2017-01-01

    Citrulline (CIT) is an endogenous amino acid produced by the intestine. Recent literature has consistently shown CIT to be an activator of muscle protein synthesis (MPS). However, the underlying mechanism is still unknown. Our working hypothesis was that CIT might regulate muscle homeostasis directly through the mTORC1/PI3K/MAPK pathways. Because CIT undergoes both interorgan and intraorgan trafficking and metabolism, we combined three approaches: in vivo, ex vivo, and in vitro. Using a model of malnourished aged rats, CIT supplementation activated the phosphorylation of S6K1 and 4E-BP1 in muscle. Interestingly, the increase in S6K1 phosphorylation was positively correlated (P < 0.05) with plasma CIT concentration. In a model of isolated incubated skeletal muscle from malnourished rats, CIT enhanced MPS (from 30 to 80% CIT vs. Ctrl, P < 0.05), and the CIT effect was abolished in the presence of wortmannin, rapamycin, and PD-98059. In vitro, on myotubes in culture, CIT led to a 2.5-fold increase in S6K1 phosphorylation and a 1.5-fold increase in 4E-BP1 phosphorylation. Both rapamycin and PD-98059 inhibited the CIT effect on S6K1, whereas only LY-294002 inhibited the CIT effect on both S6K1 and 4E-BP1. These findings show that CIT is a signaling agent for muscle homeostasis, suggesting a new role of the intestine in muscle mass control. Copyright © 2017 the American Physiological Society.

  20. AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Huei-Mei; Schmeichel, Karen L; Mian, I. Saira; Lelie`vre, Sophie; Petersen, Ole W; Bissell, Mina J

    2000-02-04

    To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.

  1. Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

    International Nuclear Information System (INIS)

    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

    2012-01-01

    The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

  2. Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?

    NARCIS (Netherlands)

    van der Poll, T.; Lowry, S. F.

    1995-01-01

    Tumor necrosis factor-alpha (TNF) exerts numerous influences which, in association with severe infection, subserve both detrimental as well as beneficial host responses. The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular

  3. Early-postoperative magnetic resonance imaging in glial tumors: prediction of tumor regrowth and recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Ekinci, Gazanfer; Akpinar, Ihsan N. E-mail: i.akpinar@mailcity.com; Baltacioglu, Feyyaz; Erzen, Canan; Kilic, Tuerker; Elmaci, Ilhan; Pamir, Necmettin

    2003-02-01

    Objective: This study investigated the value of early-postoperative magnetic resonance (EPMR) imaging in the detection of residual glial tumor and investigated the role of EPMR for the prediction of tumor regrowth and recurrence. Methods and materials: We retrospectively analyzed pre- and post-operative magnetic resonance imaging results from 50 adult patients who underwent surgical treatment for supratentorial glial tumor. There were glioblastoma multiforme in 25 patients, astrocytoma (grades II and III) in 11 patients, oligodendroglioma (grades II and III) in 9 patients, and oligoastrocytoma (grades II and III) in 5 patients. EPMR imaging was performed within 24 h after surgery. EPMR findings were compared with the neurosurgeon's intraoperative estimation of gross tumor removal. Patterns of contrast enhancement at the resection site, in residual and developing tumor tissue and blood at the resection site were evaluated on EPMR and in follow-up studies. 'Residual tumor' was defined as contrast enhancing mass at the operative site on EPMR. 'Regrowth' was defined as contrast enhancing mass detected on follow-up in the same location as the primary tumor. 'Recurrence' was defined as appearance of a mass lesion in the brain parenchyma distant from the resection bed during follow-up. Results: Nineteen patients showed no evidence of residual tumor, regrowth, or recurrence on EPMR or any of the later follow-up radiological examinations. EPMR identified 20 cases of residual tumor. Follow-up showed tumor regrowth in 10 patients, and tumor recurrence in 1 case. EPMR showed contrast enhancement of the resection bed in 45 of the 50 patients. Four of the 20 residual tumors showed a thick linear enhancement pattern, and the other 16 cases exhibited thick linear-nodular enhancement. No thin linear enhancement was observed in the residual tumor group. Nine of the 10-regrowth tumors showed a thick linear-nodular enhancement pattern, and one

  4. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  5. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Directory of Open Access Journals (Sweden)

    Sejal Desai

    Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

  6. Recommendations for standardized diagnostics, treatment and following care in tumor diseases. Geriatric patient with tumor disease

    International Nuclear Information System (INIS)

    Hagmueller, E.; Neises, M.; Queisser, W.; Richter, H.; Schneider, G.

    2001-01-01

    The recommendations for the treatment of geriatric patients with tumor disease, presented in the paper, cover: surgery; chemotherapy; radiotherapy and immunotherapy. Radiotherapy is recommended for skin tumors, pain treatment in the bone metastases (40 - 50 Gy), system diseases (with reduction of the usual size of the irradiated area), small size tumors etc. It is considered as an appropriate method (excluding wide fields) for geriatric outpatients

  7. EBP2R - an innovative enhanced biological nutrient recovery activated sludge system to produce growth medium for green microalgae cultivation.

    Science.gov (United States)

    Valverde-Pérez, Borja; Ramin, Elham; Smets, Barth F; Plósz, Benedek Gy

    2015-01-01

    Current research considers wastewater as a source of energy, nutrients and water and not just a source of pollution. So far, mainly energy intensive physical and chemical unit processes have been developed to recover some of these resources, and less energy and resource demanding alternatives are needed. Here, we present a modified enhanced biological phosphorus removal and recovery system (referred to as EBP2R) that can produce optimal culture media for downstream micro-algal growth in terms of N and P content. Phosphorus is recovered as a P-stream by diversion of some of the effluent from the upstream anaerobic reactor. By operating the process at comparably low solids retention times (SRT), the nitrogen content of wastewater is retained as free and saline ammonia, the preferred form of nitrogen for most micro-algae. Scenario simulations were carried out to assess the capacity of the EBP2R system to produce nutrient rich organic-carbon depleted algal cultivation media of target composition. Via SRT control, the quality of the constructed cultivation media can be optimized to support a wide range of green micro-algal growth requirements. Up to 75% of the influent phosphorus can be recovered, by diverting 30% of the influent flow as a P-stream at an SRT of 5 days. Through global sensitivity analysis we find that the effluent N-to-P ratio and the P recovered are mainly dependent on the influent quality rather than on biokinetics or stoichiometry. Further research is needed to demonstrate that the system performance predicted through the model-based design can be achieved in reality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Local recurrence of metastatic brain tumor after surgery

    International Nuclear Information System (INIS)

    Shinoura, Nobusada; Yamada, Ryoji; Okamoto, Koichiro; Nakamura, Osamu; Shitara, Nobuyuki; Karasawa, Katsuyuki

    2006-01-01

    We analyzed factors associated with the local recurrence of brain metastases after surgery. Forty-seven patients with 67 metastatic brain tumors underwent surgery between 1994 and 2001. The survival time in the ''no recurrence'' group (34.7 months) was significantly longer than that in the recurrence group (21.9 months) (p=0.0008; log rank test). The factors affecting the local recurrence of brain metastases after surgery were as follows: cyst (p=0.0156), dural invasion (p=0.0029) of tumors, failure to totally remove tumors (p=0.0040), and lack of post-surgical irradiation (p<0.0001). Sex, age, tumor histology, tumor size, pre-surgical radiation, dose (≥45 vs <45, ≥50 vs <50 Gy) and the method (local vs whole brain) of post-surgical radiation did not affect the local recurrence rate of brain metastases after surgery. To avoid early recurrences of metastatic brain tumors, the factors associated with local recurrence should be considered in providing optimal treatment of tumors by surgery. (author)

  9. Assessment of diagnostic value of various tumors markers (CEA, CA199, CA50) for colorectal neoplasm with logistic regression and ROC curve

    International Nuclear Information System (INIS)

    Gu Ping; Huang Gang; Han Yuan

    2007-01-01

    Objective: To assess the diagnostic value of CEA, CA199 and CA50 for colorectal neoplasm by logistic regression and ROC curve. Methods: Serum CEA (with CLIA), CA199 (with ECLIA) and CA50 (with IRMA) levels were measured in 75 patients with colorectal cancer, 35 patients with benign colorectal disorders and 49 controls. The area under the ROC curve (AUC)s of CEA, CA199, CA50 from logistic regression results were compared. Results: In the cancer-benign disorder group, the AUC of CA50 was larger than the AUC of CA199. AUC of combined CEA, CA50 was largest: not only larger than any AUC of CEA, CA50, CA199 alone but also larger than the AUC of the combined three markers (0.875 vs 0.604). In cancer-control group, the AUC of combination of CEA, CA199 and CA50 was larger than any AUC of CEA, CA199 or CA50 alone. Both in the cancer-benign disorder group or cancer-control group, the AUC of CEA was larger than the AUC of CA199 or CA50. Conclusion: CEA is of definite value in the diagnosis of colorectal cancer. For differential diagnosis, the combination of CEA and CA50 can give more information, while the combination of three tumor markers is less helpful. As an advanced statistical method, logistic regression can improve the diagnostic sensitivity and specificity. (authors)

  10. Factors associated with high physical exertion during manual lifting

    DEFF Research Database (Denmark)

    Andersen, Lars L.; Sundstrup, Emil; Brandt, Mikkel

    2018-01-01

    BACKGROUND: High physical exertion during work is a risk factor for back pain and long-term sickness absence. OBJECTIVE: To investigate which factors are associated with physical exertion during manual lifting. METHODS: From 14 workplaces across Denmark, 200 blue-collar workers reported perceived...... physical exertion (Borg-CR10) during manual lifting from floor to table height of 5, 10, 20 and 30 kg at the beginning and end of the working day. The workers also responded to a questionnaire and went through testing of isometric back muscle strength. Associations were modelled using logistic regression...... during manual lifting in blue-collar workers. These factors should be considered when planning work with manual lifting for individual workers....

  11. Exertional Rhabdomyolysis after Spinning

    OpenAIRE

    Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-01-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24?48 hours after attending a spi...

  12. Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2012-2016.

    Science.gov (United States)

    2017-03-01

    Among active component service members in 2016, there were 525 incident diagnoses of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis"). The crude incidence rate in 2016 was 40.7 cases per 100,000 person-years. Annual rates of incident diagnoses of exertional rhabdomyolysis increased 46.2% between 2013 and 2016, with the greatest percentage change occurring between 2014 and 2015. In 2016, relative to their respective counterparts, the highest incidence rates of exertional rhabdomyolysis affected service members who were male; younger than 20 years of age; and black, non-Hispanic. During the surveillance period, annual incidence rates were highest among service members of the Marine Corps, intermediate among those in the Army, and lowest among those in the Air Force and Navy. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or the Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain or swelling, limited range of motion, or the excretion of dark urine (possibly due to myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

  13. Targeted tumor theranostics using folate-conjugated and camptothecin-loaded acoustic nanodroplets in a mouse xenograft model.

    Science.gov (United States)

    Chen, Wei-Tsung; Kang, Shih-Tsung; Lin, Jian-Liang; Wang, Chung-Hsin; Chen, Ran-Chou; Yeh, Chih-Kuang

    2015-01-01

    In this study, we aimed to validate the feasibility of receptor-targeted tumor theranostics with folate-conjugated (FA) and camptothecin-loaded (CPT) acoustic nanodroplets (NDs) (collectively termed FA-CPT-NDs). The ND formulation was based on lipid-stabilized low-boiling perfluorocarbon that can undergo acoustic droplet vaporization (ADV) under ultrasound (US) exposure. Conjugation of folate enhanced the selective delivery to tumors expressing high levels of folate receptor (FR) under mediation by the enhanced permeability and retention effect. In vitro and in vivo studies were performed using FR-positive KB and FR-negative HT-1080 cell lines and mouse xenograft tumor models. Simultaneous therapy and imaging were conducted with a clinical US imaging system at mechanical indices of up to 1.4 at a center frequency of 10 MHz. The results demonstrated that FA-CPT-NDs selectively attached to KB cells, but not HT-1080 cells. The targeted ADV caused instant and delayed damage via mechanical disruption and chemical toxicity to decrease the viability of KB cells by up to 45%, a much higher decrease than that achieved by the NDs without folate conjugation. The in vivo experiments showed that FR-mediated targeting successfully enhanced the EPR of FA-CPT-NDs in KB tumors mainly on the tumor periphery as indicated by immunofluorescence microscopy and US B-mode imaging. Treatments with FA-CPT-NDs at a CPT dose of 50 μg/kg inhibited the growth of KB tumors for up to six weeks, whereas treatment with NDs lacking folate produced a 4.6-fold increase in tumor volume. For HT-1080 tumors, neither the treatments with FA-CPT-NDs nor those with the NDs lacking folate presented tumor growth inhibition. In summary, FR-targeted tumor theranostics has been successfully implemented with FA-CPT-NDs and a clinical US unit. The ligand-directed and EPR-mediated accumulation provides active and passive targeting capabilities, permitting the antitumor effects of FA-CPT-NDs to be exerted

  14. Parotid hybrid tumor

    International Nuclear Information System (INIS)

    Bravo C, Gustavo; Seymour M, Camila; Fernandez R, Lara; Villanueva I, Maria Elena; Scott C, Carlos; Celedon L, Carlos

    2012-01-01

    Tumors of the salivary glands represent 33%-10% of head and neck neoplasms. The most common location is the parotid gland, accounting for 50%-85% of the cases, with 20%-30% of them being malignant. The following are known to be indicative of a malignant tumor: fast growing, painless mass, associated facial paralysis and lymphadenopathy. Most parotid neoplasm derive from a single histological type but eventually the development of more than one type on the same gland can occur. This paper presents a case of a parotid neoplasm with two different histological tumors, with uncharacteristic clinical presentation. The patient presented initially with ear pain and otorrhoea, in the clinical examination highlighted an external auditory canal tumor. The complementary study revealed a parotid neoplasm and a total resection of the gland was performed. The biopsy revealed an adenoid-cystic carcinoma with differentiated basaloid areas. Adjuvant radio-chemotherapy was administered, and the imaging control with PET-CT showed no evidence of recurrence or dissemination of the tumor

  15. WE-EF-BRA-11: Precision Partial-Tumor Irradiation of Dorsal Rodent Mammary Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Malcolm, J [Duke Medical Physics Graduate Program, Durham, NC (United States); Boss, K [Department of Comparative Biomedical Sciences, North Carolina State University (United States); Dewhirst, M [Dpt of Radiation and Cancer Biology, Duke University, Durham, North Carolina (United States); Oldham, M [Dpt of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2015-06-15

    Purpose: To introduce a pre-clinical treatment technique on a micro-irradiator to treat specific volumes of dorsal mammary tumors in BALB/c mice while sparing lungs and spine. This technique facilitates pre-clinical investigation of tumor response to sub-optimal radiation treatments in which a portion of the tumor is unirradiated, known as a “marginal miss”. In-vitro data suggests that partial tumor radiations trigger a more aggressive phenotype in non-irradiated, regional tumor cells via bystander effects. As the lung tissue is spared, the impact of marginal miss on the development of pulmonary metastasis may be assessed. Methods: End to end test was performed on three BALB/c mice as proof of concept for larger studies. 1Gy was delivered on the micro-irradiator employing previously unexplored lateral parallel-opposed diamond and/or triangle-shaped beams. The margins of the treatment beam were defined using a combination of tumor palpation, barium fiducial markers, and real-time fluoroscopic images. The dose distribution was independently verified with kilovoltage beam Monte Carlo dose calculations with 7% statistical uncertainty and double exposure images. As a final step, the technique was used in a larger pre-clinical study (15Gy, 36 BALB/c mice) and lung metastasis in response to tumor irradiation of 100%, 50% and 0% was quantified. Results: For the Monte-Carlo dose calculations, the dose volume histograms established a maximum dose within the un-irradiated and radiated portions of the mammary tumor of 0.3Gy and 1.5Gy respectively, with a sharp gradient at the boundary. 100% of the lung volume received less than 0.5Gy. This technique proved suitable for a pre-clinical marginal miss study with 50% more lung metastases in partially-radiated mouse models compared to completely. Conclusion: We have developed a novel treatment technique for partial or full irradiation of dorsal mammary tumors incorporating lung sparing.The technique will be useful for exploring

  16. Exertional headache and coronary ischemia despite normal electrocardiographic stress testing.

    Science.gov (United States)

    Cutrer, F Michael; Huerter, Karina

    2006-01-01

    Exertional headaches may under certain conditions reflect coronary ischemia. We report the case of a patient seen in a neurology referral practice whose exertional headaches, even in the face of two normal electrocardiographic stress tests and in the absence of underlying chest pain were the sole symptoms of coronary ischemia as detected by Tc-99m Sestamibi testing SPECT stress testing. Stent placement resulted in complete resolution of headaches. Exertional headache in the absence of chest pain may reflect underlying symptomatic coronary artery disease (CAD) even when conventional electrocardiographic stress testing does not indicate ischemia.

  17. Analysis of PI3K/mTOR Pathway Biomarkers and Their Prognostic Value in Women with Hormone Receptor–Positive, HER2-Negative Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hamdy A. Azim

    2016-04-01

    Full Text Available BACKGROUND: The PI3K/AKT/mTOR pathway alterations have been shown to play significant roles in the development, progression, and metastatic spread of breast cancer. Furthermore, they have been implicated in the process of drug resistance, especially endocrinal therapies. In this study, we aimed to define the correlation between the PI3K mutations and the expression of the phosphorylated forms of different downstream molecules in women with estrogen receptor (ER–positive, human epidermal growth factor receptor 2–negative (luminal early breast cancer treated at Cairo university hospitals. METHODS: Next-generation sequencing was used to detect mutations in the PIK3CA hotspots (in exons 9 and 20. Immunohistochemistry was performed on tissue microarray blocks prepared from samples of 35 Egyptian luminal breast cancer patients in the pathology department of Centre Léon Bérard (CLB. The intensity and the percentage of stained tumor cells were integrated to define high versus low biomarker expression. The cytoplasmic and nuclear stainings were graded separately. Patients were followed for a median of 4.7 years (2.1 to 6.9 years. Correlation was done between PI3K mutations and the immunohistochemistry expression of pAKT, LKB1, p4EBP1, and pS6 ribosomal protein (pS6RP with the clinicopathologic features and disease free survival (DFS of the patients. RESULTS: Median age at diagnosis was 51.3 years (range, 25 to 82 years. Tumors were larger than 20 mm in 79.2% of the cases, whereas 57.9% had axillary lymph node deposits. Only 12.3% of the patients had SBR grade I tumors, 50.8% had grade II, and 36.8% had grade III. ERs were negative in 6 patients (17% after pathology review. Thirty-two cases were assessable for LKB1 and pAKT, 33 for p4EBP1 and pS6RP, and 24 for PI3K mutations. Nuclear LKB1, cytoplasmic LKB1, nuclear pAKT, cytoplasmic pAKT, nuclear p4EBP1, and cytoplasmic pS6RP expression was high in 65.6%, 62.5%, 62.5%, 68.8%, 42.4%, and 57

  18. Generation of autologous tumor-specific T cells for adoptive transfer based on vaccination, in vitro restimulation and CD3/CD28 dynabead-induced T cell expansion

    DEFF Research Database (Denmark)

    Brimnes, Marie Klinge; Gang, Anne Ortved; Donia, Marco

    2012-01-01

    Adoptive cell transfer (ACT) of in vitro expanded autologous tumor-infiltrating lymphocytes (TIL) has been shown to exert therapeutic efficacy in melanoma patients. We aimed to develop an ACT protocol based on tumor-specific T cells isolated from peripheral blood and in vitro expanded by Dynabeads...

  19. The clinical application of radioimmunoimaging with 99mTc labeled anti-CEA monoclonal antibody C50

    International Nuclear Information System (INIS)

    Jiang Ningyi; Sha Xiaozhen; Zhang Hua

    1996-01-01

    To evaluate the clinical value of the radioimmunoimaging (RII) for the diagnosis of tumor with 99m Tc labeled anti-CEA monoclonal antibody C50, C50 was labeled with 99m Tc using modified 2-mercaptoethanol method. 99m Tc-C50 RII was performed in 70 patients with tumor. All were pathologically proved after operation. The sensitivity of 99m Tc-C50 RII for tumor was 82.9%, the specificity was 86.2%, the false negative rate was 17.1%, and the false positive rate was 13.8%. The positive predictive value was 89.5%, the negative predictive value was 78.1%. The coincidence rates was 82.4%, 84.6% and 80.0% for the ovarial intestinal and lung tumor respectively. 99m Tc-C50 RII was useful in clinical diagnosis of tumor

  20. Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy

    International Nuclear Information System (INIS)

    Chang, Lihong; Huang, Jiancong; Wang, Kai; Li, Jingjia; Yan, Ruicheng; Zhu, Ling; Ye, Jin; Wu, Xifu; Zhuang, Shimin; Li, Daqing; Zhang, Gehua

    2016-01-01

    The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption. The online version of this article (doi:10.1186/s12885-016-2190-8) contains supplementary material, which is available to

  1. Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression.

    Science.gov (United States)

    Wang, Feng-Wei; Cai, Mu-Yan; Mai, Shi-Juan; Chen, Jie-Wei; Bai, Hai-Yan; Li, Yan; Liao, Yi-Ji; Li, Chang-Peng; Tian, Xiao-Peng; Kung, Hsiang-Fu; Guan, Xin-Yuan; Xie, Dan

    2014-08-30

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.

  2. Clinical significance of combined determination of several tumor markers (including CYFRA21-1, NSE, CA-50 and CEA) in patients with pulmonary cancer

    International Nuclear Information System (INIS)

    Zhu Mingfeng; Wen Chijun; Zhu Cuiying

    2005-01-01

    Objective: To enhance the diagnosis of pulmonary cancer by determination of optimal combinations of various tumor markers. Methods: Serum CYFRA 21-1 , NSE, CA-50 (with RIA) and CEA (with CLIA) contents were determined in 107 patients with various types of pulmonary cancers, 66 patients with various benign pulmonary diseases and 59 controls. Results: It was revealed that CYFRA 21-1 determination was most sensitive for detection of squamous cell carcinoma. The same was true for CEA in the detection of adenocarcinoma. NSE determination was very specific for small cell carcinoma. Combined determinations of either CYFRA 21- l + NSE or CYFRA 21-1 + NSE + CEA were excellent for general screening. Conclusion: Combined determination of these tumor markers could be applied expediently as supplementary diagnostic measure for pulmonary malignancies. (authors)

  3. Odontogenic tumors: analysis of 127 cases Tumores odontogênicos: análise de 127 casos

    Directory of Open Access Journals (Sweden)

    Jean Nunes SANTOS

    2001-12-01

    Full Text Available One hundred and twenty-seven cases of histologically confirmed odontogenic tumors were retrieved from a total of 5,289 oral and maxillary lesions diagnosed at the Division of Oral Pathology, Federal University of Rio Grande do Norte, during a period of 30 years (l970-l999. The most common histological diagnosis was odontoma (50.40%, followed by ameloblastoma (30.70%. The prevalence of odontogenic tumors was greater in females and the peak incidence occurred in the second and third decades of life. The main anatomical location was the mandible, and no malignant tumors were found.De uma série de 5.289 casos de lesões orais e dos maxilares diagnosticadas no Laboratório de Patologia Oral da Faculdade de Odontologia da Universidade Federal do Rio Grande do Norte no período de 30 anos (1970-1999, foram analisados 127 casos de tumores odontogênicos confirmados histologicamente. A lesão mais freqüente foi o odontoma (50,40% seguida pelo ameloblastoma (30,70%. A prevalência de tumores odontogênicos foi maior nas mulheres e o pico de incidência ocorreu na segunda e terceira décadas de vida. A localização anatômica mais comum foi a mandíbula e não foram encontrados casos de tumores malignos.

  4. Influence of permittivity on gradient force exerted on Mie spheres.

    Science.gov (United States)

    Chen, Jun; Li, Kaikai; Li, Xiao

    2018-04-01

    In optical trapping, whether a particle could be stably trapped into the focus region greatly depends on the strength of the gradient force. Individual theoretical study on gradient force exerted on a Mie particle is rare because the mathematical separation of the gradient force and the scattering force in the Mie regime is difficult. Based on the recent forces separation work by Du et al. [Sci. Rep.7, 18042 (2017)SRCEC32045-232210.1038/s41598-017-17874-1], we investigate the influence of permittivity (an important macroscopic physical quantity) on the gradient force exerted on a Mie particle by cooperating numerical calculation using fast Fourier transform and analytical analysis using multipole expansion. It is revealed that gradient forces exerted on small spheres are mainly determined by the electric dipole moment except for certain permittivity with which the real part of polarizability of the electric dipole approaches zero, and gradient forces exerted on larger spheres are complex because of the superposition of the multipole moments. The classification of permittivity corresponding to different varying tendencies of gradient forces exerted on small spheres or larger Mie particles are illustrated. Absorption of particles favors the trapping of small spheres by gradient force, while it is bad for the trapping of larger particles. Moreover, the absolute values of the maximal gradient forces exerted on larger Mie particles decline greatly versus the varied imaginary part of permittivity. This work provides elaborate investigation on the different varying tendencies of gradient forces versus permittivity, which favors more accurate and free optical trapping.

  5. HDAC inhibitor L-carnitine and proteasome inhibitor bortezomib synergistically exert anti-tumor activity in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Hongbiao Huang

    Full Text Available Combinations of proteasome inhibitors and histone deacetylases (HDAC inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21(cip1 gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like activity assay. Here we report that (i the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii the combination also synergistically inhibits tumor growth in vivo; (iii two major pathways are involved in the synergistical effects of the combinational treatment: increased p21(cip1 expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials.

  6. Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

    DEFF Research Database (Denmark)

    Trojel-Hansen, Christina; Erichsen, Kamille Dumong; Christensen, Mette Knak

    2011-01-01

    oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2a as well as mTOR pathway inhibition supports the above notion. In addition...

  7. Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

    DEFF Research Database (Denmark)

    Trojel-Hansen, Christina; Erichsen, Kamille Dumong; Christensen, Mette Knak

    2011-01-01

    oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2α as well as mTOR pathway inhibition supports the above notion. In addition...

  8. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Brock, C; Brock, B; Aziz, Q

    2017-01-01

    -VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which...

  9. Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Chapman, Christopher [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of Michigan School of Medicine, Ann Arbor, MI (United States); Rao, Aarti [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Davis, School of Medicine, Davis, CA (United States); Shen, John [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Irvine, School of Medicine, Irvine, CA (United States); Quinlan-Davidson, Sean [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Filion, Edith J. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Departement de Medecine, Service de Radio-Oncologie, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Wakelee, Heather A.; Colevas, A. Dimitrios [Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); Whyte, Richard I. [Department of Cardiothoracic Surgery, Division of General Thoracic Surgery, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); and others

    2012-09-01

    Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume {>=}12 mL) received multifraction regimens with BED {>=}100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  10. Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.

    Science.gov (United States)

    Tian, Binqiang; Zhao, Yingmei; Liang, Tao; Ye, Xuxiao; Li, Zuowei; Yan, Dongliang; Fu, Qiang; Li, Yonghui

    2017-08-01

    We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.

  11. Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived tumor xenograft models

    Science.gov (United States)

    Yang, Cheng-Yu; Lin, Chih-Kung; Tsao, Chang-Huei; Hsieh, Cheng-Chih; Lin, Gu-Jiun; Ma, Kuo-Hsing; Shieh, Yi-Shing; Sytwu, Huey-Kang; Chen, Yuan-Wu

    2017-01-01

    Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we examined whether aberrant LSD1 overexpression in OSCC is associated with poor prognosis. We also evaluated the action mechanism of melatonin against OSCC with lymphatic metastases by using the PDTX models. Our results indicated that melatonin, at pharmacological concentrations, significantly suppresses cell proliferation in a dose- and time-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that the beneficial effects of melatonin in reducing oral cancer cell proliferation are associated with reduced LSD1 expression in vivo and in vitro. PMID:28422711

  12. Connexin 43 Gene Therapy Delivered by Polymer-Modified Salmonella in Murine Tumor Models

    Directory of Open Access Journals (Sweden)

    Wei-Kuang Wang

    2014-04-01

    Full Text Available The use of preferentially tumor-targeting bacteria as vectors is one of the most innovative approaches for the treatment of cancer. This method is based on the observation that some obligate or facultative anaerobic bacteria are capable of selectively multiplying in tumors and inhibiting their growth. Previously, we found that the tumor-targeting efficiency of Salmonella could be modulated by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride (PAH, and these organisms are designated PAH-S.C. (S. choleraesuis. PAH can provide a useful platform for the chemical modification of Salmonella, perhaps by allowing a therapeutic gene to bind to tumor-targeting Salmonella. This study aimed to investigate the benefits of the use of PAH-S.C. for gene delivery. To evaluate this modulation, the invasion activity and gene transfer of DNA-PAH-S.C. were measured in vitro and in vivo. Treatment with PAH-S.C. carrying a tumor suppressor gene (connexin 43 resulted in inhibition of tumor growth, which suggested that tumor-targeted gene therapy using PAH-S.C. carrying a therapeutic gene could exert antitumor activities. This technique represents a promising strategy for the treatment of tumors.

  13. Effect of physical exertion on the biological monitoring of exposure of various solvents following exposure by inhalation in human volunteers: I. Toluene.

    Science.gov (United States)

    Nadeau, Véronique; Truchon, Ginette; Brochu, Martin; Tardif, Robert

    2006-09-01

    Physical exertion (work load) has been recognized as one of several factors that can influence the kinetics of xenobiotics within the human body. This study was undertaken to evaluate the impact of physical exertion on two exposure indicators of toluene (TOL) in human volunteers exposed under controlled conditions in an inhalation chamber. A group of four volunteers (one woman, three men) were exposed to TOL (50 ppm) according to the following scenarios involving several periods during which volunteers were asked to perform either aerobic (AERO), muscular (MUSC), or both (AERO/MUSC) types of physical exercise (exercise bicycle, treadmills, pulleys). The target intensities (W) for each exercising period of 30 min--interspaced with 15 min at rest--were the following: REST, 50 W AERO (time-weighted average intensity [TWAI]: 46 watts); 50 W AERO/MUSC (TWAI: 38 watts) and 100 W AERO (TWAI: 71 watts) for 7 hours and 50 W MUSC for 3 hours (TWAI: 29 watts). Alveolar air and urine samples were collected at different time intervals before, during, and after exposure for the measurement of unchanged TOL in expired air (TOL-A) and urinary o-cresol (o-CR). Overall, the results showed that TOL-A measured during and after all scenarios involving physical activities were higher (approximately 1.4-2.0 fold) compared with exposures at rest. All scenarios involving physical exertion also resulted in increased end-of-exposure urinary o-CR (mean +/- SD): 0.9 +/- 0.1 mg/L (REST) vs. 2.0 +/- 0.1 mg/L (TWAI 46 watts). However, exposure at a TWAI of 71 watts did not further increase o-CR excretion (1.7 +/- 0.2 mg/L). This study confirms the significant effect of work load on TOL kinetics and showed that o-CR excretion increased proportionally with work load expressed as TWAI or with the estimated mean pulmonary ventilation during the period of exposure. This study also shows that exposure to TOL (50 ppm) involving a work load of around 50 W (light intensity) or lower is likely to produce

  14. Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Raciti, Gregory Alexander; Fiory, Francesca; Campitelli, Michele; Desiderio, Antonella; Spinelli, Rosa; Longo, Michele; Nigro, Cecilia; Pepe, Giacomo; Sommella, Eduardo; Campiglia, Pietro; Formisano, Pietro; Beguinot, Francesco; Miele, Claudia

    2018-01-01

    Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1 cells adipocyte differentiation and function in vitro. We found that CAde enhances terminal adipocyte differentiation of 3T3-L1 cells raising the expression of CCAAT/enhancer binding protein beta (C/Ebpβ), peroxisome proliferator activated receptor gamma (Pparγ), glucose transporter type 4 (Glut4) and fatty acid binding protein 4 (Fabp4). CAde improves insulin-induced glucose uptake of 3T3-L1 adipocytes, as well. A focused analysis of the phases occurring in the pre-adipocytes differentiation to mature adipocytes furthermore revealed that CAde promotes the early differentiation stage by up-regulating C/ebpβ expression at 2, 4 and 8 h post the adipogenic induction and anticipating the 3T3-L1 cell cycle entry and progression during mitotic clonal expansion (MCE). These findings provide evidence that the exposure to CAde enhances in vitro fat cell differentiation of pre-adipocytes and functional capacity of mature adipocytes, and pave the way to the development of products derived from Citrus aurantium L. fruit juice, which may improve WAT functional capacity and may be effective for the prevention and/or treatment of T2D.

  15. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    International Nuclear Information System (INIS)

    Huang, Peigen; Allam, Ayman; Perez, Luis A.; Taghian, Alphonse; Freeman, Jill; Suit, Herman D.

    1995-01-01

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm 3 , mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD 50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD 50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

  16. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    Science.gov (United States)

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

  17. Radiotherapy for a cystadenolymphoma of the parotid gland (Warthin's tumor); Radiotherapie bei einem Zystadenolymphom der Parotis (Warthin-Tumor)

    Energy Technology Data Exchange (ETDEWEB)

    Stallmann, C; Vacha, P; Vesely, H; Richter, E; Feyerabend, T [Medizinische Univ., Luebeck (Germany). Klinik fuer Strahlentherapie und Nuklearmedizin

    2001-05-01

    Background: With 17.6% of all primary parotid neoformations the benign Warthin's tumor (cystadenolymphoma) is the second common parotid gland tumor. Males > 50 years are affected predominantly. After surgery the recurrence rate is less than 5%. Histomorphologically the tumor is characterized by cystoid ducts lined by epithelial cells as well as lymphoid stroma. The lymphoid component has been described as radioresponsive whereas the epithelial parts are less radiosensitive. Since 1960 only one patient treated by primary radiotherapy has been published. Case report: A 77-year-old woman suffered from cystadenolymphoma (maximal diameter 7 cm). Because of its extension and the reduced performance status of the patient surgery was no option. Radiotherapy was performed with a total dose of 50 Gy. Clinically, the tumor regressed completely after 30 Gy, which was confirmed by CT at 6 weeks after completion of radiotherapy. After 6 and 12 months the patient stayed free of tumor. Epicrisis: In our case the cystadenolymphoma was unusually large (7 cm). Radiotherapy with 50 Gy induced complete tumor regression. The good clinical response after 30 Gy suggests that the necessary dose may be lower for less extended cystadenolymphomas. Conclusion: We present a case of cystadenolymphoma treated by radiotherapy with 50 Gy resulting in a complete remission. Due to missing published experiences no common recommendation for the total dose can be given. In the following situations radiotherapy should be considered: 1. high surgical risk of damage to the facial nerve, 2. unfavorable cosmetic outcome after surgery, 3. inoperability for internal risks, 4. refusal of operation. (orig.) [German] Hintergrund: Mit einem Anteil von 17,6% an allen primaeren Parotisneubildungen ist das gutartige Warthin-Tumor (Zystadenolymphom) der zweithaeufigste Ohrspeicheldruesentumor. Es erkranken ueberwiegend Maenner ab 50 Jahren. Nach Operation liegt die Rezidivrate unter 5%. Histomorphologische Kennzeichen

  18. Primary Neuroendocrine Tumor of the Breast: Imaging Features

    International Nuclear Information System (INIS)

    Chang, Eun Deok; Kim, Min Kyun; Kim, Jeong Soo; Whang, In Yong

    2013-01-01

    Focal neuroendocrine differentiation can be found in diverse histological types of breast tumors. However, the term, neuroendocrine breast tumor, indicates the diffuse expression of neuroendocrine markers in more than 50% of the tumor cell population. The imaging features of neuroendocrine breast tumor have not been accurately described due to extreme rarity of this tumor type. We present a case of a pathologically confirmed, primary neuroendocrine breast tumor in a 42-year-old woman, with imaging findings difficult to be differentiated from that of invasive ductal carcinoma

  19. Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Cassetta, Luca; Kitamura, Takanori

    2018-01-01

    Inhibition of immune checkpoint pathways in CD8 + T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8 + T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells. However recent studies show that tumor-associated macrophages (TAM) can impede this process by different mechanisms. In this mini-review we will summarize recent studies showing the effect of TAM targeting on immune checkpoint inhibitors efficacy. We will also discuss on the limitations of the current strategies as well on the future scientific challenges for the progress of the tumor immunology field.

  20. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Oroxin B effectively exerts anti-lymphoma without obvious toxicity. • Oroxin B promotes tumor-suppressive DDIT3 and inhibits tumorigenic GRP78.

  1. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

    2015-10-15

    Oroxin B effectively exerts anti-lymphoma without obvious toxicity. • Oroxin B promotes tumor-suppressive DDIT3 and inhibits tumorigenic GRP78.

  2. Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    2015-07-01

    Full Text Available Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1 plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24 cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.

  3. A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

    International Nuclear Information System (INIS)

    Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

    2002-01-01

    Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

  4. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    Directory of Open Access Journals (Sweden)

    C.M. Souza

    2014-10-01

    Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

  5. Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Helbig, Linda [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Koi, Lydia [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Deutsches Konsortium für Translationale Krebsforschung, Site Dresden, Dresden (Germany); Brüchner, Kerstin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Institute of Radiooncology Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Gurtner, Kristin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Hess-Stumpp, Holger; Unterschemmann, Kerstin [Global Drug Discovery, Bayer Pharma, Berlin (Germany); Pruschy, Martin [Radiation Oncology, University of Zurich, Zurich (Switzerland); and others

    2014-01-01

    Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of

  6. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    Science.gov (United States)

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed.

  7. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    Science.gov (United States)

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed. PMID:27900193

  8. Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

    International Nuclear Information System (INIS)

    Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy; Chapman, Christopher; Rao, Aarti; Shen, John; Quinlan-Davidson, Sean; Filion, Edith J.; Wakelee, Heather A.; Colevas, A. Dimitrios; Whyte, Richard I.

    2012-01-01

    Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18–25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50–60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

  9. Biophysical force regulation in 3D tumor cell invasion

    Science.gov (United States)

    Wu, Mingming

    When embedded within 3D extracellular matrices (ECM), animal cells constantly probe and adapt to the ECM locally (at cell length scale) and exert forces and communicate with other cells globally (up to 10 times of cell length). It is now well accepted that mechanical crosstalk between animal cells and their microenvironment critically regulate cell function such as migration, proliferation and differentiation. Disruption of the cell-ECM crosstalk is implicated in a number of pathologic processes including tumor progression and fibrosis. Central to the problem of cell-ECM crosstalk is the physical force that cells generate. By measuring single cell generated force within 3D collagen matrices, we revealed a mechanical crosstalk mechanism between the tumor cells and the ECM. Cells generate sufficient force to stiffen collagen fiber network, and stiffer matrix, in return promotes larger cell force generation. Our work highlights the importance of fibrous nonlinear elasticity in regulating tumor cell-ECM interaction, and results may have implications in the rapid tissue stiffening commonly found in tumor progression and fibrosis. This work is partially supported by NIH Grants R21RR025801 and R21GM103388.

  10. Attitudes and barriers to evidence-based practice in optometry educators.

    Science.gov (United States)

    Suttle, Catherine M; Challinor, Kirsten L; Thompson, Rachel E; Pesudovs, Konrad; Togher, Leanne; Chiavaroli, Neville; Lee, Adrian; Junghans, Barbara; Stapleton, Fiona; Watt, Kathleen; Jalbert, Isabelle

    2015-04-01

    Evidence-based practice (EBP) is an essential component of good quality, patient-centered health care. This requires practitioners to acquire EBP skills and knowledge during undergraduate and continuing education. Evidence-based practice education exists in a range of health care disciplines, including optometry. Evidence-based practice education, however, depends on relevant skills and knowledge in educators. Courses and workshops exist for the development of EBP teaching skills in some areas of health care but not in optometry. Here, we describe a pilot workshop designed to enhance the teaching of EBP and to investigate the perspectives of optometric educators on EBP including their attitudes and perceived barriers to EBP and its teaching. Twenty-seven optometric educators including 8 facilitators participated. Of these, 14 were academics (including the 8 facilitators) and 13 were practitioners. Evidence-based practice attitudes were assessed using the Evidence-Based Practice Attitude Scale-50 with appropriate modifications for optometry. Workshop design incorporated strategies to trigger discussion among participants. A nominal group technique was used to identify, prioritize, and reach consensus on barriers to EBP. Although some participants expressed reservations about EBP, a common understanding of the contemporary definition of EBP emerged in educators. Thirty-five barriers to EBP were identified; "time" was selected in the top five barriers by most participants and attracted the highest total score, well above any other barrier (negative attitude to EBP, volume of evidence, integration with clinical practice, and lack of lifelong learning mind-set). Attitudes toward EBP were generally positive and negatively correlated with age and time since graduation, respectively. A group of optometrists and academics new to implementing education in EBP displayed positive attitudes to EBP but considered that its application and teaching could be significantly hindered

  11. Pituitary gland tumors

    International Nuclear Information System (INIS)

    Jesser, J.; Schlamp, K.; Bendszus, M.

    2014-01-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [de

  12. [Pituitary gland tumors].

    Science.gov (United States)

    Jesser, J; Schlamp, K; Bendszus, M

    2014-10-01

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15% of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65% of pituitary gland adenomas secrete hormones whereby approximately 50% secrete prolactin, 10% secrete growth hormone (somatotropin) and 6% secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10% of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland.

  13. Exertional Heat Illness and Human Gene Expression

    National Research Council Canada - National Science Library

    Sonna, L.A; Sawka, M. N; Lilly, C. M

    2007-01-01

    Microarray analysis of gene expression at the level of RNA has generated new insights into the relationship between cellular responses to acute heat shock in vitro, exercise, and exertional heat illness...

  14. Exertional heat illness: emerging concepts and advances in prehospital care.

    Science.gov (United States)

    Pryor, Riana R; Roth, Ronald N; Suyama, Joe; Hostler, David

    2015-06-01

    Exertional heat illness is a classification of disease with clinical presentations that are not always diagnosed easily. Exertional heat stroke is a significant cause of death in competitive sports, and the increasing popularity of marathons races and ultra-endurance competitions will make treating many heat illnesses more common for Emergency Medical Services (EMS) providers. Although evidence is available primarily from case series and healthy volunteer studies, the consensus for treating exertional heat illness, coupled with altered mental status, is whole body rapid cooling. Cold or ice water immersion remains the most effective treatment to achieve this goal. External thermometry is unreliable in the context of heat stress and direct internal temperature measurement by rectal or esophageal probes must be used when diagnosing heat illness and during cooling. With rapid recognition and implementation of effective cooling, most patients suffering from exertional heat stroke will recover quickly and can be discharged home with instructions to rest and to avoid heat stress and exercise for a minimum of 48 hours; although, further research pertaining to return to activity is warranted.

  15. Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

    International Nuclear Information System (INIS)

    Zips, Daniel; Hessel, Franziska; Krause, Mechthild; Schiefer, Yvonne; Hoinkis, Cordelia; Thames, Howard D.; Haberey, Martin; Baumann, Michael

    2005-01-01

    Purpose: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. Methods and materials: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD 50 ) were determined and compared to controls (carrier without PTK787/ZK222584). Results: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD 50 values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. Conclusions: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584

  16. Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

    Science.gov (United States)

    Zhang, Su-Fang; Chen, Zhe

    2017-09-01

    Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

  17. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Peigen; Allam, Ayman; Perez, Luis A; Taghian, Alphonse; Freeman, Jill; Suit, Herman D

    1995-04-30

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-{alpha}) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-{alpha} with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm{sup 3}, mice were randomly assigned to treatment: rHuTNF-{alpha} alone compared with normal saline control; or local radiation plus rHuTNF-{alpha} vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-{alpha} on this tumor. The TCD{sub 50} (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-{alpha} with local radiation. Results: Tumor growth in mice treated with a dose of 150 {mu}g/kg body weight rHuTNF-{alpha}, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-{alpha} also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-{alpha} starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD{sub 50} from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-{alpha} exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD{sub 50} value in the treatment vs. the

  18. Location of tumor affects local and distant immune cell type and number.

    Science.gov (United States)

    Hensel, Jonathan A; Khattar, Vinayak; Ashton, Reading; Lee, Carnellia; Siegal, Gene P; Ponnazhagan, Selvarangan

    2017-03-01

    Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid-derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia. In addition, immune cells from the spleen were examined from animals of both tumor locations by flow cytometry. The study demonstrates that location of tumor, and not simply the tumor itself, has a definitive role in regulating immune effectors. Among all immune cells characterized, macrophages were decreased and myeloid dendritic cell were increased in both tumor locations. This difference was more evident in subcutaneous tumors. Additionally, spleens from mice with subcutaneous tumors contained greater increases in both macrophages and myeloid dendritic cells than in mice with bone tumors. Furthermore, in subcutaneous tumors there was an increase in CD4 + and CD8 + T-cell numbers, which was also observed in their spleens. These data indicate that alterations in tumor-reactive immune cells are more pronounced at the primary site, and exert a similar change at the major secondary lymphoid organ than in the bone TME. These findings could provide translational insight into designing therapeutic strategies that account for location of metastatic foci.

  19. Impaired Player-Coach Perceptions of Exertion and Recovery During Match Congestion

    NARCIS (Netherlands)

    Doeven, Steven H.; Brink, Michel S.; Frencken, Wouter G. P.; Lemmink, Koen A. P. M.

    2017-01-01

    During intensified phases of competition, attunement of exertion and recovery is crucial to maintain performance. Although a mismatch between coach' and players' perceptions of training load is demonstrated, it is unknown if these discrepancies also exist for match exertion and recovery. PURPOSE:

  20. Sevoflurane improves gaseous exchange and exerts protective ...

    African Journals Online (AJOL)

    Sevoflurane improves gaseous exchange and exerts protective effects in ... Lung water content and cell count were estimated by standard protocols. ... It reversed LPS-induced oxidative stress, as demonstrated by increase in total antioxidant ...

  1. Paraneoplastic neurological disorders in children with benign ovarian tumors.

    Science.gov (United States)

    Hsu, Mei-Hsin; Huang, Chao-Ching; Hung, Pi-Lien; Huang, Hsiu-Mei; Huang, Li-Tung; Huang, Chao-Cheng; Sheen, Jiunn-Ming; Huang, Song-Chei; Chang, Ying-Chao

    2014-03-01

    Paraneoplastic neurological diseases (PND) are rare, but potentially treatable disorders. Paraneoplastic encephalitis is rapidly emerging as an important but likely under-recognized condition in children. The aim of this study was to assess the prevalence and spectrum of PND in children with benign ovary tumor and the long-term outcome. We retrospectively reviewed the charts of all female patients below 18years of age diagnosed with a benign ovarian tumor proven by pathology between January 1993 and December 2010. All the clinical symptoms developed within 5years of tumor diagnosis and the related investigations were recorded. There were total 133 children and adolescents with benign ovarian tumors, mostly mature teratoma. Six patients (4.5%) had neuropsychiatric manifestations and all but one were beyond age 10years. The most common neuropsychiatric presentations were depression or low mood (84%), headache (50%), mutism (50%), hypoventilation (50%), seizures (30%), hallucination (30%), vomiting and hypersalivation (30%). Three patients (2.2%) had serious PND including acute disseminated encephalomyelitis in 1 and anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in 2. Although all of three improved after tumor removal, one without immunotherapy had neurological sequelae and prolonged ICU stay. The prevalence of PND in benign ovary tumor is not so uncommon in children. It is important to survey ovary tumors in female adolescents with subacute presentation of multiple-level involvement of neuraxis where no clear alternate diagnosis is possible. Treatment of serious PND associated with ovary tumors should include immunotherapy in addition to tumor removal. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. Exertional Tolerance Assessments After Mild Traumatic Brain Injury: A Systematic Review.

    Science.gov (United States)

    Quatman-Yates, Catherine; Bailes, Anna; Constand, Sara; Sroka, Mary Claire; Nissen, Katharine; Kurowski, Brad; Hugentobler, Jason

    2018-05-01

    To review the literature to identify and summarize strategies for evaluating responses to physical exertion after mild traumatic brain injury (mTBI) for clinical and research purposes. PubMed and EBSCOhost through December 31, 2016. Two independent reviewers selected studies based on the following criteria: (1) inclusion of participants with mTBI/concussion, (2) use of a measurement of physiological or psychosomatic response to exertion, (3) a repeatable description of the exertion protocol was provided, (4) a sample of at least 10 participants with a mean age between 8 and 65 years, and (5) the article was in English. The search process yielded 2685 articles, of which 14 studies met the eligibility requirements. A quality assessment using a checklist was conducted for each study by 2 independent study team members and verified by a third team member. Data were extracted by one team member and verified by a second team member. A qualitative synthesis of the studies revealed that most protocols used a treadmill or cycle ergometer as the exercise modality. Protocol methods varied across studies including differences in initial intensity determination, progression parameters, and exertion duration. Common outcome measures were self-reported symptoms, heart rate, and blood pressure. The strongest evidence indicates that exertional assessments can provide important insight about mTBI recovery and should be administered using symptoms as a guide. Additional studies are needed to verify optimal modes and protocols for post-mTBI exertional assessments. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  3. Direct short-term effects of EBP teaching: change in knowledge, not in attitude; a cross-cultural comparison among students from European and Asian medical schools

    Directory of Open Access Journals (Sweden)

    Indah S. Widyahening

    2012-10-01

    Full Text Available Introduction: We report about the direct short-term effects of a Clinical Epidemiology and Evidence-based Medicine (CE-EBM module on the knowledge, attitude, and behavior of students in the University Medical Center Utrecht (UMCU, Universitas Indonesia (UI, and University of Malaya (UM. Methods: We used an adapted version of a 26-item validated questionnaire, including four subscales: knowledge, attitude, behavior, and future use of evidence-based practice (EBP. The four components were compared among the students in the three medical schools before the module using one-way ANOVA. At the end of the module, we measured only knowledge and attitudes. We computed Cronbach's α to assess the reliability of the responses in our population. To assess the change in knowledge and attitudes, we used the paired t-test in the comparison of scores before and after the module. Results: In total, 526 students (224 UI, 202 UM, and 100 UMCU completed the questionnaires. In the three medical schools, Cronbach's α for the pre-module total score and the four subscale scores always exceeded 0.62. UMCU students achieved the highest pre-module scores in all subscales compared to UI and UM with the comparison of average (SD score as the following: knowledge 5.04 (0.4 vs. 4.73 (0.69 and 4.24 (0.74, p<0.001; attitude 4.52 (0.64 vs. 3.85 (0.68 and 3.55 (0.63, p<0.001; behavior 2.62 (0.55 vs. 2.35 (0.71 and 2.39 (0.92, p=0.016; and future use of EBP 4.32 (0.59 vs. 4.08 (0.62 and 3.7 (0.71, p<0.01. The CE-EBM module increased the knowledge of the UMCU (from average 5.04±0.4 to 5.35±0.51; p<0.001 and UM students (from average 4.24±0.74 to 4.53±0.72; p<0.001 but not UI. The post-module scores for attitude did not change in the three medical schools. Conclusion: EBP teaching had direct short-term effects on knowledge, not on attitude. Differences in pre-module scores are most likely related to differences in the system and infrastructure of both medical schools and their

  4. 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.

  5. 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)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

    2013-01-01

    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.

  6. Radiotherapy for a cystadenolymphoma of the parotid gland (Warthin's tumor); Radiotherapie bei einem Zystadenolymphom der Parotis (Warthin-Tumor)

    Energy Technology Data Exchange (ETDEWEB)

    Stallmann, C.; Vacha, P.; Vesely, H.; Richter, E.; Feyerabend, T. [Medizinische Univ., Luebeck (Germany). Klinik fuer Strahlentherapie und Nuklearmedizin

    2001-05-01

    Background: With 17.6% of all primary parotid neoformations the benign Warthin's tumor (cystadenolymphoma) is the second common parotid gland tumor. Males > 50 years are affected predominantly. After surgery the recurrence rate is less than 5%. Histomorphologically the tumor is characterized by cystoid ducts lined by epithelial cells as well as lymphoid stroma. The lymphoid component has been described as radioresponsive whereas the epithelial parts are less radiosensitive. Since 1960 only one patient treated by primary radiotherapy has been published. Case report: A 77-year-old woman suffered from cystadenolymphoma (maximal diameter 7 cm). Because of its extension and the reduced performance status of the patient surgery was no option. Radiotherapy was performed with a total dose of 50 Gy. Clinically, the tumor regressed completely after 30 Gy, which was confirmed by CT at 6 weeks after completion of radiotherapy. After 6 and 12 months the patient stayed free of tumor. Epicrisis: In our case the cystadenolymphoma was unusually large (7 cm). Radiotherapy with 50 Gy induced complete tumor regression. The good clinical response after 30 Gy suggests that the necessary dose may be lower for less extended cystadenolymphomas. Conclusion: We present a case of cystadenolymphoma treated by radiotherapy with 50 Gy resulting in a complete remission. Due to missing published experiences no common recommendation for the total dose can be given. In the following situations radiotherapy should be considered: 1. high surgical risk of damage to the facial nerve, 2. unfavorable cosmetic outcome after surgery, 3. inoperability for internal risks, 4. refusal of operation. (orig.) [German] Hintergrund: Mit einem Anteil von 17,6% an allen primaeren Parotisneubildungen ist das gutartige Warthin-Tumor (Zystadenolymphom) der zweithaeufigste Ohrspeicheldruesentumor. Es erkranken ueberwiegend Maenner ab 50 Jahren. Nach Operation liegt die Rezidivrate unter 5%. Histomorphologische

  7. Anti-tumor effects of an engineered “killer” transfer RNA

    International Nuclear Information System (INIS)

    Zhou, Dong-hui; Lee, Jiyoung; Frankenberger, Casey; Geslain, Renaud; Rosner, Marsha; Pan, Tao

    2012-01-01

    Highlights: ► tRNA with anti-cancer effects. ► tRNA induced protein misfolding. ► tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA Ser (AAU) is an engineered human tRNA Ser with an anticodon coding for isoleucine. Here we test the possibility that tRNA Ser (AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA Ser (AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA Ser (AAU) in both tumorigenic and non-tumorigenic cells. tRNA Ser (AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA Ser (AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA Ser (AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA Ser (AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  8. Sevoflurane improves gaseous exchange and exerts protective ...

    African Journals Online (AJOL)

    mice, and exerted protective effects against acute LPS-induced lung injury. ... This is an Open Access article that uses a funding model which does not charge readers .... field microscope [20]. ... by Tukey's test were used for statistical analysis.

  9. FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

    Science.gov (United States)

    Briest, Franziska; Berg, Erika; Grass, Irina; Freitag, Helma; Kaemmerer, Daniel; Lewens, Florentine; Christen, Friederike; Arsenic, Ruza; Altendorf-Hofmann, Annelore; Kunze, Almut; Sänger, Jörg; Knösel, Thomas; Siegmund, Britta; Hummel, Michael; Grabowski, Patricia

    2015-01-01

    Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs. PMID:25797272

  10. Chronic exertional compartment syndrome with medial tibial stress syndrome in twins.

    Science.gov (United States)

    Banerjee, Purnajyoti; McLean, Christopher

    2011-06-14

    Chronic exertional compartment syndrome and medial tibial stress syndrome are uncommon conditions that affect long-distance runners or players involved in team sports that require extensive running. We report 2 cases of bilateral chronic exertional compartment syndrome, with medial tibial stress syndrome in identical twins diagnosed with the use of a Kodiag monitor (B. Braun Medical, Sheffield, United Kingdom) fulfilling the modified diagnostic criteria for chronic exertional compartment syndrome as described by Pedowitz et al, which includes: (1) pre-exercise compartment pressure level >15 mm Hg; (2) 1 minute post-exercise pressure >30 mm Hg; and (3) 5 minutes post-exercise pressure >20 mm Hg in the presence of clinical features. Both patients were treated with bilateral anterior fasciotomies through minimal incision and deep posterior fasciotomies with tibial periosteal stripping performed through longer anteromedial incisions under direct vision followed by intensive physiotherapy resulting in complete symptomatic recovery. The etiology of chronic exertional compartment syndrome is not fully understood, but it is postulated abnormal increases in intramuscular pressure during exercise impair local perfusion, causing ischemic muscle pain. No familial predisposition has been reported to date. However, some authors have found that no significant difference exists in the relative perfusion, in patients, diagnosed with chronic exertional compartment syndrome. Magnetic resonance images of affected compartments have indicated that the pain is not due to ischemia, but rather from a disproportionate oxygen supply versus demand. We believe this is the first report of chronic exertional compartment syndrome with medial tibial stress syndrome in twins, raising the question of whether there is a genetic predisposition to the causation of these conditions. Copyright 2011, SLACK Incorporated.

  11. Virilizing tumor of the ovary. Presentation of a case

    International Nuclear Information System (INIS)

    Ovies Carballo, Gisel; Yanes Quesada, Marelys; Cruz Hernandez, Jeddu

    2008-01-01

    Ovarian tumors are divided into functioning and non-functioning. Those presenting endocrine activity and producing androgenization, such as the tumors of Sertoli cells are within the latter group. A case of a 50-year-old female patient that clinically showed signs of progressive virilization was presented. A tumor on the right ovary was found by ultrasound and CAT. After performing surgery, the existence of a Sertoli-Leydig cell tumor was confirmed

  12. Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

    Science.gov (United States)

    Osada, Takuya; Chen, Minyong; Yang, Xiao Yi; Spasojevic, Ivan; Vandeusen, Jeffrey B; Hsu, David; Clary, Bryan M; Clay, Timothy M; Chen, Wei; Morse, Michael A; Lyerly, H Kim

    2011-06-15

    Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined whether niclosamide could inhibit the Wnt/β-catenin pathway in human CRCs and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling, and exerted antiproliferative effects in human colon cancer cell lines and CRC cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar antiproliferative effects in these CRC model systems. In mice implanted with human CRC xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity, and led to tumor control. Our findings support clinical explorations to reposition niclosamide for the treatment of CRC.

  13. Tumores benignos de los párpados Bening eyelid tumors

    Directory of Open Access Journals (Sweden)

    Clara G. Gómez Cabrera

    2001-12-01

    Full Text Available Se realizó un estudio descriptivo, de tipo retrospectivo de 266 expedientes clínicos correspondientes a pacientes con diagnóstico histológico de neoplasias benignas de los párpados operados en el departamento de Cirugía Oculoplástica del Hospital Oftalmológico "Ramón Pando Ferrer" en el período comprendido entre enero de 1989 y diciembre de 1999. El 36 % de los pacientes se encontraban en el grupo comprendido entre los 31 y los 50 años de edad, y solo el 6 % eran menores de 15 años. El 64 % de los casos operados correspondieron al sexo femenino. El 41 % de las neoplasias se localizaron en párpado superior y el 40 % en el inferior. Encontramos 16 tipos histológicos de tumores. Los tumores benignos de los párpados son más frecuentes a partir de la tercera década de la vida. Afectan preferentemente al sexo femenino. Se localizan preferentemente en el párpado superior e inferior. Los quistes, seguidos por los nevus y las queratosis fueron los diagnósticos histológicos más frecuentes.A descriptive and retrospective study of 266 medical histories corresponding to patients with histological diagnosis of benign eyelid neoplasias was made. They were operated on at the Oculoplastic Surgery Department of "Pando Ferrer" Ophthalmologic Hospital from January, 1989, to December, 1999. 36 % of the patients were in the group aged 31-50 and only 6 % were under 15. 64 % of the cases that underwent surgery were females. 41 % of the neoplasias were localized in the upper eyelid and 40 % in the lower eyelid. 16 histological types of tumors were found. The benign eyelid tumors are more frequent from the third decade of life on, and females are the most affected. These tumors are localized mainly in the upper and lower eyelid. Cysts, followed by nevus and keratosis were the commonest histologic diagnoses.

  14. Pressure exerted by a vesicle on a surface

    International Nuclear Information System (INIS)

    Owczarek, A L; Prellberg, T

    2014-01-01

    Several recent works have considered the pressure exerted on a wall by a model polymer. We extend this consideration to vesicles attached to a wall, and hence include osmotic pressure. We do this by considering a two-dimensional directed model, namely that of area-weighted Dyck paths. Not surprisingly, the pressure exerted by the vesicle on the wall depends on the osmotic pressure inside, especially its sign. Here, we discuss the scaling of this pressure in the different regimes, paying particular attention to the crossover between positive and negative osmotic pressure. In our directed model, there exists an underlying Airy function scaling form, from which we extract the dependence of the bulk pressure on small osmotic pressures. (paper)

  15. Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors

    NARCIS (Netherlands)

    D. Chadha; C.J. Cornelisse; A. Schabert (A.)

    1990-01-01

    textabstractAbstract The nuclear DNA content of 50 ovarian tumors initially diagnosed as granulosa cell tumors was measured by flow cytometry using paraffin-embedded archival material. The follow-up period of the patients ranged from 4 months to 19 years. Thirty-eight tumors were diploid or

  16. Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF

    DEFF Research Database (Denmark)

    Worm, Jesper; Stenvang, Jan; Petri, Andreas

    2009-01-01

    microRNA-155 (miR-155) has been implicated as a central regulator of the immune system, but its function during acute inflammatory responses is still poorly understood. Here we show that exposure of cultured macrophages and mice to lipopolysaccharide (LPS) leads to up-regulation of miR-155......-stimulating factor (G-CSF), a central regulator of granulopoiesis during inflammatory responses. Consistent with these data, we show that silencing of miR-155 in LPS-treated mice by systemically administered LNA-antimiR results in derepression of the c/ebp Beta isoforms and down-regulation of G-CSF expression...

  17. Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation

    International Nuclear Information System (INIS)

    Kocher, M.; Treuer, H.

    1995-01-01

    A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm 3 which were displaced by the growing tumor was simulated. Tumors contained 10 4 cells when irradiation started, intrinsic radiosensitivity was set to either low (α=0.3 Gy -1 , β=0.03 Gy -2 ) or high (α=0.4 Gy -1 , β=0.04 Gy -2 ) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time T pot =1, 2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (T pot =2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (T pot =1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. (orig./MG) [de

  18. Inflammatory myofibroblastic tumor of the lung in pregnancy mimicking carcinoid tumor

    Directory of Open Access Journals (Sweden)

    Venkata Nagarjuna Maturu

    2016-01-01

    Full Text Available Inflammatory myofibroblastic tumors (IMT are uncommon neoplasms of the lung in adults. They constitute less than 1% of all lung neoplasms and usually present as parenchymal masses. Diagnosis requires a high index of suspicion. They are characterized by spindle-shaped tumor cells (fibroblasts/myofibroblasts in a background of lymphoplasmacytic infiltrate. About 50% of the tumors harbor an ALK gene rearrangement. They have to be differentiated from inflammatory pseudotumors (IPT, which show increased number of IgG4 plasma cells on immunostaining and are negative for anaplastic lymphoma kinase (ALK protein. Herein, we present a case of a 28-year old female who presented with hemoptysis and was diagnosed with an IMT of lung in the first trimester of pregnancy. We have not only reviewed the occurrence of IMT during pregnancy but also discuss the management options for IMT during pregnancy.

  19. Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens

    International Nuclear Information System (INIS)

    Nielsen, Torsten; Storhoff, James; Wallden, Brett; Schaper, Carl; Ferree, Sean; Liu, Shuzhen; Gao, Dongxia; Barry, Garrett; Dowidar, Naeem; Maysuria, Malini

    2014-01-01

    NanoString’s Prosigna™ Breast Cancer Prognostic Gene Signature Assay is based on the PAM50 gene expression signature. The test outputs a risk of recurrence (ROR) score, risk category, and intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like). The studies described here were designed to validate the analytical performance of the test on the nCounter Analysis System across multiple laboratories. Analytical precision was measured by testing five breast tumor RNA samples across 3 sites. Reproducibility was measured by testing replicate tissue sections from 43 FFPE breast tumor blocks across 3 sites following independent pathology review at each site. The RNA input range was validated by comparing assay results at the extremes of the specified range to the nominal RNA input level. Interference was evaluated by including non-tumor tissue into the test. The measured standard deviation (SD) was less than 1 ROR unit within the analytical precision study and the measured total SD was 2.9 ROR units within the reproducibility study. The ROR scores for RNA inputs at the extremes of the range were the same as those at the nominal input level. Assay results were stable in the presence of moderate amounts of surrounding non-tumor tissue (<70% by area). The analytical performance of NanoString’s Prosigna assay has been validated using FFPE breast tumor specimens across multiple clinical testing laboratories

  20. Ficus umbellata Vahl. (Moraceae Stem Bark Extracts Exert Antitumor Activities In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Kevine Kamga Silihe

    2017-05-01

    Full Text Available A Ficus umbellata is used to treat cancer. The present work was therefore designed to assess antitumor potentials of F. umbellata extracts in nine different cell lines. Cell cycle, apoptosis, cell migration/invasion, levels of reactive oxygen species (ROS, mitochondrial membrane potential (MMP, caspases activities as well as Bcl-2 and Bcl-xL protein content were assessed in MDA-MB-231 cells. The 7,12-dimethylbenz(aanthracene (DMBA-induced carcinogenesis in rats were also used to investigate antitumor potential of F. umbellata extracts. The F. umbellata methanol extract exhibited a CC50 of 180 μg/mL in MDA-MB-231 cells after 24 h. It induced apoptosis in MCF-7 and MDA-MB-231 cells, while it did not alter their cell cycle phases. Further, it induced a decrease in MMP, an increase in ROS levels and caspases activities as well as a downregulation in Bcl-2 and Bcl-xL protein contents in MDA-MB-231 cells. In vivo, F. umbellata aqueous (200 mg/kg and methanol (50 mg/kg extracts significantly (p < 0.001 reduced ovarian tumor incidence (10%, total tumor burden (58% and 46%, respectively, average tumor weight (57.8% and 45.6%, respectively as compared to DMBA control group. These results suggest antitumor potential of F. umbellata constituents possibly due to apoptosis induction mediated through ROS-dependent mitochondrial pathway.

  1. Radiotherapy for a cystadenolymphoma of the parotid gland (Warthin's tumor)

    International Nuclear Information System (INIS)

    Stallmann, C.; Vacha, P.; Vesely, H.; Richter, E.; Feyerabend, T.

    2001-01-01

    Background: With 17.6% of all primary parotid neoformations the benign Warthin's tumor (cystadenolymphoma) is the second common parotid gland tumor. Males > 50 years are affected predominantly. After surgery the recurrence rate is less than 5%. Histomorphologically the tumor is characterized by cystoid ducts lined by epithelial cells as well as lymphoid stroma. The lymphoid component has been described as radioresponsive whereas the epithelial parts are less radiosensitive. Since 1960 only one patient treated by primary radiotherapy has been published. Case report: A 77-year-old woman suffered from cystadenolymphoma (maximal diameter 7 cm). Because of its extension and the reduced performance status of the patient surgery was no option. Radiotherapy was performed with a total dose of 50 Gy. Clinically, the tumor regressed completely after 30 Gy, which was confirmed by CT at 6 weeks after completion of radiotherapy. After 6 and 12 months the patient stayed free of tumor. Epicrisis: In our case the cystadenolymphoma was unusually large (7 cm). Radiotherapy with 50 Gy induced complete tumor regression. The good clinical response after 30 Gy suggests that the necessary dose may be lower for less extended cystadenolymphomas. Conclusion: We present a case of cystadenolymphoma treated by radiotherapy with 50 Gy resulting in a complete remission. Due to missing published experiences no common recommendation for the total dose can be given. In the following situations radiotherapy should be considered: 1. high surgical risk of damage to the facial nerve, 2. unfavorable cosmetic outcome after surgery, 3. inoperability for internal risks, 4. refusal of operation. (orig.) [de

  2. Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity

    Directory of Open Access Journals (Sweden)

    Vanessa Almendro

    2014-02-01

    Full Text Available Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.

  3. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

    International Nuclear Information System (INIS)

    Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; Van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

  4. Does heavy physical exertion trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Hallqvist, J; Möller, J; Ahlbom, A

    2000-01-01

    To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...

  5. Effects of fitness and self-confidence on time perception during exertion

    Directory of Open Access Journals (Sweden)

    2015-09-01

    Full Text Available Aims: Human physical and psychological features influence perceptions of the environment during activity. If during exercise an individual over-estimates time, they may interpret this as spending longer than necessary under a potentially aversive state of exertion. This may in turn decrease one’s sense of exercise success and tendency to persevere with exercise. We tested if experimentally manipulating sense of exercise self-efficacy would affect time perception during standardised physical exertion. Method: Exercise Self-Efficacy (ESE of 18 -73 year olds (N=51 was measured before and after an exercise challenge of moderate intensity. Height, weight and body fat composition were measured before participants were randomly allocated to one of three groups. After a 4-minute treadmill fitness test, participants were presented with either bogus feedback about their performance (positive or negative or no feedback (control. Before and during exercise, participants estimated a prescribed 2-minute time interval. Ratings of perceived exertion were also measured periodically. Results: Feedback on performance had no significant effect on time perception, even when controlling for individual exertion level. Reported ESE was also unaffected by whether someone received positive, negative or no feedback. Age was again found to be significantly correlated with VO2max, r(51 = .62, p < .001, but in contrast to prior findings, estimates of general fitness such as VO2max, BMI and waist circumference were unrelated to changes in time perception due to exertion. Conclusions: These findings failed to support prior findings and anecdotal evidence suggesting that exertion might alter one’s perception of time. We also failed to find any support for effects on ESE when participants were given explicit performance feedback. Finally, participants’ physical characteristics appear to be unrelated to time perception whilst exercising at moderate intensity.

  6. Physical exercise at the workplace reduces perceived physical exertion during healthcare work

    DEFF Research Database (Denmark)

    Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel

    2015-01-01

    BACKGROUND: High physical exertion during work is a risk factor for musculoskeletal pain and long-term sickness absence. Physical exertion (RPE) reflects the balance between physical work demands and physical capacity of the individual. Thus, increasing the physical capacity through physical......: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5×10 minutes per...... exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. METHODS: 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity...

  7. Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

    International Nuclear Information System (INIS)

    Kim, Sung Hee; Seong, Jin Sil

    2003-01-01

    Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 μg in 50 μl). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21 WAF1 / CIP1 and Bcl-X s in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-X L , Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment

  8. Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hee; Seong, Jin Sil [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2003-09-01

    Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 {mu}g in 50 {mu}l). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21{sup WAF1}/{sup CIP1} and Bcl-X{sub s} in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-X{sub L}, Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.

  9. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions.

    Science.gov (United States)

    Zhou, Junmin; Wu, Jinfeng; Chen, Xianghong; Fortenbery, Nicole; Eksioglu, Erika; Kodumudi, Krithika N; Pk, Epling-Burnette; Dong, Jingcheng; Djeu, Julie Y; Wei, Sheng

    2011-07-01

    3, 5,7-trihydroxy-4'-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone (ICT) is a novel derivative of Icariin (ICA), the major active ingredient of Herba Epimedii, a herb used in traditional Chinese and alternative medicine. We previously demonstrated its anti-inflammatory effect in murine innate immune cells and activated human PBMCs. We report herein that ICA or ICT treatment reduces the expression of MRP8/MRP14 and toll-like receptor 4 (TLR4) on human PBMCs. Administration of ICA or ICT inhibited tumor growth in 4T1-Neu tumor-bearing mice and considerably decreased MDSC numbers in the spleen of these mice. Further, we saw a restoration of IFN-γ production by CD8+ T cells in tumor bearing mice when treated with ICA or ICT. ICA and ICT significantly decreased the amounts of nitric oxide and reactive oxygen species in MDSC in vivo. When MDSC were treated in vitro with ICT, we saw a significant reduction in the percent of these cells with concomitant differentiation into dendritic cells and macrophages. Concomitant with this cell type conversion was a down-regulation of IL-10, IL-6 and TNF-α production. Decreased expression of S100A8/9 and inhibition of activation of STAT3 and AKT may in part be responsible for the observed results. In conclusion, our results showed that ICA, and more robustly, ICT, directly modulate MDSC signaling and therefore altered the phenotype and function of these cells, in vitro and in vivo. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Radiological imaging detection of tumors localized in fossa cranii posterior.

    Science.gov (United States)

    Kabashi, Serbeze; Muçaj, Sefedin; Ahmetgjekaj, Ilir; Gashi, Sanije; Fazliu, Ilir; Dreshaj, Shemsedin; Shala, Nexhmedin

    2008-01-01

    Intracranial tumors are characterized by a variety imaging aspects and their detection is always a challenge. Clinical application of Magnetic Resonance Imaging (MRI) and Computerized Tomography has provided an earlier detection and treatment of many CNS pathologies. The aim of this study is to estimate the role of CT and MRI in the determination of posterior fossa tumors. During period 2000-2005 in UCCK-Prishtina, 368 patients were diagnosed with intracranial tumors. Fifty-nine of them were found to have tumor localized in fossa crani posterior (FCP) without any significant difference between genders (50.8% female vs. 49.2% male, chi2 test=0.02 p=0.896). The average age of patients with FCP tumors was 33.1 (SD +/- 22.5, rank 1-70). The most of these patients were registered in 2003 (20.3%) whereas the least in 2000 (11.9%). The most affected age-group was 0-9 (25.4%) and 50-59 (23.7%) whereas the incidences was between 30-39 years of age (3.4%). Tumor types that more often were found in young's individuals were: Astrocytomas with a peak incidence in teenagers (average age was 12-year-old SD +/- 7.5, rank 3-23), next was Medulloblastomas (average age was 11-years-old, SD +/- 2.9, rank 6-16 years) and ependymomas (average age was 6.8-years-old, SD +/- 4.6, rank 1-12). Patients with osseous tumors are characterized by older age than median (61.0, SD +/- 4.2, rank 58-64), then metastases (53.0, SD +/- 5.3, rank 45-60) and meningiomas (50.8, SD +/- 7.7, rank 38-63). The overall average mortality was 0.41 cases per 100,000 inhabitants with variations through years from 0.30-0.50/100,000 inhabitants. Comparing with other countries, for some types of FCP tumors, lower morbidity is shown in Kosova, with mean incidence 0.41/100,000. The most frequent tumors in children were medulloblastomas, brainstem gliomas, astrocytomas and ependymomas whereas meningiomas and metastasis were most often found in adults. For FCP tumors detection, MRI had 100% sensitivity, specificity and

  11. A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice.

    Science.gov (United States)

    Tagliamonte, Maria; Petrizzo, Annacarmen; Napolitano, Maria; Luciano, Antonio; Rea, Domenica; Barbieri, Antonio; Arra, Claudio; Maiolino, Piera; Tornesello, Marialina; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

    2016-02-24

    The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. In the present study, the counterbalance effect of a novel metronomic chemotherapy protocol on such an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy consisted of a novel multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4(+) T cell reduction and CD8(+) T cell increase. Furthermore, a significant reduction in the percentage of both CD25(+)FoxP3(+) and CD25(+)CD127(low) regulatory T cell population was found both in the spleens and in the tumor lesions. Finally, the metronomic chemotherapy induced an intrinsic CD8(+) T cell response specific to B16 naturally expressed Trp2 TAA. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment. Consequently, the intrinsic anti-tumor T cell immunity could exert its function, targeting specific TAA and significantly containing tumor growth. Overall, the results show that this represents a promising adjuvant approach to significantly enhance efficacy of intrinsic or vaccine-elicited tumor-specific cellular immunity.

  12. Surgical treatment of tumor-induced osteomalacia: a retrospective review of 40 cases with extremity tumors.

    Science.gov (United States)

    Sun, Zhi-jian; Jin, Jin; Qiu, Gui-xing; Gao, Peng; Liu, Yong

    2015-02-26

    Tumor-induced osteomalacia (TIO) is a rare syndrome typically caused by mesenchymal tumors. It has been shown that complete tumor resection may be curative. However, to our knowledge, there has been no report of a large cohort to exam different surgical approaches. This study was aimed to assess outcomes of different surgical options of patients with tumor-induced osteomalacia at a single institution. Patients with extremity tumors treated in our hospital from January, 2004 to July, 2012 were identified. The minimum follow-up period was 12 months. Patient's demography, tumor location, preoperative preparation, type of surgeries were summarized, and clinical outcomes were recorded. Successful treatment was defined as significant symptom improvement, normal serum phosphorus and significant improvement or normalization of bone mineral density at the last follow-up. Differences between patients with soft tissue tumors and bone tumors were compared. There were 40 (24 male and 16 female) patients identified, with an average age of 44 years. The tumors were isolated in either soft tissue (25 patients) or bone (12 patients) and combined soft tissue and bone invasion was observed in 3 patients. For the primary surgery, tumor resection and tumor curettage were performed. After initial surgical treatment, six patients then received a second surgery. Four patients were found to have malignant tumors base on histopathology. With a minimum follow-up period of 12 months, 80% of patients (32/40) were treated successfully, including 50% of patients (2/4) with malignant tumors. Compared to patients with bone tumor, surgical results were better in patient with soft tissue tumor. Surgical treatment was an effective way for TIO. Other than tumor curettage surgery, tumor resection is the preferred options for these tumors.

  13. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

    Science.gov (United States)

    Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  14. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Angeliki Tiptiri-Kourpeti

    Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  15. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Science.gov (United States)

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  16. Radiosensitivity of different human tumor cells lines grown as multicellular spheroids determined from growth curves and survival data

    International Nuclear Information System (INIS)

    Schwachoefer, J.H.C.; Crooijmans, R.P.; van Gasteren, J.J.; Hoogenhout, J.; Jerusalem, C.R.; Kal, H.B.; Theeuwes, A.G.

    1989-01-01

    Five human tumor cell lines were grown as multicellular tumor spheroids (MTS) to determine whether multicellular tumor spheroids derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences paralleled clinical behavior. Multicellular tumor spheroids of two neuroblastoma, one lung adenocarcinoma, one melanoma, and a squamous cell carcinoma of the oral tongue, were studied in terms of growth delay, calculated cell survival, and spheroid control dose50 (SCD50). Growth delay and cell survival analysis for the tumor cell lines showed sensitivities that correlated well with clinical behavior of the tumor types of origin. Similar to other studies on melanoma multicellular tumor spheroids our spheroid control dose50 results for the melanoma cell line deviated from the general pattern of sensitivity. This might be due to the location of surviving cells, which prohibits proliferation of surviving cells and hence growth of melanoma multicellular tumor spheroids. This study demonstrates that radiosensitivity of human tumor cell lines can be evaluated in terms of growth delay, calculated cell survival, and spheroid control dose50 when grown as multicellular tumor spheroids. The sensitivity established from these evaluations parallels clinical behavior, thus offering a unique tool for the in vitro analysis of human tumor radiosensitivity

  17. Pediatric brain tumors; Kindliche Hirntumoren

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W.; Bodea, S. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany); Muehl-Benninghaus, R.

    2017-09-15

    Brain tumors differ between children and adults both in histology and localization. Malignant gliomas and meningiomas predominate in adults while medulloblastomas and low-grade astrocytomas are the most frequent brain tumors in children. More than one half (50-70%) of pediatric brain tumors have an infratentorial location but only approximately 30% in adults. Brain tumors can be recognized in sonography, cranial computed tomography (CCT) and magnetic resonance imaging (MRI) by their space-consuming character and by their divergent density and intensity in comparison to normal brain parenchyma. They can grow extrusively, even infiltrate the parenchyma or originate from it. Besides clinical symptoms and diagnostics this article describes the most common pediatric brain tumors, i.e. astrocytoma, medulloblastoma, brainstem glioma, craniopharyngioma, neurofibromatosis and ganglioglioma. The most important imaging criteria are outlined. (orig.) [German] Sowohl Histologie als auch Lokalisation von Hirntumoren unterscheiden sich bei Kindern und Erwachsenen. Waehrend maligne Gliome und Meningeome bei Erwachsenen vorherrschen, kommen bei Kindern ueberwiegend Medulloblastome und niedriggradige Astrozytome vor. Mehr als die Haelfte (50-70 %) aller kindlichen Hirntumoren sind infratentoriell lokalisiert, dagegen sind es bei Erwachsenen nur etwa 30 %. Im Ultraschall, in der kranialen CT (CCT) oder MRT koennen Hirntumoren durch ihren raumfordernden Charakter und ihrer zum normalen Parenchym abweichenden Dichte oder Signalintensitaet erkannt werden. Sie koennen verdraengend wachsen, z. T. auch das Parenchym infiltrieren oder von diesem ausgehen. Neben der klinischen Symptomatik und Diagnostik werden im vorliegenden Artikel die haeufigsten kindlichen Hirntumoren, das Astrozytom, Medulloblastom, Hirnstammgliom, Kraniopharyngeom, die Neurofibromatose und das Gangliogliom beschrieben. Die wichtigsten bildgebende Kriterien werden dargestellt. (orig.)

  18. Radioimmunoimaging of tumors with a pantumor antibody

    International Nuclear Information System (INIS)

    Chen, D.C.P.; Siegel, M.E.; Chen, F.; Taylor, O.R.; Epstein, A.L.

    1988-01-01

    The TNT-1 antibody was developed to bind intracellular nuclear antigens that are accessible only in degenerative or necrotic cells. Since about 50% of tumor cells are in various stages of cell degeneration or death, this antibody could serve as a pantumor antibody for tumor detection. After intravenous injection of 10 μg of TNT-1F(ab')2 fragments labeled with 20 μCi of I-131, serial images were obtained at 1 and 4 hours and daily for 6 days in mice bearing various human tumors. Accumulation of TNT-1 was imaged in a necrotic tumor as early as 4 hours after injection and because more intense at 48 hours. The tumor-muscle ratio was as high as 29:1. Intense accumulation was noted in the necrotic tumor, about nine times that of healthy tumor. In conclusion, TNT-1, a pantumor antibody, can detect necrotic tumors in animal models. It may be an ideal imaging agent for cancer detection

  19. The Influence of a Bout of Exertion on Novice Barefoot Running Dynamics.

    Science.gov (United States)

    Hashish, Rami; Samarawickrame, Sachithra D; Baker, Lucinda; Salem, George J

    2016-06-01

    Barefoot, forefoot strike (FFS) running has recently risen in popularity. Relative to shod, rear-foot strike (RFS) running, employing a FFS is associated with heightened triceps surae muscle activation and ankle mechanical demand. Novice to this pattern, it is plausible that habitually shod RFS runners exhibit fatigue to the triceps surae when acutely transitioning to barefoot running, thereby limiting their ability to attenuate impact. Therefore, the purpose was to determine how habitually shod RFS runners respond to an exertion bout of barefoot running, operationally defined as a barefoot run 20% of mean daily running distance. Twenty-one RFS runners performed novice barefoot running, before and after exertion. Ankle peak torque, triceps surae EMG median frequency, foot-strike patterns, joint energy absorption, and loading rates were evaluated. Of the 21 runners, 6 maintained a RFS, 10 adopted a mid-foot strike (MFS), and 5 adopted a FFS during novice barefoot running. In-response to exertion, MFS and FFS runners demonstrated reductions in peak torque, median frequency, and ankle energy absorption, and an increase in loading rate. RFS runners demonstrated reductions in peak torque and loading rate. These results indicate that a short bout of running may elicit fatigue to novice barefoot runners, limiting their ability to attenuate impact. Key pointsIn response to exertion, novice barefoot runners demonstrate fatigue to their soleus.In response to exertion, novice barefoot runners demonstrate a reduction in ankle energy absorptionIn response to exertion, novice barefoot runners demonstrate an increase in loading rate.

  20. 20 CFR 220.132 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Physical exertion requirements. 220.132 Section 220.132 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... of walking and standing is often necessary in carrying out job duties. Jobs are sedentary if walking...

  1. Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion.

    Science.gov (United States)

    Luethi, Matthias S; Friese, Malte; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

    2016-10-01

    Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Central nervous system tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

    1995-01-01

    Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

  3. Plasticity of gamma delta T cells: impact on the anti-tumor response

    Directory of Open Access Journals (Sweden)

    Virginie eLafont

    2014-12-01

    Full Text Available The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of gamma and delta chains (gamma delta T cells are of particular interest. gamma delta T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary and prostate cancer directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating gamma delta T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that gamma delta T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating gamma deltaT cells could exert an immunosuppressive activity by negatively regulating DC maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to gamma delta T cells and promote their differentiation into gamma delta T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of gamma delta T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying gamma delta T cell expansion, differentiation and recruitment in the tumor microenvironment.

  4. Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma

    Science.gov (United States)

    Young, Kon-Ji; Park, A-Reum; Choi, Ha-Rim; Lee, Hwa-Youn; Kim, Su-Man; Chung, Byung Yeoup; Park, Chul-Hong; Choi, Hyo Jin; Ko, Young-Hyeh; Bai, Hyoung-Woo; Kang, Hyung-Sik

    2017-01-01

    Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma. PMID:28423548

  5. Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results.

    Science.gov (United States)

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-Li; Zhang, Jian; Fu, Kai

    2008-10-01

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor alternative reading frame (ARF), exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in non-small cell lung cancer and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Observe the expression of Pokemon in NSCLC and investigate its mechanism and clinical significance. Determine the expression of Pokemon in human NSCLC cell lines as well as 55 cases of NSCLC tumor tissues, tumor adjacent tissues and surrounding tissues by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and analyze the relationship between Pokemon expression in NSCLC tumor tissues and clinicopathological features. Determine 62 NSCLC tumor tissues (5 years ago) and p14(ARF) expression with immunohistochemical technique, discuss the correlation between them and assess the effect of Pokemon on prognosis of patients with lung cancer. Pokemon mRNA and protein took on high expression in lung cancer cell lines, and the expression difference between cancer tissues, tumor adjacent tissues and surrounding tissues had statistical significance (PPokemon expression and p14(ARF) expression were negatively correlated (r=-0.287). The expression of Pokemon was determined not to be associated with the patient's sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). There was high expression of Pokemon in NSCLC

  6. Nanoparticle Delivery of Artesunate Enhances the Anti-tumor Efficiency by Activating Mitochondria-Mediated Cell Apoptosis

    Science.gov (United States)

    Liu, Rui; Yu, Xiwei; Su, Chang; Shi, Yijie; Zhao, Liang

    2017-06-01

    Artemisinin and its derivatives were considered to exert a broad spectrum of anti-cancer activities, and they induced significant anti-cancer effects in tumor cells. Artemisinin and its derivatives could be absorbed quickly, and they were widely distributed, selectively killing tumor cells. Since low concentrations of artesunate primarily depended on oncosis to induce cell death in tumor cells, its anti-tumor effects were undesirable and limited. To obtain better anti-tumor effects, in this study, we took advantage of a new nanotechnology to design novel artesunate-loaded bovine serum albumin nanoparticles to achieve the mitochondrial accumulation of artesunate and induce mitochondrial-mediated apoptosis. The results showed that when compared with free artesunate's reliance on oncotic death, artesunate-loaded bovine serum albumin nanoparticles showed higher cytotoxicity and their significant apoptotic effects were induced through the distribution of artesunate in the mitochondria. This finding indicated that artesunate-loaded bovine serum albumin nanoparticles damaged the mitochondrial integrity and activated mitochondrial-mediated cell apoptosis by upregulating apoptosis-related proteins and facilitating the rapid release of cytochrome C.

  7. Prevalence of exertional rhabdomyolysis in endurance horses in the Pacific Northwestern United States.

    Science.gov (United States)

    Wilberger, M S; McKenzie, E C; Payton, M E; Rigas, J D; Valberg, S J

    2015-03-01

    Exertional rhabdomyolysis (ER) is a reported syndrome in competing endurance horses; however, the prevalence and cause of ER in this population have not been defined. To determine the prevalence of ER in a sample of endurance racing horses and investigate factors, including relevant genetic defects, contributing to the occurrence of rhabdomyolysis in this group. Prospective clinical study. Riders of 101 horses participating in one of four 50-mile (80.5 km) distance races completed a comprehensive questionnaire regarding the medical history, management and performance of their horse. Serum creatine kinase activity (CK) was measured before and 4 h after completion of exercise. Hair samples were analysed by PCR for the R309H mutation in the glycogen synthase gene (GYS1) responsible for type 1 polysaccharide storage myopathy (PSSM) and the C7360G mutation in the ryanodine receptor 1 (RYR1) gene causing malignant hyperthermia (MH). Samples were obtained from 68 Arabians, 20 half-Arabians and 13 horses of other breeds. Serum CK was above the resting reference interval (145-633 u/l) in 38 horses after racing (median 883 u/l, range 658-3739) but was compatible with values previously reported in apparently healthy endurance horses. Pathological ER was suspected to occur in 4 horses with serum CK activities exceeding 10,000 u/l 4 h after racing (median 84,825 u/l; range 10,846-381,790) including 3 Arabians and one half-Arabian horse. GYS1 and RYR1 mutations were not present in hair samples from any horses. Exertional rhabdomyolysis occurred at a prevalence of 4.0% in a sample of horses participating in 50 mile distance events and all affected horses were Arabian or half-Arabian. The cause of ER in the endurance horse population remains unknown; however, ER in competing Arabian endurance horses is unlikely to be due to type 1 PSSM or MH. © 2014 EVJ Ltd.

  8. Role for the Wilms tumor gene in genital development?

    International Nuclear Information System (INIS)

    van Heyningen, V.; Bickmore, W.A.; Seawright, A.; Fletcher, J.M.; Maule, J.; Hastie, N.D.; Fekete, G.; Gessler, M.; Bruns, G.A.P.; Huerre-Jeanpierre, C.; Junien, C.; Williams, B.R.G.

    1990-01-01

    Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here the authors describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT). The region of overlap between this deletion and one associated with WT and similar genital anomalies but no aniridia covers a region of 350-400 kilobases, which is coincident with the extent of homozygous deletion detected in tumor tissue from a sporadic WT. A candidate WT gene located within this region has recently been isolated, suggesting nonpenetrance for tumor expression in the first individual. The inclusion within the overlap region of a gene for WT predisposition and a gene for the best-documented WT-associated genitourinary malformations leads to suggest that both of these anomalies result from a loss-of-function mutation at the same locus. This in turn implies that the WT gene exerts pleiotropic effect on both kidney and genitourinary development, a possibility supported by the observed expression pattern of the WT candidate gene in developing kidney and gonads

  9. Desmoplastic Tumor Microenvironment and Immunotherapy in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan; Lewinska, Monika; Andersen, Jesper B

    2018-01-01

    connective tissue which surrounds and infiltrates the tumor epithelium. This desmoplastic environment presents a clinical challenge, limiting drug delivery and supporting the growth of the tumor mass. In this review we attempt to highlight key pathways involved in cell to cell communication between the tumor......Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond...... to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies. CCA is characterized by marked tumor reactive stroma, a fibrogenic...

  10. Comparison of the force exerted by hippocampal and DRG growth cones.

    Science.gov (United States)

    Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

    2013-01-01

    Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm(2) and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties.

  11. Radiobiological hypoxic fraction does not correlate with pO2 measurements in eight human tumor xenografts into nude mice

    International Nuclear Information System (INIS)

    Taghian, A.; Huang, P.; Griffon, G.; Hartford, A.; Allam, A.; Costa, A. da; Kozin, S.; Suit, H.D.

    1997-01-01

    Purpose/Objective: Clinical and laboratory reports suggest that hypoxia limits local control probability in tumors treated by radiation. Significant increase in the TCD 50 (the dose of radiation needed to control 50% of the tumors) was obtained in a number of tumor models when the tumors were rendered hypoxic by clamping. Furthermore, recent data have shown the value of measuring the pO2 using electrodes in predicting the tumor response to radiation in cervical cancer. The aim of this study is to investigate the correlation between the radiobiological hypoxic fraction (HF) and the pO2 measurements of human tumor xenografts. Materials and Methods: Eight human tumor xenografts (five glioblastoma, one squamous cell carcinoma, one colon cancer, and one soft tissue sarcoma) were used in these experiments. Tumor chunks 2 mm in diameter were implanted into the hindleg of 5 Gy whole-body irradiated nude mice. When the tumor size reached 110 mm 3 , radiation was administered in a single dose ranging from 17.5 Gy to 90 Gy in hypoxic conditions. Acute hypoxia was induced by clamping the tumor bearing leg three minutes before and during the treatment. When aerobic conditions were required, the tumor bearing leg was immobilized by a hook which fitted around the ankle. Seven to 10 tumors were assigned to each dose level in each assay; there were 6 to 8 dose levels per assay. Starting at 2-3 weeks after irradiation, the animals were examined once per week and scored for presence of local tumor; if present, tumor diameters were measured. Tumor response is described in terms of radiation dose (in Gy) required to control 50% of the xenografts (TCD 50 ). The (HF) was determined using the formula of Howes (HF=e - ((TCD 50 hypoxic-TCD 50 air)(Do hypoxic)) and assuming an oxygen enhancement ratio of 3.0: (D o hyp=D o air x 3.0) (the D o air was separately determined in vitro for the corresponding cell lines). The pO2 measurements used electrodes as published (Boucher et al

  12. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

    International Nuclear Information System (INIS)

    Jang, Ji-Young; Lee, Jong-Kuen; Jeon, Yoon-Kyung; Kim, Chul-Woo

    2013-01-01

    tumor cells, which can be transferred to TAM via exosomes and inhibits TAM infiltration and M2 polarization. We suggest a novel mechanism by which EGCG exerts anti-tumor activity via regulation of TAM in tumor microenvironment

  13. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

    2014-02-26

    The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

  14. 201Tl scintigraphic evaluation of tumor mass and viability of bone and soft-tissue tumors

    International Nuclear Information System (INIS)

    Tsuda, Takatoshi; Kubota, Masahiro; Yoshida, Satoru; Shibata, Masahito; Wakabayashi, Jun-ichi; Obata, Hiroyuki; Matsuyama, Toshikatsu; Usui, Masamichi; Ishii, Sei-ichi.

    1994-01-01

    To characterize 201 Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201 Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201 Tl and both arterial and blood pool phase of 99m Tc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201 Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201 Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201 Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99m Tc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99m Tc-HMDP of 5 responders with >90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201 Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201 Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors. (author)

  15. Cathepsin D and Its Prognostic Value in Neuroepithelial Brain Tumors

    OpenAIRE

    Pigac, Biserka; Dmitrović, Branko; Marić, Svjetlana; Mašić, Silvija

    2012-01-01

    Expression of Cathepsin D (Cath D) in some primary neuroepithelial brain tumors and its prognostic value were studied. The research included 65 samples of human primary neuroepithelial brain tumors. There were 50 glial tumors (10 diffuse astrocytomas (DA), 15 anaplastic astrocytomas (AA), 25 glioblastomas (GB), 15 embryonic tumors (15 medulloblastomas (MB) as well as 5 samples of normal brain tissue. Immunohistochemical method was applied to monitor diffuse positive reaction in the cytoplasm ...

  16. A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yuan-Wu Chen

    Full Text Available Oral squamous cell carcinoma (OSCC is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

  17. An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors.

    Science.gov (United States)

    Karageorgis, Anastassia; Dufort, Sandrine; Sancey, Lucie; Henry, Maxime; Hirsjärvi, Samuli; Passirani, Catherine; Benoit, Jean-Pierre; Gravier, Julien; Texier, Isabelle; Montigon, Olivier; Benmerad, Mériem; Siroux, Valérie; Barbier, Emmanuel L; Coll, Jean-Luc

    2016-02-19

    Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines.

  18. Pituitary gland tumors; Hypophysentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Jesser, J.; Schlamp, K.; Bendszus, M. [Radiologische Klinik, Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany)

    2014-10-15

    This article gives an overview of the most common tumors of the pituitary gland and the differential diagnostics with special emphasis on radiological diagnostic criteria. A selective search of the literature in PubMed was carried out. Pituitary adenomas constitute 10-15 % of all intracranial tumors and are the most common tumors of the sellar region. Tumors smaller than 1 cm in diameter are called microadenomas while those larger than 1 cm in diameter are called macroadenomas. Approximately 65 % of pituitary gland adenomas secrete hormones whereby approximately 50 % secrete prolactin, 10 % secrete growth hormone (somatotropin) and 6 % secrete corticotropin. Other tumors located in the sella turcica can also cause endocrinological symptoms, such as an oversecretion of pituitary hormone or pituitary insufficiency by impinging on the pituitary gland or its stalk. When tumors spread into the space cranial to the sella turcica, they can impinge on the optic chiasm and cause visual disorders. A common differential diagnosis of a sellar tumor is a craniopharyngeoma. In children up to 10 % of all intracranial tumors are craniopharyngeomas. Other differential diagnoses for sellar tumors are metastases, meningiomas, epidermoids and in rare cases astrocytomas, germinomas or Rathke cleft cysts As these tumors are located in an anatomically complex region of the skull base and are often very small, a highly focused imaging protocol is required. The currently favored modality is magnetic resonance imaging (MRI) with the administration of a contrast agent. The sellar region should be mapped in thin slices. In cases of suspected microadenoma the imaging protocol should also contain a sequence with dynamic contrast administration in order to assess the specific enhancement characteristics of the tumor and the pituitary gland. (orig.) [German] Diese Arbeit ist eine Uebersicht ueber die haeufigsten Hypophysentumoren und deren Differenzialdiagnosen mit Augenmerk auf die

  19. Epilepsy and brain tumors

    Science.gov (United States)

    ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  20. Immunohistochemical detection of estrogen receptors in canine mammary tumors

    OpenAIRE

    Elena Atanaskova Petrov; Ivica Gjurovski; Trpe Ristoski; Goran Nikolovski; Pandorce Trenkoska; Plamen Trojacanec; Ksenija Ilievska; Toni Dovenski; Gordana Petrushevska

    2016-01-01

    Mammary tumors are among the most common neoplasms in intact female dogs.They have a complex morphology, usually affecting middle age and older bitches. Almost 50% of the mammary tumors in dogs are malignant neoplasms. Prognosis is based on several factors: stage, age, tumor size, metastasis, histopathology, ovariectomy status and hormone-receptor activity. Immunohistochemical (IHC) measurement has become increasingly an important diagnostic and prognostic parameter, with the development of m...

  1. Transformation of Epithelial Ovarian Cancer Stemlike Cells into Mesenchymal Lineage via EMT Results in Cellular Heterogeneity and Supports Tumor Engraftment

    Science.gov (United States)

    Jiang, Hua; Lin, Xiaolong; Liu, Yingtao; Gong, Wenjia; Ma, Xiaoling; Yu, Yinhua; Xie, Yi; Sun, Xiaoxi; Feng, Youji; Janzen, Viktor; Chen, Tong

    2012-01-01

    Ovarian cancers are heterogeneous and contain stemlike cells that are able to self-renew and are responsible for sustained tumor growth. Metastasis in the peritoneal cavity occurs more frequently in ovarian cancer than in other malignancies, but the underlying mechanism remains largely unknown. We have identified that ovarian cancer stemlike cells (CSCs), which were defined as side population (SP) cells, were present in patients’ ascitic fluid and mesenchymally transformed cell lines, ES-2 and HO-8910PM. SP cells, which were sorted from both cell lines and implanted into immunocompromised mice, were localized to the xenografted tumor boundary. In addition, SP cells exhibited an epithelial phenotype and showed a distinct gene expression profile with reduced expression of cell adhesion molecules (CAMs), indicating that SP cells exert an important role in ovarian cancer progression on the basis of their delicate interaction with the surrounding microenvironment and anatomical localization in tumors. In contrast, non-SP cells exhibited a more mesenchymal phenotype and showed more increased invasive potential than SP cells. This heterogeneity was observed as an endogenous transformation via the epithelial–mesenchymal transition (EMT) process. Inhibition of the EMT process by Snail1 silencing reduced the SP cell frequency, and affected their invasive capacity and engraftment. These findings illustrate the interplay between epithelial ovarian CSCs and the EMT, and exert a link to explain tumor heterogeneity and its necessity for ovarian cancer maintenance, metastasis and progression. PMID:22801793

  2. Osteomalacia por tumor secretor de FGF-23 Ostemalacia due to a tumor secreting FGF-23

    Directory of Open Access Journals (Sweden)

    Ariel Sánchez

    2013-02-01

    Full Text Available Se presenta un caso de osteomalacia oncogénica en un varón de 50 años, con fuertes dolores óseos y gran debilidad muscular durante 4 años. Tenía varias deformidades vertebrales dorsales en cuña, fracturas en ambas ramas iliopubianas y en una rama isquiopubiana, y una zona de Looser en la meseta tibial derecha. Se localizó un tumor de 2 cm de diámetro en el hueco poplíteo derecho mediante centellograma con octreótido marcado con tecnecio. El tumor fue extirpado quirúrgicamente. La microscopía mostró un tumor mesenquimático fosfatúrico, de tejido conectivo mixto. La inmunotinción demostró FGF-23. Hubo rápida mejoría, con consolidación de las fracturas pelvianas y de la pseudofractura tibial y normalización de las alteraciones bioquímicas.A case of oncogenic osteomalacia in a 50-year-old male is here presented. He suffered severe bone pain and marked muscular weakness of 4 years' duration. There were several vertebral deformities in the thoracic spine, bilateral fractures of the iliopubic branches, another fracture in the left ischiopubic branch, and a Looser's zone in the right proximal tibia. An octreotide-Tc scan allowed to identify a small tumor in the posterior aspect of the right knee. It was surgically removed. Microscopically, it was a phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT. Expression of FGF-23 was documented by immune-peroxidase staining. There was rapid improvement, with consolidation of the pelvic fractures and the tibial pseudo-fracture. The laboratory values returned to normal.

  3. Anti-tumor effects of an engineered 'killer' transfer RNA

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dong-hui [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Lee, Jiyoung; Frankenberger, Casey [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Geslain, Renaud, E-mail: rgeslain@depaul.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Department of Biology, DePaul University, Chicago, IL 60614 (United States); Rosner, Marsha, E-mail: m-rosner@uchicago.edu [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Pan, Tao, E-mail: taopan@uchicago.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer tRNA with anti-cancer effects. Black-Right-Pointing-Pointer tRNA induced protein misfolding. Black-Right-Pointing-Pointer tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA{sup Ser}(AAU) is an engineered human tRNA{sup Ser} with an anticodon coding for isoleucine. Here we test the possibility that tRNA{sup Ser}(AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA{sup Ser}(AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA{sup Ser}(AAU) in both tumorigenic and non-tumorigenic cells. tRNA{sup Ser}(AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA{sup Ser}(AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA{sup Ser}(AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA{sup Ser}(AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  4. Hypoxia-inducible factor 1–mediated characteristic features of cancer cells for tumor radioresistance

    International Nuclear Information System (INIS)

    Harada, Hiroshi

    2016-01-01

    Tumor hypoxia has been attracting increasing attention in the fields of radiation biology and oncology since Thomlinson and Gray detected hypoxic cells in malignant solid tumors and showed that they exert a negative impact on the outcome of radiation therapy. This unfavorable influence has, at least partly, been attributed to cancer cells acquiring a radioresistant phenotype through the activation of the transcription factor, hypoxia-inducible factor 1 (HIF-1). On the other hand, accumulating evidence has recently revealed that, even though HIF-1 is recognized as an important regulator of cellular adaptive responses to hypoxia, it may not become active and induce tumor radioresistance under hypoxic conditions only. The mechanisms by which HIF-1 is activated in cancer cells not only under hypoxic conditions, but also under normoxic conditions, through cancer-specific genetic alterations and the resultant imbalance in intermediate metabolites have been summarized herein. The relevance of the HIF-1–mediated characteristic features of cancer cells, such as the production of antioxidants through reprogramming of the glucose metabolic pathway and cell cycle regulation, for tumor radioresistance has also been reviewed

  5. Exercise, physical activity, and exertion over the business cycle.

    Science.gov (United States)

    Colman, Gregory; Dave, Dhaval

    2013-09-01

    Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Stiffness and thickness of fascia do not explain chronic exertional compartment syndrome

    DEFF Research Database (Denmark)

    Dahl, Morten; Hansen, Philip; Stål, Per

    2011-01-01

    Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown.......Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown....

  7. Tumor disease and associated congenital abnormalities on prenatal MRI.

    Science.gov (United States)

    Nemec, Stefan F; Horcher, Ernst; Kasprian, Gregor; Brugger, Peter C; Bettelheim, Dieter; Amann, Gabriele; Nemec, Ursula; Rotmensch, Siegfried; Rimoin, David L; Graham, John M; Prayer, Daniela

    2012-02-01

    Fetal tumors can have a devastating effect on the fetus, and may occur in association with congenital malformations. In view of the increasing role of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), we sought to demonstrate the visualization of fetal tumors, with regard to congenital abnormalities, on MRI. This retrospective study included 18 fetuses with tumors depicted on fetal MRI after suspicious US findings. An MRI standard protocol was used to diagnose tumors judged as benign or malignant. All organ systems were assessed for tumor-related complications and other congenital malformations. Available US results and histopathology were compared with MRI. There were 13/18 (72.2%) benign and 5/18 (27.8%) malignant tumors diagnosed: a cerebral primitive neuroectodermal tumor in 1/18, head-neck teratomas in 4/18; ventricular rhabdomyomas in 4/18; a cardiac teratoma in 1/18; a hepatoblastoma in 1/18; neuroblastomas in 2/18; a cystic hemorrhagic adrenal hyperplasia in 1/18; a pelvic leiomyoma in 1/18; sacrococcygeal teratomas in 3/18. Tumor-related complications were present in 13/18 (72.2%) cases; other congenital abnormalities in 3/18 (16.7%). MRI diagnosis and histology were concordant in 8/11 (72.7%) cases. In 6/12 (50%) cases, US and MRI diagnoses were concordant, and, in 6/12 (50%) cases, additional MRI findings changed the US diagnosis. Our MRI results demonstrate the visualization of fetal tumors, with frequently encountered tumor-related complications, and other exceptional congenital abnormalities, which may provide important information for perinatal management. Compared to prenatal US, MRI may add important findings in certain cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Tumor disease and associated congenital abnormalities on prenatal MRI

    International Nuclear Information System (INIS)

    Nemec, Stefan F.; Horcher, Ernst; Kasprian, Gregor; Brugger, Peter C.; Bettelheim, Dieter; Amann, Gabriele; Nemec, Ursula; Rotmensch, Siegfried; Rimoin, David L.; Graham, John M. Jr.; Prayer, Daniela

    2012-01-01

    Objective: Fetal tumors can have a devastating effect on the fetus, and may occur in association with congenital malformations. In view of the increasing role of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), we sought to demonstrate the visualization of fetal tumors, with regard to congenital abnormalities, on MRI. Materials and methods: This retrospective study included 18 fetuses with tumors depicted on fetal MRI after suspicious US findings. An MRI standard protocol was used to diagnose tumors judged as benign or malignant. All organ systems were assessed for tumor-related complications and other congenital malformations. Available US results and histopathology were compared with MRI. Results: There were 13/18 (72.2%) benign and 5/18 (27.8%) malignant tumors diagnosed: a cerebral primitive neuroectodermal tumor in 1/18, head–neck teratomas in 4/18; ventricular rhabdomyomas in 4/18; a cardiac teratoma in 1/18; a hepatoblastoma in 1/18; neuroblastomas in 2/18; a cystic hemorrhagic adrenal hyperplasia in 1/18; a pelvic leiomyoma in 1/18; sacrococcygeal teratomas in 3/18. Tumor-related complications were present in 13/18 (72.2%) cases; other congenital abnormalities in 3/18 (16.7%). MRI diagnosis and histology were concordant in 8/11 (72.7%) cases. In 6/12 (50%) cases, US and MRI diagnoses were concordant, and, in 6/12 (50%) cases, additional MRI findings changed the US diagnosis. Conclusion: Our MRI results demonstrate the visualization of fetal tumors, with frequently encountered tumor-related complications, and other exceptional congenital abnormalities, which may provide important information for perinatal management. Compared to prenatal US, MRI may add important findings in certain cases.

  9. Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer.

    Science.gov (United States)

    Gao, Jing; Wang, Haixing; Zang, Wanchun; Li, Beifang; Rao, Guanhua; Li, Lei; Yu, Yang; Li, Zhongwu; Dong, Bin; Lu, Zhihao; Jiang, Zhi; Shen, Lin

    2017-09-01

    Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. MR Histoanatomical Distribution of 290 Soft-tissue Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Tae Yong; Lee, In Sook; Lee, Gee Won; Kim, Jeung Il; Choi, Kyung Un; Kim, Won Taek [Pusan National University Hospital, Busan (Korea, Republic of)

    2008-12-15

    This study was designed too identify the MR histoanatomical distribution of soft-tissue tumors. A total of 290 soft-tissue tumors of 281 patients were analyzed by the use of MR imaging and were pathologically confirmed after surgical resection or a biopsy. There were 120 malignant soft-tissue tumors including tumors of an intermediate malignancy and 170 benign tumors. The histoanatomical locations were divided into three types: 'type I' with superficial layer tumors that involved the cutaneous and subcutaneous tissue, 'type II' with deep layer tumors that involved the muscle or tendon and 'type III' with soft tissue tumors that involved both the superficial and deep layers. Soft-tissue tumors with more than three cases with a frequency of more than 75% included dermatofibrosarcoma protuberans, glomus tumor, angiolipoma, leiomyosarcoma and lymphoma as 'type I' tumors. 'Type II' tumors with more than three cases with a frequency of more than 75% included liposarcoma, fibromatosis, papillary endothelial hyperplasia and rhabdomyosarcoma. 'Type III' tumors with more than three cases with a frequency of more than 50% included neurofibromatosis. The MR histoanatomical distributions of soft tissue tumors are useful in the differential pathological diagnosis when a soft-tissue tumor has a nonspecific MR appearance.

  11. The role of chronic acanthosis and subacute inflammation in tumor promotion in CD-1 mice by petroleum middle distillates.

    Science.gov (United States)

    Skisak, C

    1991-07-01

    An initiation-promotion bioassay using CD-1 mice was conducted to examine the role of chronic acanthosis and inflammation in tumor promotion by petroleum middle distillates (MD). Test groups were initiated with 7,12-dimethylbenz[a]anthracene (DMBA). Promotion with MD consisted of twice weekly treatments for 25 weeks with either 25 or 50 microliters, 50 microliters + daily treatment with 15 micrograms dexamethasone, 50 microliters + postapplication washings, or 100 microliters. Three mice from each group were euthanized at 21-day intervals (24 total per group). The skin from interim euthanized mice was examined histopathologically for tumors, acanthosis, and subacute inflammation. Tumor incidence at study termination was as follows: 25 microliters (45%), 50 microliters (43%), 50 microliters + dexamethasone (0%), 50 microliters + washing (70%), and 100 microliters (81%). A correlation of greater than 0.93 was observed at all intervals between tumor incidence and cumulative group mean degrees of acanthosis in interim euthanized mice. The correlation between subacute inflammation at early through midstudy interval weeks and tumor incidence at study termination was poor. These results support the hypothesis that induction of a lasting, albeit mild, hyperplasia is an essential, but not sufficient requirement for tumor promotion. Furthermore, subacute inflammation does not appear to be a significant factor in tumor promotion by petroleum MD.

  12. Alteration of keratinocyte differentiation and senescence by the tumor promoter dioxin

    International Nuclear Information System (INIS)

    Ray, Soma S.; Swanson, Hollie I.

    2003-01-01

    Exposure to the environmental contaminant dioxin, elicits a variety of responses, which includes tumor promotion, embryotoxicity/teratogenesis, and carcinogenesis in both animals and humans. Many of the effects of dioxin are mediated by the aryl hydrocarbon receptor (AHR), a ligand-activated bHLH (basic helix-loop-helix)/PAS transcription factor. We initiated this study to determine whether dioxin's tumor-promoting activities may lie in its ability to alter proliferation, differentiation, and/or senescence using normal human epidermal keratinocytes (HEKs). Here, we report that dioxin appears to accelerate differentiation as measured by flow cytometry and by increased expression of the differentiation markers involucrin and filaggrin. In addition, dioxin appears to increase proliferation as indicated by an increase in NADH/NADPH production and changes in cell cycle. Finally, dioxin decreases SA (senescence associated) β-galactosidase staining, an indicator of senescence, in the differentiating keratinocytes. These changes were accompanied by decreases in the expression levels of key cell cycle regulatory proteins p53, p16 INK4a , and p14 ARF . Our findings support the idea that dioxin may exert its tumor-promoting actions, in part, by downregulating the expression levels of key tumor suppressor proteins, which may impair the cell's ability to maintain its appropriate cellular status

  13. A Case of Malignant Peripheral Nerve Sheath Tumor with Rhabdomyoblastic Differentiation: Malignant Triton Tumor

    Directory of Open Access Journals (Sweden)

    Kenichiro Mae

    2013-12-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNST constitute a rare variety of soft tissue sarcomas thought to originate from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT, a very rare, highly aggressive soft tissue tumor, is a subgroup of MPNST and is comprised of malignant Schwann cells coexisting with malignant rhabdomyoblasts. We herein report the case of a 24-year-old man who presented a subcutaneous mass in his right thigh. The mass was removed surgically in its entirety and radiation therapy was applied locally to prevent tumor regrowth. Nonetheless, the patient died 10 months after surgery from metastases to the lung and brain. He presented neither cafe-au-lait spots nor cutaneous neurofibromas. The histopathology showed a transition from a neurofibroma to an MTT, making this the second report of an MTT arising from a neurofibroma without neurofibromatosis type 1, an autosomal dominant disorder with which 50-70% of tumors reported in previous studies were associated. A histopathological examination using immunostaining with desmin confirmed this diagnosis. MTT has a poorer prognosis than MPNST and should therefore be regarded as a distinct clinical entity.

  14. Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis

    Science.gov (United States)

    Garcia-Barros, Monica; Paris, Francois; Cordon-Cardo, Carlos; Lyden, David; Rafii, Shahin; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard

    2003-05-01

    About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.

  15. Anti-helminth compound niclosamide downregulates Wnt Signaling and elicits antitumor responses in tumors with activating APC mutations

    Science.gov (United States)

    Osada, Takuya; Chen, Minyong; Yang, Xiao Yi; Spasojevic, Ivan; Vandeusen, Jeffrey B.; Hsu, David; Clary, Bryan M.; Clay, Timothy M.; Chen, Wei; Morse, Michael A.; Lyerly, H. Kim

    2011-01-01

    Wnt/β-catenin pathway activation caused by APC mutations occurs in approximately 80% of sporadic colorectal cancers. The anti-helminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined if niclosamide could inhibit the Wnt/ β-catenin pathway in human colorectal cancers and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/ β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling and exerted anti-proliferative effects in human colon cancer cell lines and colorectal cancer cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar anti-proliferative effects in these colorectal cancer model systems. In mice implanted with human colorectal cancer xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity and led to tumor control. Our findings support clinical explorations to reposition niclosamide for treatment of colorectal cancer. PMID:21531761

  16. Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence of the microbeam width at constant valley dose

    International Nuclear Information System (INIS)

    Serduc, Raphael; Fonta, Caroline; Renaud, Luc; Bouchet, Audrey; Braeuer-Krisch, Elke; Sarun, Sukhena; Bravin, Alberto; Le Duc, Geraldine; Laissue, Jean A; Spiga, Jenny; Boutonnat, Jean; Siegbahn, Erik Albert; Esteve, Francois

    2009-01-01

    To analyze the effects of the microbeam width (25, 50 and 75 μm) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MRT50, MRT75), each using two orthogonally intersecting arrays of either 25, 50 or 75 μm wide microbeams, all spaced 211 μm on center, were tested. For each configuration, peak entrance doses of 860, 480 and 320 Gy, respectively, were calculated to produce an identical valley dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days after radiation treatment, 42 rats were killed to evaluate histopathologically the extent of tumor necrosis, and the presence of proliferating tumors cells and tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48 days for MRT25, 50 and 75, respectively. The combination of the highest entrance doses (860 Gy per array) with 25 μm wide beams (MRT25) resulted in a cumulative valley dose of 36 Gy and was excessively toxic, as it led to early death of all normal rats and of ∼50% of tumor-bearing rats. The short survival times, particularly of rats in the MRT25 group, restricted adequate observance of the therapeutic effect of the method on tumor-bearing rats. However, microbeams of 50 μm width led to the best median survival time after 9L gliosarcoma MRT treatment and appeared as the better compromise between tumor control and normal brain toxicity compared with 75 μm or 25 μm widths when used with a 211 μm on-center distance. Despite very high radiation doses, the tumors were not sterilized; viable proliferating tumor cells remained present at the tumor margin. This study shows that microbeam width and peak entrance doses strongly influence tumor responses and normal brain toxicity, even if valley doses are kept constant in all groups. The use

  17. Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence of the microbeam width at constant valley dose

    Energy Technology Data Exchange (ETDEWEB)

    Serduc, Raphael; Fonta, Caroline; Renaud, Luc [Universite de Toulouse, UPS, Centre de Recherche Cerveau et Cognition (France); Bouchet, Audrey; Braeuer-Krisch, Elke; Sarun, Sukhena; Bravin, Alberto; Le Duc, Geraldine [European Synchrotron Radiation Facility, F38043 Grenoble (France); Laissue, Jean A [Institute of Pathology, University of Bern (Switzerland); Spiga, Jenny [Department of Physics, University of Cagliari, s.p. Monserrato-Sestu, Monserrato (Canada) 09042 (Italy); Boutonnat, Jean [TIMC lab, UMR CNRS 5525, Univ Joseph Fourier, CHU, Grenoble (France); Siegbahn, Erik Albert [Department of Medical Physics, Karolinska Universitetssjukhuset, 17176 Stockholm (Sweden); Esteve, Francois [INSERM U836, Equipe 6, Institut des Neurosciences de Grenoble, 38043 Grenoble Cedex (France)], E-mail: raph.serduc@gmail.com

    2009-11-07

    To analyze the effects of the microbeam width (25, 50 and 75 {mu}m) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MRT50, MRT75), each using two orthogonally intersecting arrays of either 25, 50 or 75 {mu}m wide microbeams, all spaced 211 {mu}m on center, were tested. For each configuration, peak entrance doses of 860, 480 and 320 Gy, respectively, were calculated to produce an identical valley dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days after radiation treatment, 42 rats were killed to evaluate histopathologically the extent of tumor necrosis, and the presence of proliferating tumors cells and tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48 days for MRT25, 50 and 75, respectively. The combination of the highest entrance doses (860 Gy per array) with 25 {mu}m wide beams (MRT25) resulted in a cumulative valley dose of 36 Gy and was excessively toxic, as it led to early death of all normal rats and of {approx}50% of tumor-bearing rats. The short survival times, particularly of rats in the MRT25 group, restricted adequate observance of the therapeutic effect of the method on tumor-bearing rats. However, microbeams of 50 {mu}m width led to the best median survival time after 9L gliosarcoma MRT treatment and appeared as the better compromise between tumor control and normal brain toxicity compared with 75 {mu}m or 25 {mu}m widths when used with a 211 {mu}m on-center distance. Despite very high radiation doses, the tumors were not sterilized; viable proliferating tumor cells remained present at the tumor margin. This study shows that microbeam width and peak entrance doses strongly influence tumor responses and normal brain toxicity, even if valley doses are kept constant in

  18. Gastrointestinal estromal tumor: Presentation of a case

    International Nuclear Information System (INIS)

    Gil Gonzalez, Alexis; Hernandez Perez, Arnaldo; Gonzalez Rodriguez, Diana; Hernandez Fernandez, Diana M; Castanneda Munnoz, Angela

    2009-01-01

    Since the first descriptions made by Golden and Stout, this group of mesenchymal lesions is considered of muscular origin and they were named as leiomyoma, cellular leiomyoma, epithelioid leiomyoma, leiomyoblastoma, bizarre leiomyoma and leiomyosarcoma. But Mazur and Clark created the term estromal tumor only after they began to use the inmunohistochemistry and subsequently showed the absence of muscular markers, and the occasional presence of neural markers. Nowadays, gastrointestinal estromal tumors are called the primary mesenchymal CD117 positive, fusiform or epithelioid tumors of the gastrointestinal tract, epiplon, mesenterio, and retroperitoneum. The gastrointestinal estromal tumors appear at the wall of the digestive tube: stomach (50-60 %), small intestine (20-30 %), large intestine (10 %) and esophagus (5 %), and occasionally in epiplon, mesenterio, and retroperineum (5 %). In our work we present a 67 year-old patient, entered in our hospital for presenting high digestive bleeding. We studied the case, and found a 6 cm tumor of the gastric fundus. The tumor was operated and the definitive results of the pathologic anatomy showed a gastrointestinal estromal tumor

  19. Peritumoral edema associated with metastatic brain tumor

    International Nuclear Information System (INIS)

    Shirotani, Toshiki; Takiguchi, Hiroshi; Shima, Katsuji; Chigasaki, Hiroo; Tajima, Atsushi; Watanabe, Satoru.

    1992-01-01

    Computed tomographic (CT) examinations were performed in 94 lesions of 50 patients with metastatic brain tumors. Peritumoral edema (A E ) and tumor area (A T ) were measured using the planimetric method on the CT scan films that demonstrated maximum size of the tumor. Then, the volume of the peritumoral edema (V E ) and the surface area of the tumor (S T ) were claculated from these data. Eighty-three brain lesions from lung cancers were subdivided into 49 adenocarcinomas, 11 squamous cell carcinomas, 16 small cell carcinomas and 7 large cell carcinomas. Eleven metastatic tumors from breast cancers were all adenocarcinomas. There was statistical correlation between the surface area of tumor and the volume of the peritumoral edema for the adenocarcinoma (r=0.4043, p E /S T ratios in small cell carcinomas were smaller then those in non-small cell carcinomas, when the volume of the tumor was larger than 10 mm 3 . Accordingly, we suggest that the volume of the peritumoral edema in the small cell carcinoma is generally smaller than that in others. (author)

  20. Dual effects exerted in vitro by micromolar concentrations of deoxynivalenol on undifferentiated caco-2 cells.

    Science.gov (United States)

    Manda, Gina; Mocanu, Mihaela Andreea; Marin, Daniela Eliza; Taranu, Ionelia

    2015-02-16

    Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37-1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

  1. Estimation of the flow resistances exerted in coronary arteries using a vessel length-based method.

    Science.gov (United States)

    Lee, Kyung Eun; Kwon, Soon-Sung; Ji, Yoon Cheol; Shin, Eun-Seok; Choi, Jin-Ho; Kim, Sung Joon; Shim, Eun Bo

    2016-08-01

    Flow resistances exerted in the coronary arteries are the key parameters for the image-based computer simulation of coronary hemodynamics. The resistances depend on the anatomical characteristics of the coronary system. A simple and reliable estimation of the resistances is a compulsory procedure to compute the fractional flow reserve (FFR) of stenosed coronary arteries, an important clinical index of coronary artery disease. The cardiac muscle volume reconstructed from computed tomography (CT) images has been used to assess the resistance of the feeding coronary artery (muscle volume-based method). In this study, we estimate the flow resistances exerted in coronary arteries by using a novel method. Based on a physiological observation that longer coronary arteries have more daughter branches feeding a larger mass of cardiac muscle, the method measures the vessel lengths from coronary angiogram or CT images (vessel length-based method) and predicts the coronary flow resistances. The underlying equations are derived from the physiological relation among flow rate, resistance, and vessel length. To validate the present estimation method, we calculate the coronary flow division over coronary major arteries for 50 patients using the vessel length-based method as well as the muscle volume-based one. These results are compared with the direct measurements in a clinical study. Further proving the usefulness of the present method, we compute the coronary FFR from the images of optical coherence tomography.

  2. A rare case with synchronous gastric gastrointestinal stromal tumor, pancreatic neuroendocrine tumor, and uterine leiomyoma.

    Science.gov (United States)

    Arabadzhieva, Elena; Yonkov, Atanas; Bonev, Sasho; Bulanov, Dimitar; Taneva, Ivanka; Vlahova, Alexandrina; Dikov, Tihomir; Dimitrova, Violeta

    2016-11-15

    Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they comprise less than 1% of all gastrointestinal tumors. Neuroendocrine tumors (NET) of the gastro-enteropancreatic system are also rare, representing about 2% of all gastrointestinal neoplasms. Pancreatic localization of NET is extremely uncommon-these tumors are only 1-5% of all pancreatic cancers. We describe an unusual case with triple tumor localization-a gastric tumor, a formation in the pancreas, which involves the retroperitoneal space, and a uterine leiomyoma. The exact diagnosis was confirmed with immunohistochemical study after surgical treatment of the patient. Distal pancreatic resection, splenectomy, partial gastrectomy, omentectomy, and hysterectomy were performed. The histological examination proved an epithelioid type of gastric GIST. Immunostaining showed focal positive expression of c-kit and no mitotic figures per 50 HPF. Histology of the pancreatic and retroperitoneal formation proved a well-differentiated NET with origin from the islets of Langerhans. The immunohistochemical study demonstrated co-expression of chromogranin A and synaptophysin. This is the fourth case published so far of a patient with synchronous pancreatic NET and gastric GIST. The main objective of the study is to present a unique case because we have not found any reports for coexistence of the described three types of neoplasm, as in our patient, and we hope that it will be valuable in the future investigations about the genesis, diagnosis, and treatment of these types of tumors.

  3. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    International Nuclear Information System (INIS)

    Mori, Kazumasa; Hiroi, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2011-01-01

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163 + cells were significantly increased based on the pathological grade. CD163 + cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163 + cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4 + and CD8 + T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163 + TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC

  4. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  5. Efficacy of Surgical Therapy for Carotid Body Tumors

    Institute of Scientific and Technical Information of China (English)

    Li-shan Lian; Chang-wei Liu; Heng Guan; Yue-hong Zheng; Xing-ming Chen; Yong-jun Li

    2011-01-01

    Objective To evaluate the efficacy of surgical therapy for carotid body tumors.Methods A retrospective analysis was conducted,covering the diagnosis,surgical procedure,post-operative complications,and prognosis of 120 cases of carotid body tumors in Peking Union Medical College Hospital from 1949 to May,2011.Results Surgical excision was successfully performed in 111 cases with 117 tumors.In all those cases,50 underwent simple tumor resection,42 underwent resection of tumors and ligation of the external carotid arteries,7 underwent co-resection of tumors and common carotid arteries,internal carotid arteries,as well as external arteries without vascular reconstruction,and the other 12 cases experienced tumor resection and vascular reconstruction as internal carotid arteries were involved.After operation,3 cases developed cerebral infarction,30 cases showed cranial nerve palsy,including 15 cases of hypoglossal nerve damage,10 cases of vagus paralysis,and 5 cases of Horner's syndrome.Conclusion It is essential to make a proper surgical strategy,which can reduce postoperative complications.

  6. Lactate and pH evaluation in exhausted humans with prolonged TASER X26 exposure or continued exertion.

    Science.gov (United States)

    Ho, Jeffrey D; Dawes, Donald M; Cole, Jon B; Hottinger, Julie C; Overton, Kenneth G; Miner, James R

    2009-09-10

    Safety concerns about TASER Conducted Electrical Weapon (CEW) use and media reports of deaths after exposure have been expressed. CEWs are sometimes used on exhausted subjects to end resistance. The alternative is often a continued struggle. It is unclear if CEW use is metabolically different than allowing a continued struggle. We sought to determine if CEW exposure on exhausted humans caused worsening acidosis when compared with continued exertion. This was a prospective study of human volunteers recruited during a CEW training course. Volunteers were from several different occupations and represented a wide range of ages and body mass index characteristics. Medical histories, baseline pH and lactate values were obtained. Patients were assigned to one of four groups: 2 control groups consisting of Exertion only and CEW Exposure only, and the 2 experimental groups that were Exertion plus CEW Exposure and Exertion plus additional Exertion. Blood sampling occurred after Exertion and after any CEW exposure. This was repeated every 2-min until 20 min after protocol completion. Descriptive statistics were used to compare the four groups. The experimental groups and the control groups were compared individually at each time point using Wilcoxon rank sum tests. Lactate and pH association was assessed using multiple linear regression. Forty subjects were enrolled. There were no median pH or lactate differences between CEW Exposure groups at baseline, or between Exertion protocol groups immediately after completion. The CEW Exposure only group had higher pH and lower lactate values at all time points after exposure than the Exertion only group. After completing the Exertion protocol, there was no difference in the pH or lactate values between the continued Exertion group and the CEW Exposure group at any time points. Subjects who had CEW Exposure only had higher pH and lower lactate values than subjects who completed the Exertion protocol only. CEW exposure does not appear

  7. Epilepsy in primary intracranial tumors in a neurosurgical hospital in ...

    African Journals Online (AJOL)

    2015-04-06

    Apr 6, 2015 ... with epilepsy have a brain tumor,[2,3] as many as 30–50% of patients with ... and another 10–30% develop seizures in the further course of .... Percentage. 46.3 .... tumors,[32] the prophylactic use of AEDs are still common. We.

  8. Cone-Beam Computed Tomography (CBCT) Hepatic Arteriography in Chemoembolization for Hepatocellular Carcinoma: Performance Depicting Tumors and Tumor Feeders

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Joon [National Cancer Center, Department of Radiology (Korea, Republic of); Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Yin, Yong Hu; Kim, Hyo-Cheol; Kim, Young Il; Jae, Hwan Jun; Park, Jae Hyung [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology (Korea, Republic of)

    2015-10-15

    PurposeThis study was designed to analyze retrospectively the performance of cone-beam computed tomography (CBCT) hepatic arteriography in depicting tumors and their feeders and to investigate the related determining factors in chemoembolization for hepatocellular carcinoma (HCC).MethodsEighty-six patients with 142 tumors satisfying the imaging diagnosis criteria of HCC were included in this study. The performance of CBCT hepatic arteriography for chemoembolization per tumor and per patient was evaluated using maximum intensity projection images alone (MIP analysis) or MIP combined with multiplanar reformation images (MIP + MPR analysis) regarding the following three aspects: tumor depiction, confidence of tumor feeder detection, and trackability of tumor feeders. Tumor size, tumor enhancement, tumor location, number of feeders, diaphragmatic motion, portal vein enhancement, and hepatic artery to parenchyma enhancement ratio were regarded as potential determining factors.ResultsTumors were depicted in 125 (88.0 %) and 142 tumors (100 %) on MIP and MIP + MPR analysis, respectively. Imaging performances on MIP and MIP + MPR analysis were good enough to perform subsegmental chemoembolization without additional angiographic investigation in 88 (62.0 %) and 128 tumors (90.1 %) on per-tumor basis and in 43 (50 %) and 73 (84.9 %) on per-patient basis, respectively. Significant determining factors for performance in MIP + MPR analysis on per tumor basis were tumor size (p = 0.030), tumor enhancement (0.005), tumor location (p = 0.001), and diaphragmatic motion (p < 0.001).ConclusionsCBCT hepatic arteriography provided sufficient information for subsegmental chemoembolization by depicting tumors and their feeders in the vast majority of patients. Combined analysis of MIP and MPR images was essential to enhance the performance of CBCT hepatic arteriography.

  9. Morphologic classification of ductal breast tumors on ultrasound : differential diagnosis of benign and malignant tumors

    International Nuclear Information System (INIS)

    Won, Mi Sook; Chung, Soo Young; Yang, Ik; Lee, Yul; Park, Hai Jung; Lee, Myoung Hwan; Yoon, In Sook; Koh, Mi Gyoung

    1997-01-01

    To evaluate the morphologic differential diagnosis of benign and malignant ductal breast tumors, as seen on US US findings in 29 pathologically proven cases of ductal breast tumor were retrospectively reviewed. All patients were female and their mean age was 42 years. Nineteen tumors were benign and ten were malignant, and all ductal or cystic lesions showed solid masses. According to the location of the mural nodule, we classified the sonographic appearance of these tumors into three types:intraductal, intracystic and amorphic. The intraductal type was divided into three subtypes:incompletely obstructive, completely obstructive and multiple mural nodules. For the intracystic type, too, three subtypes were designated:the intracystic mural nodule (mural cyst), intracystic mural nodule with the duct (mural cyst+duct) and intracystic multiple mural nodules. The amorphic type is defined as an atypical ductal tumor with the mural nodule extending into adjacent parenchyma. The margin of the duct or cyst was smooth in 68.4% of benign, and irregular in 90% of malignant ductal tumors. Internal echogeneity of the duct or cyst usually showed homogeneity in both benign and malignant tumors. 73.7% of tumors connecting the duct were benign and 50% were malignant. In benign tumors, 52.6% of mural nodule had an irregular margin, while in malignant tumors, the corresponding proportion was 100%;both types usually showed heterogeneous hypoechogeneity. Among benign tumors, the most common morphologic type was the intraductal incompletely obstructive subtype (36.8%);among those that were malignant, the amorphic type was most common, accounting for 40% of tumors. No amorphic type was benign and no incompletely obstructive subtype was malignant. When ductal breast tumors are morphologically classified on the basis of sonographic findings, the intraductal incompletely obstructive subtype suggests benignancy, and the amorphic type, malignancy. The morphologic classification of ductal

  10. Lung metastasis fails in MMTV-PyMT oncomice lacking S100A4 due to a T-cell deficiency in primary tumors

    DEFF Research Database (Denmark)

    Grum-Schwensen, Birgitte; Klingelhöfer, Jörg; Grigorian, Mariam

    2010-01-01

    significantly reduced the metastatic burden in lungs of PyMT-induced mammary tumors. In S100A4(+/+) PyMT mice, massive leukocyte infiltration at the site of the growing tumor at the stage of malignant transition was associated with increased concentration of extracellular S100A4 in the tumor microenvironment......Interactions between tumor and stroma cells are essential for the progression of cancer from its initial growth at a primary site to its metastasis to distant organs. The metastasis-stimulating protein S100A4 exerts its function as a stroma cell-derived factor. Genetic depletion of S100A4...... monolayers. In vivo, the presence of S100A4(+/+), but not S100A4(-/-), fibroblasts significantly stimulated the attraction of T lymphocytes to the site of the growing tumor. Increased levels of T cells were also observed in the premetastatic lungs of tumor-bearing mice primed to metastasize by S100A4...

  11. The Effects of Direction of Exertion, Path, and Load Placement in Nursing Cart Pushing and Pulling Tasks: An Electromyographical Study.

    Science.gov (United States)

    Kao, Huei Chu; Lin, Chiuhsiang Joe; Lee, Yung Hui; Chen, Su Huang

    2015-01-01

    The purpose of this study was to explore the effects of direction of exertion (DOE) (pushing, pulling), path (walking in a straight line, turning left, walking uphill), and load placement (LP) (the 18 blocks were indicated by X, Y and Z axis; there were 3 levels on the X axis, 2 levels on the Y axis, and 3 levels on the Z axis) on muscle activity and ratings of perceived exertion in nursing cart pushing and pulling tasks. Ten participants who were female students and not experienced nurses were recruited to participate in the experiment. Each participant performed 108 experimental trials in the study, consisting of 2 directions of exertion (push and pull), 3 paths, and 18 load placements (indicated by X, Y and Z axes). A 23kg load was placed into one load placement. The dependent variables were electromyographic (EMG) data of four muscles collected bilaterally as follows: Left (L) and right (R) trapezius (TR), flexor digitorum superficialis (FDS), extensor digitorum (ED), and erector spinae (ES) and subjective ratings of perceived exertion (RPE). Split-split-plot ANOVA was conducted to analyze significant differences between DOE, path, and LP in the EMG and RPE data. Pulling cart tasks produced a significantly higher activation of the muscles (RTR:54.4%, LTR:50.3%, LFDS:57.0%, LED:63.4%, RES:40.7%, LES:36.7%) than pushing cart tasks (RTR:42.4%, LTR:35.1%, LFDS:32.3%, LED:55.1%, RES:33.3%, LES:32.1%). A significantly greater perceived exertion was found in pulling cart tasks than pushing cart tasks. Significantly higher activation of all muscles and perceived exertion were observed for walking uphill than walking in a straight line and turning left. Significantly lower muscle activity of all muscles and subject ratings were observed for the central position on the X axis, the bottom position on the Y axis, and the posterior position on the Z axis. These findings suggest that nursing staff should adopt forward pushing when moving a nursing cart, instead of backward

  12. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

    Science.gov (United States)

    Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

    2011-08-01

    The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

  13. Relationships between recall of perceived exertion and blood lactate concentration in a judo competition.

    Science.gov (United States)

    Serrano, M A; Salvador, A; González-Bono, E G; Sanchís, C; Suay, F

    2001-06-01

    Relationships between perceived exertion and blood lactate have usually been studied in laboratory or training contexts but not in competition, the most important setting in which sports performance is evaluated. The purpose of this study was to examine the relationships between psychological and physiological indices of the physical effort in a competition setting, taking into account the duration of effort. For this, we employed two Ratings of Perceived Exertion (RPE and CR-10) and lactic acid plasma concentration as a biological marker of the effort performed. 13 male judo fighters who participated in a sports club competition provided capillary blood samples to assay lactate concentrations and indicated on scale their Recall of Perceived Exertion in the total competition and again in just the Last Fight to compare the usefulness of RPE and CR-10 in assessing discrete bouts of effort and a whole session. Analysis showed that perceived exertion or the effort made during the whole competition was positively and significantly related to maximal lactate concentration and lactate increase in competition, thus extending the validity of this scale to sports contests. The Recall of Perceived Exertion scores were not significantly correlated with the duration of effort.

  14. The effect of low-dose total body irradiation on tumor control

    International Nuclear Information System (INIS)

    Sakamoto, Kiyohiko; Miyamoto, Miyako; Watabe, Nobuyuki.

    1987-01-01

    Total body irradiation (TBI) is considered to bring about an immunosuppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. However, there are no data on how low-dose TBI affects an organism. Over the last five years, we have been studying the effects of low-dose TBI on normal or tumor-bearing mice and the immunological background of these effects. In experimental studies, an increase in the TD50 value (the number of cells required for a tumor incidence of 50 %) in mice exposed to 10 rad was recognized and showed a remarkable increase at 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. In order to clarify the mechanism of this kind of effect, some immunological studies were performed using several immunological procedures, and the results suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials in some patients with advanced tumors are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising, although it is too early to draw conclusions. (author)

  15. The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action.

    Science.gov (United States)

    Griveau, A; Devailly, G; Eberst, L; Navaratnam, N; Le Calvé, B; Ferrand, M; Faull, P; Augert, A; Dante, R; Vanacker, J M; Vindrieux, D; Bernard, D

    2016-09-22

    Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

  16. Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and İmmunity with Special Emphasis for Brain Tumors.

    Science.gov (United States)

    Altinoz, Meric Adil; Elmaci, Ilhan; Ince, Bahri; Ozpinar, Aysel; Sav, Aydin Murat

    2016-05-01

    In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS). HBs mediate coping with hypoxia and free radical stress in normal and tumor cells, and they are increased in certain tumors including breast, lung, colon, and squamous cell cancers. Recent studies showed HBs in meningioma, in the cyst fluid of craniopharyngioma, in the cerebrospinal fluid (CSF) of pediatric patients with posterior fossa tumors, and in glioblastoma cell lines. Hemorphins, abundant brain peptides formed via HB-chain cleavage, exert opioid activity and antiproliferative and immunomodifier effects. Hence mutations in HBs may modify brain tumorigenesis via influencing hemorphins and perturbing regulations of immune surveillance and cell growth in the neuroectodermal tissues. The β-globin gene cluster resides in the chromosome region 11p15.5, harboring important immunity genes and IGF2, H19, PHLDA2/TSSC3, TRIM3, and SLC22A18 genes associated with cancers and gliomas. 11p15.5 is a prominent region subject to epigenetic regulation. Thus the β-globin loci may exert haplotypal interactions with these. Some clues support this theory. It is well established that iron load induces liver cancer in thalassemia major; however iron load-independent associations also exist. Enhanced rates of hematologic malignancies are associated with HB Lepore, association of hemoglobin E with cholangiocarcinoma, and enhanced gastric cancer rates in the thalassemia trait. In

  17. Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

    African Journals Online (AJOL)

    Original Research Article. Juglans regia Hexane Extract Exerts Antitumor Effect,. Apoptosis Induction and Cell Circle Arrest in Prostate. Cancer Cells In vitro. Wei Li1, De-Yuan Li2*, ... composition of walnut is juglone (5-hydroxy-1, 4- naphthoquinone), the .... extract was confirmed by studying apoptotic body formation using ...

  18. Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways.

    Science.gov (United States)

    Jiang, Rulan; Lönnerdal, Bo

    2017-02-01

    Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

  19. Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis.

    Science.gov (United States)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette; Zahl, Per-Henrik

    2017-03-07

    Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Cohort study. Denmark from 1980 to 2010. Women aged 35 to 84 years. Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times. Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas. Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]). Regional differences complicate interpretation. Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%). None.

  20. Tumoral calcinosis with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Kannan Subramanian

    2008-01-01

    Full Text Available A 50-year-old woman presented with recurrent calcified mass in the left gluteal region. The clinical, radiological, and biochemical profile confirmed the diagnosis of tumoral calcinosis. She also had associated vitamin D deficiency. The patient underwent surgical removal of the mass to relieve the sciatic nerve compression and was managed with acetazolamide, calcium carbonate, and aluminium hydroxide gel with which she showed significant improve-ment. The management implications and effect of vitamin D deficiency on phosphate metabolism in the setting of tumoral calcinosis is discussed.

  1. meta-analysis of Serum Tumor Markers in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xianfeng LU

    2010-12-01

    Full Text Available Background and objective The detection of serum tumor markers is of great value for early diagnosis of lung cancer. The aim of this study is to summarize the clinic significance characteristics of serum markers contributing to the detection of lung cancer. Methods References about serum markers of lung cancer were estimated using meta-analysis method. 712 references which included more than 20 cases, 20 controls, the serum markers of 52 832 patients with malignancies and 32 037 patients as controls were evaluated. Results Overall the detection of 13 markers play a significant part in lung cancer diagnosis. The sensitivity of CEA, CA125, CYFRA21-1, TPA, SCCAg, DKK1, NSE, ProGRP in the patients’ serum with lung cancer were 47.50%, 50.11%, 57.00%, 50.93%, 49.00%, 69.50%, 39.73%, 51.48% and the specificity were 92.34%, 80.19%, 90.16%, 88.41%, 91.07%, 92.20%, 89.11%, 94.89%. In the combined analysis of tumor markers: the sensitivity, specificity of NSE+ProGRP were 88.90% and 72.82% in diagnosis of small cell lung cancer, respectively. In diagnosis of squamous corcinoma, the sensitivity and specificity of TSGF+SCCAg+CYFRA21-1 were 95.30% and 74.20%. The the sensitivity and specificity of CA153+Ferrtin+CEA were 91.90% and 44.00% in diagnosis of lung cancer. Conclusion Although the assay of tumor markers in serum is useful for diagnosis of early lung cancer, the sensitivity and specificity are low. Combined detection of these tumor markers could increase sensitivity and specificity.

  2. Three-dimensional quantitation of pediatric tumor bulk

    International Nuclear Information System (INIS)

    Eggli, K.D.; Close, P.; Dillon, P.W.; Umlauf, M.; Hopper, K.D.

    1995-01-01

    Will 3-dimensional (3-D) volumetric determination improve our ability to assess tumor response to therapy? Forty-five CT scans of pediatric patients with unresectable thoracic or abdominal neoplasia were assessed for tumor bulk by the standard ''2-dimensional (2-D)'' volume formula (cross-sectional areaxlength) and by 3-D volumetric analysis. Thirty-two examinations were performed in follow-up, and percent change in tumor size was calculated. The 2-D volume calculation overestimated tumor volume by more than 50% on all but two examinations when the 2-D volume was compared with the 3-D volume. In 28% of follow-up examinations, the 2-D calculation of percent change differed by more than 10% from the 3-D volume. Fifteen percent differed by over 25%. This changed the response category of one patient from ''no response'' to ''partial response''. 3-D volumetric analysis, give more accurate assessment of the actual tumor bulk and its subsequent changes in size in response to therapy. (orig.)

  3. Interdependence of the rad50 hook and globular domain functions.

    Science.gov (United States)

    Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

    2015-02-05

    Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Forces exerted by jumping children: A pilot study

    NARCIS (Netherlands)

    Moes, C.C.M.; Bakker, H.E.

    1998-01-01

    This article reports on a pilot study of the loads exerted vertically by children when jumping. The subjects of the study were 17 children, aged from two to twelve years. Measurements were made using video recordings and a force-plate. The influence of the stiffness of the base and of jumping with

  5. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor.

    Science.gov (United States)

    Adachi, Keishi; Kano, Yosuke; Nagai, Tomohiko; Okuyama, Namiko; Sakoda, Yukimi; Tamada, Koji

    2018-04-01

    Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 × 19 CAR-T cell therapy. Depletion of recipient T cells before 7 × 19 CAR-T cell administration dampened the therapeutic effects of 7 × 19 CAR-T cell treatment, suggesting that CAR-T cells and recipient immune cells collaborated to exert anti-tumor activity. Following treatment of mice with 7 × 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.

  6. High self-perceived exercise exertion before bedtime is associated with greater objectively assessed sleep efficiency.

    Science.gov (United States)

    Brand, Serge; Kalak, Nadeem; Gerber, Markus; Kirov, Roumen; Pühse, Uwe; Holsboer-Trachsler, Edith

    2014-09-01

    To assess the association between self-perceived exercise exertion before bedtime and objectively measured sleep. Fifty-two regularly exercising young adults (mean age, 19.70 years; 54% females) underwent sleep electroencephalographic recordings 1.5 h after completing moderate to vigorous exercise in the evening. Before sleeping, participants answered questions regarding degree of exertion of the exercise undertaken. Greater self-perceived exertion before bedtime was associated with higher objectively assessed sleep efficiency (r = 0.69, P associated with more deep sleep, shortened sleep onset time, fewer awakenings after sleep onset, and shorter wake duration after sleep onset. Multiple linear regression analysis showed that objective sleep efficiency was predicted by increased exercise exertion, shortened sleep onset time, increased deep sleep, and decreased light sleep. Against expectations and general recommendations for sleep hygiene, high self-perceived exercise exertion before bedtime was associated with better sleep patterns in a sample of healthy young adults. Further studies should also focus on elderly adults and adults suffering from insomnia. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Benign vascular sexual headache and exertional headache: interrelationships and long term prognosis.

    OpenAIRE

    Silbert, P L; Edis, R H; Stewart-Wynne, E G; Gubbay, S S

    1991-01-01

    There is a definite relationship between the vascular type of benign sexual headache and benign exertional headache. Forty five patients with benign vascular sexual headache were reviewed. Twenty seven (60%) experienced benign vascular sexual headache alone and eighteen (40%) had experienced both benign vascular sexual headache and benign exertional headache on at least one occasion. The mean age was 34.3 years with a male:female ratio of 5.4:1. Thirty patients with a history of benign vascul...

  8. Tumores de la nasofaringe en la infancia

    Directory of Open Access Journals (Sweden)

    José Vargas Díaz

    2002-03-01

    Full Text Available Los tumores de la nasofaringe son poco frecuentes en la infancia. Su forma clínica de presentación característica y la posibilidad de realizar un diagnóstico temprano e indicar el tratamiento oportuno, permitiría modificar favorablemente la evolución y el pronóstico de estos pacientes. Se reporta una serie de 4 niños con tumores de la nasofaringe (2 linfoepiteliomas y 2 neuroblastomas atendidos en el Hospital Infantil Docente "Pedro Borrás Astorga". Todos los pacientes mostraron en algún momento de su evolución obstrucción nasal unilateral y epistaxis. El 50 % de los casos comenzó su enfermedad presentando cefaleas y uno de ellos lo hizo con compromiso de pares craneales (VII, VI, IV, VI. La radioterapia representa la modalidad de tratamiento más útil y la resonancia magnética nuclear resulta de gran valor para el diagnóstico inicial, así como para la identificación de la recidiva tumoral.Nasopharyngeal tumors are infrequent in childhood. Their characteristic clinical presentation and the possibility of making an early diagnosis and indicating an adequate treatment will allow positively changing the development and prognosis of the patients. Four children with nasopharyngeal tumors (two lymphoepitheliomas and two neuroblastomas, who were seen at "Pedro Borrás Astorga" Teaching Pediatric Hospital, are reported. All the patients showed at some moment of the disease development unilateral nasal obstruction and epistaxis. 50% of the cases had headaches at the beginning of the disease whereas one of them had involvement of cranial pairs (7th,6th, 4th,6th. Radiotherapy represents the most useful treatment and nuclear magnetic resonance is of great value for the initial diagnosis and the identification of tumor relapse.

  9. Exertional Rhabdomyolysis in a 21-Year-Old Healthy Woman: A Case Report.

    Science.gov (United States)

    McKay, Brianna D; Yeo, Noelle M; Jenkins, Nathaniel D M; Miramonti, Amelia A; Cramer, Joel T

    2017-05-01

    McKay, BD, Yeo, NM, Jenkins, NDM, Miramonti, AA, and Cramer, JT. Exertional rhabdomyolysis in a 21-year-old healthy woman: a case report. J Strength Cond Res 31(5): 1403-1410, 2017-The optimal resistance training program to elicit muscle hypertrophy has been recently debated and researched. Although 3 sets of 10 repetitions at 70-80% of the 1 repetition maximum (1RM) are widely recommended, recent studies have shown that low-load (∼30% 1RM) high-repetition (3 sets of 30-40 repetitions) resistance training can elicit similar muscular hypertrophy. Incidentally, this type of resistance training has gained popularity. In the process of testing this hypothesis in a research study in our laboratory, a subject was diagnosed with exertional rhabdomyolysis after completing a resistance training session that involved 3 sets to failure at 30% 1RM. Reviewed were the events leading up to and throughout the diagnosis of exertional rhabdomyolysis in a healthy recreationally-trained 21-year-old woman who was enrolled in a study that compared the acute effects of high-load low-repetition vs. low-load high-repetition resistance training. The subject completed a total of 143 repetitions of the bilateral dumbbell biceps curl exercise. Three days after exercise, she reported excessive muscle soreness and swelling and sought medical attention. She was briefly hospitalized and then discharged with instructions to take acetaminophen for soreness, drink plenty of water, rest, and monitor her creatine kinase (CK) concentrations. Changes in the subject's CK concentrations, ultrasound-determined muscle thickness, and echo intensity monitored over a 14-day period are reported. This case illustrates the potential risk of developing exertional rhabdomyolysis after a low-load high-repetition resistance training session in healthy, young, recreationally-trained women. The fact that exertional rhabdomyolysis is a possible outcome may warrant caution when prescribing this type of resistance

  10. Prevalence of bone and soft tissue tumors.

    Science.gov (United States)

    Yücetürk, Güven; Sabah, Dündar; Keçeci, Burçin; Kara, Ahmet Duran; Yalçinkaya, Selçuk

    2011-01-01

    Multidisciplinary approach is a necessity for the appropriate diagnosis and treatment of bone and soft tissue tumors. The Ege University Musculoskeletal Tumor Council offers consultation services to other hospitals in the Aegean region. Since 1988 the Council has met weekly and spent approximately 1,500 hours evaluating almost 6,000 patients with suspected skeletal system tumors. Our objective was to present the data obtained from this patient group. A total of 5,658 patients, suspected to have a musculoskeletal tumor, were evaluated retrospectively. Multiple records of the patients due to multiple attendance to the Council were excluded. The prevalance of the bone and soft tissue tumors in these patients were analysed. Malignant mesenchymal tumors accounted for 39.7% of the total patients, benign tumors for 17%, tumor-like lesions for 17.8% and metastatic carsinomas for 8.6%. Malignant bone tumors were 50.2% and malignant soft tissue tumors were 49.8% of all the sarcomas. Among the malignant bone tumors the most common was osteosarcomas at a rate of 33.6%, followed by Ewing-PNET at 25.5%, chondrosarcomas at 19.4% and haematopoietic tumors at 17.6%. Pleomorphic sarcomas (24.5%), liposarcoma (16.4%), synovial sarcoma (13%) and undifferential sarcomas (8.8%) were the most common types of malignant sof tissue tumors. Benign soft tissue tumors (48%), benign cartilage tumors (28%), giant cell tumor (15%) and osteogenic tumors (9%) were found among the benign tumors. Hemangioma, lipoma, agressive fibromatosis, enchondroma, solitary chondroma and osteoid osteoma were the most common tumors in their groups. Lung (27%), breast (24%), gastrointestinal system (10.5%) and kidney (8.2%) carcinomas were the most common primary sites of the bone metastasis. Turkey still lacks a comprehensive series indicating the incidence and diagnostic distribution of bone and soft tissue tumors. The presented data would add to our knowledge on the specific rates of the bone and soft tissue

  11. Gastrointestinal stromal tumor: a case report and review of the literature

    International Nuclear Information System (INIS)

    Macedo, Leonardo Lopes de; Torres, Lucas Rios; Faucz, Rafael Artigas; Tornin, Olger de Souza; Souza, Ricardo Pires de; Fonseca, Carlos Alberto Marcovechio

    2006-01-01

    Gastrointestinal stromal tumors are the most common mesenchymal tumors and are characterized by expression of KIT (CD117), a tyrosine-kinase growth factor receptor. They occur in individuals over 50 years of age and commonly arise in stomach or in the small intestine. To emphasize our paper we report a case of gastrointestinal stromal tumor that showed the typical image and pathologic findings of the primary lesion and its metastases. (author)

  12. Effect of fractionated radiotherapy using a hypoxic cell radiosensitizer, RK-28, on experimental murine tumor

    International Nuclear Information System (INIS)

    Tanaka, Shukaku

    1990-01-01

    The effect of a hypoxic cell radiosensitizer RK-28, on fractionated radiotherapy was studied using mice with implanted tumors. Experimental animal tumors were third generation isoplants of a mammary carcinoma which arose spontaneously in a C 3 H/He mouse. RK-28 was given to the mice at two dosages: 0.4 mg/g,b.wt. and 0.2 mg/g.b.wt. Total dose of irradiation was 20 Gy which was divided into the first 10 Gy irradiation and the second 10 Gy performed after a proper time interval such as 1, 24, 48 and 72 hours after the first 10 Gy irradiation. Tumor growth was evaluated by TGT 50 /3 times, which was defined as the time required for 50% of the tumors to regrow to the 3 times value of its initial volume. Tumor volume was measured every day and TGT 50 /3 times was calculated by logit analysis method. No significant differences were found in the TGT 50 /3 times among the groups treated by radiation alone, those treated by RK-administration alone and those without any treatment. TGT 50 value of control group without any treatment was 3.40 (days). TGT 50 value of another group treated by RK-28 alone was 3.46. and TGT 50 value of 20 Gy X-ray irradiation alone was 10.23. Under the fractionated X-ray irradiation alone, TGT 50 values of the various time interval such as 9, 14, 48 and 72 hours were 11.26, 10.42, 12.14 and 1.10. Under the combined treatment of the fractionated X-ray irradiation and RK-28 administration, TGT 50 values were 17.84, 16.42, 16.59 and 17.49. These TGT 50 /3 times values showed that RK-28 had a radiosensitizing effect when given with fractionated radiotherapy even at lower doses of RK-28 administration and radiation. Therefore, it was suggested that fractionated radiotherapy using RK-28 was useful in the cancer treatment. (author) 52 refs

  13. Tumores cardíacos primarios

    Directory of Open Access Journals (Sweden)

    Rosa Eugenia Díaz Garriga

    2013-10-01

    Full Text Available Introducción: los tumores cardíacos primarios son aquellos que se originan en Miocardio o Pericardio. El 90% son benignos, no son invasivos, pero debido a su localización pueden provocar alteraciones hemodinámicas graves y arrítmias. Presentación del caso: dos casos portadores de tumores cardíacos diagnosticados en la etapa prenatal, una gestante de 32 años, portadora de una Neurofribromatosis que en la ecocardiografía fetal de su hijo, se identifican dos tipos de tumores cardíacos, un mixoma auricular y un fibroma, y un niño que desde la etapa prenatal se diagnosticó un rabdomioma, lo cual se confirmó al nacimiento y que regresó espontáneamente. Conclusiones: a ecocardiografía fetal permite cada vez con más frecuencia, el diagnóstico intraútero de tumores cardíacos. Los rabdomiomas regresan en más del 50% de los casos, pero pueden ser un marcador de Esclerosis Tuberosa. Los tumores cardiacos se asocian a otras afecciones congénitas y requieren de tratamiento quirúrgico. Aspectos todos a tener en consideración para realizar el asesoramiento genético a la familia.

  14. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

    2004-01-01

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  15. Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-02-01

    Full Text Available Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON, raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37–1.50 μM, relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

  16. Stereotactic gamma radiosurgery of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Tatsuya; Kida, Yoshihisa; Tanaka, Takayuki; Oyama, Hirofumi; Yoshida, Kazuo; Maesawa, Satoshi; Kai, Osamu; Nakamura, Mototoshi; Arahata, Masashige [Komaki City Hospital, Aichi (Japan)

    1996-06-01

    One thousand cases with various head and neck diseases have been treated by gamma radiosurgery at Komaki City Hospital since May 1991. Five hundred and sixty-eight out of 1,000 cases were neoplastic lesions which consisted of 173 cases of neurinoma, 108 of metastatic tumors, 103 of meningioma, 69 of gliomas, 27 of pituitary adenoma, 26 of craniopharyngioma, 13 of pineal tumors, 11 of chordoma, 6 of malignant lymphoma, 5 of hemangioblastoma and so on. The most effective result has been shown in metastatic brain tumors. The complete response (disappearance of the lesion) was obtained in more than 50% of the treated lesions, and the control rate of 85% was maintained for more than 12 months. Next effective results were shown in craniopharyngioma, malignant pineal tumors and malignant lymphoma. There was a group which showed moderate response but no tumor disappearance. Those were pituitary adenoma, acoustic neurinoma, meningioma and chordoma. Gliomas showed less response and even progression of tumor at relatively higher rate. It has been found that malignant gliomas showed difficult control of the tumor and progression rate of 70%, while benign gliomas showed the control rate of more than 90%. Besides intracranial lesions, malignant skull base tumors such as chordoma, naso-pharyngeal cancer, adenoid cystic cancer showed better response to gamma radiosurgery and higher control rate for longer period of time with high QOL compaired to conventional irradiation. (author)

  17. Tumor-specific antivascular effect of TZT-1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy

    International Nuclear Information System (INIS)

    Natsume, Tsugitaka; Watanabe, Junichi; Kobayashi, Motohiro; Ogawa, Kenji; Yasumura, Kazuhiko

    2007-01-01

    TZT-1027 (soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect. (author)

  18. Clinical application and research of tumor markers in colorectal cancer

    International Nuclear Information System (INIS)

    Chen Yumei

    2005-01-01

    Colorectal cancer is one of the most common malignant tumors. There are many tumor markers for detecting colorectal cancer, some of which have been widely used in clinical area. However, still lack an ideal tumor marker of colorectal cancer. In this review, we simply characterized some common tumor markers including carcinoembryonic antigen, CA19-9, CA50, CA242 etc and their dignostic value. And here we discussed some combined detecting procedures which improve diagnostic accuracy of colorectal cancer. In addition, with the development of the biomoleculer technique, some newly discovered tumor markers and genetic marekers have gained great progress in the research of colorectal cancer, and will become a promissing technique in the diagnosis of colorectal cancer. (authors)

  19. Electron beam combined with hydrothermal treatment for enhancing the enzymatic convertibility of sugarcane bagasse

    International Nuclear Information System (INIS)

    Duarte, C.L.; Ribeiro, M.A.; Oikawa, H.; Mori, M.N.; Napolitano, C.M.; Galvão, C.A.

    2012-01-01

    The use of microbial cellulolytic enzymes is the most efficient process to liberate glucose from cellulose in biomass without the formation of fermentation inhibitors. A combination of pretreatment technologies is an alternative way to increase the access of enzymes to cellulose, and consequently, the conversion yield. In this way, the present study reports on the enzymatic hydrolysis of SCB submitted to three kinds of pretreatment: electron beam processing (EBP), and EBP followed by hydrothermal (TH) and diluted acid (AH) treatment. SCB samples were irradiated using a radiation dynamics electron beam accelerator, and then submitted to thermal and acid (0.1% sulfuric acid) hydrolysis for 40 and 60 min at 180 °C. These samples were submitted to enzymatic hydrolysis (EH) using commercial preparations, including Celluclast 1.5 L and beta-glycosidase. The addition of diluted acid improved TH treatment allowing for a shorter application time. EBP with 50 kGy increased the enzymatic hydrolysis yield of cellulose by 20% after TH and 30% after AH. - Highlights: ► We study the enzymatic hydrolysis of cellulose and hemicellulose in sugarcane bagasse. ► We study the combination of three pretreatments: electron beam processing, EBP followed by hydrothermal and by diluted acid treatment. ► The electron beam processing increased the enzymatic hydrolysis from 8% to 15% with 20 kGy. ► The enzymes used were commercial preparations, as Celluclast 1.5 L and β-glycosidase. ► The EBP with 50 kGy increased on 20% the yield of EH of cellulose after TH and 30% after AH.

  20. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    Science.gov (United States)

    Shrotriya, Shiva; Walsh, Declan; Bennani-Baiti, Nabila; Thomas, Shirley; Lorton, Cliona

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence. MeSH (Medical Subject Heading) terms were used to search multiple electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, EBM-Cochrane). Two independent reviewers selected research papers. We also included a quality Assessment (QA) score. Reports with QA scores <50% were excluded. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology was utilized for this review (S1 PRISMA Checklist). 271 articles were identified for final review. There were 45% prospective studies and 52% retrospective. 264 had intermediate QA score (≥50% but <80%); Seven were adequate (80% -100%); A high CRP was predictive of prognosis in 90% (245/271) of studies-80% of the 245 studies by multivariate analysis, 20% by univariate analysis. Many (52%) of the articles were about gastrointestinal malignancies (GI) or kidney malignancies. A high CRP was prognostic in 90% (127 of 141) of the reports in those groups of tumors. CRP was also prognostic in most reports in other solid tumors primary sites. A high CRP was associated with higher mortality in 90% of reports in people with solid tumors primary sites. This was particularly notable in GI malignancies and kidney malignancies. In other solid tumors (lung, pancreas, hepatocellular cancer, and bladder) an elevated CRP also predicted prognosis. In addition there is also evidence to support the use of CRP to help decide treatment response and identify tumor recurrence. Better designed large scale studies should be conducted to examine these issues more comprehensively.

  1. Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force, and Marine Corps, 2011-2015.

    Science.gov (United States)

    Armed Forces Health Surveillance Branch

    2016-03-01

    Among active component members of the U.S. Army, Navy, Air Force, and Marine Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and 2015. In 2015, the highest incidence rates occurred in service members who were male; younger than 20 years of age; black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

  2. Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

    International Nuclear Information System (INIS)

    Liniecki, J.; Rembelska, M.; Koniarek, B.

    1983-01-01

    Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

  3. IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells

    Science.gov (United States)

    Fisher, Daniel T.; Chen, Qing; Skitzki, Joseph J.; Muhitch, Jason B.; Zhou, Lei; Appenheimer, Michelle M.; Vardam, Trupti D.; Weis, Emily L.; Passanese, Jessica; Wang, Wan-Chao; Gollnick, Sandra O.; Dewhirst, Mark W.; Rose-John, Stefan; Repasky, Elizabeth A.; Baumann, Heinz; Evans, Sharon S.

    2011-01-01

    Immune cells are key regulators of neoplastic progression, which is often mediated through their release of cytokines. Inflammatory cytokines such as IL-6 exert tumor-promoting activities by driving growth and survival of neoplastic cells. However, whether these cytokines also have a role in recruiting mediators of adaptive anticancer immunity has not been investigated. Here, we report that homeostatic trafficking of tumor-reactive CD8+ T cells across microvascular checkpoints is limited in tumors despite the presence of inflammatory cytokines. Intravital imaging in tumor-bearing mice revealed that systemic thermal therapy (core temperature elevated to 39.5°C ± 0.5°C for 6 hours) activated an IL-6 trans-signaling program in the tumor blood vessels that modified the vasculature such that it could support enhanced trafficking of CD8+ effector/memory T cells (Tems) into tumors. A concomitant decrease in tumor infiltration by Tregs during systemic thermal therapy resulted in substantial enhancement of Tem/Treg ratios. Mechanistically, IL-6 produced by nonhematopoietic stromal cells acted cooperatively with soluble IL-6 receptor–α and thermally induced gp130 to promote E/P-selectin– and ICAM-1–dependent extravasation of cytotoxic T cells in tumors. Parallel increases in vascular adhesion were induced by IL-6/soluble IL-6 receptor–α fusion protein in mouse tumors and patient tumor explants. Finally, a causal link was established between IL-6–dependent licensing of tumor vessels for Tem trafficking and apoptosis of tumor targets. These findings suggest that the unique IL-6–rich tumor microenvironment can be exploited to create a therapeutic window to boost T cell–mediated antitumor immunity and immunotherapy. PMID:21926464

  4. Axon Regeneration Is Regulated by Ets-C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Chun Li

    2015-10-01

    Full Text Available The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. In Caenorhabditis elegans, the JNK and p38 MAPK pathways are important for axon regeneration. Axonal injury induces expression of the svh-2 gene encoding a receptor tyrosine kinase, stimulation of which by the SVH-1 growth factor leads to activation of the JNK pathway. Here, we identify ETS-4 and CEBP-1, related to mammalian Ets and C/EBP, respectively, as transcriptional activators of svh-2 expression following axon injury. ETS-4 and CEBP-1 function downstream of the cAMP and Ca2+-p38 MAPK pathways, respectively. We show that PKA-dependent phosphorylation of ETS-4 promotes its complex formation with CEBP-1. Furthermore, activation of both cAMP and Ca2+ signaling is required for activation of svh-2 expression. Thus, the cAMP/Ca2+ signaling pathways cooperatively activate the JNK pathway, which then promotes axon regeneration.

  5. Imaging melanin cancer growth in-vivo using raster-scan optoacoustic mesoscopy (RSOM) at 50 MHz and 100 MHz

    Science.gov (United States)

    Omar, Murad; Schwarz, Mathias; Soliman, Dominik; Symvoulidis, Panagiotis; Ntziachristos, Vasilis

    2016-03-01

    We used raster-scan optoacoustic mesoscopy (RSOM) at 50 MHz, and at 100 MHz, to monitor tumor growth, and tumor angiogenesis, which is a central hallmark of cancer, in-vivo. In this study we compared the performance, and the effect of the 50 MHz, and the 100 MHz frequencies on the quality of the final image. The system is based on a reflection-mode implementation of RSOM. The detectors used are custom made, ultrawideband, and spherically focused. The use of such detectors enables light coupling from the same side as the detector, thus reflection-mode. Light is in turn coupled using a fiber bundle, and the detector is raster scanned in the xy-plane. Subsequently, to retrieve small features, the raw data are reconstructed using a multi-bandwidth, beamforming reconstruction algorithm. Comparison of the system performance at the different frequencies shows as expected a higher resolution in case of the 100 MHz detector compared to the 50 MHz. On the other hand the 50 MHz has a better SNR, can detect features from deeper layers, and has higher angular acceptance. Based on these characteristics the 50 MHz detector was mostly used. After comparing the performance we monitored the growth of B16F10 cells, melanin tumor, over the course of 9 days. We see correspondence between the optoacoustic measurements and the cryoslice validations. Additionally, in areas close to the tumor we see sprouting of new vessels, starting at day 4-5, which corresponds to tumor angiogenesis.

  6. Ilexgenin A exerts anti-inflammation and anti-angiogenesis effects through inhibition of STAT3 and PI3K pathways and exhibits synergistic effects with Sorafenib on hepatoma growth

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hao [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu (China); Institute of Pharmacology and Toxicology, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222000, Jiangsu (China); Wang, Juan [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu (China); Fan, Jin-hong; Zhang, Ya-qi; Zhao, Jun-xian [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); Dai, Xiao-jun [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); Chinese Medicine Hospital of Yangzhou City, Yangzhou 225009, Jiangsu (China); Liu, Qi; Shen, Yan-jun [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu (China); Liu, Chang [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); Sun, Wei-dong, E-mail: zyykjc@sina.com [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); Chinese Medicine Hospital of Yangzhou City, Yangzhou 225009, Jiangsu (China); Sun, Yun, E-mail: ysun@yzu.edu.cn [Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu (China); College of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu (China)

    2017-01-15

    Recently, we reported that Ilexgenin A exhibits anti-cancer activities and induces cell arrest. Here, we investigated the effect of Ilexgenin A on the inflammation, angiogenesis and tumor growth of hepatocellular carcinoma (HCC). Our current study revealed that Ilexgenin A significantly inhibited the inflammatory cytokines TNF-α and IL-6 levels and downregulated pro-angiogenic factor VEGF production and transcription in HepG2 cells. The underlying mechanism for Ilexgenin A effects appears to be through inhibiting STAT3 and PI3K pathways. Furthermore, we found that not only Ilexgenin A inhibited STAT3 and PI3K pathways in HepG2 cells but also blocked these signaling pathways in HUVECs. Most importantly, by employing two HCC xenografts models - HepG2 and H22, we showed that Ilexgenin A reduced tumor growth and exhibited synergy effect with Sorafenib. ELISA assay, histological analysis and immunohistochemistry examination revealed that the expression of VEGF and MVD was significantly decreased after the treatment with Ilexgenin A and the combination. Moreover, Ilexgenin A could enhance caspase-3/7 activity in vitro and transmission electron microscope indicated that the combination induced evident apoptosis of tumor cells and caused the structural changes of mitochondria in vivo. Although no apparent adverse effects occurred during the treatment period, Sorafenib monotherapy elicited hepatotoxicity for specific expression in the increased level of AST and the ratio of AST/ALT. However, the combination could remedy this adverse effect. In conclusion, the results described in the present study identifies Ilexgenin A as a promising therapeutic candidate that modulates inflammation, angiogenesis, and HCC growth. - Highlights: • Ilexgenin A exerts anti-inflammatory and anti-angiogenesis effects in hepatoma. • Ilexgenin A may exert these effects through inhibition of STAT3 and PI3K pathways. • Ilexgenin A exhibits synergistic effects with Sorafenib on hepatoma growth

  7. Loss of PINK1 attenuates HIF-1α induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia.

    Science.gov (United States)

    Lin, William; Wadlington, Natasha L; Chen, Linan; Zhuang, Xiaoxi; Brorson, James R; Kang, Un Jung

    2014-02-19

    Parkinson's disease (PD) has multiple proposed etiologies with implication of abnormalities in cellular homeostasis ranging from proteostasis to mitochondrial dynamics to energy metabolism. PINK1 mutations are associated with familial PD and here we discover a novel PINK1 mechanism in cellular stress response. Using hypoxia as a physiological trigger of oxidative stress and disruption in energy metabolism, we demonstrate that PINK1(-/-) mouse cells exhibited significantly reduced induction of HIF-1α protein, HIF-1α transcriptional activity, and hypoxia-responsive gene upregulation. Loss of PINK1 impairs both hypoxia-induced 4E-BP1 dephosphorylation and increase in the ratio of internal ribosomal entry site (IRES)-dependent to cap-dependent translation. These data suggest that PINK1 mediates adaptive responses by activating IRES-dependent translation, and the impairments in translation and the HIF-1α pathway may contribute to PINK1-associated PD pathogenesis that manifests under cellular stress.

  8. Composition and mechanism of anti-tumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice

    Science.gov (United States)

    We investigated anti-tumor effects of the following four extracts of freeze-dried Hericium erinaceus mushrooms in Balb/c mice intracutaneously transplanted on the backs with CT-26 colon cancer cells: HWE, hot-water extraction by boiling in water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W...

  9. Perivascular Epithelioid Cell Tumor in the Stomach

    Directory of Open Access Journals (Sweden)

    Sun Ah Shin

    2017-07-01

    Full Text Available Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST, and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

  10. Effects of Acanthus ebracteatus Vahl on tumor angiogenesis and on tumor growth in nude mice implanted with cervical cancer

    International Nuclear Information System (INIS)

    Mahasiripanth, Taksanee; Hokputsa, Sanya; Niruthisard, Somchai; Bhattarakosol, Parvapan; Patumraj, Suthiluk

    2012-01-01

    The aim of this study was to examine the effects of the crude extract of Acanthus ebracteatus Vahl (AE) on tumor growth and angiogenesis by utilizing a tumor model in which nude mice were implanted with cervical cancer cells containing human papillomavirus 16 DNA (HPV-16 DNA). The growth-inhibitory effect of AE was investigated in four different cell types: CaSki (HPV-16 positive), HeLa (HPV-18 positive), hepatocellular carcinoma cells (HepG2), and human dermal fibroblast cells (HDFs). The cell viabilities and IC 50 values of AE were determined in cells incubated with AE for different lengths of time. To conduct studies in vivo, female BALB/c nude mice (aged 6–7 weeks, weighing 20–25 g) were used. A cervical cancer-derived cell line (CaSki) with integrated HPV-16 DNA was injected subcutaneously (1 × 10 7 cells/200 μL) in the middle dorsum of each animal (HPV group). One week after injection, mice were fed orally with AE crude extract at either 300 or 3000 mg/kg body weight/day for 14 or 28 days (HPV-AE groups). Tumor microvasculature and capillary vascularity were determined using laser scanning confocal microscopy. Tumor tissue was collected from each mouse to evaluate tumor histology and vascular endothelial growth factor (VEGF) immunostaining. The time-response curves of AE and the dose-dependent effect of AE on growth inhibition were determined. After a 48-hour incubation period, the IC 50 of AE in CaSki was discovered to be significantly different from that of HDFs (P < 0.05). A microvascular network was observed around the tumor area in the HPV group on days 21 and 35. Tumor capillary vascularity in the HPV group was significantly increased compared with the control group (P < 0.001). High-dose treatment of AE extract (HPV-3000AE group) significantly attenuated the increase in VEGF expression and tumor angiogenesis in mice that received either the 14- or 28-day treatment period (P < 0.001). Our novel findings demonstrated that AE crude extract could

  11. Adenovirus-mediated interleukin-12 gene transfer combined with cytosine deaminase followed by 5-fluorocytosine treatment exerts potent antitumor activity in Renca tumor-bearing mice

    International Nuclear Information System (INIS)

    Hwang, Kyung-Sun; Cho, Won-Kyung; Yoo, Jinsang; Yun, Hwan-Jung; Kim, Samyong; Im, Dong-Soo

    2005-01-01

    Therapeutic gene transfer affords a clinically feasible and safe approach to cancer treatment but a more effective modality is needed to improve clinical outcomes. Combined transfer of therapeutic genes with different modes of actions may be a means to this end. Interleukin-12 (IL-12), a heterodimeric immunoregulatory cytokine composed of covalently linked p35 and p40 subunits, has antitumor activity in animal models. The enzyme/prodrug strategy using cytosine deaminase (CD) and 5-fluorocytosine (5-FC) has been used for cancer gene therapy. We have evaluated the antitumor effect of combining IL-12 with CD gene transfer in mice bearing renal cell carcinoma (Renca) tumors. Adenoviral vectors were constructed encoding one or both subunits of murine IL-12 (Ad.p35, Ad.p40 and Ad.IL-12) or cytosine deaminase (Ad.CD). The functionality of the IL-12 or CD gene products expressed from these vectors was validated by splenic interferon (IFN)-γ production or viability assays in cultured cells. Ad.p35 plus Ad.p40, or Ad.IL-12, with or without Ad.CD, were administered (single-dose) intratumorally to Renca tumor-bearing mice. The animals injected with Ad.CD also received 5-FC intraperitoneally. The antitumor effects were then evaluated by measuring tumor regression, mean animal survival time, splenic natural killer (NK) cell activity and IFN-γ production. The inhibition of tumor growth in mice treated with Ad.p35 plus Ad.p40 and Ad.CD, followed by injection of 5-FC, was significantly greater than that in mice treated with Ad.CD/5-FC, a mixture of Ad.p35 plus Ad.p40, or Ad.GFP (control). The combined gene transfer increased splenic NK cell activity and IFN-γ production by splenocytes. Ad.CD/5-FC treatment significantly increased the antitumor effect of Ad.IL-12 in terms of tumor growth inhibition and mean animal survival time. The results suggest that adenovirus-mediated IL-12 gene transfer combined with Ad.CD followed by 5-FC treatment may be useful for treating cancers

  12. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck and soft tissue sarcoma

    International Nuclear Information System (INIS)

    Brizel, David M.; Dewhirst, Mark W.; Sibley, Gregory S.; Scully, Sean P.; Harrelson, John M.; Scher, Richard L.; Prosnitz, Leonard R.

    1996-01-01

    Purpose The development of modern polarographic electrode technology has led to a resurgence in the clinical assessment of tumor oxygenation. Tumor hypoxia adversely affects short term clinical radiation response of head and neck cancer lymph node metastases and long term disease-free survival (DFS) in cervix carcinoma. This study was performed to evaluate the influence that tumor hypoxia exerts on the DFS of patients with soft tissue sarcoma (STS) and squamous carcinoma of the head and neck (SCCHN). Methods and Materials Pretreatment tumor pO 2 was assessed in STS and SCCHN patients using the Eppendorf polarographic electrode system. pO 2 probe placement was performed under CT scan guidance to ensure that measurements were obtained only from the tumor and in order to avoid measurement through areas of overt necrosis. A minimum of 3 measurement tracks that ranged in length from 10-35 mm was obtained from each tumor. A minimum of 100 measured points was taken from each tumor. All SCCHN patients had pO 2 measurements taken from locally advanced primaries (T3 or T4) or neck nodes ≥ 1.5 cm diameter. Treatment consisted of once or twice daily irradiation (70-75 Gy) +/- planned neck dissection (for ≥N2A disease) according to institutional treatment protocols. All STS patients had high grade tumors and received preoperative irradiation (2 Gy/day to 50 Gy) + hyperthermia followed by resection. DFS was measured by the Kaplan-Meier product limit method. The log rank technique was used to compare the DFS of different groups of patients. Single factor analysis of variance was used to compare tumor median pO 2 and tumor volume (STS) or stage (SCCHN) in those patients who relapsed versus those who did not. Correlation coefficients were calculated to examine the relationship between tumor volume and tumor oxygenation. Results Since November, 1992, 28 SCCHN and 33 STS patients have undergone tumor pO 2 measurement and have minimum followup of 6 months. The actuarial DFS at 12

  13. Rating of Perceived Exertion and Physiological Responses in Water-Based Exercise

    Directory of Open Access Journals (Sweden)

    Santana Pinto Stephanie

    2015-12-01

    Full Text Available The aim of the present study was to relate the overall rating of perceived exertion (RPE-overall with cardiorespiratory and neuromuscular variables during stationary running with the elbow flexion/extension performed with water-floating equipment. The sample consisted of eleven women that performed the water-based exercise at submaximal cadences. The heart rate, oxygen uptake, ventilation, and electromyographic signal (EMG from biceps brachii (%EMG BB, triceps brachii (%EMG TB, biceps femoris (%EMG BF and rectus femoris (%EMG RF muscles were measured during the exercise, and the overall RPE was measured immediately following its completion. The Pearson product-moment linear correlation was used to investigate associations between the variables analyzed in the present study. Significant relationships were observed between the RPE-overall and all the cardiorespiratory variables, with the r values ranging from 0.60 to 0.70 (p<0.05. In addition, the RPE-overall showed a significant (p<0.05 relationship with %EMG BB (r=0.55 and %EMG BF (r=0.50. These results suggest an association between the RPE-overall with all cardiorespiratory and two neuromuscular variables during the execution of a water-based aerobic exercise using water-floating equipment.

  14. Cellular and Tumor Radiosensitivity is Correlated to Epidermal Growth Factor Receptor Protein Expression Level in Tumors Without EGFR Amplification

    International Nuclear Information System (INIS)

    Kasten-Pisula, Ulla; Saker, Jarob; Eicheler, Wolfgang; Krause, Mechthild; Yaromina, Ala; Meyer-Staeckling, Soenke; Scherkl, Benjamin; Kriegs, Malte; Brandt, Burkhard; Grenman, Reidar; Petersen, Cordula; Baumann, Michael; Dikomey, Ekkehard

    2011-01-01

    Purpose: There is conflicting evidence for whether the expression of epidermal growth factor receptor in human tumors can be used as a marker of radioresponse. Therefore, this association was studied in a systematic manner using squamous cell carcinoma (SCC) cell lines grown as cell cultures and xenografts. Methods and Materials: The study was performed with 24 tumor cell lines of different tumor types, including 10 SCC lines, which were also investigated as xenografts on nude mice. Egfr gene dose and the length of CA-repeats in intron 1 were determined by polymerase chain reaction, protein expression in vitro by Western blot and in vivo by enzyme-linked immunosorbent assay, and radiosensitivity in vitro by colony formation. Data were correlated with previously published tumor control dose 50% data after fractionated irradiation of xenografts of the 10 SCC. Results: EGFR protein expression varies considerably, with most tumor cell lines showing moderate and only few showing pronounced upregulation. EGFR upregulation could only be attributed to massive gene amplification in the latter. In the case of little or no amplification, in vitro EGFR expression correlated with both cellular and tumor radioresponse. In vivo EGFR expression did not show this correlation. Conclusions: Local tumor control after the fractionated irradiation of tumors with little or no gene amplification seems to be dependent on in vitro EGFR via its effect on cellular radiosensitivity.

  15. Self-reported post-exertional fatigue in Gulf War veterans: roles of autonomic testing

    Science.gov (United States)

    Li, Mian; Xu, Changqing; Yao, Wenguo; Mahan, Clare M.; Kang, Han K.; Sandbrink, Friedhelm; Zhai, Ping; Karasik, Pamela A.

    2014-01-01

    To determine if objective evidence of autonomic dysfunction exists from a group of Gulf War veterans with self-reported post-exertional fatigue, we evaluated 16 Gulf War ill veterans and 12 Gulf War controls. Participants of the ill group had self- reported, unexplained chronic post-exertional fatigue and the illness symptoms had persisted for years until the current clinical study. The controls had no self-reported post-exertional fatigue either at the time of initial survey nor at the time of the current study. We intended to identify clinical autonomic disorders using autonomic and neurophysiologic testing in the clinical context. We compared the autonomic measures between the 2 groups on cardiovascular function at both baseline and head-up tilt, and sudomotor function. We identified 1 participant with orthostatic hypotension, 1 posture orthostatic tachycardia syndrome, 2 distal small fiber neuropathy, and 1 length dependent distal neuropathy affecting both large and small fiber in the ill group; whereas none of above definable diagnoses was noted in the controls. The ill group had a significantly higher baseline heart rate compared to controls. Compound autonomic scoring scale showed a significant higher score (95% CI of mean: 1.72–2.67) among ill group compared to controls (0.58–1.59). We conclude that objective autonomic testing is necessary for the evaluation of self-reported, unexplained post-exertional fatigue among some Gulf War veterans with multi-symptom illnesses. Our observation that ill veterans with self-reported post-exertional fatigue had objective autonomic measures that were worse than controls warrants validation in a larger clinical series. PMID:24431987

  16. Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

    National Research Council Canada - National Science Library

    Tsan, Min-Fu; Gao, Baochong

    2005-01-01

    Tumor-associated macrophages may comprise up to 50% of the tumor mass in breast cancer and are capable of producing estrogen and angiogenic cytokines that regulate the growth and angiogenesis of breast cancer...

  17. Identification of anti-tumoral effect of a polypeptide isolated from Scorpionfish Scorpaena plumieri venom and assessment of its potential use for tumor diagnosis

    International Nuclear Information System (INIS)

    Soprani, Juliana

    2008-01-01

    Cancer has killed millions of people worldwide. Despite the increasing knowledge about the molecular basis of tumor development, few advances have been reached in clinical therapy and diagnoses, which shows the importance of new drugs development for therapeutic and diagnosis purpose. Venomous creatures have been studied as potential sources of pharmacological agents and physiological tools. A lot of work has been done about biological activity of terrestrial animals, but comparatively less research has been undertaken on venomous marine creature, particularly fish, which means that marine toxins represent a vast and unexplored source of novel molecules with therapeutical potential. In this work, the scorpion fish Scorpaena plumieri crude venom (SPB) and a gelatinolytic protease purified from this venom (SPGP) were evaluated for their applicability for in vivo tumor detection. In vitro results showed that both. SPB and SPGP, possess a powerful antitumor effects on p53-wild-type glioblastoma cells (LD 50 = 3,9 ± 0,98μg/mL and 8,00 x 10 -12 ± 2,94 x 10 -12 M, respectively) and Ehrlich ascites carcinoma cells (LD 50 =14,05 ± 2,95 μg/mL and 1,22 x 10 -11 ± 6,56 x 10 -12 M, respectively). P53 mutant glioblastoma cells were more resistant to both, SPB and SPGP treatment (LD 50 > 125 μg/mL and LD 50 > 1,39 x 10 -9 M, respectively). The morphological changes observed in the cell lines treated with SPB and SPGP, and the data of DAPI staining, indicate that the antitumor effect of these substances occurs via apoptosis. Radioactive probes of SPB ([ 99m Tc] SPB) and SPGP ([ 125 I] SPGP) with high specific activity and high radiochemical purity were synthesized. Data of biodistribution studies, performed by intravenous injections in Swiss mice bearing Ehrlich carcinoma cells, showed that SPB has poor uptake in tumor region. On the other hand, SPGP had a substantial uptake in tumor at ali analyzed times. Intratumoral administration of [ 125 I]SPGP increased its uptake by

  18. Nestin expression in neuroepithelial tumors.

    Science.gov (United States)

    Schiffer, Davide; Manazza, Andrea; Tamagno, Ilaria

    2006-05-29

    Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.

  19. Plasticity of cognitive functions before and after awake brain tumor surgery

    Directory of Open Access Journals (Sweden)

    Djaina Satoer

    2015-04-01

    Results: P1 and P2 showed opposite preoperative cognitive profiles. P1 obtained normal cognitive results and P2 had clinically significant impairments in all cognitive domains, (language, memory, attentional and executive deficits (z-score ≥-1.50. P3 and P4 also demonstrate opposite preoperative profiles. P4 obtained intact cognitive results, whereas P3 was impaired in memory and executive functions (z-score ≥-1.50. Intraoperatively, in both P3 and P4 positive language sites were found (left inferior frontal gyrus and left parietal lobe. At 3 months postoperatively, P3 presented language deficits followed by recovery at 12 months, whereas P4 appeared to have recovered at 3 months postoperatively from the observed premorbid impairments in memory and executive functioning (z-score <-1.50. Pathological examination revealed a slow growing brain tumor (low-grade in P1 and P3 and a fast growing brain tumor (high-grade in P2 and P4. Conclusion: In patients with similar brain tumor localizations, we found distinct cognitive profiles, possibly affected by different neural plasticity processes. Preoperatively, a favorable plasticity effect on cognition was found in P1 (temporoparietal area, potentially affected by tumor grade. Preserved cognitive functions was possibly facilitated by the slow growth rate of a low-grade tumor allowing functional reorganization (Mandonnet et al., 2003. However, P2 with a brain tumor in the same area showed preoperative deficits in several domains (language, memory and attention/executive functions. A faster growth rate of a high-grade tumor could have more aggressively affected cognition. In P3 and P4 with the same localization (insula, we found a different effect on the cognitive recovery process; at short term (3 months, improvement of the preoperatively observed cognitive impairments in a low-grade tumor P3, whereas a more gradual functional reorganization was found in language (3-12 months in P4, a high-grade tumor, contrasting Habets

  20. Cerebrospinal fluid hypovolemia in childhood and adolescence. Clinical features and outcomes

    International Nuclear Information System (INIS)

    Takahashi, Koichi; Mima, Tatsuo

    2011-01-01

    Cerebrospinal fluid (CSF) hypovolemia has increasingly been recognized, but few investigations have examined younger patients. This study investigated 50 cases of CSF hypovolemia onset in childhood and adolescence. We analyzed causes, outcomes, and clinical features of these child and adolescent CSF hypovolemia cases. The 50 patients (25 boys, 25 girls) had shown the onset earlier than age 15. Diagnosis of probable CSF hypovolemia was made basically on clinical symptoms and findings of magnetic resonance imaging (MRI) and Radioisotope (RI) cisternography. For treatment, we defined epidural blood patch (EBP) indication as the early bladder filling (early BF) and all of the 50 cases received EBP. All patients suffered from one or more symptoms such as intractable headache, neck pain, vertigo, fatigue, tinnitus and visual disturbance. These symptoms did not recover with any conventional treatments. Twenty eight cases (56.0%) showed normal results on MRI. In RI cisternography, 16 cases (32.0%) showed CSF leaks (CL), 34 cases (68.0%) showed early BF. About 90% of the patients were improved by EBP. In particular, 96.0% of cases showed good or moderate recovery when onset of CSF hypovolemia and the first treatment was less than 1 year. CSF hypovolemia is not yet well recognized particularly in child and adolescent cases. Some children were misdiagnosed as autonomic nervous system dysfunction, orthostatic dysregulation, Barre-Lieou syndrome or depression. This study indicated that EBP is also effective for younger patients. If patients suffer from various intractable symptoms including orthostatic headache, CSF hypovolemia should be considered for the differential diagnosis. (author)

  1. Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

    2007-09-15

    We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.

  2. Tumores desmoides: cuadro clínico y sobrevida

    Directory of Open Access Journals (Sweden)

    Juan Díaz-Plasencia

    1998-04-01

    Full Text Available Objetivos: Identificar el cuadro clínico, la recurrencia y sobrevida quinquenal por tumor desmoide. Material y métodos: Analizamos 18 pacientes manejados en el Hospital Belén, Trujillo, Perú, desde 1966 a 1994. Resultados: Los antecedentes más frecuentes fueron embarazo reciente (n=8, cirugía previa (n=3 y traumatismo (n=1. La edad promedio fue de 29.5 ± 16.7 años (rango, 5 meses a 75 años. El 50% de los casos se presentó en la tercera década de la vida. Hubo 6 hombres y 12 mujeres (H:M, 1:2.El síntoma y signo más común fue tumor (100%, acompañado por dolor (66.7%, impotencia funcional (22.2% y parestesias (16.7%. El diámetro tumoral promedio fue 10.9 ± 5.6 cm. Las neoplasias se localizaron en pared abdominal (n=12, cabeza - cuello (n=3 y miembros inferiores (n=3. El tratamiento más utilizado fue el quirúrgico (n=14, y la radioterapia se utilizó en 2 casos irresecables. En los 10 pacientes que tuvo seguimiento completo la tasa de recurrencia quinquenal fue de 33.3%, siendo ésta menor con el tratamiento quirúrgico (25% que con el radioterápico (50%. Además, hubo menor recurrencia con la cirugía amplia y radical (16.7% en comparación con la resección local simple (50%. La sobrevida quinquenal en la serie total fue de 87.5%, siendo ésta menor con el tratamiento quirúrgico (83.3% que con el radioterápico (100%. Conclusiones: La localización más frecuente de estos tumores estuvo en la pared abdominal. El tratamiento quirúrgico con un margen amplio de resección ofrece un mejor control local de los tumores desmoides. (Rev Med Hered 1998; 9:69-76 .

  3. Synovial sarcoma mimicking benign peripheral nerve sheath tumor

    Energy Technology Data Exchange (ETDEWEB)

    Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2017-11-15

    To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

  4. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    International Nuclear Information System (INIS)

    Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

    2000-01-01

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

  5. Esophageal Gastrointestinal Stromal Tumor: Diagnostic Complexity and Management Pitfalls

    Directory of Open Access Journals (Sweden)

    Charalampos G. Markakis

    2013-01-01

    Full Text Available Introduction. Gastrointestinal stromal tumors of the esophagus are rare. Case Presentation. This is a case of a 50-year-old male patient who was referred to our department complaining of atypical chest pain. A chest computed tomographic scan and endoscopic ultrasound revealed a submucosal esophageal tumor measuring 5 cm in its largest diameter. Suspecting a leiomyoma, we performed enucleation via right thoracotomy. The pathology report yielded a diagnosis of an esophageal gastrointestinal stromal tumor. The patient has shown no evidence of recurrence one year postoperatively. Conclusions. This report illustrates the complexity and dilemmas inherent in diagnosing and treating esophageal GISTs.

  6. Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Miyamoto

    Full Text Available Lipoapoptosis occurring due to an excess of saturated free fatty acids such as palmitate is a key pathogenic event in the initiation of nonalcoholic fatty liver disease. Palmitate loading of cells activates the endoplasmic reticulum stress response, including induction of the proapoptotic transcription factor C/EBP homologous protein (CHOP. Furthermore, the loss of microRNAs is implicated in regulating apoptosis under conditions of endoplasmic reticulum (ER stress. The aim of this study was to identify specific microRNAs regulating CHOP expression during palmitate-induced ER stress. Five microRNAs were repressed under palmitate-induced endoplasmic reticulum stress conditions in hepatocyte cell lines (miR-92b-3p, miR-328-3p, miR-484, miR-574-5p, and miR-615-3p. We identified miR-615-3p as a candidate microRNA which was repressed by palmitate treatment and regulated CHOP protein expression, by RNA sequencing and in silico analyses, respectively. There is a single miR-615-3p binding site in the 3'untranslated region (UTR of the Chop transcript. We characterized this as a functional binding site using a reporter gene-based assay. Augmentation of miR-615-3p levels, using a precursor molecule, repressed CHOP expression; and under these conditions palmitate- or tunicamycin-induced cell death were significantly reduced. Our results suggest that palmitate-induced apoptosis requires maximal expression of CHOP which is achieved via the downregulation of its repressive microRNA, miR-615-3p. We speculate that enhancement of miR-615-3p levels may be of therapeutic benefit by inhibiting palmitate-induced hepatocyte lipoapoptosis.

  7. Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

    National Research Council Canada - National Science Library

    Tsan, Min-Fu

    2004-01-01

    Tumor-associated macrophages (TAM) may comprise up to 50% of the tumor mass in breast cancer and are capable of producing estrogen and angiogenic cytokines that regulate the growth and angiogenesis of breast cancer...

  8. Does circumferential tumor location affect the circumferential resection margin status in mid and low rectal cancer?

    Directory of Open Access Journals (Sweden)

    Byung Mo Kang

    2018-05-01

    Full Text Available Summary: Background/Objective: The purpose of this study was to assess the impact of circumferential tumor location on circumferential resection margin (CRM status and the depth of tumor invasion in mid and low rectal cancer. Methods: We retrospectively analyzed whole-mount slides of 58 patients who underwent total mesorectal excision for mid and low rectal cancer. The rate of tumor-positive CRM was compared according to the circumferential tumor location. In 31 patients, morphometric analyses of whole-mount specimens were performed to measure the depth of tumor invasion according to circumferential tumor location. Results: Among 58 patients, 50% of tumors were anterior tumor and 50% were nonanterior. A tumor-positive CRM was more observed frequently in anterior tumors than in nonanterior tumors (41.1% vs. 10.3%, p = 0.007. In a multivariate analysis, anterior tumor was the only independent risk factor for a positive CRM (odds ratio 4.725, 95% confidence interval 1.102–20.261, p = 0.037. In a morphometric analysis of 31 patients, the depth of tumor invasion from the muscularis mucosa was greater (11.9 mm vs. 6.6 mm, p = 0.028 in those with anterior tumors. Conclusion: Anterior tumors are associated with a higher risk of tumor-positive CRM and tend to exhibit deeper invasion in mid and low rectal cancer. Keywords: circumferential resection margin, depth of invasion, rectal cancer, tumor location

  9. Interstitial administration of perfluorochemical emulsions for reoxygenation of hypoxic tumor cells

    International Nuclear Information System (INIS)

    Woo, D.V.; Seegenschmiedt, H.; Schweighardt, F.K.; Emrich, J.; McGarvey, K.; Caridi, M.; Brady, L.W.

    1987-01-01

    Microparticulate perfluorochemical (PFC) emulsions have the capacity to solubilize significant quantities of oxygen compared to water. Although systemic administration of such emulsions may enhance oxygen delivery to some tissues, hypoxic tumor cells have marginal vascular supplies. The authors report studies which directly attempt to oxygenate hypoxic tumor cells by interstitial administration of oxygenated PFC emulsions followed by radiation therapy. Fortner MMI malignant melanomas (21 day old) grown in Syrian Golden hamsters were injected directly with either oxygenated PFC emulsions or Ringers solution. The volume of test substance administered was equal to 50% of the tumor volume. The tumors were immediately irradiated with 25 Gy of 10 MeV photons (Clinac 18). The tumor dimensions were measured daily post irradiation and the tumor doubling time determined. The results suggest that interstitial administration of oxygenated PFC emulsions directly into tumors followed by radiation therapy may increase the likelihood of killing hypoxic tumor cells

  10. SU-E-T-529: Is MFO-IMPT Robust Enough for the Treatment of Head and Neck Tumors? A 2-Year Outcome Analysis Following Proton Therapy On the First 50 Oropharynx Patients at the MD Anderson Cancer Center

    Energy Technology Data Exchange (ETDEWEB)

    Frank, S; Garden, A; Anderson, M; Rosenthal, D; Morrison, W; Gunn, B; Fuller, C; Phan, J; Zhang, X; Poenisch, F; Wu, R; Li, H; Gautam, A; Sahoo, N; Gillin, M; Zhu, X [MD Anderson Cancer Ctr., Houston, TX (United States)

    2015-06-15

    Purpose: Multi-field optimization intensity modulated proton therapy (MFO-IMPT) for oropharyngeal tumors has been established using robust planning, robust analysis, and robust optimization techniques. While there are inherent uncertainties in proton therapy treatment planning and delivery, outcome reporting are important to validate the proton treatment process. The purpose of this study is to report the first 50 oropharyngeal tumor patients treated de-novo at a single institution with MFO-IMPT. Methods: The data from the first 50 patients with squamous cell carcinoma of the oropharynx treated at MD Anderson Cancer Center from January 2011 to December 2014 on a prospective IRB approved protocol were analyzed. Outcomes were analyzed to include local, regional, and distant treatment failures. Acute and late toxicities were analyzed by CTCAE v4.0. Results: All patients were treated with definitive intent. The median follow-up time of the 50 patients was 25 months. Patients by gender were male (84%) and female (16%). The average age was 61 years. 50% of patients were never smokers and 4% were current smokers. Presentation by stage; I–1, II–0, III– 9, IVA–37 (74%), IVB–3. 88% of patients were HPV/p16+. Patients were treated to 66–70 CGE. One local failure was reported at 13 months following treatment. One neck failure was reported at 12 months. 94% of patients were alive with no evidence of disease. One patient died without evidence of disease. There were no Grade 4 or Grade 5 toxicities. Conclusion: MFO-IMPT for oropharyngeal tumors is robust and provides excellent outcomes 2 years after treatment. A randomized trial is underway to determine if proton therapy will reduce chronic late toxicities of IMRT.

  11. Inhibition of the promotion of hepatocarcinogenesis by 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) by the deletion of the p50 subunit of NF-κB in mice

    International Nuclear Information System (INIS)

    Glauert, Howard P.; Tharappel, Job C.; Banerjee, Subhashis; Chan, Nelson L.S.; Kania-Korwel, Izabela; Lehmler, Hans-Joachim; Lee, Eun Y.; Robertson, Larry W.; Spear, Brett T.

    2008-01-01

    Polychlorinated biphenyls (PCBs) are persistent and ubiquitous environmental chemicals that bioaccumulate and have hepatic tumor promoting activity in rodents. The present study examined the effect of deleting the p50 subunit of NF-κB on the hepatic tumor promoting activity of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) in mice. Both wild-type and p50-/- male mice were injected i.p. with diethylnitrosamine (DEN, 90 mg/kg) and then subsequently injected biweekly with 20 i.p. injections of PCB-153 (300 μmol/kg/injection). p50 deletion decreased the tumor incidence in both PCB- and vehicle-treated mice, whereas PCB-153 slightly (P = 0.09) increased the tumor incidence in wild-type and p50-/- mice. PCB-153 increased the total tumor volume in both wild-type and p50-/- mice, but the total tumor volume was not affected by p50 deletion in either PCB- or vehicle-treated mice. The volume of tumors that were positive for glutamine synthetase (GS), which is indicative of mutations in the beta-catenin gene, was increased in both wild-type and p50-/- mice administered PCB-153 compared to vehicle controls, and inhibited in p50-/- mice compared to wild-type mice (in both PCB- and vehicle-treated mice). The volume of tumors that were negative for GS was increased in p50-/- mice compared to wild-type mice but was not affected by PCB-153. PCB-153 increased cell proliferation in normal hepatocytes in wild-type but not p50-/- mice; this increase was inhibited in p50-/- mice. In hepatic tumors, the rate of cell proliferation was much higher than in normal hepatocytes, but was not affected by PCB treatment or p50 deletion. The rate of apoptosis, as measured by the TUNEL assay, was not affected by PCB-153 or p50 deletion in normal hepatocytes. In hepatic tumors, the rate of apoptosis was lower than in normal hepatocytes; PCB-153 slightly (P = 0.10) increased apoptosis in p50-/- but not wild-type mice; p50 deletion had no effect. Taken together, these data indicate that the absence of

  12. Diagnostic value of magnetic resonance imaging and the pathologic basis of parotid Warthin's tumor in 46 cases

    International Nuclear Information System (INIS)

    Yuan Jianpeng; Huang Suiqiao; Xie Bangkun; Zhong Jinglian; Li Yong

    2004-01-01

    Objective: To summarize MR manifestations of parotid Warthin's tumor and to investigate their pathological fundament. MR findings of parotid Warthin's tumor including shape, margin, signal intensity on T 1 WI and T 2 WI, homogeneity of the signal, enhancement were analyzed retrospectively in this study. Methods: In total 46 cases (54 lesions) of parotid Warthin's tumor proved by surgery were enrolled. MRI manifestations were comparatively studied with pathological findings. T 1 WI and T 2 WI sequence were used in non-contrast scan, while both non-contrast and enhanced scan were performed in 50 lesions out of 54. Results: The shapes of Warthin's tumor were regular (51/54); the edges were clear (54/54); more than half of the lesions (33/54) presented with low or equal signal intensity on T 2 WI; 50 Warthin's tumors enhanced slightly. The MR features of Warthin's tumors were different from pleomorphic adenoma and other parotid benign tumors. Conclusion: There are certain characteristics of Warthin's tumors on MR images, and these are helpful in determining the histological nature of the tumor

  13. Low dose radiation enhancing inhibitory effect of tumor-associated antigen peptide extract on H-22 hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zuyue, Sun; Jingyi, Fu; Yong, Zhao [Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Inst. of Zoology, Chinese Academy of Sciences, Beijing (China); Jianxiang, Liu; Zhibo, Fu; Xiuyi, Li; Shuzheng, Liu; Shouliang, Gong

    2005-06-15

    Objective: To determine whether there is synergically inhibitory effect of low dose radiation (LDR) and tumor-associated antigen peptides (TAP) on tumor growth in vivo, which may provide experimental basis for potential clinical co-application of these two approaches to treat cancers. Methods: TAP extract (MW {<=}3x10{sup 6}) from tumor cell membrane was prepared with mild acid elution method , as reported. The mice were whole-bodily irradiated with 75 mGy X-rays 12 h before immunization with TAP extract. After immunization , the levels of CD3, CD69, TCR{alpha}{beta} cells and T cell subsets in the spleen were detected with FACS. The tumor growth rate was estimated, and the responses to Con A, the cytokine productions and CTL activities of splenocytes were also analyzed 7 d after immunization with TAP. Results: The present experimental results showed that the TAP extract significantly reduced the incidence of the transplanted tumor, delayed the average appearing time and decreased the growth speed of the tumor. The response of splenocytes from mice immunized with TAP extract to Con A increased significantly compared with that in the control group. Irradiation with 75 mGy X-rays 12 h before immunization further enhanced the inhibitory effect of TAP extract on tumor growth, and increased the percentage of CD8{sup +} splenocytes. Conclusion: These results suggest that whole-body irradiation with LDR exerts a synergic inhibitory effect with TAP on tumor growth in vivo, in which enhanced cellular immune responses may be involved. (authors)

  14. Preclinical Efficacy of [V4Q5]dDAVP, a Second Generation Vasopressin Analog, on Metastatic Spread and Tumor-Associated Angiogenesis in Colorectal Cancer.

    Science.gov (United States)

    Garona, Juan; Sobol, Natasha T; Pifano, Marina; Segatori, Valeria I; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F

    2018-06-01

    Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4Q5]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of AVPR2 present in endothelial and tumor cells, [V4Q5]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V4Q5]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V4Q5]dDAVP, both in vitro and in vivo. In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained i.v. treatment with [V4Q5]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V4Q5]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 µM) and addition to 5-FU resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. The present preclinical study establishes for the first time the efficacy of [V4Q5]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.

  15. Loss of ERβ expression as a common step in estrogen-dependent tumor progression

    Science.gov (United States)

    Bardin, Allison; Boulle, Nathalie; Lazennec, Gwendal; Vignon, Françoise; Pujol, Pascal

    2004-01-01

    The characterization of estrogen receptor beta (ERβ) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues and the mitogenic effects of estrogen in these tissues (e.g. breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERβ expression in cancer as compared to benign tumors or normal tissues, whereas ERα expression persists. The loss of ERβ expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERα target genes by ERβ, or ERβ specific gene induction could indicate that ERβ has a differential effect on proliferation as compared to ERα. ERβ may exert a protective effect and thus constitute a new target for hormone therapy, e.g. via ligand specific activation. The potential distinct roles of ERα and ERβ expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review. PMID:15369453

  16. How emotion context modulates unconscious goal activation during motor force exertion.

    Science.gov (United States)

    Blakemore, Rebekah L; Neveu, Rémi; Vuilleumier, Patrik

    2017-02-01

    Priming participants with emotional or action-related concepts influences goal formation and motor force output during effort exertion tasks, even without awareness of priming information. However, little is known about neural processes underpinning how emotional cues interact with action (or inaction) goals to motivate (or demotivate) motor behaviour. In a novel functional neuroimaging paradigm, visible emotional images followed by subliminal action or inaction word primes were presented before participants performed a maximal force exertion. In neutral emotional contexts, maximum force was lower following inaction than action primes. However, arousing emotional images had interactive motivational effects on the motor system: Unpleasant images prior to inaction primes increased force output (enhanced effort exertion) relative to control primes, and engaged a motivation-related network involving ventral striatum, extended amygdala, as well as right inferior frontal cortex. Conversely, pleasant images presented before action (versus control) primes decreased force and activated regions of the default-mode network, including inferior parietal lobule and medial prefrontal cortex. These findings show that emotional context can determine how unconscious goal representations influence motivational processes and are transformed into actual motor output, without direct rewarding contingencies. Furthermore, they provide insight into altered motor behaviour in psychopathological disorders with dysfunctional motivational processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

    Science.gov (United States)

    Wang, Piwen; Solorzano, Walter; Diaz, Tanya; Magyar, Clara E.; Henning, Susanne M.; Vadgama, Jaydutt V.

    2017-01-01

    The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower doses (< 2μM) significantly inhibited the proliferation of LNCaP and LAPC-4 cells by 30-50% at 48h compared to control, and inhibited WPE1-NA22 cells by 75%, while did not affect normal prostate epithelial cells. Male severe combined immunodeficiency (SCID) mice were implanted subcutaneously with LAPC-4 cells for in vivo studies. In one experiment, the intervention started one week after tumor implantation. Mice received arctigenin at 50mg/kg (LD) or 100mg/kg (HD) b.w. daily or vehicle control by oral gavage. After 6 weeks, tumor growth was inhibited by 50% (LD) and 70% (HD) compared to control. A stronger tumor inhibitory effect was observed in a second experiment where arctigenin intervention started two weeks prior to tumor implantation. Arc was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 μM in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker Ki67, total and nuclear androgen receptor, and growth factors including VEGF, EGF, and FGF-β were significantly decreased by Arc, along with an increase in apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and miR-21-5p. This study provides the first in vivo evidence of the strong anticancer activity of arctigenin in prostate cancer. The effective dose of arctigenin in vitro is physiologically achievable in vivo, which provides a high promise in its translation to human application

  18. Preoperative tumor localization of primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Morita, Yutaka; Shinohara, Masahiro; Ito, Kazuo; Imamura, Fumimoto; Kasai, Yoichi; Ishizuka, Reiki.

    1983-01-01

    The diagnostic rate of each methods were discussed in thirty six cases and following conclusions were made. 1. The diagnostic rate of US, RI, AG and VS was 64.7%, 50%, 57.9%, 60.7% respectively. 2. Ultrasonography and subtruction-scintigraphy were useful screening examination for localization of parathyroid tumor. 3. The reasonable diagnostic procedures were as follows. 1) In the cases of palpable, reno-uretrolithiasic type, and biochemical type: US → RI → VS 2) In the cases of nonpalpable osteolytic type, and previous neck surgery: US → RI → AG → VS These results indicate that the systemic diagnosis are useful to predict localization of parathyroid tumors. (author)

  19. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    NARCIS (Netherlands)

    Scalco, R.S.; Snoeck, M.; Quinlivan, R.; Treves, S.; Laforet, P.; Jungbluth, H.; Voermans, N.C.

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild

  20. Robotic partial nephrectomy for complex renal tumors: surgical technique.

    Science.gov (United States)

    Rogers, Craig G; Singh, Amar; Blatt, Adam M; Linehan, W Marston; Pinto, Peter A

    2008-03-01

    Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n=5), endophytic tumors (n=4), and/or multiple tumors (n=3). Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy.

  1. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  2. Motor performance of tongue with a computer-integrated system under different levels of background physical exertion

    Science.gov (United States)

    Huo, Xueliang; Johnson-Long, Ashley N.; Ghovanloo, Maysam; Shinohara, Minoru

    2015-01-01

    The purpose of this study was to compare the motor performance of tongue, using Tongue Drive System, to hand operation for relatively complex tasks under different levels of background physical exertion. Thirteen young able-bodied adults performed tasks that tested the accuracy and variability in tracking a sinusoidal waveform, and the performance in playing two video games that require accurate and rapid movements with cognitive processing using tongue and hand under two levels of background physical exertion. Results show additional background physical activity did not influence rapid and accurate displacement motor performance, but compromised the slow waveform tracking and shooting performances in both hand and tongue. Slow waveform tracking performance by the tongue was compromised with an additional motor or cognitive task, but with an additional motor task only for the hand. Practitioner Summary We investigated the influence of task complexity and background physical exertion on the motor performance of tongue and hand. Results indicate the task performance degrades with an additional concurrent task or physical exertion due to the limited attentional resources available for handling both the motor task and background exertion. PMID:24003900

  3. Efficacy and biological effects of techniques used to induce hypoxia in tumors

    International Nuclear Information System (INIS)

    Rockwell, S.; Moulder, J.E.; Martin, D.F.

    1985-01-01

    The authors tested several aspects of the assumptions using BA1112 rat rhabdomyosacromas and EMT6 mouse mammary tumors. Both techniques were effective in producing hypoxia: survival curves for tumors made hypoxic by the 2 techniques were the same, and were indistinguishable from survival curves for hypoxic tumor cells in vitro. Induction of hypoxia for the 30-60 min necessary for irradiation did not alter the yield or clonogenicity of cells suspended from the tumors. Longer clamping was cytotoxic. Clamping did not alter tumor growth unless a major blood vessel was injured. However, clamping BA1112 tumors for 30 min and removing the clamp just before irradiation altered the tumor cell survival curve and TCD/sub 50/. Anesthesia or restrain, often used during clamping, can have major effects

  4. Salivary gland tumors of the parotid gland: CT and MR imaging findings with emphasis on intratumoral cystic components

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki; Watanabe, Haruo [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Gifu University Hospital, High-Level Imaging Diagnosis Center, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan)

    2014-09-15

    The purpose of this study was to assess computed tomography (CT) and magnetic resonance (MR) imaging findings of salivary gland tumors of the parotid gland with emphasis on intratumoral cystic components. Seventy-two histopathologically confirmed salivary gland tumors of the parotid gland (44 benign and 28 malignant), which underwent both CT and MR imaging including contrast-enhanced study, were included in this study. We retrospectively reviewed images for the presence, number, occupying rate, margin characteristics, distribution, and predominant MR signal intensity of intratumoral cystic components. The prevalence of cystic components was greater in malignant than benign tumors (79 vs. 50 %, p < 0.05). The number and occupying rate were similar between benign and malignant tumors. The irregular margins were more frequent in malignant than benign tumors (73 vs. 27 %, p < 0.01). The frequency of eccentric location was greater in benign than malignant tumors (91 vs. 55 %, p < 0.01), whereas the frequency of centric location was greater in malignant than benign tumors (32 vs. 0 %, p < 0.01). On T1-weighted images, the frequency of hyperintensity was greater in benign than malignant tumors (50 vs. 9 %, p < 0.01), whereas that of isointensity was greater in malignant than benign tumors (50 vs. 0 %, p < 0.01). Multiple logistic regression analysis showed that the absence of irregular margins of cystic components only was significantly correlated with the presence of benign salivary gland tumors (p < 0.01). Imaging features of intratumoral cystic components may help to differentiate benign from malignant tumors of the parotid salivary gland. (orig.)

  5. Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease.

    Science.gov (United States)

    Freitag, Helma; Christen, Friederike; Lewens, Florentine; Grass, Irina; Briest, Franziska; Iwaszkiewicz, Sara; Siegmund, Britta; Grabowski, Patricia

    2017-01-01

    The characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, the current therapy options are not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and mTORC1/C2. We assessed the effects of PKI-587 in different GEP-NEN tumor models, including the poorly differentiated cell line LCC-18, and compared them with those of the established mTORC1 inhibitor everolimus. We treated BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We assessed the impact of the treatments on viability (WST-1 assay), on apoptotic processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow cytometry). We determined alterations in signaling mediators by phosphor-specific Western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology). In all cell lines, PKI-587 dose-dependently inhibited proliferation, whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest and induction of apoptosis and successfully suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this paper. PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials. © 2016 The Author(s) Published by S. Karger AG, Basel.

  6. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

    Science.gov (United States)

    Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

    2017-12-09

    Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

  7. Protein kinase C is differentially regulated by thrombin, insulin, and epidermal growth factor in human mammary tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, M.L.; Tellez-Inon, M.T. (Instituto de Ingenieria Genetica y Biologia Molecular, Buenos Aires (Argentina)); Medrano, E.E.; Cafferatta, E.G.A. (Instituto de Investigaciones Bioquimicas Fundacion Campomar, Buenos Aires (Argentina))

    1988-03-01

    The exposure of serum-deprived mammary tumor cells MCF-7 and T-47D to insulin, thrombin, and epidermal growth factor (EGF) resulted in dramatic modifications in the activity and in the translocation capacity of protein kinase C from cytosol to membrane fractions. Insulin induces a 600% activation of the enzyme after 5 h of exposure to the hormone in MCF-7 cells; thrombin either activates (200% in MCF-7) or down-regulates (in T-47D), and EGF exerts only a moderate effect. Thus, the growth factors studied modulate differentially the protein kinase C activity in human mammary tumor cells. The physiological significance of the results obtained are discussed in terms of the growth response elicited by insulin, thrombin, and EGF.

  8. Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Yu [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Zhan, Qian [The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xu, Hongying [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Li, Lili; Li, Chen [Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute (Hong Kong); Xiao, Qian; Xiang, Shili; Hui, Tianli [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Xiang, Tingxiu, E-mail: larissaxiang@163.com [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rengs726@126.com [Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2016-06-10

    The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

  9. Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

    International Nuclear Information System (INIS)

    Fan, Yu; Zhan, Qian; Xu, Hongying; Li, Lili; Li, Chen; Xiao, Qian; Xiang, Shili; Hui, Tianli; Xiang, Tingxiu; Ren, Guosheng

    2016-01-01

    The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

  10. Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone.

    Science.gov (United States)

    Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

    2015-09-24

    The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using devitalized tumor-bearing bones for the repairing of segmental defects after tumor resection. Twenty-seven eligible patients treated from February 2004 to May 2012 were included. The segmental tumor bone (mean length, 14 cm) was resected, and then devitalized in 20% sterile saline at 65 °C for 30 min after the tumor tissue was removed. The devitalized bone was implanted back into the defect by using nails or plates. Complete healing of 50 osteotomy ends was achieved at a median time of 11 months (interquartile range (IQR) 9-13 months). Major complications included bone nonunion in four bone junctions (7.4%), devitalized bone fracture in one patient (3.7%), deep infection in three patients (11.1%), and fixation failure in two patients (7.4%). The bone union rates at 1 and 2 years were 74.1 and 92.6%, respectively. The average functional score according to the Musculoskeletal Tumor Society (MSTS) 93 scoring system was 93 % (IQR 80-96.7%). Incubation in 20% sterile saline at 65 °C for 30 min is an effective method of devitalization of tumor-bearing bone. The retrieved bone graft may provide as a less expensive alternative for limb salvage. The structural bone and the preserved osteoinductivity of protein may improve bone union.

  11. CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

    Science.gov (United States)

    Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

    2017-03-01

    Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.

    Science.gov (United States)

    Bergamino, Maurizio; Hamilton, David J; Castelletti, Lara; Barletta, Laura; Castellan, Lucio

    2015-03-01

    In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.0, while the graphical user interface was created using PHP and HTML, thus making it easily accessible through a web browser. This web-based approach allows for multiple institutions to potentially access the database. The BT Database can record brain tumor patient information (e.g. clinical features, anatomical attributes, and radiological characteristics) and be used for clinical and research purposes. Analytic tools to automatically generate statistics and different plots are provided. The BT Database is a free and powerful user-friendly tool with a wide range of possible clinical and research applications in neurology and neurosurgery. The BT Database graphical user interface source code and manual are freely available at http://tumorsdatabase.altervista.org. © The Author(s) 2013.

  13. Clinical significance of serum thymosin α1 assay in tumor patients

    International Nuclear Information System (INIS)

    Wang Jiamin; Lv Ming'en; Zhao Xiaojuan; Gao Weiqiang; Bai Xia; Wang Zhaoyue

    2003-01-01

    Objective: To investigate the clinical significance of thymosin α1(Tα1) measurement in evaluating clinical status of patients with solid malignant tumors. Methods: Tα1 levels in serum of 50 normal adults, 20 patients with benign tumors and 63 patients with malignant tumors were measured by enzyme linked immunosorbent assay (ELISA). The association of Tα1 level with tumor invasion, metastasis and its alteration after different treatment in patients with malignant tumors were also studied. Results: The serum Tα1 level was 0.69±0.35 μg/L in normal adults, 0.96±0.37 μg/L in patients with benign tumors and 1.46±0.90 μg/L in patients with malignant tumors. In comparison